Textbook of Chemical Peels: Superficial, Medium and Deep Peels in Cosmetic Practice

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Textbook of Chemical Peels

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SERIES IN COSMETIC AND LASER THERAPY Published in association with the Journal of Cosmetic and Laser Therapy Already available David Goldberg, Fillers in Cosmetic Dermatology ISBN 1841845094

Forthcoming C William Hanke, Gerhard Sattler, Boris Sommer, Textbook of Liposuction ISBN 1841845329

Of related interest Robert Baran, Howard I Maibach, Textbook of Cosmetic Dermatology, third edition ISBN 1841843113 Anthony Benedetto, Botulinum Toxin in Clinical Dermatology ISBN 1842142445 Jean Carruthers, Alistair Carruthers, Using Botulinum Toxins Cosmetically ISBN 1841842176 David Goldberg, Ablative and Non-Ablative Facial Skin Rejuvenation ISBN 1841841757 David Goldberg, Complications in Cutaneous Laser Surgery ISBN 1841842451 Nicholas J Lowe, Textbook of Facial Rejuvenation ISBN 1841840955 Shirley Madhere, Esthetic Mesotherapy and Injection Lipolysis in Cosmetic Practice ISBN 1841845531

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Textbook of Chemical Peels Superficial, Medium and Deep Peels in Cosmetic Practice Philippe Deprez MD Medical Director Policlinica Estetica & Anti-Aging Empuriabrava Spain

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© 2007 Informa UK Ltd First published in the United Kingdom in 2007 by Informa Healthcare, 4 Park Square, Milton Park, Abingdon, Oxon OX14 4RN. Informa Healthcare is a trading division of Informa UK Ltd. Registered Office: 37/41 Mortimer Street, London W1T 3JH. Registered in England and Wales number 1072954. Tel: +44 (0)20 7017 6000 Fax: +44 (0)20 7017 6699 Email: [email protected] Website: www.informahealthcare.com All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior permission of the publisher or in accordance with the provisions of the Copyright, Designs and Patents Act 1988 or under the terms of any licence permitting limited copying issued by the Copyright Licensing Agency, 90 Tottenham Court Road, London W1P 0LP. Although every effort has been made to ensure that all owners of copyright material have been acknowledged in this publication, we would be glad to acknowledge in subsequent reprints or editions any omissions brought to our attention. The Author has asserted his right under the Copyright, Designs and Patents Act 1988 to be identified as the Author of this Work. Although every effort has been made to ensure that drug doses and other information are presented accurately in this publication, the ultimate responsibility rests with the prescribing physician. Neither the publishers nor the authors can be held responsible for errors or for any consequences arising from the use of information contained herein. For detailed prescribing information or instructions on the use of any product or procedure discussed herein, please consult the prescribing information or instructional material issued by the manufacturer. A CIP record for this book is available from the British Library. Library of Congress Cataloging-in-Publication Data Data available on application ISBN-10: 1 84184 495 0 ISBN-13: 978 1 84184 495 4 Distributed in North and South America by Taylor & Francis 6000 Broken Sound Parkway, NW, (Suite 300) Boca Raton, FL 33487, USA Within Continental USA Tel: 1 (800) 272 7737; Fax: 1 (800) 374 3401 Outside Continental USA Tel: (561) 994 0555; Fax: (561) 361 6018 Email: [email protected] Distributed in the rest of the world by Thomson Publishing Services Cheriton House North Way Andover, Hampshire SP10 5BE, UK Tel: +44 (0)1264 332424 Email: [email protected] Composition by Scribe Design Ltd, Ashford, Kent, UK Printed and bound in India by Replika Press Pvt Ltd

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Contents

Acknowledgment 1

vii

Chemical peels: definition and classification

1

2

Pre-peel care

5

3

Post-peel care

13

4

Factors influencing chemical peels

27

5

Choosing the right peel

31

6

Alpha-hydroxy acids: chemistry, pH and pKa, and mechanism of action

47

Alpha-hydroxy acids: histology and factors influencing penetration

53

7 8 9 10 11

12

13 14

109

Treating melasma, chloasma and post-inflammatory hyperpigmentation

121

17

Treating acne

125

18

Treating multiple keratoses on the scalp

131

Treating aging of the hands and forearms

135

20

Treating the neck and décolletage

141

21

Stretch marks and scars: dermabrasion and peeling

145

22

Actinic keratoses and lentigines

167

23

Trichloroacetic acid to the papillary dermis: Unideep®

177

Resorcinol: Unna’s paste/Jessner’s solution

183

Phenol: chemistry, formulations and adjuvants

193

26

Phenol: properties and histology

203

27

Phenol: skin penetration and detoxification

209

Toxicity of phenol: causes, prevention and treatment

213

Phenol: choice of peel and combination treatments

225

16

19

Alpha-hydroxy acids: indications and results

55

Alpha-hydroxy acids: application as cosmetics and as peels

59

Alpha-hydroxy acids: side-effects of AHAs

67

Alpha-hydroxy acids: a new slowrelease AHA complex with no neutralization required

Easy TCA®: basic protocol and skin aging

15

24 25

69

Trichloroacetic acid: general information, toxicity, formulations and histology

79

Trichloroacetic acid: indications and contraindications

95

28

Trichloroacetic acid: classic semiology 105

29

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Phenol: indications

31

Phenol: contraindications, precautions and safety

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32

Phenol: pre-peel preparation

253

33

Full-face phenol: nerve block anesthesia and/or sedation

261

Full-face phenol: application

273

34

233

35

Phenol: post-peel care

283

36

Phenol: chemical blepharoplasty and cheiloplasty

295

37

Complications of chemical peels

313

38

Combination of techniques

371

Index

377

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Acknowledgment

The publication of this work has been assisted by an educational grant from Skin Tech (www.skintech.info; www.peeling.com). It should be noted that this textbook is comprehensive about all available peel products, but that there are many

ancillary products (such as sunscreens) manufactured in comparable formulations about which it cannot be expected to be comprehensive; the author is most familiar with and recommends those from Skin Tech, but does not imply by this that other products may not be comparable.

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1 Chemical peels: definition and classification

Definition of a chemical peel A chemical peel is a skin treatment intended to visibly improve the structure of treated tissue by the external application of a caustic solution. It can simply accelerate the natural processes of exfoliation, but can also completely destroy the epidermis and a more or less large proportion of the dermis, essentially by protein coagulation or lysis. The effect of any peel reaches the dermis, directly or indirectly and to varying depths, where the processes of regeneration are induced to a greater or lesser degree, depending on the molecule or molecules used and the application procedure. Chemical peels are among the oldest forms of skin rejuvenation and form a group of treatments in their own right. They are both flexible and effective, with a histological, chemical, toxicological and clinical basis. They have an ancient history, have evolved rapidly and can be adapted to almost any circumstances within the limits of their indications. Most peels, to varying degrees, cause the same types of histological changes, whose clinical results lead to a more or less rejuvenating effect on all or part of the skin. Classification is always restrictive, as it forces highly variable events into a rigid framework. We will see in this book that so many different factors come into play that it becomes difficult to fit all chemical peels into a simplified and rigid classification of ‘superficial’, ‘medium’ and ‘deep’. Let us take the well-known glycolic acid peel as an example: its depth of action depends on the patient’s skin type, the presence of associated disorders (e.g. seborrheic dermatitis), skin preparation in the long, medium and short term, the galenical form (gel, liquid, mask or self-neutralizing pseudogel), the concentration of the product, the m/m, m/v or m+v calculation, whether or not it is combined with other acid molecules (e.g. lactic or kojic), the pH of the solution (e.g. 0.5 or 3.5) and therefore the fraction of free glycolic acid, what it is applied with (brush, cotton pad, etc.), the number of coats, how forcefully it is applied, whether it is applied on the face or body, the exact location on the face (e.g. nostrils or eyelids1), the contact time, how or whether it is neutralized or diluted at the end of the peel, the immediate postpeel care, the quality of care between peels, the number and frequency of repeat sessions,... And the list goes on!

It is clear that it does not take much to turn a very light glycolic acid peel into a medium-depth peel that can even reach the deeper layers of the dermis and risk discoloration or even scarring. All it takes is for the peel not to be neutralized properly. The same goes for all of these caustic molecules, which is why, until recently, it was usually necessary to have a thorough knowledge of chemical peels and skin anatomy before undertaking this kind of treatment. Every practitioner, through personal experience and practice, should aim to standardize their treatments in order to eliminate the maximum number of variables. Fortunately, new chemical peel formulas are now available that are easier, safer and quicker to use, allowing young physicians to get on with the job of peeling without losing sleep and having post-peel nightmares. Sound knowledge and experience are still essential for peels to the papillary dermis.

Criteria for classification Molecular dependence It is very simple to understand that phenol is more aggressive than lactic acid.

Doctor dependence Classification may be personal; it may be related to the practice of one particular doctor who has standardized his methods of treatment with a view to limiting uncontrollable variables. But such a classification would not allow for any scientific exchange. What would produce a superficial peel with one practitioner could in fact result in a medium peel with another who uses the same product with a different application technique. This is why peels are often considered to be ‘doctor-dependent’. How can we give a valid classification for a treatment that is doctor-dependent? We should also compare products of the same type only, and yet the quality of the preparations and excipients is highly variable and impossible to control.

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Chemical dependence

Patient dependence

It is known that trichloroacetic acid (TCA) crystals, for example, are very hydrophilic, which means that they must be kept in perfect conditions so that the pharmacist can prepare the solutions we prescribe properly. How can we know how long the pharmacist’s bottle of TCA crystals has been open? If the crystals have not been hydrated inadvertently (if the pharmacist closes the bottle as soon as he has taken out the required amount), the final concentration will be correct. If, on the other hand, the crystals are mostly hydrated (if the pharmacist leaves the bottle of TCA open in order to serve another customer), the concentration of the solution provided by the pharmacy will be abnormally low and not very effective. Peels are therefore also considered to be ‘chemical-dependent’.

Each patient has a skin type that is genotypically and phenotypically unique. The skin has a history that the doctor must know about. Stable products that are properly prepared and applied with precise methodology, in the same way, by the same doctor, on the same day, can produce different results on different patients. Every morning, or maybe several times a day, patients go through their own particular skincare routine that the doctor doing the peel does not necessarily know about. Let us take for example the application of large quantities of topical benzoyl peroxide, which some teenagers use secretly for acne. It reduces the thickness of the stratum corneum and makes the skin more permeable. This of course makes it easier for the acids used for skin peeling to penetrate the skin, and can, in

Table 1.1 Summary of chemical peels Molecule

Depth

Application

Glycolic acid

Very superficial

25–50% partially buffered, for 1–2 min

Superficial

50–70% partially buffered, for 2–10 min

Medium (not recommended)

70% unbuffered, for 5–10 min

Mixture of AHAs

Dermal and epidermal stimulation

Easy Phytic®: pH 0.5, but slow-release effect + self-neutralizing

Jessner (Resorcinol)

Very superficial

1–3 layers

Superficial

4–8 layers

Medium (not recommended)

4–8 layers combined with 25% m/m TCA

Superficial

One application of 30% paste for 5 min

Intermediate

Two applications of 40% paste for 30 min

Medium

Three applications of 40% paste for 30 min, after skin preparation

Very superficial

• One application of 10% TCA • 10–20% TCA solution, depending on number of coats and skin preparation

Superficial

• Easy TCA® or 10–15% m/m solutions, depending on number of coats and preparation, or in combination (e.g. Abrasion, Dry Ice, Jessner)

Medium

• Unideep® • Solutions of >35% m/m

Deep

• Sandpaper abrasion + Easy TCA® • Unideep® • Only Touch® (AHA + TCA > 40% m/m – localized deep)

Localized deep

Lip & Eyelid® (wrinkles on lips and eyelids)

Full-face deep

Lip & Eyelid®, Baker, Litton, Exoderm, etc.

Unna (Resorcinol)

TCA

Phenol

AHA, alpha-hydroxy acid; TCA, trichloroacetic acid.

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some cases, cause unexpected burns. A similar situation arises with patients who want to present their doctors with perfectly clean skin and use abrasive creams – the intention is noble but the consequences are sometimes unpleasant. A peel is therefore also ‘patient-dependent’. If we leave aside these variables, we can fit the different types of peels into their appropriate slots. This is just for the beauty of the exercise however, as the variables still need to be taken into account. It is clearly possible to perform a superficial or medium peel using phenol. But, given the inherent toxicity of phenol, what would be the point? What is more, 70% unbuffered glycolic acid that is left for 10–15 minutes on a thin, sensitive skin that has been prepared with retinoic acid can result in a cosmetic disaster. It is possible to carry out good-quality, deep peels with TCA, but the risks can be greater than if phenol is used correctly.

Summary table Table 1.1 is intentionally incomplete. A peel is considered as ‘very superficial’ when its action is limited to the stratum corneum, ‘superficial’ if it does not go beyond the basal

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layer of the epidermis, ‘medium’ if it reaches the papillary dermis and ‘deep’ if it reaches the reticular dermis. In reality, it is better to determine the depth of a peel by clinically observing what is happening to the skin during the course of the treatment than by blindly applying set recipes. When we say that the result of a glycolic acid peel is ‘time-dependent’, this does not mean having to watch the clock but rather continuously analyzing how the skin is reacting in order to determine the best moment to start neutralization. There is one basic principle to be respected: a peel should not be unnecessarily deep or unnecessarily superficial. There is no point completely destroying the papillary dermis when treating a purely epidermal problem, and it is pointless and ineffective to use an intraepidermal peel, even repeatedly, to treat a dermal problem.

Notes 1.

The nostrils can tolerate glycolic acid better than the skin around the eyelids, and many application procedures for glycolic acid peels recommend avoiding application to the eyelids.

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2 Pre-peel care

Is it necessary to prepare the skin? Depending on the type of peel, preparing the skin can be essential, completely pointless or even dangerous. The chapters devoted to the different types of peels give details of the preparation recommended in each particular case. This chapter deals with the generalities of pre-peel care.

Medium- and long-term preparation Alpha-hydroxy acid (AHA) peels produce the best results if they are preceded by careful preparation and followed by long-term daily cosmetic care. Easy Phytic® solution, on the other hand, does not allow any pre-peel preparation that is likely to accelerate penetration of the acids, as the stratum corneum must be intact for the peel to be safe. Classic trichloroacetic acid peels, in a simple aqueous solution in gel or mask form (TCA–SAS) always require around 1 month’s intensive pre-peel preparation. This preparation stimulates keratinocyte regeneration and reduces the risk of post-inflammatory pigmentary changes and/or scarring. It blocks the first stages of the biochemical conversion of tyrosine into indole groups and melanin and limits the reaction of melanocytes to ultraviolet light. Easy TCA® requires no preparation under its basic protocol (until scattered pinpoint or cloudy white frosting appears). The preparation required for its special deep-peel protocol or when combined with abrasion is discussed later in this book. Resorcinol produces far better results and fewer complications if the skin is well prepared. Phenol does not usually require any specific preparation, but needs careful post-peel care. As a general rule, it is worthwhile preparing the skin carefully with tyrosinase inhibitors if there is any risk of post-peel pigmentary changes or to optimize results when treating melasma. Retinoic acid and sometimes glycolic acid are used to make transepidermal penetration more even or to deepen the action of the acid solution.

Immediate pre-peel preparation Generally, patients must wash their skin with soap and water before going to the appointment. The doctor will disinfect the skin with alcohol and degrease it with acetone or ether. These degreasing products allow the peel solutions, which are usually hydrophilic and have difficulty penetrating the skin’s protective oils, to penetrate more deeply and evenly. They break down some of the proteins and phospholipids in the cell membranes, which enhances the action of the acids applied afterwards. AHA peels require very careful preparation before being applied. The skin should be cleaned with soapy water, rinsed thoroughly, degreased with acetone and disinfected with alcohol. Unlike the classic AHA peels, with Easy Phytic®, the skin must be cleaned with a gentle, nonaggressive cleansing foam that only contains surfactants, so that the acids do not penetrate the skin too quickly and saturate its natural buffer capacity, making it impossible for it to neutralize the sudden inflow of acids in time. Thorough cleansing and degreasing of the skin before Easy Phytic® would oblige the doctor to neutralize it in the classic manner – when there is no prior preparation, there is no need to neutralize it. With TCA–SAS, resorcinol, salicylic acid, azelaic acid or phenol peels, the skin needs to be thoroughly cleansed of make-up, degreased and disinfected. Easy TCA® solution, on the other hand, contains saponins that make pre-peel make-up removal and degreasing unnecessary; the skin’s natural defenses are only very slightly diminished by this peel, and therefore there is no need for any particular prepeel preparation against infections.

Products used to prepare the skin The products usually used to prepare the skin are sunscreens, tretinoin, AHAs and tyrosinase inhibitors. Jessner’s solution is sometimes used as a pre-peel preparation. It is often necessary to take measures to prevent infection, especially herpes.

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Prevention of infection Prevention of the herpes simplex virus is essential for patients who have a history of the infection (a single incidence of herpes is enough). Herpes prevention is necessary with a peel to the papillary dermis. It is also worthwhile when a more superficial peel is usually accompanied by a severe inflammatory reaction, as is the case with resorcinol, ‘classic’ AHAs and TCA–SAS. It is not necessary when using Easy TCA® under its basic protocol or Easy Phytic®. General infection prevention measures should be taken, depending on the depth of the peel. For more information, see the discussion of infections in Chapter 37.

Pre-peel sun protection It can be beneficial to protect the skin against the sun before certain peels. Effective sun protection should start 2 weeks before a medium or deep peel and even before a series of superficial peels to inhibit melanocyte activity and avoid excessive stimulation of melanin production before the peel.

Prevention of pigmentary changes Before any ‘classic’ peel, steps must be taken to limit the risk of pigmentary changes. Preparing the skin with tyrosinase inhibitors (hydroquinone, kojic acid, azelaic acid, arbutin, Morus Alba, licorice extracts, etc.) is especially recommended to curb the enthusiasm that certain melanocytes have for converting tyrosine into melanin. Preventive measures should begin 3–4 weeks before a medium or deep peel. Combinations of hydroquinone (2–4%) plus kojic acid (2–3%) or hydroquinone (2–4%) plus glycolic acid (8–10%) are effective, as are certain formulas containing several tyrosinase inhibitors, antioxidants and concentrated retinol (Blending Bleaching® cream). Some patients may develop hyperpigmentation, or even ochronosis, when treated with hydroquinone. Patients with dark skin types are most at risk. Long-term use of high-concentration hydroquinone can also cause confetti-like depigmentation (Figure 2.1). Hydroquinone is prohibited from sale as an ingredient in cosmetic or cosmeceutical products in many countries (although it is available on medical prescription) and has been successfully replaced by new formulas combining other tyrosinase inhibitors. Creams containing azelaic acid (usually at a concentration of 20%) are considered slightly bleaching when used for at least 4–6 months. Azelaic acid is an irritant, and is used mainly when other formulations cannot be used. For oily or thick skins, tyrosinase inhibitors can be prescribed in a gel form that penetrates the skin more easily and allows instant and easy application of make-up. For more information, see the discussion of pigmentary changes in Chapter 37.

Figure 2.1 Confetti-like depigmentation.

Even penetration of acids and stimulation of skin regeneration To perform a medium or deep TCA–SAS peel, the active molecule in the peel solution has to penetrate more deeply and the skin must regenerate more quickly. We have two large groups of molecules at our disposal: AHAs and retinoids. AHAs (e.g. 10–15% glycolic acid) break down corneodesmosomes that maintain intercorneocyte cohesion; they make it easier to shed this layer of dead cells (which are, however, essential to the skin’s defenses, as they are largely responsible for maintaining the permeability barrier function in the skin as a whole). The epidermis is thinned by the AHAs, making the stratum corneum more permeable, and the acids can penetrate more deeply and evenly. The risk with this preparation is that the epidermis may become too permeable and the effect of the peel can go too deep. A peel that is meant to reach the papillary dermis could penetrate as far as the reticular dermis as a result of too ‘strong’ a preparation of AHAs. A peel that is meant to remain intraepidermal could become intradermal and result in post-peel complications and more downtime: an intraepidermal peel removes several layers of ‘skin-color’ keratinocytes in light flakes for around 3 days, whereas an intradermal peel removes the entire epidermis in the form of strips of brownish skin. The darker the skin type, the more visible is the flaking. Retinoids form a growing range of products with everwidening indications. The retinoid most used in pre-peel preparation is tretinoin. Among other things, it stimulates keratinocyte growth in the basal layer and causes an overall thickening of the epidermis but also a relative thinning of the stratum corneum. The pre-peel use of tretinoin

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enhances penetration of the acids at the same time as stimulating the regeneration processes in the keratinocytes of the basal layer. The choice of one or another of these molecules depends on the condition of the patient’s skin. Tretinoin is not used if the patient has many telangiectasias; AHAs are avoided if the skin is very thin. Conversely, the two products can be mixed in the same prescription, in variable concentrations, depending on the skin type and the desired effect. The concentration of tretinoin would be increased to stimulate reepithelialization; the concentration of glycolic acid would be increased to improve and even out transcorneal penetration.

Tretinoin Tretinoin (all-trans-retinoic acid, ATRA) is the carboxylic acid form of vitamin A (retinol). It is one of the first-generation retinoids and has been used since the 1970s to treat acne complaints and dyskeratosis. It is important to know all about this molecule in order to obtain benefit from its actions.

Histological changes During long-term treatment with tretinoin, the results can first be seen through a microscope, long before they are clinically visible. These histological changes explain the indisputable clinical efficacy of continuous treatment. The epidermis increases in thickness by 10–40%, with a thickening of the stratum granulosum to the detriment of the superficial stratum corneum (which decreases by about 25%); the overall water content of the epidermis is thus increased and the skin appears more hydrated. This epidermal hyperplasia is observed both on the face and on the rest of the body, especially on the arms or forearms. Unfortunately, it is not certain whether the improvement is permanent, as some studies show a reversibility of the action of tretinoin (a habituation phenomenon?) after 6 months’ treatment on the forearms and the disappearance of histological improvement altogether 1 year after the start of the treatment, whereas clinically the improvement persists. Normal epidermal differentiation is restored and keratinocyte abnormalities gradually decrease. The atypical keratinocytes are eliminated and the tretinoin prevents or delays keratoses from reappearing. The melanocyte clusters in the basal layer gradually disperse as a result of the increased cell turnover. The marks on the skin thus tend to be more diffuse, or even to disappear. The overall pigmentation in the epidermis decreases in patients with black skin (32%1 and 23%2) and in patients with yellow skin (41%3). One year after the start of treatment, the melanin content of the epidermis continues to decrease and causes the skin to lighten in the long term. As with chemical peels, a newly formed collagen layer appears, in horizontal bands, just

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beneath the basal membrane, in the Grenz zone. New active fibroblasts appear in the dermis, and new elastic and collagen fibers are secreted. An increase in glycosaminoglycans thickens the dermis, and elastotic tissue is pushed deeper down. After 26 months of daily treatment with 0.05% tretinoin, the events described above are extensive enough to push the elastotic tissue deep down and hide it under the new vascular, elastic, collagen and epidermal growth. It must be noted, however, that not all authors accept the existence of these histological changes in the dermis in the long term. In particular, a study by Gilchrest4 on 500 biopsies carried out during a 5-year observation of daily topical tretinoin treatments (in concentrations between 0.001% and 0.1%) could not find any evidence of histological changes in the dermal parameters. This is surprising, and contradicts the established fact that clinically visible angiogenesis exists.

Mechanism of action Tretinoin is a synthetic (all trans) retinoic acid. Retinol and retinaldehyde are also converted into retinoic acid in the target cell where it participates in metabolic activity. The retinoic acid penetrates the cell’s nucleus, where it binds with a retinoic acid receptor (RAR). The complex formed by the retinoic acid and the RAR (RA–RAR) interferes with certain areas of DNA by modulating the expression of some genes. It appears that retinoic acid alters the regulation of the cell cycle.4 For many years, tretinoin was considered capable of reducing sebum production in the sebaceous glands, but serious doubt has been cast on this theory. It is generally thought that the mode of action of tretinoin is essentially linked to the increase in epidermal turnover and enhanced exfoliation of the stratum corneum, which makes it easier for the pilosebaceous units to drain. A reduction in melanin production has also been observed. Used specifically as a pre-peel preparation, tretinoin evens out the thickness of the stratum corneum and reduces overall skin thickness. In these conditions, skin permeability increases significantly. Tretinoin also stimulates keratinocyte division and thus facilitates the regeneration phase, which can sometimes be too slow with certain peels. Topical tretinoin stimulates fibroblast production of collagen as well as other components of the dermal extracellular matrix, and sometimes creates a new layer of ‘repair’ collagen that is laid on top of the photodamaged collagen.

Indications Clinical results appear slowly and gradually, after histological improvement. The skin soon appears to be intensely hydrated, once the erythema has disappeared or subsided. Clinically, it takes a year for the rejuvenating action of tretinoin to show. Patients, who hope to see rapid

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improvement, are not best pleased with these slow clinical results on aging skin. Progress can sometimes be seen more quickly when treating dyschromia: some results may be seen after 1 month of daily application of 0.1% tretinoin cream. Comedonal acne and acne rosacea respond well to tretinoin. In fact, the anti-aging effect of tretinoin was first observed in patients being treated with tretinoin for comedonal acne: their skin texture and skin tone were gradually seen to improve. Oral isotretinoin (9-cis-retinoic acid) is often used in treating severe or stubborn acne rosacea. A 1994 study5 compared the treatment of rosacea with 10 mg/day lowdose oral isotretinoin, 0.025% low-dose topical tretinoin and a combination of the two. The results showed that before the 16th week of treatment, isotretinoin was more effective, but that afterwards there was no difference between tretinoin and isotretinoin. The combination of systemic and topical treatment does not give any further improvement in low doses. It is generally accepted that tretinoin with a concentration of 0.05% is as active as 5% benzoyl peroxide. Topical tretinoin makes the skin smoother: the same patients who benefited from the visible rejuvenating effect of tretinoin when being treated for acne noticed, among other things, that their skin had become smoother and softer after treatment. The improvement brought about by this topical treatment is therefore visual as well as tactile. The application of topical tretinoin improves senile atrophy of the skin: a decrease in cell abnormalities and dysplasias can be seen, as well as an antitumor effect that persists after the end of treatment if it has been administered correctly and for a sufficiently long period.6 Topical tretinoin reduces the size and number of lentigines and other age-related discolorations. In some cases, however, because of its photosensitizing potential, tretinoin can aggravate certain types of dyschromia. This can be problematic for Asian patients, for whom hyperpigmentation is more of a problem than wrinkles as they age. The study by Griffiths et al3 proved (clinically, histologically and by colorimetry) that 0.1% tretinoin significantly improved hyperpigmentation in these patients. There was a 41% improvement with tretinoin, compared with a 37% aggravation in patients receiving the vehicle alone. Post-inflammatory hyperpigmentation is also improved by tretinoin, as proved clinically, histologically and by colorimetry, in a study by Bulengo-Ransby et al2 on subjects with black skin. A 40% improvement can be expected after 40 weeks of treatment with 0.1% tretinoin. In the treatment of melasma, topical 0.1% tretinoin was studied in comparison with the vehicle alone in black patients.1 A 10-month treatment lightened the melasma by 32% (an improvement factor established both clinically and by colorimetry). Histological studies have shown a significant decrease in epidermal pigmentation in patients treated with tretinoin

compared with placebo. Of the patients treated with tretinoin, 67% developed only one side-effect, a mild ‘retinoid dermatitis’ (which is to be expected when using a concentration of 0.1%). This study also showed that the finest wrinkles disappeared and other wrinkles improved. Overall, skin tone improves because of the combination of histological events in the dermis and epidermis described above. The skin takes on a rosier complexion as a result of angiogenesis occurring deep down.

How to prescribe tretinoin One study7 showed that a tretinoin concentration of 0.01% is effective for the face, hands and forearms, whereas another8 showed that there is no difference between placebo, 0.01% tretinoin and 0.001% tretinoin. A concentration between 0.05% and 0.1% is, on the other hand, always considered active. The average concentration used is 0.05%, but different skin types or sensitivities may require different concentrations, and it is recommended to start any treatment with a trial dose of 0.02% or 0.03%. The following is one frequently used formulation (0.025%): tretinoin urea (carbamide) water Neribase® cream or Eucerin® O/W

15 mg 6g 4g ad 60 g ad 60 g

If this dose is well tolerated, it is possible to go immediately or gradually to a concentration of 0.05%. This concentration is common in proprietary medicines, but if prescription medicines are preferred, it is possible to prescribe 0.05% tretinoin in the following formulation: tretinoin urea (carbamide) water Neribase® cream or Eucerin® O/W

30 mg 6g 4g ad 60 g ad 60 g

Formulations in alcohol gels dry out the skin, increase the penetration of the tretinoin and make the treatment more uncomfortable. Gels should only be used on thick and oily skins. When the patient can tolerate a concentration of 0.05% without any notable side-effects, the concentration can gradually be increased to 0.07%, 0.09% and 0.1%. Concentrations higher than this are rarely used. If, on the other hand, the skin is very sensitive and becomes irritated in spite of a low concentration of 0.025%, the concentration must be decreased to 0.0125%9 or the patient should be asked to do one of the following. The skin can be sprayed with warm water immediately before applying a small

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quantity of cream. The cream will spread more easily and less of the active ingredient will be applied on the skin. Alternatively, the tretinoin cream can be mixed in the palm of the hand with an equal quantity of hydrating vitamin E cream10 in order to halve the final concentration. If the skin is still sensitive to the treatment, as a last resort, the treatment can be applied every other day or once every 3 days for the first month. Experience shows that daily application of low concentrations is a better way to prepare the skin for higher doses than applying higher concentrations two or three times a week. The ‘normal’ concentration for daily application (0.05%) is reached gradually over 2–3 months. It makes little sense to combine tretinoin with a topical corticosteroid to limit the inflammatory reaction. It may well be that this combination is supposed to stop inflammation, but inflammation is beneficial in that it stimulates the process of skin repair. Furthermore, the combined effect of corticosteroid and tretinoin could potentially cause telangiectasia. The tretinoin would stop skin atrophy as a result of the application of topical corticosteroid, whereas it should increase the thickness of the epidermis overall. A large part of the effect would therefore be lost. Finally, corticosteroids should not be applied to the skin for a prolonged period, whereas long-term application of tretinoin is necessary. If the skin is resistant from the start and does not respond at all to the above formulation at 0.05%, a concentration of 0.1% can be used. This high concentration has been shown to produce results rapidly, but can often have serious side-effects. Therefore, before such a sudden increase in concentration, there are a few ‘therapeutic tricks’ that can be tried: when the skin appears not to respond to a single daily application of 0.05%, a 0.05% cream can be applied twice a day – once in the morning followed by a sunscreen and again in the evening. To increase the effect, it is possible to prescribe an alcohol gel, starting with a concentration of 0.05%, and increasing to 0.1% if the patient can tolerate this. To increase the potency of the tretinoin, the impermeability of the skin barrier can be decreased, either by applying a 10% glycolic acid cream 20 minutes before applying the tretinoin or by using a mildly abrasive sponge (Buf-Puf®) on the skin before using the tretinoin. In some extreme cases, a light facial or body scrub twice a week increases skin permeability and makes it easier for the tretinoin to penetrate. Very superficial microdermabrasion with corundum crystals or sandpaper can also make the skin more permeable.

Age for starting treatment The lighter the phototype, the better it is to start treatment at a young age. For example, individuals with skin phototype II can start treatment in their 20s, whereas individuals with skin phototype IV should only start in their 30s.

9

Various recommendations Tretinoin cream should be kept out of direct sunlight and away from heat sources, to which it is sensitive. In spite of these precautions, it gradually loses its efficacy and it is recommended that the prescription be renewed every 3 months. Tretinoin is sensitive to oxidation, heat and ultraviolet light: the refrigerator (4°C) seems to be the best place to store this cream. The by-products of degradation turn the cream a yellowish color, in which case it should no longer be used. Tretinoin is photosensitizing, and it is therefore preferable to apply the cream in the evening and to use a hydrating antioxidant or a cream such as Blending Bleaching® combined with a sunscreen (UVB + UVA + HSP) of factor 20 or above in the morning. The tretinoin cream is applied after washing the skin with a mild soap (Avene® or Skin Tech’s Pre-Peel Cleanser®), and is rubbed gently onto the face and neck (very gently on the neck where the skin is more sensitive). It is striking to note that the earlobe is often missed out in skin rejuvenation or tretinoin cream treatments – and can be a telltale sign of a person’s real age. When tretinoin is applied to skin with seborrheic dermatitis (even when this is subclinical), it is common for erythema to develop, often in the middle of the face. One week’s preventive treatment with topical nystatin can often prevent erythema, and considerably improves treatment compliance. Men whose skin tends to become irritated or infected after shaving can use tretinoin as an aftershave cream. Shaving soon becomes more comfortable: within 48 hours, the irritation or potential acneform dermatitis has subsided or disappeared altogether. The tretinoin cream should be applied every day for at least 12–18 months and two or three times a week thereafter to maintain the results. When the treatment ends, the effect does not last indefinitely, and the skin slowly returns to a state close to its original condition. However, if the treatment is followed with one to three applications a week afterwards, the positive effects remain visible.11 When the treatment lasts 5–6 years, the elastotic material in the dermis is gradually replaced by new collagen and elastic structures.12 The results should last a long time if the skin is protected from factors that accelerate the aging process. Combining tretinoin and benzoyl peroxide could inactivate the tretinoin. If absolutely necessary, benzoyl peroxide can be applied in the morning and tretinoin in the evening.

Side-effects Patients should be warned of the high probability of adverse effects, which fortunately are only temporary. Tretinoin is more irritant than glycolic acid. The irritation is usually mild, but can take the form of ‘retinoid dermatitis’ if high concentrations are used or if the skin is delicate. This dermatitis is in fact a positive side-effect when tretinoin is used to prepare for a TCA–SAS peel, at least to

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the level of the papillary dermis, as it helps the TCA penetrate more deeply and evenly. A concentration of 0.05% tretinoin should be used once or twice a day (depending on the thickness and sensitivity of the skin) for 1 week; the following week, the concentration is increased to 0.07% and the third week to 0.1%. This relatively aggressive preparation improves the penetration, evenness and re-epithelialization of the TCA–SAS peel, but will not improve the cosmetic results (or will do so only very slightly). If the skin is not properly hydrated during treatment with tretinoin, it will usually flake visibly and fairly rapidly after a few days of treatment. Erythema is to be expected with effective tretinoin treatment. This is not an adverse effect, but rather is collateral and natural. The skin of a patient properly treated with tretinoin is pinker than normal, and this provides the doctor with an essential means of observation: a patient showing no erythema is undertreated or incorrectly treated. Erythema that appears very rapidly, 2–3 days after treatment begins, and that is localized in patches may be seborrheic dermatitis; it soon clears up with nystatin cream. Erythema that appears in the medium or long term, 1 or more weeks later, can spread over the whole face and sometimes to the neck in patients with very sensitive skin. If this should happen, treatment should be stopped for 1–2 weeks and started again at a lower dose, as explained above, to avoid excessive neoangiogenesis. More often than not, retinoid erythema does not last long in patients with a dark skin phototype, whereas patients with a lighter phototype can suffer from persistent, if not permanent, retinoid erythema. Sometimes, the redness is more of a passing flush than fully established erythema. The skin becomes more sensitive to the sun, perfumes and detergents. In fact, right from the start of treatment, the skin becomes more sensitive to any irritant: beware of chemical hair removal products, waxes, dyes, etc. People who use tretinoin often report that their skin is more sensitive to the sun and burns more easily. This photosensitization is better explained by the thinning of the stratum corneum rather than by a photochemical reaction between the tretinoin and the sun’s rays. It is therefore essential to recommend the use of a sunscreen (SPF 25–50 UVA + UVB + HSP induction) to patients being treated with tretinoin. It should also be borne in mind that there is a potential risk of skin cancers developing as a result of the stratum corneum thinning and the enhanced penetration of the sun’s rays. Nevertheless, it appears that patients on longterm tretinoin treatment do not have a higher incidence of skin cancers. Tretinoin has in fact proved to be effective in the treatment of photoaging and actinic keratoses.

Teratogenicity of tretinoin There is one important thing to note about the risk of teratogenicity: to date, and in spite of the fact that no terato-

genicity has been officially attributed to tretinoin,13 we do not have all the necessary facts at our disposal to allow its unreserved use during pregnancy or in women who wish to become pregnant. Despite the fact that application of tretinoin under occlusion on more than 30% of the body has not been found to lead to any abnormal increase in plasma levels, and despite there being no higher incidence of fetal deformities among the children of women who have used tretinoin during the first months of pregnancy, it is nonetheless possible for retinoic acid to penetrate the cell nucleus and alter the expression of certain genes.4 Caution dictates that one should not go ahead with treatment in a particular case until all the necessary facts are available to allow a risk-free choice to be made. Hypervitaminosis A is theoretically possible and could be insidious and chronic. 14 Practitioners should remain on their guard and make sure that patients are not taking extra vitamin A supplements.

Benefits of skin preparation Major benefits Avoiding various side-effects Preparing the skin before a TCA–SAS peel helps prevent herpes and bacterial and mycotic infections. It also helps reduce the risk of inadequate results (thanks to combination with other treatments).

Improved penetration of the active product Preparation with AHAs or tretinoin reduces the thickness of the stratum corneum, the skin’s natural barrier. As the barrier is not as thick, it is easier for the products applied to the skin to penetrate to the basal layer of the epidermis and more deeply into the dermis. It should be noted that not all peels require this kind of preparation.15

Even penetration of the peel The skin does not have the same thickness all over, and this can produce differences in the level of penetration. Correct preparation with AHAs and/or tretinoin tends to even out the thickness of the skin and allow the active products of the peel to penetrate evenly. Areas of hyperkeratosis (senile keratoses, and flat and seborrheic warts) are a perfect example of this difference in the level of penetration. Keratoses, which are characterized by a localized thickening of the stratum corneum, are less permeable to the acids. Pre-peel preparation with tretinoin evens out the thickness of the stratum corneum and hence the overall permeability of the epidermis.

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11

Reduced risk of pigmentary change

Monitoring skin preparation

Patients with olive and dark skin, or of Hispanic or Asian origin, are more prone to pigmentary changes than patients of Caucasian origin. It should be remembered that genotype does not always correspond to phenotype and that there are light skins that react in the same way as dark skins.16 Tretinoin, even more than AHAs, disperses melanin granules and reduces the overall quantity of melanin in the epidermis. This reduces the risk of postinflammatory or post-peel pigmentary changes. Tyrosinase inhibitors should be used in post-peel treatment as well as in pre-peel preparation (1 month before the peel when there is a risk of pigmentary change, i.e. when TCA–SAS or AHA peels are used). Some commercial creams have interesting formulations with AHAs (to enhance penetration of the other active products), tretinoin precursors, lactic acid, extracts of Morus Alba and kojic acid, combined with Transcutol®, an adjuvant that concentrates the active products near the basal layer and the melanocytes.

Monitoring the preparation process can give an idea of how reactive and sensitive the skin is. Thus, a patient who cannot tolerate hydroquinone during pre-peel preparation will tolerate it even less in the days following the treatment as the skin becomes more sensitive to any irritant. Similarly, if the patient develops an allergy to one of the products used in the preparation, it can be isolated and avoided after the peel.

Combination treatments Other treatments can be combined with the pre-peel preparation: shave excision, electrocoagulation, ablations, botulinum toxin, dermal filling, mesotherapy, etc. Some peels can be used simultaneously with these techniques. For example, a phenol peel can be immediately preceded by shave excision of raised benign lesions. Easy TCA® can be immediately preceded by botulinum toxin, dermal filling, electrocoagulation of telangiectasias (Figure 2.2), mesolift, IPL, depilation, etc.

Accelerated healing of the skin After a peel, the skin needs to heal as quickly as possible in order to maintain homeostasis of the whole organism. Tretinoin accelerates re-epithelialization if used before the peeling. For this it must be used at a dose of 0.05%–0.1%, sometimes to the point of irritative dermatitis. Ideally, the treatment should start 3–4 weeks before a TCA–SAS peel. It is accepted scientifically that the preventive application of tretinoin promotes post-peel healing of the skin. In contrast, applying tretinoin during the post-peel period appears to slow down skin regeneration. Not all peels require this help with re-epitheliazation.

Minor benefits Testing patient compliance A patient who refuses to comply with instructions for preparing the skin before a peel will not be naturally inclined to heed advice for care during or after the peel sessions either. It is always preferable not to ‘peel’ a patient who is incapable of understanding or accepting these instructions. Testing patient compliance is all the more important since preparing the skin and keeping up cosmetic care afterwards affect the quality of the results.

Getting an idea of follow-up care For patients who accept it, preparation gives them a foretaste of between- and post-peel care.

Figure 2.2 Treatment of telangiectasias by (Ellman®) radiofrequency immediately before the application of Easy TCA®. Scattered pinpoint frosting signals the penetration of the acid at each point treated by radiofrequency. This combination significantly reduces scabbing and includes a ‘pixillized’ deeper peeling.

Notes 1. Kimbrough-Green CK, Griffiths CE, Finkel LJ, et al. Topical retinoic acid (tretinoin) for melasma in black patients. A vehicle-controlled clinical trial. Arch Dermatol 1994; 130: 727–33. 2. Bulengo-Ransby SM, Griffiths CE, Kimbrough-Green CK, et al. Retinoic acid treatment for hyperpigmented lesions caused by inflammation of the skin in black patients. N Engl J Med 1993; 328: 1486–7. 3. Griffiths CE, Goldfarb MT, Finkel LJ, et al. Retinoic acid treatment of hyperpigmented lesions associated with photoaging in Chinese and Japanese persons. J Am Acad Dermatol 1994; 30: 76–84

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4. Gilchrest BA. Retinoids and photodamage. Br J Dermatol 1992; 127(Suppl 41): 14–20. 5. Ertl GA, Levine N, Kligman AM. A comparison of the efficacy of topical tretinoin and low-dose oral isotretinoin in rosacea. Arch Dermatol 1994; 130: 319–24. 6. Published studies disagree on the efficacy of tretinoin. 7. Andreano JM, Bergfeld WF, Medandorp SV. Tretinoin emollient cream 0.01% for the treatment of photoaged skin. Cleve Clin J Med 1993; 60: 49–55. 8. Olsen EA, Katz HI, Levine N, et al. Tretinoin emollient cream: a new therapy for photodamaged skin. J Am Acad Dermatol 1992; 26: 215–29. 9. By altering the formulations given above: 7.5 mg tretinoin in 60 g of cream.

10. Vit E antioxidant® (Skin Tech) or a similar cream. 11. Thorne EG. Long-term clinical experience with a topical retinoid. Br J Dermatol 1992; 127 (Suppl 41): 31–6. 12. Not all studies endorse this long-term treatment. 13. Guzzo CA, Lazarus GS, Werth VP. Dermatological pharmacology. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG, eds. Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 9th edn. New York: McGrawHill, 1996: 1600. 14. Farnes SW, Setness PA. Retinoid therapy for aging skin and acne. Postgrad Med 1992; 92: 191–6, 199–200. 15. For example: Easy TCA® and Easy Phytic® need no pre-peel preparation. 16. Which is why it is important to question the patient.

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3 Post-peel care

Immediate post-peel care is described in detail in the chapters dealing with each type of peel. As a general rule, tretinoin and creams with an alpha-hydroxy acid (AHA) concentration of over 10% should be avoided before the exfoliation phase is completely finished.

Sun protection Any peel, even a very superficial one, reduces the thickness of the stratum corneum that protects the skin against the effects of radiation: the diffractive and reflective protection usually afforded in these outermost layers is no longer available, and the overall quantity of rays that penetrate the skin increases. This extra radiation can cause actinic damage in cells that are usually physically protected by the thickness of the skin. Melanocytes are more strongly stimulated, and there is an increased likelihood of pigmentary change. All peels thus allow the sun’s rays to penetrate more easily to at least the basal layer of the epidermis, where keratinocytes ensure re-epithelialization and melanocytes can induce hyperpigmentations. Greater irradiation increases the risk of these cells being genetically modified. All peels put the skin at risk of light stress, which makes the use of sun protection creams essential. A powerful, broad-spectrum sunscreen provides greater protection. The deeper the peel, the more important it is to use sun protection. After any medium or deep peel, it is necessary to use an effective sunscreen of factor 25–50 (Figure 3.1) (UVA + UVB + HSP inducers) for 6–12 weeks (depending on the depth of the peel). The sunscreen should be applied immediately after washing in the morning, preferably with a cleansing lotion. Post-peel sun protection should be re-applied every 3 hours on average under any make-up, even if the make-up itself is considered to be photoprotective. After a peel, sun protection is necessary even if the patient does not go outside and even in foggy or cloudy weather: windows block out most UVB but not UVA, and not all clouds filter UV. Halogen lamps and spotlights and cathode-ray screens also appear to produce a sufficient quantity of radiation to induce post-inflammatory hyperpigmentation (PIH) in sensitive individuals.

Effective sun protection factor The sun protection factor should be even more ‘aggressive’ when treating post-inflammatory hyperpigmentation, and should protect against UVA as well as UVB. Protection from the sun means not only avoiding lying on the beach but also avoiding daylight. The skin is subjected to many light shocks; it is constantly under attack from the sun and daylight. One pitfall to be avoided is applying sunscreens that contain tanning accelerators that could have a harmful effect.1 Between peels and during the first few weeks after a peel, a generous amount of Melablock HSP® 50+ sun cream, for example, should be applied every 3 hours.2 Thereafter, daily sun protection can be lighter: for example Melablock HSP® 25+ every 3 hours. Patients should be advised to keep their backs to the sun and to wear light protective clothing. UV is not the only cause of hyperpigmentary reactions: infrared can also cause them.

Heat-shock proteins (HSPs) The process of wound healing after thermal injury (e.g. from laser treatment) involves re-epithelialization that starts within the first few hours after injury and continues throughout the different proliferative phases of skin repair. Viable keratinocytes (Figure 3.2) that are at the edge of the wound and have not suffered lethal or sublethal heat shock

110 100 90 80 70 60 50 40 30 20 10 0

 90

% UVB blocked

ch03

 96

 98

 50

0 SPF0

SPF2

SPF10

SPF25

SPF50

Figure 3.1 An SPF of 50 protects the skin against 98% of UV. A higher protection factor is not necessary.

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Figure 3.2 Diagram of the peripheral thermal damage after ablative laser treatment. The number of lethal lesions is proportional to the degree of shading. The skin is repaired from peripheral keratinocytes: some have suffered sublethal damage. Heatshock protein (HSP) inducers help improve keratinocyte resistance to heat shock.

migrate horizontally and centripetally in order to form an initial single cell layer of keratinocytes, the ‘new basal layer’, before starting vertical growth that will regenerate a normal epidermal structure. Re-epithelialization uses up a lot of proteins, both during the synthesis of the temporary matrix that acts as a protein highway for the new keratinocytes and during the intense mitotic activity that creates new skin cells. Proteins are absolutely essential to cell life; each enzyme in the body is a protein whose unique three-dimensional structure is responsible for its highly specific action. They have vital functions that are specific and strictly linked to their threedimensional structure. The spatial structure of proteins is altered by even the slightest increase in temperature;3 any thermal stress can ‘unfold’ the cell proteins, making them ineffective and leading to apoptosis (programmed all death). In laser or flashlamp treatments, the temperature of the target must be raised in order to destroy it, but the normal cells around the target also undergo sufficient heat stress to induce apoptosis or severely disrupt cell function. The rise in temperature thus creates a central zone of lesions that are lethal to cells, surrounded by a peripheral zone of sublethal damage in which the heat-damaged cells must be repaired or replaced. As a result, skin regeneration may be slower than it should be as the cells on the edge of the treated area grow and migrate. Preventive protection of the proteins in the cells surrounding the target, increasing their resistance to heat, can help enhance the skin healing process and reduce the incidence of complications associated with slow re-epithelialization. Where there is sublethal damage, or very light damage, the cells must eliminate or repair the damaged and ineffective proteins, increase protection of the proteins that did

resist the heat and synthesize new replacement proteins. This is where heat-shock proteins (HSPs or stress proteins) are necessary. HSPs were discovered at the beginning of the 1960s in the fruit fly in response to an increase in cell temperature of just a few degrees. These proteins were subsequently found in all types of living cells; they are secreted in response to any kind of stress, not only in response to increased temperatures. HSP70 and other similar stress proteins appear rapidly in the cytoplasm and mitochondrial matrix of cells that are subjected to stress. Essentially, their role is to ensure protein viability. HSP70 binds to polypeptide chains as soon as the latter have been synthesized in ribosomes (which translate RNA information into the amino acid sequence of the polypeptide) and facilitate the folding of these chains into the three-dimensional structure essential for protein activity. The HSP70 then separates from the folded protein. HSP70 is a member of a group of diverse proteins (also including HSP60 and the chaperonins) that play an essential role in creating the appropriate three-dimensional structures of other proteins – but do not themselves form part of that final structure. This group of proteins are also known as ‘molecular chaperones’ and have a fivefold role: do well as providing the correct spatial structure for a new protein coming out of the ribosome, they also protect the structure of existing proteins, repair damaged proteins by refolding them correctly, and act as protein transporters, carrying proteins from one place to another within the cell and eliminating proteins that are irreparable. Some HSPs are constitutional and others are inducible. The latter are synthesized in greater numbers after stress and give the cell increased resistance to future stress, thus allowing the cell more time to repair itself without having to resort immediately to apoptosis. With age, HSP function deteriorates in human skin, and aging cells are increasingly more prone to protein destruction.

Sun protection and HSPs It is therefore beneficial to boost the synthesis of HSPs in the cytoplasm and mitochondrial matrix of cells subjected to heat and light stress, thus improving not only their resistance but also their defenses and better equipping them to repair proteins in case of stress. An interesting disaccharide, trehalose (Figure 3.3), was isolated from cells of organisms that can survive in extreme conditions such as dehydration; having this disaccharide in sufficient concentrations allows these organisms to increase their resistance to the lack of water. It has been shown4 that trehalose can stimulate HSP70 production. An interesting experiment showed that this disaccharide increases cell viability after exposure to UVB. The study involved subjecting a culture of keratinocytes to a slight increase in temperature of 3°C for 1 hour in order to induce slight heat stress. The ker-

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H

H

H

HO O H

OH

O O

HO

OH

H

OH

HO

H

H

H

H

H

OH HO

Figure 3.3 Chemical structure of trehalose.

atinocytes were then cultured for 6 hours either in a medium containing trehalose or in a medium without the disaccharide. After 6 hours, the culture medium was replaced by physiological saline solution and the keratinocytes were exposed to UVB radiation. Cell viability was studied after 48 hours. There was a huge difference in keratinocyte survival in the cells from the different culture media: only around 4% of viable keratinocytes remain when cultured without trehalose eter, whereas the survival rate was nearer 40% in the group of keratinocytes cultured in the medium rich in trehalose (Figure 3.4).

Keratinocytes percentage survival

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40 35 30 25 20 15 10 5 0

0%

0.5%

1%

Trehalose eter concentration

Figure 3.4 The viability of keratinocytes exposed to UV after a 3ºC increase in temperature is very low: just a few percent. When cultivated in an environment rich in trehalose eter, the viability is close to 40% under the same conditions.

Specific care for different peels AHAs If an AHA peel is done correctly, no particular medical care is necessary, no matter what concentration or pH is used. In general, after an AHA peel, all that is necessary is good hydration and effective sun protection for 2 weeks. AHA peels weaken the barrier function of the stratum corneum

15

and thus increase its permeability; they make it easier for the active molecules to penetrate the epidermis when creams are applied both immediately after and between peeling sessions. The type of cream depends on the problem being treated. The results for acne treatment can, for example, be improved by applying a layer of anti-acne cream immediately after a ‘classic’ AHA peel has been neutralized and leaving it to act under an occlusive dressing5 for around 30 minutes. The patient can apply the same cream twice daily thereafter. The same applies for melasma and aging or sagging skin, etc.6 After an AHA peel, the patient’s daily care routine plays an essential role in determining the quality of the results. Mesotherapy can be combined with AHA peels in a number of ways: the ‘mesolift’ mixture7 can be injected before the peel or immediately after the peel has been neutralized and before creams are applied under occlusion. There is no danger of the glycolic acid penetrating beneath the skin through the perforations made by the mesotherapy needle. Most often, however, the treatments are alternated every other week: in the first week, the peel and the cream under occlusion are applied, and in the following week, the mesolift is injected, followed by the cream under occlusion. If an AHA peel is done correctly, there is usually no downtime. Nevertheless, there can be complications, which are described in Chapter 10.

Resorcinol Resorcinol in paste form9 is used in a very specific manner: the paste is usually applied three times, once a day for 3 days in a row. Post-peel care is very important during the following week: the skin should not be hydrated at all, as it has to dry out completely for the peel to be effective and, above all, the patient must not pull off or pick at the flaking skin. Only the doctor can safely cut off any strips of flaking skin with sterile scissors. Cosmeceutical creams for age spots, acne, aging or sagging skin, etc. should only be applied after the skin has flaked. Effective sun protection (UVA + UVB + HSP inducers) is absolutely essential for approximately 6 weeks after the peel. Downtime may be around 4–5 days. After the first application of the paste, the patient can usually have a normal social life, but subsequent applications dry out the skin and leave it looking papery.

TCA–SAS Trichloroacetic acid in simple aqueous solution (TCA–SAS) involves pre-peel preparation, application of the TCA–SAS solution to the required depth (usually the papillary dermis), flaking, natural skin regeneration and post-peel care. The post-peel period for TCA–SAS requires special attention and, even if the peel is applied correctly, pigmentary changes are the most common and benign complication. It

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is clear from the many illustrations in books on TCA–SAS peels that there is an astonishing variety of post-TCA pigmentary changes, with varying degrees of severity. If pre-peel prevention does not prove effective, or in cases of localized overpeeling, post-inflammatory hyperpigmentation (PIH) usually appears within a week after the peel in the form of dark patches or persistent erythema that will become pigmented under the effect of the sun’s rays. For more information, see the section on hyperpigmentation in Chapter 37. These genuine pigmentary changes should not be confused with the darkening of epidermal melasma appearing the next day after the peeling, and caused by dehydration of the hydrophilic spaces between melanosomes, which makes the skin seem to have a greater concentration of melanin and hence appear darker. This darkening, which is temporary, is a positive sign and will fade at the end of the first week. Flaking should not be helped along under any circumstances. Peeling off any bits of skin can result in uneven skin tone, infection, hyperpigmentation, scars or localized achromia. It is also essential to take preventive measures against infection after a papillary TCA–SAS peel, as the latter destroys most of the skin’s defenses. An antibiotic cream is applied during the first week after the peel. The skin should be cleaned before each application of cream, and any occurrence of contact allergies, which can sometimes be confused with secondary infections, should be monitored. The results of a TCA–SAS peel also depend on the quality and consistent use of cosmeceuticals after the peel. It is clear that a melasma treatment will produce better results if the TCA–SAS peel is followed by the application of a retinol–anti-tyrosinase–anti-oxidant cream or a hydroquinone-based preparation. For acne or aging or sagging skin, the same comments apply as for AHAs above. These creams can be applied as soon as flaking is finished, usually on the 7th day. Effective sun protection is absolutely essential and should be used in the first few days after the peel, before the skin has stopped flaking. Even a total sunblock is not enough to avoid pigmentary changes altogether, and the patient should be told to completely avoid exposure to the sun. Sun creams containing tanning accelerators should, of course, not be used after the peel.9 Chemical tanning with sprays containing dihydroxyacetone should also be avoided, as these products, which are non-toxic when picked up by the corneocytes and eliminated within 1 week, are not intended for keratinocytes, which are the cells exposed to the external environment during the first days after a peel. Downtime is around 1 week following a TCA–SAS peel, after which make-up can be used from the 8th day to cover up any persistent erythema.

Easy TCA® Easy TCA® is an exception among TCA peels, and should be distinguished from TCA–SAS, as it does not require pre-

peel care in the medium term nor any immediate pre-peel preparation, and pigmentary changes are very rare if the ‘basic protocol’ is followed.10 Some brown discoloration is possible after the first or second application, but this should fade after the following peel. Flaking skin can be peeled off or a light cosmetic scrub can be used. With deeper protocols, which are not usually necessary with this peel, there is a greater likelihood of complications. Combining Easy TCA® with appropriate post-peel cosmeceuticals helps improve and maintain results. The cosmeceuticals should be applied the day after the first peel and continued between sessions and for at least 6 weeks after the last application. As with any peel, effective sun protection is necessary to make up for the temporary loss of the stratum corneum. Easy TCA® causes the skin to flake, but not so much as to disrupt the patient’s social life, although certain activities may be compromised: television presenting, customer contact in the food industry, etc. Easy Phytic® is recommended in these cases as there is almost no visible flaking of the skin (see Chapter 11).

Phenol Phenol entails the most complex post-peel care: occlusive masks, healing masks and cosmetic care during the months following the peel. Chapters 25–36 are devoted to this technique. The expected downtime is between 7 and 15 days, depending on the formula used. The patient will have to wear camouflage make-up to hide any redness, which can last for several weeks or months.

Post-peel cosmetics Chemical peels do not always treat the underlying cause of a skin problem. For example, there can be many causes of acne, and chemical peels do not alter the synthesis of testosterone or the potency of the 5α-reductase that converts testosterone into its active derivative, dihydrotestosterone. Acne may also be partly due to excessive cell cohesion that blocks the sebaceous glands or to an immunodeficiency of genetic origin. Chemical peels do not alter an individual’s genetic make-up. Follow-up care should come after the peel, which is only the first phase of the treatment. Topical anti-acne treatments or cosmetics should be used between and after the peels to improve and prolong results. The same goes for blemishes, melasma and aging. Peels can provide quick cosmetic results, but it is the care between and afterwards that improves and maintains them. This is why the same peel may be indicated for the treatment of acne, which typically affects young patients, as for aging, which affects older patients. In short, we can say that chemical peels regenerate, restructure and stimulate the skin, and that care between and after peels widens their

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indications to problems such as acne, dyschromia and aging.11 There are cosmetic products that have been specially created for application very soon after a peel. They can be used the morning after the first AHA peel, Easy Phytic® or Easy TCA®. With TCA–SAS, Only Touch® or phenol peels, cosmetics usually are not applied until the 8th day after the peel. With Unideep®, an anti-oxidant cream (Renutriv ACE Lipoic Complex®) can be applied two days after the peel.

Treatment for acne Tretinoin should be avoided between and after sequential peels, as it would irritate the skin and increase penetration of the acids during the next peel. Other topical products can be used. Glycolic acid can be applied in low concentrations (8%); it makes the skin softer to the touch. Like retinol, it prevents pores from clogging, helps the pilosebaceous units to drain and stimulates skin turnover. Tocopheryl acetate can be used as an antioxidant to combat the free radicals generated by inflammation. Triclosan12 is antiseptic, anti-inflammatory and antimycotic. Glycyrrhetinic acid is used for its hydrating, antipruritic and anti-allergic properties. It stops patients scratching. Tea tree oil (Melaleuca alternifomlia) is extracted from an Australian shrub and has a similar action to benzoyl peroxide but without its pro-oxidant effects. It is antiseptic (antibacterial: anti-gram-positive and -negative), anti-inflammatory (it can suppress the production of pro-inflammatory mediators), antimycotic (anti-candida and anti-dermatophyte) and even antiviral, acting before and after viral adsorption. Other topical treatments can also be applied: azelaic acid, antibiotic creams, disinfectants, etc.

Treatment for hyperpigmentation Chemical peels are one of the preferred indications for hyperpigmentation. A number of cosmetics can be used between and after peels. Hydroquinone was used for a long time, and still is in many countries. Its cosmetic use, however, is forbidden in Europe. There are many depigmenting derivatives that can be used in its place. Kojic acid can be used pure or as an extract of Aspergillus, and has an antityrosinase and antioxidant action. It even potentializes leukocyte phagocytosis. Glabridin (a licorice extract) inhibits the pigmentation and erythema caused by UV; it is anti-tyrosinase and anti-inflammatory. Liquiritin contains glycyrrhizin and glycyrrhetinic acid (which are antiinflammatory as they inhibit the degradation of endogenous cortisol) and antioxidant flavonoids. Extracts of Morus alba contain arbutin and mulberroside F, which are both tyrosinase inhibitors. Mulberroside F is also an antioxidant. Transcutol® helps build up a reserve of active products near the dermoepidermal junction and improves

Figure 3.5 Blending bleaching cream, contains antityrosinases and antioxidants.

the action of tyrosinase inhibitors (Figure 3.5). AHAs can be used to enhance penetration of active products through the skin. Lactic acid has also been described as having a tyrosinase-inhibiting action. Finally, various vitamins (A, C and E) can be used in the treatment of hyperpigmentation: they are antioxidant and anti-inflammatory, protect against UV damage and stimulate epidermal turnover. The well-known Kligman’s formulas combine the action of tretinoin, a corticosteroid and hydroquinone, but are more irritating than medical cosmetics. The cosmetics used for hyperpigmentation should be applied very soon after the peels (if possible the very next day). If possible they should be applied two or three times a day, before effective sun protection. For more information on topical depigmenting agents, see the section on hyperpigmentation in Chapter 37.

Treatment for aging The author’s cosmetic post-peel treatment for aging skin is simple.

Patients under 40–45 years old The main thrust of the treatment is daily oxidation. In the morning, an antioxidant cream with vitamin E should be applied, and in the evening another anti-oxidant cream: Renutriv ACE Lipoic Complex®. Vit E Antioxidant® is a cream with a relatively complex but complete formulation. It does not contain AHAs, so

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can be applied daily without the risk of interference with the protective function of the corneocytes. It has been specially formulated for use very soon after a chemical peel. Its qualitative formulation is as follows: ■ Biosaccharides: these are polymers of the sugar, fucose. – They have filmogenic properties that induce immediate hydration. – They are slowly metabolized on the surface of the skin, giving a long-term hydrating effect. – They have an anti-inflammatory effect. ■ Ceramides: these are natural components of the skin. – They have an anti-aging action. – They have hydrating and protecting actions. – They encourage skin repair after different types of injury. ■ Vitamin E: this protects against anti-free radicals. The tocopheryl acetate used in this cream is one of the most stable derivatives of vitamin E, and forms a reservoir in the skin after penetration ■ Glycyrrhetinic acid: this is hydrating and anti-allergic; it reduces itching. ■ Natural moisturizing factor (NMF): this comprises amino acids + hexoses + urea + aspartic acid + hexylnicotinate ■ PFPE (perfluoro polymethyl isopropyl ether): this is a filmogenic polymer that protects the skin without any occlusive effect. Renutriv ACE Lipoic Complex® is ideal for dry skin, and can also be applied in the morning. With normal or oily skin, it is better applied in the evening. It does not contain any AHAs, for the reasons explained above. Its qualitative formulation includes the following ingredients: ■ ■ ■ ■

vitamin A: pure encapsulated retinol vitamin C: pure encapsulated ascorbic acid vitamin E: tocopheryl acetate lipoic acid

Lipoic acid exists in different racemic forms. Only the R form is active (Figure 3.6). Lipoic acid is absorbed rapidly both orally and topically. Enzymes in cell cytoplasm convert it into dihydrolipoate (DHLA). DHLA penetrates the cell and mitochondrial membranes easily. It is a mitochondrial cofactor that boosts mitochondrial activity at the

O HO

Figure 3.6 Chemical structure of (R)-lipoic acid.

SH

S

Fe2+

O O

O

S

S

O–

Fe2+

Figure 3.7 Iron chelation by lipoic acid.

same time as protecting against excess production of free radicals. Lipoic acid has the major advantage of being both fat-soluble and water-soluble, which means that it is active at all levels in the cell. It recycles vitamin C, when it is converted into the ascorbyl radical after acquiring a free electron, thus restoring its antioxidant activity. It also recycles vitamin E indirectly. Lipoic acid protects the natural enzymatic antioxidant defenses, such as catalase, coenzyme Q10, glutathione and cysteine. It is an iron, copper, mercury and aluminum chelator (Figure 3.7). It combats excessive secondary cell apoptosis resulting from various stresses.

Patients over 40–45 years old The fight against aging should take into account not only the damage caused by the various sources of cell oxidation but also the fall in hormone levels. For menopausal or postmenopausal women, a standard formula is testosterone propionate 100 mg, estrone 5 mg, estradiol benzoate 5 mg, and water in oil excipient ad 100 g. Extracts of Mexican wild yam (Dioscorea) can also be used, or other estrogen precursors or dehydroepiandrosterone (DHEA).

S H

S

Sagging skin – DMAE One of the common signs of aging is loss of skin elasticity. The skin appears devitalized and slack. One substance that

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A

19

B

Figure 3.8 A tightening effect can be seen after the first application of N,N-dimethylaminoethanol (DMAE) in the form of Skin Tech’s Actilift®: (a) before; (b) after. Photograph by John Jairo Hoyos, Colombia.

is of special interest in the treatment of sagging skin is N,N-dimethylaminoethanol (DMAE) (Figure 3.8). DMAE has been used for several years as a topical application to produce a ‘face-lift’ effect. Even if there is no doubt that it produces a tightening effect on the face, there is no definitive evidence regarding its mode of action. We will see below what type of skin structures respond to DMAE and why it would be difficult to explain this action by an improvement in tension of the striated muscle mass of the face.

Chemistry of DMAE DMAE (also called deanol, dimethylethanolamine and norcholine) is a small hydrophilic molecule. Its low molecular weight (89.1) allows it to penetrate the skin easily. DMAE is a precursor of acetylcholine (ACh), via choline (Figure 3.9). It is a viscous liquid, as transparent as water, that is often said to smell like ammonia but is in fact more reminiscent of fish long past its sell-by-date. Anchovies, sardines and salmon are important natural sources of DMAE. It is naturally present in the body, and there are traces of it in the brain. DMAE is a very basic molecule (pH 11) that cannot be used in its pure state without the risk of causing chemical skin burns. It must be partially neutralized for use at pH 7. Many derivatives have been used in its place (e.g. DMAE bitartrate or acetamidobenzoate), but these are more suitable for oral rather than topical use. DMAE formulations tend to give only the total dosage of the DMAE derivative used, of which pure DMAE is only

(CH3)2NCH2CH2OH DMAE (CH3)3N+CH2CH2OH Choline O > (CH3)3N+CH2CH2OCCH3 Acetylcholine

Figure 3.9 Chemical structures of N,N-dimethylaminoethanol (DMAE), choline and acetylcholine.

part of the weight. For example, 100 mg of DMAE cyclohexylcarboxylate contains only 33 mg of pure DMAE, while 350 mg of DMAE bitartrate contains 130 mg of pure DMAE. The author prefers to use a formulation with DMAE lactate (Skin Tech’s Actilift®) in order to benefit from the properties of an AHA (lactic acid) combined with the DMAE.

Side-effects and precautions The high pH of DMAE means that the pure compound should not be brought into contact with strong acids, mucous membranes or the eyes. Pure DMAE is also incompatible with copper and zinc. DMAE is volatile and should be contained in sealed tubes rather than bottles, to prevent its evaporation. Some cases of allergic dermatitis have been reported after prolonged contact with very high

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concentrations of DMAE, and it should be applied with extreme caution around the eyelids of atopic subjects. DMAE is not considered to be carcinogenic, cocarcinogenic or immunosuppressive. Chronic exposure to concentrated fumes of DMAE in the workplace can cause visual problems.

Toxicity DMAE has mostly been used orally. It is most widely available in 100 mg tablets for the treatment of cognitive disorders associated with senile dementia, at a dose of 600 mg/day. The LD50 for oral administration in rats is 2 g/kg. The LD50 in rabbits after application to the skin is 1.370 mg/kg. For subcutaneous injection in mice, the LD50 is 961 mg/kg. In a human clinical study,13 oral administration of 1600 mg/day showed no side-effects. The doses used in topical applications are nowhere near the theoretical toxicity limit. It takes a twice-daily application of around 30–50 mg of DMAE on the skin to improve skin tension and achieve the ‘lifting’ effect. It is important to remember that a topical application, even if it is very effective, cannot as yet compete with a surgical procedure. DMAE and N,N-dimethylisopropanolamine (DMIPA) solutions are used in high concentrations (45–50%) in industry, especially in the printing industry. They are used in sprays, and a study was conducted on their role in the appearance of intermittent corneal opacity in workers in certain types of printing works.14 The corneal opacities caused blurry vision on the way home from work. These problems were only evident from Mondays to Thursdays, but never at the end of the week. Eye tests revealed the appearance of intermittent and reversible corneal opacity, limited to the part of the cornea in contact with the droplets of vaporized solution and lasting just a few hours. A complete study was undertaken that put the blame on DMIPA but cleared DMAE of involvement. Lowering the concentrations of DMIPA without changing the concentrations of DMAE solved the problem once and for all and produced no visual sequelae. DMAE has also been claimed to be teratogenic. Studies on this subject remain controversial: some have shown that DMAE can be teratogenic in mouse embryos at high doses;15,16 other studies have shown no evidence of toxicity in rodents.17 In my knowledge nothing has been published on teratogenic effects in humans, and no research has shown teratogenicity in humans, despite the wide use of DMAE in industry.

Historical and ‘usual’ use of DMAE Procaine, which is used widely in mesotherapy, is one of the active principles of the well-known (and at times much

O  CO.CH2CH2N(C2H5)2

NH2

Figure 3.10 Chemical structure of procaine.

criticized) Gerovital H3 developed by Dr Ana Aslan of Rumania. Procaine or 2-diethylaminoethyl 4-aminobenzoate hydrochloride (Figure 3.10) was synthesized in 1905 by the German chemist Alfred Einhorn, who called it ‘novocaine’ (from the Latin novus = new, with the added suffix of cocaine, a gold-standard product up until then). Another German, Dr Heinrich Braun, introduced the use of novocaine in medicine. In the body, the ester link of procaine is hydrolyzed, yielding p-aminobenzoic acid (PABA) and N,N-diethylaminoethanol (DEAE), an analog of DMAE. It is PABA (Figure 3.11) that is responsible for the large majority of allergic reactions to ‘procaine’; it is excreted rapidly by the kidneys. PABA is most often used as a sunscreen, but is sometimes called ‘vitamin B-x’, although it is not essential for humans and the body cannot synthesize folate from PABA. According to some authors, the ‘Aslan’ method relies solely on the combined action of PABA and DEAE/DMAE. It is assumed that the action of PABA is due to its anti-free-radical properties. O NH2

C OH

Figure 3.11 Chemical structure of p-aminobenzoic acid (PABA)

Another local anesthetic used in mesotherapy, lidocaine, goes through a different metabolic pathway from procaine, being converted into monoethylglycine, xylididide (MEGX) and acetaldehyde. Its action in this context must therefore have a different basis from that of procaine. As well as having an anti-oxidant19 and anti-inflammatory effect, DMAE taken orally has been claimed to have many properties: an anti-aging effect, improvement of memory and intelligence, increased synthesis of acetylcholine, amelioration of depressive states, improvement in motor coordination, improvement in compulsive, impulsive, hyperactive or antisocial behavior, reduction of chronic fatigue and improvement in the quality of sleep, aid in giving up alcohol and tobacco, reduction of headaches, improved ability to concentrate, improvement in schizophrenia, improved muscle tone, and overall higher energy levels. DMAE can be incorporated into the membrane structure of cells, where its anti-oxidant properties improve

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membrane resistance to the oxidative stress resulting from the release of free radicals from the phospholipid bilayer and the production of eicosanoids associated with skin inflammation. The degradation of cell membranes and subsequent inactivation of the transmembrane proteins and receptors are considered to be the main factors responsible for cell aging. Carbachol (Figure 3.12), and the closely related bethanechol, is a powerful cholinergic agent (used to induce miosis). Its structure is similar to that of choline and its precursor, DMAE. Other muscarinic agents (e.g. pilocarpine), have a completely different chemical structure to choline. O 

(CH3)3N+CH2CH2CNH2

Figure 3.12 Chemical structure of carbachol. Note the similarity between part of the molecule and DMAE and choline.

Topical skin application of DMAE Topical application of DMAE has a visible tightening, firming effect, often called the ‘lifting effect’. This tightening effect can already be felt 20–30 minutes after the product has been applied to the skin, and, when only one side of the face is treated with DMAE, the difference in tension between the two sides is clear. Skin tension continues to improve during the first 6 months of twice-daily application, with individual variations, and remains stable for 4–8 weeks after topical treatment is finished. This would seem to indicate that the product accumulates in the skin and forms a reservoir.

Potential mode(s) of action of DMAE DMAE is a precursor of choline; it also inhibits the metabolism of choline in the tissues. As there is more choline available, the biochemical reactions may tip the balance towards an increase in ACh synthesis. DMAE may stimulate macrophage activity and improve the skin’s defenses. The mode of action of DMAE is not yet fully understood, and its action as a local application even less so. We must therefore put forward several hypotheses in an attempt to understand this tightening effect.

Action on the striated facial muscles Botulinum toxin (BTX), which is used to ‘smooth the skin’, like DMAE, acts on ACh, although its action is the reverse

21

of that of DMAE. BTX relaxes the muscles, whereas DMAE increases muscle tone. Are these two compounds therefore incompatible? It appears not, as they have different targets, and the muscle cells that are deactivated by BTX are not the same as those activated by DMAE. BTX is a large molecule with a high molecular weight, which means that it cannot pass through the skin when applied topically. To achieve a cosmetic result, BTX must be injected directly into the muscle to be paralyzed. BTX has no effect on the epidermis or dermis, as it blocks cholinergic transmission in the neuromuscular junction of the striated muscles and in this way limits the facial expressions that cause expression lines. BTX is picked up immediately, and there is no chance of it diffusing up through the hypodermal fat layer. DMAE, on the other hand, is a very small hydrophilic molecule with a molecular weight of 89.1 that can easily penetrate the epidermis and the dermis but cannot penetrate the hypodermal fatty layer. DMAE cannot act on the striated muscle groups that produce voluntary facial movements, and so cannot counter the effects of BTX. This physiological hypothesis is confirmed clinically when the two treatments are used together. The physicochemical properties of DMAE give this molecule a great affinity for the dermis and epidermis. As the action kinetics of DMAE lead to the hypothesis of a cutaneous ‘reservoir’, this could only be located in the deep epidermal layers, as, if it was in the dermis, this small molecule would soon be eliminated by venous or lymphatic resorption because of its concentration gradient. The way in which they are administered, their targets, their characteristics and their different modes of action do not make BTX and DMAE incompatible: administering one will not alter the effectiveness of the other. There is no established link between age-related sagging skin and muscles and a deficiency in ACh in the muscles. Any action of DMAE on striated facial muscles is thus not only unlikely but also pointless. We must therefore look for other more likely modes of action than muscle stimulation, especially as there have been reports of improvements in tone and younger-looking skin around the eyes and lips after only a few days of treatment. Given that it is accepted that paralysis (or hypotonia) of the muscles by BTX ‘smoothes’ the skin, it would be illogical to claim that stimulating the same muscle groups (with DMAE) can give similar results. We must therefore look elsewhere: in the skin structures that have cholinergic receptors.

Epidermal action Human keratinocytes express cholinergic receptors in the cells of the stratum basale, the stratum spinosum and the stratum granulosum. They use ACh, among other things, to stick together. They also synthesize, store, degrade and release ACh. ACh synthesis has been shown to occur in the perinuclear regions of human keratinocytes due to the presence of

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a choline acetyltransferase (this enzyme converts acetyl coenzyme A into ACh). On the other side of the cell, inside or near the cell membranes, an acetylcholinesterase has been identified. This enzyme degrades ACh in order to prevent a toxic build-up. Keratinocytes can move, which is essential during the second phase of healing, thanks to cytoplasmic myosin and actin: the actin moves in relation to the myosin when the two interact,19 in the same way that an oar stroke moves a kayak or an athlete runs on a treadmill (the athlete representing the myosin and the treadmill the actin). It has recently been shown, by immunohistochemistry, that there are free nerve endings in all of the layers of the epidermis, and it is now suspected that keratinocytes have a neurotropic function. The ACh acts locally, in the epidermis, like a hormone that can also be a ‘messenger’ stimulating the dermis. We can then suppose that an epidermal reservoir of DMAE can interact with the dermis via ACh, of which it is a precursor. DMAE is also assumed to inhibit formation and enhance elimination of lipofuchsin, a waste product of the aging cell metabolism of fatty acids. Experiments have shown that lipofuchsin is eliminated from the liver by DMAE. This build-up, which occurs in all organs, has not been associated with any disorder apart from lentigines. Some authors have reported a gradual reduction in lentigines on the hands with oral DMAE treatment. To date, there have been no studies published on the topical use of DMAE in the treatment of lentigines.

Dermal action DMAE is used for its antioxidant properties, membrane stabilization and inhibition or repair of protein cross-links that clearly play a role in the aging process. It could thus help maintain good-quality collagen and elastin and slow down dermal aging.

that contribute to the overall rejuvenating effect observed when DMAE is applied topically.

Effect on myofilaments and smooth muscle cells Myofilaments make up the endoskeleton of a cell (Figure 3.13). They can be found in the smooth muscle cells (SMCs) and in the cytoplasm of ‘non-muscle’ cells, where they are capable of moving and contracting. SMCs can regulate contraction far more subtly than striated muscle cells. SMCs can shorten to a greater extent than striated muscle cells. Shortening of striated muscle cells is limited to movement within the sarcomere, whereas with SMCs, the myosin filaments can move over a far greater distance, along the network of actin filaments in the cytosol. The force generated by SMCs is less than that generated by striated muscle cells, but can be sustained for much longer. The arrector pili muscle is under adrenergic control and does not respond to a local increase in ACh concentration. The fibroblasts and myofibroblasts are very interesting cells as far as the possibilities of the action of DMAE is concerned. Fibroblasts have cytoplasmic myofilaments that help them move in the dermis when necessary.20 There are different types of fibroblast subpopulations. Some authors maintain that these different subpopulations expand when they are needed through different phenotype expressions, whereas others believe that these subpopulations coexist permanently in the dermis. These two hypotheses are not incompatible. Myofibroblasts (MFBs) are phenotypically modified fibroblasts that have the secretory capacity of fibroblasts, which helps them synthesize strong fibronectin fibers. They express the phenotypic characteristics of ‘nonmuscle’ cells, but with the contractile capacities (of SMCs) that make them responsible for most of the phenomena of fibrotic contraction in the body. The fibronectin fibers syn-

Vasomotor effect The dermal blood vessels are innervated by adrenergic fibers, which cause vasoconstriction, and cholinergic fibers, which cause vasodilation. DMAE, as a precursor of ACh, could cause vasodilation that is clinically undetectable but sufficient to produce temporary edema, a build-up of water in the hydrophilic structures of the dermis, and, as a result, a tightening of the skin. This hypothesis only partly explains the particular kinetics of topical DMAE. The fact that treating one side of the face only shows improvement on one side only suggests that the DMAE has a purely local action and is not converted into ACh throughout the organism. Local blood flow, which decreases with age, is vital for the nutrition and defense of the dermis and epidermis. Constant slight vasodilation would thus improve skin perfusion – especially in smokers – and by diffusion would bring in more of the elements

Network tightened with actin microfibrils

Direction of displacement ‘Stress’ contractile fibers + Microtubule

+ Cellular center Nucleus

Radial network with actin microfibrils

+ +

+

+ + Dense bodies

+

+

+

Loose network with actin microfibrils in all cytosol

Figure 3.13 Different types of organization of actin microfibrils (MF) and microtubules (MT) in a moving cell – organized polarization of the MF and the MT.

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thesized by the MFBs serve as a support for them to ‘pull’ on during contraction, which helps the wound to close by as much as 40%. MFBs synthesize far more actin fibers than ‘standard’ fibroblasts, and also have myosin fibers that, when interacting with actin, constitute the contractile motor activity of MFBs. MFBs are found in healing tissue, of which they form 40% of the total number of fibroblasts present. A large number of MFBs are also found in the periprosthetic capsule of encapsulated breast implants, while there is no evidence of MFBs if no capsule has formed around the prosthesis. In pathology, abnormal quantities of MFBs are found in diseases such as pulmonary fibrosis and Crohn’s disease. Many SMCs respond to a kind of paracrine stimulation, where the mediator is released into the environment of the target cells and diffuses towards the cell, where it interacts with a membrane receptor. MFBs are not linked to any synapse, which would make it impossible for them to move, but the exposure of MFBs to certain mediators causes significant contraction, comparable to that in SMCs. We can imagine the contractile potential of these SMCs when we recall that the nipples, as well as the scrotum, have many contractile cells of this type that are sensitive to different stimuli. The difference is that the contraction of MFBs during wound healing is irreversible. Fibroblasts and MFBs, like many SMCs, have numerous receptors on their surface for different mediators: ACh, adrenaline (epinephrine), noradrenaline (norepinephrine), oxytocin, vasopressin, histamine, angiotensin II and prostaglandins. As ACh is a small water-soluble molecule, its membrane receptor can be a ligand-gated ion channel receptor or can be coupled with the heterotrimeric G proteins (RCPGs) that control the activity of a target protein, which can be an enzyme or an ion channel. Opening and closing of the ion channels causes polarization or depolarization of the myofilaments, and the SMCs (e.g. endothelial cells) contract or dilate. The G protein acts as a transducer. As ACh is a small ligand, the N-terminus of the G protein in the extracellular environment will be small. The presence of a larger quantity of ACh in the pericellular environment of the MFBs could then stimulate certain membrane receptors more strongly and increase their contractile potential. DMAE, a precursor of ACh, might then stimulate the contraction of MFBs. However there must be a reactivity threshold for MFBs to ACh, to guard against unnecessary contraction of these cells and the formation of pathological fibroses. The hypothesis put forward here is that a slight increase in the extracellular concentration of ACh (by conversion from DMAE) could slightly stimulate the contraction of the fibroblasts and do so reversibly, without fibrosis setting in, as, clinically, the effect of a topical application of DMAE is reversible 4–8 weeks after treatment has stopped. This improved tone, the reversible contraction of the fibroblasts, could explain the clinical kinetics of DMAE in a topical application.

23

Exocrine glands The sweat glands have cholinergic innervation.21 The eccrine sweat glands, which open directly onto the skin, have denser autonomous innervation than the apocrine sweat glands associated with pilosebaceous units. ACh is the active neurotransmitter at this level, and the response of the sweat gland will depend on the dose of ACh that stimulates it. The myoepithelial cells contract in response to the ACh. In strong doses,22 the muscarinic receptors are stimulated, and the gland reacts by producing large drops of sweat. At lower concentrations,23 the nicotinic receptor is stimulated, and the gland will react by producing tiny droplets of sweat. The possible increase in ACh caused by the application of DMAE cannot, of course, stimulate the muscarinic receptors, and no profuse sweating has been noted after application of DMAE. On the other hand, a slight increase in the concentration of dermal ACh could stimulate the sweat glands’ nicotinic receptors – in a paracrine manner – and increase hydration of the stratum corneum, making the skin more ‘supple’ and resistant. The sweat glands themselves are controlled by circulating hormones and are not under cholinergic control. DMAE will not alter their function.

Conclusions DMAE is a precursor of ACh, a neuromediator that is important to the skin. Keratinocytes, as well as fibroblasts, myofibroblasts, sweat glands and endothelial cells, have receptors that respond to ACh. They are not stimulated pre- or post-synaptically but by paracrine diffusion, which can activate specific membrane receptors. The hypothesis is that DMAE in a topical application cannot stimulate the striated muscle fibers, to which it has no access. Furthermore, muscle sagging associated with aging is not caused by a deficiency in ACh. The tightening effect of DMAE may result from cholinergic stimulation of the membrane receptors of (myo)fibroblasts and stimulate the gradual contraction of the myofilaments in their cytosol. DMAE also has anti-free-radical and anti-lipofuchsin activities and repairs protein (collagen and elastin) cross-linking. The mode of action of topical DMAE could therefore stem from a combination of effects working together at different levels: tension of the ‘non-muscle’ dermal cells, keratinocyte cohesion and movement, hydration and suppleness of the stratum corneum, improved skin nourishment and defense, antioxidant, and skin tone evener. As a result, it is very effective at improving skin tone and firmness.

Summary of the main cosmeceuticals used post peel See Table 3.1 for a list of post-peel cosmeceuticals according to skin type, together with their times of application.

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Table 3.1 Main cosmeceuticals used post peel Skin type

Daily care product

When and how often to apply

Sagging skin

Dimethylaminoethanol (DMEA): Actilift® face cream or Actilift® body lotion (Figure 3.14)

Morning and evening

Patients under 40–45: skin aging

Vit E Antioxidant®

Morning

Lentigines

Re-Nutriv ACE Lipoic Complex®

Evening

Patients over 40–45: skin aging

DHEA–PHYTO®

Morning

Lentigines

Re-Nutriv ACE Lipoic Complex®

Evening

Acne

Purifying cream or gel Purifying cream or gel

Morning (all over) Evening (only on the lesions)

Hyperpigmentation (melasma–lentigines) (Avoid exposure to sun: Melablock® HSP 50+ at 9 AM, 11 AM, 2 PM; serious cases: 3–4 times a day)

Blending Bleaching® cream

Morning (all over)

Blending Bleaching® cream

Evening (only on the lesions)

Dry skin

Vit E Antioxidant®

Morning, midday, evening

Post-peel sun protection

Melablock HSP® 50+

Every 3 hours

Everyday sun protection

Melablock HSP® 25+

Every 3 hours

Trolamine Trolamine (triethanolamine salicylate, TEAS) is a salicylate derivative, which is also known as ‘topical aspirin’. It is an amino alcohol that is used for its topical analgesic and antiinflammatory properties. Like the better-known salicylate derivative, methyl salicylate – which has a rubefacient action used to good effect in sports injuries and rheumatism – TEAS is rapidly absorbed through normal skin after topical application. It is used widely for treating sunburn.

of mild erythema, while a superficial second-degree burn consists of painful blisters but does not reach the dermis. Medical advice is essential before applying the product to a second-degree burn.

Mode of action and absorption Various studies show that salicylate derivatives act as much through direct local diffusion as through absorption by the dermal blood vessels and redistribution of salicylates in the whole body. The blood level of salicylates increases in direct proportion to the quantity applied, the resorption surface and the number of topical applications. A large amount of salicylates can be absorbed through the skin. When TEAS is applied unilaterally on one limb, the concentration of salicylates has been found to be identical in the corresponding tissues of the contralateral limb. This supports the theory of action by redistribution through the blood. The use of radiolabeled TEAS also shows renal and fecal elimination. Phonophoresis helps salicylates penetrate further into the skin.

How to apply trolamine Salicylate derivatives, especially trolamine, are applied to first- and second-degree burns. A first-degree burn consists

Figure 3.14 Actilift® cream with pure DMAE. There is a face cream and body lotion.

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Post-peel care

Precautions Trolamine must not be applied in cases of infection: salicylates can accelerate the penetration of microbes into the skin and aggravate any pre-existing infection. It has been shown to cause local skin irritation and scabs to form on the areas to which it has been applied. Skin irritation increases the more it is applied. In smaller quantities, repeated application only induces epidermal hyperplasia. Some authors consider TEAS to be a potential cytotoxic agent. It is a potential skin irritant that makes the skin sensitive and can cause contact allergies. Trolamine is a salicylate derivative, and salicylic acid is a keratolytic agent that dissolves the intercorneocyte amorphous matrix and impairs the barrier function of the stratum corneum. Symptoms of salicylism can appear with chemical peels when large amounts of salicylate derivatives are applied on the skin, on large surface areas or repeatedly, causing a high blood level of salicylates. In cases of toxic levels of salicylate in the blood, an increase in oxygen consumption causes hyperthermia by the uncoupling of oxidative phosphorylation. Trolamine should therefore not be used during the immediate post peel period.

Tips for the care of sensitive skin ■ Prolonged use of creams containing more than 8–10% of AHAs can make some skins more sensitive by reducing the thickness of the stratum corneum for long periods. ■ Use cleansing milks, lotions or mineral water sprays to wash. ■ Do not let water dry on the skin; when it evaporates, it soon dries the skin out. Damp skin should be dried with a soft cloth or paper tissues. ■ Avoid exfoliating scrubs, repeated micropeels and creams containing microcrystals on sensitive skins. Do not use any masks that might dry out the skin. ■ Do not use aggressive soaps. ■ Tretinoin (vitamin A acid) makes the skin more sensitive. One Easy TCA® peel per week for 4 weeks can restructure the skin and eliminate any abnormal sensitivity. In this indication, the cosmeceuticals that can be combined with it are restricted to Vit E Antioxidant® cream in the morning and the more nourishing Renutriv ACE Lipoic Complex® cream in the evening.

Characteristics of ‘normal skin’ Normal skin should be:

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■ Firm: contain a sufficient quantity of elastin and collagen ■ Soft: compact stratum corneum protected by skin lipids ■ Hydrated and unwrinkled: hydrated keratinocytes and dermis ■ High in color: active microcirculation; pink color visible through the skin ■ Resistant to external aggression: active protective function •■ Unscarred: no stellate or secondary scars

Notes 1. Even though this type of sunscreen can protect the skin against free radicals some could also cause post-inflammatory hyperpigmentation. 2. SPF 50+ protects the skin against 98% of UV, while SPF 25+ protects against about 96% of UV. 3. A typical example of this is seen when cooking an egg white as it goes from transparent to white as a result of structural modification of the proteins under the effect of heat. 4. By polymerase chain reaction (PCR). 5. Occlusion consists in applyng an impermeable plastic film. 6. In the case of sagging skin, Actilift® face or body can be applied as appropriate. 7. Example of mesolift mixture: 2.5 cm3 non-cross-linked 2% hyaluronic acid + 2.5 cm3 organic silicium + 2 cm3 vitamin C + 2 cc of NA-nocleinate + 1 cm3 lidocaine. 8. Unna’s paste (see Chapter 24). 9. Molecules similar to tyrosine are used: e.g. Tyrosilane C®. 10. Summary of Easy TCA® ‘basic protocol’: no pre-peel treatment, application of the solution until scattered pinpoint or cloudy white frosting appears, application of the post-peel cream (tyrosinase inhibiting, anti-oxidant, stimulating). Repeat this process four times at weekly intervals. 11. This paragraph particularly concerns superficial peels or peels to the ‘Grenz zone’. Papillary dermal peels are not really indicated in cases of active acne. 12. Triclosan can be used as it is or encapsulated in cyclodextrins. 13. Casey DE, Denney D, Dimethylaminoethanol in tardive dyskinesia. N Engl J Med 1974; 291: 797. 14. NIOSH Publications Office. Health Hazard Evaluation Report 2002-03 79-2901 Superior Label Systems. May 2003; Cincinnati; Ohio. 15. Fisher MC, Zeisel SH, Mar MH, Sadler TW. Inhibitors of choline uptake and metabolism cause developmental abnormalities in neurulating mouse embryos. Teratology 2001; 64: 114–24. 16. Fisher MC, Zeisel SH, Mar MH, Sadler TW. Perturbations in choline metabolism cause neural tube defects in mouse embryos in vitro. FASEB J 2002; 12: 619–21. 17. Leung HW, Tyl RW, Ballantyne B, Klonne DR. Developmental toxicity study in Fischer 344 rats by whole-body exposure to N,N-dimethylethanolamine vapor. J Appl Toxicol 1996; 16: 533–8. 18. The antioxidant effect of DMAE has been shown by electron spin resonance (ESR) for the hydroxyl radical. It does not seem to have any anti-superoxide action.

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19. There are different types of myosin for different types of movement; cell movements (myosin II) are not facilitated by the same myosin that permits endocytosis (myosin VI) or the movement of vesicles between cells (Myosin V). 20. For example, movement along the fibrin/fibronectin fibers during the healing process.

21. Catecholamines, vasoactive intestinal peptide and natriuretic peptide have also been detected near the sweat glands. 22. Intradermal injection of 0.1 mg of ACh: postganglionic cholinergic stimulation (Biology of the Skin: 58). 23. Hurley HJ. The eccrine sweat glands: structure and function. In: The Biology of the Skin, Parthenon Publishing, Lancaster 2001; 47–76.

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4 Factors influencing chemical peels

Allergies These are common when using antibiotic creams or ointments in the post-peel period: between 5% and 10% of allergies should be expected when using antibiotic creams containing neomycin after a peel. The temporary thinning of the stratum corneum allows products applied on the skin after peels to penetrate more easily, which promotes the development of contact allergies.

Infections These are more common when patients have to undertake complex post-peel care themselves. The basic principles of sterility are not widely known by the public and require special training in order to be effective. The more patients have to take part in the post-peel care, the higher the risk of infection.

Pulling off small scabs This often leads to infection, prolonged erythema and even scarring. The less patients touch their skin, the better!

The sun It should be remembered that direct exposure to the sun for 10 minutes is enough to trigger pigmentary changes in sensitive individuals during the post-peel period. See the section on effective sun protection in Chapter 3.

line® immediately improves the pruritus and the feeling of tightness in the skin after a medium or deep peel. Sterile white Vaseline® is an excellent topical ointment that can be applied to the treated areas in the first few days after a medium peel or after removing the healing mask (after the 8th day) following a phenol peel. Only a thin layer need be applied to avoid itching caused by the drying out of surface keratinocytes that have not yet differentiated into corneocytes. The Vaseline® creates an impermeable layer on the surface of the skin and prevents the water in the epidermis from evaporating. The water accumulates under the layer of Vaseline® and provides instant natural hydration that soon relieves the itching caused by the keratinocytes drying out.

Influence of age post peel Older patients Intraepidermal and dermal peels are performed as usual even on patients aged 80 or over. With elderly people, there seem to be fewer pigmentary changes, but the theoretical risk of infection is higher. In theory, the weakened capacities of the keratinocytes to regenerate, the presence of numerous cell abnormalities, dormant fibroblasts and underlying vascular sclerosis should slow down healing after a peel in older people. In practice, the only real problem is increased susceptibility to infection resulting from a weakened immune system. A more important factor seems to be the degree of skin photoaging rather than age itself. Many phenol peels have been performed on patients who are well into their 80s, without any particular problems.

Young patients Dehydration of the skin after a peel Drying and flaking skin causes an irresistible urge to scratch and therefore a risk of complications (including secondary infections, inflammation and scars). Applying white Vase-

At the other end of the scale, what is the minimum age for having a chemical peel? The answer is simple: in the majority of cases, a peel is only necessary for young patients if they have acne. Acne responds extremely well to intraepidermal peels or peels to the basal layer of the epidermis. Deeper peels are not recommended when the skin is infected. Very young patients benefit from relatively superficial techniques

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with a high safety level (Easy Phytic®). The presence of acne means that the young patient’s developing hormone system has created an adult skin – thick and oily and resistant to acids.

Use of corticosteroids Topical corticosteroids These are only indicated in cases of serious edema or pruritus during the first few days after an aggressive peel. It is always best to start with a short-acting corticosteroid (hydrocortisone or betamethasone). A cortisone-based cream can be used during the first few days after a peel to reduce excessive edema or pruritus. The deeper the peel, the greater is the need for emollients. Hydration after a peel is vital (except after a peel with Unna’s paste); the hydrating cream should contain no alcohol or perfumes.

Oral corticosteroids These are very rarely indicated in combination with peels, and then only in the case of very specific problems (see Chapter 37).

Intravenous corticosteroids These can be used before a deep peel to limit edema immediately after the peel and avoid any allergic or laryngeal reactions.1 They reduce post-peel inflammation, which is in fact necessary to initiate the skin repair processes. If the degree of inflammation is reduced, there is a risk of slowing down the first stages of skin regeneration.

Understanding the healing process Understanding the skin healing process after a peel allows evaluation of the risks of scarring, infection and dyschromia. For more information on how the skin heals in relation to the depth of the peel and on risk evaluation, see the section on scars in Chapter 37. Histologically, the skin healing process follows a precise sequence of different stages. The process starts almost immediately: neutrophils enter the treated area as soon as the peel has been applied, and stay there for 3–5 days. Macrophages are present from the 3rd to the 10th day and lymphocytes from the 6th or 7th day. Re-epithelialization starts just 24 hours after the peel and first manifests as a centripetal migration of keratinocytes, followed by rapid cell proliferation. After the re-epithelialization phase, dermal collagen is regenerated over a 2- to 3-month period. Assessing the final results of a peel calls for patience.

How quickly the skin regenerates after a medium peel depends on the concentration of pilosebaceous units (PSUs) in the treated area: the face has many PSUs, and the nose and forehead have more than the cheeks and temples. Statistically, the cheeks and temples prove more sensitive to scarring. The dermis of the eyelids is thinner but denser than the rest of the face, and the dermoepidermal junction is flatter. The skin on the back of the hand has few PSUs and little subcutaneous fat. Atrophy develops there fairly rapidly. The skin on the back is very thick, and its dermis is dense in collagen. Nevertheless, it has fewer PSUs than the face, and the risk of developing post-peel scars there is higher. The dermis of badly sun-damaged skin has a depleted cell population, and is thin and slower at detoxifying acids. The effect of the acids is therefore increased, and peels on sun-aged skin are more dangerous than on young, well-hydrated skin. Moreover, skin with actinic damage has fewer appendages (PSUs), and tends to regenerate more slowly. Healing is slower when a wound is left to heal in the open air than when the wound is covered. This does not matter much for intraepidermal peels, but is more important when dealing with medium or deep peels. One advantage that peels have over laser treatments is that they leave a layer of dead, but protective, skin in place, and this enhances re-epithelialization. The strips of skin that remain after a peel should be left alone, as they protect the regenerating skin. Lasers, on the other hand, gradually vaporize the layers of skin to be removed, and the skin is left to heal uncovered. The colloid dressings available on the market (e.g. Convatec, Omniderm, Vigilon) allow better-quality healing, in a moist environment, after laser treatment. The problem with occlusive dressings is that there is an increased risk of infection, and they need to be monitored carefully, as bacteria are known to proliferate much more quickly under an occlusive dressing than in the open air. As bacterial proliferation increases under occlusive dressings and as the skin’s immune defenses are reduced after a deep peel, it is often preferable for the skin to heal ‘under a scab’. To do this, a mask of bismuth subgallate should be used (Figure 4.1, and see Chapter 35).

Preparing the skin This is worthwhile when the patient is willing and when it is carried out under medical supervision. Unsupervised or secret use of aggressive products by the patient can sometimes cause problems for the doctor who has not been informed of the patient’s self-administered treatment. The doctor should watch out for unacknowledged use of tretinoin or other retinoids, concentrated glycolic acid, benzoyl peroxide, or any other product that increases penetration of the acids, making them penetrate more quickly and deeply than originally intended. Some patients can

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The fact that in most cases they cannot use camouflage make-up makes it difficult to carry out a local or full phenol peel. Moreover, phenol peels produce less spectacular results on thick skins than on thin skins. Shaving does not pose a problem, as a peel to the basal layer of the epidermis does not rule out shaving, even with a blade. For a peel to the papillary or reticular dermis, it is best not to shave while the skin is flaking. It is usually possible to shave after the 8th day. Alcohol-based aftershaves should be avoided, and a hydrating, anti-oxidant or firming cream should be used instead, followed by effective sun protection.

Make-up Figure 4.1 After a phenol peel the crust of bismuth subgallate appears dry but actually helps healing in a moist environment.

turn up with their skin thoroughly scrubbed (with an abrasive sponge or creams), wanting to impress the doctor with skin that is nice and clean, but also hyperpermeable and dangerous.

Skin color This must be taken into account when choosing a peel: Fitzpatrick skin phototypes I–III can tolerate any kind of peel. Patients of type IV with light-colored eyes have fewer problems with dyschromia after a peel than dark-eyed patients of the same type. Type V and VI patients are at most risk with peels, and it is recommended not to go beyond the papillary dermis with these patients to avoid hypochromia. Type V patients are also quick to develop hyperpigmentation. Special care should be taken with patients who have prolonged hyperpigmentation with mosquito bites or small wounds. Localized phenol peels should only be carried out on patients with a skin phototype lower than IV, so that the area treated with phenol is not left lighter than the surrounding skin, even if it has been treated with a medium peel to even out the color. The same applies to patients with many freckles, which mostly disappear after a peel to the papillary dermis.

Patients often ask about make-up. The general principle is that it is possible to wear make-up, even when the skin is flaking, after an epidermal peel or a peel to the basal layer, but it is unlikely to look good. After a peel to the papillary or reticular dermis, make-up is usually allowed, and even recommended, on the 8th day. Patients who do not like wearing make-up should be warned of the likelihood of post-peel erythema, depending on the depth of the treatment. Some patients are thus ruled out, as their professional lives do not allow any visible erythema or they cannot stand the idea of wearing make-up. In these cases, it is recommended to repeat an Easy TCA® peel four times rather than use Unideep®.2

Smoking and peels It is generally accepted that the free radicals produced each time smoke is inhaled contributes to the overall aging of the body and of the skin in particular. Publications that show the difference in skin quality between two twins, one of whom is a smoker and the other not, speak for themselves, so marked is the deterioration of the smoker’s skin. Smoking causes repeated vasoconstriction and chronic microvascular damage, which contribute to the overall impoverishment and aging of the skin. There are no major problems, however, with heavy smokers who have peels to the papillary dermis. Full-face phenol peels should be carried out with caution because of the increased risk of laryngeal edema. A localized phenol peel does not pose this kind of problem, and phenol can, for example, be applied around the edges of the mouth (which is usually very damaged in smokers), while the rest of the face is treated with a trichloroacetic acid peel to the papillary dermis.

Chemical peels for men There is an increasing demand from men for basic treatments. Their skin is thicker, and results are not as good as for women. On the other hand, as men have more PSUs, they heal more quickly and pose fewer risks of scarring.

Mental retardation and peels The more severe the retardation, the more superficial the peel should be. The same applies to hypersensitive patients.

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Nutrition and peels The patient’s nutritional condition at the time of a peel is an important factor in the treatment. For all the phases of healing to take place correctly, a perfect balance of nutrition and micronutrition is necessary. It is clear that poor nutritional balance will have more impact on healing after a deep peel than after a light peel – all the more so as deep peels, rather than light peels, are usually intended for older people. Many proteins are synthesized during healing after an intraepidermal peel: many amino acids are needed to form the provisional matrix as well as to synthesize new collagen. Catabolic patients, or patients who have recently had significant, involuntary weight loss, do not have sufficient protein reserves for the skin to regenerate properly. A dermal peel also induces stress, which causes a hypercatabolic state that is more or less acute depending on the depth of the peel. Patients with insulin-dependent diabetes or patients who have recently undergone significant trauma or surgery, who have liver or kidney deficiencies, or who suffer from chronic inflammation are not the best candidates for dermal peels, as the need for protein increases sharply. The average daily protein requirement is 1.5 g/kg per day. The amino acids considered most essential include arginine and glutamine. However, to date, it has not been proved that supplements improve the quality of wound healing. Arginine is a precursor of proline and collagen, and the recommended dose is between 15–25 g/day. It acts as a local stimulant of lymphocytes and a general stimulant of human growth hormone (HGH) and insulin-like growth factor I (IGF-I) production. Glutamine also stimulates the production of HGH, and is an anti-oxidant and an energy source for fibroblasts, keratinocytes, lymphocytes and macrophages. A daily intake of 10–30 g/day is recommended.

Carbohydrates and fatty acids are also necessary for rapid and good-quality skin regeneration. The extracellular matrix is made up of glycosaminoglycans and proteoglycans, which are polysaccharides linked to proteins. Omega6 fatty acids are essential for cell membrane formation. Supplements of linoleic and linolenic acid can be recommended when the patient’s blood is not properly balanced.3 Numerous trace elements are necessary for many enzymes to function properly: copper is needed for the formation of the collagen network and the anti-oxidant action of superoxide dismutase; iron is needed for collagen synthesis; zinc is a cofactor for DNA and RNA polymerases, plays a part in protein synthesis and stimulates cell division. Vitamins also play a role in the healing process. Vitamin A is involved in angiogenesis and keratinocyte differentiation, stimulates collagen synthesis, and enhances intercellular adhesion and skin immunity. Vitamin E can be used as a lipophilic antioxidant. Vitamin C is necessary for collagen synthesis, and for stabilizing the collagen triple helix. Between 500 and 1000 mg/day can be given before and after an intradermal peel.

Notes 1. 2.

3.

Preventing laryngeal edema in smokers undergoing a phenol peel. Unideep® (Skin Tech) TCA peel: to the papillary dermis, with a qualitative formulation based on Easy TCA®, but with a more concentrated solution and post-peel cream. The Roman Pais laboratory in Nivelles, Belgium, provides – among other nutritional and micronutritional tests – a very precise and scientifically annotated blood count of circulating fatty acids.

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5 Choosing the right peel

The possibilities for treatment with chemical peels are many and varied and depend on the agent chosen as much as on the way in which it is used. We can, of course, take the narrow view of peels as the destruction of damaged tissue with acid.1 From this perspective, a result can only be achieved by ‘destroying beneath the lesion’. This is, of course, often the case, but we must not forget that chemical peels help to stimulate as much as destroy. Many of their positive effects are largely due to this stimulation. Let us take glycolic acid, for example, whose action is mainly intraepidermal2 but which is associated with activation of the papillary dermal fibroblasts. The destructive effect, which removes the stratum corneum and even part of the epidermis (depending on the concentration used), improves the appearance of rough skin, while the effects of remote stimulation improve the extracellular matrix constituents secreted by the fibroblasts. Choosing the right peel is often a source of stress for a doctor who is starting his career in peeling: opting for a technique that is too superficial will satisfy neither patient nor doctor, while using a medium-strength product could cause unexpected side-effects that can be hard to cope with, especially if the results are mediocre. Deep peels have their own particular indications and their own particular risks. Sometimes, only a deep peel can solve a cosmetic problem, but the level of complexity and danger of such peels means that they are often rejected by beginners, who will instead attempt to push the limits of a peel and do a medium peel with an agent that is intended to be superficial. They will often pay for the consequences in cash. When choosing a peel, a simple equation should be taken into account: the results expected from the peel must be greater than the sum of the fear of the treatment’s complexity, the risk of complications, and the downtime and financial cost for the patient. The ratio [Results/(complexity + complications + downtime + cost)] must always be positive. During the preliminary consultation, the doctor should first discuss downtime and treatment cost with the patient, who always expects breathtaking results. It is easier to deal with these two factors first before embarking on the complexity of the technique and the potential risks and

complications. In this way, the treatment can quickly be oriented to what the patient is prepared to go through. If patients say straight off that they cannot accept any downtime or have limited funds, it is pointless wasting their time, which is as precious as yours, explaining unnecessary technical details about deep peels.

A few logical rules make it easier to choose ■ Sagging skin only responds to a phenol peel and only if the skin is relatively thin. Peels are not indicated for sagging in thick skins or for nasolabial folds. Chemical peels cannot compete with surgical face-lifts; they cannot stretch the skin as well as the latter do. ■ The neck does not respond well to chemical peels. Results are often disappointing. ■ Expression wrinkles benefit from treatment with botulinum toxin prior to any peel; it allows the skin to regenerate on a non-moving base. ■ Photoaging and free-radical aging from smoking and pollution can be treated with a peel; the speed and quality of the results depend on the depth of the treatment. ■ Active acne should only be treated by a medium peel after it has been treated medically and the infection has cleared up;3 it can, however, be treated by lighter peels even during the active infectious phase. ■ Facial acne scars are difficult to treat, sometimes even with phenol. Acne scars on the back, décolletage or face can fade or improve with a combined technique of chemical peeling and dermabrasion. It is still difficult, however, to get rid of them completely. ■ Results of the treatment of hyperpigmentation disorders depend entirely on the depth of the problem and the depth of the treatment. They are frequently treated with peels that reach or go beyond the Grenz zone, in conjunction with appropriate daily care. The only way to treat melasma permanently is by completely destroying the cells that produce melanin, by peeling ‘beneath the

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lesion’ with an agent that is toxic to melanocytes, which is a fairly aggressive treatment. Another option is to treat the skin more superficially in order to reduce the risk of complications. Only a certain proportion of melanocytes are destroyed in order to lighten the melasma at the same time as stimulating keratinocyte turnover. The relative increase in the number of keratinocytes compared with the number of melanocytes dilutes the melanin produced in the epidermal cells (the blending effect). Melanogenesis is reduced with tyrosinase inhibitors and antioxidants, which are applied in the long term and combined with effective sun protection (bleaching effect). Solar or senile lentigines respond partially to peels to the Grenz zone and the papillary dermis. They sometimes require a peel to the reticular dermis to get rid of them completely. This deep peeling can be local. Stretch marks can only be treated definitively by applying aggressive treatments that can improve the epidermal and dermal atrophy that accompanies them. Peels are not indicated for hypertrophic scars. Some fine facial scars (from a face-lift, for example) improve vastly after local application of some phenol peels; others are improved by a combination of abrasion and peeling. Body peels produce fewer results and more problems that facial peels. Peels on the backs of the hands are very easy and cause few complications with trichloroacetic acid in the form of Easy TCA®.

Nothing speaks louder than pictures when it comes to chemical peels: we will look at different clinical cases to discuss the choice of an appropriate peel.

Start of photoaging The patient shown in Figure 5.1, who is approaching 40, has a few lentigines and a thick and oily skin with dilated pores. There are no wrinkles, but a slight sagging of the skin that is only noticeable in a standing position. A deep peel would not be the best way to treat this patient, as the ratio of results to complexity + complications + downtime + cost would not be favorable. The possibility of a medium peel to the papillary dermis could be discussed, if the patient wanted fairly quick results or if she did not have enough time for a series of lighter peels. She could also be advised to have a series of peels, either intraepidermal (to remove the epidermis) or down to the basal layer, combined with appropriate daily care. Another possibility would be one alpha-hydroxy acid (AHA) peel per week for 6–10 weeks or one Easy TCA® (pinpoint frosting) per week for 4 weeks. The daily care routine should include DMAE4 to firm the skin, tyrosinase inhibitors and antioxidants to limit melanin production,5

Figure 5.1 Stimulating superficial peels and appropriate daily care are indicated for this patient.

and, of course, effective sun protection. If the lentigines do not clear quickly, they should be treated locally with a single careful application of Only Touch®, immediately before the last of the four Easy TCA® peels.

Under-eye bags Many patients want to get rid of or improve under-eye bags (Figure 5.2) that leave them looking permanently tired. This is a purely surgical problem, although it has been suggested that local injections of phosphatidycholine would dissolve the fat, but this treatment can be very risky.6 Peels and cosmetic products cannot improve them. In some circumstances, a phenol peel can improve bluish circles under the eyes if it succeeds in making the thin skin in this area thicker. The best treatment is to remove the weak veins of the inner and outer canthus with a Müller hook, followed by treatment with blue laser light.7

Figure 5.2 A peel is not an indication for under-eye bags.

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Sagging skin Apart from an improvement in overall skin quality and tone, the patient shown in Figure 5.3 will not benefit from any peeling technique – either repeated superficial peels or a deep phenol peel. Actinic damage is light and there are not many lines or wrinkles. On the other hand, the folds of sagging skin are very marked in this patient, who is a heavy smoker. Examination and palpation show that the dermis has emptied of its ground substance and atrophied. The daily care routine should combine powerful antioxidants,8 DMAE and possibly DHEA. This patient refused to have any surgical treatment, and was treated with a phenol peel in an attempt to get the skin to retract. Unfortunately, on a dermal base totally emptied of ground substance, this treatment resulted in an ‘accordion effect’.9 This patient would only benefit cosmetically from a surgical face-lift, possibly followed by peels to the Grenz zone to improve the quality of the skin. The patient in Figure 5.4, on the other hand, received much benefit from the stimulating and evening effect of Easy Phytic® on the epidermis and dermis.

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The skin tension is better and the yellow discoloration caused by actinic damage has been reduced. The daily care routine also consists here in Actilift® (DMAE cream) and DHEA-Phyto®: see Chapters 2 and 3 for more information on these two products. When retightening is indicated, Easy Phytic® can be applied in a single layer every morning for several days, depending on how the skin reacts. The results are surprisingly quick, and the skin soon tightens visibly (see Chapter 11).

Comedonal acne Comedonal acne (Figure 5.5) can be treated with an intraepidermal peel or a peel to the basal layer. A trichloroacetic acid (TCA) peel to the papillary or reticular dermis could be considered, but such a deep treatment would be pointless for this type of disorder, which can be treated with a lighter peel and, in any case, requires longterm maintenance treatment. It is essential to ‘clean’ the skin beforehand with a comedone extractor to limit damage to the skin; the skin should be cleaned in this way a week before an alpha-hydroxy acid (AHA) peel10 or immediately before each of four Easy TCA® peels. Removing the comedones helps produce quicker results and prevents post-peel infections.

Macrocomedones (1–2 mm in diameter) These can be treated locally with Only Touch®, a solution with a high concentration of saponified and stabilized TCA.

Figure 5.3 General sagging of the skin with little actinic damage: this is not a good indication for a peel.

Figure 5.4 (a, b) A moderate improvement in sagging skin can sometimes be achieved by applying superficial peels: here, after three Easy Phytic® peels.

Figure 5.5 Comedonal acne.

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Either the applicator provided with the product or the point of a 30G1/2 needle should be used to limit the action precisely to the head of the comedone. In 95% of cases, comedolysis is achieved. Very large macrocomedones (>2 mm in diameter) can benefit from careful infiltration of Easy TCA® or Easy Phytic® solution into the center of the comedone. Post-peel care, which is very important, consists in avoiding comedogenic cosmetics, having the skin cleansed professionally once a month, and applying an antiacne cream containing AHAs, tretinoin or precursors, disinfectants, anti-inflammatories, tea-tree oil, etc.11 once or twice a day. For details of this treatment, see Chapter 15.

Photoaging

The patient shown in Figure 5.6(a) has numerous treatments to choose from. She does, however, have an important restriction to take into account: downtime must be minimal and the overall cost low. Resorcinol, TCA to the papillary dermis and phenol are all automatically ruled out. However, a relatively strong acid is needed to treat the lentigines that can be seen at the top of Figure 5.6(a). For this, Only Touch® can be used, applied locally and precisely on the lentigines, with Easy TCA® being applied on the rest of the face to treat the dyschromia, superficial lentigines, photoaging and acne and to even out the result. See Chapter 15 for details on applying this product. Daily post-peel care should consist of an anti-acne cream and a blending and bleaching cream to even skin tone. Figure 5.6(b) shows the lentigines clearing up, an improvement in the overall appearance of the skin and the dyschromia evening out. This improvement can still be seen 1 year after treatment.

The more severe the photoaging, the more important it is to consider the depth of the peel. The patient shown in Figure 5.7 has a light skin type that is sensitive to the sun’s rays. She has developed a number of solar lentigines and fine wrinkles caused by UV rays. The eyelids are very wrinkled and the nasolabial folds and marionette lines are slack. In the long term, this patient’s nasolabial folds and marionette lines will only improve slightly, even with a deep peel. Other techniques12 should be used to treat them. There are many peels to choose from. The wrinkles on the lower eyelids can be softened with a TCA peel to the Grenz zone (Easy TCA®) or to the papillary dermis (Unideep®), but only phenol can be guaranteed to get rid of them. Many lentigines respond to a TCA peel to the basal layer of the epidermis, the majority to a TCA to the papillary dermis, while the deepest should be treated to the reticular dermis. Fine wrinkles on the cheeks can improve with TCA,13 but only phenol can really get rid of them and tighten the skin. There are two choices of treatment open to this patient. The first option would be an aggressive treatment, to be done in a single session: a full-face phenol peel that will treat all the symptoms of photoaging at once and tighten the skin. If the patient opts for this treatment, she must accept at least 8 days’ downtime and a high treatment cost. The second option is a less aggressive, more gradual and stimulating treatment that can be combined with a local phenol peel on the lower eyelids. Only Touch® is applied locally on the deeper lentigines and Easy TCA® on the rest of the face to even out the result and improve the fine wrinkles. A localized phenol peel on the lower eyelids14 is recommended if the patient wants to get rid of her eyelid wrinkles. If this course of action is chosen, the possibility of combining a localized phenol peel with Unideep®, a TCA

A

B

Lentigines, acne and dyschromia

Figure 5.6 (a) Combination of lentigines, acne and dyschromia. (b) Results 1 year after combining Easy TCA® and Only Touch®.

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hyperpigmentation that the patient hid for years under camouflage make-up. Given the extent of the problems to be treated, a full-face phenol peel was suggested straightaway, but was then ruled out because of the high cost of the treatment. The glabellar scar could not be improved by anything but a phenol peel, which was then applied locally, as can be seen in Figure 5.8(b): this photograph shows the pure white frosting resulting from the local application of

A

Figure 5.7 More severe photoaging.

peel to the papillary dermis, should be discussed. With phenol, the downtime is 8 days and it might be more appropriate to combine the local phenol peel with a single session of Unideep® that has a downtime of 5–6 days, instead of having four weekly sessions of Easy TCA®. As the results are comparable,15 the decision is often based on cost or the risk of complications, which is higher with a dermal peel. Depending on requirements, daily post-peel care should include a vitamin E antioxidant cream, a blending and bleaching cream, and/or a DMAE cream.16 Some solar and senile lentigines may only respond to peels to the reticular dermis as, histologically, the lentigines may be characterized by deep dermal papillae and elongated rete ridges with golf club-shaped extensions.

Post-inflammatory hyperpigmentation and scarring The patient shown in Figure 5.8(a) had had a serious road accident 6 years before the treatment. The surgeon did a perfect job given that the face had been completely lacerated by the car’s windscreen. Severe post-traumatic inflammation quickly turned into post-inflammatory

B

C

Figure 5.8 (a) Post-traumatic scars and hyperpigmentation. (b) Following treatment with a local phenol peel. (c) Four Easy TCA® peels and Blending Bleaching® cream were applied to even out the skin color.

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phenol. The skin color was evened out by applying four Easy TCA® peels until a cloudy white frosting was achieved, combined with Blending Bleaching® cream that was applied twice a day from the day after the first peel and continued for at least 6 months (Figure 5.8(c)). An effective sunscreen (see Chapters 3 and 35) must be applied every day between the four weekly peels and until the end of the maintenance treatment.

Severe aging of the skin The patient shown in Figure 5.9 has thin skin marked by expression wrinkles, sagging skin and photoaging. Using a peel that does not reach the dermis is always disappointing in cases like this. Some light peels might tighten the skin temporarily as a result of the edema that occurs afterwards. It would be impossible to attempt to correct all of these wrinkles, even by frequent repetitions of an intraepidermal peel or even a peel to the Grenz zone. A peel to the papillary dermis might improve the finer wrinkles and the quality of the skin, but only a full-face phenol peel could tighten the skin definitively through a ‘three-dimensional facelift’.17 The expression wrinkles should be treated first – 1 week before the phenol – with botulinum toxin, which will allow the skin to regenerate without the movements that would soon reimprint the wrinkles on a healing dermis.

Perioral wrinkles Perioral wrinkles (around the upper lip and chin) only respond to very deep peels (Figure 5.10). Many different agents have been tried: e.g. pyruvic acid, that has a high potential for scarring, and this particular agent, which is difficult to control in concentrated solutions, is very rarely used. Chemical cheiloplasty can only be considered under three conditions: ■ The natural skin color allows treatment without the risk of pigmentary changes. ■ The skin around the area to be treated is in good enough condition that the demarcation line will not be too obvious. ■ Other treatments (i.e. hyaluronic acid, collagen, etc.) would have no effect. Patients with skin phototype above IV are therefore ruled out from this treatment, as are patients with a light skin phototype but a lot of freckles,18 and patients whose skin is severely photoaged. Phototype IV patients should make a choice between deep wrinkles and a possible depigmentation. Lip & Eyelid® formula was originally developed to treat only the lips and eyelids before its indications were extended to the full face. It can be applied locally without nerve blocks or any kind of anesthetic (see Chapter 36). A TCA Unideep® peel (to the papillary dermis) is applied to the rest of the face immediately after the phenol peel has been applied locally (Figure 5.11). The Unideep® must not come into contact with the skin that has been treated with phenol. Botulinum toxin often has to be used at the same time as a deep peel on patients with thick skins in order to limit the contractions of the orbicular muscle of the lips and to improve/maintain results. The horizontal fold between the lower lip and the prominence of the chin does not usually respond well to peels, even deep ones. It can easily be filled in, however, together with the nasolabial folds 1–2 months after the phenol peel.

Dermal atrophy

Figure 5.9 A clear indication for a phenol peel.

The wrinkles on the cheeks of the patient shown in Figure 5.12(a) have been caused by dermal and hypodermal atrophy. Only a deep peel could improve the cosmetic appearance of this patient. Dermal fillers are, however, another possibility for treatment. Figure 5.12(b) shows the rejuvenating effect of injecting 2.5 cm3 of Bioalcamid® 19 in each cheek. The deep wrinkles have completely disappeared and the shape of the face has been restored to look like it did in a photograph of the patient when younger. Note the persistent bruising in the injected areas. This bruising can largely be avoided by using a trocar or blunt-tipped needle instead

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A A

B

Figure 5.11 B

(a, b) Wrinkles on the upper lip treated with a single application of Lip & Eyelid®, with the rest of the face being treated with a Unideep® peel in the same session. Note the excellent results for facial skin tension with TCA.

of a conventional needle. This treatment can of course be combined with a peel: Bioalcamid® can be used perfectly safely with Easy TCA® in the same session. The peel is performed after the liquid implant has been injected. A deeper peel, on the other hand, should only be applied a few weeks after the filling to avoid interference with the necessary process of encapsulation that fixes the filler material in place.

C

Deep wrinkles

Figure 5.10

If the patients in Figures 5.13(a) and 5.14(a) want quick rejuvenation that will last around 15 years, a phenol peel is the only indication (Figures 5.13(b) and 5.14(b)). The extent of the problems would be beyond dermal fillers, and if these were used, the results would be temporary.

(a) Deep wrinkles on the upper lip and chin. (b) Bismuth subgallate powder mask during the first few days after a phenol peel. (c) Results after treatment of these wrinkles with Lip & Eyelid® formula (phenol peel – chemical cheiloplasty).

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A

B

Figure 5.12 (a) This patient’s wrinkles are caused by severe skin atrophy. A peel is not the best indication. (b) Results of treatment with a dermal filler: 2.5 cm3 of Bioalcamid® in each cheek.

Botulinum toxin, used alone, would only partially improve the areas around the eyes, lips and cheeks. A surgical facelift would tighten the neck and the cheeks, but it would not treat the crow’s feet satisfactorily and would have no effect at all on the wrinkles on the lips and the overall skin quality. A light peel would only improve skin quality and even out skin tone, but would not get rid of the wrinkles. A peel to the papillary dermis would have a similar and more noticeable effect, but would not get rid of these deep and long-standing wrinkles. An experienced

doctor could use full-face dermabrasion. Full-face carbon dioxide laser treatment used to be very popular, but is gradually being abandoned because of the serious complications faced by both patients and doctors. A phenol peel will treat the sun-damaged skin and tighten these patients’ faces. An inexperienced doctor should not, of course, use this type of peel. Treating the deep wrinkles on the upper lip often calls for a combination of techniques: phenol plus dermabrasion, phenol plus botulinum toxin, second phenol treatment, etc.

B

Figure 5.13 A

(a) Deep wrinkles. (b) Results after a session of full-face Exoderm®.

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B

Figure 5.14 (a) Deep wrinkles. (b) Results after a full-face phenol peel; second treatment of the upper lip.

Melasma Many techniques are now available for treating melasma. Some are more aggressive, some more effective and others more costly or complex. Only one technique can provide a definitive and effective treatment in one single session: a phenol peel. After a phenol peel, melanocytes can no longer produce melanin. If we rule out this treatment, which would be extreme for melasma alone, then the basic principle is relatively clear, if not always 100% effective. The existing melanin reserves must be eliminated by carrying out one or more peels, and melanin must be prevented from building up again by long-term topical post-peel treatment and effective sun protection. How quickly the melanin reserves can be eliminated depends on the strength of the peel: an intraepidermal peel will be extremely slow, a peel to the basal layer will be slow, a peel to the Grenz zone will be quicker, and a peel that destroys most of the papillary dermis will be quicker still. This progression raises the following problems: if the peel acts too slowly, either the patient will tire of the treatment, or the skin, once exposed to the sun’s rays, will resynthesize the melanin as it is being eliminated; if the peel is deeper, to the papillary dermis, and the inflammation is not controlled, the skin might react and develop post-inflammatory

hyperpigmentation. In any event, success depends on sun protection/avoidance and long-term topical treatment. Patients who refuse to go through with post-peel care should not be accepted for melasma treatment. The choice of treatment for the patient shown in Figure 5.15(a) was four sessions of Easy TCA® (Figure 5.15(b)). The solution was first applied to the melasma spots until cloudy white frosting appeared; it was then applied to the whole face to even out skin tone.20 One session was done per week. Antityrosinase and antioxidant Blending Bleaching® cream was used twice a day. The cream was first applied the morning after the first peel, on the whole face in the morning and on the melasma spots in the evening. Any melasma treatment (apart from phenol) must be accompanied by long-term care with antioxidants, tyrosinase inhibitors and effective sun protection for a minimum of 6 months (although 1 year would be more effective).

Complexity of choosing a TCA peel TCA peels are doctor-, chemical- and patient-dependent. Penetration depends on how the skin is prepared, and the

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A

B

Figure 5.15 (a) Melasma before treatment. (b) After four Easy TCA® peels and Blending Bleaching® cream.

doctor’s choice of preparation depends on the patient and the method of application (when pre-peel preparation is indicated). It also depends on how rigorously the actual patients, who will only really benefit from TCA in simple aqueous solution (TCA–SAS) when the skin has reached the stage of ‘retinoid dermatitis’, prepare their skin. The results of a TCA peel vary – from ‘inadequate’ to ‘excellent’. As there is no general toxicity, the peel can be applied to all areas of the skin. Pigmentary changes are always a risk with TCA–SAS, and should be prevented as much as treated. There is also a risk of scarring when the concentration of TCA is higher than 35% m/m. Treating the neck and décolletage is dangerous, as effective treatment depends on relatively high concentrations of TCA–SAS being applied to an area that is quick to scar because it has few appendages, because of its histological structure and because of the twisting and stretching movements it is constantly undergoing. For an inexperienced doctor, the choice may seem daunting! What is the best way to deal with general skin aging of ‘average severity’? Phenol would be too aggressive and glycolic acid not strong enough. A TCA peel would be more appropriate, but how much preparation would the patient accept? What concentration of TCA should be

used? 25%, 35% or 50%? m/m, m/v or m + v? How much acid solution should be applied and how many coats? What depth should be reached? How much pressure should be applied on the gauze pad? And is it better to use gauze or a cotton swab? Or a brush? What kind of postpeel care should be used? What are the usual developments? What will the results be? What complications could arise? Should the peel be repeated? If so, how many times and how often? The questions posed to an inexperienced doctor are endless. Fortunately, a new concept in TCA peels came into being in the second half of the 1990s: Easy TCA®. This peel can be performed in a doctor’s surgery, without preparation, without anesthetics, without close follow-up, on all skin types, on all areas of the skin and in all seasons.

Differences between Easy TCA® (ETCA) and TCA in simple aqueous solution (TCA–SAS) There are many differences between ETCA and TCA–SAS applied in the classic manner.

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ETCA logic versus TCA–SAS logic The logic behind a TCA–SAS peel is different to that for ETCA. TCA–SAS is used to destroy damaged tissue (removing the papillary dermis) with the skin being left to heal naturally. It is a destructive rather than a stimulating process. The indications for ‘destructive’ peels are different to those for ‘stimulating’ peels. An ETCA peel is stimulating rather than destructive: it does not destroy much skin (the Grenz zone or basal epidermis is removed: see Chapter 12), but strongly stimulates the regeneration process. All peels induce inflammation (tumor – dolor – rubor – calor), which is responsible for the redness, swelling and most of the pain21 and heat felt in the treated skin. The swelling and edema come from rapid permeation of the dermal blood vessels, which pour out a large quantity of neutralizing serum, oxygen and pro-inflammatory components into the dermis and maintain vasodilation. Free radicals are also soon released and damage all the surrounding structures, especially those needed for re-epithelialization. Every peel has to take the advantages and disadvantages of inflammation into account:

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Box 5.1 Surfactants Emulsifiers are necessary to allow water and lipids to combine. A surfactant is an amphiphilic molecule that has affinities for fats as well as water and that can be incorporated into lamellar lipid structures (e.g. cell walls). Surfactants increase the fluidity of the lipid structures by partitioning into the lipid membranes, as their lateral interactions with the membrane-forming lipids reduce the force of their attractive interaction. The mobility of the membrane lipids increases considerably in a similar manner to when a liquid crystal is converted into a gel. Finally, lipids can be seen to micellize or simply dissolve. Membranes lose their relative impermeability. See Figure 5.16.

Normal membrane structure: active transmembrane protein

■ The upside is the stimulation without which regeneration could not take place. ■ The downside is the self-maintained production of free radicals that damage the skin and slow down re-epithelialization. An ETCA peel attempts to make the most of the positive effects of inflammation at the same time as limiting, as far as possible, the negative effects of oxidation with the help of the post-peel cream. TCA–SAS, on the other hand, has to contend with the good and bad sides of inflammation.

ETCA solution versus TCA–SAS solution TCA–SAS TCA–SAS is a simple dilution of TCA in water. Its characteristics are described at length in Chapter 12, together with the various approaches used to counter the difficulties arising in its use. TCA–SAS is usually considered to be effective from 25% m/m.

ETCA ETCA consists of a base solution to which the doctor must add a specific quantity of TCA to make up a peel solution that contains 15% m/m TCA. This solution is saponified, stabilized and adjuvanted. Saponins are natural extracts, glycosides, which have lathering and binding properties for water-soluble prod-

Lipid breakdown: inactive transmembrane protein

Figure 5.16 Effect of surfactants on cell membranes.

ucts in the skin’s lipids. They help the acids spread and penetrate evenly, on and through the skin. Some studies have shown that saponins have antimicrobial properties that enhance skin regeneration after a peel. ETCA solution also contains the surfactant (Box 5.1) sodium laureth sulfate (SLES).22 SLES degreases the skin, emulsifies fats and holds skin impurities in suspension. Coconut fatty acid monoethanolamide (cocamide) improves the effectiveness of saponins. Citric acid is a tricarboxylic AHA, an antioxidant, chelator and buffer that helps break down corneodesmosomes and makes it easier for the TCA to penetrate the epidermis. Ascorbic acid has a

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dual role, acting as a buffer and protecting against free radicals. It protects the solution as well as the skin from oxidation.

epidermal pinpoint frosting appears, contains tretinoin precursors that boost the LCs and improve their antigenpresenting function.

Pre-peel ETCA versus pre-peel TCA–SAS

Immediate pre-peel ETCA versus TCA–SAS

TCA–SAS should be preceded by several weeks of skin preparation to even out and reduce the thickness of the stratum corneum, reduce melanocyte activity and enhance re-epithelialization. ETCA, on the other hand, is applied on unprepared skin, as the acid and the post-peel cream penetrate evenly; the risk of pigmentary changes (basic protocol) is extremely low and re-epithelialization takes place without prestimulation.

With a TCA–SAS peel to the papillary or reticular dermis the patient’s skin needs to be properly cleansed, cleaned of make-up, disinfected (with alcohol) and degreased (with acetone). The doctor must disinfect his hands properly and the patient must be kept away from any potentially infectious staff. The TCA–SAS cannot penetrate the skin properly through grease and make-up, and the skin must be disinfected to limit the risk of post-peel secondary infection. ETCA is usually applied without any prior cleansing, make-up removal, degreasing or disinfection. The peel solution can even be applied on top of make-up, as the emulsifiers in the base solution hold these molecules in suspension and allow the TCA to come into contact with the skin. The endpoint of ETCA treatment is scattered pinpoint frosting or cloudy white frosting, and there is therefore no need to increase penetration of the peel solution artificially. Make-up removal, disinfection and degreasing are not forbidden before an ETCA peel, but could increase skin permeability and cause the solution to penetrate too deeply and destroy the dermis. A TCA to the dermis is not the same as an ETCA peel.

Calculating the solution mix: ETCA versus TCA–SAS We saw that preparing a TCA–SAS solution appears easy at first sight but that numerous factors come into play that can change the behavior of a solution, gel or paste considerably. ETCA provides a standardized solution that always produces the same results when the same protocol used.

Herpes prevention: ETCA versus TCA–SAS Herpes prevention is essential before a TCA–SAS peel, as the dermis of the skin has to be destroyed for the peel to be effective, and the skin’s immune defenses suffer from this destruction. ETCA is more stimulating than destructive; it will not destroy the skin’s immune defenses. On the contrary, repeated peels appear instead to stimulate it. No herpes prevention is necessary before using ETCA in the ‘basic protocol’ (scattered pinpoint or cloudy white frosting).

Bacteria prevention: ETCA versus TCA–SAS For the same reasons outlined above, the risk of secondary bacterial infection is considerably lower with ETCA than with TCA–SAS. Systematic prevention of infection is not necessary with ETCA: no antibiotics, no disinfectants. The Langerhans cells (LCs) in the epidermis and papillary dermis are not destroyed, nor are the other antigen-presenting cells, and they continue to prepare the body’s defenses against microscopic predators. The lymphocytes, macrophages and other defense cells remain present in the dermis. The ‘post-peel cream’, applied as soon as the first

Depth of peel: ETCA versus TCA–SAS TCA–SAS is applied with a view to destroying damaged (usually sun-damaged) skin structures and benefiting from the skin regeneration that naturally follows a peel. It is really effective when it destroys the papillary dermis. With ETCA, the aim is not to destroy the dermis in the hope of its rebuilding later, but rather to stimulate all the phenomena of skin repair repeatedly, in all the different layers of the skin. With frequently repeated ETCA sessions (every 8 days), the sum of the results is comparable to that of a papillary peel without any of the drawbacks. The ‘basic protocol’ for ETCA is intended to reach the basal layer of the epidermis or the Grenz zone. There are (many) other deeper protocols but they are not as straightforward as ETCA and the risk of complications is relatively much higher. ETCA is not necessarily a light peel; it can be used to reach all depths, from the basal layer of the epidermis to the reticular dermis, depending on the protocol used. The relatively superficial action of the ETCA solution (basic protocol) strongly stimulates the skin regeneration

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process and increases the permeability of the epidermis. The ETCA post-peel cream penetrates the skin more easily, as it is permeabilized by the peel solution.

Anesthesia, pain, monitoring: ETCA versus TCA–SAS A TCA–SAS peel to the dermis is painful and requires the use of analgesics. Some resistant patients can tolerate a peel reaching the superficial dermis, but are left with such unpleasant memories that they might well refuse further treatment. A peel to the papillary dermis should not be done without facial nerve blocks (FNB) and/or sedation. Performing FNB requires a whole series of measures, including pulse oximetry at the very least. Any painful intervention can trigger vagal reactions for which the doctor must be prepared. Pain after a peel can be dealt with easily by prescribing oral analgesics (e.g. acetaminophen (paracetamol) or codeine/ acetaminophen). ETCA does not require any type of anesthetic, sedation or analgesics. Any mild pain caused by the application of the ETCA solution can be dealt with immediately, as soon as frosting occurs, by applying the post-peel cream.23 No pulse oximetry monitoring is necessary and no vagal reaction has been described, perhaps because it is a short procedure.

Length of peel: ETCA versus TCA–SAS It takes 10 minutes to apply ETCA to the basal layer or the Grenz zone, from the time patients lie down to when they get up. Applying a TCA–SAS peel, usually to the papillary dermis, takes a lot longer: at least an hour should be allowed for settling the patient in, disinfection, make-up removal, setting up the monitoring equipment, FNB or sedation, a series of applications and letting the patient rest after the peel.

Post-peel care day 1 to day 8: ETCA versus TCA–SAS Post-ETCA care consists simply of asking patients to protect their skin from the sun (Melablock®-HSP) and to apply the most suitable cosmeceutical for their particular problem (see Chapter 3). They should start the very day after the first of the four peels and continue until the end of the 6th week after the last peel. The post-treatment care after a TCA–SAS peel is more complex and needs much closer monitoring, as the risk of complications is much higher. Follow-up monitoring after a TCA peel to the papillary dermis is described in Chapter 23.

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Repeating peels: ETCA versus TCA–SAS A TCA–SAS peel can only be repeated after a rest period of usually 6 weeks to allow the skin to regenerate completely. It provides a single strong stimulation that decreases with time. ETCA is repeated four times at weekly intervals to provide ideal stimulation of the skin regeneration processes. The post-peel cream and ETCA application technique allows for this repetition. If the ETCA were repeated less often (once every 2–3 weeks), the effects of stimulation would not be cumulative. Weekly repetition, in contrast, ‘stimulates the stimulation’ resulting from the previous peel.

Combination treatments: ETCA versus TCA–SAS TCA–SAS allows hardly any concomitant combinations, and most of the treatments that one might wish to combine it with must be carried out 8–15 days before the peel. For example, nothing can be injected immediately before a TCA–SAS peel. It is, of course, possible to inject botulinum toxin in the upper part of the face just before or after applying a TCA–SAS peel to the area around the lips, but the toxin should not be injected before applying a TCA–SAS peel in the same area. The immediate inflammation induced by the peel could cause the toxin to migrate. ETCA, on the other hand, allows all concomitant combinations.

Botulinum toxin This can be injected immediately before applying ETCA in the same area. The technique is simple: inject the toxin, wait 5 minutes, apply the ETCA until pinpoint frosting appears and then apply the post-peel cream. The cream has an immediate and pronounced anti-inflammatory effect, which prevents edema and toxin migration. The restructuring of the skin by the peel improves the results of the toxin, and resting the muscles improves an even collagen deposition.

Filling wrinkles Filling techniques can also be used immediately before ETCA, as the ETCA post-peel cream soon stops inflammation and oxidation. The cream can also absorb the free radicals that are released by the peel and that could damage the three-dimensional structure of dermal fillers, such as hyaluronic acid. In fact, the instructions for most dermal filler products specify not to apply a peel after the filler, but

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this does not apply to ETCA.

Flashlamps ETCA can be used after flashlamp treatment24 when treating pigmentation or photoaging on the face, décolletage or hands. It is preferable to start with the lamp and to follow up with the peel, for the following reasons: ■ Epidermal permeability does not seem to change significantly after the lamp and there is no marked change in the penetration of the ETCA. Caution is, however, advised when applying ETCA solution to make sure that it does not penetrate the skin further than anticipated: the cotton-tipped applicators should be squeezed out properly after the first application and the treatment should not go beyond scattered pinpoint frosting. ■ Applying ETCA and the post-peel cream before the flashlamp would change the refractive and diffractive properties of the epidermis, as well as its water content and color.

Risk of complications: ETCA versus TCA–SAS ETCA carries far fewer risks for the patient than TCA–SAS.

Infections As described above, no herpes or bacteria prevention is necessary with ETCA, unlike TCA–SAS.

Risk of exhausting the skin’s resources At the level of the dermis, the fibroblast is a cell of major interest in understanding how peels work. Like Langerhans cells, they have dendritic morphology; they are fusiform or stellate but have no antigen-presenting activity. Fibroblasts synthesize all the constituents of the extracellular matrix and play an essential role in the formation and contraction of granulation tissue during wound repair. Peels to the dermis destroy a large number of fibroblasts, and the survivors must multiply in order to reconstitute the fibroblast population. Each time they do this, their telomeres shorten, which gradually exhausts their capacity for future multiplication. Peels to the dermis should therefore not be repeated too often. ETCA, on the other hand, does not destroy dermal fibroblasts (and there is no shortening of telomeres), but stimulates their metabolism and obliges them to produce more and more rapidly. Logically, repeating ETCA (basic protocol) cannot accelerate skin aging, which is not the case with repeated peels to the dermis.

Scarring During the healing process, hybrid cells, known as myofibroblasts, appear in the dermis. They have the morphological characteristics of both fibroblasts and smooth muscle cells. They are responsible for tissue contraction–retraction during healing. Their cytoplasm contains networks of myofilaments that are in contact with specialized zones of the plasma membrane and can interact with the adjacent cells or connective tissue. These myofibroblasts appear to be differentiated fibroblasts that have acquired the properties of smooth muscle cells. Controlled stimulation with DMAE, for example, is a good way to achieve a tightening effect on the skin. Correlating this theoretical data with the clinical data on peels is not without interest, as it allows us to anticipate which peels might potentially cause scarring and which ones will not. Deep peels, which go beyond the upper reticular dermis and practically lay the hypodermis ‘bare’, are more dangerous as far as retractile scarring is concerned, as they stimulate the conversion of fibroblasts into retractile myofibroblasts that can cause scarring. Not all agents are equally potent; there are more descriptions in the literature of problems with scarring with deep TCA peels than with phenol-based peels. There is no reason why peels that do not go beyond the Grenz zone should stimulate the conversion of fibroblasts into myofibroblasts, as there is no ‘laying bare’ of the internal tissue and hence no need for retraction. Retractile scar reactions are therefore extremely rare with the basic ETCA protocol; they can only occur when the peel has not been applied correctly. Peels that reach the Grenz zone or the papillary dermis stimulate small fibroblasts that are parallel to the epidermis and have dendritic processes that connect with several collagen and elastin bundles. The synthesized collagen is aligned horizontally in the border zone (Grenz zone), and the resulting tension from the activity of any potential myofibroblasts produces a positive cosmetic effect: improved tension in the papillary dermis, which can be called the ‘lifting effect’. The ‘lifting effect’ achieved with medium-depth peels in no way compares with the lift achieved when sagging skin and muscle mass are treated surgically. In some cases, doctor and patient can be sent off on the wrong track and delay taking the often dreaded and sometimes formidable decision to go ahead with surgery.

Post-inflammatory hyperpigmentation (PIH) It is clear from the medical literature on chemical peels that TCA–SAS is the agent responsible for the majority of postpeel pigmentary problems. Photographs abound in specialist books. A TCA–SAS peel does in fact cause severe inflammation after the peel, and it is therefore not surpris-

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ing to come across many cases of post-inflammatory hyperpigmentation (PIH).25 ETCA, in the basic protocol, causes almost no PIH. Generally, IV, V and ‘light VI’ skin phototypes are at greater risk of PIH.

Downtime During the post-peel period after a TCA peel to the papillary dermis, the patient has to put up with a week of edema, scabbing, erythema, pain and other inconveniences. Any form of social life is out of the question, and the patient can only return to normal social activities, with the help of make-up, after the 8th day. It is several weeks before the skin returns to normal. With ETCA (basic protocol), on the other hand, the patient can lead an almost perfectly normal social life, as the flaking is no more serious than with sunburn and only lasts for 48–72 hours.

Notes 1. Although some peels with an alkaline formulation do exist. 2. Apart from Easy Phytic® Solution, whose acids can penetrate to the papillary dermis. 3. With Easy TCA® and Easy Phytic®, papulopustular acne can be treated during its active phase. 4. Dimethylaminoethanol, a precursor of acetylcholine. See the section on DMAE in Chapter 3. 5. Blending Bleaching® cream (see www.skintech.info) 6. By injecting phophatidylcholine/deoxycholate into undereye bags, there is a risk – among other complications – of disrupting the adipocyte cell walls as well as the muscle cells that come into contact with this product. Moreover, it triggers severe and painful edematous erythema that lasts several days and is only really effective after several sessions. For the moment, fatty bags under the eyes can only be treated surgically. 7. Source: Dr Robert Vergereau, Spain. 8. For example Renutriv ACE Lipoic Complex®: vitamins A + C + E and lipoic acid. 9. See the section on the area around the mouth in Chapter 37. 10. The same applies for Easy Phytic® solution. 11. For example, Purifying cream® by Skin Tech. 12. Depending on preliminary examination of the patient and the doctor’s experience: dermal filling, botulinum toxin,

45

cannulation, threading, etc. 13. Either four Easy TCA® peels to the basal layer or a Unideep® peel to the papillary dermis. 14. See Chapter 34 for application of the Lip & Eyelid® formula. 15. Although it must be taken into account that four peels to the Grenz zone are not necessarily as efficient as one peel to the papillary dermis. The latter can destroy a large number of lesions that peels to the Grenz zone do not always reach. 16. Some studies suggest that DMAE can eliminate the lipofuchsin in lentigines. 17. As the much missed Dr Yoram Fintsi called it. 18. To avoid leaving an obvious demarcation line. 19. This is a permanent polyalkylimide filler in the form of a removable endoprothesis. Fat transfer is used more often, as there is no risk of rejection and the implant is autologous. 20. See the details of melasma treatment in Chapter 15. 21. The ‘burning’ sensation soon improves on application of a cold pack. 22. SLES is not the same as sodium lauryl sulfate (SLS, also known as sodium dodecyl sulfate (SDS)), a powerful surfactant and very irritating to the skin, with which it is often confused. 23. It is not neutralizing, however, as we shall see further on. 24. Provided that this is classic flashlamp treatment and not a device combining pulsed light and radiofrequency, for example. These machines significantly change skin permeability and can cause the acids to penetrate too far, with the risk of scarring. 25. See Chapter 37 for more details.

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6 Alpha-hydroxy acids: chemistry, pH and pKa, and mechanism of action

Glycolic acid

—

Glycolic acid (hydroxyethanoic acid, hydroxyacetic acid) is the shortest AHA, with just two carbon atoms (Figure 6.2). It was originally extracted from sugar cane, but the acid used in treatment today is synthesized chemically. AHAs have become popularized as ‘fruit acids’, and this benignsounding name has had a great influence on the interest shown by patients. The situation is similar to that when patients talk of lasers, gold threads or caviar rejuvenating creams. These words evoke dreams of miracle cures in the imaginations of some: odorless, colorless and painless, permanently effective and, of course, without side-effects. Glycolic acid is extremely hydrophilic, and a pure aqueous solution of glycolic acid, saturated at a concentration of about 80%, has a pH of 0.5. This pH, considerably lower than its pKa of 3.83, shows that the solution consists mostly of pure acid and is effective for performing a peel. The pH of a glycolic acid solution determines its acidifying power on the skin: a 3% glycolic acid solution at pH 3 can acidify the first five layers of corneocytes, whereas at 10% and pH 3, it causes a deeper and more rapid acidification of the

Carboxylic acid group

—

H

O



Hydroxy group  OH O  R — Cα — C  OH H

cannot or do not want their skin to flake, often because of their professional activities, which are incompatible with visible peeling. A number of AHAs have been proposed for medical use: glycolic acid, lactic acid, malic acid (with two COOH groups), tartaric acid (with two OH and two COOH groups), citric acid (with three COOH groups) and mandelic acid (which has an aromatic (phenyl) group attached to the alpha carbon atom) – see Table 6.1 below.

—

H—C—C

Figure 6.1

General chemical structure of an alpha-hydroxy acid. α indicates the alpha carbon atom; R represents a general organic group.

—

Alpha hydroxy acids (AHAs) occur naturally in a number of fruits (from where they get their ‘eco-friendly’ name of fruit acids) and dairy products. This class of acids contains a number of molecules that have in common the presence of a carboxylic acid group (COOH) and a hydroxy group (OH) in the alpha position relative to the acid group (Figure 6.1). As early as 1946, the application of a 3% lactic acid solution at pH 3.8 was already considered a treatment for ichthyosis, although cosmetic dermatologists only really started using AHAs when in 1974 Van Scott and Yu described how effective they were in the treatment of dry or ichthyotic skin. From then on, the scope of AHAs broadened, and some authors reported their beneficial effects on acne, photoaging and benign hyperplastic epidermal lesions. It was often suggested that AHAs should be used to treat age-related wrinkles and sagging skin. Although the direct target of AHAs seems to be corneodesmosomes, the indirect action of topically applied AHAs affects not only the whole of the epidermis but also the papillary dermis and the pilosebaceous units. However, while all peels produce similar1 histological effects on the different layers of the skin, clinical results clearly show that AHAs, used as light peels, do not improve the skin’s appearance to the same extent as TCA or phenol. Moreover, indications for glycolic acid peels tend to be restricted to the treatment of sun-damaged or acneic skin, especially in patients who



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Figure 6.2 Chemical structure of glycolic acid.

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epidermis.2 Note that ‘acidification of the epidermis’ does not mean ‘peeling effect’. Acidifying several layers of the skin does not necessarily mean destroying the cells. Up to a certain point, cells resist acidification.

—

HO

O



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H3C — C — C H

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OH

Figure 6.3 Chemical structure of lactic acid.

Lactic acid Lactic acid (2-hydroxypropanoic acid, α-hydroxypropionic acid) is the next shortest AHA after glycolic acid. A methyl group (CH3) replaces the terminal hydrogen atom on the alpha carbon (Figure 6.3). It has a pKa of 3.86, which is close to that of glycolic acid. Lactic acid occurs naturally in sour milk. After penetrating the skin, lactic acid is converted automatically and reversibly into pyruvic acid, the alpha-keto acid derivative of lactic acid: a keto (=O) function replaces the hydroxy (–OH) function on the alpha carbon. At identical concentrations, lactic acid destroys the epidermis more slowly than glycolic acid. Concentrations of lactic acid of 10–20% or stronger begin to destroy the stratum corneum and stimulate skin regeneration, the renewal of epidermal cells. However, some studies have shown that cell renewal is not maintained uniformly during long-term treatments with 3% lactic acid

at pH 3. In fact, cell renewal gradually falls off during the first 10 weeks of treatment with 3% glycolic or lactic acid at pH 3, decreasing to 29.3% and 28.3%, respectively.3 When applied regularly, lactic and glycolic acids (at 3%, pH 3) lose a significant percentage of their capacity to destroy corneocytes and renew the epidermis around the 12th week. Salicylic acid (a beta-hydroxy acid), on the other hand, retains its ability to destroy corneocytes much longer. At a concentration of 50–70%, lactic acid produces the same amount of exfoliation as glycolic acid. As early as 1974, it had been shown that lactic acid improved skin hydration and suppleness and that a pH of 3 was more effective than a pH of 5. Lactic acid is also a better hydrator than urea or glycerol. Some studies tend to show that 3 weeks of daily application of 12% lactic acid would allow as much collagen to be deposited in the papillary dermis as

Table 6.1 Hydroxy and keto acids used in cosmetic treatments Acida

pKa

Chemical structure and alternative names

Tartaric acid

pKa1 = 3.02 pKa2 = 4.54

HOOC.CH(OH).CH(OH).COOH (+)-2,3-dihydroxybutanedioic acid; d-2,3-dihydroxysuccinic acid (only the dextrorotatory (+, or d) form is active) [dicarboxy dialpha-hydroxy acid]

Citric acid MW 192.13

pKa1 = 3.06 pKa2 = 4.74 pKa3 = 5.40

HOOC.CH2.C(OH)(COOH).CH2COOH 2-Hydroxy-1,2,3-propanetricarboxylic acid [Tricarboxy alpha-hydroxy acid]

Mandelic acid MW = 122.14

pKa = 3.36

C6H5.CH(OH).COOH (+)-phenylhydroxyethanoic acid; d-α-hydroxyphenylacetic acid; d-phenylglycolic acid; amygdalic acid [alpha-hydroxy acid]

Pyruvic acid MW = 88.06

pKa = 2.50

CH3.CO.COOH 2-Oxopropanoic acid; acetylformic acid; α-ketopropionic acid; pyroracemic acid [alpha-keto acid]

Malic acid MW = 134.09

pKa1 = 3.40 pKa2 = 5.5

HOOC.CH2.CH(OH).COOH hydroxybutanedioic acid; hydroxysuccinic acid, [dicarboxy alpha-hydroxy acid] HOCH2.(CHOH)4.COOH 2,3,4,5,6-pentahydroxyhexacetic acid

D-Gluconic acid MW = 196.16

pKa = 3.86

α,β,γ,δ,ε-pentahydroxycaproic acid; dextronic acid; glycogenic acid; glyconic acid; maltonic acid [alpha-hydroxy acid]

Salicylic acid MW = 138.12

pKa = 2.98

HO.C6H4.COOH o-Hydroxybenzoic acid, [beta-hydroxy acid]

a

MW, molecular weight.

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applying 25% trichloroacetic acid (TCA) or phenol. We must remember, however, that histological findings, as important as they are, do not always translate into cosmetically visible clinical results and that laying down new collagen is only one of the changes associated with peels.

Buffers In low concentrations, the pH of a glycolic acid solution varies with the concentration of acid: an unbuffered glycolic acid solution, at less than 1%, has a pH of approximately 2.5.4 At 2%, the pH is 2.1. When the concentration reaches 5%, the pH goes down to 1.9. It is 1.7 for a 10% unbuffered glycolic acid solution. Higher concentrations, 50–80%, have a pH close to 0.5. At identical pH about 0.5, a solution with a concentration of 80% is more aggressive than a 50% solution. A concentrated glycolic acid solution at pH 0.5 consists of free and active acid, and is aggressive to the skin. It is a thousand times more acidic than a solution at pH 3.5.5 A solution this strong needs to be properly neutralized by the doctor applying it. Applying a 70% non-neutralized glycolic acid solution to the skin can destroy the epidermis in 2–7 minutes, depending on the skin type, the thickness of the stratum corneum, the degree of photoaging and the pre-peel preparation of the skin. The pH values on the surface of normal skin vary between 4.5 and 6, and up to a certain point the skin has the ability to defend itself against pH variations and can maintain a stable pH in the face of moderate acid or alkali attacks. This is the skin’s ‘buffer’ capacity (Box 6.1). Applying large quantities of pure acid to the skin (during a glycolic acid peel with a non-neutralized solution) saturates its natural buffer capacity, and the excess acid must be neutralized to avoid burning the skin. The contact time for a glycolic acid peel, as well as for other AHAs, is the time between applying the peel6 and

Other hydroxy and keto acids Many other hydroxy acids (and the related keto acids) are used in cosmetic treatments (Table 6.1). Ascorbic acid (vitamin C) is an alpha-hydroxy acid derivative. It has been shown to stimulate collagen production and reduce melanin production. Under identical conditions, classification of the acids described above in order of strength would give the top three as: 1. pyruvic acid 2. glycolic acid 3. lactic acid In the rest of this chapter, it is mainly the use of glycolic acid that will be discussed – and by default this is what the information given applies to. It is clear, however, that, as a general rule, and even if some acids have specific properties, most of the hydroxy acids (alpha or beta), carboxylic acids (containing the COOH group), dicarboxylic acids and alpha-keto acids produce the same positive effects on the skin, depending on the concentration, the pH of the solution (Figure 6.4) and how they are applied.

0

1.5

Easy TCA® Unideep®

3 Lemon juice

5.5 Red wine

7 Milk Saliva

9.5

11

12.5

14

Egg white Seawater

ACIDIC

BASIC

70% unbuffered glycolic acid 1 M HCl

Gastric juices

Beer Phenol peel

Coca Cola® Vinegar

EMLA Sodium bicarbonate Human blood Tears

pH 3 is 10 times more acidic than pH 4 pH 3 is 100 times more acidic than pH 5 pH 0.5 is 1000 times more acidic than pH 3.5

Figure 6.4 pH of various substances.

49

Ammonia

1 M NaOH

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Box 6.1 Importance of buffers in the body The body’s – and the skin’s – enzyme reactions are pHsensitive. It is vital for the body to keep the pH of an organ stable in order to stabilize enzyme reactions. Protection against pH variations – the buffer capacity – must be extremely active and strong, as natural metabolic processes permanently synthesize acids and alkalis that are liable to modify the pH. The blood, for example, is protected by two important buffer systems: the hemoglobin system and the bicarbonate system, which stabilize its pH between 7.37 and 7.43. The bicarbonate system is the most important buffer for plasma and interstitial fluids. Neutralizing the skin with sodium bicarbonate is the most ‘natural’ method.

neutralizing it. The contact times for partially buffered AHAs, at pH>2.5, are far longer than for pure unbuffered AHA solutions at pH 0.5,7 which are a hundred times more acidic.

Box 6.2 Effect of dilution on the pH of a solution 5 ml of the base solution has pH 2.7–3. Adding 20 cm3 of water does not change the pH. The total volume must be brought up to 85 ml for the pH to rise from 3 to 4. See Figure 12.9.

Neutralizing an AHA peel consists in applying a base solution (usually pH 9–10) to the treated area. Rinsing with water only dilutes the acid without neutralizing it (Table 6.2) – an acid is neutralized by a base. However, dilution does have the merit of reducing the proton concentration8 and so eventually increases the pH (without changing the pKa, of course) when enough water is added. The high acidity of concentrated and unbuffered AHA solutions, as well as the complications that stem from such treatments, has brought the pH of many glycolic acid solutions to around pH 4–5.5.9 Ammonium salts, sodium bicarbonate or sodium hydroxide (NaOH) are often used for this. The resulting chemical reaction produces a salt10 and water – the pH increases and the potency of the acid solution decreases: glycolic acid + NaOH ← sodium glycolate + H2O

pKa The natural pH of an aqueous solution of 60% glycolic acid is 0.5. The gradual addition of a base slowly raises the pH of

this solution. When the pH reaches a value of 3.83 as a result of the gradual addition of the base, we know that this solution contains exactly 50% of active free acid and 50% of salt produced by the reaction of the glycolic acid with the base (e.g. sodium glycolate or ammonium glycolate). A pH of 3.83 corresponds to the pKa value of a glycolic acid solution. If we keep on adding a base solution to the glycolic acid solution, the pH will gradually increase, while the proportion of free and active acid and the strength of the solution decrease. A glycolic acid solution whose pH had been brought up to 7 would be completely neutralized or buffered and inactive. A glycolic acid solution at pH 5 is partially neutralized or buffered and partially inactive, as it does not contain much free acid. It is far less aggressive to the skin, of course, but it is also less active. The pKa is therefore an important notion that allows us to understand and anticipate how aggressive an AHA peel solution will be, on condition that we also know the pH of the solution. Knowing the pKa alone, which is a definitive and set parameter for each acid, does not help determine how aggressive a peel solution is. The pKa of glycolic acid is and will always be 3.83, whereas the pH of the solution could vary between 0.5 and 7 or above. The greater the pH than the pKa of an acid solution is, the less aggressive it will be. The lower the pH than the pKa of an acid solution is, the more aggressive it will be. It is therefore not possible to choose the pKa of the solution that we want to use, as this parameter has been determined chemically, once and for all, for each acid, and it gives the exact pH at which 50% of the active molecules remain. We can, on the other hand, change the pH of the solution and make it lower than the pKa to make the solution more aggressive. We can also raise the pH above the pKa to soften the effect. A partially neutralized solution at pH 4 still contains enough free acid to achieve a clinical effect, but is far less effective than a solution at a lower pH. Partial neutralization of a glycolic acid solution is therefore a compromise between effect and risk. It is, in fact, surprising that glycolic acid is still partially active at pH levels of around 5. It seems that the alpha position of the hydroxy group in a small molecule like glycolic acid is the reason for this partially maintained effectiveness, even if the pH is relatively high. Other AHAs do not appear to remain active at high pH levels. Using a partially neutralized solution at pH 4.5 achieves the same results in a few months that could be obtained in a few weeks with the same unbuffered concentration. It is therefore true to say that it is possible to achieve the same results using neutralized or non-neutralized peel solutions. But patients would then have to be convinced to have many more peels, which, on top of the inconvenience of repeated visits to the surgery, means more expense – and that is never appreciated. The doctor may think it necessary to sacrifice effectiveness to safety,

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but the patient usually thinks that the doctor should find a quicker and more effective solution without sacrificing safety. An application of dansyl chloride accumulates in the epidermis and stains the skin. It is possible to measure the rate of disappearance of this coloration after the application of different hydroxy acid solutions at a constant pH. The rate at which the color disappears is correlated with the rate of cell replacement, and therefore provides information on the stimulation of epidermal turnover and on the capacity of the acid to stimulate skin regeneration. TCA (which is not a hydroxy acid), at 0.5%, stimulates skin renewal up to 50%, lactic acid (at 4%, pH 3) stimulates up to 34%, acetic acid (3%, pH 3) up to 30%, and pyruvic acid (4%, pH 3) up to 23%. Partial neutralization of these solutions, to pH 5, quite clearly reduces the rate of renewal, and neutralizing these same solutions to pH 7 takes away all of their clinical effectiveness. The ultimate goal of treatment with AHAs is to stimulate skin regeneration at the same time as avoiding as far as possible the side-effects that stem from their irritant potential. It is not easy to achieve this goal, as a very acid pH is required to ensure optimum clinical effectiveness. The aggressiveness of these acid solutions usually entails a higher risk of complications. We shall see further on that it is possible, however, to use a solution made up of different AHAs at a concentration higher than 60% and pH 0.5, at the same time as limiting the risk of complications: Easy Phytic® is an unbuffered solution of three AHAs, at pH 0.5. This solution uses a slow-release technology that does not need neutralizing in spite of its very acid pH, which is much lower than its pKa.

Mechanism of action AHAs do not coagulate proteins. Applying them in a peel should not therefore produce a ‘whitening effect’. According to Forestier, the mechanism of action of AHAs is as follows. Even at low concentrations, AHAs can insert themselves between two protein chains. Here, they build a sort of bridge that reduces corneocyte cohesion. As a result of the lytic action of AHAs on corneodesmosomes, corneocytes are shed more easily from the skin, and the thickness of the stratum corneum is reduced. The skin appears more hydrated as the stratum corneum is thinned or disappears temporarily. AHAs, even at low concentrations, acidify the upper layers of the skin. Experimentally, at pH facial skin > skin on torso > skin on upper and lower limbs.

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8 Alpha-hydroxy acids: indications and results

The results following daily topical application of low concentrations of glycolic acid in a simple aqueous solution start to show after 2–3 months of continuous treatment, if the concentration is higher than 8%. Alpha-hydroxy acids (AHAs) produce almost no results after a single application;1 they have to be repeated several times to produce clinical results. Whatever the number of AHA peels, the results for wrinkles, dyschromia or photoaging will never compare with the results of a medium or deep peel (cf. the indications for phenol), except in rare cases where the dermatological problem being treated is very superficial in origin. The results are not permanent, and biological analysis shows a return to the original condition 1–2 years after AHA peels. We must accept these limitations of superficial peels. AHAs are not toxic to melanocytes, and can therefore be applied on dark skins and in all seasons, on condition that effective sun protection is used.2 Contact time (Table 8.1) depends on skin type, peel concentration and formulation, its pH, the method of application, preliminary skin preparation, etc. At an identical pH, a 50% concentration of glycolic acid will penetrate half as deep as a 70% concentration, and will take twice as long to do so.

Table 8.1 Suggested contact times for glycolic acid Condition

Glycolic acid concentration (%)

Contact time (min)

Acne Keratoses Fine wrinkles Back

50–70 70 50–70 70

1–3 4–8 4–8 4–10

in the follicles is also reduced, and this stops the follicle canals closing. AHAs are excellent comedolytics: glycolic acid eliminates the hyperkeratosis responsible for the clogged pores. After a glycolic acid peel, the top of the lesion will sometimes whiten to a certain degree as a result of the increase in epidermal permeability around the edge of the inflamed lesion. The whitened areas will disappear in a few days, allowing the sebaceous glands to open and drain. When treating facial acne, concentrations of 50% or more seem to be the most effective, with contact times of 1–3 minutes. Higher concentrations or prolonged contact times cause unexpected frosting (areas of epidermolysis) and slow down post-peel healing. When treating the back, a concentration of 50% is not enough, and concentrations of 70% should be used for 4–10 minutes. If frosting occurs on the back, it is a sign of greater effectiveness, in contrast to facial treatment. Maximum effectiveness is achieved when treating active inflammatory acne. Superficial scars are only rarely and very slightly improved by repeated AHA peels. Ice-pick acne scars are not an indication for superficial peels, and deep scars only respond to a combination of other treatments: dermabrasion, punch elevation, deep peels, filling, dermal stimulation or laser. Treatment of active acne (comedonal, papular or papulopustular) involves a combination of skin preparation, weekly sessions of glycolic acid peels and appropriate and effective daily cosmetic care (see Chapter 3). AHAs produce only a cosmetic result and do not alter the particular genetic traits that lead to acne in some patients: a peel does not change the blood testosterone level, the activity of 5α-reductase, receptor sensitivity or the tendency of the corneocytes to stick together and block the pilosebaceous units. AHA peels must be accompanied by appropriate long-term anti acne daily cosmetic care (Skin Tech’s Purifying® cream or gel).

Acne The use of AHAs (especially glycolic or lactic acid) in treating acne has often given good or even excellent results. Easy Phytic® solution (see Chapter 11) is especially safe, effective and comfortable for this indication. Keratinocyte cohesion

Aging of the skin AHAs were first used to treat dry skin (hyperkeratinization and xerosis) before the positive effects on photoaging skin

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gradually came to light. Photoaging causes the stratum corneum to thicken (the skin becomes dry and rough), local proliferation of melanocytes (lentigines and pigmented hyperkeratosis) and dermal elastosis (wrinkles, fine lines and sagging skin). AHAs can partially help to fight these three types of involution that progressively and inexorably make the quality of the skin deteriorate. AHAs can only provide superficial treatments, whose direct action is limited to the epidermis. However, for the careful observer equipped with good photographs, longterm repetition of AHA peels shows a gradual improvement in the quality and tone of the skin, which becomes softer and more even in tone, as well as partial correction of the appearance of fine lines.3 Contact times can be relatively short when AHAs are being used to prevent aging, but when the photodamage is more severe, the length of contact time between the glycolic acid peel and the skin before neutralization should be increased to help improve penetration, as sun-damaged skin is more resistant.4 When using glycolic acid creams, the photodamaged skin soon becomes less dry and rough: results start to show after 3–4 weeks of daily treatment, but obvious clinical results can be seen more clearly after several months of treatment. Patients should never be led to expect too much too soon. Even though patients soon feel an improvement in the ‘feel’ and quality of their skin, it is pointless to exaggerate and promise that wrinkles, folds or fine lines will disappear altogether: a long series of 50–70% unbuffered glycolic acid peels (for 6–12 months) only moderately improves fine lines. Wrinkles and skin folds are not indications for AHAs. A histological study did not show any significant change after four monthly AHA peels.5 The long rest period between peels could be to blame for the lack of histological results, as the peels must be repeated in relatively close succession to be effective and benefit from the gradual cumulative effect of the stimulation produced by the different peels. Once a month is too infrequent and, clinically, weekly repetition is far more effective. Weekly sessions should be kept up for the first 4–6 weeks of treatment, if the patient’s skin can tolerate it. Thereafter, peels should be repeated twice monthly, and eventually once a month as maintenance treatment. Treatment for aging skin should, of course, be accompanied by active daily cosmetic care: DHEA-Phyto®, Actilift® or Renutriv ACE Lipoic Complex®.6 Treatment of photoaging is the second preferred indication for Easy Phytic® solution, and results (tightening effect) appear rapidly, after the first few sessions.

There is relatively little risk of post-peel pigmentary changes if the peel is applied correctly, but this risk cannot be ruled out, even when the glycolic acid peel has been kept in technically perfect conditions (see Figure 37.28, p 331). When treating hyperpigmentation, the skin must be cleansed and degreased with the utmost care before the peel, since if the skin is handled too roughly, too much glycolic acid could penetrate too quickly locally and cause post-inflammatory hyperpigmentation.

Dyschromia – melasma

Xerosis, ichthyosis and warts

Combining glycolic acid in a 50% peel and daily creams of 8–12% helps moderately improve dyschromia of a purely epidermal origin.

AHAs have been prescribed for a long time in the treatment of xerosis, ichthyosis and sometimes warts. Dry and rough skins are an excellent indication for AHA creams and peels.

Use of an AHA cream alone More often than not, it takes 3–4 months of daily applications of AHA creams alone to get a clinical result. AHAs are not renowned for their anti-tyrosinase action; they limit melanin synthesis mainly through their antioxidant power and increase the turnover and renewal of cells laden with pigment. Using just AHA creams as the only form of treatment for melasma is disappointing.

AHA cream and peel Combining regularly applied glycolic acid peels with AHA daily care creams increases the effectiveness of both. One of the mechanisms of action of AHAs is to facilitate penetration of the components of cosmeceutical creams used between the different peel sessions. AHA peels help rid the superficial layers of the epidermis of an excess of melanin, and AHA creams applied daily increase keratinocyte turnover, with the melanin produced being diluted in the increased number of keratinocytes. Combined used of effective sun protection reduces melanocyte production and improves the results.

AHA peels and non-AHA cosmetics Combining regular peels with Blending Bleaching® cream and effective sun protection (see Chapters 2 and 3) is the most effective option for treating melasma. Tretinoin can be combined with other cosmetics, as can hydroquinone, tyrosinase inhibitors and antioxidants. It has been proved that applying a depigmenting cream between peeling sessions is more effective than applying a glycolic acid cream. It has also been proved that a treatment combining peels and a depigmenting cream is more effective than treatment with depigmenting cream alone. AHA peels are not, of course, the first choice of treatment for melasma.

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Easy Phytic® (see Chapter 11) solution is particularly well tolerated by patients with ichthyosis, who soon feel an improvement in the elasticity of the superficial layers of the skin, which ‘pulls less’ after the first applications.

Hyperkeratotic eczema Glycolic or lactic acid 15–20% has been used in the treatment of hyperkeratotic eczema and hyperkeratosis of the palms and soles.

Glycolic acid as a pre-peel treatment Glycolic acid helps to increase penetration and enhances the action of the active molecules in the cosmeceuticals or medication applied between peeling sessions. It may act as an antioxidant and chelate iron ions (reducing the production of free radicals). Applying a 12% glycolic acid cream after exposure to the sun helps reduce the duration of the erythema. Glycolic acid has also been used as a preparation for a medium-depth peel, to enhance the penetration of trichloroacetic acid (TCA) to the papillary dermis (i.e. before a 35% m/v TCA), for example. However, in my opinion, the uneven penetration of the glycolic acid peel is not ideal for enhancing TCA penetration. The TCA will penetrate more deeply where the glycolic acid penetrated most, and the overall result could be uneven. AHA peels have been used unsuccessfully in the treatment of stretch marks, both as monotherapy and in combination with corundum crystal microdermabrasion before the peel. Treating the stretch marks with microdermabrasion beforehand enhances AHA penetration, but does so linearly, in the form of claw marks (Figure 8.1). The results are poor, even on fine, white, superficial stretch marks.

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Effectiveness of AHA peels The effectiveness, in cosmetic terms, of a glycolic acid peel can sometimes be miraculous, sometimes non-existent. Some patients are delighted and others are deeply disappointed, but more often than not the result of a series of peels with glycolic acid in an aqueous solution is considered ‘average’. However, long repetition of the peels can maintain the appearance of the skin or even visibly improve it. One clear advantage of glycolic acid lies in the fact that patients can carry on with their professional and social lives immediately after the peel, without any visible signs of flaking7 in the days following the treatment. Cosmetic improvement is very gradual, and often, if there is no good-quality pre-treatment photographic record, the patient as well as the practitioner may wonder if the treatment has really been effective. Although the patient’s immediate entourage might not really notice any difference, the people the patient meets less often will notice some change and might comment on how rested or youthful they look. Repeating peels over a long period of time ensures the progressive effectiveness of peels with glycolic acid in an aqueous solution.

Effectiveness is doctor-dependent The application technique used by the doctor, how carefully he applies the peel and his experience are all factors that influence the outcome of treatment.

Effectiveness depends on the galenical form Not all glycolic acid peels are the same as far as the skin is concerned. The peels that are the most difficult to use are glycolic acid in simple aqueous solution and glycolic acid masks (because it is difficult to monitor how the skin is reacting). The most effective peel would be one that does not need neutralizing, in spite of having a pH of 0.5 for a solution with a pKa between 3 and 4.

Effectiveness is doubly timedependent

Figure 8.1 Alpha hydroxy acids peel after microdermabrasion.

The effectiveness of a peel with glycolic acid in aqueous solution depends on the amount of time for which the acid is contact with the skin and therefore on how soon it is neutralized.8 Neutralizing too soon only allows a small proportion of the acid to act. Effectiveness also depends on the number of sessions. The greater the number of sessions, the more visible are the results. The effectiveness of glycolic acid is therefore entirely dependent on time in both the short and long

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term. In the short term, the same concentration will reach the deeper layers if it is left on longer before being neutralized. In the long term, for the results to be visible, a number of repeated peels are necessary, even with 70% unbuffered glycolic acid on a well-prepared skin. A single application of partially buffered 50% glycolic acid only allows exfoliation ‘just beneath the surface’ – plainly subclinical.

Effectiveness is patient-dependent Preparing the skin properly during the weeks before the peel helps the glycolic acid penetrate more evenly and deeply. The quality of the results will be better if the patient follows the doctor’s recommendations to the letter. Some patients underestimate the importance of preparation and do not put on the creams they have been prescribed. The upshot is inadequate and uneven penetration, which leads to inadequate results and an increased risk of complications. Some overenthusiastic patients, on the other hand, think they can get into the doctor’s good books by applying the pre-peel treatment more often or more liberally than prescribed. This results in an unexpected increase in skin permeability that deepens the effect of the glycolic acid and increases the risk of complications, without the advantage of a better outcome. With Easy Phytic®, there should be no pre-peel preparation, as the stratum corneum must be intact to allow it to act progressively. Creams likely to facilitate AHA penetration should be stopped 2 weeks before the first Easy Phytic® treatment.

should be a specially detailed file recording the various events of the peel and the treatments accompanying it.

Effectiveness on wrinkles, fine lines and folds A glycolic acid peel is not an effective treatment for folds and wrinkles. Fine lines can improve gradually over the course of repeated glycolic acid peels. New collagen synthesis has been noted in the papillary dermis, but what seems to be responsible for a large part of the results of a glycolic acid peel on fine lines is the edema that is caused and maintained by the repeated application of the acid. The tautening and filling effect on the skin is sadly only temporary. Whatever the case may be, it is interesting to note that it is possible to improve fine lines, if only slightly, without causing skin necrosis. The treatment plan must be rigorous, and care between and after peels is of vital importance.

Notes 1. 2. 3.

4.

A glycolic acid peel is not an ‘end in itself’ A glycolic acid peel should never be considered as an end in itself, but as part of an overall care plan for the past and future of a patient’s skin. Pre- and post-peel care plays a large part in the final outcome. For the follow-up, there

5.

6. 7. 8.

Except that the skin’s texture may feel smoother. Peyronnet B. Acide trichloracétique ou acide glycolique? J Med Esth Chir Derm 1994; XXI (84): 257–60. Wrinkles can only be improved by using deep peels; folds usually only respond to surgery, support threads or fillers. An improvement in the appearance of fine lines can be seen after 4–6 months of daily application of 10–12% glycolic acid cream. The stratum corneum is thicker and so more impermeable in photoaged skin. Piacquadio D, Grove MJ, Dobry M. Efficacy of glycolic acid peels questioned for photodamaged skin: a pilot study. Dermatol Times 1992; May: 52. Skin Tech (www.skintech.info). If the glycotic acid is neutralized as soon as erythema appears and before any frosting appears. In other words, it depends on the ‘contact time’.

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9 Alpha-hydroxy acids: application as cosmetics and as peels

Cosmetic application of glycolic acid Since the application of glycolic acid at first reduces the thickness of the epidermis, the skin can no longer provide the same protection against light, and it is essential to use effective sun protection to avoid the risk of accelerated photoaging. A glycolic acid cream or gel can easily be prepared in a pharmacy dispensary, at concentrations of 8–15%. There are many commercial preparations of glycolic acid that have the combined advantage of spreading evenly and a galenical form that allows better penetration of the acid. These low-concentration, daily topical treatments are mainly indicated for preparing the skin for other techniques, for follow-up treatment between peels or for maintenance treatment afterwards. In general, patients who use glycolic acid as a cosmetic do not expect or will not accept any flaking. If the skin does flake, treatment should be stopped and started again a few days later at a lower concentration (or warm water can be sprayed on the face before applying the glycotic acid cream to dilute it). As monotherapy, 8–15% gels (which can be buffered to the physiological pH to 4.55)1 are applied twice a day, after washing the face with a mild soap (e.g. Avene®) if the skin is ‘normal’. If the skin is dry, care should be taken not to degrease the skin, so that the gel does not penetrate too deeply. If the skin is oily and/or acneic, it should be degreased with a glycolic acid-based cleanser before applying the gel. It is essential to use effective sun protection. As a precaution, the initial concentration of glycolic acid should not be more than 8% and the gel should be applied every other day at first. The concentration and frequency of application can be increased, depending on the skin’s response and tolerance. When treating severe photoaging, the concentration of the glycolic acid should be gradually increased from 8% to 12%, 15% or possibly 20%. Alpha-hydroxy acids (AHAs) can be applied on the face as well as the neck, décolletage, hands, forearms and other parts of the body. It must be remembered that the skin on the face is far more permeable than the skin on the limbs or torso.

Combination of AHAs and tretinoin Shared effects Tretinoin and AHAs act on the epidermis and the dermis. When used over a long period of time, they both have the following effects: ■ an increase in the overall thickness of the epidermis at the same time as a decrease in the thickness of the stratum corneum: the skin appears smoother and more hydrated ■ increased dermal thickness and new synthesis of collagen and elastin fibers

Specific effects Retinoids induce neoangiogenesis, whereas AHAs act on the dermis without necessarily going through a phase of inflammatory reaction. We can therefore assume that their combined effects can produce better results at the same time as reducing the incidence of side-effects thanks to the use of lower doses of each of these two potential irritants. For example, if there is resistance to (daily or twice daily) monotherapy with tretinoin2 at 0.1%, applying an 8–10% glycolic acid gel beforehand helps the retinoid to penetrate more efficiently. Tretinoin and AHAs can be applied separately, but they can also be mixed in the same gel. If, on the other hand, a patient cannot tolerate a concentration of tretinoin at 0.05%, applying an 8–10% glycolic acid cream in the morning will make a tretinoin cream at 0.015% applied in the evening more effective, at the same time as reducing the irritation caused by the retinoid. These combinations must always be used under close medical supervision, however, as in dual therapy, skin reactions can be highly unpredictable and severe in some patients. More sensitive skins can be treated as follows: ■ days 1–15: 8–10% glycolic acid cream in the morning

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■ days 15–30: 10–12% glycolic acid in the morning ■ days 30–60: 8–10% glycolic acid in the morning plus 0.015% tretinoin in the evening The doses of each product should be increased gradually thereafter. If the patient has a tendency to erythema, photosensitivity or telangiectasias, the glycolic acid should be increased and the concentration of the tretinoin decreased. If the patient has thin skin, the tretinoin should be increased more quickly than the glycolic acid.

Combination of AHAs and hydroquinone There is no point combining hydroquinone and AHAs in a peel solution, as hydroquinone has a tyrosinase-inhibiting action that can only establish itself gradually and act on the first biochemical stages of melanin synthesis. On the other hand, it is worthwhile combining the two in the daily treatment of melasma between or after peels. The pharmacist should be asked to add 3–8% hydroquinone to a water-in-oil cream with an 8–10% glycolic acid concentration. Gels are more active and better tolerated by oily skins, while the most suitable galenical form for dry skins is cream. Kojic acid (2–5%) can also be added gradually to the combined glycolic acid plus hydroquinone formulation to enhance its action.

Combination of AHAs and other topical pharmaceuticals The reduction in corneocyte cohesion caused by AHAs allows topical preparations containing cortisone, antifungal and antimitotic agents, etc. to penetrate more easily. 5-Fluorouracil (5-FU) has been widely combined with glycolic acid in the treatment of severe photoaging. Application should be ‘pulsed’ to limit the inflammatory reaction caused by daily application of 5-FU. Glycolic acid 10% should be applied once or twice a day while the 5-FU (as a cream with a concentration of 1–5%) should only be applied on two consecutive days per week, every other week. Actinic keratoses on the scalp can tolerate a weekly application of 5-FU combined with glycolic acid. David R. Harris3 reports treating actinic cheilitis by applying a Vaseline® or silicone ointment containing 5% glycolic acid and paraffin. This treatment can be deepened by periodic applications of 5-FU and/or light trichloroacetic acid (TCA) peels. AHA peels can be used to treat patients of all skin phototypes who cannot accept any downtime. Results are, however, difficult to predict: some patients show a rapid

improvement in the quality and color of the skin, while others do not notice any cosmetically visible change. The unexpected, though rare, occurrence of complications always poses a major problem when a treatment has been guaranteed ‘not be noticed by a third party’.

Application of glycolic acid peels Pre-peel preparation Long-term preparation Long-term preparation starts 4–6 weeks before a waterbased AHA peel. It can be non-specific or specific. It is not essential, but noticeably improves results by ensuring deeper and more even penetration of the glycolic acid peel. Greater vigilance is required when applying the peel, however, as it must be neutralized more quickly. Non-specific preparation to make a water-based AHA peel deeper and more even In the evening, a 0.05% tretinoin cream should be applied (see Chapter 2). This cream reduces the thickness of the stratum corneum and provides a deeper peel with the same concentration. A 10% (non-photosensitizing) glycolic acid gel could be applied on younger women in the morning. Specific preparation: to give patients a focused care plan Preparing a patient who has acne is not the same as preparing a patient with photoaging or melasma. Hyperpigmentation of all sorts responds extremely well to pre-peel treatments. Menopausal or post-menopausal women can benefit from a hormone cream as part of anti-aging treatment. The following formulation can be prescribed: testosterone propionate 100 mg estrone 5 mg estradiol benzoate 5 mg eucerin® O/W 45 g or Neribase® 45 g See Chapter 2 for more details.

Medium-term preparation This concerns combined treatments used before the peels as well as the cosmeceuticals or pharmaceutical products used by the patient (see above). Medium-term preparation starts 2–4 weeks before a peel.

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Folds, wrinkles and fine lines should be treated beforehand with dermal fillers, thread lifts, mesotherapy, stimulation or any other treatment chosen by the doctor. Benign tumors can be excised or treated by shave biopsy or lasers. Rosacea should be treated before the peel during this same period. Botulinum toxin, ideally should be injected 8 days before the first water-based glycolic acid peel.

Short-term preparation It is preferable not to put on any cream that could permeabilize the skin or use any technique likely to damage the stratum corneum during the few days before an AHA peel. Small retention cysts can be removed with a needle or number 11 scalpel blade 1 week before applying the waterbased glycolic acid.

Desquamation Buffered solutions of glycolic acid, when applied correctly, only produce virtual desquamation. Water-based glycolic acid does not penetrate evenly, and the risk of localized overpeeling, scabbing or post-inflammatory hyperpigmentation is not insignificant. The destruction of the epidermis that causes visible flaking depends on how the peel is applied, as well as on the type of peel used. A short contact time with a 50% glycolic acid peel at pH 3.5 produces almost no visible flaking, while a longer contact time with 70% glycolic acid at pH 0.5 induces epidermolysis and the appearance of small scabs and visible flaking. The correct contact time with a water-based 70% glycolic acid at pH 0.54 causes little or no flaking, but repeating it too soon could trigger visible flaking. Applying a water-based 70% glycolic acid peel at pH 0.5 with a flat brush will cause less flaking than if it is applied with a gauze pad (which is slightly abrasive) after the skin has been disinfected with alcohol or degreased with acetone or ether, or after the skin has been prepared for several weeks with tretinoin cream. All other conditions being equal, applying a greater quantity of AHA causes more of the epidermis to be destroyed and more visible flaking. Easy Phytic® solution, in spite of its pH of 0.5, causes almost no flaking and penetrates more evenly than other AHAs, because of its formulation and application procedure.

Treating the face or body AHA peels have mostly been used to treat the face, but can also be used to treat other areas of the body. Facial skin is more permeable to AHA peels than the skin on the rest of the body. The neck, décolletage, hands and forearms can be treated with a combination of AHA peels and effective post-peel care (see Chapter 3).

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With these body treatments, we can expect an improvement in the quality of the structure of the skin, improved hydration and some temporary lightening of the complexion. Lentigines and keratoses should be treated by another method in parallel with AHA peels. There are other, more efficient, techniques to treat these problems: liquid nitrogen, dry ice, Only Touch® peel, ‘intense pulsed light’ (IPL), laser, etc. Dr Robert Vergereau (France) compared the use of dry ice, Erbium laser, Q-switched laser, coagulation and Only Touch® peel. He concluded that: ‘If all these methods are satisfactory, in my opinion, the technique using trichloroacetic acid5 is the most beneficial’. Treatment of other areas of the body with AHAs is not often described, because of the poor penetration of these acids through the skin of the body. A technique combining abrasion and an application of Easy Phytic® solution (see Chapter 11) is more successful on the legs, arms and torso.

Buffered or unbuffered AHAs? The results produced by buffered AHA peels can, in a way, be compared to those produced by unbuffered peels, but only when applied over a longer period of time and more frequently. From a histological point of view, all peels produce comparable results depending on the strength of the peel. The action of an AHA peel with a pH higher than its pKa and close to the skin’s physiological pH (4.5–6) is very slow. A buffered solution will often only be applied for the first ‘reconnaissance’ peels or on sensitive skins. Thereafter, the peels will be performed with 70% unbuffered glycolic acid solution in a gel or Easy Phytic® solution.

How many sessions should be anticipated? AHA peels should be considered a long-term treatment. No noticeably visible improvement, except for a softer skin, should be expected until after many sessions. Sometimes, the results do not become obvious until after 8–10 sessions of water-based unbuffered 70% glycolic acid peels. How frequently the sessions should be repeated depends on how the skin reacts or how sensitive it is. Some thin and sensitive skins will not tolerate more than one session every 2 weeks, whereas thicker or oilier skins will easily tolerate a weekly session or even more. It is clearly difficult for people who can only tolerate one session a month to achieve visible results. Even the most willing patients can be worn down by the boredom of repeated sessions that can sometimes be unpleasant and have a limited effect. Patients who cannot be treated more than once a month often give up treatment long before it has finished.

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Classic application technique for glycolic acid A glycolic acid peel can be applied in an aqueous solution or in a gel, with a gauze pad, a brush, presoaked cotton swabs or pads, gloved fingers, etc. Compact and opaque AHA masks have been used, but monitoring the skin while the mask is on is neither easy nor certain. The glycolic acid solution is applied quickly (in 15–20 seconds maximum), so that the contact time is the same for the whole face. The solution should be applied to the most resistant areas first (the forehead) and to the more sensitive areas last (the eyelids). It is important to develop application habits and always use the same system, both for applying and neutralizing the peel. Partially squeezing out the applicator before using it guards against the product forming ‘pools’ on the skin. Massaging the skin with a gloved finger allows more even penetration or deeper local penetration if the doctor considers it necessary. By closely monitoring changes in skin color, the AHA solution can be neutralized before any frosting occurs. To a certain degree, the contact time is more important than the total quantity of AHAs applied to the skin: a low overall quantity of glycolic acid left to act for a longer time can penetrate the skin more deeply than a larger quantity that is neutralized immediately. As well as the choice of peel, monitoring the contact time is an essential part of any glycolic acid peel. This is why the glycolic acid peel has been called ‘time-dependent’, prompting the purchase of many completely redundant timers. Glycolic acid can be applied up to a few millimeters from the eyelashes, no matter what its concentration. If any glycolic acid comes into contact with the eyes, they should be rinsed immediately with plenty of water, and drops of artificial tears or physiological solution should be applied. Glycolic acid is not a protein coagulant like TCA or phenol, and the risk of damage to the eye after contact is not high. In fact, dilution from teardrops appears to be enough to avert most of the danger. The author has never come across any objective ocular damage, even in the extremely rare case of contact between glycolic acid and the eyes. Sometimes, a very small quantity of glycolic acid can be drawn up into the eye by capillarity if the peel is applied too close to the conjunctivae. This immediately causes the formation of tears, which dilute the acid and reduce its aggressiveness. Patients should be asked to keep their eyes shut while waiting to have eye drops put in that will bring immediate relief.

Contact time The contact time is the time during which the AHA is left to act before being neutralized and stopping its effect. It depends more on the appearance of erythema than on the

Table 9.1 Correlation between skin appearance and depth of AHA peel No erythema Spots of erythema Patches of erythema Widespread erythema Frosting

Virtual peeling effect Very, very superficial Very superficial Superficial peel, suitable depth for AHAs Too deep for an AHA peel

concentration, the pH, the total volume applied, the number of applications, etc. AHAs in aqueous solution do not penetrate the epidermis evenly, and the erythema, which is the first sign of the skin reacting to a peel (Table 9.1), does not appear evenly either, but rather in spots or patches. It is therefore essential for the doctor to stay beside the patient during this phase of the peel and not to take his eyes off the treated area. The safety limits are not very flexible when using AHA in aqueous solution, and a peel can go from ‘too superficial’ to ‘too deep’6 very quickly. Contact time should end as soon as erythema begins. The problem is that it is not long before erythema turns to frosting, and the doctor is often faced with the following dilemma: neutralize too soon and have limited results, or try to neutralize a bit later and risk complications. It was to avoid this dilemma that the author developed Easy Phytic® solution.

Contact time for a glycolic acid peel Each patient’s skin reactivity should be tested by an initial application of a less concentrated and/or a partially neutralized peel (e.g. 50% at pH 3.5). As a precaution, the initial contact times should be short, in order to test the skin’s reactivity. When we say that an AHA peel is ‘time-dependent’, we mean that the contact time depends on examining the skin directly and not on the clock. We do not really need to know exactly how long the product should be left to act: the right contact time is enough time for erythema to occur, but no frosting at all. Table 9.2 shows, as an approximate guide, the depths reached by unbuffered 70% glycolic acid (pH 0.5) with different contact times on the face. It should always be remembered, however, that AHAs should never be used to do anything other an epidermal peel. Each patient has their own particular level of sensitivity and contact time. It is therefore important to take precise notes on the treatment given: the type of solution, the concentration used, the contact time (except in the case of Easy Phytic® solution, which does not need neutralizing), the places where erythema first appears,7 the number of coats,

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Table 9.2 Depths reached by unbuffered 70% glycotic acid (pH 0.5) as a function of contact time Contact time (min)

Depth of effect

1–5

Gradually deepening epidermolysis, depending on contact time and skin sensitivity

5

The acid reaches the dermoepidermal junction

10

The acid reaches the dermis – which is not desirable, as its effect, locally, will be similar to that of 30–35% TCA m/v

15

The depth of skin necrosis, locally, is histologically comparable to or greater than that reached with 35–40% TCA m/v

The problem with AHA peels clearly lies in the neutralization. Easy Phytic® provides a solution to this difficult problem, as, in spite of its pH of 0.5, this peel does not need to be neutralized and therefore benefits from the effectiveness of 100% of the molecules applied to the skin. It should be remembered that rinsing with pure water dilutes an acid (lowers its concentration), whereas a base solution neutralizes it (raises its pH). The neutralizing solution should be prepared before the peel so that it is instantly available when neutralization is necessary (Box 9.1). Skin burns as a result of neutralizing too late because of lack of preliminary preparation of the neutralizer would always be considered as professional misconduct by an expert.

Box 9.1 Preparing the neutralizing solution The simplest neutralizing solution consists of a solution saturated with sodium bicarbonate: fill a bowl with warm water and gradually add the sodium bicarbonate powder (Figure 9.1a), stirring all the time. When the sodium bicarbonate no longer dissolves and forms a sediment in the bottom of the bowl, the solution is saturated (Figure 9.1b). There is no point trying to get a more concentrated solution.

the type of neutralizing solution applied, etc. These notes will come in very useful for working out any potential change in contact time for subsequent peels. A cautious contact time of 2 minutes for a first peel with 70% glycolic acid, pH 0.5, on a patient with healthy skin of normal thickness can gradually be prolonged by 30–60 seconds in subsequent peels, if the skin can tolerate it – that is to say as long as there is no frosting.

Neutralization An AHA peel should be neutralized as soon as erythema appears and before (or, at the very latest, just as) the first pinpoints of protein coagulation (frosting) appear. The peel can be neutralized with a solution saturated with sodium bicarbonate, for example. We saw above that the ‘bicarbonate system’ is a natural and powerful system for neutralizing organic acids. Neutralizing an AHA peel with a bicarbonate solution immediately stops its action. The reaction of an acid with a base produces a salt that has no peeling activity. The question is then what proportion of acid was effective during the AHA peel. If unbuffered 70% glycolic acid is applied and neutralized after a few minutes’ contact time, what is the proportion of free acid that will have been effective: 30% or 50%? If a solution is applied with a concentration of 70% but buffered at exactly pH 3.83 (which is the pKa of any glycolic acid solution), it contains only 50% free and active glycolic acid; the other 50% consists of an inactive salt. In reality, this solution corresponds to only 50% of the 70%, that is 35% of pure glycolic acid. Rapid neutralization of this solution reduces its effectiveness even further.

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A

B

Figure 9.1 (a) Sodium bicarbonate powder. (b) Saturated solution of sodium bicarbonate.

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The doctor and assistant should carefully monitor all the areas treated with acid. Surfaces that develop any local erythema should be neutralized there and then with the tip of a sponge soaked in saturated bicarbonate solution (sodium bicarbonate is readily available at pharmacies). It is possible to apply corticosteroid cream to the localized erythema. When several areas have become erythematous and been neutralized, the whole face should be neutralized by applying strips of paper, for example,8 soaked in the neutralizing bicarbonate solution (Figure 9.2). If the glycolic acid is not completely neutralized, applying a solution of sodium bicarbonate triggers a chemical reaction that produces a warm tingling sensation and may contribute to the development of temporary postneutralization erythema together with bubbles. The skin is

completely neutralized when no more ‘bubbles’ are felt. Neutralizing with a bicarbonate solution, or any other commercial neutralizing solution, is only obligatory when using unbuffered solutions. When the pH is close to the physiological limits (pH >4), thoroughly rinsing with running water is enough,9 since the relatively high pH of these partially buffered solutions is not too aggressive for the skin, and diluting the acid is all that is needed to increase its pH sufficiently. AHAs are the only peels where neutralization is important – TCA, resorcinol, salicylic acid and phenol do not need neutralizing. Glycolic acid is not a protein coagulant. It does not combine with proteins and is not neutralized, like TCA. It remains aggressive until it is neutralized, diluted or picked up by the skin’s buffer systems. After neutralization, the patient may continue to feel the acid burning in places. The patient can be given a cotton pad soaked in bicarbonate solution and asked to neutralize the more sensitive areas more thoroughly until the burning sensation has completely gone. The patient will often go back to the nostrils and eyebrows several times. More sensitive areas can actually be protected before the peel with Vaseline® applied on a cotton bud.

Neutralizing partially buffered solutions A

A (partially) buffered solution has an artificially high pH that makes it less aggressive. In fact, to allow doctors to do their job properly, the pH of glycolic acid or other AHA solutions should be given on the bottle. When using a prescription solution from a pharmacy dispensary, it is vital for the doctor to take the trouble to check the pH of each solution himself (with a pH test strip, pH meter, etc.). Checking the pH personally can sometimes bring surprises – and confirms the need to do so. In case of doubt or if the pH is not known, it is, in any event, better to opt for neutralization: there is no danger in neutralizing a peel, whereas it can be disastrous not to (Table 9.3). In the interests of caution, it is best to neutralize the peel in the face of any doubt. After neutralization, spraying the skin with warm water gets rid of any excess bicarbonate, and the face can then be dried.

Table 9.3 Neutralization of glycotic acid peels: appropriate guide B

pH of peel

Procedure

Figure 9.2

>3.5 0.5–3.5

Rinse with water Neutralize, then rinse with warm water

(a) Soaking paper strips in the bicarbonate saturated solution. (b) Application of paper strips.

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Post-peel care

Maintaining the results after peels

Further information is available in Chapter 3.

When it comes to the patient’s overall treatment plan, he or she will often ask how best to maintain or improve the results achieved. A monthly maintenance peel can be recommended, as well as continued use of the treatment started between peels. Sun protection is indicated in all cases to limit UV penetration through a temporarily thinned and hyperpermeable skin. See Chapter 3.

Immediate post-peel care The appearance of uniform erythema indicates that the glycolic acid has penetrated properly, and is the signal for neutralization. After neutralization, spraying with warm water cleans the skin of any residual chemicals. Immediately after the glycolic acid peel, the skin is very permeable, and products applied to it during this period will penetrate more deeply and thoroughly. This is an ideal time to apply the classic post-peel care treatments: see Table 3.1 in Chapter 3.

Care between peels Glycolic acid peels help cosmetic or medical treatments applied between peeling sessions to penetrate more easily. Tretinoin should be used carefully during the days immediately following a peel, especially when the skin is thin and dry. The choice of vehicle should be discussed with patients: a patient with oily skin will not always like using creams and might prefer a gel; the same gel would be unpleasant for a patient with thin, dry skin.

Notes 1. 2.

3.

4. 5. 6. 7. 8. 9.

See comments on buffering AHAs later in this chapter. Resistance to tretinoin: no visible signs and no discomfort, even with relatively high doses; there is no erythema and no unpleasant sensation in the skin. Harris DR. Treatment of aging skin with glycolic acid. In: Elson ML, ed. Evaluation and Treatment of the Aging Face; Springer-Verlag, NY. 1995: 31. Effective neutralization as soon as erythema appears. Author’s note: The comparison was made using Only Touch® peel combined with Easy TCA®. That is, too deep in relation to the peel used: a glycolic acid peel should be superficial. During the next peel, the AHA should be applied last on the areas where erythema appeared soonest. Cotton pads or any other means of application can also be used. It is often when rinsing with a lot of water that a drop of acid can come into contact with the eye.

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10 Alpha-hydroxy acids: side-effects of AHAs Complications with alpha-hydroxy acid (AHA) peels are rare, easily avoided, and often spontaneously reversible or treatable by simple topical applications. More details on complications, their origins, prevention and treatment can be found in Chapter 37.

Allergies The author is not aware of any documented case of allergy to glycolic acid or other AHAs. In the case of an allergic reaction, the doctor should test for allergies to the solvents or additives in the AHA solution. Some allergic-type reactions are, in fact, caused by the AHA penetrating the dermis, which triggers a limited and localized inflammatory reaction whose symptoms are redness and swelling. This reaction disappears without treatment within 48 hours.

Pain There may be some irritation and a burning sensation, especially at the beginning of treatment. Even AHA creams (or especially gels) can cause irritation at the start of treatment. The more the skin has been ‘prepared’ or the thinner it is, the more painful it will feel when the peel is applied. The pain is proportional to the concentration of the acid and inversely proportional to the pH. A 70% peel is more painful than a 50% peel. A 50% peel at pH 3.5 is not as painful as a peel at pH 1.5. A 70% unbuffered solution applied to a thin skin prepared with tretinoin will be more painful than a 50% solution at pH 4 applied to an oily, unprepared skin. Whatever the case, this pain – a kind of tingling or burning sensation – is quite bearable. There is no need for anesthesia, analgesia or nerve blocks. More nervous patients might appreciate having their faces fanned (with an electric or hand-held fan) or the calming effect of a voice during the peel. Neutralizing the peel with sodium bicarbonate solution stops the pain.

pale pink; this coloring lasts between 15 and 60 minutes. Solutions that are too highly concentrated or are left on too long and allowed to penetrate too deeply locally can cause the formation of scabs, which, if pulled off, leave persistent erythema for several weeks or months. This eventually resolves naturally and leaves the skin a little softer. It is best to increase concentrations and contact times gradually with patients whose professional lives will not allow them to spend time locked away recovering.

Telangiectasias Although there is evidence of a certain degree of angiogenesis with AHAs, telangiectasias are rare.

Dryness, desquamation, sensitization Long-term topical use of 8–15% glycolic acid creams gradually reduces corneocyte cohesion and can cause the skin to flake. This effect is not as pronounced as with tretinoin. Dampening the skin before applying the cream dilutes the product and reduces the risk of skin sensitization. Daily use of progressively higher concentrations of AHAs can, however, cause continuous lysis of the corneodesmosomes and permeabilization – a long-term thinning of the epidermis. Patients may then complain that their skin is getting more and more sensitive. However, some histological studies show that the skin thickens with long-term treatment with AHAs.

Hyperpigmentation Post-inflammatory hyperpigmentation (PIH) is rare after an AHA peel. It may result from an error in assessment, indication or monitoring, but sometimes it can occur suddenly when a peel has been performed and neutralized correctly. PIH can be treated: for more details, see Chapter 37.

Erythema

Bacterial or viral infections

The skin must be neutralized as soon as erythema appears. At the end of the peel, after neutralizing, the skin is usually

Bacterial infections result from scratch lesions or epidermolysis from overpeeling. Bacterial infections do not occur

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when using topical treatments with 8–15% AHA cream. The incidence of herpes outbreaks after a glycolic peel has been performed correctly is no higher than in the untreated population at large. In instances of overpeeling and epidermolysis, the probability of a secondary herpes infection increases with the depth of injury. There is no need for systematic herpes prevention before an AHA peel, but if a patient is very prone to herpes, it would be wise to prescribe valaciclovir to be taken before the peel.

ate, could seriously damage the skin and produce unsightly scars. Any danger of scarring can be avoided by neutralizing areas of local erythema with sodium bicarbonate solution and not allowing any frosting to occur. If the texture of the skin should become uneven as a result of particularly uneven penetration, it can be evened out in the course of later peels.

Shiny skin Scarring A correctly applied glycolic acid peel does not reach the reticular dermis, and there is therefore no reason for it to cause scarring. I have never come across any cases of scarring after a glycolic peel, no matter what skin preparation or concentration of acid has been used. It is obvious, though, that a combination of technical errors can result in a cosmetic disaster. Applying 70% unbuffered glycolic acid in multiple coats with a gauze pad pressed firmly onto a thin and dry skin that has been irritated by a strong dose of tretinoin, without constant monitoring and diluting simply in water instead of neutralizing with sodium bicarbon-

The effect of AHAs on corneodesmosomes can cause all the pores of the skin to unblock and allow all the sebaceous glands to empty at the same time. The skin will remain shiny until it is next washed.

Achromia If the peel penetrates too deeply in a particular place, causing scabbing and delayed healing, it could lead to total and irreversible depigmentation that, fortunately, is limited to the surface area of the scab. It is a rare complication of AHA peels.

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11 Alpha-hydroxy acids: a new slow-release AHA complex with no neutralization required

General remarks Since the 1980s, alpha-hydroxy acids (AHAs) have been used alone or in combination with other acids with a view to achieving good cosmetic results, locally or generally, temporarily or permanently, and without running the risks of deeper peels. The natural origins of the first AHAs – fruit or dairy extracts – account for much of their resounding success. How could anyone resist such a benign-sounding name as ‘fruit acids’? The AHA most often used is without doubt glycolic acid, a small molecule with a low molecular weight that has no difficulty penetrating the stratum corneum, where it acts as a ‘corneodesmosome chainsaw’. It was for this property that it was first indicated in the treatment of ichthyosis and other disorders involving hyperkeratinization. An AHA applied to a clean and degreased skin breaks down the protein structures that form corneodesmosomes. The superficial cell layers are then shed from the epidermis. The skin immediately feels more hydrated, as the fingers no longer touch the dead and dehydrated corneocytes that have been shed but rather living and well-hydrated keratinocytes. AHAs are not toxic to melanocytes, and can therefore be applied on all skin types. They can also be used at any time of the year, on condition that they are combined with a strong sunscreen. AHA peels have other advantages as well: they are non-toxic and hypoallergenic, do not cause protein coagulation, have an excellent safety record, are easy to use and produce satisfactory results in a variety of indications. There is one sizeable cloud on this bright horizon, however: AHAs have to be neutralized at the right moment to limit their penetration. If they are not neutralized, AHAs will continue working until they go beyond their desired effect. Neutralizing too late may cause serious side-effects, while neutralizing too soon makes the peel completely ineffective. Nor is neutralizing the peel the easiest part of the procedure either: the action of the acids has to be stopped when erythema occurs and before the first pinpoint frosting appears. The moment the AHAs have to be neutralized comes between two events that are open to subjective judgment, which increases the degree of risk. Many doctors will

run through the following interior monologue: ‘I should have left the product to act longer for it to be effective’, or worse, ‘I should have neutralized the AHAs much earlier, because now there are going to be complications and unwanted reactions after the peel.’ With the second scenario comes a long period of uncertainty for the doctor, sleepless nights and early mornings filled with anxiety, because complications resulting from neutralizing AHAs too late can only be treated slowly and gradually, sometimes taking several months. The problems raised by neutralization are well known, and various solutions have been put forward to minimize the danger and risk involved with neutralizing conventional AHAs too late. Partially neutralized, less aggressive AHAs with a pH of between 3.5 and 5 can be found on the market. These acid solutions do not need neutralizing, but they do need diluting with water before any frosting occurs. Less risk, however welcome, goes hand in hand with a less effective peel. Another drawback to having to neutralize conventional AHAs with a very acid pH is that the effectiveness of an AHA largely depends on how long the acid is left in contact with the skin. The longer the contact time, the more active the peel will be. Hence, there is a temptation to leave an AHA peel to act as long as possible, in spite of the risk of facing complications. The aim of neutralizing is to stop the effect of the acid. A contact time of just a few minutes before neutralizing the peel gives it just a few minutes to be effective. I therefore aimed to develop a low-pH formulation – between 0 and 1 for maximum effectiveness – that does not need neutralizing. Easy Phytic® solution (EPS: Figure 11.1) was the first of this new class of low-pH AHAs that are active with no need for neutralization. Its pH of 0.5–1 (Figure 11.2) is much lower than the pKa of the different components in the solution,1 which consists mostly of free acid with no ineffective salts.2 Not having to neutralize the solution also means that there is only a minor risk of side-effects, even when each molecule is left to achieve its full effect, undisturbed by external neutralization. It is the skin itself that neutralizes the acids in the EPS. EPS can therefore be defined as a slow-release AHA solution for patients who do not want any visible flaking (it is a

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Figure 11.1 Bottle of Easy Phytic®.

Figure 11.2 Easy Phytic® solution has a pH of 0.5.

non-flaking peel) or for doctors who want to minimize the risk of the sometimes serious complications of conventional AHAs. The solution is saponified3 and adjuvanted, and consists of glycolic, lactic, mandelic (phenylglycolic) and phytic acids. The peel solution – which does not need neutralizing – allows the acids to work gradually and to full effect. This particular property allows a ‘bipolar’ action: the solution starts working on the superficial layers of the epidermis, shedding corneocytes in the same way as conventional AHAs. It then continues working its way through the skin to reach the deeper layers, slowly and not too aggressively. The acid molecules gradually lose their effectiveness as they are neutralized by the natural buffer capacity of the epidermis. The skin can in fact defend itself perfectly well against acid or base attacks thanks to its buffer capacity, which is its ability to maintain the homeostasis of its pH as long as the attack is not disproportionate to its defenses.

When its defenses are overwhelmed by a massive acid or base attack,4 the skin cannot defend itself, and its proteins are destroyed, denatured or coagulated; the skin is ‘chemically burned’. With EPS, the acid molecules in the peel solution are stabilized on the surface of the skin and concentrate in the stratum corneum.5 They are released slowly and therefore reach the epidermis gradually. This ‘slow release’ allows the epidermis to use its full buffer capacity to neutralize the acid molecules that are slowly attacking it. Unfortunately, there is another significant problem with water-based AHAs: they do not penetrate evenly.6 They penetrate more quickly in areas where the stratum corneum is thinner – and therefore more permeable – and more slowly where the stratum corneum is thicker. They penetrate more slowly on the oilier6 parts of the face and more quickly where the skin is dry, infected or irritated. It is therefore essential to prepare the skin for 2–3 weeks before the first water-based AHA peel to even out the thickness of the stratum corneum. The melanocytes also need to be ‘stabilized’ to avoid any potential pigmentary changes. With EPS, the AHAs penetrate far more evenly because of the type of vehicle used and the slow-release mechanism, which eliminates the need for pre-peel preparation. The different types of AHAs used in EPS are important: the three AHAs in the solution actually penetrate at different speeds. Small molecules penetrate the skin more rapidly than larger molecules: the glycolic acid is therefore the first to penetrate, followed by the lactic acid and finally the mandelic acid, the largest molecule, which relies on the lytic action of the other acids on the corneodesmosomes to help it penetrate the skin more easily. Phytic acid, the other active component in the solution, is not an AHA. It is a large molecule: inositol hexaphosphoric acid or cyclohexanehexyl hexaphosphate (Figure 11.3). Because of its high molecular weight, 660.08, it does not pass easily through the epidermis. The action of the three AHAs combined with the phytic acid in the solution, however, makes the stratum corneum more permeable and O O

HO HO

OH

O O

O

O

O

HO

P

O

HO OH

Figure 11.3

OH P

O

P O

Phytic acid.

OH

O

P

HO

P

P

HO

OH

O

OH

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therefore easier for the phytic acid to penetrate. Phytic acid is well known for its anti-tyrosinase and antioxidant action. It is also an iron chelator. This molecule is therefore a good indication for skin-lightening and anti-aging treatments. Finally, phytic acid scavenges the free radicals produced by the inflammation that follows any peel and breaks the usual vicious cycle of post-peel inflammation: peel → inflammation7 → vasodilation → O2 intake + pro-inflammatory components → free-radical production → cell damage → self-perpetuating inflammation → more free radicals ⇒ vicious cycle established There are two sides to inflammation. The first is positive, as it is an essential trigger for post-peel regeneration and the synthesis of new dermal components – no inflammation, no repair. The other side is negative, as the combination of vasodilation (which, among other things, helps improve tissue oxygenation) and pro-inflammatory components increases the generation of free radicals that damage the cell structures upon which the body relies to repair the skin. The presence of phytic acid, an excellent antioxidant thanks to its 12 hydroxy groups, could reduce the incidence of post-peel inflammatory reactions.

Indications AHAs thicken the epidermis and papillary dermis, increase the production of mucopolysaccharides, improve the quality of the elastin produced and increase collagen density.8 Patients treated with EPS also describe an appreciable tightening effect. Although EPS can be used for the same indications as other AHAs, its two areas of choice are aging and acne. EPS can be used as a combined treatment or as a maintenance peel with other deeper treatments; it can also be used alongside other techniques such as mesotherapy and pulsed light.9 EPS is more of a stimulating and regenerating treatment than an actual peel, as there is almost no visible flaking. The epidermis flakes almost cell by cell and not in ‘cell plates’. Patients who are put off having a ‘peel’ for fear of downtime seem to prefer EPS being presented as a ‘stimulating solution’. The term ‘superficial peel’ conjures up images of something relatively ineffective that causes unsightly flaking. EPS can be combined with ‘mesolift’ mesotherapy to particularly good effect: alternating a mesolift and EPS every other week would seem to be the best way to proceed.

Aging skin Aging skin is an excellent indication for EPS. Note, however, that it is still a relatively superficial peel and cannot claim to eliminate folds or wrinkles, which have to be

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treated by surgery and deep peels or laser treatments. EPS could be called a ‘lunchtime peel’, as it can be performed during the lunch hour and the patient can go back to work immediately.

EPS as a classic anti-aging treatment The classic treatment consists of weekly applications of EPS together with use of a suitable cosmeceutical cream (see Chapters 2 and 3,10 and also the section later in this chapter application protocol). The total number of peels will vary between 6 to 10, depending on the skin and how it reacts. At the end of the active phase of the treatment, a maintenance peel can be applied once every 2 weeks and eventually once every month.

EPS combined with mesotherapy A mesolift is a mesotherapy technique that involves injecting stimulating, relaxing or tensing or filling agents such as hyaluronic acid, polymerized DNA, vitamins, trace elements, dimethylaminoethanol (DMAE), eligopeptides, etc. into the dermis. Facial mesotherapy can be rather painful, however, and may require the use of topical anesthetics such as EMLA. The side-effects are not always invisible either: redness, swelling and minor bruising may occur. EPS is therefore ideal for use with a mesolift: mesolift one week, EPS the week after. It is wiser not to apply EPS immediately after a mesolift, because the multiple needle perforations in the dermis and epidermis would enhance local penetration of the peel solution. Similarly, a mesolift performed immediately after an EPS peel would be extremely painful for the patient and the acids in the EPS solution would penetrate through to the deep dermis. Nevertheless, many European, American and Asian doctors have reported using a combination of ‘EPS + mesolift’ or ‘mesolift + EPS’ at the same time, and have achieved excellent results.

EPS combined with botulinum toxin Ideally, the botulinum toxin should be injected a few days before the first EPS session. In this way, the two products can work together to good effect (Figure 11.4). If preferred, the botulinum toxin can of course be used after the EPS. If the botulinum toxin is injected immediately after the EPS, the needle will have to go through the non-neutralized acid solution on the skin and will take a few acid molecules into the dermis, which will make the injection more painful. It is not known how botulinum toxin and the AHAs in EPS interact in the body. The injection could be given, say, a

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A

B

Figure 11.4 (a) Before treatment with botulinum toxin and EPS. (b) After botulinum toxin and two sessions of EPS.

quarter of an hour before the EPS. Another potential problem is that the post-peel inflammatory reaction – even if minor – could move the toxin. Leaving a few days between EPS and the botulinum toxin would seem to be a wise choice. Handling the skin during the peels and post-peel vasodilation11 does not seem to have much effect on the outcome of the botulinum toxin injection. In 10 years of experience injecting botulinum toxin immediately before applying the trichloroacetic acid peel Easy TCA®, I have seen no evidence of any direct interaction between these two procedures.

Combining EPS and ‘flashlamp’ in anti-aging treatments The use of ‘intense pulsed light’ (IPL) for treating aging skin (Figure 11.5) is a widely used technique nowadays. However, many doctors are disappointed with the results obtained with pulsed light as a monotherapy and are look-

Figure 11.5 Sun aging, thinning skin, yellowish color.

ing for a combination of treatments that will benefit their patients. Phototherapy should not be used immediately after EPS, as the light rays will have a much greater depth of action, and may cause photochemical reactions. The presence of EPS on the skin could also refract the pulsed light. EPS can be used after flashlamp treatment, but it is best to be cautious, as the energy from the lamp might breach the stratum corneum and the acids in the EPS might penetrate more quickly. The doctor should be ready to neutralize the peel at the least sign of protein coagulation (frosting). It is a good idea to alternate flashlamp treatment and EPS, as with the mesolift: EPS one week and flashlamp the following week.

Anti-aging treatment for the body EPS does not penetrate body skin as easily as it does facial skin. Several coats are needed to trigger erythema and large amounts of solution have to be used. Treating the body with EPS takes a long time and large quantities of the product. A combination of sandpaper abrasion and EPS (Figure 11.6) can be used to treat photoaging on the back, upper or lower limbs. Light abrasion12 can thin the stratum corneum enough to allow the EPS solution to penetrate the skin

Figure 11.6 Day 4 after EPS preceded by superficial abrasion with 3M Wetordry® sandpaper P220.

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more easily and more quickly. The sandpaper should be used gently and evenly, without causing any unpleasant sensation, pain or bleeding. Only the most superficial layer of the stratum corneum should be removed. Any deeper abrasion that destroys the stratum corneum completely is to be avoided, as the active components of the EPS would penetrate the skin too quickly and soon saturate its defenses, its buffer capacity. When using this abrasive technique, it is essential to have the necessary equipment at hand to neutralize the peel (see the section on neutralizing glycolic acid in Chapter 9) in case it penetrates more deeply than desired. This technique can be repeated at a minimum of 2-weekly intervals only. A

More frequent application Another application technique for EPS can be considered, especially for patients with resistant skin who would benefit from a more intense tightening effect. EPS is applied following the usual protocol as described later on in this chapter, but it is repeated more frequently. Applying the solution more frequently requires great care and experience. Daily applications of EPS allow the peel to gradually penetrate more deeply. After a few days, small scabs will start to appear, signaling that the maximum depth has been reached and must not be passed. Within about 2 weeks, the scabs will have healed, and daily applications can be started again. Appropriate cosmeceuticals should be used between the two series of daily peels. For quicker results, the EPS can also be applied two or three times a week (e.g. on Saturday, Monday and Wednesday), especially on thick and oily male skin or in cases of acne.

B

Used as an anti-aging maintenance treatment EPS can be used to maintain the results of other peels when the patient wants a maintenance treatment without visible flaking. It should then be applied once a month.

Acne EPS is an excellent treatment for mild comedonal, papular or papulopustular acne. Peels are obviously not indicated in more severe cases of acne, for which only dermatological treatments will do. Comedones, microcysts and ‘whiteheads’ should be removed13 during the week before the first EPS to avoid handling the skin immediately before the peel at the risk of the EPS penetrating too deeply. Some doctors report removal of comedones or microcysts immediately before EPS, with good results. EPS can improve the appearance of acneic skin in just a few sessions when it is combined with Skin Tech’s Purifying® cream, which consists of glycolic acid, retinol, vitamin E, tri-

C

Figure 11.7 (a) Active papulopustular acne and post-acne pigmentation. (b) After four EPS and Purifying® cream. The acne has almost disappeared. (c) Substitution of Purifying® cream with Blending Bleach® cream for PIH treatment.

closan, glycyrrhetinic acid and tea-tree oil. As can be seen in Figure 11.7(a, b) (see also Figure 11.8), four EPS peels used in conjunction with Purifying® cream can vastly improve a patient’s pustular acne. After four sessions, the acne is almost

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inactive. The oldest post-acne pigmentation persisted, however, and in this case we continued to apply EPS once a week (four extra sessions), combining it with Blending Bleaching® cream (containing tyrosinase inhibitors and antioxidants) to treat the persistent pigmentation. After eight sessions of EPS, of which the first four were combined with Purifying® cream and the last four with Blending Bleaching® cream, the patient’s skin started to look healthier (Figure 11.7c).

Pigmentation disorders and other indications EPS acts similarly to other AHAs. A

Unwanted effects – precautions

B

EPS is a very particular peel and has its own particular sideeffect. The day after application, an average of 2% of patients develop an allergic-type reaction consisting of small, slightly pruritic pinkish nodules (Figure 11.9). This reaction is only seen with this peel. It can often result from using products before a peel that enhance penetration of the acids or from post-peel treatments that are unnecessarily aggressive or incompatible. Questioning patients closely about their cosmetic routine may provide an answer. In most cases, however, it seems to be for the following reason: in classic AHA peels,14 the AHAs have to be neutralized, but with EPS they are not; as they are not neutralized, the acids may penetrate as far as the dermis and cause a local inflammatory reaction (a source of fibroblast stimulation and new collagen production as well) in the ‘highest’ dermal papillae. This inflammatory reaction subsides by

C

Figure 11.8 (a,b) Papulopustular acne before treatment. (c) After four sessions of EPS and Purifying® cream, the acne is no longer active. After cleaning active acne, the Purifying® cream should be replaced by Blending Bleaching® cream to get rid of the pigmentation.

Figure 11.9 A complication that is specific to EPS: an acne-like reaction that lasts 24–48 hours and subsides by itself, occurring in average 2% of patients.

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patient was showing areas of local erythema that were treated with topical cortisone. On the 10th day, there were no visible sequelae. Other complications caused by AHAs are extremely rare with EPS. Infection or pigmentation problems are often caused by errors made when neutralizing AHA peels. EPS is automatically neutralized by the skin’s buffer capacity, and post-peel complications are far rarer than with conventional AHA peels.

Application protocol Pre-peel preparation This is likely to increase the penetration of the acids unnecessarily. EPS was designed to avoid any pre-peel treatment. Application of EPS should be delayed for 2 weeks if there has been any pre-peel preparation: EPS uses the stratum corneum as a reservoir for the slow release of the acids, and if it has been damaged, it can no longer fulfil this role and the acids will penetrate too rapidly through the thinned layer of skin. Body skin is much less permeable than face skin. This is why an abrasive technique has been described earlier in this chapter.

Figure 11.10 Abnormally deep penetration in a young patient who had been applying benzoyl peroxide locally for acne.

itself within 1–2 days at most. An allergic reaction is also theoretically possible, and should be treated accordingly. That will also disappear within a few days. This type of reaction should be seen as purely inflammatory – a positive reaction if the inflammation is controlled by antioxidants and does not last more than 2 days. If it does go on any longer, it could be considered an allergy. Contact of EPS with the eyes should be avoided: in the case of contact, the eyes should be rinsed with artificial tears or physiological saline solution. EPS may also, in some cases, penetrate too deeply or too quickly if the patient has been using skincare products that thin or remove the stratum corneum. Patients using topical retinoids, AHA creams or benzoyl peroxide should stop using them 2 weeks before EPS to ensure that the stratum corneum regains its normal thickness and function. Figure 11.10 shows the results of overpeeling in a young patient who had been using a benzoyl peroxide cream. Benzoyl peroxide is a powerful pro-oxidant used in the antibacterial treatment of acne, and it reduces the stratum corneum’s impermeability properties. The EPS can then penetrate more deeply into the skin. In this case, a fluorocortisone cream was applied immediately. Between the second and sixth day, the

Figure 11.11 Pre-peel cleanser with a physiological pH (6.5).

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Cleaning the skin Any make-up should be removed and the skin cleansed twice with Skin Tech’s cleanser (foam without glycolic acid (Figure 11.11–11.13)); the skin should then be rinsed with

warm water and dried with a swab. Alcohol or acetone should not be used before EPS: these products remove surface lipids and increase skin permeability (which is not necessary with EPS).

Application

Figure 11.12 Skin Tech cleanser has a neutral pH.

Small cotton wool balls seem to be the best method of application. A syringe is used to draw out 2–2.5 cm3 of the EPS. The cotton wool ball is soaked (not too much), and the solution is applied evenly and quickly over the whole face. Two coats are usually enough to produce a tingling sensation on the skin. When the patient can feel some tingling, one last coat is applied with the same applicator. There should be no frosting. In the case of inadvertent frosting,15 a neutralizing solution of sodium bicarbonate should be applied immediately. If there is no frosting, a neutralizing solution should not be applied – the skin neutralizes EPS automatically. Patients with very permeable skin may feel some tingling as soon as the first coat is applied. They should be given a total of two coats only: the first triggers the tingling and the second finishes off the peel. Patients with thick skin may not feel anything before the third coat. They should be given a total of four coats (Box 11.1). The treated area should be massaged with a gloved hand to ensure even penetration until the tingling sensation

Box 11.1 Average number of EPS Coats Thin skin: Normal skin: Thick skins:

Figure 11.13 Pre peel skin cleansing using the pre peel cleanser foam.

2 2–3 3–4

Figure 11.14 Post-peel occlusion with a suitable cosmeceutical for a duration of 15–30 minutes.

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8 days

8 days

8 days

8 days

15 days

4–6 weeks

7

7

7

7

7

7

77

Time line

1st EPS

2nd

3rd

4th

5th

6th

7th

Figure 11.15 Diagram of repeated EPS peels.

subsides. Slight tingling is normal and can last between 30 to 60 minutes after the application of this slow-release solution.

Immediate post-peel period As soon as the patient says that the tingling has subsided, the skincare cream best suited to the patient’s skin should be rubbed in: Purifying® cream in the case of acne, Blending Bleaching® cream in the case of pigmented marks, DHEA cream for anti-aging in the over-40s and Renutriv ACE® with lipoic acid to prevent aging in the under-40s. Actilift® cream with DMAE can be used to increase skin firmness. These creams penetrate much more easily immediately after the AHAs have been applied, but using a plastic occlusive film (Figure 11.14) for 20–30 minutes further enhances penetration of the skincare creams. In vivo, the natural water content of the stratum corneum is relatively low. When the surface of the skin is occluded with an impermeable plastic film, the water that normally evaporates through the epidermis (TEWL16) can no longer do so, and water of endogenous origin gradually soaks the stratum corneum, which can absorb up to 5–6 times its dry weight. The thickness of the stratum corneum increases in proportion to the amount of endogenous water absorbed and can become up to four times thicker.17 It is then far more permeable to the water-soluble ingredients, and this improved permeability lasts for several hours after the occlusive film has been removed. Occlusion raises the temperature of the hyperhydrated epidermis and makes the various hydrophilic ingredients in the creams more soluble. Finally, occlusion prevents the active components in the creams from evaporating too quickly. The plastic film is then removed and any excess cream is rubbed in to enhance penetration one last time. All of the products – EPS and cream – are left on the skin until the following morning, when the patient can wash his or her face.

vitamin E but without fruit acids (Vit E Antioxidant®), and the cream most appropriate for the problem under treatment should continue to be used – this will often be the same cream applied to the skin immediately after the peel (see Table 3.1 in Chapter 3).

Period between peels (between two EPS sessions) The appropriate cream should continue to be used between peels. Exposure to the sun’s rays must be avoided: this means keeping out of the sun and using an effective sun protection cream for 2 weeks after the last peel.

Repeating the peel When EPS is the main treatment, it can be repeated once or several times a week (see above). When EPS is used as a maintenance treatment with other peels, it can be repeated once or twice a month. In standard treatment, EPS can be applied once a week for 6–8 weeks. Thereafter, it is applied as a maintenance treatment: four extra EPS peels, once every 2 weeks. Finally, in the long term, EPS can be applied once every 4–6 weeks (Figure 11.15).

Contraindications ■ Women who are pregnant or breast-feeding (as a precaution) ■ Presence of herpes or other active lesions ■ Lesions of unknown origin ■ Allergy to one of the components ■ Unrealistic hopes

Post-peel period (3–4 days)

Conclusions

The skin flakes only very slightly, usually unseen by the naked eye, because it practically flakes ‘cell by cell’. The skin should be kept fully hydrated with a cream containing

EPS is the first slow-release AHA peel not to need neutralizing, in spite of its pH of 0.5–1. This makes it extremely safe to use. It combines the known superficial peeling

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effects of three AHAs with the antioxidant, chelating and tyrosinase-inhibiting action of phytic acid. It is a new type of peel that overcomes all the problems associated with neutralizing conventional AHAs. It allows each of the molecules in the solution to act to full effect, without being neutralized. The best indications for EPS are the treatment of adolescent acne and aging skin, on which it has a tightening effect.

Notes 1. Glycolic acid has a pKa of 3.83, lactic acid a pKa of 3.86 and mandelic acid a pKa of 3.36. 2. See Chapter 6 for a reminder of pKa. 3. Saponification allows the acids to act more evenly. 4. As is the case when unbuffered peel solutions are applied to the skin. 5. It is therefore essential for the stratum corneum to be complete when using EPS. If any preliminary treatments reduce its thickness, the solution may penetrate too quickly and saturate the skin’s buffer capacity. 6. AHAs are water-soluble. 7. Dolor – Rubor – Tumor – Calor.

8. Ditre CM, Griffin TD, Murphy GF, Sucki H et al. Effects of alpha-hydroxy acids on photoaged skin: a pilot clinical, histologic, and ultrastructural study. J Am Acad Dermatol 1996; 34(2 pt 1): 187–95. 9. EPS can be applied after pulsed light treatment, unless the skin has been made excessively permeable. See later in this chapter. 10. Although EPS does not require any specific pre-peel care. 11. It should be noted that EPS and Easy TCA® are both used in conjunction with anti-free radicals that control the post-peel inflammatory reaction. This is not the case with the majority of other peels. My experience is only based on the combination of botulinum toxin and EPS or Easy TCA®. Combinations with other peels have not been tested. 12. For example with 3M Wetordry® sandpaper P220. 13. Comedone remover, No.11 scalpel blade, point of a needle. 14. For example, a 70% unbuffered glycolic acid peel. 15. Frosting has rarely been described – I have never personally come across it. 16. Transepidermal water loss: 5–20 g of water/m2 of skin under normal physiological conditions. 17. The increase in permeability is also due to a reduction in corneocyte cohesion related to the unusual hyperhydration of the stratum corneum.

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12 Trichloroacetic acid: general information, toxicity, formulations and histology

Haloacetic acids Haloacetic acids are derivatives of acetic acid in which one or more hydrogen atoms on the alpha carbon1 are replaced by halogens (fluorine, chlorine, bromine or iodine) (Figure 12.1). The haloacetic acid most commonly used in peels is trichloroacetic acid, and we will therefore look at the chlorine derivatives of acetic acid.



X O  Y — Cα — C  OH Z

General chemical structure of a haloacetic acid. α indicates the alpha carbon atom. X, Y and Z represent hydrogen (H) or a halogen (F, Cl, Br or I) – at least one of these must be a halogen.

Acetic acid Acetic acid (Figure 12.2), also known as echanoic acid, has a low molecular weight of 60.05 and a pKa of 4.76.2 It is obtained by distilling vinegar (the acetic acid which comes from the action of certain aerobic bacteria on dilute alcohol) or through the Monsanto process by the reaction of carbon monoxide with methanol at high temperature and pressure. It is a strong irritant to the eyes, mucous mem-

Monochloroacetic acid (Figure 12.3), also known as chloroacetic acid and chloroethanoic acid, which has a molecular weight of 94.5, can be obtained from the reaction between acetic acid and chlorine under high pressure. The pH of an 80% MCA solution is lower than 1 and its pKa is 2.82. In both its acid form and its salt forms (e.g. sodium monochloroacetate), MCA is highly toxic to the skeletal muscles, the renal system and cardiovascular system and is rapidly absorbed through the skin and mucous membranes. MCA poisoning by ingestion, inhalation or exposure of more than 5% of the body surface area is frequently lethal. The symptoms of poisoning are not immediate: they can appear between 1 and 4 hours after exposure. The non-corrosive sodium salt does not penetrate the skin and is not toxic by skin contact (unlike MCA, which passes through the skin very easily). It is, on the other hand, highly toxic by the oral route. There are no data available on the parenteral administration of MCA in humans. In laboratory animals, H

— H—C—C —



H—C—C H

OH

—

—

—

OH O

CI



—

Figure 12.1

H

branes and skin. Prolonged contact between the skin and ‘glacial’ acetic acid3 can cause skin necrosis. Applying 6–8% acetic acid to the skin of patients with seborrheic dermatitis can trigger temporary frosting through protein coagulation. This disorder is in fact often improved by daily application of white vinegar (which contains 4–8% acetic acid), used as an aftershave before the morning shower (to avoid smelling of vinegar!). Acetic acid has disinfectant and fungicidal properties. It is not carcinogenic, mutagenic or teratogenic to animals or humans. The oral LD50 in rats is 3.310 mg/kg.

Monochloroacetic acid (MCA)

Carboxylic acid group

—

ch12

O

Figure 12.2

Figure 12.3

Chemical structure of acetic acid.

Chemical structure of monochloroacetic acid (MCA).

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Dichloroacetic acid (DCA)

H

OH

—

however, an injection is rapidly lethal. MCA accumulates in the liver and kidneys before it accumulates in the brain. Elimination of MCA is renal in humans: most of it is eliminated in its free form, with a small part being eliminated in conjugated form with glutathione. The mechanism of MCA toxicity seems to be via inhibition of the enzyme pyruvate dehydrogenase; this inhibition blocks the Krebs (tricarboxylic acid) cycle and disrupts the cell’s energy supply. Almost immediately, the cell finds itself without energy. Ketoglutarate dehydrogenase activity is also reduced, which causes lactic acidosis. The MCA also damages the blood–brain barrier, probably through the formation of vascular endothelial microlesions. Symptoms of poisoning begin with nausea and vomiting, diarrhea, and central nervous system (CNS) excitation with disorientation. The effects observed later on or with higher doses include CNS depression, cerebral edema, severe myocardial depression, coma and cardiogenic shock resulting from non-specific myocardial lesions and significant arrhythmias. Within the first few hours, severe metabolic acidosis4 with hypokalemia occurs. The severity of the rhabdomolysis causes myoglobinuria severe enough to cause kidney failure5 in those who survive it. One treatment involves administering dichloroacetate by slow (in 10 minutes) intravenous injection (50 mg/kg), if possible before metabolic acidosis begins. The dichloroacetate is only active as long as all the pyruvate and ketoglutarate dehydrogenase molecules have not been deactivated by the MCA. The severity of poisoning due to skin contact depends on the surface area of skin exposed: applying an 80% MCA solution on less than 5% of the body surface area can cause severe poisoning, while exposing 6–10% of the body surface to MCA is often lethal. MCA has nevertheless been suggested as a dermatological treatment for mosaic warts or periungual warts at a concentration of 80% or 60 g of MCA + 10 ml of water. Treating warts involves MCA coming into contact with a very limited area of skin, which explains the absence of poisoning when the treatment is carried out carefully. MCA has also been combined with salicylic acid and is considered more effective than dichloro- or trichloroacetic acid in the treatment of warts. Because of this product’s very high and potentially fatal toxicity, its use and indications should be strictly limited. Monofluoroacetic acid is even more toxic than MCA, being fatal after ingested doses of 2 mg/kg whereas MCA is fatal after doses of 50 mg/kg.6

CI — C — C CI



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ch12

O

Figure 12.4 Chemical structure of dichloroacetic acid (DCA).

DCA has been used in the treatment of severe lactic acidosis. No clinical side-effects have been observed after parenteral administration. On the contrary, intravenous administration of DCA during experimental poisoning of rodents with MCA increased the survival rate, bringing it from 8% to 83% after an injection of 50 mg/kg and from 8% to 100% after an injection of 100 mg/kg. There are strict protocols for the injection of DCA in the case of MCA poisoning. When ingested, DCA is rapidly absorbed by the digestive tract. In animals, only 1–2% of the quantity ingested is found in the feces, which means that the acid is almost completely absorbed. Only 1% is found, in free form, in the urine. In humans, up to 5% of DCA can be found in the urine, very soon after DCA has been absorbed. Peak plasma levels are reached within 15–20 minutes in humans. Intoxication by inhalation is rare, as DCA is not a very volatile substance. DCA causes the liver to increase in volume as a result of a build-up of glycogen. Increases in aminotransferase (transaminase) levels have been observed during treatment with high doses of DCA, in both rodents and humans. DCA can cause focal, or even widespread, hepatocellular necrosis in mice, but no cases have been described in rats, dogs or humans, even when administered in high doses. Neurological toxicity in humans is limited to sedation and potential peripheral neuropathy that is reversible. DCA undergoes oxidative dechlorination that converts it into glyoxylate,7 which is in turn oxidized into oxalate,8 reduced into glycolate9 and eventually transaminated into glycine.10 However, in certain individuals, the DCA can be partially converted into MCA. This has been described in a child suffering from congenital lactic acidosis. It appears that the DCA may enhance the development of hepatocellular carcinoma in animals, although not in humans.11 DCA is genotoxic in vitro and in vivo and induces DNA hypomethylation in vivo. The oral LD50 in rats is 2.820 mg/kg. The human toxicity of DCA is mainly local, through chemical burns, but DCA could be considered to be potentially carcinogenic in humans. To date, there is no convincing data on this subject.

Chemistry and toxicity of DCA

Application protocol for DCA

Dichloroacetic acid (Figure 12.4), also known as bichloroacetic acid and dichloroethanoic acid, has a molecular weight of 128.94 and a pKa of 1.3. It is soluble in water, alcohol and ether.

DCA has been shown to stimulate keratinocyte growth and differentiation in vitro.12 It has been used in the treatment of human papillomas, without much success,13 as well as in the treatment of epistaxis.

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DCA is used as a cauterizing agent in the treatment of all types of warts, calluses, corns, xanthelasma, seborrheic keratoses, ingrown toenails, etc. It is just as effective as other methods such as electrodessication or dry ice. DCA is a powerful keratolytic and it is important to apply it only to the lesion being treated. Before any treatment, Vaseline® should be applied around the lesion to prevent any contact with healthy skin. The doctor should also have some water at hand to wash the skin in case of inadvertent contact. A neutralizing solution of sodium bicarbonate can also be used immediately in case of accidental contact with the skin. The quantity of DCA required largely depends on the type of lesion being treated. Very thick and horny lesions are treated using a cotton bud. A wooden toothpick soaked in DCA solution can also be used; it should be pushed inside the callus or wart. Three to five applications are necessary to get results on very thick lesions, whereas only one or sometimes two applications are enough on relatively flat lesions. The depth of application is monitored by watching out for the appearance of protein coagulation, which turns the skin a whitish-grey color. A combination of shave excision and chemical coagulation can also be used. The top of the wart is first removed with an electrosurgical or radiofrequency knife. The DCA is applied after the edges of the wart have been protected with a thin layer of Vaseline®. Foot calluses should be pared surgically before the acid is applied. Post-treatment care consists of covering the skin with Vaseline® to help it flake more quickly. Large calluses often have to be treated several times. Treating xanthelasma with DCA is fairly common.14 The skin around the xanthelasma must be protected with Vaseline® and the DCA applied carefully and not to excess. The scars are mostly invisible. Treating xanthelasma with phenol, however, leaves no scarring (see Chapter 36). The potential toxicity of DCA means that it cannot be used on a large absorbent surface area. The author has found no significant references to the use of DCA in full-face or body peels.

Trichloroacetic acid (TCA) Chemistry and toxicity of TCA Trichloroacetic acid (Figure 12.5), also known as trichloroethanoic acid and trichloromethane carboxylic acid, comes in the form of colorless or white crystals and has a distinctive sharp, pungent odor. As far as its toxicity is CI

—

—

OH

CI



CI — C — C —

ch12

O

Figure 12.5 Chemical structure of trichloroacetic acid.

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concerned, industrial accidents have been reported in which individuals were subjected to high doses of TCA, either by being splashed with the solution over large areas of the body or by accidental ingestion or inhalation of concentrated vapors. However, such toxicity has never been described when TCA has been used as a chemical peel. It is nevertheless worthwhile becoming acquainted with the potential symptoms of industrial poisoning. TCA is readily absorbed through the respiratory and digestive tracts. Acute accidental exposure to TCA has caused skin necrosis. Contact with the eyes causes burns or irritation, depending on the concentration of the acid. Exposure of the eye to small amounts of solution with a concentration equal to or lower than 15% m/m does not appear to cause any irreversible damage to the cornea. Immediate dilution with physiological saline solution instantly stops the burning and any risk of damage to the eye. However, the proteins in the cornea could coagulate with larger amounts of low-concentration TCA or smaller amounts of high-concentration TCA. Inhaling concentrated vapors of TCA can irritate the respiratory tract. Poisoning through inhaling high doses of TCA can cause headache accompanied by nausea, vomiting and coughing. Higher concentrations cause weakness, dizziness, bronchitis and/or pneumonia. Acute poisoning with TCA vapor can lead to chest pains, breathing difficulties, low blood pressure, edema of the respiratory tract, suffocation and death. Accidental ingestion of TCA causes irritation and burns in the digestive tract, vomiting, diarrhea, and low blood pressure. Accidental ingestion of high concentrations can erode the teeth and cause necrosis of the jaw. Controlled ingestion of 3 mg/kg of TCA in three male volunteers showed a half-life of 50 hours. Liver toxicity has been studied in mice: hepatomegaly (30% enlargement) was observed in male mice given water containing 1 g/l of TCA for 52 weeks. In a group given water with a concentration of 2 g/l of TCA, the liver enlarged by 63%. The incidence of liver carcinoma did not increase, irrespective of the administered dose. In another study, it was proved that TCA does not cause adenomas or liver cell carcinoma, even in rodents pretreated with ethylnitrosourea, conventionally used to induce carcinomas. No in vitro studies using human cells have shown any chromosomal abnormalities after contact with TCA. To the best of my knowledge, no studies have shown any link between even chronic exposure to TCA15 and cancer in humans. When TCA is applied to the skin, it is not absorbed, and is therefore not toxic in this application.

Aqueous solutions of TCA Hydrophilicity of TCA crystals TCA crystals are very hydrophilic and therefore unstable in the presence of water: they readily dissolve on exposure to

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atmospheric humidity. This extreme hydrophilicity can cause problems when TCA solutions are made up in a pharmacy. In fact, the packaging of pure TCA crystals usually allows for the preparation of far more peel solution than the doctor actually needs. The pharmacist does not usually dissolve all the crystals at one time, as this would produce a large quantity of solution that is difficult to store. He will usually measure out the quantity of crystals needed for each order of peel solution. Every time the bottle is opened and every time the pure TCA crystals are taken out, they come into contact with atmospheric water, which gradually hydrates them. The larger the bottle, the more likely it is that the remaining crystals will be hydrated every time the bottle is opened. The longer it takes to weigh the crystals, the more hydrated they will become. Peel solutions are therefore prepared by diluting crystals that are gradually becoming more and more hydrated: at the same weight, the pharmacist is in fact weighing TCA crystals that are slowly swelling with water. The solutions that he prepares are more and more diluted and therefore less and less effective. The doctor, for his part, gets into the habit of applying increasingly weaker TCA peels with increasing firmness, in spite of the fact that the same labels show the same concentration. The doctor therefore gets used to applying ever increasing volumes of peel solution to achieve the same results – until the day when the pharmacist starts using a new bottle of pure TCA crystals and makes up a peel solution with fresh, anhydrous crystals that are more aggressive than the ‘old’ hydrated crystals. Applying this new and more concentrated solution of course results in a peel that is deeper than the doctor expected, and the risk of complications is increased, even though there is no apparent difference in the application procedure. Unlike pure crystals, TCA solutions do not hydrate by themselves. It is therefore safer not to keep TCA in crystal form and instead to use reconstituted solutions whose concentration is more stable than crystals.

Inhomogeneity of TCA solutions A solution is said to be homogeneous when the different elements of which it is made up are evenly distributed in the container that holds it. The homogeneity of peel solutions is one of the essential elements of their safety.

Simple aqueous solutions of TCA (TCA–SAS) Unfortunately, TCA–SAS16 solutions are neither homogeneous nor stable. The TCA molecule is very mobile in the solution and its motion has both a random element and a component determined by its chemical structure. When an aqueous solution of TCA is left in an unmoving container, the concentration of the solution does not remain uniform. The TCA temporarily becomes more

concentrated in some parts of the container and more dilute in others. For example, if a TCA solution of 33% m/m is prepared and left at room temperature, some regions of the solution will have a concentration of 35% for a certain length of time while neighboring regions will have concentrations of 30% or 40% (Figure 12.6). As this process continues, the region that just had a concentration of 35% will now have a concentration of 37%, while other areas of the solution will have different concentrations again, for example 25% and 29%, and so on and so forth.17 Depending on the position of the tip of the needle used for taking the acid out of the bottle, the solution will be more concentrated or more dilute. A solution that is too dilute or too concentrated could be applied to different parts of the face. Simple aqueous solutions of TCA have to be mixed continuously, both when they are being taken out of the bottle and while they are being used. Certain complications that arise unexpectedly after a TCA–SAS peel can be explained – at least partially – by this phenomenon of inhomogeneity. Awareness of this problem led to the rapid development of new TCA peel formulas between 1990 and 2000. One of the first solutions put forward was the New Peel® combination of TCA and Mikuda® complex. The soft Peel® formulation used asiaticosides and ginsenoids, glycerol, urea (carbamide), sorbitan monolaurate and methyldibromoglutaronitrile, among other ingredients. Easy TCA®, Unideep® and Only Touch Peel® (OTP) provided another answer to the problem: these stabilized solutions consist of a base solution to which a determined quantity of 50% m/m TCA is added. There are no complicated calculations to be performed, the directions for use state precisely what volume of 50% m/m TCA solution should be added to the base solution to make up the Easy TCA®, Unideep® and OTP solutions, which provide peels to the basal layer, the papillary dermis and the reticular dermis, respectively.

Calculating the concentration of TCA Since TCA peels first came into use, practitioners have suffered from a lack of standardization regarding how a solution’s concentration is to be calculated. The calculation can be done in different ways: by mass per mass (m/m), mass per volume (m/v) or mass plus volume (m + v, e.g. m + 100 ml). There are also different formulas for diluting these solutions using approximate curves. Therefore, ‘50%’ TCA does not really mean very much if we do not know whether the calculation is m/m, m/v or m + 100 ml. In 1995 and 1996, Trauchessec and Pissot18,19 suggested standardizing the calculation of the concentration of a TCA solution by expressing it in mass per mass (m/m), which is the only logical way of calculating a percentage. It should be possible to make a strict comparison of the terms of a percent-

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Figure 12.6 Inhomogeneity of simple aqueous solutions of TCA. (a) A solution with a presumed concentration of 33% contains mobile regions of different concentrations. (b) At a later time, same TCA solution with a presumed concentration of 33% contains mobile areas of concentrations that are different.

30%

29% 25%

37%

15%

40%

age. For example, the carbohydrate content of a meal is given in %: a content of 20% carbohydrate means that 100 g contains 20 g of carbohydrate and 80 g of something else. Unless it is clearly indicated on the packaging, there is no way of knowing that a volume of 100 ml of this meal would contain 20 g of carbohydrate. It would be impossible to understand exactly how much carbohydrate is in the food. Unfortunately, it is this very type of calculation (weight by volume, w/v) that is widely used in some countries: a volume of 100 ml of TCA solution contains x grams of TCA. If we know the concentration in w + v only, it is difficult to calculate the exact amount of TCA in the solution. To get the correct answer, one has to calculate mass with mass, volume with volume, and not volume with mass.20 Examples of calculations of concentration using the w/w, m/v and w + v methods are given in Boxes 12.1–12.3. Methods of calculation based on volume lead to values of concentrations that can be as high as 140%. Since a ‘0% solution’ is pure water and a ‘100% solution’ pure TCA, values greater than 100% are essentially meaningless. Ideally, therefore, these methods should not be employed for the calculation of concentrations – only the m/m method should be used. Nevertheless, for the sake of simplicity, pharmacists often prefer to use dilutions in volume whenever possible, as they can buy ‘standardized’ TCA solutions at 20%, 50%, etc. – then, in theory, all the pharmacist has to do is add 100 ml of water to 100 ml of TCA solution at ‘50%’ to get a ‘25%’ solution. It is not easy for a doctor to calculate how

Box 12.1 TCA solution at 50% mass per mass (m/m)a 100 g of TCA solution at 50% m/m contains 50 g of pure, unhydrated TCA crystals and 50 g of water. 100 g of this solution is not, however, 100 ml, but only 79 ml. In fact, 1 g of TCA displaces 0.6 ml and not 1 ml of water.b Scientifically, this is the most rigorous method of calculation, as 100 ml of a solution at 50% m/m would contain (50/79) × 100 = 63.3 g of TCA. %

Mass of TCA (g)

Volume of water (ml)

Final mass (g)

Final volume (ml)

10 20 30 40 50 60 70

10 20 30 40 50 60 70

90 80 70 60 50 40 30

100 100 100 100 100 100 100

96 92 88 83 79 75 71

a Taken from Trauchessec JM, Pissot F. Solutions d’acide trichloroacétique masse pour masse pour peelings dermatologiques. Nouv Dermatol 1996; 15: 252–5, with the authors’ permission. b According to Trauchessec, the exact value is 0.59 ± 0.01. The value of the constant 0.60 used here is an acceptable approximation. It means that 1 g of TCA displaces 0.6 ml of pure water, whatver the concentration of the solution.

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Box 12.2 TCA solution at 50% mass per volume (m/v)a This solution is prepared in the following manner: 50 g of TCA is diluted in a small amount of distilled water to get a small amount of solution, then the volume is made up by adding distilled water until the final volume reaches 100 ml. To get 100 ml of solution and an end mass of 121 g, 50 g of TCA will be dissolved in 71 ml of water. This method of calculation is easy for the pharmacist, as 100 ml of solution contains 50 g of TCA (100 g of this solution would contain 41.32 g of TCA). %

Mass of TCA (g)

Volume of water (ml)

Final mass (g)

Final volume (ml)

10 20 30 40 50 60 70

10 20 30 40 50 60 70

94 88 82 77 71 65 59

104 108 112 117 121 125 129

100 100 100 100 100 100 100

a Taken from Trauchessec JM, Pissot F. Solutions d’acide trichloroacétique masse pour masee pour peelings dermatologiques. Nouv Dermatol 1996; 15: 252–5, with the authors’ permission.

much TCA these solutions contain! Examples of calculations of dilutions using the m/m, m/v and m + v methods are given in Boxes 12.4–12.6 and Tables 12.1 and 12.2.

Publications can be misleading A major problem arises when reading publications from different sources. Suppose that an American doctor wants to use a peeling technique described by a European author who gives concentrations in m/m but does not mention this in the publication, as is too often the case. The American

Box 12.4 Dilution of a base solution at 50% mass per mass (m/m) 100 g of a solution of TCA at 50% m/m contains 50 g of TCA and 50 g of water (50 g of water is in fact equivalent to 50 ml of water) and has a volume of 79 ml. If 79 ml of solution contains 50 g of TCA, then 1 ml contains 0.633 g of TCA and so 100 ml of TCA solution at 50% m/m contains 63.3 g of TCA. If this solution is diluted with the same volume of water (i.e. 100 ml), it produces 200 ml (but not 200 g) of TCA solution, in which there is still 63.3 g of TCA. Therefore, 100 ml of the new diluted solution contains 31.65 g of pure TCA.

Box 12.3 TCA solution at 50% mass + volume (m + 100 ml)a

Box 12.5 Dilution of a base solution at 50% mass per volume (m/v)

This method of preparation involves adding 100 ml of water to 50 g of pure TCA crystals. The final volume of this solution is 129 ml for a mass of 150 g. 100 ml of this solution contains 38.75 g of TCA, while 100 g of this solution m + 100 ml contains 33.33 g of TCA. This is the easiest but also the worst method of calculation, as it is extremely difficult to work out the exact amount of TCA.

100 ml of TCA solution at 50% m/v contains 50 g of TCA diluted in 71 ml of water, to give a solution with a volume of 100 ml for a mass of 121 g. If 100 ml of pure water is added to 100 ml of solution at 50% m/v, it produces 200 ml of solution, which weighs 221 g and contains 50 g of TCA. 100 g of this solution contains 22.6 g of TCA, while 100 ml of the same solution contains 25 g.

%

Mass of TCA (g)

Volume of water (ml)

Final mass (g)

Final volume (ml)

10 20 30 40 50 60 70

10 20 30 40 50 60 70

100 100 100 100 100 100 100

110 120 130 140 150 160 170

106 112 117 123 129 135 141

a Taken from Trauchessec JM, Pissot F. Solutions d’acide trichloroacétique masse pour masse pour peelings dermatologiques. Nouv Dermatol 1996; 15: 252–5, with the authors’ permission.

Box 12.6 Dilution of a base solution at 50% mass + volume (m + 100 ml) 100 ml of TCA solution at 50% m+100 ml contains 38.75 g of pure TCA for a mass of 116.27 g. Adding 100 ml of water with the aim of converting the theoretical concentration into 25% therefore gives a solution of volume 200 ml, whose mass is 226.27 g and which still contains the same 38.75 g of TCA. 100 g of the new solution therefore contains 17.12 g of TCA. 100 ml of the new solution contains half of the 38.75 g, which is 19.38 g of TCA.

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Table 12.1 Calculation of a TCA solution at 50% in mass or in volume Method of calculation

Grams of TCA in 100 ml Grams of TCA in 100 g

m/m

m/v

m + 100 ml

63.3 50

50 41.32

38.75 33.33

Table 12.2 Obtaining a solution at ‘25%’ by adding 100 ml of water to a solution at ‘50%’ Method of calculation

Grams of TCA in 100 ml Grams of TCA in 100 g

m/m

m/v

m + 100 ml

31.65 25

25 22.6

19.38 17.12

doctor gets his pharmacist to make up the solution as described by the European doctor. The American pharmacist, however, prepares a solution in m/v or m+v, or even dilutes it as described above. The European technique may well be based on an aggressive TCA, with a concentration of 45% m/m. The American doctor orders a solution at 45% from his pharmacy, but is in fact using a concentration of 38.1% m/m when the calculation has been made at 45% in m + 100 ml. A solution with a concentration of 31% m/m will clearly not produce the same results as a concentration of 45% m/m. The American doctor cannot achieve the same results as the European author, whose results might therefore easily be considered exaggerated or even rigged. The situation is more serious when a European doctor wants to use an American application technique with a TCA solution at 50% m + 100 ml. This solution contains 50 g of pure TCA to which 100 g of water is added. The final volume of the solution will be 129 ml for a mass of 150 g, and 100 g of this solution is actually equivalent to 33% m/m. The American author who applies a TCA solution at 50% m/v – which is in fact a European 33% m/m solution – to a patient’s face can achieve excellent results. The European doctor, who wants to achieve the same results by applying a solution at 50% m/m provided by the pharmacist, is running a huge risk of burning the patient’s skin and causing hypo- or hyperpigmentation, scarring,21 etc. It is therefore essential to stipulate the type of concentration to use, and this is one of the first pitfalls awaiting any doctor who is new to peeling. The technique for applying TCA, which is actually very easy, has for a long time been made difficult because of the different methods for calculating concentrations (see above) and the approximate explanations given in many

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publications.22 There are many inconsistencies: some publications consider a TCA peel at 50% to be a ‘superficial peel’. Yet we know that a peel at 50% reaches the reticular dermis easily and quickly, and can sometimes even go beyond it: this is a deep peel – in most cases too deep. This solution penetrates the whole of the papillary dermis immediately, achieving a ‘medium’ or ‘deep’ peel, but certainly not a superficial one. The same solution at 50%, but calculated in m + 100 ml, would be equivalent to a 33.3% m/m solution, and the first coat of TCA at 33% m/m would soon reach the papillary dermis. It is then difficult to understand how anyone can say that a ‘TCA peel at 50% produces a superficial peel’: in whatever way the calculation is made, it is wrong and a TCA solution at 50% will produce, at the very least, a medium-depth peel even if it is calibrated in m + 100 ml. The type of applicator used, the number of coats and the total quantity of TCA applied to the skin, as well as any pre-peel preparation, etc. must also be taken into account. There have been histological studies comparing the depths reached by different concentrations of TCA used in conjunction with different techniques such as dry ice or prior application of Jessner’s solution. A histological study by Brody and Stegman, at 3, 30 and 90 days,23 showed that the deeper the injury, the more necrosis and regeneration are histologically visible. It has thus been shown that three successive applications of TCA cause deeper necrosis than one application.24 The technique used in this study involved the application of TCA at a concentration of 35% – presumably calculated in mass per volume, although it was not stated whether this was a w/v calculation, m + 100 ml calculation or a dilution of TCA solution. The Jessner’s solution in the study was supposed to be prepared from lactic acid crystals rather than from an 80% (w/w, w/v?) lactic acid solution. This solution was applied with a cotton bud: the volume, form and texture of the cotton bud has an influence on the quantity of solution that comes into contact with the skin. The dry ice was applied firmly (how firmly was not stated) in acetone (exactly how much and at exactly what temperature were also not stated) for 15 seconds. The importance of studies such as this should not be underestimated, but it is necessary to draw attention to the number and importance of the variables that have to be taken into account when evaluating results.

A good method of calculation A consistent method of calculating concentrations must be adopted. It would of course be preferable to use pharmacological concepts such as molar mass, but practitioners are not used to handling such data. From a practical point of view, there are two units of measurement that are easily accessible: mass and volume. As we have just seen, the only acceptable values are calculations in m/m (if we are referring to mass) or in m/v (if we are referring to volume).

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Measurements in m + 100 ml are too approximate, as is using dilutions of pre-existing solutions. Anyone is capable of measuring an approximate volume, although not an exact one, and this introduces another margin of error. With the help of precision scales, it is possible to measure a mass precisely – more precisely, in any case, than by judging gradients on a measuring glass with the naked eye. This confusion over concentrations is extremely dangerous, and a standardized concentration should be used to avoid disappointment as well as complications. McCullough25 has drawn attention to the discrepancies between calculations of TCA concentrations, but prefers to use the m/v method. We have chosen to calculate the concentration in m/m for the following reasons, as expressed by Trauchessec:19 1. Measuring mass is more precise than measuring volume. 2. A real percentage can only be calculated m/m or v/v. 3. The use of approximate dilution curves is avoided with m/m calculations. 4. With m/m calculations, there can be no potential errors caused by the existence of three types of mass per volume concentrations: m/v in QS, adding 100 ml of water to a mass of TCA or diluting pre-existing TCA solutions. 5. The m/m calculation does not produce values of TCA ‘concentrations’ reaching 140% – which make no sense. 6. Finally, the size of TCA crystals, how compact the mass of crystals is and the temperature of the solution are all elements that have to be taken into account when making m/v or m + v calculations. The m/m calculation does not depend on these parameters.

Easy TCA®, Unideep® and Only Touch® solutions Easy TCA® is a stabilized,26 homogeneous and adjuvanted solution with a final TCA concentration of 15% m/m, combined with alpha hydroxy acids (AHAs), antioxidants, vitamins and saponins. Unideep® is a TCA peel based on the same principles as Easy TCA® and reaches the papillary dermis readily and evenly; it has a TCA concentration of 23% m/m. The application protocols for these two peels allow all depths to be reached. There is no point using higher concentrations that could cause complications (see Chapter 37).

TCA in simple aqueous solution (TCA–SAS) Simply diluting TCA crystals in water produces an unstable solution whose characteristics have been discussed

above. TCA-SAS solutions are the cheapest a doctor can buy. They are also the most dangerous.27,28 It is clear from the literature on chemical peels how dangerous these solutions are – most photographs of serious complications show patients treated with TCA–SAS. It is clear that an experienced doctor can avoid most of the serious complications, but an inexperienced one can easily fall into each and every trap that these cheap solutions set. To paraphrase: it is definitely cheaper to spend the night on a park bench in a big city than to rent a room in a decent hotel, but it is nonetheless true that you would get a much better and safer night’s sleep in a hotel room than you would in the park or subway! Even though some of the world’s best peelers can use TCA–SAS with complete safety, it is still true that the vast majority of all complications occur after the application of these cheap solutions. Some ill-informed doctors have ended up claiming that TCA simply cannot be used to treat melasma, for example. Reading the textbooks on chemical peels is very instructive, and the pictures of complications often reflect the complexity of using TCA–SAS correctly. Today’s new TCA peel solutions have been developed with a view to convenience and safety. I can already hear reproaches from those who claim the contrary and are perfectly able to use TCA–SAS safely, but I can also hear the sobs and regrets of those who listened to them and whose patients have suffered for it. The simple aqueous solution of TCA was born in the 19th century: it has had its day – let us move on!

‘Adjuvanted’ TCA Applying TCA–SAS to the skin causes frosting that is rarely even,28 especially when using intermediate concentrations. Applying TCA–SAS at 10% m/m does not usually cause any frosting at all and is almost risk-free; applying TCA–SAS at 50% m/m causes very rapid frosting whose depth is difficult to evaluate and control.29 Intermediate aqueous concentrations (e.g. at 25% or 30% m/m) do not penetrate evenly and produce intraepidermal peel zones next to peel zones to the papillary or reticular dermis. It is difficult to get even frosting, and the results of the peel are not homogeneous: undertreated areas are next to overtreated areas that could easily create problems with post-inflammatory hyperpigmentation (PIH), hypopigmentation, or even scarring (Figure 12.7). Various adjuvants have been added to TCA to even out its effect. The term ‘adjuvanted’ is used to describe a TCA solution to which something has been added to enhance or even out its action. Many different products have been added to TCA.

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H | H — C — OH | H — C — OH | H — C — OH | H

Figure 12.8 Chemical structure of glycerol.

tein stabilizer (which seems a little paradoxical, considering that the effect sought by applying TCA is the destruction of proteins). Soft Peel® was presented as a solution for improving the tolerance and effectiveness of TCA. Nevertheless, adding glycerol did not remove the need to prepare the skin beforehand, 3 weeks before the peel:30

Figure 12.7 Technical error during the treatment of stretch marks using an abrasive procedure (see Chapter 21). Typically, a halo of hyperpigmentation surrounds the depigmented area, which in turn surround a scar response. Hyperpigmentation develops where the peel solution goes slightly deeper than it should, and scars form where the peel is much too deep.

Glycerol Glycerol (Figure 12.8), also known as glycerine, glycerin, 1,2,3-propanetriol or 1,2,3-trihydroxypropane, has a molecular weight of 92.09. It is often used as an antimicrobial preservative (in concentrations >20%), a humectant (≤ 30%), an emollient (≤ 30%) or a solvent. It is used in cosmetic products, as well as in parenteral or oral preparations. Adding glycerol to a solution increases its viscosity. Glycerol does not oxidize easily on contact with air. It is not toxic: after absorption by the digestive tract, it is metabolized into carbon dioxide and glycogen or is used for lipid synthesis. High doses of glycerol taken orally have a laxative effect and can cause headaches, hyperglycemia, thirst and nausea. Glycerol is also used in the laboratory as a pro-

■ with a depigmenting formula to prevent pigmentary changes in patients with a high skin phototype (over Fitzpatrick IV); it was also necessary to wear a total sunblock before this peel – this suggests that pigmentary changes are common after this type of peel ■ with retinoids or benzoyl peroxide in cases of acne: treatment with isotretinoin was not given as a strict contraindication to Soft Peel® on condition that the daily prescribed dose 2 or 3 weeks earlier did not exceed 0.3 mg/kg per day ■ with tretinoin at 0.05% once a day in the evening combined or not with glycolic acid to increase and even out penetration of the TCA and accelerate regeneration of the epidermis after the peel, which suggests that the solution did not penetrate evenly and readily and that healing was slow The total number of ‘soft peels’ required was 5–10, with an interval of 8–21 days in between, depending on the depth reached by each peel. The peel solution had to be ‘neutralized’ with water as soon as frosting occurred.31 It should be remembered, however, that adding water to an acid solution does not neutralize it but simply dilutes it. The pH increases very slowly when the solution is diluted, and large quantities of water are needed (Figure 12.9). Rinsing with water was necessary, however, to remove the excess solution that was no longer needed after the appearance of frosting on the skin. It would be more correct to say ‘remove any surplus solution with water as soon as frosting appears’ instead of ‘neutralize the acid’. Without rinsing, the TCA in the TCA–glycerol solution would continue to destroy the skin proteins and deepen the effect of the peel. Choosing the right moment to rinse is therefore essential and has to be timed very carefully, which is not easy for an inexperienced doctor. Some formulations

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H | H —C — H | H — C — OH | H — C — OH | H

Figure 12.11 Chemical structure of propylene glycol.

Figure 12.9 Effect of dilution on the pH of 5 ml of an organic acid solution at pH 2.7: 80 ml of water must be added before the pH rises a little more than 1 point.

(called ‘composite’ or ‘compositum’) still use solutions with glycerol and the post-peel rinsing technique, which is both restrictive and the source of errors. It is also important to make sure that the water does not carry the TCA into the eyes or onto the neck and décolletage, where it will cause an accidental peel.

Glyceryl monooleate Some glycerol derivatives can be used as adjuvants. Glyceryl monooleate (Figure 12.10), for example, is a nonionic surfactant and polar lipid with a molecular weight of 356.55. It is a monoester of glycerol in which one of the hydroxy groups is replaced by a long side-chain derived from oleic acid (CH3(CH2)7CH=CH(CH2)7COOH).32 H O | || H — C — O — C —C17H33 | H — C — OH | H — C — OH | H

Figure 12.10 Chemical structure of glyceryl monooleate.

Propylene glycol Propylene glycol (Figure 12.11), also known as 1,2propanediol and 1,2-dihydroxypropane, has a molecular weight of 76.1. It is used as an antimicrobial preservative (at 15–30%), a disinfectant, a humectant (at 15%), a solvent or co-solvent, and a stabilizer for vitamins, both in

cosmetics and in parenteral pharmaceuticals (10–60%). Although propylene glycol is considered to be non-toxic, parenteral administration of high doses can cause problems, especially in patients with renal insufficiency. Its disinfecting power is slightly lower than that of ethanol. Propylene glycol is stable at low temperatures. At high temperatures, it tends to oxidize and form lactic acid, acetic acid, pyruvic acid and propionaldehyde. Locally, propylene glycol is more of an irritant than glycerol, especially if it comes into contact with the mucous membranes or is used under occlusion. It is neither mutagenic nor teratogenic.

Stability of TCA solutions with glycerol or propylene glycol Attempts to stabilize TCA solutions by adding glycerol (‘soft peeling’31) or propylene glycol improved the safety of TCA peels, although they did not necessarily make them completely stable. Moreover, the addition of glycerol or its derivatives was still empirical and varied from one doctor to another – more of a do-it-yourself approach than a professional one. It is difficult to compare the different solutions, since the exact concentrations of these adjuvants were neither uniform nor even known for certain. Soft Peel® involved the ad hoc combination of TCA at variable concentrations with the same quantity (volume) of glycerol.

Other adjuvants Other attempts to stabilize and even out TCA were made in the 1990s.

‘Enzymatic’ TCA An enzyme is, by definition, a protein. TCA coagulates proteins. It is therefore difficult to include active proteins and TCA in the same solution, since, even if some enzymes are acid resistant (e.g. in the stomach), the conditions for acid resistance are strict and not reproducible in a TCA solution. To my knowledge, there is no preparative approach that would allow proteins to be encapsulated in nanosomes, liposomes, cyclodextrins, etc. to protect them from the coagulating action of concentrated TCA.

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Sorbitan monoesters are partial esters of sorbitol with fatty acids (monolaurate in this case). They have a molecular weight of between 346 and 964. Sorbitan monolaurate is widely used in cosmetics, the food industry and pharmaceutical preparations. Sorbitan monoesters are non-ionic surfactants, dissolving and dispersing agents. One of the problems of using sorbitan monoesters is that in the presence of strong acids (like TCA) they tend to form soaps that have no power to attack the skin. This is partly why TCA ‘adjuvanted’ with sorbitan monolaurate is less aggressive for the skin.

therefore presented as the ultimate solution to all the problems posed by TCA. The most scientific-sounding explanation seems to be of a specific technique where, and I quote, ‘the TCA binds to metallic ions in bentonite clay’. It is not therefore strictly chelation, which would imply the binding of metallic poisons and their elimination through urine. But it is partly true insofar as an organic substance (the TCA) binds with silicon and metal ions (aluminum and magnesium). Even if the process is the exact opposite of chelation – since in this case it is the TCA itself that is the chelating agent – this explanation merits closer examination to understand the possible interactions between the TCA and the structure of the clay.

Phenoxyethanol

TCA in clay masks

Phenoxyethanol, C6H5OCH2CH2OH, also known as ethylene glycol monophenyl ether, 2-hydroxyethyl phenyl ether, 1-hydroxy-2-phenoxyethane, β-phenoxy-ethyl alcohol and 2-phenoxyethanol, has a molecular weight of 138.16. It is a simple disinfectant in the adjuvant solution, an antimicrobial agent that seems not to have a real adjuvant effect on the peel.

TCA sometimes comes in the form of a clay paste. Generally, clays consist of two types of compounds: aluminum silicates (bentonites) and magnesium silicates (hectorites). Clays36 are made up of stacked three-layer platelets (Figure 12.12): a middle layer of magnesium oxide (in the case of hectorites) or aluminum oxide (in the case of bentonites), surrounded by two layers of silicon dioxide (silica). The lateral surfaces of each platelet are positively charged37 and the lower and upper surfaces are negatively charged.38 The clay platelet therefore reacts like a dipole, and the different particles rearrange themselves depending on the electrical charges that encourage contact between the lateral surface and the upper surface. Clay has a ‘house of cards’ structure, and macroscopically forms a coarse gel with a grainy texture in the aqueous phase. The TCA molecule is itself electrically neutral. When it is in an unbuffered solution, it more or less completely breaks up, releasing its proton (H+) into the solution, which then becomes acidic. The TCA, without its proton (i.e. trichloroacetate anion), has an overall negative charge that can therefore combine electrically with the positively charged lateral surfaces of the clay, while the positively charged protons will combine more readily with the lower and upper surfaces of the negatively charged clay particles (Figure 12.13). The protons therefore combine with the

Sorbitan monolaurate

Chelation of TCA Some TCA masks33 have been presented as ‘chelated’ TCA. Chelation34 is a medical therapy that aims to detoxify the body of harmful minerals and metals. Chemically, chelation is the process by which an organic substance (the chelator) binds metal ions (iron, copper, lead, calcium, etc.) into inactive, non-toxic and water-soluble complexes that are easily eliminated in the urine. Intravenous chelation therapy (e.g. with ethylenediamine tetra acetic acid, EDTA) is often used to treat poisoning with heavy metals, including lead. The use of the term ‘chelation’ therefore seems inappropriate as far as TCA is concerned, and has no chemical basis since TCA is not a metal. The little information available states that chelation reduces the speed of penetration of TCA and therefore its depth of action.35 Might what we call chelation be partial inactivation of the TCA? The directions of use for Accu Peel® state that a ‘process called chelation allows the TCA to reach an even depth at the same time as using lower concentrations of TCA’. Might chelation, on the contrary, be a process that activates the TCA? But how can TCA be activated? The directions for use of TCA Cream Peel® tell us that, thanks to chelation, not only is this peel as deep and smooth (sic) as regular TCA but also that it uses much milder concentrations (the stakes are being raised) and so there is less pain and stinging and healing is faster. Is chelation the ultimate answer for TCA? The Holy Grail of the peeler? The Plastic Surgery Group states that ‘chelation’ of Accu Peel®, on the contrary, provides a superficial peel that heals more quickly – which at least seems logical. Chelation is

Figure 12.12 Clays consist of a stack of platelets that are electrically linked. This diagram shows the typical structure of a clay platelet and its electrical charge.

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Figure 12.14 TCA green clay mask (TCArcil® mask). The hands and forearms are covered in a clay paste layer that spreads easily.

Figure 12.13 A possible arrangement of TCA in a solution with clay in the gel phase, on the basis of electrical charges.

oxygen atoms of the silica molecules on the lower and upper surfaces, whereas the negatively charged trichloroacetate anion will combine with the metallic cations on the other surfaces of the clay particles. This then explains how the TCA binds with metallic ions. It is easy to understand how this might stabilize the TCA, as once it has broken up, it binds electrically with the different parts of the clay particles. It is, however, difficult to understand the real clinical advantage of this combination, as the protons that produce the peeling effect are still attached to the part of the TCA that has not broken up or else they have to break away from the clay in order to be effective. It could then be argued that the protons (and the trichloroacetate) and the clay are relatively united and that the TCA in a clay mask will act more slowly and be less aggressive. It is difficult to reconcile this with the statement that a low-concentration TCA clay mask produces the same effect as a more concentrated water-based TCA in which all the molecules exert their peeling effect at the same time. It cannot seriously be claimed that a clay paste of ‘chelated’ TCA at 20% is equivalent to any other TCA liquid at 45–50%. Even then, it would be necessary to know whether the concentration is m/m, m/v or m + v. It cannot possibly be m/m, as a TCA at 50% m/m is extremely aggressive and causes more complications than effective results. Besides, 20% TCA masks are marketed as superficial peels, which is incompatible with the gratuitous claim that ‘20% in mask form is equivalent to 50% in liquid form’, but completely compatible with the scientific explanation given above. Another major problem comes from the fact that the clay mask forms a coarse and opaque layer: it is impossible to observe the effect of the TCA directly and continuously through the clay mask (Figure 12.14). One common method of monitoring the peel consists in using a tongue depressor to remove the clay from a small area to

see if, or how much, frosting has occurred. If there is no frosting, the acidified clay is replaced. This examination is repeated after a few minutes or if the patient makes any comment. It should be noted that removing the clay with a spatula creates an abrasion on the skin where the acid can penetrate more deeply. The next time, therefore, the same area must be checked again as well as a different area. When a TCA paste is called ‘homogeneous’, it should not automatically be assumed that the TCA is distributed evenly, although it may well be. It should be assumed that the paste itself has a homogeneous consistency and is not grainy. It is possible – though not easy – to spread TCA homogeneously in a clay paste. However, the even distribution of TCA in a paste does not in itself guarantee that the acid will penetrate the skin evenly. Another argument that counters the claim that lower concentrations are more effective is that the application technique for a TCA mask involves degreasing the skin and applying glycolic acid or tretinoin beforehand.35 This makes the skin far more permeable and enhances the penetration of the TCA,39 which means being very careful about how long the paste remains in contact with the skin. Some TCA clay pastes are presented as causing simple erythema with no protein coagulation, but they nevertheless have a downtime of 6–8 days.35 The absence of frosting is compatible with a superficial peel – but not with an improvement in the appearance of deep wrinkles, which can only be treated with a deep peel. Then again, a downtime of 6–8 days is not compatible with a superficial peel, as it is the same as the downtime following a ‘medium’ TCA peel to the papillary dermis. The TCA mask is not the easiest40 or safest of peels, as it is not possible to check in real time whether the TCA is penetrating too deeply under the mask. It does, however, make application a little easier for doctors who doubt their ability to apply a superficial TCA peel evenly. We can therefore conclude by saying that TCA masks are easy to apply but difficult to monitor. Even if ‘chelation’ makes the clay mask less aggressive, it is on the whole not as safe as an ‘open’ TCA peel, which can be monitored at all times. My experience with a TCA mask preceded by a glycolic acid mask is in the context of a regular medium-depth TCA peel to the papillary dermis.

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effects of four different types of peels against a control group:

Histology Even though histological sections taken 30 minutes after the application of a medium-depth TCA peel on the skin have not revealed any skin necrosis, and even though histologically everything appears normal, it is certain that necrosis is taking place both clinically and chemically. The epidermis is functionally dead, although it appears to be histologically normal. Maybe this can be explained by the protein-coagulating action of the TCA: with conventional histology, it is not possible to see membrane proteins (essential to cell life) coagulating. It is only later on that necrosis can be detected histologically when the normal cell structure has radically changed as a result of its protein membranes becoming devitalized. The overall histological effect of a TCA peel consists in the destruction of the living cells of the epidermis and possibly the dermis (the depth of destruction depends on the concentration used). Abnormal keratinocytes are replaced by healthy cells from deep surviving islets of keratinocytes, the pilosebaceous units and the sweat glands.41 As the skin re-epithelializes, new collagen is formed. The depth of skin necrosis is directly proportional to the concentration of the TCA. Necrosis should not be the only endpoint of a TCA peel – stimulation also plays an important role. Repeated application of less concentrated TCA helps rebuild the papillary dermis directly and/or indirectly as a result of the repeated dermal irritation of the peelinduced inflammation. It is possible to reach the dermis using a low-concentration solution applied to an epidermis that has been made temporarily more permeable by a prior peel or ‘robust’ preparation. TCA peels allow different depths of penetration to be reached (Table 12.3). A study by Roenigk41 shows that regeneration of dermal collagen starts within 2–3 weeks. The increase in papillary dermal collagen and the production of elastic fibers continues for 6 months. Another study42 on mice artificially photoaged by exposure to UV rays compared the histological

■ ■ ■ ■

50% glycolic acid 30% TCA (m/v or m + v? – not specified) 50% TCA (m/v or m + v? – not specified) Phenol peel (Baker Gordon’s formula).

In all of the peel groups, the concentration of collagen increased from the 3rd day, fell around the 7th day and reached a positive peak around the 28th day. There was more of an increase with the TCA and phenol peels than with the glycolic acid. There was a significant increase in the concentration of glycosaminoglycans with the 50% TCA and phenol at 14 and 28 days. On the 60th day, the dermal concentrations both of collagen and glycosaminoglycans had returned to their original values in all of the groups. These findings cannot be considered as proof that these peels are not clinically effective, as the structure of the epidermis and dermis improved histologically, the collagen fibers were significantly rearranged in the papillary and reticular dermis and elastotic material disappeared in the deep TCA and phenol groups. At the same time, it was noticed that the elastic fibers rearranged themselves. These positive histological changes are more marked in the deep TCA and phenol groups than in the other peel groups. As for the global effect, the study shows an overall increase in dermal thickness with the deeper peels. In the long term, the histological changes brought about by TCA are temporary when the TCA penetrates superficially and long lasting when the TCA penetrates to the papillary dermis at least. Dermal fibroplasia causes hypertrophic scarring, scar adhesions and keloids. Black or dark skins are more likely to develop this type of reaction. The shoulder girdle and the lower thorax are both high-risk areas, as is the jaw area on the face. This type of scarring does not occur when necrosis goes no further than the upper reticular dermis.

Table 12.3 The depths of peelings, type of action and duration of change. Level of destruction

Type of action

Duration of change

Upper stratum corneum

Exfoliation

Very temporary

Intraepidermal

Partial destruction of the epidermis

Very temporary

Basal layer

Destruction of the basal layer

Temporary

Grenz zone

Destruction of the Grenz zone

Medium duration

Papillary dermis

Destruction of the papillary dermis

Long lasting

Upper reticular dermis (with vertical fibers)

Destruction of the upper reticular dermis

Permanent

Deep reticular dermis (with horizontal fibers)

Destruction of the deep reticular dermis

Permanent; risk of scarring

Hypodermis

Scarring

Permanent

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Apart from a few exceptional cases (e.g. Ehlers–Danlos syndrome), the destruction of the papillary dermis does not cause hypertrophic scarring. There is a risk of skin atrophy when all of the appendages of a treated area undergo necrosis. The skin does not have any source of supply to regenerate cells quickly. The keratinocyte clones can only come from the (distant) edges of the necrotic areas; they cannot be produced in sufficient numbers for rapid skin regeneration if the lesion is more than a few centimeters in diameter. Lesions smaller than 1 cm in diameter, even in the deep reticular dermis, do not pose a high risk of scarring unless there is a secondary infection or the patient scratches the scabs. When all of the appendages have undergone necrosis, the melanocyte reserve as well as the keratinocyte reserve suffers, and scarring will be hypopigmented or unpigmented.

Occlusion of TCA Following the example of phenol, it was suggested in the past that occluding TCA could potentially enhance penetration. A histological study by Stegman43 in 1980 throws some light on this question. Occlusion does in fact increase the depth of action of phenol, but actually reduces that of TCA. An occlusive dressing applied quickly after phenol helps it macerate and deepens its action. An occlusive dressing applied immediately after TCA creates a barrier to epidermal water evaporation and to the water in the solution itself. Under occlusion, this water accumulates in the uppermost layers of the skin, where it dilutes the TCA fairly rapidly. With phenol, this slight dilution enhances its penetration. An occlusive dressing applied 30 minutes after TCA does not dilute the acid, as it has had enough time to coagulate the proteins in the skin and neutralize itself by combining with the proteins before occlusion can dilute it. Applying a greasy substance, such as Vaseline® or an antibiotic ointment, immediately after a TCA peel is equivalent to occlusion, and can reduce the depth of necrosis caused by the TCA.

Increasing the permeability of the stratum corneum The thicker the stratum corneum, the less the TCA penetrates, and any method used to make the stratum corneum thinner before applying TCA deepens its action. Applying tretinoin for 2 weeks before a TCA peel thins the skin and causes the keratinocytes and corneocytes to dedifferentiate. Acetone degreases the skin and causes chemical changes in the membrane lipids, which increase the skin’s permeability and the depth of action of the peels. Applying a given concentration of TCA to a thin and

permeable skin will cause deeper necrosis than application to a thick and impermeable skin. Another way of increasing the depth of skin necrosis would be to use higher concentrations of TCA, but this method produces variable results because of the wide variation in penetration of TCA in an aqueous solution. The risk of scarring increases with the concentration of the TCA.

Notes 1. The alpha carbon atom is that adjacent to the COOH group (as with alpha-hydroxyl acids – cf Chapter 6). 2. Which means that at a pH of 4.76, 50% acetic acid in an aqueous solution is in the form of acetate. 3. ‘Glacial’ acetic acid is 100% acetic acid – it is so called because of its tendency to solidify near room temperature (the melting point of acetic acid is 16.7°C). 4. Through the accumulation of lactic and/or glycolic acid. Tubular necrosis develops rapidly. 5. Due to precipitation of myoglobin and oxalate crystals in the renal tubules. 6. Bismuth Ch. Toxicologie clinique, 5° ed. Paris: Editions Médecine–sciences, Flammarion, 2000. 7. Ketoacetic acid, oxoethanoic acid. 8. Oxalic acid (ethandioic acid) is HOOC.COOH, with pKa1= 1.23 and pKa2 = 4.19. 9. Glycolic acid is HO.CH2.COOH, with pKa = 3.83 (see Chapter 6). Glyoxylate is converted into glycolate by glyoxylate reductase. 10. Glycine (aminoacetic acid, aminoethanoic acid) is H2N. CH2.COOH, with pKa = 2.4. It is transaminated by an alanine–glyoxylate aminotransferase. The glycine can then be incorporated into proteins and used for serine synthesis or simply be degraded. 11. DCA was administered orally in the drinking water of rodents. No specific data have been reported in humans. 12. Kitamura N, Ota Y, Mimura K. Effects of diisopropylamine dichloroacetate on proliferation and differentiation of normal keratinocytes in vitro. Skin Pharmacol Appl Skin Physiol 1999; 12: 317–325. 13. Johnson K, with the Canadian Task Force on the Periodic Health Examination. Periodic Health Examination, 1995 update: 1. Screening for human papillomavirus infection in asymptotic women. CMAJ 1995; 152: 483–93. 14. Although using the new phenol formulas seems to be safer (see Chapter 36). 15. TCA is often found in drinking water as a by-product of disinfection. 16. Obtained by simple dilution of TCA crystals in water. 17. I beg any chemist reading this to forgive this explanatory short cut. 18. Trauchessec JM, Pissot F. Solution d’acide trichloracétique masse par masse pour peelings dermatologiques, nécessité d’une formulation explicite pour les solutions d’acide trichloracétique. 18° réunion du GRCD, Perpignan, 9 Septembre 1995: 28–38. 19. Trauchessec JM, Pissot F. Solutions d’acide trichloracétique

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20. 21.

22.

23. 24. 25.

26.

27.

28.

masse par masse pour peelings dermatologique. Nouv Dermatol 1996; 15: 252–5. One apple plus one apple equals two apples, whereas one apple plus one pineapple equals two pieces of fruit! According to Roenigk, applying TCA at 70% m/v on the face usually causes scarring, while in gynecology, treating vaginal or cervical condylomas does not produce any scarring. McCollough EG, Langsdon PR, Maloney BP. Chemical Peel with Phenol. Roenigk RK, Roenigk HH (eds.), Dermatologic Surgery, Principles and Practice, 2nd edn. 1147–60. 1996 UK, Oxford, Marcel Decker Ltd. Rereading the textbooks that I used at the beginning of my career as a ‘peeler’ now makes me realize why it was so difficult to get an overall grasp of the field and to understand the consistency of the technique. Brody H, Stegman S. Histological study by Harold Brody and Samuel Stegman, at 3, 30 and 90 days. TCA therefore does not have an ‘all or nothing’ action. McCollough EG, Langsdon PR, Maloney BP. Chemical Peel with Phenol. In: Roenigk RK, Roenigk HH (eds.), Dermatologic Surgery, Principles and Practice, 2nd edn. 1147–60. 1996, UK, Oxford, Marcel Decker Ltd. Easy TCA® and Unideep® consist of peel solutions as well as a post-peel cream whose ingredients help achieve better results and avoid complications. Only Touch® consists of a solution alone, but has to be combined with Easy TCA® or Unideep®, and thus benefits from the application of the post-peel cream of these peels as well. Chiarello SE, Resnik BI, Resnik SS. The TCA masque. A new cream formulation used alone and in combination with Jessner’s solution. Dermatol Surg 1996; 22: 687–90. Vergereau R, Trauchessec JM, Peyronnet B. Le new peel. J Med Esth Chir Derm 1990; XXII (68): 243–55.

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29. See the many previously published works on the semiology of TCA–SAS peels. 30. See Chapter 2. 31. Peyronnet B, Trauchessec JM, Vergereau R. Le peeling doux. J Med Esth Chir Derm 1991; XXIII (69); 33–7. 32. In fact, the commercially available ‘glyceryl monooleate’ is a mixture of esters of glycerol with a number of fatty acids (long-chain carboxylic acids), the major component of which is the monoester with oleic acid. 33. TCA Masque®, Accu Peel® cream and TCA cream peel®. 34. From the Greek chele, meaning ‘claw’. 35. Cabaní I. Nuestra experiencia en la aplicación de la nueva máscara de TCA. Medicina estética (SEME) 1995; 39: 25–9. 36. A clay is a friable sedimentary rock that can be molded when soaked in water. 37. Thanks to the metallic cations of the crystalline lattice. 38. Thanks to the oxygen atoms of the silica molecules. 39. Which would be pointless – even dangerous – if the TCA mask at 20% had the same effect as 50% TCA. 40. Prior application of a glycolic acid mask, and close and difficult monitoring of the contact time and downtime are necessary. 41. McCollough EG, Langsdon PR, Maloney BP. Chemical Peel with Phenol. In: Roenigk RK, Roenigk HH (Eds.), Dermatologic Surgery, Principles and Practice, 2nd edn. 1147–60. 1996, UK, Oxford, Marcel Decker Ltd. 42. Butler P, Gonzales S, Randolp M et al. Quantitative and qualitative effects of chemical peeling on photo aged skin: an experimental study. Plast Reconstr Surg 2001; 107: 222–8. 43. Stegman SJ. A study of dermabrasion and chemical peels in an animal model. J Dermatol Surg Oncol 1980; 6(6): 490–7.

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13 Trichloroacetic acid: indications and contraindications

Main indications for trichloroacetic acid Trichloroacetic acid (TCA) is an extremely versatile peel that can reach all depths, and can be applied to all skin types, on all parts of the body and in a great many indications. Using solutions that are properly prepared and following strict protocols ensures a safe and effective peel. Repeating several easy peels, such as Easy TCA®, can boost collagen and elastin production to the same degree as a deeper peel; repetition may even be preferable to using a more aggressive peel when the aim is to stimulate the skin and renew the epidermis, as is the case in the treatment of photoaging. On the other hand, when the desired effect is destruction of deeper layers of the dermis and epidermis to eliminate certain lesions, a single deeper peel may be a better indication than repeating several peels to the Grenz zone, as is the case when treating lentigines and mixed or dermal melasma.

Photoaging Early photoaging (Figure 13.1) is one of the best indications for a TCA peel. In short, it improves and evens out the complexion, reduces or gets rid of lentigines, improves elastosis and fine lines, improves skin tone, and generally brightens the skin. TCA peels have often been combined with tretinoin in this indication (see Chapter 2). Photoaging on the hands is an excellent and easy indication for TCA (see below and Figure 13.3).

Solar elastosis The papillary dermis is sometimes so atrophic that the epidermis appears to be lying directly on the middle dermis,

Folds and wrinkles Deep wrinkles and folds are not a good indication for TCA peels: ■ Folds cannot be treated by peels, and require surgery, dermal fillers or thread lifts. Deep nasolabial folds and marionette lines do not always respond to phenol. ■ Dynamic wrinkles respond well to a combination of botulinum toxin and peels: the peels restructure the epidermis and the dermis on an unmoving base and the clinical results are better when these two treatments are combined than when used alone. ■ Fine sun-related wrinkles respond well to TCA, but deeper ones respond better to phenol. ■ Wrinkles around the mouth and eyes are very poor indications for TCA, even in high concentrations; phenol is far more effective (see Chapter 36).

Figure 13.1 Early photoaging: a good indication for TCA.

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without the intervening Grenz zone. The epidermis then becomes ‘too big’ for the underlying dermis, and wrinkles appear – like baggy clothes that crease on a body that has grown too thin. In theory, only a very deep peel can treat solar elastosis, by producing enough good-quality collagen and elastin in the papillary dermis to fill the atrophied dermis and bury the sun-damaged fibers deep down (see Chapter 26). Repeating certain types of peel to the Grenz zone1 once a week may be effective enough to improve the appearance of the skin without the downtime that inevitably follows medium or deep peels. Of course, the deeper peels will be more effective: there is no comparison between the results of a phenol peel and those of an AHA, resorcinol or TCA peel! On the other hand, dermatologically and toxicologically, phenol is a risky option for treating anything but facial skin. Body skin only benefits from other agents. Solar elastosis appears in several forms. It starts with the appearance of limited areas of elastosis that as yet have no or little clinical expression. Its maximum expression is seen when the skin has a cobblestone appearance (Figure 13.2). The type of treatment depends on whether the elastosis is in its very early stages or if it is more advanced (Figure 13.2). Early elastosis, which is characterized by very fine lines and an uneven complexion, can be treated successfully with four Easy TCA® peels or one Unideep® peel, while advanced elastosis can only benefit from a deep reticular peel (fullface Lip & Eyelid® formula) and a major restructuring of the skin. TCA would have no effect on the deep wrinkles in Figure 13.2, no matter which concentration, adjuvants or other combined treatments were used. Solar elastosis often affects the legs if they are frequently exposed to the sun, which is the case with women who wear skirts. The skin between the knee and the malleolus is sometimes affected by visible elastosis that can be improved by combining abrasion and Easy Phytic® solu-

Figure 13.3 Overall rejuvenation of the hands after four sessions of Easy TCA® at a rate of one session every 2 weeks.

Figure 13.4

Figure 13.2 Solar elastosis (skin with a cobblestone appearance): this is not the best indication for TCA.

Lentiginosis and photoaging. (a) Before treatment, there are about 40 lentigines and/or actinic keratoses. (b) After four sessions of Easy TCA® peels to the Grenz zone, there are only about 10 lentigines/keratoses left. The signs of photoaging are visibly reduced: fine lines, quality of the skin, improved eyelid tension, etc.

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tion (see Chapter 11). The hands and forearms respond extremely well to Easy TCA®, with no side-effects (Figure 13.3).

Lentiginosis2 TCA is effective in treating solar lentigines: the concentration of the TCA is chosen depending on the assumed depth of the lentigo. Relatively superficial lentigines are easily treated with Easy TCA® (Figure 13.4). Lentigines of medium depth respond to Unideep®. Lentigines originating from the deepest dermal papillae and embedded deep in the dermis only respond to very concentrated TCA (Only Touch®), or even phenol (Lip & Eyelid® formula), applied locally and combined with Easy TCA® (or Unideep®) to even out the results and treat the smaller subclinical lesions (Figure 13.5). It should be noted that a TCA peel, even to the papillary dermis, does not always treat lentigines definitively and that several peels to the papillary dermis may be necessary for long-term results.

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Figure 13.5 Photoaging, actinic keratoses and lentigines. (a) Before and (b) after a peel to the papillary dermis with TCA (Unideep®) and phenol (Lip & Eyelid® formula) around the mouth and on the large lentigo on the left temple only. (c) Before and (d) on the 6th day after the peel. For more details, see Chapter 23.

Perioral wrinkles Very fine lines around the mouth can be improved by a combination of filling techniques (e.g. hyaluronic acid) and one or more TCA peels to the papillary dermis, but the results achieved with TCA never equal or even come anywhere near those achieved with phenol, which is preferred in chemical labioplasty or cheiloplasty (see Chapter 36) in combination with botulinum toxin, if possible.

Prevention of skin aging The wisest patients go to see their doctor before the clinical signs of aging appear and seek advice on how to prevent skin aging. The preventive treatments that might be suggested to these patients are straightforward and superficial procedures that do not disrupt their social lives too much. They may simply be prescribed cosmeceuticals: DHEAPhyto®, Actilift® (dimethylaminoethanol (DMAE) cream), Renutriv ACE Lipoic Complex® (an antioxidant) or Vit E

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Figure 13.6 Early photoaging: treatment of rosacea on the cheeks with a radiofrequency device (Ellman) and four applications of Easy TCA® (basic protocol). Daily care: Vit E Antioxidant® cream.

Antioxidant® (a hydrating antioxidant). These cosmeceuticals should be combined with sun protection against UVA, UVB. A series of AHA peels or TCA peels to the basal layer of the epidermis can be repeated on a yearly basis. If the signs of aging are beginning to show clinically, Easy Phytic® solution can be extremely beneficial. When the signs are more obvious, Easy TCA® is the best choice of peel (Figure 13.6). Very obvious photoaging can benefit from Unideep®, a papillary intraepidermal peel. An excellent treatment for preventing photoaging is a combination of a mesolift3 and a peel, sometimes called a ‘mesopeel’: a peel and a mesolift are used alternatively every other week or sometimes even in the same session when mesotherapy is combined with Easy TCA®. The need for a surgical facelift or a deep phenol peel can be put off for several years.

Melasma and chloasma Melasma (Figure 13.7) is a common acquired hyperpigmentation disorder of the face, neck and forearms. It is usually symmetrical. The density of color in the hyperpigmented area can vary, but is clearly delimited. Patients with a dark skin phototype are more prone and can get melasma earlier in life than light skin phototypes.4 Melasma appears almost exclusively on areas of skin that have been exposed to the sun. It can be of the following types: ■ Purely epidermal: there is a lot of melanin in the basal and suprabasal layers of the epidermis. It is occasionally found throughout the epidermis. A Wood’s light5 increases the contrast between the melasma and normal skin. This is the most common type of melasma. ■ Dermal: the melanin accumulates in the macrophages of the papillary and/or reticular dermis. A Wood’s light does not increase the contrast.

Figure 13.7 Melasma on the forehead: centrofacial. Other kinds of melasma include malar and mandibular.

■ Mixed epidermal–dermal: a Wood’s light accentuates the contrast in some areas and not in others, but an ‘epidermal’ area can hide an ‘underlying dermal’ area. The cause of melasma is still widely debated, and potential pathogenic factors include the influence of UVs, the hyperpigmenting effect of some cosmetics,6 genetic predisposition, hormone therapy and pregnancy.7 Estrogens and possibly progestogens can trigger melasma. Topical treatments for melasma usually include tyrosinase inhibitors, with or without tretinoin or one of its precursors. Azelaic acid is also a viable treatment option. A corticosteroid can be combined with it to counter any potential active inflammation. Lasers, intense pulsed light (IPL), dermabrasion and microdermabrasion have also been suggested, but often cause post-inflammatory hyperpigmentation. TCA can be an excellent treatment for melasma: it eliminates the melanin stored in the papillary dermis and epidermis (Figure 13.8). Mesotherapy has been recently reputed as an effective treatment of melasma.8

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Figure 13.8 Melasma on the forehead in a patient with skin phototype VI: (a) The condition before peeling. (b) Results of the following treatment: two sessions of Easy TCA® to the Grenz zone, combined with Blending Bleaching® cream. As the results were unsatisfactory, it was decided to use a deeper treatment. After two Easy TCA® peels, the patient was given two Unideep® peels to the papillary dermis, (c) still combined with Blending Bleaching® cream and Melablock® 50+. The peel to the papillary dermis was applied locally to the most resistant parts of the melasma. (d) End result.

If the melanin responsible for the melasma is too deep, TCA will only be effective after many repeated sessions. In any event, the TCA peel must be combined with effective sun protection and appropriate post-peel care in the long term. Simple aqueous solutions of TCA also require the skin to be prepared, in order to even out penetration and prevent common pigmentary changes. See Chapter 16 for the exact protocol for treating melasma.

Post-inflammatory hyperpigmentation and berloque dermatitis Post-inflammatory hyperpigmentation (PIH) (Figure 13.9) and berloque dermatitis9 usually respond well to TCA; they can be treated in the same way as melasma, but have a better prognosis as the original trauma disappears

after treatment, unlike melasma, which often persists or recurs.

Freckles Freckles (Figure 13.10) are small, clearly delimited, benign pigmented macules that appear on areas of sun-exposed skin in patients with a light skin phototype. They are never present at birth, but can start to appear from the age of 3 years, and there is an autosomal dominant pattern of genetic transmission. They result from melanocyte hypertrophy, although not from an increase in melanocyte numbers. In the basal and suprabasal layers, more melanin is synthesized and transferred between the melanocytes and keratinocytes. This increased melanin synthesis could result from melanocyte clones that have mutated following UV exposure. The structure of the epidermis remains normal, apart from the parabasal keratinocytes, which contain more melanin in relation to the neighboring unpigmented cells.

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Figure 13.11 Freckles before (a) and after (b) a peel to the papillary dermis (Unideep®). A peel to the papillary dermis improves the quality of the skin, removes the freckles and improves the fine lines, but does not treat wrinkles.

Post-acne scarring Figure 13.9 Post-inflammatory hyperpigmentation after a road accident (see Chapter 5).

TCA has some effect on shallow scars, but can only improve the general condition of the skin and cannot get rid of scars altogether. TCA can be combined with sandpaper abrasion (see the discussion of abrasive peels in Chapter 15) or scar subcision before the acid is applied. Even a phenol peel cannot always guarantee to heal acne scars. High concentrations of TCA can be directly applied on acne scars, levelly, with good results.

Dilated pores

Figure 13.10 Freckles.

A peel to the basal layer lightens the freckles, sometimes only temporarily. A peel to the Grenz zone removes many freckles and lightens others. A peel to the papillary or reticular dermis gets rid of freckles altogether (Figure 13.11). Easy TCA®, Unideep® (TCA) and Lip & Eyelid® (phenol) can all be used as treatments for freckles, although phenol will generally not be used as the TCA can get rid of them by itself. Other treatments have been suggested. As freckles grow darker on exposure to UV rays, using a sunscreen helps to lighten them. Tyrosinase inhibitors, antioxidants, and tretinoin and its precursors can be used in conjunction with the peels to improve or prolong results.

Although it has been claimed that TCA has a ‘circular contraction’ effect that ‘narrows the follicle opening’, it appears that it has a limited effect on dilated pores, or, at best, the results are difficult to predict. Patients should never be promised visible results for dilated pores. Any results should be considered a bonus and not taken for granted. Using an abrasive technique before applying Easy TCA® may give promising results, but this remains to be confirmed with more experience. High concentration TCA can be successfully used for treating dilated pores or pike acne scars.

Seborrheic dermatitis Seborrheic dermatitis, resulting from an excess production of sebum and overgrowth of the commensal yeast Pityrosporum ovale,10 improves rapidly but only temporarily after the application of TCA peels. Follow-up treatment after the peels consists simply of applying vinegar every morning before showering (for the antiseptic qualities of the acetic acid) and the use of antimycotic creams. In some cases, the reaction of the yeast and metabolites causes eczema, which can be treated with topical corticosteroids. It should be noted that Easy Phytic®

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solution rapidly improves the inflammation associated with seborrheic dermatitis, without having to resort to corticosteroids.11

Widespread flat warts Flat warts are localized skin-colored papules that mostly appear on the back of the hands, the forearms and the face. Clinically visible flat warts do not respond to moderate concentrations of TCA (10–30%), and higher concentrations (40–50% m/m) often produce only temporary or incomplete results. Figure 13.12 shows how flat warts on the back of the hand reacted to a combined treatment of Only Touch® and Easy TCA®. Smaller flat warts can disappear completely, as can subclinical flat warts. Medium-size warts will come back, and they will sometimes need shaving with a radiofrequency scalpel (Ellman), for example. Not only are larger warts impermeable to TCA, but also their very size prevents the TCA from getting round them to ‘undermine’ and treat them from underneath (Figure 13.13). They should be treated by shave excision at the same time as the others are being treated with a peel.

Figure 13.12 Appearance of the hand after two sessions of Only Touch® and three sessions of Easy TCA® (for further details, see Chapter 15). The flat warts have disappeared. Note that the flat wart treated with radiofrequency is still healing. The fine visible flaking all over the hand comes from an Easy TCA® peel applied to even out the Only Touch® and treat the subclinical lesions.

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Sensitive skin Abnormal skin sensitivity is a clear sign of dysfunction of the skin’s protective properties against a hostile environment. Sensitive skin should be treated until its tolerance to external aggression returns to normal. Many products cause skin allergies that are not always easy to identify since they may manifest as ‘over-reactive’ or ‘oversensitive skin’.

B

Figure 13.13 (a) Multiple flat warts. (b) Localized frosting of the flat warts after multiple applications of Only Touch®. Note that the thicker dome of the flat warts is impermeable even to concentrated TCA. The wart in the middle is too thick, and should be shaved with (Ellman) radiofrequency.

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Figure 13.14 Keratoses: peel solutions penetrate the keratoses slowly. This photograph shows the slow penetration of phenol through keratoses during a full-face peel.

In the case of allergy, it is best to avoid using too many cosmetic products and stick to a few well tolerated creams.

Figure 13.15 Appearance of keratoses during treatment with 5-FU.

Actinic keratoses The treatment of actinic keratoses, like photoaging, is a common indication for chemical peels (Figure 13.14). The chemical elimination of actinic keratoses reduces the incidence of basocellular and/or spinocellular cancers.12 Other localized treatments (e.g. cryotherapy or laser) could also be suggested, but they are only applied to visible lesions and leave clinically undetectable microlesions to develop. A chemical peel, on the other hand, will treat all lesions, both visible and subclinical ones, and will improve long-term prognosis. In comparisons between TCA peels to the papillary dermis and the application of a 5-fluorouracil (5-FU) cream, the peels fare better, as applying 5FU gradually causes severe and rather nasty-looking dermatitis (Figure 13.15). Patients and friends can find the long-drawn-out treatment difficult to bear. A mediumdepth TCA peel, on the other hand, is generally a one-off treatment (few sessions at most).

Oncological indications As Vergereau et al12 reminds us, after a biopsy to confirm the diagnosis and depth of a lesion, TCA is indicated in the treatment of primitive malignant intraepidermal and intradermal tumors (depending on the depth of action of the TCA). Keratoses that have developed into microinvasive spinocellular or basocellular carcinomas can be treated

with TCA without leaving any scars: Only Touch® easily reaches the reticular dermis. Non-degenerated lentigo maligna (Hutchinson’s freckle or Dubreuilh’s melanosis) is also given as a potential indication for TCA, although phenol is no doubt more effective.

Acne All common types of acne can be treated with TCA. Severe acne, such as ‘acne necrotica’, ‘acne conglobata’ or ‘acne fulminans’, should first be treated medically and the inflammation eliminated before the cosmetic use of peels. Oral isotretinoin (13-cis-retinoic acid) is the gold-standard treatment for severe acne (Box 13.1), but new retinoids come to light regularly. Here too a combination of techniques proves worthwhile. Acne responds well to a TCA peel to the basal layer or the Grenz zone, whether it is comedonal, microcystic (Figure 13.16), papular or papulopustular. Deeper peels, to the papillary dermis, should not be used when acne is still active, because of the increased risk of infection (see Chapter 37). The number of open or closed comedones can be expected to decrease after several TCA peels. We shall see how the Easy TCA® technique allows comedones and microcysts to be opened immediately before the peel, which gives faster and better results. Seborrhea is often reduced after TCA

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high concentrations required make it relatively dangerous compared with the ‘chemical blepharoplasty’ technique using phenol, which is more effective and easier to control than highly concentrated TCA. It must be remembered that xanthelasma is associated with dyslipidemia in 50% of cases. It can also be symptomatic of hepatobiliary disorders (biliary atresia and biliary cirrhosis) when associated with cholesterol deposits that start to build up in the hands and feet before spreading. Monoclonal gammapathies have also been described in association with xanthelasma.

Stretch marks Figure 13.16 TCA will reduce the number of lesions and the inflammation of this type of microcystic acne. Opening the microcysts with a No. 11 scalpel blade or a needle and removing the blackheads with a comedone extractor immediately before applying Easy TCA® will produce faster and better results.

Box 13.1 Isotretinoin for acne Tablets dosed at 10 mg or 20 mg Total cumulative dose 120 mg/kg Daily dose 0.3–0.5 mg/kg For example – weight of 70 kg: Total cumulative dose 8400 mg • Daily dose of 0.3 mg/kg = 21 mg/day ⇒ accumulated dose for a month 600 mg ⇒ total duration of treatment 8400/600 = 14 months • Daily dose of 0.5 mg/kg = 35 mg/day ⇒ accumulated dose for a month 1050 mg ⇒ total duration of treatment 8400/1050 = 8 months

peels and seborrheic dermatitis improves significantly (although only temporarily). Acne in fact improves more quickly when treated with easy TCA than it does when treated with tretinoin, benzoyl peroxide13 creams, glycolic or azelaic acid creams, or ‘purifying’ creams used alone. These creams do, however, play an important part in the post-peel treatment of acne. Pigmented acne scars usually respond well to TCA. Shallow scars gradually soften. Ice-pick scars do not respond at all to TCA. A combination of sandpaper abrasion followed by Easy TCA® – a technique similar to the one described below for the treatment of stretch marks – can significantly improve post-acne scarring, even on the back.

Xanthelasma Eyelid xanthelasma has been presented as a good indication for TCA and dichloroacetic acid. Nevertheless, the

Countless suggestions have been made for the treatment of stretch marks, but none of them have really been effective. Some techniques are not deep enough and others not extensive enough. Superficial, intraepidermal, basal, Grenz zone and papillary techniques can only improve the appearance of stretch marks temporarily, but cannot reduce their size or depth. Some peels have been developed to give the atrophic base of the stretch marks a similar color to that of the surrounding skin; they contain resorcinol, which is oxidized to match the normal skin color. The results of these peels are good, but only temporary. Deep techniques, limited to the deepest part of the stretch marks, can do no more than tighten the little collagen that is left and slightly stimulate the few surviving fibroblasts: in spite of the fact that these localized treatments reach the deepest part of the stretch marks, the results are always disappointing. That is why I developed a technique for treating stretch marks consisting of sandpaper abrasion followed by Easy TCA® peel solution and post-peel cream. The excellent results achieved with this method are due to the fact that the atrophic base of the stretch marks contracts at the same time that the cells on the edge of the stretch marks being stimulated. The results seem to be permanent. See the section describing this technique in Chapter 15.

Other indications These include alopecia areata, liposuction scars, neurogenic excoriations and rosacea. TCA has often been tried on vitiligo, but without success.

General contraindications for TCA–SAS ■ ■ ■ ■

General run-down condition Epidermolysis or dermolysis bullosa Active bacterial, mycotic or viral skin infections Depression or personality disorders

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■ Tendency to scratch ■ IQ insufficient to understand the events surrounding the application of the peel solution ■ Expectations of miraculous and life-changing results ■ Refusal to go through with follow-up visits ■ Severe progressive neoplasic disorders ■ Immunodeficiency ■ Insulin-dependent diabetes: depending on the depth of the peel and the risk of infection. Type 2 diabetes is not a contraindication for peels. Patients with stable insulin-dependent diabetes can be given a peel to the Grenz zone ■ Prior treatment with isotretinoin, if the peel is to the Grenz zone ■ Ehlers–Danlos syndrome, keloid scars, if the peel is to the papillary dermis ■ Extensive telangiectasias: these should be treated before peeling

Notes 1. Easy TCA® in the basic protocol. 2. For more details, see Chapter 1. 3. A mesolift is a mesotherapy technique that involves injecting various products into the dermis: hyaluronic acid, vitamins, trace elements, DMAE, polylactic acid, etc. 4. In South Asian, South-East Asian or Middle Eastern patients, melasma can appear before the age of 10, while it is rarely seen in Caucasian patients before puberty. 5. It is not possible to do a Wood’s light examination on very dark skin types.

6. To date, however, it has not been possible to reproduce the melasma by applying these cosmetics intentionally. 7. The mask of pregnancy tends to lighten naturally and even disappear in patients with a light phototype unless they are taking estrogens and progestogens, which can cause the mask of pregnancy to persist. 8. www.astheticdermal.com 9. Berloque dermatitis is an acquired hypermelanosis resulting from contact photodermatitis caused by a sensitizing agent (perfume or metal in jewelry). Berloque, or berlock, dermatitis gets its (misspelled) name from the French word ‘breloque’ meaning a trinket or charm that is attached to a bracelet. These charms are often of poor quality and cause contact allergies in the shape of the trinket itself. 10. It should be noted that the precise pathogenic relationships between hyperseborrhea and yeast colonization are still controversial, even though ketoconazole can (temporarily) eradicate seborrheic dermatitis. It is suspected that it is caused by a more fundamental immunological disturbance. 11. The trial protocol currently being used is the following: apply a single layer of Easy Phytic® solution in the morning and leave it to act during the time it takes to brush the teeth. Take a shower. Repeat the application every day for 3 consecutive days. 12. McCollough EG, Langsdon PR, Maloney BP. Chemical Peel with Phenol. In: Roenigk RK, Roenigk HH (Eds.), Dermatologic Surgery, Principles and Practice, 2nd edn. 1147–60. 1996, UK, Oxford, Marcel Decker Ltd. 13. Vergereau R, Trauchessec JM, Peyronnet B. Le new peel. J Med Esth Chir Derm 1990, XXII (68): 243–55. 14. Recall that benzoyl peroxide, alpha-hydroxy acids and tretinoin thin the stratum corneum and enhance penetration of the acids.

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14 Trichloroacetic acid: classic semiology Preparing the skin Pre-peel care is discussed in Chapter 2. Further information can be found in Chapter 12. The safety of peels employing trichloroacetic acid in simple aqueous solution (TCA-SAS) has been greatly improved by systematic preparation of the skin before peeling. Preparing the skin helps improve microcirculation, increase glycosaminoglycan synthesis, increase the number of mitoses in the basal layer keratinocytes, stimulate production of epidermal growth factors, deactivate melanocytes and even out and deepen the effect of the TCA. One month before a peel with TCA-SAS (Soft Peel®), the patient should apply a cream consisting of hydroquinone (4 g), micronized hydrocortisone acetate (0.5 g), paraffin oil (16 g), or emulsifier based on polyglycol stearate (21.5 g) and excipient qs 100 g, twice a day. Tretinoin is then mixed into this cream in gradually increasing quantities. The concentration of tretinoin is increased every week to reach a final concentration of 0.3%.1 Dermatitis develops due to the tretinoin: irritation with flaking and redness signals that the skin has been properly prepared, and guarantees a successful peel. However, the need to use a technique to enhance and even out penetration of the TCA–SAS proves that the action of TCA–SAS is uneven and inadequate. The need to apply hydroquinone twice a day at a concentration of 4% as a preventive shows how aggressive the peel is to the skin and how it triggers postinflammatory pigmentary changes. In short, the introduction of skin preparation before a TCA–SAS peel and adding adjuvants greatly improved safety, and is still essential to compensate for the inadequate and uneven penetration of this type of peel, as well as to reduce the risk of complications, especially pigmentary changes. For the record, it is interesting to note that the first time I presented Easy TCA® at a congress of the Belgian Society of Cosmetic Medicine in Brussels in 1997, there was an outcry. The peel was shouted down, demonized and criticized even before it was presented, as it flew in the face of the all too recent dogma of aggressive skin preparation that then held sway. Anyone tempted to use it was told that their worst nightmares would come true if they did not prepare the skin beforehand. It was soon proved that the Easy TCA®2 technique is perfectly valid and that, apart

from certain specific cases such as the treatment of stretch marks or resistant melasma, this peel does not require any skin preparation. The doom-mongers, partisans of the dogma of preparation, gradually fell silent, and the sworn enemies of Easy TCA® started to talk about the relative merits of preparation and eventually the pointlessness of preparing the skin in many cases. Everything has finally fallen into place, and preparing the skin is now considered as an additional tool for many peels, a weapon that is optional in some cases, but that still remains essential when using TCA–SAS. Treatment with oral isotretinoin is sometimes essential in cases of severe acne, but is contraindicated before a peel to the papillary dermis. An Easy TCA® peel to the basal layer,3 on the other hand, can be performed without any risk of complications, and can produce excellent results for severe acne that has been treated beforehand with oral isotretinoin.

Application of TCA–SAS It is easy to summarize the application of TCA-SAS.

Day –30 to day 0 Pre-peel preparation (see also Chapter 2) involves the following: ■ ■ ■ ■

deactivation of melanocytes thinning and evening out of the stratum corneum stimulation of keratinocyte regeneration botulinum toxin, coagulation of telangiectasias, excision of benign tumors, cleaning the skin, etc. ■ obtaining photographs, informed consent and other legal documents.

Day 0 This involves the taking of photographs, settling in, disinfection and degreasing. The patient is photographed from five angles, with and without flash (see Chapter 34). The patient is placed in the dorsal supine position; good

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lighting is needed to monitor the skin and any changes in skin tone. The skin is disinfected with a sterile swab soaked in alcohol, and degreased with a sterile swab soaked in acetone. Good ventilation must be ensured so that the patient does not breathe in the alcohol or acetone fumes.

The depth of action of the same peel solution can therefore be varied simply by changing the applicator or the pressure of application.

Local anesthetic

The speed of application of TCA is not in itself important, because: ■ unlike alpha-hydroxy acid (AHA) solutions, TCA does not have to be neutralized ■ unlike phenol solutions, TCA is not toxic.

Local anesthetic is never needed when TCA is used to treat the epidermis to the Grenz zone. It may be necessary when the TCA reaches the papillary or reticular dermis.

Applying the TCA–SAS TCA–SAS can be applied with any type of applicator.

Effect of the type of applicator A rough-textured applicator (sterile gauze) abrades the skin, causing surface injury as it deposits the acid on the skin: this helps the TCA penetrate more deeply.

Effect of pressure of application The pressure of application also plays a role in determining the depth of action of the TCA. The harder the solution is applied, the more deeply will the TCA penetrate. A swab held in the hand has less abrasive force than a swab held with Kocher forceps. A smooth applicator does not abrade the skin while depositing the acid and the action of the TCA remains more superficial. Using a brush to apply the same number of coats of the same TCA solution with the same concentration produces a more superficial peel than using a swab.

Effect of speed of application

The speed of application depends on: ■ The patient’s sensitivity: a very sensitive patient will find it difficult to stand the burning sensation of the TCA on the whole face, and will be better off if the TCA is applied zone by zone. ■ The surface area being treated: Only Touch® can be applied quickly on lentigines, as only small areas are affected by the burning from the acid. Large areas (e.g. the back) should be treated by TCA zone by zone for the patient’s comfort. ■ The depth of the peel: applying TCA is painful, but an intradermal peel is far more painful than an intraepidermal peel. An intradermal peel should be applied zone by zone for the patient’s comfort, while an intraepidermal peel can be done in one go.

Symptomatology of TCA application Applying TCA causes protein coagulation more or less rapidly, depending on the formulation of the peel, its concentration, prior preparation of the skin, the pressure of

Table 14.1 Symptoms following TCA application 1. Erythema: the peel is intraepidermal

No or little risk of visible flaking

2. Scattered pinpoint frosting: the peel is near the basal layer (Figure 14.1)

Sunburn-type flaking (Figure 14.2)

3. Cloudy-white frosting: the peel has reached the Grenz zone (Figure 14.3)

Flaking: light, thin skin (Figure 14.4)

4. 4. 4. 4.

Flaking: more or less brownish skin, depending on phototype and photodamage (Figures 14.7 and 14.8)

Even pink-white frosting (Figure 14.5) and ‘epidermal sliding’ (Figure 14.6): the TCA is in the papillary dermis. The sliding (wrinkling) can be seen when the skin is pinched, and corresponds to the coagulation of anchoring fibers between the dermis and epidermis

5. Pure white frosting (Figure 14.9), gradual disappearance of epidermal 4. sliding: the TCA has reached the reticular dermis 6. Gray-white frosting, epidermal sliding has gone: the TCA is in the 4. reticular dermis 7. Gray frosting and/or yellowish patches (phenol): deep reticular dermis

TCA should no longer be used for peels to the deep reticular dermis

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application, the skin type, etc. A 35% m/m TCA coagulates proteins. Different symptoms appear gradually: see Table 14.1 and Figures 14.1–14.9. A low-concentration formula is applied in several coats; the doctor can progressively see each of the symptoms described in Table 14.1, and can stop whenever he wants. A high-concentration formula penetrates very rapidly, and the symptoms come in such quick succession that it is impossible to see them clearly. The technique is much quicker but the doctor cannot choose when to stop.

Figure 14.3 Cloudy-white frosting.

Figure 14.4 Flaking after cloudy-white frosting.

Figure 14.1 Scattered pinpoint frosting.

Figure 14.5 Figure 14.2 Flaking after scattered pinpoint frosting.

Even pink-white frosting (the differences in color come from the presence of melasma). The contours of the eyes have been chemically resurfaced locally.

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Figure 14.6

Figure 14.8

The skin wrinkles when pinched between the fingers.

Flaking after a papillary peel on a light skin phototype that has been badly damaged by the sun.

Figure 14.7 Flaking after a papillary peel on a light skin phototype with little photodamage.

Two endpoints are worthy of more attention: ■ Scattered pinpoint and cloudy-white frosting signal the most superficial peel to the dermis: this is the limit of effectiveness (see Chapter 15). ■ Even pink–white frosting signals a peel to the papillary dermis: this is the safety limit (see Chapter 23).

Figure 14.9 Pure white frosting from a peel to the reticular dermis.

peel solution is extremely easy – you do not need a university degree to take a cotton bud and get skin to frost gradually! The choice of indications and managing postpeel care are different matters entirely, and a thorough knowledge of medicine is essential to do these properly.

Notes Post-peel care Post-peel care is also discussed in Chapter 3. In short, post-peel care is extremely important and depends on the skin type, the depth of the peel and the dermatological problem being treated. It is more important than preparation when using Easy TCA® or Unideep®. Any ‘peeler’ very soon learns that applying a

1. 2.

3.

Preparing the skin with tretinoin before the peel accelerates post-peel healing. Easy TCA® was called ‘Easy Peel’ at the time. The name was changed when Easy Phytic® peel came out, in order to avoid any confusion between the two ‘Easy’ peels: Easy TCA®, a combination of a TCA peel and Easy Phytic®, uses AHAs and phytic acid. See Chapter 11 for more information on this peel. The peel produces scattered pinpoint frosting only.

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15 Easy TCA®: basic protocol and skin aging

In 1968, Paul Langerhans discovered the presence of a particular type of epidermal cell in humans, which is now named after him. The Langerhans cell (LC) is a mobile dendritic cell that has no desmosomes and is found in most multilayered malpighian epithelia. LCs make up 2–5% of epidermal cells. They come from the medulla and migrate towards and within the skin and stay within the epidermis for 2 weeks at the most. LCs have three functions: ■ constant monitoring of the antigenic environment ■ inspection of foreign molecules ■ custody of the foreign invaders while the lymphocyte system reacts with an appropriate immune response It is easy to understand how important LCs are when one imagines the impressive number of potential antigen contacts over the entire epithelial surface of the body. When the entire epidermis is destroyed by certain peels, this not only affects the keratinocytes and the LCs but also other dermal dendritic cells (DDCs) that are potentially antigenpresenting cells. New generations of sentinel cells migrate rapidly from the bone marrow to the epidermis, which is being rebuilt after the peel, but this process is not effective immediately. What is more, the first LCs to arrive as reinforcements on the battlefield of the skin are ‘overwhelmed’ as soon as they reach the dermis by the different types of antigen stimulation that they have to face on skin that has lost its impermeability and physical defenses. The stratum corneum can be compared to the ramparts of a medieval city and the Langerhans cells to the soldiers who have to defend it. The likelihood of unexpected bacterial and viral complications occurring will be even higher, as there are fewer cells in the skin capable of an immune response. It is important to consider these basic notions of biology to get a better understanding of what happens and anticipate which type of peel might be associated with a higher incidence of complications in the form of bacterial or viral infections. It then seems obvious why applying peel solutions capable of destroying the epidermis and part of the

dermis on a skin with active herpes, acne or other infectious disorders is strongly contraindicated. Any medical staff suffering from respiratory or nose-and-throat infections should be kept well away from the patient, and the doctor’s hands should always be surgically disinfected before applying medium or deep peel solutions. Superficial peels with alpha-hydroxy acids (AHAs), on the other hand, are known to cause very few bacterial or viral complications after peeling, as their direct action is limited to breaking up the spaces between corneocytes.1 Even if the peel penetrates too deeply in places, it is, quite logically, exceedingly rare for an AHA peel to cause complications in the form of infection, when the endpoint is focal or localized frosting. With AHAs, the stratum disjunctum (SD), the outermost layer of the epidermis that makes the skin feel rough, flakes immediately. The skin, having lost its topmost layer, immediately feels softer to the touch. The risk of bacterial or viral complications with medium or deep peels could lead doctors to think that, in order to avoid these problems, only superficial peels should be performed and patients with active acne or herpes should not be treated at all. With a medium or deep peel, herpes prevention – as far as it goes – consists in a sandwich treatment with aciclovir, which is not well tolerated by patients with sensitive stomachs. With acne, caution limits the range of treatment choice to careful superficial peels (which have limited effectiveness even after repeated sessions). We are forced to put off, sometimes indefinitely, performing ‘medium-depth’ peels on patients with acne or herpes that have not responded to preliminary medical treatment. With the development of Easy TCA® (ETCA), another possibility for treatment has opened up, however. In many indications, ETCA can produce the results of a medium peel with only the complication risks – usually non-existent – of a superficial peel. ETCA can be applied quite successfully to active acne lesions, and the presence of herpes lesions on the lips is only a formal contraindication to the peel applied following the basic protocol. It is still advisable to avoid treating patients with active herpes, however. Then again, if herpes were to develop in the course of an

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ETCA peel, it would be reasonable to think that it was fortuitous and not directly related to the treatment. To date, there has been no reported incidence of herpes spreading after the application of ETCA (basic protocol). With regard to acne, in 80% of cases, the first application of ETCA to active papulopustular facial lesions improves their number and severity by 50%, and the lesions seem to heal without scarring. ETCA is applied on the basis of one peel per week for 4 weeks that clear the lesions almost completely without having to resort to antibiotics. Deep wrinkles and acne scars do not disappear: they lie deep under the skin and even phenol or carbon dioxide laser resurfacing cannot always treat them. A combination of several different techniques is clearly needed in these indications. Although the face can be treated separately, the neck should always be treated at the same time – to at least the seventh cervical vertebra – to ensure a better ‘tightening effect’. Ideally, all ‘visible areas’ should be treated: face, neck, décolletage, forearms and hands.

General remarks Presentation A growing number of doctors consider ETCA to be the safest and easiest TCA peel, and it is used in over 50 countries worldwide. ETCA now comes in two different kits. The first kit (Figure 15.1) consists of 12 phials of base solution and three tubes of post-peel cream for 12 facial peels – enough to treat three patients on the basis of four peels per patient. The second kit (Figure 15.2) consists of two bottles of base solution for 24 peels – enough to treat six patients on the basis of four peels per patient, and a large tube of post-peel cream.

Figure 15.2 Easy TCA® kit for 24 peels.

The phials, introduced more recently, are safer for the patient and prevent any cross-contamination. With both kits, the doctor adds TCA to the base solution to activate the peel: the quantity of TCA to be added to the base solution may vary from country to country and from kit to kit. To avoid any confusion, it is best to refer to the volumes that are clearly indicated on the inside cover of each kit.

Post-peel mask cream The post-peel mask cream, which is highly antioxidant, contains vitamins, trace elements, growth factor, fatty acids and tyrosinase inhibitors. The doctor applies it only once, immediately after the required level of frosting has been achieved. Its formulation is responsible for a significant proportion2 of the beneficial results of ETCA. It stops the burning sensation almost immediately and greatly reduces the risk of post-peel complications (see Chapter 5, p41). Its components are as follows.

Vitamin C

Figure 15.1 ‘Classic’ Easy TCA® kit for 12 facial peels.

Magnesium ascorbyl phosphate (MAP) is more effective than ascorbyl palmitate (AP), as the protection of its active function by esterification protects the MAP against oxidation and provides an antioxidant effect that is of better quality and longer lasting than that of ascorbyl palmitate, a molecule in which the enediol function of the ‘2’ carbon atom is not protected by esterification. Vitamin C is a powerful antioxidant, effective in aqueous solutions, that scavenges free radicals and prevents the breakdown of protein chains. It protects other antioxidants, which is an advantage in situations involving oxidative stress, such as infected or uninfected wounds and in the post-peel healing period.

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Urea (carbamide) A keratolytic agent used in the treatment of dry skin, this increases skin permeability.

Silicion (trimethylsilanol monomannuronate) This is strongly linked to proteoglycans and mucopolysaccharides, hyaluronic acid, and chondroitin sulfate. Silicion plays an important role in skin healing and is essential in anti-aging treatments.

Citric acid A tricarboxylic AHA, this is an antioxidant, chelator and buffer.

Phytic acid An antioxidant and tyrosinase inhibitor, this protects against the risk of hyperpigmentation and post-peel inflammation.

Vitamin A The post-peel mask cream contains retinol microencapsulated in a cyclodextrin. Vitamin A is involved in the processes of cell division and differentiation that help the epidermis regenerate after the peel from the cells of the basal layer. Retinol induces the expression of retinoic acid-binding protein (RABP) and regulates cell migration in the skin epithelium, which is vital for skin regeneration after a peel. Encapsulating retinol provides better bioavailability of the vitamin and protects the skin against oxidation. Keratinocytes have the enzyme tools required to convert retinol into retinoic acid (the corresponding carboxylic acid), which is the molecule ultimately responsible for the effect of vitamin A.

Selenium This is a trace element that accelerates skin healing; it has been proved to penetrate more easily when combined with methionine. The post-peel mask contains a combination of selenium and methionine, which improves healing after laser resurfacing or a peel, and prevents seborrheic dermatitis. Selenium is a component of glutathione peroxidase (GPX), an antioxidant enzyme that helps fight against peroxidation. Selenium helps reduce inflammation by lowering the number of hydroperoxide intermediates in cyclooxygenase and lipoxygenase reactions. It prevents the production of inflammatory and immunosuppressive cytokines and stimulates cellular immunity as well as humoral immunity. Combining it with vitamin E rein-

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forces its protective action. Selenium and methionine have a tretinoin-like effect without having an irritative effect.

Vitamin E Tocopheryl acetate is the most stable ester of vitamin E. It is readily hydrolyzed by esterases into pure vitamin E after it has been absorbed by the skin. The advantage of the acetate form is that it forms a reservoir that gradually releases the vitamin E inside the skin. Vitamin E scavenges free radicals that could damage neighboring tissue. It blocks oxidative chain reactions by inhibiting the formation of lipoperoxides inside the cell, and in this way protects the nucleic acids and proteins.

Propylene glycol A disinfectant, moisturizer and vitamin stabilizer, this reduces corneocyte cohesion, enhancing penetration of the other active ingredients in the post-peel mask.

Phenoxyethanol An antibacterial agent, this is used to disinfect wounds and burns.

Coenzyme R (biotin, vitamin H, vitamin B8) The metabolic action of biotin is mediated through biotindependent enzymes that actively synthesize purines. It is a stable monocarboxylic acid, soluble in water and alcohol, and acts as a coenzyme as well as a growth factor, even in very small quantities. Biotin deficiencies cause scaly dermatitis, hyperkeratosis and alopecia. Topical application of biotin reduces the secretion of sebum.

Note The fact that the peel solution has been applied on the skin beforehand has a significant effect on the rate of penetration of the cream’s ingredients. The cream penetrates much more deeply after a peel than on untreated skin: the skin is far more permeable immediately after a peel; sebum and corneocytes no longer function as a barrier and the purely water-soluble ingredients can penetrate the altered epidermis rapidly. In this way, large quantities of stimulants and antioxidants can reach the dermis. The post-peel mask has a pH of 6.5: it is not a neutralizing cream.

Base solution ETCA solution, reconstituted by the addition of acid, has a pH