Dermatoscopy in Clinical Practice: Beyond Pigmented Lesions (Series in Dermatological Treatment)

Citation preview

Dermatoscopy in Clinical Practice

Beyond Pigmented Lesions

Edited by

Giuseppe Micali Francesco Lacarrubba

Dermatoscopy in Clinical Practice

Series in Dermatological Treatment Published in association with the Journal of Dermatological Treatment Series editors: Steven R Feldman and Peter van de Kerkhof

1

Robert Baran, Roderick Hay, Eckhart Haneke, Antonella Tosti Onychomycosis, second edition, ISBN 9780415385794

2

Ronald Marks, Facial Skin Disorders, ISBN 9781841842103

3

Sakari Reitamo, Thomas Luger, Martin Steinhoff Textbook of Atopic Dermatitis, ISBN 9781841842462

4

Calum Lyon, Amanda J Smith Abdominal Stomas and their Skin Disorders, Second Edition, ISBN 9781841844312

5

Leonard Goldberg Atlas of Flaps of the Face, ISBN 9781853177262

6

Antonella Tosti, Maria Pia De Padova, Kenneth R Beer Acne Scars: Classification and Treatment, ISBN 9781841846873

7

Bertrand Richert, Nilton di Chiacchio, Eckart Haneke Nail Surgery, ISBN 9780415472333

8

Giuseppe Micali, Francesco Lacarrubba Dermatoscopy in Clinical Practice: Beyond Pigmented Lesions, ISBN 9780415468732

Dermatoscopy in Clinical Practice Beyond Pigmented Lesions Edited by Giuseppe Micali, MD Professor and Chairman Department of Dermatology AOU Policlinico-Vittorio Emanuele Catania, Italy and Francesco Lacarrubba, MD Researcher Department of Dermatology AOU Policlinico-Vittorio Emanuele Catania, Italy

© 2010 Informa UK Ltd First published in 2010 by Informa Healthcare, Telephone House, 69-77 Paul Street, London EC2A 4LQ. 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. 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. A CIP record for this book is available from the British Library. Library of Congress Cataloging-in-Publication Data Data available on application ISBN-13: 9780415468732 Orders Informa Healthcare Sheepen Place Colchester Essex CO3 3LP UK Telephone: +44 (0)20 7017 5540 Email: [email protected] Typeset by C&M Digitals (P) Ltd, Chennai, India Printed and bound in Great Britain by MPG Books, Bodmin, Cornwall, UK

Contents

List of Contributors

vii

1

Introduction Giuseppe Micali and Francesco Lacarrubba

1

2

Equipment Pietro Rubegni, Marco Burroni, Niccolò Nami, and Michele Fimiani

2

3

Parasitoses   3.1 Scabies and pediculosis: Biologic cycle and diagnosis Ani L Tajirian and Robert A Schwartz

7

  3.2 Videodermatoscopy and scabies Francesco Lacarrubba, Nella Pulvirenti, and Giuseppe Micali

11

  3.3 Videodermatoscopy and pediculosis Giuseppe Micali, Marianna Umana, and Francesco Lacarrubba

16

  3.4 Therapy of scabies and pediculosis: Potential and pitfalls Lee E West, Beatrice Nardone, and Dennis P West

20

  3.5 Therapeutic monitoring of parasitoses with videodermatoscopy Giuseppe Micali, Aurora Tedeschi, and Francesco Lacarrubba

25

  3.6 Tungiasis Elvira Moscarella, Renato Bakos, and Giuseppe Argenziano

29

4

Hair loss Antonella Tosti and Bruna Duque Estrada

31

5

Nail diseases Antonella Tosti, Bianca Maria Piraccini, and Débora Cadore de Farias

45

6

Diseases characterized by altered vascular pattern 6.1 Psoriasis 6.1A Vascular pattern under videodermatoscopy observation Giorgio Filosa, Rossella De Angelis, and Leonardo Bugatti

52

6.1B Histopathological correlations † Daniele Innocenzi, Maria Concetta Potenza, and Ilaria Proietti

57

6.1C Palmoplantar psoriasis Francesco Lacarrubba, Maria Letizia Musumeci, and Giuseppe Micali

61



contents

7

8

6.1D Psoriatic balanitis Giuseppe Micali, Maria Rita Nasca, and Francesco Lacarrubba

64

6.1E Scalp psoriasis Paolo Rosina

67

  6.2 Clear cell acanthoma Francesco Lacarrubba, Orazia D’Agata, Federica Dall’Oglio, and Giuseppe Micali

70

  6.3 HPV infections Pompeo Donofrio and Maria Grazia Francia

73

  6.4 Venular malformations (port wine stain type) Francisco Vázquez-López

75

  6.5 Bowen’s disease Leonardo Bugatti, Giorgio Filosa, and Alessandra Filosa

82

  6.6 Pyogenic granuloma Pedro Zaballos Diego

86

Miscellanea   7.1 Lichen ruber planus Francisco Vázquez-López

90

  7.2 Urticaria and urticarial vasculitis Francisco Vázquez-López

96

  7.3 Disorders of collagen tissues Paolo Rosina

100

  7.4 Rosacea Paolo Rosina

103

  7.5 Molluscum contagiosum Pedro Zaballos Diego

106

  7.6 Sebaceous hyperplasia Pedro Zaballos Diego

109

  7.7 Pigmented purpuric dermatoses Pedro Zaballos Diego

112

  7.8 Actinic porokeratosis Pedro Zaballos Diego

115

  7.9 Xanthomatous lesions Filomena Mandato, Maurizio Biagioli, and Pietro Rubegni

118

Dermatoscopy in cosmetic applications Warren Wallo

121

Index



127

List of contributors

Giuseppe Argenziano Department of Dermatology Second University of Naples Naples, Italy Renato Bakos Department of Dermatology Universidade Federal do Rio Grande do Sul Porte Alegre, Brazil Maurizio Biagioli Section of Dermatology Department of Clinical Medicine and Immunological Science University of Siena Siena, Italy Leonardo Bugatti Dermatology Unit Augusto Murri Hospital Jesi, Italy Marco Burroni Section of Dermatology Department of Clinical Medicine and Immunological Science University of Siena Siena, Italy

Orazia D’Agata Department of Dermatology University of Catania Catania Italy Federica Dall’Oglio Department of Dermatology University of Catania Catania, Italy Rossella De Angelis Rheumatology Unit Department of Molecular Pathology and Innovative Therapy Polytechnic University of the Marche Ancona, Italy Pedro Zaballos Diego Dermatology Department Hospital Sant Pau i Santa Tecla Tarragona, Spain Pompeo Donofrio Section of Dermatology Department of Systemic Pathology Genito-Dermatologic Ambulatory Unit University of Naples Federico II Naples, Italy

Débora Cadore de Farias Department of Dermatology Santa Casa de São Paulo Hospital São Paulo, Brazil

Bruna Duque Estrada Instituto de Dermatologia Prof. Rubem David Azulay Rio de Janeiro, Brazil

Maria Concetta Potenza Department of Dermatology - Polo Pontino University of Rome “Sapienza” Rome, Italy

Alessandra Filosa Dermatology Unit Augusto Murri Hospital Jesi, Italy



list of contributors

Giorgio Filosa Dermatology Unit Augusto Murri Hospital Jesi, Italy Michele Fimiani Section of Dermatology Department of Clinical Medicine and Immunological Science University of Siena Siena, Italy Maria Grazia Francia Section of Dermatology Department of Systemic Pathology University of Naples Federico II Naples, Italy Daniele Innocenzi Department of Dermatology - Polo Pontino University of Rome “Sapienza” Rome, Italy Tragically deceased 2009

Maria Letizia Musumeci Department of Dermatology University of Catania Catania Italy Niccolò Nami Section of Dermatology Department of Clinical Medicine and Immunological Science University of Siena Siena, Italy Beatrice Nardone Department of Dermatology University of Catania Catania Italy

†

Francesco Lacarrubba Department of Dermatology A.O.U. Policlinico-Vittorio Emanuele Catania, Italy Filomena Mandato Section of Dermatology Department of Clinical Medicine and Immunological Science University of Siena Siena, Italy Giuseppe Micali Department of Dermatology A.O.U. Policlinico-Vittorio Emanuele Catania, Italy Elvira Moscarella Department of Dermatology Second University of Naples Naples, Italy



Maria Rita Nasca Department of Dermatology University of Catania Catania Italy Bianca Maria Piraccini Department of Dermatology University of Bologna Bologna, Italy Ilaria Proietti Department of Dermatology - Polo Pontino University of Rome “Sapienza” Rome, Italy Nella Pulvirenti Department of Dermatology University of Catania Catania Italy Paolo Rosina Section of Dermatology and Venereology Department of Biomedical and Surgical Sciences University of Verona Verona, Italy

list of contributors

Pietro Rubegni Section of Dermatology Department of Clinical Medicine and Immunological Science University of Siena Siena, Italy Robert A Schwartz Department of Dermatology New Jersey Medical School Newark, New Jersey, USA Ani L Tajirian Department of Dermatology New Jersey Medical School Newark, New Jersey, USA Aurora Tedeschi Department of Dermatology University of Catania Catania Italy Antonella Tosti Department of Dermatology University of Bologna Bologna, Italy

Marianna Umana Department of Dermatology University of Catania Catania Italy Francisco Vázquez-López Department of Dermatology Hospital Universitario Central de Asturias Oviedo, Asturias, Spain Warren Wallo Johnson & Johnson Consumer Companies, Inc. Skillman, New Jersey, USA Dennis P West Department of Dermatology The Feinberg School of Medicine Northwestern University Chicago, Illinois, USA Lee E West Department of Pharmacy Northwestern Memorial Hospital Chicago, Illinois, USA



We dedicate this book to the memory of Daniele Innocenzi, an extraordinary and outstanding dermatologist and friend

1

Introduction Giuseppe Micali and Francesco Lacarrubba

Dermatoscopy (D) - also called “dermoscopy” or “incident light microscopy” - is a non-invasive technique that allows a rapid and magnified in vivo observation of the skin with the visualization of morphologic features invisible to the naked eye. It may be performed with manual devices that do not require any computer “assistance” and allow magnifications up to X20, or with digital systems requiring a video camera equipped with optic fibers and lenses that ensure magnifications of up to X1000; in the latter instance the term videodermatoscopy (VD) is more usual. The images obtained are visualized on a monitor and stored on a personal computer, in order to process them and compare any possible changes over time. In many ways, VD represents the evolution of D. In this book the term “dermatoscopy” will be referred to the use of manual devices and “videodermatoscopy” to the use of digital systems operating at high magnifications. Both D and VD are widely used in the differential diagnosis of pigmented skin lesions, usually through the technique called epiluminescence microscopy, which involves the application of a liquid (oil, alcohol, or water) to the skin to eliminate light reflection; recently, new systems utilizing polarized light may achieve similar results without the need for liquids. However, apart from their most common use for the differential diagno­ sis of pigmented skin lesions, it has been demonstrated that

D/VD have expanded applications in dermatology. Alternative applications of D/VD include inflammatory dis­eases, parasitoses, hair and nails abnormalities, and a large vari­ety of other dermatologic conditions as well as cosmetology. Importantly, for many of these disorders the use of high magnifications is needed for research as well as for clinical purpose. Depending on the skin disorder, D/VD may be useful for differen­tial diagnosis, prognostic evaluation, and monitoring response to treatment. Moreover, the capability to capture digital images is perfectly suited to teledermatology - the “store-and-forward” technique that allows exchange of opinions between dermatologists - and might be useful when on-site D/VD services are not available. The aim of this book is to advance knowledge of enhanced visualization/digital imaging using D or VD beyond the traditional indication of pigmented lesions of the skin. In particular, the book focuses on those con­ditions in which the techniques are more useful, describing the clinical and histopathological correlations associated with the procedure. The book has plenty of images that will be useful in the daily clinical prac­tice of a dermatologist, who should thus be encouraged to utilize D/VD in the routine evaluation of skin diseases. The book will serve as an important yet relatively simple aid in daily office practice.



2

Equipment Pietro Rubegni, Marco Burroni, Niccolò Nami, and Michele Fimiani

introduction The optical dermoscope is an instrument containing a light source that enables skin structures invisible to the naked eye to be seen. A medium such as ultrasound gel or Vaseline oil is applied to the skin to make the stratum corneum transparent, while the objective of the dermoscope is placed against the skin surface. The instrument makes it possible to observe a vast new range of dermatological signs. Dermoscopy is currently used in rou­ tine dermatology. The various specialist courses held in recent years have led to the definition of new methods for improving the diagnosis of neoplastic and other skin disorders. Videodermoscopy Analogue Videodermoscopy Between 1980 and 1990, advances in video technology led to the development of instruments that displayed dermoscopic images on a screen.(1) The first videodermoscope had a tele­ camera with video resolution connected to an optical dermo­ scope and a television screen with video recorders to record examinations. However, during this period, the dermoscopic examination using these equipment produced only low-quality images, which is due to the low resolution of the first-genera­ tion video cameras, and other cumbersome documentation and data-saving procedures; for example, the maximum television resolution is 768 x 576 pixel for the European PAL broadcast system and less for the American NTSC, where pixel is the basic image unit; analogue video recorders of the 1980s often had less than 400 horizontal lines. Low quality and technical limitations prevented the widespread use of videodermoscopy.(2) Digital Videodermoscopy Between 1990 and 2000, computerized instruments for digitizing images from telecameras connected to videodermoscopes became common. Digital dermoscopic images can be obtained by conver­ sion from video telecameras connected to digital cards or by use of high-resolution digital telecameras or digital cameras coupled with special dermoscopy adaptors. Computerized systems proved more practical for managing examinations because they offered the pos­ sibility of saving personal and private data of patients, together with digital images of pigmented skin lesions (Figure 2.1).(2, 3) In the case of video telecameras, the signal acquisition peripheral required a charge-coupled device (3CCD) or sen­ sor for the red, green, and blue bands, in order to keep image quality high during sampling.(1, 4) Digital telecameras have better quality for the equivalent video characteristics because they do not require any conversion. They can have a USB (usu­ ally amateur grade) or Firewire (professional grade, faster and



Figure 2.1  Instrument for digital dermoscopy.

Figure 2.2  “Real-time” digital dermoscopy analyzer. better quality) interface. Much higher resolution is possible with digital telecameras than is possible with analogue video telecameras and this has clear diagnostic advantages, as digital dermoscopy systems of this type can reach a picture resolution of 1280 x 1,024 pixels, with images observed in vivo at 15 to 25 photograms per second on computer screens (Figure 2.2). Digital cameras provide exceptionally high resolutions (up to 3,000 x 2,000 are common) but have the disadvantage of not providing full resolution images in vivo but only after the images have been saved.

equipment (A)

(B)

Figure 2.3  A: Image at 512 x 384 pixel resolution (42.8 KB). B: The same image at 1,024 x 768 pixel resolution (326 KB).

Figure 2.4  Dermoimage software for image storage (Ergon srl, Strada Massetana Romana 50/A 53,100 Siena, e-mail: dermoim­ [email protected]). The two types of digital instruments are, therefore, designed for different users. Clinicians who use video or digital telecameras (usually specialist centers) carry out many examinations to diag­ nose melanoma or inflammatory skin diseases and observe many lesions by digital technology. Digital cameras are largely used to document lesions first observed by traditional dermoscopy.(5) It is commonly thought that a higher number of pixels implies better quality images; this is untrue, even if resolution is the imaging system’s ability to reproduce details. Image quality is important for early diagnosis of melanoma and depends on factors such as the optical system of the instrument, illumina­ tion, type of instrument, and resolution.(6) Digital dermoscopy images generally have resolutions between 768 x 576 and 1,600 x 1,200 pixel; lower resolution compromises diagnosis and higher resolution is unnecessary (Figure 2.3). The definition of magnification is only valid for integrated instruments with

always the same screens. Field of view is a preferable param­ eter. Dermoscopy optical systems generally enable a horizontal “field of view” between 2 mm and 3 cm. Overall magnification M of digital dermoscopes is calculated as the ratio of screen diagonal D to field of view diagonal d: M = D/d. Illumination must be homogeneous and sufficiently strong while incident intensity should be modified by the lens dia­ phragm rather than by varying electrical potential so as to keep the color of the study area constant. Reddish or saturated images are due to low-quality equipment or failure of white balancing during chromatic calibration. Contact, noncontact, and polarized dermoscopy Today there are many types of dermoscopes. Contact incident light dermoscopes use a glass window placed in contact with the skin, illu­ minated at an angle of about 30 to 45 degrees so as to eliminate direct



rubegni, burroni, nami, and fimiani Table 2.1  Selected Commercially Available Database Software for Dermatological Digital Image Management. Specificallyfor dermatology Image (preset updatable Specific tags for modification index and tags) image retrieval tool

Confidentiality with username and password protection

Network compatible with image History sharing via the import Internet option Cost

Mirror software, product information available at www.canfieldsci.com/ Imaging_Products_ Imaging.asp

No

Yes

Only in the $2,500 or over version

Yes

Yes

No

$825 ($2,500 with DPS tools)

Imagestore for healthcare, product information available at www .ttlsoftware.com

Yes

Yes

Yes

Securely access images from any Internetconnected PC

Yes

No

not available

Dermo-Image, product information available atwww.dermoimage.com

Yes

Yes

Yes

Powerful and Yes flexible permission system

Yes

$900

Software/contact

avoiding transmission of infections and ischemia caused by pressure of the window on the skin.(8)

Figure 2.5  Images can be stored and analyzed using DB-Mips System; Biomips Engineering, S.R.L., Siena, Italy), with com­ puterized instrument providing a visual database and objective evaluations of pigmented skin lesions.

reflection, and a magnifying lens system.(7) A liquid fills the space between the skin and the glass, rendering the skin translucent and revealing subcutaneous patterns invisible to the naked eye.(8, 9) Two polarizing filters can be added to this simple optical system, one before the telecamera sensor and one on the light source, so as to eliminate light reflected by cross-polarization. Light reflected from the skin surface maintaining the polariza­ tion of the light source is eliminated by the polarizer in front of the sensor; this enables skin patterns to be observed to a greater depth. Polarization makes it possible to dispense with the glass window in contact with the skin. This has the advantage of



Data Storage Digital telecameras and photocameras are now used by all medical centers, especially dermatology clinics, to acquire skin images.(10, 11) Initially these instruments were used nonroutinely by enthu­ siasts, but soon the need emerged to develop software to store the data acquired. Such software enables images to be saved and stored in clinical records together with personal, confidential, and multi­ media data.(12) Some examples for dermatologists are Imagestore for Healthcare, Mirror Software, and Dermo-Image (Table 2.1). Only Dermo-Image (Figure 2.4) and Imagestore for Healthcare include a preset, updatable index of dermatological disorders ready to imple­ ment.(13) The latter enables overlay of multiple images and fade between them, using the compare feature, and includes retrieval of digital images by diagnosis, treatment, and anatomical site. Mirror Software was developed specifically for medical professionals; the basic management functions of storing, retrieving, viewing, and printing images were all designed with the workflow of a medical practice in mind. The loop tool allows practitioners to critically examine skin features to target problem areas. Images can be trans­ ferred to other programs like Word and Power Point. The software includes classification by pathology, patient, or examination, and an advanced image retrieval system based on personalized crite­ ria. Imagestore for Healthcare, Mirror, and Dermo-Image have these features and also enable comparison of two or more digital images. This function is useful for assessing results of treatment and evolu­ tion of lesions.(13) Software for Objective Assessment and Assisted Diagnosis Many research groups have worked on image processing and numerical assessment of image features for diagnostic purposes

equipment Table 2.2  Instruments for Digital Dermoscopy Analysis. Instrument

Web site

Light source

Magnification

Camera

Board

DB-Mips

www.skinlesions.net

Molemax II

www.derma.co.at

Halogen, 3,200 K, X16 to 25, global 3CCD, 768 X 576 lines, 150 W 750 lines RBG sync, 16 M colors Circular X30 fixed 1CCD Not reported polarized

Videocap

www.dsmedigroup.it

Medical records processing, two statistical classifiers (neural network, similarity) Medical record db image processing, statistical classifier (diagnostic algorithms) PCI multiinput, Medical records, db images, 16 M colors measurements

1CCD

Dermogenius www.dermogenious.com

Halogen, 3,200 K, X10, X25, X50, 150 W X100, X200, X400, X500, X700 Not reported Fixed

Microderm

www.visiomed.de

Not reported

Variable but not reported

3CCD

Solarscan

www.polartechnics.com.av Halogen

X10

1CCD or Not reported 3CCD

in the last few years (Table 2.2). The process generally consists in detecting the borders of the skin area to assess, identifying the object(s) to examine, and evaluating a number of variables to differentiate various diagnostic situations (Figure 2.5). Many recent studies have been concerned with objective computer­ ized analysis of digital images acquired by dermoscopy.(14–16) In the case of pigmented skin lesions, this has involved iden­ tification of variables such as circularity, maximum diameter, symmetry, and internal clusters of color, for objective evalua­ tion of all possible types.(15) The new path taken by research­ ers envisages definition of new, unambiguous, reproducible variables. Objective evaluation also offers the opportunity of using assisted diagnosis systems to provide diagnostic sugges­ tions.(17, 18) On the basis of morphochromatic characteristics of lesions, it is possible to build a classifier that can evaluate the statistical probability of malignancy with the aid of a special thesaurus. These instruments have also been used in trichology and aes­ thetics with interesting results. Sensitive tools have been devel­ oped to monitor hair loss and treatment responses. Recently, the Tricho-scan was launched as a method combining epilumines­ cence microscopy with automatic digital image analysis.(19) The diagnostic validity and significance of new numerical vari­ ables obtained by digital dermoscopy analysis can be useful to der­ matologists but only when there has been scientific validation. Conclusions The continuing evolution of digital imaging has led to the obso­ lescence of costly video equipment and the introduction of new digital cameras and telecameras that offer greater chromatic and spatial quality. Through this technology, dermatologists are dis­ covering new horizons for research, teaching, and health care.

Software

1CCD or Not reported 3CCD Not reported

Medical records processing, statistical classifier (diagnostic algorithms) Medical records processing, statistical classifier (neural network) Medical record processing, statistical classifier

References   1. Gutenev A, Skladnev VN, Varvel D. Acquisition-time image quality control in digital dermatoscopy of skin lesions. Comput Med Imaging Graph 2001; 25(6): 495–9.   2. Schindewolf T, Schiffner R, Stolz W et al. Evaluation of different image acquisition techniques for a computer vision system in the diagnosis of malignant melanoma. J Am Acad Dermatol 1994; 31(1): 33–41.   3. Elbaum M. Computer-aided melanoma diagnosis. Der­ matol Clin 2002; 20(4): 735–47.   4. Sheeler I, Koczan P, Wallage W, de Lusignan S. Low-cost three-channel video for assessment of the clinical consul­ tation. Inform Prim Care 2007; 15(1): 25–31.   5. Ratner D, Thomas CO, Bickers D. The uses of digital photogra­ phy in dermatology. J Am Acad Dermatol 1999; 41: 749–56.   6. Levy JL, Trelles MA, Levy A, Besson R. Photography in der­ matology: comparison between slides and digital imaging. J Cosmet Dermatol 2003; 2: 131–4.   7. Benvenuto-Andrade C, Dusza SW, Agero AL et al. Differ­ ences between polarized light dermoscopy and immersion contact dermoscopy for the evaluation of skin lesions. Arch Dermatol 2007; 143(3): 329–38.   8. Wang SQ, Dusza SW, Scope A et al. Differences in der­ moscopic images from nonpolarized dermoscope and polarized dermoscope influence the diagnostic accuracy and confidence level: a pilot study. Dermatol Surg 2008; 34(10): 1389–95.   9. Pan Y, Gareau DS, Scope A et al. Polarized and nonpolar­ ized dermoscopy: the explanation for the observed differ­ ences. Arch Dermatol 2008; 144(6): 828–9. 10. Scheinfeld NS, Flanigan K, Moshiyakhov M, Weinberg JM. Trends in the use of cameras and computer technology



rubegni, burroni, nami, and fimiani

11.

12.

13.

14.

15.



among dermatologists in New York City 2001–2002. Dermatol Surg 2003; 29: 822–5. Graschew G, Roelofs TA, Rakowsky S et al. New trends in the virtualization of hospitals––tools for global e-Health. Stud Health Technol Inform 2006; 121: 168–75. Starr JC. Integrating digital image management software for improved patient care and optimal practice manage­ ment. Dermatol Surg 2006; 32: 834–40. Rubegni P, Nami N, Tataranno D, Fimiani M. Gestione delle immagini digitali. Un software dedicato per la ges­ tione dell’archivio elettronico. Hi Tech Dermo(Italy) 2008; 3(3): 43–9. Pressley ZM, Foster JK, Kolm P et al. Digital image analy­ sis: a reliable tool in the quantitative evaluation of cuta­ neous lesions and beyond. Arch Dermatol 2007; 143(10): 1331–3. Rubegni P, Burroni M, Andreassi A, Fimiani M. The role of dermoscopy and digital dermoscopy analysis in the

16.

17.

18.

19.

diagnosis of pigmented skin lesions. Arch Dermatol 2005; 141: 1444–6. Rubegni P, Burroni M, Sbano P, Andreassi L. Digital der­ moscopy analysis and internet-based program for dis­ crimination of pigmented skin lesion dermoscopic images. Br J Dermatol 2005; 152(2): 395–6. Perrinaud A, Gaide O, French LE et al. Can automated der­ moscopy image analysis instruments provide added ben­ efit for the dermatologist? A study comparing the results of three systems. Br J Dermatol; 157(5): 926–33. Piccolo D, Ferrari A, Peris K et al. Dermoscopic diagnosis by a trained clinician vs. a clinician with minimal dermos­ copy training vs. computer-aided diagnosis of 341 pig­ mented skin lesions: a comparative study. Br J Dermatol 2002; 147(3): 481–6. Hoffmann R, Van Neste D. Recent findings with com­ puterized methods for scalp hair growth measurements. J Invest Dermatol Symp Proc 2005; 10(3): 285–8.

3.1

Scabies and pediculosis: Biologic cycle and diagnosis Ani L Tajirian and Robert A Schwartz

SCABIES Introduction Scabies is a common ectoparasite infection. It is caused by the mite Sarcoptes scabiei variety hominis. Sarcoptes is derived from the Greek work “sarx” (flesh) and “koptein” (to smile or cute) and the Latin word “scabere” (to scratch).(1) It is endemic worldwide, particularly in impoverished communities. Epidemics may be be evident during famine and war. Infestations occur when the scabies mite burrows into the skin, invading the host epidermis. The disease process is mediated through an inflammatory and allergy-like reaction to mite products, leading to intense pruritus. Scabies Mite/ Biologic Cycle S. scabiei is part of the arachnid family. The nymph and adult stages have four pairs of legs; the larvae possess three. Adult females are between 0.3 to 0.5 mm in length and are bigger compared to males, the small males reaching a size between 0.21 to 0.29 mm.(2) The adult male can be distinguished from the female by its smaller size, darker color, and the presence of stalked pulvilli on leg 4, as leg 4 in the female adult ends in long setae.(3) The mites can crawl up to 2.5 cm per minute on warm skin and live for approximately 30 days.(4–7) S. scabiei can survive outside of the host for 24 to 36 hours.(8–10) The scabies mite cannot penetrate deeper than the stratum corneum because oxygen delivery is by diffusion through the body surface. Mating occurs on the skin surface; males die shortly thereafter. Females then dig tunnel-like burrows in the stratum corneum using their mandibles. They lay approximately 2 to 3 eggs daily. During her lifetime, a female mite will lay 60 to 90 eggs and usually does not leave the burrow. Larvae hatch at 2 to 4 days, become a protonymph after 3 to 4 days, develop into a tritonymph after 2 to 5 days, and after an additional 5 to 6 days, evolve into sexually mature males or females. Skin entry can occur at any time and occurs in less than 30 minutes through secretion of enzymes that digest the skin, which is then consumed by the mite as a nutrient. An infested host contains approximately 10 to 15 adult female mites on his or her body at any given time; patients with crusted scabies, however, can have millions of mites on their skin surface. Epidemiology Scabies is most prevalent and endemic in tropical regions. In industrialized nations, scabies is usually observed in sporadic individual cases and institutional outbreaks. Past research estimates suggested that globally scabies might infect about 300 million by the end of the 20th century. Prevalence of scabies is not gender specific, as it can attack both sexes. Ethnic

differences are most likely related to socioeconomic conditions, overpopulation, and behavioral factors rather than race. Risk factors include poverty, poor nutrition, homelessness, dementia, and poor hygiene.(11–13) Outbreaks frequently occur in institutions such as hospitals, nursing homes, prisons, and elementary schools. Transmission Transmission of scabies is by direct skin-to-skin contact, which occurs through close personal contact, sexual or otherwise, or indirectly through fomites. Incidence and prevalence is higher in children and sexually active individuals. Among adults, sexual contact is the most common means of transmission. Shaking hands and use of common objects is usually not sufficiently long for transmission, as it can take up to 15 to 20 minutes for transmission to occur. Scabies is not easily transmitted by clothing and bed sheets. Clinical Features/Pathogenesis The pathognomonic sign of scabies is the burrow (Figure 3.1), which represents the tunnel that a female mite excavates while laying eggs. Nocturnal pruritus and erythematous papules also form the basis of diagnosis. Burrows are white serpiginous lines in the upper dermis ranging from 1 to 10 mm in length and are typically located on the interdigital spaces of the hand, the flexure surface of the wrist, elbows, genitalia, axillae, umbilicus, belt line, elbows, nipples, buttocks, and penile shaft. Scabies mites prefer regions with a relatively high temperature and thin stratum corneum. The back is rarely involved. Head and neck are usually spared with the exception of infants and the immunocompromized, in which case, the scalp and face may also be affected. Cutaneous lesions are usually symmetrical. In men, the penis and scrotum are often involved, whereas in women, the areola, nipples, and genital area are commonly affected. The intense pruritus is most severe at night and is exacerbated by a hot shower or bath. The severe pruritus and papulovesicles result from a delayed type-IV hypersensitivity reaction to the mite, its saliva, eggs, or excrements (scybala). In first-time infections, it usually takes the host’s immune system 2 to 6 weeks to become sensitized to the mite and its excrements; however, upon reinfestation, it usually takes a few days to develop symptoms. The immune response, washing, and scratching are reasons why immunocompetent hosts harbor only 11 to 12 buried female mites despite regular deposition of eggs.(2) With intense personal hygiene, the number can be lower (often called scabies of the cleanly) without a decrease in pruritus.(14) In immunocompromized patients, the mites can replicate uncontrollably, thus resulting in millions found on

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tajirian and schwartz the microscope on low power for the presence of adult mites, eggs, and/or feces. Scrapings should preferably be from a fresh, nonexcoriated burrow in the interdigital areas of the hand. Often, repeated scrapings are needed because the sensitivity is quite low. Burrows can also be visualized using the burrow ink test in which burrows will absorb the ink from a marker and become apparent. Videodermatoscopy is another technique for diagnosing scabies, especially in children, using magnifications up to 600 times.(19–21)

Figure 3.1  The burrow, pathognomonic sign of scabies. the body. Even after successful treatment, pruritus and papules can persist for 2 to 4 weeks; this is often referred to as “postscabietic pruritus” and is a manifestation of the delayed-type immune reaction. Scabies may be evident atypically in infants, the elderly, and the immunocompromized, and is often misdiagnosed. Infantile scabies usually affects the axillae, head, face, diaper area, and occasionally, the palms and soles, and is seen with with vesicles, pustules, and nodules.(15, 16) Secondary bacterial infection by group A streptococci or Staphylococcus aureus commonly occurs in the lesions, particularly in hands and feet of young children, and should be treated first. Nodular scabies is a clinical variant occurring in about 7% of scabies cases. It is composed of extremely pruritic reddish-brown nodules 2 to 20 mm in size present on the male genitalia, buttocks, groin, and axillary region. The nodules represent an intense hypersensitivity reaction to mite products, can persist for weeks after treatment, and often require treatment with corticosteroid injections.(1) Crusted scabies or Norwegian scabies is another variant. It is found most commonly in HIV patients, the elderly, or other immunosuppressed individuals. However, about 40% of patients have no identifiable risk factor, suggesting the possibility of a genetic predisposition.(17) It is evident as a hyperkeratotic dermatitis resembling psoriasis and distributed most prominently over the elbows, knees, hands, and feet. Approximately half of affected patients do not report pruritus. (17, 18) Crusted scabies is much more infectious, as the mite burden can total over 1 million. Diagnosis Scabies is usually diagnosed through skin scraping. The burrow should be unroofed using an oil-covered scalpel blade. The oil helps the scraped material adhere to the blade. The contents are then brought onto a slide with a coverslip and examined under

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Differential Diagnosis All diseases causing pruritus and papules should be considered, unless skin burrows are clearly seen on examination. The differential diagnosis is extensive and includes atopic dermatitis, neurodermatitis, animal scabies (whose mites cannot complete the life cycle on human hosts because they cannot burrow), papular urticaria, folliculitis, dermatitis herpetiformis, prurigo nodularis, and bites from mosquitoes, fleas, bed bugs, chiggers, or other mites.(22–28) PEDICULOSIS HEAD LICE Introduction/Epidemiology Head lice or pediculosis capitis, caused by Pediculus humanus capitis, is a common health problem that has plagued mankind for thousands of years. In the United States, pediculosis capitis affects about 6 to 12 million people every year.(1, 16, 25, 29) Infestation occurs most commonly in children, with a peak incidence between 5 and 13 years of age. It is found worldwide without predilection for a particular age, sex, race, or socioeconomic class. Girls are twice as likely as boys to have head lice because of their longer hair and sharing of brushes and hair accessories. (30) Head lice is rare in African Americans due to the anatomy of their hair shaft, which is more oval, making it harder to be grasped.(23, 31) Pathogenesis Pediculus humanus capitis is a host-specific arthropod that belongs to the order Anoplura. It measures approximately the size of a sesame seed (2–3 mm) and is grayish-white in color. It is wingless, has narrow sucking mouthparts concealed within the head, short antennae, and three pairs of clawed legs for hair grasping. The louse moves by grasping hairs and is incapable of flying or jumping. It feeds by piercing the skin of the host with its mouthparts and sucking blood every 4 to 6 hours. The female louse lives approximately 30 days and lays about 5 to 10 eggs a day on hair shafts. Eggs, also known as nits, are 0.8 mm in length and are laid within 1 to 2 mm of the scalp surface for warmth. The nits are firmly glued to the individual hairs by a proteinaceous matrix and are difficult to remove. Head lice can survive for up to 3 days off the host; nits can live for 10 days away from their host.

scabies and pediculosis: biologic cycle and diagnosis Clinical Features Pruritus of the scalp is the primary symptom; a number of patients are asymptomatic yet considered carriers. Pruritus may not be seen with the first lice infestation, as it takes 1 to 2 months to develop sensitivity.(31) In repeat infestations, pruritus develops within the first 24 to 48 hours. Nits are often found in the occipital scalp and postauricular portions of the head and are easier to identify than adult lice. Transmission occurs through direct head-to-head contact for an extended period of time. Diagnosis The diagnosis is established by identification of viable nits or an adult louse on the scalp. Visual inspection without combing is difficult, as head lice avoid light and crawl quickly. Louse combs are useful tools, as they increase the chance of finding live lice fourfold over direct visual examination.(32, 33) Viable eggs are tan to brown in color, and hatched eggs are clear to white. Recognition can be facilitated through the use of a magnifying glass. Wood’s lamp examination reveals a yellow-green fluorescence of the lice and their nits. Dermoscopy is also a possible aid in diagnosis.(34–36) Dead eggs can remain affixed to the hair shafts as long as 6 months and can lead to a false-positive diagnosis of an active infestation, as it may be difficult to distinguish between viable and empty eggs. Differential Diagnosis The differential diagnosis for scalp pruritus includes seborrheic dermatitis and psoriasis; however, the presence of nits or lice is diagnostic. Nits can be confused with debris on the hair shaft left by hair spray, with dandruff or with accumulated flakes of seborrheic dermatitis. Hair casts may also closely resemble nits stuck to hair shafts and can be noticed by a parent, teacher, or school nurse, who mistakes them for nits.(29) In contrast to nits, they are freely moveable along the hair shaft. CRAB LICE Introduction/ Epidemiology Crab lice or pediculosis pubis infestation is spread as a sexually transmitted disease. It is slightly more prevalent in men probably due to their increased amount of coarse body hair. It can be seen in all ethnic groups though it is less common in people whose families originated in China, Japan, or Korea, or those with minimal pubic hair. The highest prevalence is in men who are sexually active with other men. It is most common in men in the age group of 15 to 40 years, those engaging more in sexual activities during this period. Crab lice may be more common in the winter months.(37) Pathogenesis Infestation with crab lice is caused by Phthirus pubis which is approximately 0.8 to 1.2 mm in length. It has a shorter body than head lice and resembles microscopic crabs. Phthirus pubis have serrated edges on their anterior claws that allow them increased traction and mobility on the entire body.(38) Females

Figure 3.2  Crab lice (circles) of the pubic region. lay up to 3 eggs a day with an incubation period of 7 to 10 days. The adult crab louse can live up to 2 weeks on the host and about 36 hours outside of the host. Clinical Features Crab lice commonly affect pubic (Figure 3.2), axillary, chest hair, and more rarely eyelashes, and are evident as with pruritus of the pubic area. The eggs may be visible to the naked eye as 0.5 mm brown-opalescent ovals. Macula caerulea is a characteristic finding with infestation. They are asymptomatic bluish-gray macules on the trunk and thighs caused by bites of the crab louse. Underwear can also sometimes be stained with small drops of blood. As crab lice are transmitted sexually, patients with pediculosis pubis should be investigated for other sexually transmitted diseases including HIV, syphilis, scabies, gonorrhea, chlamydia, herpes, warts, and trichomoniasis. Approximately 30% of patients with crab lice will have a concurrent sexually transmitted disease.(29) Evidence of P. pubis in a child may occasionally reflect sexual abuse. Diagnosis The identification of crab lice and their nits with the naked eye or a magnifying glass is diagnostic. However, sometimes the number of living lice can be small and diagnosis can be aided by the use of dermoscopy.(36) Differential Diagnosis Nits on the pubic hair can be misdiagnosed for white piedra or trichomycosis pubis.(39, 40) If extensive excoriations are present, scabies or contact dermatitis should be considered. References   1. Hengge UR, Currie BJ, Jager G, Lupi O, Schwartz RA. Scabies: a ubiquitous neglected skin disease. Lancet Infect Dis 2006; 6: 769–79.

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tajirian and schwartz   2. Burgess I. Sarcoptes scabiei and scabies. Adv Parasitol 1994; 33: 235–92.   3. Walton SF, Currie BJ. Problems in diagnosing scabies, a global disease in human and animal populations. Clin Microbiol Rev 2007; 20: 268–79.   4. Sterling GB, Janniger CK, Kihiczak G, Schwartz RA, Fox MD. Scabies. Am Fam Physician 1992; 46: 1237–41.   5. Haag ML, Brozena SJ, Fenske NA. Attack of the scabies: what to do when an outbreak occurs. Geriatrics 1993; 48: 45–6.   6. Hogan DJ, Schachner L, Tanglertsampan C. Diagnosis and treatment of childhood scabies and pediculosis. Pediatr Clin North Am 1991; 38: 941–57.   7. Molinaro MJ, Schwartz RA, Janniger CK. Scabies. Cutis 1995; 56: 317–21.   8. Arlian LG, Runyan RA, Achar S, Estes SA. Survival and infectivity of Sarcoptes scabiei var. canis and var. hominis. J Am Acad Dermatol 1984; 11: 210–5.   9. Arlian LG, Vyszenski-Moher DL, Pole MJ. Survival of adults and development stages of Sarcoptes scabiei var. canis when off the host. Exp Appl Acarol 1989; 6: 181–7. 10. Heukelbach J, Feldmeier H. Scabies. Lancet 2006; 367: 1767–74. 11. Walton SF, McBroom J, Mathews JD, Kemp DJ, Currie BJ. Crusted scabies: a molecular analysis of Sarcoptes scabiei variety hominis populations from patients with repeated infestations. Clin Infect Dis 1999; 29: 1226–30. 12. Badiaga S, Menard A, Tissot Dupont H et al. Prevalence of skin infections in sheltered homeless. Eur J Dermatol 2005; 15: 382–6. 13. Tsutsumi M, Nishiura H, Kobayashi T. Dementia-specific risks of scabies: retrospective epidemiologic analysis of an unveiled nosocomial outbreak in Japan from 1989–90. BMC Infect Dis 2005; 5: 85. 14. Sunderkotter C, Mayser P, Folster-Holst R et al. Scabies. J Dtsch Dermatol Ges 2007; 5: 424–30. 15. Janniger CK, Micali G, Hengge U et al. Scabies. eMedicine Pediatrics [journal serial online]. 2009. Available at http:// emedicine.medscape.com/article/911033-overview 16. Wozniacka A, Hawro T, Schwartz RA. Bullous scabies: a diagnostic challenge. Cutis 2008; 350–2. 17. Roberts LJ, Huffam SE, Walton SF, Currie BJ. Crusted scabies: clinical and immunological findings in seventy-eight patients and a review of the literature. J Infect 2005; 50: 375–81. 18. O’Donnell BF, O’Loughlin S, Powell FC. Management of crusted scabies. Int J Dermatol 1990; 29: 258–66. 19. Micali G, Lacarrubba F, Tedeschi A. Videodermatoscopy enhances the ability to monitor efficacy of scabies treatment and allows optimal timing of drug application. J Eur Acad Dermatol Venereol 2004; 18: 153–4. 20. Lacarrubba F, Musumeci ML, Caltabiano R et al. Highmagnification videodermatoscopy: a new noninvasive dia­ gnostic tool for scabies in children. Pediatr Dermatol 2001; 18: 439–41.

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21. Micali G, Lacarrubba F, Lo Guzzo G. Scraping versus videodermatoscopy for the diagnosis of scabies: a comparative study. Acta Derm Venereol 1999; 79: 396. 22. Stibich AS, Schwartz RA. Papular urticaria. Cutis 2001; 68: 89–91. 23. Steen CJ, Carbonaro PA, Schwartz RA. Arthropods in dermatology. J Am Acad Dermatol 2004; 50: 819–42. 24. Thomas I, Kihiczak GG, Schwartz RA. Bedbug bites: a review. Int J Dermatol 2004; 43: 430–3. 25. Nutanson I, Steen C, Schwartz RA. Pediculosis corporis: an ancient itch. Acta Dermatovenerol Croat 2007; 15: 33–8. 26. Vaidya DC, Schwartz RA. Prurigo nodularis: a benign dermatosis derived from a persistent pruritus. Acta Dermatovenerol Croat 2008; 16: 38–44. 27. Schwartz RA. Papular urticaria. eMedicine Dermatology [Journal serial online]. 2009. http://emedicine.medscape. com/article/1051461-overview 28. Schwartz RA. Bedbug bites. eMedicine Dermatology [journal serial online]. 2009. Available at: http://emedicine.medscape.com/article/1088931-overview 29. Ko CJ, Elston DM. Pediculosis. J Am Acad Dermatol 2004; 50: 1–12. 30. Burgess I. The life of a head louse. Nurs Times 2002; 98: 54. 31. Frankowski BL, Weiner LB. Head lice. Pediatrics 2002; 110: 638–43. 32. Mumcuoglu KY, Friger M, Ioffe-Uspensky I, Ben-Ishai F, Miller J. Louse comb versus direct visual examination for the diagnosis of head louse infestations. Pediatr Dermatol 2001; 18: 9–12. 33. De Maeseneer J, Blokland I, Willems S, Vander Stichele R, Meersschaut F. Wet combing versus traditional scalp inspection to detect head lice in schoolchildren: observational study. BMJ 2000; 321: 1187–8. 34. Bakos RM, Bakos L. Dermoscopy for diagnosis of pediculosis capitis. J Am Acad Dermatol 2007; 57: 727–8. 35. Di Stefani A, Hofmann-Wellenhof R, Zalaudek I. Dermoscopy for diagnosis and treatment monitoring of pediculosis capitis. J Am Acad Dermatol 2006; 54: 909–11. 36. Chuh A, Lee A, Wong W, Ooi C, Zawar V. Diagnosis of Pediculosis pubis: a novel application of digital epiluminescence dermatoscopy. J Eur Acad Dermatol Venereol 2007; 21: 837–8. 37. Mimouni D, Ankol OE, Gdalevich M et al. Seasonality trends of pediculosis capitis and phthirus pubis in a young adult population: follow-up of 20 years. J Eur Acad Dermatol Venereol 2002; 16: 257–9. 38. Burkhart CG , Burkhart CN. Oral ivermectin for Phthirus pubis. J Am Acad Dermatol 2004; 51: 1037. 39. Schwartz RA, Altman R: Piedra. eMedicine Dermatology [Journal serial online]. 2009. http://emedicine.medscape. com/article/1092330-overview 40. Schwartz RA. Superficial fungal infections. Lancet 2004; 364: 1173–82.

3.2 Videodermatoscopy and scabies

Francesco Lacarrubba, Nella Pulvirenti, and Giuseppe Micali

The standard technique for the diagnosis of scabies involves identification of the mite, eggs, or excreta by microscopic examination of scales obtained by skin scraping, but this method may cause discomfort and fear, especially in younger patients. As the results generally depend on the scraped areas, repeated tests are sometimes necessary for a conclusive diagnosis. For these reasons, scraping is not well accepted by patients, who may not cooperate, or even decline the examination. Follow-up tests, useful to assess recovery from therapy or to rule out persisting pruritus due to use of irritant topical agents, are troublesome, and patients may refuse further scraping, considering it a useless “torture.” Moreover, handling and processing scrapings rapidly and effectively in the office is not always straightforward.(1–2) In 1992 Kreusch (3) suggested the use of epiluminescence microscopy in diagnosing scabies, as this technique allows the inspection of the skin surface down to the superficial dermis. The first study was performed by Argenziano et al., which, using the epiluminescence microscopy technique at X40 magnification, made a repetitive finding, a small dark brown triangular structure located at the end of a subtle linear segment in 93% of 70 patients affected by scabies; together, both structures resembled a jet with contrail.(4–5) On microscopic examination, the jet-shaped triangular structure corresponded to the pigmented anterior part of the mite (mouth parts and two anterior pairs of legs); the contrail-shaped segment was thought to be the burrow of the mite along with its eggs and fecal pellets.(4–5) In 2000, we conducted at our institution a comparative study (6) of scraping versus high magnification videodermatoscopy (VD) in 38 patients suspected of being infested with scabies (patients were in the age range between 1 month and 81 years). VD was performed using a Video Microscope System Hi-Scope KH-2,200 [Hirox Co. Ltd., Tokyo, Japan], allowing the skin observation at magnifications ranging from X4 up to X1,000. Both scraping and VD examinations were carried out in each patient by two independent operators, and exchange of information was not allowed. The use of VD allowed a detailed inspection of the skin with rapid identification of burrows, mites, feces, and eggs in 16 out of 38 patients and, in most cases, it was possible to observe the mites moving inside the burrows. Microscopic examination of the scales obtained by skin scraping gave similar results. Interestingly, two cases were positive only by scraping and this fact was probably due to impetiginization that hampered VD examination (Figure 3.3); conversely, the two other cases, characterized by minimal lesions, were found positive only at VD (Figure 3.4).(6) On the basis of these results, we conducted a large-scale study in children in which VD was the only diagnostic tool.(1) A total of 100 young patients (43 boys

Figure 3.3  A case of impetiginized scabies in which VD examination may be hampered and may give false-negative result.

Figure 3.4  A case of scabies with minimal lesions in which traditional skin-scraping may give false-negative result. and 57 girls, aged between 1 month and 16 years) suspected to be affected by scabies were enrolled in the study. Patient examination was first performed using a relatively low magnification (about X100), and suspicious lesions (i.e. burrows) were analyzed at higher magnification (up to X600). No use of oil or slide on the skin was necessary as image resolution was of good quality. VD allowed a detailed inspection of the skin in all patients. Diagnosis of scabies was established in 62 out of

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lacarrubba, pulvirenti, and micali

Figure 3.5  Burrow at VD observation: The roundish body of Sarcoptes scabiei (circle) may be observed at one end of the burrow (X100).

Figure 3.6  Burrow at VD observation: Sarcoptes scabiei may be observed at the end of the burrow (X200).

Figure 3.7  Sarcoptes scabiei at VD observation (X500): the roundish body is translucent, whereas the anterior part of the mite (head and anterior legs) is pigmented (arrow).

Figure 3.8  Eggs (ovular and translucent) and feces (roundish and white) of Sarcoptes scabiei at VD observation (X500).

100 patients and was based on identification of mites, eggs and feces. None of the 38 negative patients showed signs of infestation at a 2-week follow-up examination. The study showed that high magnification VD is very effective and sensitive, especially in cases with not specific clinical features, allowing clear detection of some details (e.g., mites in migration, eggs, and feces) usually not appreciable at lower magnifications.(1) The effectiveness of dermoscopy both at low and high magnification in diagnosing scabies has been confirmed by several other studies.(2, 7–12) A study comparing the dermoscopic diagnosis of scabies using a pocket, handheld dermoscope and allowing 10X magnification with traditional skin scraping in 238 patients has shown that dermoscopy achieves comparable high diagnostic

sensitivity values as scraping (91% vs. 90%, respectively). Under 10X magnification, after paraffin oil application on the glass plate of the dermatoscope, Sarcoptes scabiei appears as a characteristic triangular shape, resembling a circumflex accent (e.g., in French letter ‘‘ô’’) that corresponds to head and front legs of the mite.(11) Dermoscopy affords several advantages compared to traditional skin scraping. First, it is not invasive and it is well accepted by the patients, especially by children and those more sensitive patients who may have had repeated negative results at skin scraping, as it does not cause physical or psychological discomfort. It is easy and quick to perform, allowing inspection of the entire skin surface usually within few minutes and is significantly less time consuming than ex vivo microscopic examination.(1, 5)

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videodermatoscopy and scabies

Figure 3.9a  Burrow at low-magnification VD observation: The “circumflex accent” that corresponds to head and front legs of mite structure may be observed (arrow) (X20).

Figure 3.9b  The same burrow at X40 magnification: The “jet with contrail” structure is more evident.

Figure 3.9c  The same burrow at X400 magnification: both the mite (on the left) and the eggs (on the right) are clearly evident.

Figure3.9d  The same eggs at X600 magnification.

It is useful for nontraumatic screening of family members who might refuse skin scraping being asymptomatic. Moreover, being noninvasive, this technique minimizes the risk of accidental infections from blood-transmissible agents such as HIV or HCV. Finally, dermoscopy has demonstrated to be useful in diagnosing scabies through the technique of teledermatology. In one study, this approach, which involves sharing digital pictures by capturing dermoscopic images at the remote site and reviewing them later at the host site, appeared to be a relatively cost-effective means of providing this service from a distance when on-site dermatology services is not available.(13) An important issue to address is which magnification gives the best performance, considering also that most systems come equipped with lenses up to X1,000. We recommend the use of

VD wherever possible, as it allows a detailed inspection of the skin with rapid and clear detection of the diagnostic features of scabies, such as burrows at magnifications ranging from X40 to X100, and mites, eggs, or feces at higher magnifications (up to X600) (Figure 3.5–3.8). Using these magnifications, false-negative results are rare and there is no chance of false-positive results, as the images obtained are unequivocal: The round, translucent body of the mite (invisible at low magnifications) is clearly visible and it is always possible to visualize the other anatomical structures of the mite, that is, its legs (anterior and posterior) and rostrum; in most cases, it is also possible to detect the mite moving inside the burrows. (6–7) Finally, the use of oil and slides is messy and time consuming and is unnecessary at high magnification, as it does not enhance image quality.

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lacarrubba, pulvirenti, and micali

Figure 3.10a  Sarcoptes scabiei (arrow) out of the burrow at low-magnification VD observation: The “circumflex accent” is hardly visible (X20).

Figure 3.10b  The same mite at X500 magnification is easily recognizable.

VD is particularly useful for posttherapeutic follow-up, showing the possible presence of viable mites and thus reducing the risk, in cases of unsuccessful therapy, of persistence and diffusion of the infestation.(1, 14) Again, patients are more willing to undergo posttherapeutic VD examination rather than skin scraping. In our experience, however, the use of low magnifications (X10–X40) may have some limitations, and one of them is that it does not always allow, especially to nonexperienced operators, a clear differentiation between the “circumflex accent” (or the “jet-shaped” structure) and minor excoriations and/or splinters (that may frequently occur in scabies due to repeated scratching). In addition, low magnifications do not facilitate visualization of eggs and feces, which are quite often the only diagnostic clues available to suspect the presence of mites. Another limitation is that mite viability cannot be assessed at these magnifications; therefore, posttherapeutic monitoring cannot be performed. Finally, the use of hand-held dermoscope, as recently suggested, may be troublesome when used in hairy body areas, where a clear visualization of the skin may be hampered. In addition, the use of hand-held dermatoscopy in or around the genital region may cause embarrassment because of close contact between dermoscopist’s head and patient’s skin surface.(11) In conclusion, considering the possible risk of false-negative and/or false-positive results, the use of hand-held dermoscopy might be limited to those cases in which no VD facilities are available or to a preliminary screening of suspect lesions before skin scraping is carried out.(11) The importance of the use of high magnifications may be better understood by viewing the same lesion at different magnifications (Figure 3.9–3.10). Finally, when we use the dermoscope or the videodermatoscope in diagnosing scabies, the possibility of indirect contamination of the patients through the instrument might be

considered, as mites survive in the outside environment (away from the host) for up to 72 hours; therefore, disinfection of the device after each examination is recommended.(11)

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REFERENCES   1. Lacarrubba F, Musumeci ML, Caltabiano R et al. Highmagnification videodermatoscopy: a new noninvasive diag­ nostic tool for scabies in children. Ped Dermatol 2001; 18: 439–41.   2. Neynaber S, Wolff H. Diagnosis of scabies with dermoscopy. CMAJ 2008; 178: 1540–1.   3. Kreusch J. Incident light microscopy: reflection on microscopy of the living skin. Int J Dermatol 1992; 31: 618–20.   4. Argenziano G, Fabbrocini G, Delfino M. Epiluminescence microscopy. A new approach to in vivo detection of Sarcoptes scabiei. Arch Dermatol 1997; 133: 751–3.   5. Zalaudek I, Giacomel J, Cabo H et al. Entodermoscopy: a new tool for diagnosing skin infections and infestations. Dermatology 2008; 216: 14–23.   6. Micali G, Lacarrubba F, Lo Guzzo G. Scraping versus videodermatoscopy for the diagnosis of scabies: a comparative study (Letter). Acta Derm Venereol 2000; 79: 396.   7. Brunetti B, Vitiello A, Delfino S, Sammarco E. Findings in vivo of Sarcoptes scabiei with incident light microscopy. Eur J Dermatol 1998; 8: 266–7.   8. Bauer J, Blum A, Sönnichsen K et al. Nodular scabies detected by computed dermatoscopy. Dermatology 2001; 203(2): 190–1.   9. Prins C, Stucki L, French L, Saurat JH, Braun RP. Dermoscopy for the in vivo detection of sarcoptes scabiei. Dermatology 2004; 208(3): 241–3. 10. Fox GN, Usatine RP. Itching and rash in a boy and his grandmother. J Fam Pract 2006; 55: 679–84.

videodermatoscopy and scabies 11. Dupuy A, Dehen L, Bourrat E et al. Accuracy of standard dermoscopy for diagnosing scabies. J Am Acad Dermatol 2007; 56: 53–62. 12. Ishii N. Executive committee of guideline for the diagnosis. Guideline for the diagnosis and treatment of scabies in Japan (2nd edition). J Dermatol 2008; 35: 378–93.

13. Weinstock MA, Kempton SA. Case report: teledermatology and epiluminescence microscopy for the diagnosis of scabies. Cutis 2000; 66: 61–2. 14. Lacarrubba F, Micali G. Parasitoses of the scalp. In: Tosti A, (ed). Dermoscopy of Hair and Scalp Disorders: Pathological and Clinical Correlation. Informa Healthcare Ltd, UK, 2007.

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3.3 Videodermatoscopy and pediculosis

Giuseppe Micali, Marianna Umana, and Francesco Lacarrubba

Pediculosis Capitis Pediculosis capitis (head lice) is a worldwide infestation due to Pediculus humanus capitis (Figure 3.11), a blood-sucking insect and specific human parasite, which affects predominantly children aged between 4 and 14 years. It causes itching and, occasionally, secondary bacterial infections resulting from scratching with an associated local retroauricular adenopathy. Generally, the diagnosis of pediculosis capitis is clinical, as both mites and their nits may be detectable with close-up examination; however, search of the mite is time consuming and, because the head louse moves quickly and avoids light, it is often not visible.(1) Therefore, the diagnosis is traditionally based on a combination of scalp itching, eventually accompanied by local bite reactions and/or cervical lymphadenopathy and the presence of nits.(1) Sometimes nits may be overlooked and nits containing vital nymphs can be difficult to differentiate from empty nits and so-called pseudo nits, such as hair casts, debris of hair spray or gel, or scales from seborrheic dermatitis.(1) In 2003, we described the use of videodermatoscopy (VD) in pediculosis.(2) In case of infestation, VD unequivocally shows the presence of the nits fixed to the hair shaft (Figure 3.12), allowing a rapid differentiation from scales of different origin (pseudo nits) that appear as amorphous, whitish structures (3) (Figure 3.13). Moreover, VD allows a more detailed identification of full versus empty nits, where the full nits, which contain nymphs and indicate a potential active infestation, appear like ovoid, brown structures with a convex extremity (Figure 3.14a),

Figure 3.12  Nit fixed to the hair shaft (X80).

Figure 3.13  A scale of seborrheic dermatitis (pseudo nit) appear­ ing as an amorphous, whitish structure (X80).

Figure 3.11  VD observation of Pediculus humanus capitis on a glass slide (X80).

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whereas the empty nits, which may persist after the recovery, are translucent and typically show a plane and fissured free ending (Figure 3.14b).(1, 3) The differentiation between vital and empty nits provides useful information about therapeutic response. Furthermore, VD does not require hair pulling; therefore, a large scalp area can be investigated without discomfort to the patient. With a little patience, it is also possible to detect the lice. In this case VD allows an in vivo evaluation of the movements and physiology of lice (Figure 3.15) and may be

videodermatoscopy and pediculosis

Figure 3.14a  Full nits, which contain nymphs, appear like ovoid, brown structures with a convex extremity (X100).

Figure 3.15  Pediculus humanus “in action” in the hair shafts (X80).

Figure 3.16  Phthirus pubis firmly attached to the pubic hairs (X80). Figure 3.14b  Empty nits are translucent and typically show a plane and fissured free ending (X100). useful to evaluate the pediculocidal activity of different topical products.(4) In conclusion VD can be used as an easy, safe, and reliable diagnostic tool in head lice infestation and the procedure can rapidly confirm the diagnosis in some puzzling cases where parasites and nits may be not easily identified. Other authors have reported obtaining similar results by a contact, hand-held dermatoscope both in vivo and nipping and placing hairs, presenting nits on the adherent side of a piece of transparent adhesive tape.(1, 5) Phthiriasis Pubis The same technique of VD may be extended to diagnosing phthiriasis pubis (crab lice).(2, 6) Phthirus pubis infests mainly the hair of the pubic and inguinal region, rarely those of axillae, chest, and limbs. In children, the edges of scalp hair and eyelashes

Figure 3.17  Phthirus pubis at VD observation (X80).

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micali, umana, and lacarrubba

Figure 3.18  Full nit of Phthirus pubis (X60).

(a)

Figure 3.19  Phthiriasis palpebrarum. Insert: VD observation of lice and nits (X80). (b)

Figure 3.20a–b  Nits of the eyelashes (a) versus scales of atopic dermatitis (b) at VD observation (X50). (phthiriasis palpebrarum) are the most common site of infestation because of the lack of terminal hairs on most body regions. In the majority of cases the diagnosis of pubic lice is clinical and there is no need for further investigation. VD clearly shows the presence of the crab lice firmly attached to the pubic hairs (Figure 3.16–3.17). In most cases, it is possible to recognize the parasite sucking the blood. Moreover, as observed in pediculosis capitis, VD allows a more detailed identification of full versus empty nits (Figure 3.18). In case of phthiriasis palpebrarum, the lice are sometimes difficult to identify because of their semitransparency and deep burrowing in the lid margin, so the infestation may exist for a long time before being recognized (7) and generally misdiagnosed with atopic dermatitis or allergic conjunctivitis. In these cases, VD can rapidly clarify any doubt by revealing the presence of lice and/or nits (Figure 3.19–3.20).

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Finally, VD examination may enhance patient compliance to therapy both in head and crab lice, by clearly showing on the VD monitor their presence, persistence, or resolution of the infestation (6). REFERENCES 1. Di Stefani A, Hofmann-Wellenhof R, Zalaudek I. Dermoscopy for diagnosis and treatment monitoring of pediculosis capitis. J Am Acad Dermatol 2006; 54: 909–11. 2. Micali G, Lacarrubba F. Possible applications of videodermatoscopy beyond pigmented lesions. Int J Dermatol 2003; 42: 430–3. 3. Zalaudek I, Giacomel J, Cabo H et al. Entodermoscopy: a new tool for diagnosing skin infections and infestations. Dermatology 2008; 216: 14–23.

videodermatoscopy and pediculosis 4. Lacarrubba F, Nardone B, Milani M, Botta G, Micali G. Head lice: ex vivo videodermatoscopy evaluation of the pediculocidal activity of two different topical products. G Ital Dermatol Venereol 2006; 141: 233–5. 5. Bakos RM, Bakos L. Dermoscopy for diagnosis of pediculosis capitis. J Am Acad Dermatol 2007; 57: 727–8.

6. Chuh A, Lee A, Wong W, Ooi C, Zawar V. Diagnosis of Pediculosis pubis: a novel application of digital epiluminescence dermatoscopy. J Eur Acad Dermatol Venereol 2007; 21: 837–8. 7. Yoon KC, Park HY, Seo MS, Park YG. Mechanical treatment of phthiriasis palpebrarum. Korean J Ophthalmol 2003; 17: 71–3.

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3.4 Therapy of scabies and pediculosis: Potential and pitfalls Lee E West, Beatrice Nardone, and Dennis P West

Introduction A great pitfall for scabies and pediculosis therapeutic studies to date is that primary and secondary study outcomes are indirectly assessed (presence or absence of live parasites, including eggs, determined by gross clinical inspection) and data timepoints are nonstandardized (highly variable) relative to time of therapeutic application. Certainly, kill times and kill rates are rarely determined or reported. Indeed, meta-analyses of randomized, controlled clinical trials for these parasitoses are scarce and, by nature, analyses are based on highly variable assessment methodology and data collection, followed by highly variable interpretation and reporting.(1, 2) Utilization of high-resolution, high-magnification videodermatoscopy (VD) in establishing highly definitive and precise quantitative data products used in the treatment of scabies and pediculosis provides enormous advantages in the quest to establish reproducible quantitative methodology for efficacy studies in these parasitoses.(3–6) Unfortunately, determination of the risk–benefit ratio for reported treatments does not involve uniform or precise methodology such as VD and, as a result, subjective weighing of literature reports is used to determine efficacy, and, subsequently, benefit–risk categorization. Clearly, standard methods such as VD allow for uniform data and, ultimately, uniform comparison and categorization of efficacy. Considering these significant limitations in efficacy studies to date for both scabies and pediculosis, the following overview provides insight into the topical and systemic pharmacologic and nonpharmacologic approaches to treatment that are reported to be used in the clinical management of such infestations. See Table 3.1 for a combined subjective and objective relative assessment of efficacy and safety to provide a current guide to risk–benefit ratio as categorized for selected agents reported to be used in scabies and/or pediculosis. Pediculosis A high percentage of cases of head lice are treated without medical supervision and with products that may be prone to overuse, leading to increased risk of developing resistance to such products. Resistance to virtually all topical products for treatment of pediculosis, including permethrin, pyrethrins, malathion monotherapy, and lindane, has been reported.(7–9) While treatment failure may be due to resistance in some cases, noncompliance or underuse of medication should always be considered. Whether changing treatment product or applying further doses, the importance of consultation and patient education should be emphasized.(10) Some causes



of treatment failure may be related to misdiagnosis or reinfestation. Usually an initial treatment is followed by a second application after 7 to 10 days to ensure that any hatching nymphs are destroyed. Spread of head lice is by transfer of live lice only; nits or nit cases will not cause infestations.(11) Scabies It is important to treat close physical contacts, even if asymptomatic, as well as the infested patient, to minimize the risk of reinfestation. Topical and systemic agents are quite effective in killing and eradicating the parasite. Pruritus may increase and persist for up to 2 weeks after successful treatment due to continuing reactivity to substances released from the dying mites. Patients need to be reassured that itching is not always indicative of infestation after treatment. Pruritus lasting longer than 2 weeks after treatment may indicate treatment failure or resistance. Generally, a repeat treatment 7 days after the initial treatment is given to ensure that hatching larvae are destroyed. New lesions present after 4 weeks may indicate treatment failure or reinfestation.(12) Bed linens and towels should be washed after treatment and areas of frequent body contact such as carpets, chairs, and sofas should be vacuumed.(13) The vacuum-cleaner bag should be removed immediately after vacuuming, sealed in a plastic bag, and discarded. The use of insecticides on inanimate objects, such as furniture, has not been proven to be of benefit. Physical Removal—Pediculosis Nit Combs Wet combing “bug busting” is a procedure that involves combing wet hair with a fine-tooth comb every 3 to 4 days for at least 2 weeks to physically remove live lice and nits. Wetness of hair is important because water slows the motility of lice, making it easier for removal.(14) Removed lice can then be placed on adhesive paper. Studies that compared bug busting with malathion monotherapy found malathion to be twice as effective.(15) While this method is labor intensive and poses recurrent infestation issues, the advantages of low cost and unlimited repetition with no side effects may warrant further investigation.(16) While combs and other devices may help remove lice and nits, treatment is considered more thorough. Fine tooth combs designed to effectively remove nits and may be used with hair conditioner or active agent.(17) Shaving the head is not recommended since this can cause significant and long-lasting emotional trauma as well as embarrassment.

therapy of scabies and pediculosis: potential and pitfalls Table 3.1  Combined Subjective and Objective Relative Assessment of Reported Efficacy and Safety to Provide a Risk–Benefit Ratio Category for Selected Agents Used in Scabies and/or Pediculosis. Agent

Condition

Benefit:Risk

Benzyl alcohol Topical Dimethicone Topical Ivermectin Topical Ivermectin Systemic Malathion/terpineols combination therapy (United States) Topical Permethrin Topical Benzyl benzoate Topical Cotrimoxazole (trimethoprim/ sulfamethoxazole) Systemic Crotamiton Topical Lindane Topical Malathion Monotherapy (UK) Petrolatum/Mineral Oil/ Vegetable (eg; Olive) Oils Topical Pyrethrins/Piperonyl Butoxide Topical Sulfur Topical Albendazole Systemic Carbaryl Topical Citronella Topical Levamisole Systemic Butter/Margarine/ Mayonnaise Topical Kerosene/Gasoline/ Petroleum Distillates Topical

Pediculosis

1

Pediculosis

1

Pediculosis

1

Scabies and pediculosis

1

Scabies and pediculosis

1

scabies & pediculosis

1

Scabies and pediculosis

2

Pediculosis

2

Scabies and pediculosis

2

Scabies and pediculosis

2

Scabies and pediculosis

2

Pediculosis

2

Pediculosis

2

Scabies

2

Pediculosis

3

Pediculosis

3

Pediculosis

3

Pediculosis

3

Pediculosis

na

Pediculosis

1=benefit:risk balanced. 2=benefit:risk decreased. 3=benefit:risk marginal. na=benefit:risk not acceptable.

na

Topical Treatment Benzyl Alcohol—Pediculosis Topical lotion, containing benzyl alcohol (5%), is a nonneurotoxic pediculocide that acts to fix the spiracles of the louse in an open position, thus permitting blockage and asphyxiation. Note that unlike benzyl alcohol, some so-called asphyxiator products only temporarily stun the spiracles in an open position, thus allowing the louse to quickly recover and continue infestation. Complete treatment consists of two 10-minute applications (hair saturation followed by rinsing) 1 week apart. Benzyl Benzoate—Scabies and Pediculosis Benzyl benzoate, a long-standing scabicide and pediculocide, is known to partially biotransform to benzyl alcohol. Benzyl benzoate is available in various topical dosage forms for use in scabies and pediculosis at concentrations as high as 35%. It is widely used in some countries, but in a study compared to oral ivermectin, it showed inferior efficacy to ivermectin.(18) The mechanism of action is unknown. Carbaryl—Pediculosis This topical agent functions similarly to malathion by binding to the same acetylcholinesterase enzyme site to cause respiratory paralysis in the louse. Unfortunately, even though toxicity of this compound is specific to the louse (and not the human host) in the topical concentration being used (0.5%), this agent is reported to be mutagenic and may or may not prove to be carcinogenic, thus limiting its utility in pediatric populations.(19) Crotamiton—Scabies and Pediculosis Marketed as a 10% topical cream for pruritus, this agent has been reported to be effective in scabies and has limited reporting of effectiveness in pediculosis. Crotamiton is relatively nontoxic to the human host and the mechanism of action is unknown.(20) Although relatively safe for use in children, it is not recommended for use in pregnant or lactating women. Dimethicone—Pediculosis Similar to other agents that interfere with the respiratory system (interrupted oxygen supply), topical dimethicone (up to 92% concentration) has shown efficacy and yet is considered safe to the human host, including children and pregnant or lactating women.(21, 22) Ivermectin—Scabies and Pediculosis Although topical ivermectin was reported as beneficial in the treatment of pediculosis over a decade ago, (23) it is just now undergoing US trials. Lindane—Scabies and Pediculosis Lindane is used as a second-line therapy. Package sizes are limited to the amount necessary for treatment of one person in an effort to prevent overuse. The use of lindane has been banned

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west, nardone, and west in the state of California and some countries, due to potential toxicity to the human host.(24) Although there are advantages to using lindane, including its utility as a pediculicide and ovicide, disadvantages are also many, including percutaneous absorption that may result in neurotoxicity. Lindane is not for use in patients with seizure and other neurologic disorders or in those with known, lowered seizure threshold. Lindane persists in fatty tissues and in the environment over very prolonged periods. Use with caution for patients weighing less than 50 kg. Lindane is categorized as U.S. FDA Pregnancy Category C. Malathion—Scabies and Pediculosis Malathion in combination with terpineols may be a useful approach to treatment because it has very little reported resistance. However, malathion as monotherapy (not in combination with terpineols) has a relatively high rate of resistance. There are advantages to using the malathion/terpineols combination: It is highly effective, functions as both a pediculicide and ovicide, and may have residual therapeutic effects. Disadvantages include an unpleasant odor and that it is not indicated for use in children under 6 years of age in some countries. There are emerging resistance data for malathion monotherapy. Permethrin—Scabies and Pediculosis Permethrin is used widely for treatment of head lice in a 1% cream-rinse formulation, and permethrin cream at 5% is used widely for scabies. Advantages include low toxicity to the human host, ability to function as both a pediculicide and ovicide, and it may have residual therapeutic effect. Disadvantages are that there are emerging resistance data and it is messy to use on hairy areas. Pyrethrins—Pediculosis Pyrethrins are available in combination with piperonyl butoxide to increase efficacy. This agent functions as a pediculicide but not as an ovicide. Disadvantages also include no residual activity, irritant and/ or allergic contact dermatitis potential, and it may produce systemic toxicity.(25)

Citronella—Pediculosis Topical citronella has been reported to be more effective than vehicle but otherwise scarce published information exists about safety of topical use and potential for irritant effect.(27) Sulfur—Scabies Precipitated sulfur at 6% in petrolatum ointment is used an extemporaneously compounded topical agent for scabies treatment.(28) Advantages of using sulfur include its relatively low cost, relatively low potential for toxicity, suitability to treat infants younger than 2 months of age (except premature infants), and it is safe for use in pregnant and lactating women. Disadvantages are that it must be applied for at least three consecutive overnights, and the ointment is messy with an objectionable odor and is capable of staining clothing and bedding. Petrolatum Occlusive products such as petrolatum (petroleum jelly) have been reported as home remedies that are liberally applied to the entire scalp at night, occluded with a shower cap, then washed out daily for several days, and the lice removed by combing. Lice are potentially suffocated or slowed down, and then physically removed by combing, as it will take several washings to remove the petrolatum.(11) The ongoing hair grooming connected with daily shampooing may, in effect, account for lice removal.(29) Tea Tree Oil—Pediculosis An herbal shampoo containing extract of paw paw, thymol, and tea tree oil has reported to be effective in treatment of head lice infestations.(30) Disadvantages are that tea tree oil may cause allergic contact dermatitis and formulations are nonstandardized (unregulated and unknown amounts of tea tree oil due to variation in purity). Alternative Unproven Remedies Butter/Margarine/Mayonnaise—Pediculosis Remedies such as mayonnaise, softened margarine, or butter have been reported to be used, but these are not proven to be efficacious, as these are also bacterial-growth media. A disadvantage includes risk of serious and/or life-threatening infection, including septicemia.

Other topicals—Scabies Topical corticosteroids may be used for pruritus that may occur for up to 2 weeks after successful therapy for scabies. If secondary skin infections develop, topical or systemic antibiotics may be necessary.

Kerosene/Gasoline/Petroleum Distillates—Pediculosis Treatment with kerosene or gasoline and other petroleum distillate products is extremely dangerous as a fire hazard and potential inhalant and should never be used. Disadvantages are serious risk of physical harm and systemic toxicity

Natural Products

Systemic Treatment

Acetic Acid (Vinegar)/Formic Acid—Pediculosis Diluted vinegar or formic acid can be used as a hair rinse to aid in the removal of nits.(26)

Albendazole Albendazole as an oral agent has been shown to be effective against head lice. Advantages include simple therapy and



therapy of scabies and pediculosis: potential and pitfalls enhanced compliance. It is apparently not synergistic with permethrin for pediculosis.(31) Ivermectin—Scabies and Pediculosis Ivermectin as a single, oral dose of 200 mcg/kg is effective in destroying lice but not nits. A second dose after 7 to 10 days is needed to kill hatching nymphs. Oral ivermectin has also been used for the treatment of recalcitrant pediculosis. Oral ivermectin is also reported to be beneficial in cases of HIV-infected patients and in outbreaks occurring in institutionalized patients and hospitals.(32) Because the serum halflife of ivermectin is about 16 hours, the 7-day repeat dose may not always be necessary. In HIV patients, however, it may be necessary to dose a second time at 14 days.(33) Advantages include high patient compliance with simple dosing and low toxicity potential. Pruritus usually resolves relatively quickly within 48 hours. Disadvantages are that it is not ovicidal and not intended for children under 5 years of age or who weigh less than 15 kg. Cotrimoxazole (trimethoprim/ sulfamethoxazole)—Pediculosis Oral TMP-SMX may be combined with topical permethrin to enhance efficacy of topical permethrin.(34) Although this therapy may be used for resistant infestations or treatment failures, it should not be used in sulfonamide-allergic patients, considering its serious systemic side effects. Indomethacin—Pediculosis Indomethacin is known to decrease cellular glutathione-5transferase, and because resistance of lice to pyrethrins and permethrin may be related to the parasite’s decreased ability to detoxify the pesticides by conjugation with reduced glutathione, this area of interest has led to reporting the use of “enhancing” or “optimizing” agents such as indomethacin in the treatment of resistant pediculosis.(35) Levamisole Levamisole has been examined in an open-label study as a daily oral dose of 3.5 mg/kg once daily for 10 days.(36) Disadvantages include the potential for systemic side effects and the lack of randomized control trials to establish efficacy. Conclusions In general, the incidence of scabies and pediculosis is not decreasing (perhaps partly due to improved reporting) while evidence and patterns of increased resistance are well documented. Patients, as well as parents, are increasingly frustrated with the lack of efficacy of several topical products and alternative home remedies and are concerned about repeated exposure to agents that may produce toxicity. Moreover, increased use and widespread beliefs that alternative agents pose less hazard than proven treatments has lead to even greater perception that

resistance to treatment exists even when proven therapies may not yet have been utilized. For pediculosis, the topical agent of choice may be related more to geographic location and economic considerations than other factors such as toxicity and ease of use. In the United States, the malathion/terpineols combination product, though it produces objectionable odor and is difficult to use, is highly efficacious as one of the first-line agents with minimal toxicity concerns (no reported human toxicity for the topical concentration used) and no proven resistance. Other first-line topical agents that are both safe and effective include agents such as benzyl alcohol and dimethicone. Unchecked scabies infestations in patients with normal immune status will usually cause extreme discomfort from pruritus, possible secondary bacterial infection from excoriations, and will be more likely to spread to other persons. Geographic area, toxicity, and economic status are some of the factors key to measuring the prevalence of scabies. Until quantifiable and precise data on organism kill times and kill rates are generated, analyzed, and reported, particularly using videodermatoscopy technology, we can rely only on indirect measurements of efficacy for agents used in the treatment of scabies and pediculosis. References   1. Hu S, Bigby M. Treating scabies: results from an updated Cochrane review. Arch Dermatol 2008; 144(12): 1638–40.   2. Burkhart CN, Burkhart CG. Recommendation to standardize pediculicidal and ovicidal testing for head lice (Anoplura: Pediculidae). J Med Entomol 2001; 38(2): 127–9.   3. Micali G, Lacarrubba F, Tedeschi A. Videodermatoscopy enhances the ability to monitor efficacy of scabies treatment and allows optimal timing of drug application. J Eur Acad Dermatol Venereol 2004; 18(2): 153–4.   4. Lacarrubba F, Musumeci ML, Caltabiano R et al. Highmagnification videodermatoscopy: a new noninvasive dia­g­ nostic tool for scabies in children. Pediatr Dermatol 2001; 18(5): 439–41.   5. Micali G, Lacarrubba F. Possible applications of videodermatoscopy beyond pigmented lesions. Int J Dermatol 2003; 42(6): 430–3.   6. Lacarrubba F, Nardone B, Milani M, Botta G, Micali G. Head lice: ex vivo videodermatoscopy evaluation of the pediculocidal activity of two different topical products. G Ital Dermatol Venereol 2006; 141: 233–6.   7. Burkhart CG, Burkhart CN. Clinical evidence of lice resistance to over-the-counter products. J Cutan Med Surg 2000; 4: 199–201.   8. Pollack RJ, Kiszewski A, Armstrong P et al. Differential permethrin susceptibility of head lice sampled in the United States and Borneo. Arch Pediatr Adolesc Med 1999; 153: 969–73.

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west, nardone, and west   9. Downs AM, Stafford KA, Harvey I et al. Evidence for double resistance to permethrin and malathion in head lice. Br J Dermatol 1999; 141: 508–11. 10. Chosidow O. Scabies and Pediculosis. Lancet 2000; 355: 819–26. 11. Frankowski BL, Weiner LB. Head lice. Pediatrics 2002; 110: 638–43. 12. Orkin M, Maibach HI. Scabies treatment: current considerations. Curr Prob Dermatol 1996; 24: 151–6. 13. Elston DM. Controversies concerning the treatment of lice and scabies. J Am Acad Dermatol 2002; 46: 794–6. 14. Ko CJ, Elston DM. Pediculosis. J Am Acad Dermatol 2004; 50: 1–12. 15. Roberts RJ, Casey D, Morgan DA et al. Comparison of wet combing with malathion for treatment of head lice in the UK: a pragmatic randomized controlled trial. Lancet 2000; 356: 540–4. 16. Lapeere H, Vander Stichele RH, Naeyaert JM. Evidence in the treatment of head lice: drowning in a swamp of reviews. Clin Infect Dis 2003; 37: 1580–2. 17. Speare R, Canyon DV, Cahill C, Thomas G. Comparative efficacy of two nit combs in removing head lice (Pediculus humanus var. capitis) and their eggs. Int J Dermatol 2007; 46(12): 1275–8. 18. Glaziou P, Cartel JL, Alzieu P et al. Comparison of ivermectin and benzyl benzoate for treatment of scabies. Trop Med Parasitol 1993; 44(4): 331–2. 19. Grover IS, Ladhar SS, Randhawa SK. Carbaryl-A selective genotoxicant. Environ Pollut 1989; 58(4): 313–23. 20. Ishii N. Executive committee of guideline for the diagnosis. Guideline for the diagnosis and treatment of scabies in Japan (second edition). J Dermatol 2008; 35(6): 378–93. 21. Heukelbach J, Pilger D, Oliveira FA et al. A highly efficacious pediculicide based on dimeticone: randomized observer blinded comparative trial. BMC Infect Dis; 8: 115. 22. Burgess IF, Lee PN, Matlock G. Randomised, controlled, assessor blind trial comparing 4% dimeticone lotion with 0.5% malathion liquid for head louse infestation. PLoS One 2007; 2(11): e1127.

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23. Youssef MY, Sadaka HA, Eissa MM, el-Ariny AF. Topical application of ivermectin for human ectoparasites. Am J Trop Med Hyg 1995; 53(6): 652–3. 24. California Safety Code Section 111246. Sherman Food, Drug, and Cosmetic Law, Division 104, Part 5, California Health and Safety Code Section 111246, www.dhs.ca.gov/ fdb/local/PDF/Sherman_2007.PDF, accessed 09-23-09. 25. Hammond K, Leikin JB. Topical pyrethrin toxicity leading to acute-onset stuttering in a toddler. Am J Ther 2008; 15(4): 323–4. 26. De Felice J, Rumsfield J, Bernstein JE et al. Clinical evaluation of an after-pediculicide nit removal system. Int J Dermatol 1989; 28: 468–70. 27. Mumcuoglu KY, Magdassi S, Miller J et al. Repellency of citronella for head lice: double-blind randomized trial of efficacy and safety. Isr Med Assoc J 2004; 6(12): 756–9. 28. Pruksachatkunakorn C, Damrongsak M, Sinthupuan S. Sulfur for scabies outbreaks in orphanages.Pediatr Dermatol 2002; 19(5): 448–53. 29. Schachner LA. Treatment resistant head lice: alternative therapeutic approaches. Pediatr Dermatol 1997; 14(5): 409–10. 30. McCage CM, Ward SM, Paling CA et al. Development of a paw paw herbal shampoo for the removal of head lice. Phytomedicine 2002; 98: 743–8. 31. Akisu C, Delibas SB, Aksoy U. Albendazole: single or combination therapy with permethrin against pediculosis capitis. Pediatr Dermatol 2006; 23(2): 179–82. 32. Buffet M, Dupin N. Current treatments for scabies. Fundam Clin Pharmacol 2003; 17: 217–25. 33. Fawcett RS. Ivermectin use in scabies. Am Fam Physician 2003; 68: 1089–92. 34. Hipolito RB, Mallorca FG, Zuniga-Macaraig ZO. Head lice infestation: single drug versus combination therapy with one percent permethrin and trimethoprim/sulfamethoxazole. Pediatrics 2001; 107: E30. 35. Namazi MR. The potential utility of indomethacin in enhancing the pediculocidal activity of permethrin, pyrethrins, and DDT. Med Hypotheses 2008; 71(4): 607–8. 36. Namazi MR. Levamisole: a safe and economical weapon against pediculosis. Int J Dermatol 2001; 40(4): 292–4. Erratum in: Int J Dermatol 2001; 40(12): 794.

3.5 Therapeutic monitoring of parasitoses with videodermatoscopy Giuseppe Micali, Aurora Tedeschi, and Francesco Lacarrubba

Previous studies demonstrated that videodermatoscopy (VD) is a very effective and sensitive diagnostic tool for some cutaneous parasitoses, in particular scabies and pediculosis.(1–3) An important advantage of VD is its high compliance, as it does not cause pain or physical discomfort. For these reasons, VD seems to be a useful technique for evaluation of response to therapy, especially in those cases in which itch persists after treatment or patient compliance is doubtful. Based on these considerations, some studies have been carried out to evaluate VD ability to monitor efficacy of scabies and pediculosis treatment and whether VD allows determination of the optimal timing of drug application. SCABIES The first study (4) to assess the use of epiluminescence light microscopy (ELM) for monitoring antiscabietic therapy was performed in 2001. The authors examined the mite’s morphological changes in vivo, the temporal progression of these changes, and their effectiveness as criteria for treatment. A total of 20 patients affected by scabies were observed, 7 patients received 12 mg of ivermectin as a single dose, and 13 patients were treated with lindane or benzyl benzoate for 3 days. ELM was performed using X8.25 and X20.8 magnification. Before treatment, the average number of adult female mites on both hands and feet of all patients was 8.2. Epimeres (chitinous internal structures attached to legs), anterior outline, eating tools, and both pairs of forelegs and hind legs of Sarcoptes scabiei were observed. One week after treatment, the average number of adult female mites had dropped to 5.0. After 2 weeks, the mites began to degrade, and their outlines disappeared gradually; however, epimeres were even more distinct now, especially in children. A granular hem was noticed in some cases. After 3 weeks, structures had progressively broken down or were missing. Statistically, no differences were found between patients treated orally and those treated locally. After 4 weeks, there were no visible remains. The authors suggested the decrease in number of mites might have resulted from both scratching and the renewal process of the corneal layer itself. Once the mite was dead it was slowly promoted upward under a progressively thinning cover; this explained why the durable chitinous epimeres became even more distinct with time. The progressive degradation of its other, less durable components and its gradually disappearing outline suggested that the mite had degraded rather than simply been scratched away. Probably, the granular hem was a product of catabolism resulting from treatment.(4) In our experience, (5) we evaluated a group of patients affected by scabies undergoing topical treatment with a thermolabile foam of pyrethrins (0,165%) synergized with piperonyl

butoxide (1,65%), to determine whether VD would enhance monitoring of the clinical response to treatment and whether VD would indicate the optimal timing of drug application. A total of 20 patients (12 males, 8 females; aged between 1 and 65 years) who were affected by scabies (diagnosis confirmed by VD) and were treatment naïve were included in the study. The foam was applied to the entire body, once at bedtime for two consecutive days. In order to detect treatment response, VD evaluation of two selected skin areas for each patient was performed at baseline, and after 12, 24, 36, and 48 hours. VD examination was performed with a Video Microscope System Hi-Scope KH-2,200 (Hirox Co. Ltd., Tokyo, Japan) equipped with a zoom lens that allows skin observation with incidental light at magnifications ranging from X20 to X600. At 48 hours, skin scraping of the selected areas followed by microscopic observation was performed. In all patients, VD showed mite migration within burrows at 12 hours. At 24 hours, there was no evidence of active mite migration; at that timepoint most patients reported that itching symptoms had subsided. At 48 hours, the mites were generally no longer appreciable and an amorphous material, probably resulting from mite decomposition, was generally detectable at one end of an empty burrow (Figure 3.21–3.22). At this time, skin scraping followed by microscopic observation showed only mite remnants in all patients. None of the 20 patients showed evidence of infestation at a 2-week follow-up. VD confirmed that the foam was effective in the management of scabies, killing the mites at about 24 hours, when their immobilization could be established. At 48 hours, shrinkage and breakdown of the mite with formation of an amorphous material was observed. At that time, microscopic examination following skin scraping confirmed that this material was composed of mite remnants. In this study, the use of high magnification (up to X600) allowed to recognize early the death of mites. In another single-arm multicenter study (6) including adults and children from 3 months of age with proven scabies, 5% permethrin cream formulation was tested. In this study, the evaluation of efficacy was performed with the stereo epiluminescence microscope of Kreusch (Fa. Wolfgang Kocher Feinmechanik, Mössingen, Germany, or a comparable device of another manufacturer) or with a video microscope with X20 to X60 magnification. In conclusion, VD enhances the monitoring of clinical response to treatment (4) and allows determination of the optimal timing of drug application. This may be particularly important in minimizing the risk of overtreatment, reducing the potential for side effects, and enhancing patient compliance.

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micali, tedeschi, and lacarrubba (a)

(b)

Figure 3.21a–b  VD evaluation showing the presence of Sarcoptes scabiei (arrows) at baseline (X100). (a)

(b)

Figure 3.22a–b  After 48 hours of treatment the mites were no longer appreciable (X100). PEDICULOSIS Pediculosis is a very frequent parasitosis usually treated with topical compounds with insecticidal activity (pyrethrin, permethrin, and malathion) or with so-called natural products with mechanical action (e.g., essential oil) or with systemic drugs, such as antibiotics (trimetroprim) or ivermectin.(7) However, for many of these products, data about their real therapeutic efficacy or rapidity of action are not readily available. Moreover, evaluation methods have been based on very simplistic criteria (i.e. clinical examination before and after treatment). VD can be used as a diagnostic tool in head and pubic lice infestation: It permits an easy identification of parasite and nits when these are not visible to the naked eye.(8) The differentiation between vital and empty nits provides useful information about therapeutic response. An in vivo study (8) was performed by mean of a noncontact hand-held dermoscope (Dermlite; 3gen, LLC). An 8-year-old

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boy affected by pediculus capitis was treated with permethrin (1%) according to established protocols. One week after the first treatment cycle, dermoscopic follow-up still revealed the presence of dark-brown eggs containing nymphs, and two additional therapeutic cycles were performed. At the last visit, 3 weeks after diagnosis, no nits were observed and treatment was discontinued. In this case, the dermoscopic examination allowed a safe and reliable differentiation of eggs containing nymphs from the empty cases of hatched louses and also from amorphous pseudo nits. The characteristic dermoscopic features let the authors not only establish a rapid diagnosis but were also useful for the treatment monitoring because vital eggs were still present after the first treatment cycle. Therefore, in vivo dermoscopy may replace the more time consuming ex vivo microscopic examination of the affected hairs in the daily routine.(8) In our experience, VD allowed the therapeutic monitoring with mercurial ointment in a case of phthiriasis palpebrarum.

therapeutic monitoring of parasitoses with videodermatoscopy (a)

(b)

Figure 3.23a–b  Phthiriasis palpebrarum. A: lice and nits at VD observation (X60). B: VD evaluation after 5 days treatment with mercurial ointment: persistence of few full nits not visible to naked eye (X60).

Figure 3.24  VD examination of an adult specimen of Pediculus humanus treated with the application of a topical compound that acts through a mechanical action of “choking” (X80). After 5 days of treatment, VD showed the persistence of few full nits not visible to naked eye (Figure 3.23a–3.23b). VD permits an in vivo evaluation of the movements and physiology of lice and eggs. Isolation of an adult parasite allows to observe through VD the louse and to prove its viability in ex vivo conditions (by means of a Petri’s capsule). Through the isolation of Pediculus humanus capitis (that cannot be reared in laboratory conditions) and through VD evaluation, it is also possible to assess the efficacy and rapidity in pediculocidal activity of topical pediculocides. In 2006 we performed a study (9) using VD to assess the pediculocidal efficacy and rapidity of action of two different medications indicated in the treatment of head lice.

A formulation of synergized pyrethrin in thermophobic foam (Milice®; Mipharm) was compared to a coconut and aniseed oil–based spray, with a mechanical action obtained by suffocation (Paranix®; Chefaro). Ten experiments were performed on the same number of adults’ specimens of Pediculus humanus capitis obtained from three subjects with head lice infestation, using a fine-tooth comb. Each louse was placed in a Petri’s capsule with gauze on the bottom in order to improve the VD visualization. VD examination was performed using a Video Microscope System Hirox Hi-Scope KH-2,200 equipped with lenses allowing magnifications ranging from X20 to X600. An initial observation by VD of 180-second duration was performed to evaluate movements and peristaltic intestinal activity (that is visible in transparency) as an indicator of lice viability. After this time, a minimal quantity of pyrethrin thermophobic foam was applied on five parasites and the oil-based spray was applied on another batch of 5 parasites. The activity of parasites were then observed and recorded for 120 minutes. In the case of pyrethrin thermophobic foam product, in all the tests performed, the absence of movements of lice was observed within 10 seconds from the contact with the product; the absence of peristalsis was noted within 60 seconds, which was interpreted as mite death. With the essential oil-based product the lice was alive after a continuous observation of 120 minutes after the application of the medication (the product’s package showed the time for optimal product activity to be around 15 minutes). Recently, we performed another similar preliminary study with a topical compound that acts through a mechanical action of “choking” of the mite within few minutes (Figure 3.24). In conclusion, VD is indeed a valid research tool for evaluating the efficacy and the time of action taken by topical agents/ pediculocides to act while treating.(8–10) A further and future use of VD could be measured by studying possible lice resistance to commonly used substances with pediculocidal activity,

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micali, tedeschi, and lacarrubba in order to contribute to the identification of alternative and appropriate therapeutic options.   6. REFERENCES   1. Argenziano G, Fabbrocini G, Delfino M. Epiluminescence microscopy. A new approach to in vivo detection of Sarcoptes scabiei. Arch Dermatol 1997; 133: 751–3.   2. Micali G, Lacarrubba F, Lo Guzzo G. Scraping versus videodermatoscopy for the diagnosis of scabies: a comparative study. Acta Derm Venereol 2000; 79: 396.   3. Lacarrubba F, Musumeci ML, Caltabiano R et al. Highmagnification videodermatoscopy: a new noninvasive diag­ nostic tool for scabies in children. Pediatr Dermatol 2001; 18: 439–41.   4. Haas N, Sterry W. The use of ELM to monitor the success of antiscabietic treatment. Arch Dermatol 2001; 137: 1656–7.   5. Micali G, Lacarrubba F, Tedeschi A. Videodermatoscopy enhances the ability to monitor efficacy of scabies

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  7.   8.

  9.

10.

treatment and allows optimal timing of drug application. J Eur Acad Dermatol 2004; 18: 153–4. Hamm H, Beiteke U, Höger PH et al. Treatment of scabies with 5% permethrin cream: results of a German multicenter study. J Dtsch Dermatol Ges 2006; 4(5): 407–13. Dodd CS. Interventions for treating headlice. Cochrane Database Syst Rev 2001; 2: CDOO1165. Di Stefani A, Hofmann-Wellenhof R, Zalaudek I. Dermoscopy for diagnosis and treatment monitoring of pediculosis capitis. J Am Acad Dermatol 2006; 54(5): 909–11. Lacarrubba F, Nardone B, Milani M, Botta G, Micali G. Head lice: ex vivo videodermatoscopy evaluation of the pediculocidal activity of two different topical products. G Ital Dermatol Venereol 2006; 141: 233–5. Zalaudek I, Giacomel J, Cabo H et al. Entodermoscopy: a new tool for diagnosing skin infections and infestations. Dermatology 2008; 216(1): 14–23.

3.6 Tungiasis

Elvira Moscarella, Renato Bakos, and Giuseppe Argenziano

Tungiasis is an ectoparasitic disease caused by the flea Tunga penetrans, which is endemic in some parts of South and Central America, Africa, Asia, and the Caribbean. Data on tungiasis prevalence are variable and are not always available, especially for African states. Tungiasis is reported to be very frequent in Trinidad with prevalence varying from 15.7% to 31.4%.(1, 2) A surveillance performed in communities of lower socioeconomic status of northeast Brazil has demonstrated prevalence rates of up to 54.5% among the residents of such areas.(3) In a recent study conducted in a rural community in Lagos, the prevalence was 45.2%.(4) Only one autochthon case has been reported in Europe (5) where all reports are about imported cases in which the disease was contracted after traveling in endemic areas. Tunga penetrans is a sand flea that infests the skin of humans and can have various animals (pigs, cows, cats, dogs, and rats) serving as usual reservoirs.(6, 7) The disease is usually acquired by walking barefoot in humid sand contaminated by the flea. Therefore, the feet are the preferred site of penetration. The flea is not able to jump high, even so, ectopic lesions have been reported in almost all parts of the body and are associated with high infestation grades and young age.(8) Both male and female flea may penetrate the skin, but after copulation, the male dies, whereas the female remains into the skin completing her vital cycle that lasts about 4 to 6 weeks. The flea penetrates the skin with the head of the exoskeleton, creating a cavity that reaches the superficial dermis where it is nourished by the blood of the dermal vascular plexus. After penetration into the skin, the female starts producing eggs and enlarging her body from 1 mm to about 1 cm in diameter. Eggs and feces are eliminated through a small opening in the epidermis and then the flea dies in the cavity. The natural history of the disease has been divided into 5 phases (9): (1) penetration, (2) hypertrophy, (3) the white halo phase, (4) inoculation, and (5) rest of the fleas in the host’s cutis. The diagnosis is essentially clinical in endemic areas. It typically presents multiple, confluent, roundish papules or nodules located on the feet. The lesions are white-gray-yellowish in color and exhibit a small, central, brown opening. Penetration of the flea is asymptomatic or may be followed by an itching sensation. Only when the parasite enlarges its diameter an inflammatory process causes pain to the host (10), sometimes reported as very intense and debilitating. In nonendemic areas, the lesion is usually single and can be easily misdiagnosed and confused with several other diseases like viral warts, foreign body reaction, fungal and bacterial infections, tumors, myiasis, and vasculitis. Early diagnosis and correct therapy are crucial to avoid frequent complications that may be caused by bacterial superinfections.(11)

Nowadays, traveling-associated dermatoses are more frequently seen by physicians that may not be very familiar to them.(12) In this scenario, dermoscopy can facilitate the early diagnosis of tungiasis, thus leading to the correct treatment that consists of complete surgical excision of the lesion (Figures 3.25 and 3.26). Mechanical removal, curettage, and cryotherapy may also be considered. Histopathologic examination reveals hyperkeratosis and acanthosis of the epidermis. The flea is located between the epidermis and the superficial dermis, embedded in a pseudocystic cavity that presents a small opening through which eggs and feces are expelled. An inflammatory perilesional infiltrate is also present that is constituted by lymphocytes, neutrophils, and eosinophils. Bauer et al. (13, 14) first described the dermoscopic aspects of tungiasis, identifying the dark spot as a pigmented ring with a central pore. This corresponds to the pigmented chitin surrounding the posterior opening of the flea exoskeleton. Di Stefani et al. (15) found a dermoscopic grey-blue blotch, which they inferred to be related to developing eggs. The direct identification of eggs by dermoscopy has been described by Cabrera et al.(16) Reaching the dermis by sequential and careful shaving of the epidermis and gently compressing the edges of the wound, a jelly-like bag will emerge, which is visible as a bag full of eggs during dermoscopy. Bakos et al. (17) recently described a further dermoscopic feature defined as “whitish chains.” They visualized using dermoscopy the presence of whitish structures

Figure 3.25  On dermoscopy, the lesion appears as a white to light brown yellowish papule with a central brownish opening. The opening corresponds to the posterior part of the flea’s exoskeleton. Gray-blue blotches, sometimes shaped as a comma, can also be seen and may represent the intestinal part of the flea (X10).

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moscarella, bakos, and argenziano

Figure 3.26  Another image of tungiasis seen by dermoscopy, showing comma-like gray-blue blotches, together with whitish structures forming a chain-like structure and expelled eggs (X10). in a chain-like distribution perfectly matching in vivo with the jelly bag described by Cabrera. Dermoscopy can also allow a rapid differential diagnosis (18) with plantar warts and pigmented melanocytic lesions (a case of Tunga penetrans simulating acral melanoma has been described)(6). In viral warts, the diagnosis is based on the presence of a verrucous, yellowish unstructured area exhibiting a variable number of irregularly distributed, red, brown, or black dots or linear streaks caused by chronic high vascular pressure at plantar sites. Pigmented acral melanoma can also be easily differentiated for the presence of specific dermoscopic features such as the parallel ridge pattern. REFERENCES   1. Chadee DD. Distribution patterns of tunga penetrans within a community in Trinidad, West Indies. Trop Med Hyg 1994; 97: 167–70.   2. Chadee DD. Tungiasis among five communities in south western Trinidad, West Indies. Ann Trop Med Parassitol 1998; 92: 107–13.   3. Heukelbach J, Costa AML, Wilckle T, Mencke N, Feldmeier H. The animal reservoir of tunga penetrans in severely affected communities of north est Brazil. Med Vet Entomol 2004; 18: 329–35.

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  4. Ugnomoiko US, Ofoezie IE, Heukelbach J. Tungiasis: high prevalence, parasite load, and morbidity in a rural community in Lagos State, Nigeria. Int J Dermatol 2007; 46: 475–81.   5. Veraldi S, Carrera C, Schianchi R. Tungiasis had reached Europe. Dermatology 2000; 201: 382.   6. Franck S, Feldmeier H, Heukelbach J. Tungiasis: more than an exotic nuisance. Travel Med Infect Dis 2003; 1: 159–66.   7. Kimpel S, Mehlhorn H, Heukelbach J, Feldmeier H, Mencke N. Field trial of the efficacy of a combination of imidacloprid and permetrin against Tunga penetrans (sand flea, jigger flea) in dogs in Brazil. Parassitol Res 2005; 97: S113–S119.   8. Heukelbach J, Wicke T, Eisele M, feldmeier H. Ectopic localization of tungiasis. Am J Trop Med Hyg 2002; 67: 214–6.   9. Eisele M, Heukelbach J, Van Marck E et al. Investigations on the biology, epidemiology, pathology and control of Tunga penetrans in Brazil: I. Natural history of tungiasis in man. Parasitol Res 2003; 9(2): 87–99. 10. Van Bruskirk C, Burd EM, Lee M. A painful, drainig black lesion on the right heel. Tungiasis. Clin Infect Dis 2006; 43: 65–6. 11. Feldmeier H, Heukelbach J, Eisele M et al. Bacterial superinfection in human tungiasis. Trop Med Int Health 2002; 7: 559–64. 12. Caumes E, Carriere J, Guermonprez G et al. Dermatosis associated with travel to tropical countries: a prospective study of the diagnosis and manaagment of 269 patients presenting to a tropical disease unit. Clin Infect Dis 1995; 20: 542–8. 13. Bauer J, Forschner A, Garbe C, Rocken M. Dermoscopy of tungiasis. Arch Dermatol 2004; 140 (6): 761–3. 14. Bauer J, Forschner A, Garbe C, Rocken M. Variability of dermoscopic features of tungiasis. Arch Dermatol 2005; 141 (5): 643–4. 15. Di Stefani A, Rudolph CM, Hofmann-Wellwnohf R, Mullegger RR. An additional dermoscopic feature of tungiasis. Arch Dermatol 2005; 141 (8): 1045–6. 16. Cabrera R, Daza F. Tungiasis: eggs seen with dermoscopy. Br J Dermatol. 2008; 158 (3): 635–6. 17. Bakos RM, Bakos L. “Whitish chains”: a remarkable in vivo dermoscopic finding of tungiasis. B J Dermatol 2008, 159: 991–2. 18. Zalaudek I, Giacomel J, Cabo H et al. Entodermoscopy: a new tool for diagnosing skin infections and infestations. Dermatology 2008; 216 (1): 14–23.

4

Hair loss Antonella Tosti and Bruna Duque Estrada

In the last few years, dermoscopy has been increasingly used in the evaluation of patients with hair loss. We believe that this technique is a very important tool, as it not only improves diagnostic accuracy of hair and scalp disorders but also provides clues for better understanding the pathogenesis of some conditions. This diagnostic method has provided new clinical signs for recognizing hair diseases and enhanced features previously seen with the naked eye. For scalp examination, dermatologists may use a manual dermoscope (x10 magnification) or a videodermoscope equipped with various lenses (from x20 to x1,000 magnification). Both epiluminescent and nonepiluminescent modes are employed, and alcohol or thermal water can be used as interface solutions. Dermoscopy findings in hair and scalp disorders include follicular and interfollicular patterns, as well as hair shaft’s characteristics (Table 4.1). Normal Scalp Examination of the normal scalp shows a diffuse white color and often simple fine red loops, which represent capillary loops in the dermal papilla.(1) Follicular units contain 2 to 3 terminal hairs and 1 or 2 vellus hairs inside (Figure 4.1). In dark-skinned individuals (phototypes V and VI), a perifollicular pigmented network (honeycomb pattern) is well appreciated. The network consists of hyperchromic lines that represent melanocytes in the rete ridge system in contrast with hypochromic areas formed by fewer melanocytes localized in the suprapapillary epidermis.(1) Small, white dots regularly distributed among follicular units are also appreciated (Figure 4.2).

Figure 4.1  Normal scalp of a Caucasian patient. Note the diffuse white color of the scalp and the follicular units containing 1 to 3 terminal hairs (x20).

Table 1  Videodermoscopic Patterns Seen in Normal and Patho­ logical Scalp. Interfollicular patterns: Vascular patterns Simple red loops Twisted red loops Arborizing red lines Red dots Pigment pattern: honeycomb pigmented network Blue-grey dots Brown halo (peripilar sign) White dots Dirty dots Follicular patterns: Yellow dots Keratotic plugs Black dots (cadaverized hairs)

Figure 4.2  Scalp dermoscopy of a dark-skinned patient. Note the honeycomb pigmented network around the follicular units (x20). Particles of dirt, dust, loose fibers, and other small particulate debris, which we defined as dirty dots, may be appreciated in children aged between 1 and 12 years (Figure 4.3 and 4.4). These particles are most prominent in the vertex scalp and disappear immediately after shampooing, but reappear as soon as 24 hours after shampooing. Dirty dots disappear at puberty when sebaceous excretion possibly prevents deposition of environmental particles on the scalp.(2)

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tosti and estrada

Figure 4.3  Particles of dust, powder and debris can be seen as dirty dots in scalp dermoscopy of this Caucasian patient (x20).

Figure 4.5  A variability in the hair shaft diameter of more than 20% of hair shafts is diagnostic of androgenetic alopecia (x20).

Figure 4.4  Small dirty dots are observed in scalp dermoscopy of this African-American child (x20).

Figure 4.6  A variability of the hair shaft diameter is well observed, as well as many follicular units compound of single hair shafts (x20).

Androgenetic Alopecia Androgenetic alopecia (AGA) is the most common form of hair loss, affecting up to 80% of men and 50% of women. Patients typically present with progressive thinning and shortening of hair in androgen-dependent scalp regions including frontal, temporal, and vertex areas.

examination.(3) A hair diameter diversity of >20% is diagnostic of androgenetic alopecia and is significantly correlated to follicle miniaturization by histological analysis (Figure 4.5). (4) Using this parameter, Lacharrière proposed a severity scale based on dermoscopic findings as diameter-diversity and hairdensity scores.(4) Videodermoscopy allows measurement and monitoring of hair shaft thickness in androgenetic alopecia, and thus may also help in calculating the terminal to vellus hair ratio.(3, 5) Under higher magnifications on videodermoscopy, it is possible to identify and count vellus hairs (with less than 0.03 mm in width).(4, 5) It is worthwhile to note that follicular ostia in AGA show predominance of single hairs, instead of 2 to 4 hair shafts observed in normal subjects (Figure 4.6).(5)

Dermoscopic Features Hair Diameter Diversity In general, scalp examination in AGA should be taken in an area delineated at the cross between nose line and ear implantation line. The progressive miniaturization of hair with visualization of hairs with different calibers are enhanced by dermoscopic

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hair loss Secondary Signs In patients with advanced androgenetic alopecia, yellow dots can be observed.(1) These dots represent distention of the affected follicular infundibulum with keratinous material and sebum. Thinning of the hair shafts leads to decrease on sebum drainage and thus to distention of the infundibular portion of the hair follicle. A honeycomb-like pigmented network is found in scalp areas that are sun exposed with progression of baldness. This pigmentation is well appreciated when comparing parietal scalp affected with AGA, and unaffected occipital scalp of patients with phototypes I to IV.

Figure 4.7  Patient presenting long lasting AGA with diffuse pattern.

Alopecia Areata Alopecia areata is an autoimmune, nonscarring form of alopecia. A wide range of clinical presentations can occur, from single patch of alopecia to complete loss of scalp hair (alopecia totalis) or the entire body (alopecia universalis). The disease affects most commonly scalp hairs, but it may also involve eyebrows, eyelashes, beard, pubic, axilary, and all body hairs. Dermoscopic Features Yellow Dots The presence of yellow dots is a characteristic finding in alopecia areata. This pattern is characterized by a distinctive array of yellow to yellow-red, round, and polycyclic dots that vary in size and correspond to the dilated follicular openings with or without hairs shafts (Figure 4.9).(1, 8, 9) The dots are best visualized under epiluminescent dermoscopy, although the nonepiluminescent mode provides a better view of their protuberant and greasy aspect. Degreasing the affected area with acetone results in diminished dot sizes.(1) Dry dermoscopy (dermoscopy without immersion gel) has also been reported as a useful technique in diagnosis and follow-up of patients with alopecia areata. With this method, one can see more clearly a

Figure 4.8  Dermoscopy of the patient with long lasting AGA demonstrates focal atrichia with absence of follicular ostia (x40). Empty follicular ostia are often seen. They are expression of the kenogen phase of the hair cycle, which corresponds to the interval between extrusion of the telogen hair and emergence of a new anagen hair. Kenogen frequency and duration are greater in men and women with androgenetic alopecia than in controls and an increased number of kenogen follicles has been associated with the progression of female AGA.(6) In women with longstanding AGA, dermoscopy often shows small areas of follicular loss (focal atrichia) (Figure 4.7 and 4.8). Peripilar signs The presence of a brown halo at the follicular ostium is mostly found in patients with high hair density and this finding have been related to superficial perifollicular lymphocytic infiltrates in early androgenetic alopecia of male and females (Figure 4.5).(7)

Figure 4.9  Yellow-red, round, and polycyclic dots correspond to the dilated follicular ostia without hairs shafts (x20).

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tosti and estrada

Figure 4.10  An African-American patient with alopecia areata in which the yellow dots are difficult to visualize. Vellus hairs and short broken hairs are also observed inside the plaque (x20).

Figure 4.12  Black dots are observed inside the yellow dots and represent cadaverized hairs that are broken before scalp emergence (x70).

Figure 4.11  Cadaverized hairs, as black dots, short broken hairs, and exclamation mark hairs are observed inside an active plaque of alopecia areata (x20).

Figure 4.13  Exclamation mark hairs are characterized by a distal and wide tip in comparison with the proximal portion of the shaft (x20).

keratotic plaque with multiple depressed follicular ostia.(10) It has been suggested that this depressed pattern may correspond to abnormal hair follicles containing incompletely differentiated hair shafts, the so called nanogen hairs, which cannot be morphologically categorized as anagen, catagen, or telogen hairs.(10) The frequency of observation of yellow dots in Asian patients has been shown to be lower than that reported in Caucasians. (1, 9) We have also observed a lower incidence of yellow dots in patients with phototypes V and VI, possibly because the yellowish color of Asian patients and the presence of the pigmented network in black patients makes it more difficult to perceive the yellow dots (Figure 4.10).

Dystrophic Hairs Dystrophic hair shafts are well appreciated by dermoscopy even at lower magnification (X 20). In active alopecia areata, the anagen arrest causes hair shafts to fracture before their emergence from the scalp: these cadaverized hairs appear as black dots at dermoscopy (Figures 4.11 and 4.12).(1, 5, 9) Growing of the broken shafts leads to formation of exclamation mark hairs, which are characterized by a distal, irregular, fractured tip that is wider than the proximal portion of the shaft (Figure 4.13). Monilethrix-like changes are observed due to variation in the caliber of the hair shaft as the result of intermittent inflammatory process affecting the hair bulb (Figure 4.14). A variable degree of hair shaft hypopigmentation is sometimes the unique mark of alopecia areata.

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Figure 4.14  The variation in the caliber of the hair shaft, as the result of intermittent inflammatory process affecting the hair bulb, composes the monilethrix-like hair shaft (x20).

Figure 4.16  Alopecia areata incognita. A female patient with acute and severe thinning of the hair. Clinical aspect is difficult to differentiate from androgenetic alopecia and telogen effluvium. Alopecia Areata Incognita Alopecia areata incognita was first described by Rebora in 1987; it is characterized by acute onset of diffuse shedding of telogen hairs in the absence of typical patches (Figure 4.16).(12) Patients often concern about severe thinning in a few months. Differential diagnosis with androgenetic alopecia and telogen effluvium is often difficult, and dermoscopy has proved to be an important tool in this challenging diagnosis. Figure 4.15  Short vellus hairs, with less than 10mm length, inside a plaque of alopecia areata are found in both acute and chronic diseases (x20). Short regrowing, miniaturized, and vellus hairs (shorter than 10 mm) are also a common feature observed in both acute and chronic alopecia areata. These hairs represent miniaturized nanogen hairs that are not able to prolong their anagen phase and undergo continuous recycling (Figure 4.15).(11) Recently, statistical analysis made by Inui et al. demonstrated that for diagnosis of alopecia areata, yellow dots and short vellus hairs were the most sensitive markers. Black dots, exclamation-mark hairs, and broken hairs were the most specific markers. The presence of black dots, exclamation-mark hairs, and vellus hairs indicate disease activity. Black dots, yellow dots, and clustered short vellus hairs correlated with the severity of disease.(9)

Dermoscopic Features Yellow Dots Using the epiluminescent mode, scalp demonstrates diffuse, round, and polycyclic yellow dots, with varied size and uniform distribution. The dots are evident within the follicular ostium with and without hair shafts and affects about 70% of the follicles (Figure 4.17).(13) Scalp biopsies show that the yellow dots correspond to dilated infundibula filed with cornified cells and sebaceous material. Short regrowing hairs Short, miniaturized, and tapered hairs (2–4 mm long) are a characteristic dermoscopic feature of alopecia areata incognita. The association of yellow dots with a large number of short regrowing hairs is very suggestive of alopecia areata incognita

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Figure 4.17  Alopecia areata incognita. Yellow dots are observed within the follicular ostium of both empty and hair-bearing follicles. Short regrowing hairs are also a characteristic feature of this subtype of alopecia areata (x40).

Figure 4.18  Alopecia areata incognita. Note the absence of the typical plaque and the presence of dystrophic and short broken hairs in a diffuse distribution (x20). (Figure 4.17). Inui et al. reported the usefulness of dry dermoscopy (dermoscopy without immersion gel) in detecting tiny hairs in a patient with diffuse alopecia in which differential diagnosis with androgenetic alopecia and telogen effluvium is often difficult.(10) Histopathology reveals high percentages of telogen hairs and/or miniaturized hairs. The typical peribulbar lymphocytic infiltrate may not be present. The pathological diagnosis is suggested by the presence of a subtle lymphocytic infiltrate around miniaturized follicles in the papillary dermis that correlates with the short regrowing hairs observed on dermoscopy.(13)

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Figure 4.19  Trichotilomania. Broken hair shafts at different lengths are frequent findings. Despite its similarity with alopecia areata, exclamation mark hairs are not observed in trichotilomania (x40).

Figure 4.20  An African-American patient with the characteristic longitudinal splitting of the shafts in trichotilomania (x30). Dystrophic Hairs Exclamation mark hairs and cadaverized hairs are not common in our experience (Figure 4.18).(13) Trichotilomania Trichotilomania is a compulsive disorder in which individuals pull out hair, from scalp or any other body area, resulting in alopecic patches. It is relatively more common in children. On physical exam, irregular patches of hair loss, with typical bizarre borders are observed. Inside the plaques, short broken hairs with variable lengths are evident. Dermoscopy is useful to diagnose the disease and to show patients the signs of plucking who do not admit their habit of pulling out hairs.

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Figure 4.21  Congenital Triagular alopecia. Dermoscopy shows many vellus hairs and normal follicular ostia. Terminal hairs of the normal scalp are well appreciated around the plaque (x20).

Figure 4.22  Lichen Planopilaris. Dermoscopy shows the typical perifollicular casts and areas with absence of follicular openings (x20).

Dermoscopic findings Short coiled hairs are distributed along the alopecic area with broken hair shafts with different lengths. These findings are considered evidence of plucking at different times. Longitudinal splitting of the hair shafts are also well appreciated in many cases (Figure 4.19 and 4.20).

sites to take biopsies, as well as to provide new information about the diseases.

Congenital Triangular Alopecia Congenital triangular alopecia usually presents in children in the age between 3 and 6 years as a triangular or oval patch of alopecia most frequently localized in the frontotemporal hairline. Other scalp regions may occasionally be affected. The triangular or lance-shaped alopecic area contains vellus hairs and has a typical stable course. The condition may be bilateral. Dermoscopy is helpful in the diagnosis when the triangular alopecia has an atypical location.(14) Dermoscopy of the patch shows normal follicular openings and numerous vellus hairs surrounded by normal terminal hairs in the adjacent scalp (Figure 4.21). Scarring Alopecia Cicatricial alopecias include a group of hair disorders that cause permanent destruction of the hair follicles. Cicatricial alopecias are the most challenging hair diseases for differential diagnosis and treatment. Causes of cicatricial alopecias are categorized as primary or secondary. Primary cicatricial alopecias specifically target the hair follicle and results in its destruction. In secondary scarring, alopecias the hair follicle destruction is secondary to diffuse scarring of the dermis.(15) Differential diagnosis of cicatricial alopecias requires a scalp biopsy. Dermoscopy has shown to be useful to find appropriate

Dermoscopic Features In all types of cicatricial alopecias, scalp examination reveals a variable degree of absence of follicular ostia. This feature is more appreciated in patients with dark skin (phototypes V and VI) and patients with long-standing alopecia, which develops the pigmented network secondary to sun exposure in the affected area. Lichen Planopilaris Lichen planopilaris (LPP) is the most common cause of cicatricial alopecia and most frequently middle-aged women. Patients present with scalp itching and tenderness. Scalp examination shows irregular patches of hair loss, which become confluent, affecting most frequently the pariental and vertex regions. The disease has a progressive course and severe alopecia may develop in some patients. Dermoscopic Features Dermoscopy reveals absence of follicular openings and the presence of characteristic perifollicular scales (peripilar casts) at the periphery of the patch. As scaling becomes more prominent, follicular plugging may be observed (Figure 4.22). Perifollicular erythema characterized by the presence of arborizing vessels around the follicular ostia is also observed (Figure 4.23). The pigmented network is still well appreciated inside the LPP plaques of dark-skinned individuals. As interfollicular epidermis is commonly unaffected by the inflammatory process in LPP, we believe that this sign may help in differentiating this type of alopecia from other scarring alopecias, such as discoid lupus erythematosus of the scalp (Figure 4.24).

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Figure 4.23  Lichen Planopilaris. Arborizing vessels are responsible for the perifollicular erythema observed in these patients. The absence of follicular ostia is also evident (x20).

Figure 4.24  Dermoscopy of a dark-skinned patient with LPP. The pigmented network and the white dots regularly distributed among are much more appreciated inside the alopecic plaque (x20). Kossard observed white pale dots in a dark-skinned patient (Figure 4.25).(16) Blue-grey dots may be found in some patients, especially those with dark skin (Figure 4.26). A peculiar pattern of round perifollicular blue-grey dots—“target pattern”—may be observed in some dark patients with LPP (Figure 4.27). Histopathologically, these dots are caused by loose melanin, fine melanin particles, or melanin “dust” in melanophages or free-floating in the deep papillary or reticular dermis. The target pattern is associated with the presence of melophages predominantly around hair follicles, sparing interfollicular epidermis. Usually, LPP spares some terminal hair follicles inside the alopecic patches.

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Figure 4.25  Liche planopilaris in an African-American patient. The regular distribution of the white dots is well appreciated, especially in comparison to the round and wider white holes that represent the follicular ostia (x10).

Figure 4.26  Blue-grey dots are appreciated in LPP, representing pigmentar incontinence inside the lesion (x20). In frontal fibrosing alopecia, a clinical variant of lichen planopilaris, the most prominent dermoscopic findings are loss of follicular openings, peripilar scale, and peripilar erythema (Figure 4.28). Discoid Lupus Erythematosus Discoid lupus erythematosus (DLE) of the scalp is characterized by single or multiple alopecic patches. Affected scalp shows erythema, scaling, follicular plugging, atrophy, and telangiectasias. Despite the fact that it is considered as part of the group of cicatricial alopecias, DLE often shows hair regrowth if promptly treated. In this way, early diagnosis is important for patients’ prognosis.

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Figure 4.27  Dark-skinned patient with LPP in which the blue-grey dots formed a peculiar “target-pattern” around the follicular units (x10).

Figure 4.28  Frontal fibrosing alopecia. Dermoscopic features are the same observed in classic LPP, as perifollicular scale and erythema (x10). Dermoscopic features Scalp atrophy is represented by a diffuse white color of the scalp (Figure 4.29). This pattern is well appreciated in dark-skinned patients, who loose the normally seen pigmented network within the lesion. Indeed, the honeycomb pigmented network might be seen at the periphery of the plaque of DLE. Arborizing and tortuous vessels are the most common vascular patterns seen inside DLE plaques (Figure 4.29). Some patients also present peculiar red to pink-red, round, and polycyclic dots that are uniform in size and regularly distributed around follicular openings (Figure 4.30). Hyperkeratotic follicular pluggings are observed in the follicles around the patches. Blue-grey dots may be observed, with a diffuse and speckled pattern of distribution along the patch (Figures 4.29 and 4.31).

Figure 4.29  In discoid lupus erythematosus of the scalp, a white plaque is well appreciated in the active border, associated with tortuous vessels, pigmentary (x40).

Figure 4.30  Polycyclic red dots distributed around follicular openings are observed inside a DLE lesion of the scalp together with arborizing vessels (x20). These dots represent pigmentar incontinence in the papillary dermis of follicular and interfollicular epidermis. We believe that the different patterns of blue-grey dots described may be a novel and interesting feature to help dermoscopic differentiation between DLE and LPP.(17) Folliculitis Decalvans Folliculitis decalvans (FD) is a neutrophilic variant of cicatricial alopecias, which accounts for approximately 11% of all primary cicatricial alopecias.(18) FD usually starts with follicular papules and pustules on the vertex and/or occipital area of the scalp, followed by intense inflammatory reaction and development of an indurated and boggy scarring patch. Multiple hair tufts are often found emerging from a common,

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Figure 4.31  Pigmentar incontinence represented by blue-grey dots in a speckled pattern inside the DLE plaque (x20).

Figure 4.32  Absence of follicular units, diffuse erythema and arborizing vessels in a patient with FD (x40). dilated, follicular opening. Purulent discharge can be observed if pressure is applied to the perifollicular area. S. aureus can be isolated from FD lesions and seems to play an important role in the inflammatory process. Dermoscopic Findings Marked diffuse scalp erythema and absence of follicular units are characteristic of FD (Figure 4.32). Dermoscopy also shows severe scaling and crusting, which can be prominent around follicular units. Pustular lesions are also evident. The intense inflammatory process is best seen in x50 or higher magnification. Multiple-coiled, dilated capillary loops, similar to those observed in psoriasis, and arborizing red lines are typical findings seen all over the affected scalp (Figures 4.33, 4.34, 4.35).(1)

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Figure 4.33  Neovascularization is a typical feature of FD, which is observed as multiple coiled capillary loops and arborzing red lines in the scalp (x20).

Figure 4.34  Pustular lesion inside a plaque of FD (x20). Tufted folliculitis, with several hair shafts emerging from the scalp, is often seen in advanced cases (Figure 4.36). Dermoscopy in the Differential Diagnosis of Alopecia of the Scalp Margin In patients who present with alopecia of the scalp margin, dermoscopy can be very useful, as the differential diagnosis between traction, alopecia areata, or frontal fibrosing alopecia extending to the temporal regions may be difficult. A new entity described as cicatricial, marginal alopecia (19) should also be considered in the differential diagnosis. Dermoscopic Features Alopecia areata affecting the scalp margin include ophiasis and sisaipho subtypes. The most relevant dermoscopic findings, as

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Figure 4.35  Tufted folliculitis is frequently observed in chronic FD. It is characterized by the emergency of many hair shafts from the same ostium (x40).

Figure 4.37  Dermoscopy of the previous patient shows the characteristic features of AA: yellow dots, dystrophic hairs and vellus hairs (x20).

Figure 4.36  A female patient with alopecia in the scalp margin due to alopecia areata – sisaipho subtype. discussed previously, are yellow dots, dystrophic hairs, and vellus hairs (Figure 4.36 and 4.37).(1, 3, 5, 8, 9) Frontal fibrosing alopecia, a variant of lichen planopilaris, is characterized by frontotemporal hair recession, eyebrow loss, and histopathology identical to lichen planopilaris (Figure 4.38). Dermoscopy shows absence of follicular openings, perifollicular scale, and a variable degree of perifollicular erythema (Figure 4.28).(20) The periphery of the scalp is the site of predilection of traction alopecia. Usually the disease affects the frontal, temporal, and vertex scalp (Figure 4.39). Patients present history of hairdressing associated with traction of hair scalp for many years, which include use of elastic bands, plaits, or extensions. Dermoscopy of alopecic patches highlights several miniaturized

Figure 4.38  Recession of the frontotemporal hairline and alopecia of the eyebrows in a patient with frontal fibrosing alopecia. hairs, as well as white dots. Sometimes, fractured hair shafts are seen as a sign of severe traction (Figures 4.40 and 4.41). A distinctive pattern of alopecia has been recently described by Goldberg as cicatricial marginal alopecia.(19) Around 40% of them had no history of traction hair styling. Patients

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Figure 4.41  Traction alopecia. A black dot represents a fracture of the shaft due to severe traction (x20).

Figure 4.39  Traction alopecia of the frontotemporal hairline in an African-American patient with some remaining vellus hairs in the frontal portion of the alopecic area.

Figure 4.42  Cicatricial marginal alopecia. A Caucasian patient presenting hair loss in the marginal scalp – occipital margin.

Figure 4.40  Dermoscopy of traction alopecia demonstrates miniaturized hairs inside the patch, and also the pigmented network and white dots seen in dark-skinned patients (x20).

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present hair loss limited to the periphery of the scalp, including frontal, temporal, and occipital margins. Dermoscopy demonstrated low hair density and loss of follicular ostia in all cases. Remaining hairs show reduced diameter of the shafts. Perifollicular hyperkeratosis, abnormal scalp vessels, or signs of traction alopecia are not observed (Figures 4.42–4.45). As described by Goldberg (19), histological features demonstrate a reduced number of hair follicles with the absence of terminal anagen hairs, few vellus hair follicles, and normal and intact sebaceous glands. Inflammatory infiltrates are typically absent. Replacement of hair follicles by columns of fibrous tissue (fibrous tracts) are appreciated at the hypodermis.

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Figure 4.43  Dermoscopy of cicatricial marginal alopecia demonstrates loss of follicular ostia and reduced number of shafts per follicular units (x40).

Figure 4.44  Cicatricial marginal alopecia. The hair loss in the frontotemporal region resembles frontal fibrosing alopecia. Therapeutic Monitoring of Hair Loss with Videodermatoscopy The combination of special software programs and videodermoscope has offered new tools for monitoring treatment of hair and scalp disorders. Macrophotographs of the scalp are

Figure 4.45  Cicatricial marginal alopecia. Dermoscopy also shows perifollicular erythema as arborizing vessels (x20).

very helpful to evaluate response to treatment. Comparison of dermoscopic photographs can be made by marking the scalp areas that are analyzed during treatment. When possible, a small nevus can be chosen as reference in order to avoid tattooing. In androgenetic alopecia, measurement of hair shaft diameter and evaluating the hair diameter diversity allows a significant comparison. In diseases that present dermoscopic signs of active lesions, such as alopecia areata and discoid lupus of the scalp, response to treatment can be better assessed by using videodermoscope. The phototricogram is a noninvasive technique that allows the in vivo study of the physiology of the hair cycle and the quantification of the amount of the effluvium. Thanks to the advent of the computer-assisted image analysis, today the technique has been improved. This method permits an accurate distinction between anagen and telogen hairs and avoids the technical problem of classic trichogram.(21) It also evaluates total hair density, an important index of the degree of the effluvium. The most important advantage of phototrichogram is that it is possible to repeat the examination on the same area of the scalp on a monthly basis, in order that each hair strand can be identified and followed across the various phases of the hair cycle. In this way, a virtual map of the anagen and telogen hairs of the scalp can de drawn. This allows the study of the hair cycle and the changes linked to therapies and aging. With the classic trichogram, however, these studies are not possible. References   1. Ross EK, Vincenzi C, Tosti A. Videodermoscopy in the evaluation of hair and scalp disorders. J Am Acad Dermatol 2006; 55: 799–806.   2. Fu J, Starace M, Tosti. A dirty dots: a new dermoscopic finding in healthy children. Arch Dermatol 2009; 145: 596–7.

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tosti and estrada   3. Lacarrubba F, Dall’Oglio F, Nasca MR, Micali G. Videodermatoscopy enhances diagnostic capability in some forms of hair loss. Am J Clin Dermatol 2004; 5: 205–8.   4. de Lacharrière O, Deloche C, Misciali C et al. Hair diameter diversity: a clinical sign reflecting the follicle miniaturization. Arch Dermatol 2001; 137: 641–6.   5. Rudnika L, Olzewska M, Rakowska A et al. Trichoscopy: a new method for diagnosis of hair loss. J Drugs Dermatol 2008; 7(7): 651–4.   6. Guarrera M, Rebora A. Kenogen in female androgenetic alopecia. A longitudinal study. Dermatol 2005; 210(1): 18–20.   7. Deloche C, de Lacharriere O, Misciali C et al. Histological features of peripilar signs associated with androgenic alopecia. Arch Dermatol Res 2004; 295: 422–8.   8. Ben Hassines M, Crickx B, Descamps V. Vidéomicroscopie au cours de la pelade. Ann Dermatol Vemerol 2007; 34: 35–8.   9. Inui S, Nakajima T, Nakagawa K et al. Clinical significance of dermoscopy in alopecia areata: analysis of 300 cases. Int J Dermatol 2008; 47: 688–93. 10. Inui S, Nakajima T, Itami S. Dry dermoscopy in clinical treatment of alopecia areata. J Dermatol 2007; 34: 635–9. 11. Whiting DA. Histopathologic features of alopecia areata. Arch Dermatol 2003; 139: 1555–9.

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12. Rebora A. Alopecia areata incognita: a hypothesis. Dermatologica 1897; 174: 214–8. 13. Tosti A, Whiting D, Iorizzo M. The role of scalp dermoscopy in the diagnosis of alopecia areata incognita. J Am Acad Dermatol 2008; 59: 64–7. 14. Iorizzo M, Pazzaglia M, Starace M et al. Videodermoscopy: a useful tool for diagnosing congenital triangular alopecia. Pediatr Dermatol 2008; 25(6): 652–4. 15. McElwee KJ. Etiology of cicatricial alopecias: a basic science point of view. Dermatol Ther 2008; 21: 212–20. 16. Kossard S, Zagarella S. Spotted cicatricial alopecia in dark skin. A dermoscopic clue to fibrous tracts. Australas J Dermatol 1993; 34(2): 49–51. 17. Duque-Estrada B, Tamler C, Pereira FBC, Barcaui CB, Sodré CT. Dermoscopic patterns of cicatricial alopecia due to Discoid Lupus Erythematosus and Lichen Planopilaris. An Bras Dermatol. In press. 18. Otberg N, Kang H, Alzolibani AA et al. Folliculitis decalvans. Dermatol Ther 2008; 21: 238–44. 19. Goldberg LJ. Cicatricial marginal alopecia: is it all traction? Brit J Dermatol 2009 ; 160(1): 62–8. 20. Inui S, Nakajima T, Shono F et al. Dermocscopic findings in frontal fibrosing alopecia: report of four cases. Int J Dermatol 2008; 47: 796–9. 21. D’Amico D,Vaccaro M, Guarnieri F et al. Phototrichogram using videomicroscopy: a useful technique in the evaluation of scalp hair. Eur J Dermatol 2001; 11(1): 17–20.

5

Nail diseases Antonella Tosti, Bianca Maria Piraccini, and Débora Cadore de Farias

The application of dermoscopy in the evaluation of nail disorders is still new and the real benefits of this technique in the diagnosis of nail conditions are not known. In particular, there are not evidence-based data showing that the use of dermoscopy may decrease the necessity of nail biopsies. As dermoscopy is becoming widely accepted and used in the medical community, there is now the need to standardize the dermoscopic findings observed in the nails in order to share information in this field. The dermoscopic examination can be performed on the following:

Nail plate Hyponychium Distal edge of the nail plate Proximal nail fold Nail bed (directly) and matrix (intraoperative dermoscopy)

Nail plate dermoscopy On the nail plate, gel immersion (ultrasound gel or cosmetic gel) is required because of the convex shape of the nail. This gel will fill the gap between the convex nail surface and the hand-held or videodermoscopy device. An exception would be the examination of nail plate surface for abnormalities, where it is better to use mineral oil, water, or alcohol solution. Examination is usually made with a magnification of 10× with a hand-held dermoscope, but digital videodermoscopic systems provide higher magnifications, and therefore, better information.(1) Nail plate dermoscopy has been mainly utilized for evaluation of nail pigmentation. Diagnosis and follow-up of other nail diseases can also possibly benefit from the use of dermoscopy, as it may detect subclinical nail plate surface abnormalities, visualize progression of onychomychosis, show abnormalities in the nail bed vessels, and possibly be helpful in the diagnosis of nonpigmented tumors of the nail. Dermoscopy of the hyponychium Examination of the hyponychium can be performed using mineral oil, gel, water, or alcohol solution. Polarized devices that do not require the application of immersion fluids can also be utilized in this area. The simple architecture of the hyponychium capillary network makes capillary loops in this anatomic area appear as

regular red dots because of their perpendicular arrangement to the skin (each red dot observed represents the top of one loop). Use of dermoscopy in the hyponychium can detect the following: 1. Micro-Hutchinson’s sign: pigmentation of the periungual tissues that could not be seen with the naked eye. This may be important for early diagnosis of subungual melanoma. 2. Vascular abnormality: increase/decrease of the vessel number, abnormalities in the vessel shape, and distribution. Dermoscopy of the distal edge of the nail plate Originally described by Braun et al. in 2006, it is useful to localize the pigment within the nail plate.(2) This is important for understanding the site of melanin production, as pigmentation in the ventral nail plate indicates that the lesion is localized in the distal nail matrix, whereas pigmentation in the dorsal nail plate indicates that the lesion is localized in the proximal nail matrix. Distal-edge dermoscopy can then be used as a preoperative tool to select the anatomical site of excision. It is also useful to confirm the clinical diagnosis of onychomatricoma. Dermoscopy of the proximal nail fold Examination of the proximal nail fold can be performed using mineral oil, gel, water, or alcohol solution. Polarized devices can also be utilized in this area. Proximal nail-fold dermoscopy is very important in the diagnosis and follow-up of connective-tissue disorders. It can also be useful to evaluate pigmentation of the periungual tissues. Intraoperative dermoscopy It is better to use polarized devices that do not require the application of immersion fluids; this allows examination with no direct contact, maintaining aseptic conditions. The main problem of nail plate dermoscopy in the evaluation of nail pigmentation is that we do not examine the site of melanin production but just the site of melanin deposition. Hirata et al. suggested intraoperative, polarized, light dermoscopic examination of the nail bed and matrix for better evaluation of pigmented lesions.(3, 4) Intraoperative dermoscopy visualizes the site of melanin production and can also help the surgeons to select the surgical margins, as it visualizes even

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tosti, piraccini, and de farias small pigmented foci. However, this is an invasive procedure that cannot be used routinely. PSORIASIS The clinical and dermoscopic features of nail psoriasis depend on which parts of the nail apparatus are affected by the disease. Nail matrix psoriasis produces nail plate surface abnormalities such as pitting and nail crumbling. Nail bed psoriasis causes onycholysis, salmon patches, splinter hemorrhages, and nail bed hyperkeratosis. Dermoscopy can better visualize nail plate and nail bed abnormalities and detect vascular changes that are indicative of the disease. Nail plate dermoscopy A magnification power of 40X to 70X is utilized to better visualize nail plate and nail bed abnormalities. High magnification permits to detect subclinical signs that can be very helpful for a definitive diagnosis of nail psoriasis in doubtful cases. Dermoscopy Findings: (Figure 5.1) •• Pits: irregular in shape and size, present a peripheral white border; •• Salmon patches: red-to-orange patches of nail bed discoloration that are irregular in size and shape; •• Onycholysis: The area can be homogeneously white or present multiple, thin, longitudinal, white striae. Dermo­ scopy often permits to visualize the presence of a “subclinical” erythematous border as a patchy red-to-orange discoloration of the nail bed surrounding the white onycholytic area. This finding is quite specific for a diagnosis of nail psoriasis •• Splinter hemorrhages: brown, purple-to-black spots arranged in a longitudinal fashion. These are due to pinpoint bleeding in the longitudinally arranged nail bed capillaries and successive incorporation of the blood in the ventral nail plate. Splinter hemorrhages are not necessarily an indicator of psoriasis, as they commonly occur in onychomychosis, contact dermatitis, and traumatic nail disorders as well. •• Dilation and tortuosity of the capillary of the distal nail bed is also commonly observed in psoriasis. Hyponychium dermoscopy In psoriasis, dermoscopic examination of hyponychium shows dilated, tortuous, and elongated capillaries with an irregular distribution (Figure 5.2). Capillary density is positively correlated with disease severity. A magnification power of 40X is best for visualizing and counting the abnormal capillaries.(5) A dermoscopic examination of the hyponychium is in our experience the best tool for confirming the diagnosis of psoriasis in patients with simple onycholysis or mild nail bed hyperkeratosis.

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Figure 5.1  Nail plate dermoscopy in psoriasis. Dermoscopy shows onycholysis characterized by a homogeneously white area with multiple, thin, longitudinal white striae. Pits irregular in shape and size are filled by gel and show a peripheral white border. Also note patchy, orange discoloration of the nail bed, splinter hemorrhages, and dilaltion and tortuosity of the capillaries in the distal nail bed (x20).

Figure 5.2  Hyponychium dermoscopy in psoriasis. Dermoscopy shows increased capillary density with dilated, tortuous, and elongated capillaries, with an irregular distribution (x20). Proximal nail-fold dermoscopy Nail-fold dermoscopy is useful to evaluate severity of psoriasis, as it reflects the degree of microvascular changes.(6) Nail-fold capillaries present both quantitative and morphological abnormalities. Zarik et al. (1982) reported a significantly shorter mean capillary loop length in psoriasis patients as compared to controls.(7) Bhushan et al. (2000) showed that the number of capillaries in the nail fold was significantly reduced in psoriasis when

nail diseases The scleroderma pattern is characterized by the presence of giant capillaries and microhemorrhages in early stages and loss of capillaries with avascular areas in late stages.(10, 11) The dermatomyositis pattern is often similar to the scleroderma pattern. Two or more of the following findings in at least two nail folds are considered consistent for dermatomyositis: enlargement of capillary loops, loss of capillaries, disorganization of the normal distribution of capillaries, bushy capillaries, twisted enlarged capillaries, and capillary hemorrhages.(12, 13) In systemic lupus erythematosus (SLE), capillary density is normal, but capillaries are tortuous, elongated, and dilated.(14)

Figure 5.3  Brittle nails. Nail plate dermoscopy shows irregular longitudinal fissures and grooves. The pigmentation is due to deposition of exogenous particles (x20). compared to normal controls. Capillaries in psoriasis also presented a decreased diameter of the arterial limb.(8) Brittle Nails Brittle nails are a common complaint characterized by weak fragile nails that split, flake, and crumble. Nail fragility may be a consequence of factors that alter the nail plate production and/or factors that damage the already keratinized nail plate. In the latter case, environmental and occupational conditions that reduce the water content of the nail plate have an important additional role. Nail plate dermoscopy The nail plate presents irregular longitudinal fissures and grooves that often appear pigmented due to deposition of exogenous particles. The distal nail margin is often white due to scaling and exfoliation (Figure 5.3). Dermoscopy may be used to score severity of fissuring and exfoliation and evaluate improvement with treatment. Collagen Tissue Disorders Morphological changes in the nail-fold capillaries confirm the diagnosis of autoimmune connective tissue diseases, and severity in the capillary changes is related with systemic disease activity. Nail-fold capillaroscopy is, therefore, useful both as a diagnostic tool and as a predictor of disease progression.(9) Magnifications of 30X to 50X are usually utilized. Nail-fold dermoscopy In normal conditions, the microvascular pattern is characterized by a regular array of microvessels with large intra- or inter-individual variability. However, capillary loss and giant capillaries are not seen in normal pattern.(10)

Onychomychosis Onychomycosis refers to the invasion of the nail plate by dermatophytes, yeasts, or nondermatophytic moulds. Different clinical patterns of infection depend on the way and the extent to which fungi colonize the nail: - In distal subungual onychomycosis (DSO), the most common type, fungi reach the nail from the hyponychium and colonize the nail bed; - In proximal subungual onychomycosis (PSO), fungi penetrate the nail matrix via the proximal nail fold and colonize the deep portion of proximal nail plate; - In white superficial onychomycosis (WSO), fungi are localized on the nail plate surface; Some fungi can produce melanin and cause longitudinal melanonychia. These include certain moulds: S. dimidiatum, A. alternata, Wangiella dermatitidis, and Microascus cirrosus (syn. M.desmosporus), and Trichophyton rubrum var. nigricans. Nail plate dermoscopy In distal subungual onychomychosis, dermoscopy is useful to better delimitate proximal progression of the infection and detect subclinical streaks (Figure 5.4). In white superficial onychomychosis, the nail plate presents irregular, white-to-yellowish patches of different size and shape. The surface of these areas is opaque with superficial and peripheral scaling. At high magnification (50X to 70X) it is possible to detect subclinical spotted lesions. In onychomycosis due to fungi that produce melanin, dermoscopy reveals a homogenous, brown-to-black, pigmented band that is devoid of visible melanin inclusions, and thus helps to correctly identify hyperchromia of nonmelanocytic origin.(15) Subungual Hemathoma Subungual hematomas are common nail bed injuries caused by trauma to the fingers or toes. The affected nail shows a patchy or diffuse pigmentation that migrates distally with nail growth. Hemathoma does not exclude malignancy as patients with melanoma of the nail unit may experience spontaneous bleeding.

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tosti, piraccini, and de farias

Figure 5.4  Onychomycosis. Nail plate dermoscopy shows the white–yellow streaks and is useful to establish degree of proximal progression (x20).

Figure 5.6  Onychopapilloma. Nail plate dermoscopy shows a pale red longitudinal band extending from the proximal nail fold to the distal edge. The band contains a longitudinal, darkbrown stria (x20). Nail plate dermoscopy The nail plate shows longitudinal white lines that correspond to the channels that contain the tumor projections. The proximal part of the tumor shows purple-to-brown splinter hemorrhages. Distal edge of the nail plate dermoscopy Dermoscopy of the distal edge of the nail plate is pathognomonic, as would show small woodworm-like cavities within the nail plate. Onichopapilloma Onychopapilloma is clinically characterized by longitudinal erythronychia, which, in some patients, is associated with hemorrhagic longitudinal lines.(18) The distal portion of the nail bed presents a keratinized expansion that often produces a fissure in the distal nail plate.

Figure 5.5  Hemathoma. Nail plate dermoscopy shows an irregular area, purple to brown in color, with round, red spots at the periphery and a “filamentous” distal end (x20). Nail plate dermoscopy Blood deposition appears as a dark band or an irregularly shaped purple to brown–black area. It is typical to see round, dark-red spots at the periphery and a “filamentous” distal end (Figure 5.5). Nail Tumors Onichomatrichoma Onychomatrichoma is a benign tumor of the nail matrix that develops within the nail plate. The nail is thickened and presents an increased lateral overcurvature. The nail plate overlying the tumor shows a yellow discoloration and multiple splinter hemorrhages.(16) This tumor can occur both in fingernails and toenails and has no sex prevalence.(17)

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Nail plate dermoscopy The nail plate presents a homogeneous, pale red, longitudinal band extending from the proximal nail fold to the distal edge. The proximal border of the band has a characteristic convex shape and its distal part may appear white because of onycholysis. The band may contain one or more longitudinal, dark red-to-black streaks that correspond to splinter hemorrhages (Figure 5.6). The distal nail plate usually presents longitudinal splitting and a wedge-shaped notch. Distal edge of the nail plate dermoscopy Shows the small subungual keratotic mass that often contains hemorrhagic vessels (Figure 5.7). Pyogenic granuloma Pyogenic granuloma is a common, acquired, benign vascular lesion. It usually presents as a solitary, rapidly growing, papule that bleeds easily after minor trauma. It occurs more often on

nail diseases

Figure 5.7  Onychopapilloma. Dermoscopy of the distal edge of the nail plate shows a keratotic nail bed expansion with some brown tiny spots that correspond to hemorrhages (x20).

Figure 5.8  Glomous tumor. Nail plate dermoscopy of shows an irregular reddish area with longitudinal filamentous projections (x20).

the fingers, where it may have a periungual or a subungual location. Pyogenic granuloma of the toes may be subungual. Differential diagnosis of solitary lesions should always take in account amelanotic melanoma. The dermoscopic examination of the lesion shows a reddish homogeneous area that often presents a white collarette at the periphery. White lines similar to a double rail may intersect older lesions. Ulceration and hemorrhagic crusts are typically seen in longstanding lesions.(19)

longitudinal melanonychia (LM). Pigmented lesions in the nail bed usually do not cause LM and are viewed through the nail as grayish-brown or black spots. Nail pigmentation may be caused by melanocytic activation or by benign or malignant melanocyte hyperplasia. Melanonychia is the first symptom of nail melanoma in most cases.

Warts Warts are the most common benign tumor of the nail unit and occur more frequently in children and young adults as well as in patients who are immunocompromized.(20) Dermoscopy shows black dots corresponding to vessels within the keratotic lesion. Glomus tumor Glomus tumor is a rare benign tumor that characteristically causes severe pain and increases in severity, which temperature changes and pressure. The lesion may be barely visible as a red violaceous patch in the nail bed. Other clinical signs include erythronychia, distal onycholysis, and an increase in the Lovibond’s angle.(21) Nail plate dermoscopy It is useful to detect subclinical lesions that are seen as a reddish irregular area of variable size that may contain teleangiectasic vessels (Figure 5.8). Melanonychia The term melanonychia describes the presence of melanin in the nail plate. Most commonly, melanonychia appears as a longitudinal, brown-to-black band of nail pigmentation,

Melanocyte activation Causes of nail matrix melanocyte activation include drugs and postinflammatory, traumatic, systemic, and neoplastic nail disorders. Transverse melanonychia is always due to melanocytic activation. Melanocyte hyperplasia Melanocytic hyperplasia is defined as an increase in the number of nail matrix melanocytes. Benign melanocytic hyperplasia can be subdivided into lentigo when nests are absent or nevus when at least one nest is present. Malignant melanocytic hyperplasia includes in situ and invasive melanoma of the nail apparatus. Nail Matrix Nevi Nevi can be congenital or acquired. The nail presents one or more longitudinal pigmented bands varying in size from few millimeters to the whole nail width and light brown to black in color. Melanoma Clinical presentation depends on the site of origin, whether pigmented or not. Nail matrix melanoma: usually causes a band of longitudinal melanonychia.(22, 23) The nail plate may present a fissure or a split corresponding to the band, indicating compression or destruction of the nail matrix epithelium by the melanoma.

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tosti, piraccini, and de farias

Figura 5.9  Drug-induced melanocyte activation. Nail plate dermoscopy shows a grayish background with thin, gray, regular, longitudinal, parallel lines (x20).

Figure 5.11  Melanoma. Nail plate dermoscopy shows a darkbrown band with irregular longitudinal lines. Note irregularities in thickness, spacing, and color (x20). In traumatic melanocyte activation, tiny dark red-to-brown spots caused by splinter hemorrhages may also be seen. Bands with a brown background are indicative of melanocyte hyperplasia . These bands vary in color from light brown to black. (A)

(B)

Figure 5.10  Nevus. Nail plate dermoscopy shows a brown band with regular, longitudinal, parallel lines (x20). Nail bed melanoma: causes a pigmented or a nonpigmented (25% to 30% of cases) subungual nodule. Nail bed ulceration and bleeding occur when the tumor grows. Although nail plate dermoscopy has been proposed as an effective tool to help the clinician in the differential diagnosis of nail pigmentation, experience in this field is still very limited and specificity and sensitivity of the technique have not been validated.(24) Nail plate dermoscopy The following dermoscopic patterns have been reported using nail plate dermoscopy in melanonychia of different etiology.(1, 25–27) Bands with a grayish background are indicative of melanocyte activation. The color of these bands vary from light to dark gray and the band often contains thin, gray, regular, longitudinal, parallel lines (Figure 5.9).

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Bands due to nail matrix nevi usually have sharply delimited lateral borders and contain thin, regular, longitudinal parallel lines that are brown or black in color. In children, black DOTS similar to those described in skin melanocytic lesions are frequently observed (Figure 5.10). Bands due to nail matrix melanoma have blurred lateral margin and contain longitudinal lines of different thickness and color with disruption of parallelism (Figure 5.11).

Distal edge of the nail plate dermoscopy With this technique, we can identify whether the lesion is localized in the proximal or in the distal matrix. A pigmentation of the ventral nail plate originates from the distal matrix and a pigmentation of the dorsal nail plate originates from proximal nail matrix. Hyponychium and proximal nail-fold dermoscopy Micro-Hutchinson’s sign: periungual pigmentation, not detected with naked eye, but detected with the dermoscopy. It is an extension of brown–black pigmentation from the matrix and nail bed to the surrounding tissues and represents the radial growth phase of subungual melanoma (Figure 5.12). The presence of micro-Hutchinson’s sign is very indicative but not exclusive of melanoma, as congenital nevi often involve the nail folds and the hyponychium. Very dark bands are often associated with pigmentation of the cuticle due to the fact that the dark pigmentation on the nail plate is visible through the transparent nail fold. This is referred as pseudo Hutchinson’s sign and is not a sign of malignancy.

nail diseases

Figure 5.12  Melanoma. Dermoscopy of the hyponychium shows the micro-Hutchinson’s sign (x20). Nail bed and matrix dermoscopy Intraoperative dermoscopy permits direct visualization of the melanocytic lesion. In melanocyte activation, intraoperative dermoscopy reveals gray lines. In melanocyte hyperplasia, it shows brown lines that are regular and associated with globules in nevi but irregular in melanoma (Hirata unpublished). REFERENCES   1. Thomas L, Dalle S. Dermoscopy provides useful information for the management of melanonychia striata. Dermatol Ther 2007; 20: 3–10.   2. Braun RP, Baran R, Saurat JH, Thomas L. Surgical Pearl: dermoscopy of the free edge of the nail to determine the level of nail plate pigmentation and the location of its probable origin in the proximal or distal nail matrix. J Am Acad Dermatol 2006; 55: 512–3.   3. Hirata SH, Yamada S, Almeida FA et al. Dermoscopy of the nail bed and matrix to assess melanonychia striata. J Am Acad Dermatol 2005; 53: 884–6.   4. Hirata SH, Yamada S, Almeida FA et al. Dermoscopic examination of the nail bed and matrix. Int J Dermatol 2006; 45: 28–30.   5. Iorizzo M, Dahdah M, Vincenti C, Tosti A. Videodermoscopy of the hyponychium in nail bed psoriasis. J Am Acad Dermatol 2008; 58: 714–5.   6. Ohtsuka T, Yamakage A, Miyachi Y. Statistical definition of nailfold capillary pattern in patients with psoriasis. Int J Dermatol 1994; 33: 779–82.   7. Zaric D, Clemmensen OJ, Worm AM, Stahl D. Capillary microscopy of the nail fold in patients with psoriasis and psoriatic arthritis. Dermatologica 1982; 164: 10–4.   8. Bhushan M, Moore T, Herrick AL, Griffiths CEM. Nailfold video capillaroscopy in psoriasis. Br J Dermatol 2000; 142: 1171–6.

  9. Blockmans D, Beyens G, Verhaeghe R. Predictive value of nailfold capillaroscopy in the diagnosis of connective tissue diseases. Clin Rheumatol 1996; 15: 148–53. 10. Cutolo M, Sulli A, Secchi ME, Paolino S, Pizzorni C. Nailfold capillaroscopy is useful for the diagnosis and followup of autoimmune rheumatic diseases. A future tool for the analysis of microvascular heart involvement? Rheumatology 2006; 45: 43–6. 11. Cutolo M, Matucci Cerinic M. Nailfold capillaroscopy and classification criteria for systemic sclerosis. Clin Exp Rheumatol 2007; 25: 663–5. 12. Bergman R, Sharony L, Schapira D et al. The handheld dermatoscope as a nail-fold capillaroscopic instrument. Arch Dermatol 2003; 139: 1027–30. 13. Klyscz T, Bogenschutz O, Junger M, Rassner G. Microangiopathic changes and functional disorders of nail fold capillaries in dermatomyositis. Hautarzt 1996; 47: 289–93. 14. Keberle M, Tony HP, Jahns R et al. Assessment of microvascular changes in Raynaud’s phenomenon and connective tissue disease using colour Doppler ultrasound. Rheumatology 2000; 39:1206–13. 15. Braun RP, Baran R, Le Gal FA et al. Diagnosis and management of nail pigmentations. J Am Acad Dermatol 2007; 56: 835–47. 16. Faylor J, Baran R, Perrin CH et al. Onychomatricoma with misleading features. Acta Dermatol Venereol 2000; 80: 370–2. 17. Piraccini BM, Antonucci A, Rech G et al. Onychomatricoma: first description in a Child. Pediatr Dermatol 2007; 24: 46–8. 18. Baran R, Perrin C. Longitudinal erythronychia with distal subungual keratosis: onychopapilloma of the nail bed and Bowen’s disease. Br J Dermatol 2000; 143: 132–5. 19. Zaballos P, Llambrich A, Cuellar F, Puig S, Malvehy J. Dermoscopy of pyogenic granuloma. Br J Dermatol 2006; 154: 1108–11. 20. Tosti A, Piraccini BM. Warts of the nail unit: surgical and nonsurgical approaches. Dermatol Surg 2001: 27: 235–9. 21. Dominguez Cherit J, Chanussot Deprez C, Maria Sarti H et al. Nail unit tumors: a study of 234 patients in the dermatology department of the ‘‘Dr Manuel Gea Gonzalez’’ general hospital in Mexico City. Dermatol Surg 2008; 34:1363–71. 22. Kato T, Suetake T, Sugiyama Y et al. Epidemiology and prognosis of subungual melanoma in 34 Japanese patients. Br J Dermatol 1996; 134: 383–7. 23. Thai KE, Young R, Sinclair RD. Nail apparatus melanoma. Australas J Dermatol 2001; 42: 71–81. 24. Tosti A, Piraccini BM, Farias DC. Dealing with melanonychia. Semin Cutan Med Surg 2009; 28(1): 49–54. 25. Ronger S, Touzet S, Ligeron C et al. Dermatoscopic examination of nail pigmentation. Arch Dermatol 2002; 138: 1327–33. 26. Andre J, Lateur N. Pigmented nail disorders. Dermatol Clin 2006; 24: 329–39. 27. Lateur N, Andre J. Melanonychia diagnosis and treatment. Dermatol Ther 2002; 15: 131–41.

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6.1a Vascular pattern under videodermatoscopy observation Giorgio Filosa, Rossella De Angelis, and Leonardo Bugatti

Definition of Psoriasis Psoriasis is a papulosquamous disease with variable morphology, distribution, severity, and course (1), affecting about 1.5% of the Caucasian population.(2) Psoriatic lesions are sharply demarcated, red in color, and slightly raised, with silverwhitish scales.(2) The microscopic alterations of psoriatic plaques include infiltration of immune cells in the dermis and epidermis, dilatation, and increase in the number of blood vessels in the upper dermis, and extremely thickened epidermis with keratinocyte differentiation.(2) The immune system plays an important role in the pathogenesis of psoriasis, and there is strong evidence that activated T cells make the first move in the inflammatory reaction. Recently made discoveries regarding T cell populations, dendritic cells, macrophages, keratinocyte signal transduction, and novel cytokines, including interleukin (IL)-22, IL-23, and IL-20, suggest that the pathogenesis of psoriasis consists of distinct subsequent stages in which different cell types have a governing role.(2) Angiogenesis and Psoriasis The microvasculature is of pathologic relevance to psoriasis and excessive dermal angiogenesis is a characteristic feature. Until now, it is still a matter of debate whether the early changes in psoriasis are referred to the epidermis or to the vasculature. There is evidence that epidermal hyperplasia cannot occur without vascular proliferation, which is represented as an abnormal growth of endothelial cells in the microvessels around the perilesional skin.(3) Also, the existence of dilatation and increased tortuosity of dermal capillary loops before dermal hyperplasia is demonstrated.(4) The starting event of psoriasis seems to be the initial vasodilatation that is accompanied by exudates of inflammatory cells and serum in the papilla.(4) Nevertheless, some authors have provided evidence that keratinocyte-derived proangiogenic cytokines such as IL-1 and vascular endothelial growth factor (VEGF) are increased in psoriatic epidermis.(5, 6) Furthermore, the fact that epidermal changes may initiate lesions is substantiated by the observation that even nonlesional psoriatic skin showed an enhanced production of cytokines and appeared to be primed for leukocyte adherence.(7) There is considerable support about the role of TNF-α in expansion of the dermal microvasculature in psoriasis. (5, 8–11) TNF-α is recognized in raising the expression of adhesion molecules and vascular cell adhesion molecules on keratinocytes (11) and in inducing the VEGF production, which stimulates endothelial mitogenic activity in the skin. (5) The exhibition of adhesion molecules and chemokines results in the enrolment of additional inflammatory cells

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to the plaque. The recruited cells can then produce further TNF-α and γ-interferon, potentially amplifying local inflammation and keratinocyte proliferation.(11) During plaque formation, the superficial papillary micro­ vessels undergo elongation, thus widening and tortuosity. These blood vessels must, therefore, play an important but probably secondary role in the pathogenesis of clinical lesions in psoriasis.(12) Videodermatoscopy and videocapillaroscopy in psoriasis The cutaneous microcirculation is organized as two horizontal plexuses. One is situated 1.5 mm below the skin surface and the other at the dermal–subcutaneous junction and connected by ascending arterioles and descending venules. From the upper layer, arterial capillaries rise to form the dermal capillary loops that represent the nutritive component of the skin circulation.(13) In psoriasis, the overall organization of the dermal microcirculation is the same as in normal skin. However, it displays many anatomical and physiological changes, mainly described in the intrapapillary portion of the loops. Each papilla continues to be served by a single capillary, but the limbs are twisted along their major axis.(12) The outside endothelial diameters of the loops are also wider (6–17 μm) than the corresponding segments in normal skin (3.5–6 μm).(12) The papillary microvessel changes are homogeneously distributed throughout clinical lesions.(12) A comprehensive evaluation of the cutaneous microvascular structure is possible using different tools, including videocapillaroscopy (VCP) and/or high magnification videodermatoscopy (VD). VD is a noninvasive technique, which consists of in vivo skin observation with a video camera that allows magnifications ranging from x4 to x1,000.(14) Visibility of vessels strongly depends on the method of examination. The glass plate of a videodermatoscope is placed carefully upon the skin, to reach a minimal compression of capillaries, which is then easily visualized. The application of a conspicuous amount of high-viscosity gel is advisable and appropriate. VCP is a widely used method to study the morphology and dynamics of microcirculation, by means of a computerized video microscope, equipped with optic contact probes and magnifications ranging between x50 and x500. A drop of cedar oil is generally used to improve capillary visibility. An appropriate knowledge of the vascular pattern in normal skin is a prerequisite for recognizing the psoriasis microvessels, which appear different in shape and morphology. In normal skin observed by VD, vessels come out as tiny red dots, regularly

vascular pattern under videodermatoscopy observation

Figure 6.1  Videocapillaroscopy, x 200 magnification. Normal skin: “comma-like” appearance of the capillary loops.

Figure 6.2  Videodermatoscopy, x70 magnification. Psoriatic skin: “bushy” capillaries. dispersed over the skin surface (15); in glabrous skin, these red dots are aligned along the crests of the ridges. The upper dermal plexus is visible as a coarse network of broader vessels.(15) Under VCP observation, especially after x100 and x200 magnification, capillary loops appear with the major axis running perpendicular to the skin surface, and are, therefore, characterized by a comma-like appearance inside the dermal papilla (Figure 6.1). The normal capillaroscopic picture differs according to the body areas: in some districts, such as the dorsum of the hand, and not all of the capillaries run perpendicular to the skin surface, and visibility is not limited to the apical portion; in the forehead; for example, all capillaries run parallel to the skin surface, with a network appearance. The evidence of the deep venular subpapillary plexus depends on the skin transparency.

Vascular patterns in psoriasis A few studies in the past have described some dermoscopic features of psoriasis as a homogeneous arrangement of vascular structures (Figure 6.2) (16, 17), and systematic effort to identify the dermoscopic features of the psoriatic microvasculature are only recently available.(4, 18) A latest study including 300 lesions from 255 patients with solitary, red, scaly patches or plaque features tried to describe the most significant morphologic findings seen on VD, in order to formulate a diagnostic model based on these characteristics. For psoriasis, the significant features identified were a homogeneous vascular pattern, red dots, and light-red background, yielding a diagnostic probability of 99% if all three features were present.(18) Red dots were seen in all examples of psoriasis studied (Figure 6.3). The presence of arborizing vessels was the most valuable negative feature in differentiating psoriasis from basal-cell carcinoma and intraepidermal carcinoma.(18) In hair and scalp disorders, the observation of twisted loops in both psoriasis and psoriasis-like forms of seborrheic dermatitis reflect true overlap disease, as captured by the term sebopsoriasis.(19) The capillaroscopic picture of plaque psoriasis has been extensively described in literature (10, 20–22), reporting that examination of the untreated psoriatic skin shows many uniformly arranged tortuous and dilated capillaries, appearing as “bushy,” with a highly distinctive pattern (Figure 6.4, Figure 6.5). Moreover, the VCP technique allows the obtaining of additional information about distribution, morphology, and density of capillaries in the psoriatic plaques. Corresponding to the perilesional skin, capillary loops show a parallel course with respect to the skin surface and with a lengthened apex directed toward the marginal zone of the lesion (10) (Figure 6.6). The number of capillary loops per area unit seems to increase in perilesional skin compared to lesional skin (42.8 ± 4.05 vs. 29.73 ± 3.53).(12) A minimal shift of the probe from the perilesional to normal-appearing skin allows the visualization of capillary loops that gradually become perpendicular. These studies lead to the recognition of a critical pathogenetic role of angiogenesis in sustaining and spreading out of the psoriasis lesions. Therapy monitoring There are a number of studies that report morphological modifications and loop changes after local and systemic treatments, which goes to show that the role of VD and VCP in psoriasis for in vivo therapy monitoring is a subject pursued with growing interest.(17, 20, 23, 24) VD may help in revealing that the overuse of topical steroids results in the appearance of clinically imperceptible but dermoscopically evident “red lines” (“linear telangiectasias”) in the treated plaques/skin adjacent (p < 0.03), before the atrophy becomes permanent.(17) VD evaluation at the fingernail hyponichium (between x20 and x70) in patients with nail-bed psoriasis after a 3-month

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filosa, angelis, and bugatti

Figure 6.3  Videodermatoscopy, x50 magnification. Psoriatic skin: red dots aligned along the dermatoglyphics.

Figure 6.4  Videocapillaroscopy, x200 magnification. Psoriatic skin showing many uniformly arranged tortuous. course of calcipotriol treatment showed a significant decrease in the number of capillaries, especially for patients with lichen planus.(24) By means of a VD with x200 magnification, the grossly dilated and tortuous aspect of the untreated psoriatic capillaries appeared to be reduced in five patients after the application of tacalcitol ointment 4 µg/g, with a marked simplification of the coiling of the capillary ball occurring after 3 weeks in 2 cases.(20) A 3-month treatment course with cyclosporine (4 mg/ kg/day) produced a statistical reduction in microcirculatoy alterations, as assessed by digital capillaroscopy (x300 magnification), and in 70% of the subjects treated, especially in the

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Figure 6.5  Videocapillaroscopy, x200 magnification. Psoriatic skin showing many uniformly arranged dilated capillaries.

Figure 6.6  Videocapillaroscopy, x200 magnification. Psoriatic perilesional skin: capillary loops show a parallel course, with respect to the skin surface, with a lengthened apex directed toward the marginal zone of the lesion. dimension of the capillaries (p = 0.0005).(23) Modification of the capillaroscopic aspects took place in a progressive manner in all the patients and according to the length of the therapy.(23) Investigation of microcirculation by capillaroscopy in psoriatic skin after biologic therapies had brought to light considerable information about the role of angiogenesis. A single infusion of infliximab induced significant morphological changes to the capillary loops in psoriatic lesions, which appeared less tortuous and dilated, showing an evident reduction in shape and size (25) (Figure 6.7, Figure 6.8). The number of “bushy” loops was manifestly reduced, which suggests

vascular pattern under videodermatoscopy observation

Figure 6.7  Videocapillaroscopy, x200 magnification. Untreated psoriatic skin.

Figure 6.8  Videocapillaroscopy, x200 magnification. The number of “bushy” loops are manifestly reduced, after infliximab treatment. that infliximab may achieve its results, in part by targeting the angiogenetic properties of TNF-α As comprehensive studies are required to further establish the modalities of action of TNF-α blockers in reducing psoriatic lesions (25, 26), both VD and VCP represent reproducible techniques that may allow an easy and accurate assessment of microvascular modifications of the psoriatic skin after topic and systemic therapies. References   1. Langley RG, Krueger GG, Griffiths CE. Psoriasis: epidemiology. Clinical features and quality of life. Ann Rheum Dis 2005; 64(Suppl 2): 18–23.   2. Sabat R, Philipp S, Höflich C et al. Immunopathogenesis of psoriasis. Exp Dermatol 2007; 16: 779–98.

  3. Folkmann J. Angiogenesis in cancer, vascular, rheumatoid and other diseases. Nat Med 1995; 1: 27–31.   4. Creamer JD, Barker JNWN. Vascular proliferation and angiogenic factors in psoriasis. Clin Exp Dermatol 1995; 20: 6–9.   5. Detmar M, Brown LF, Claffey KP et al. Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 1994; 180: 1141–6.   6. Debets R, Hegmans JPJJ, Troost RJJ et al. Enhanced production of biologically active interleukin-1α and interleukin-1β by psoriatic epidermal cells ex vivo: evidence of increased cytosolic interleukin-1β levels and facilitated interleukin-1 release. Eur J Immunol 1995; 25: 1624–30.   7. Prens EP, Debets R. Reply to the letter of Li et al. J Am Acad Dermatol 1996; 1020–1.   8. Creamer D, Allen MH, Sousa A et al. Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis. Br J Dermatol 1997; 136: 859–65.   9. Ettehadi P, Greaves W, Wallach D et al. Elevated tumor necrosis factor-alpha (TNF-α) biological activity in psoriatic skin lesions. Clin Exp Immunol 1994; 96: 146–51. 10. De Angelis R, Bugatti L, Del Medico P et al. Videocapillaroscopic findings in the microcirculation of the psoriatic plaque. Dermatology 2002; 204: 236–9. 11. Krueger JG. The immunologic basis for the treatment of psoriasis with new biologic agents. J Am Acad Dermatol 2002; 46: 1–23. 12. Hern S, Mortimer PS. In vivo quantification of microvessels in clinically uninvolved psoriatic skin and in normal skin. Br J Dermatol 2007; 156: 1224–9. 13. Braverman IM. The cutaneous microcirculation. J Invest Derm Symp Proc 2000; 5: 3–9. 14. Micali G, Nardone B, Scuderi A, Lacarrubba F. Videodermatoscopy enhances the diagnostic capability of palmar and/or plantar psoriasis. Am J Clin Dermatol 2008; 9: 119–22. 15. Kreusch JF. Vascular patterns in skin tumors. Clin Dermatol 2002; 20: 248–54. 16. Vasquez-Lopez F, Manjon-Haces JA, Maldonado-Seral C et al. Dermoscopic features of plaque psoriasis and lichen planus: new observation. Dermatology 2003; 207: 151–6. 17. Vasquez-Lopez F, Marghoob AA. Dermoscopic assessment of long-term topical therapies with potent steroids in chronic psoriasis. J Am Acad Dermatol 2004; 51: 811–3. 18. Pan Y, Chamberlain AJ, Bailey M et al. Dermatoscopy aids in the diagnosis of the solitary red scaly patch or plaquefeatures distinguishing superficial basal cell carcinoma, intraepidermal carcinoma and psoriasis. J Am Acad Dermatol 2008; 59: 268–74. 19. Ross EK, Vincenzi C, Tosti A. Videodermoscopy in the evaluation of hair and scalp disorders. J Am Acad Dermatol 2006; 55: 799–806.

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filosa, angelis, and bugatti 20. Strumia R, Altieri E, Romani I et al. Tacalcitol in psoriasis: a video-microscopy study. Acta Derm Venereol (Stock) 1994; Suppl 186; 85–7. 21. Fuga GC, Marmo W, Acierno F et al. Cutaneous microcirculation in psoriasis. A videocapillaroscopic morphofunctional study. Acta Derm Venereol (Stock) 1994; Suppl 186: 138. 22. Okada N, Nakatani S, Ozawa K et al. Video macroscopic study of psoriasis. J Am Acad Dermatol 1991; 25: 1077–8. 23. Stinco G, Lautieri S, Valente F, Patrone P. Cutaneous vascular alterations in psoriatic patients treated with cyclosporine. Acta Derm Venereol 2007; 87: 152–4.

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24. Iorizzo M, Dahadah M, Vincenzi C, Tosti A. Videodermoscopy of the hyponychium in nail bed psoriasis. J Am Acad Dermatol 2008; 58: 714–5. 25. De Angelis R, Gasparini S, Bugatti L, Filosa G. Early videocapillaroscopic changes of the psoriatic skin after antitumour necrosis factor-alpha treatment. Dermatology 2005; 210: 241–3. 26. Nickoloff BJ, Nestle FO. Recent insights into the immunopathogenesis of psoriasis provide new therapeutic opportunities. J Clin Invest 2004; 113: 1664–75.

6.1b Histopathological correlations †

Daniele Innocenzi, Maria Concetta Potenza, and Ilaria Proietti

Introduction Psoriasis is a common, chronic, relapsing, inflammatory, and hyperproliferative skin disorder with genetic predisposition and multifactorial pathogenesis.(1) There is not a typical clinical and histological picture of psoriasis, and there is no standard treatment available.(2) The classical presentation of this skin disorder is plaques psoriasis, and, as this form is usually easy to identify, histopathologic examination is generally not required. In this case, the diagnosis is made on clinical grounds by a “visually literate” clinician.(3) However, all dermatologists recognize the difficulty in identifying the disease in many instances, especially when the appearance is not typical. Psoriasis is the prototype of a group of cutaneous disorders (psoriasiform dermatitis) that show psoriasiform epidermal hyperplasia, defined as regular elongation of the rete ridges with preservation of the rete ridge–dermal papillae pattern.(4) Other histologic clues to the diagnosis of psoriasis include more dilated and tortuous papillary blood vessels, neutrophils within the epidermis associated with spongiosis (spongiform pustules), neutrophils beneath the cornified layer (subcorneal pustules), neutrophils within the cornified and parakeratotic horn, hypogranulosis, and more keratinocytic mitotic figures above the basal-cell layer.(5–6) Plaques Psoriasis In its classical presentation (plaques psoriasis), the disease is characterized by well-circumscribed, reddish, and scaly papules and plaques typically located on elbows, knees, scalp, and other cutaneous sites.(2) Psoriasis is characterized by abnormal

keratinocytic proliferation resulting in thickening of epidermis (producing well-circumscribed clinical plaques) and stratum corneum (producing scales).(7) As compared with normal skin, psoriatic lesions show up to 27 times the mitotic activity, a 12-fold decrease in the cell-cycle time of basal and suprabasal keratinocytes, and a greater than 7-fold increase in the epidermis turnover time (7 days in psoriatic skin vs. 56 days in normal skin). There is also an increase in the apoptotic rate, in concert with a reduction of bcl-2 (an antiapoptotic protein) expression in basal cells. In psoriatic skin, basal keratinocytes maintain expression of K5 and K14 (the keratins typical of basal keratinocytes in normal skin), whereas K1 and K10 (the keratins typical of suprabasal cells in normal skin) are replaced by socalled hyperproliferation-associated keratins, K6 and K16, in addition to K17.(8) We must also consider the “histodynamic” of the psoriatic plaque. Psoriasis shows lesions with different clinicopathological aspect according to the moment in which the lesion is taken. Clinically, in the psoriatic plaque, we can observe essentially three phases: •• A nonspecific initial phase characterized by the presence of erythematous edematous plaques, in rapid evolution toward the other phases. •• The intermediate or steady-state phase (divided in early and late steady state), which, for us, is the most interesting because this is the moment when we visit the patients.

Figure 6.9  Clinical and histological features of the initial phase.

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innocenzi, potenza, and proietti

Figure 6.10  Clinical and histological features of the early steady-state phase.

•• The final erythematodesquamative phase (phase of resolution) is usually observed after successful treatments and representing the phase of progressive resolution and clearing. These different clinical aspects can coexist in the same patient because, psoriasis plaques not always show synchronous development. Clinical polymorphism correspond to different and specific histological stages. •• The initial phase, clinically characterized by erithematous and edematous lesions, is aspecific, fleeting, and quickly slips toward following steps. The earliest changes can be nonspecific, with a preponderance of dermal changes, including a sparse, superficial, and perivascular T-lymphocytic infiltrate (Figure 6.9). •• This intermediate phase, a well-developed plaque phase, can be divided from an histopathological point of view in. •• Early steady-state phase, which clinically corresponds to plaque elevation, is characterized by acanthosis with regular elongation of the rete ridges, thickening in their lower portion, thinning of the suprapapillary epidermis with occasional presence of small spongiform pustules, pallor of the upper layers of the epidermis, diminished to absent granular layer, confluent parakeratosis, and presence of Munro microabscesses (Figure 6.10). It is possible to find elongation and edema of the dermal papillae and dilated and tortuous capillaries. It is still not entirely clear what causes these changes in plaque skin. One possibility is that in psoriasis the dermal microvessels may receive a specific trigger/stimulus. There are now a considerable evidences indicating that angiogenesis plays a role in triggering the microcirculatory changes in psoriatic skin.(9, 10) Elongation and

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Figure 6.11  Videodermatoscopy of dwarf handles and bush vases in a psoriatic plaque at early steady-state phase (X200).

tortuosity of the dermal papillary vessels are not, however, exclusive to psoriasis. Also, an increase in capillary width may be seen in other skin conditions such as port wine stains, eczema, lichen planus, and dermatitis herpetiformis.(11) The striking difference in psoriasis is that the papillary vessel changes are dramatic and uniformly distributed throughout clinical lesions.(9) The combination of superficial dermal capillaries and overlying suprapapillary epidermal thinning is responsible for the erythematous appearance of psoriatic lesion and the Auspitz sign (pinpoint bleeding points on removal of the scale). This stage corresponds to the increase in number of dwarf handles or bush vases at videodermatoscopy (Figure 6.11).

histopathological correlations

Figure 6.12  Clinical and histological features of the late steady state.

Figure 6.13  Videodermatoscopy of a psoriatic plaque at late steady stage (X200).

•• Late steady-state phase clinically corresponds to fully developed clinical plaques because it shows marked epidermal hyperplasia. This phase is histologically characterized by club-shaped thickening of the lower rete pegs with coalescence of these in some areas. Lesions show silvery scales as result of the ortokeratosis of corneus and an intact granular layer with parakeratosis. Exocytosis of inflammatory cells is usually mild, and there is some thickening of the suprapapillary plates and fine fibrillary collagen (Figure 6.12). This stage relates to the presence of white-silvery images on a red background during videodermatoscopy (Figure 6.13). •• The phase of resolution corresponds to resolving or treated plaques of psoriasis (Figure 6.14). It initially shows progressive reduction in the presence of neutrophils within the stratum corneum and parakeratosis, with reformation of the granular zone and orthokeratosis. The epidermal hyperplastic changes resolve later.

Figure 6.14  Clinical and histological features of the resolution phase.

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innocenzi, potenza, and proietti There may be residual, mild, superficial, dermal fibrosis with persistence of papillary dermal capillary dilatation and tortuosity as the only histopathologic clues to this disease. The clinical resolution of lesions is associated with the abnormal-to-normal return of plaques’ micro­ vessels.(12) As the plaques regress, they often start to clear in the center, with a persistent marginal activity at the borders, which confers an annular or polycyclic appearance. Hypopigmentation is usually associated with clearing (psoriatic leukoderma). These different aspects of the psoriatic plaque correspond to different biochemical events that occurs in the psoriatic lesion. For that reason we understand that making a correct diagnosis and deciding the appropriate treatment for different patients is not so easy; in order to better chose the therapy, it would be really helpful to understand how the single plaque responds to the treatment depending on its histopathological phase. REFERENCES   1. Gudjonsson JE, Elder JT. Psoriasis: epidemiology Clin Dermatol 2007; 25(6): 535–46.   2. Naldi L, Gambini D. The clinical spectrum of psoriasis. Clin Dermatol 2007; 25(6): 510–8.   3. Jackson R. The importance of being visually literate. Observations on the art and science of making a morphological diagnosis in dermatology. Arch Dermatol 1975; 111: 632–6.

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  4. Murphy M, Kerr P, Grant-Kels JM. The histopathologic spectrum of psoriasis.Clin Dermatol 2007; 25(6): 524–8.   5. Cox AJ, Watson W. Histological variations in lesions of psoriasis. Arch Dermatol 1972; 106: 503–6.   6. Gordon M, Johnson WC, Burgoon Jr CF. Histopathology and histochemistry of psoriasis: II. Dynamics of lesions during treatment. Arch Pathol 1967; 84: 443–50.   7. Ragaz A, Ackerman AB. Evolution, maturation, and regression of lesions of psoriasis. New observations and correlation of clinical and histologic findings. Am J Dermatopathol 1979; 1: 199–214.   8. Leigh IM, Navsaria H, Purkis PE et al. Keratins (K16 and K17) as markers of keratinocyte hyperproliferation in psoriasis in vivo and in vitro. Br J Dermatol 1995; 133: 501–11.   9. Creamer D, Allen MH, Sousa A, Poston R, Barker JN. Localization of endothelial proliferation and microvascular expansion in active plaque psoriasis. Br J Dermatol 1997; 136(6): 859–65. 10. Bacharach-Buhles M, el Gammal S, Panz B, Altmeyer P. In psoriasis the epidermis, including the subepidermal vascular plexus, grows downwards into the dermis. Br J Dermatol 1997; 136(1): 97–101. 11. Braverman IM. The role of blood vessels and lymphatics in cutaneous inflammatory processes: an overview. Br J Dermatol 1983; 109(25):89–98. 12. Hern S, Mortimer PS. In vivo quantification of microvessels in clinically uninvolved psoriatic skin and in normal skin. Br J Dermatol 2007; 156(6): 1224–9.

6.1c Palmoplantar psoriasis

Francesco Lacarrubba, Maria Letizia Musumeci, and Giuseppe Micali

The diagnosis of palmar and/or plantar psoriasis is usually uncomplicated, especially when typical anatomic sites are involved. However, in cases with only palmar and/or plantar involvement, it may be troublesome, often requiring skin biopsy with histopathological evaluation. Differential diagnosis includes eczematous dermatitis (allergic, irritative), tinea manuum/ pedis, lichen planus, porokeratosis, pityriasis rubra pilaris, keratodermas, mycosis fungoides, epidermolysis bullosa, syphilis, scabies, and drug reactions. Videotermatoscopy (VD) may be helpful to address the diagnosis of palmoplantar psoriasis in the presence of no readily apparent diagnostic features through the evaluation of superficial vascular structures. VD examination must be performed with the epiluminescence technique, carefully avoiding vessels blanching and applying to the skin the least possible pressure with the contact plate. In normal palmoplantar skin surface, VD examination at X100 to X200 magnification shows the presence of capillary loops linearly arranged along the furrows of dermatoglyphics (Figure 6.15A–6.15B). In palmoplantar psoriasis, the evaluation of the vascular structure by VD shows dilated and tortuous capillaries, homogeneously appearing as “bushy” (1–4) and linearly arranged along the furrows of dermatoglyphics (Figure 6.16A–6.16D). A major limitation in this anatomical site, which may interfere with a reliable VD evaluation, is represented by the frequent presence of excessive hyperkeratosis that may hamper vascular structure analysis; in such cases, VD examination might be performed in residual erythematous areas or after application of keratolytic products (such as 30%–50% urea) for 3 to 4 days.

(A)

The efficacy of VD in recognizing palmoplantar psoriasis has been demonstrated in a series of patients affected by palmar and/ or plantar dermatoses with no otherwise specific diagnostic features.(5) A total of 32 subjects (12 males and 20 females; mean age = 50 years, age range between 20 and 72 years) were enrolled in an open study. Inclusion criteria were the presence of clinically nonspecific, active, and untreated palmar and/or plantar, erythematous, scaly lesions with no other skin involvement. Exclusion criteria were past medical history positive for psoriasis or eczema, pustular psoriasis, presence of comorbid disorders potentially altering microcirculation (diabetes), use of vasodilator drugs, presence of excessively hyperkeratotic lesions, use of systemic and/or topical drugs within 4 and 2 weeks of study entry, respectively. Twenty-two cases presented with palmar lesions only, 7 with plantar involvement; and 3 patients had palmar/plantar localization. A video microscope system, Hi-Scope KH-2,200 [Hirox Co., Tokyo, Japan], equipped with a zoom lens, was used for vascular pattern evaluation that was performed under standard environmental conditions (temperature, humidity). An average of three fields for each lesion was examined with two magnifications, X50 and X200, after covering each field with immersion oil in order to avoid light reflection and thus allowing a good visualization of vascular structures. After VD examination, a skin biopsy from the affected areas was taken from each patient for H&E stain. At the end of the study, VD was able to identify the cases of palmoplantar psoriasis, as later confirmed by histopathological examination, showing in all examined fields at low magnification (X50) the presence of pinpoint-like capillaries linearly arranged along the furrows of dermatoglyphics;

(B)

Figure 6.15A–6.15B  VD examination of normal palmar skin surface: presence of capillary loops arranged linearly along the furrows of dermatoglyphics at X100 (A) and X200 (B) magnifications.

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lacarrubba, musumeci, and micali (A)

(C)

(D)

(B)

Figure 6.16A–6.16D  Plantar psoriasis. A: clinical aspect. B: VD examination shows at X50 magnification the presence of pinpoint-like capillaries arranged linearly along the furrows of dermatoglyphics. C: at X200 magnification, the same capillaries appear dilated and tortuous, with a “bushy” aspect. Insert: normal capillaries at the same magnification (X200). D: bushy capillaries at X400 magnification.

at X200 magnification, the same capillaries appeared dilated and tortuous, with a bushy, homogeneous aspect (Figure 6.17A–6.17B). In the other cases, the diagnosis of psoriasis was excluded; in fact, in some of these patients, VD showed no relevant features at X50

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magnification and a normal capillary pattern at X200 magnification (Figure 6.18A–6.18B), and in the remaining patients it showed the presence of pinpoint-like capillaries at X50 magnification but did not show bushy capillaries at X200 magnification. In these two

palmoplantar psoriasis (A)

(A)

(B)

(B)

Figure 6.17A–6.17B  A: palmar dermatosis with no specific clinical features. B: VD examination showing at X200 magnification the presence of “bushy” capillaries, suggesting a diagnosis of psoriasis, later confirmed by histopathology.

Figure 6.18A–6.18B  A: palmar dermatosis with no specific clinical features: B: VD examination showing at X200 magnification normal capillaries. In this case, a diagnosis of psoriasis was excluded.

last groups, histopathology showed a pattern consistent with a diagnosis of eczematous dermatitis. In conclusion, analysis of superficial vascular pattern by VD represents a promising noninvasive diagnostic tool in palmar and/or plantar localization of psoriasis. For capillary pattern evaluation the use of both low (50X) and high (200X) magnifications is recommended as, in our experience in some subjects, low magnification identified a pinpoint-like vascular pattern that did not correspond to bushy capillaries at higher magnification.

2. Okada N, Nakatani S, Ozawa K, Sato K, Yoshikawa K. Video macroscopic study of psoriasis. J Am Acad Dermatol 1991; 25: 1077–8. 3. Bull RH, Bates DO, Mortimer PS. Intravital video-capillaroscopy for the study of the microcirculation in psoriasis. Br J Dermatol 1992; 126: 436–45. 4. Hern S, Stanton AWB, Mellor RH et al. In vivo quantification of the structural abnormalities in psoriatic microvessels before and after pulsed dye laser treatment. Br J Dermatol 2005; 152: 505–11. 5. Micali G, Nardone B, Scuderi A, Lacarrubba F. Video­ dermatoscopy enhances the diagnostic capability of palmar and/or plantar psoriasis. Am J Clin Dermatol 2008; 9: 119–22.

REFERENCES 1. De Angelis R, Bugatti L, Del Medico P, Nicolini M, Filosa G. Videocapillaroscopic findings in the microcirculation of the psoriatic plaque. Dermatology 2002; 204: 236–9.

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6.1d Psoriatic balanitis

Giuseppe Micali, Maria Rita Nasca, and Francesco Lacarrubba

The term balanitis defines an inflammation of glans penis that may be caused by a wide range of conditions including infectious, neoplastic, and inflammatory dermatoses, and among these, candidiasis, contact dermatitis, erythroplasia of Queyrat, lichen sclerosus, lichen planus, Zoon’s balanitis, and psoriasis. Psoriatic balanitis is clinically characterized by erithematous, nonscaling plaques most commonly located proximally on the glans and under the prepuce.(1) In general, genital psoriasis is part of a more generalized cutaneous disorder. However, in case of exclusive penile involvement, the correct diagnosis may be troublesome, and several investigations, including skin biopsy, are often necessary.(2) Videodermatoscopic (VD) examination of glans in healthy subjects shows at X100 magnification the presence of normal capillary loops (Figure 6.19). Similarly to cutaneous lesions of psoriasis (3–6), VD evaluation of psoriasis of the glans shows dilated and tortuous capillaries homogeneously appearing as “bushy.” In this site, however, due to the absence of scales, the visualization of vascular structures is easy. We examined by VD a series of patients affected by psoriatic balanitis in order to establish whether this technique may be able, by evaluating the superficial vascular pattern, to provide additional information useful to address the diagnosis beyond standard clinical observation.(7) Six subjects (mean age 49.1 years, age ranging between 41 and 70 years) were enrolled in an open study. Inclusion criteria were the presence (A)

Figure 6.20  (continued)

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Figure 6.19  VD examination of normal glans penis: presence of normal capillary loops (X100). of biopsy-proven psoriatic balanitis and no other skin involvement. Exclusion criteria were the presence of comorbid disorders and the use of systemic and/or topical medications for 4 and 2 weeks, respectively. VD was performed using a video microscope system, Hi-Scope KH-2,200 [Hirox Co. Ltd., Tokyo, Japan], allowing the observation at incident light of skin magnifications ranging from X20 up to X600. In order to evaluate the vascular pattern, VD examination (X100-X400) was performed (B)

psoriatic balanitis (C)

(D)

Figure 6.20  Psoriatic balanitis––A: clinical aspect. B: VD examination showing dilated and tortuous capillaries, with a “bushy” aspect (X100). Insert: normal capillaries at the same magnification (X100). C: the same “bushy” capillaries at X200. D: “bushy” capillaries at higher magnification (X400). (A)

(C)

(B)

(D)

Figure 6.21–6.22  Psoriatic balanitis––A: clinical aspect. B: VD examination showing dilated and tortuous capillaries, with a “bushy” aspect (X200).

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micali, nasca, and lacarrubba (A)

(B)

Figure 6.23  Lichen ruber planus––A: clinical aspect. B: VD examination showing a not specific vascular pattern with dilated, linear, irregularly distributed capillaries (X200).

after covering each field with immersion oil to eliminate light reflection and achieve optimal visualization of capillaries. In addition, six cases of nonpsoriatic balanitis, histologically or microbiologically proven (2 lichen planus, 1 lichen sclerosus, 1 Zoon’s balanitis and 2 candidiasis) were also evaluated by VD. At the end of the study, VD showed in all subjects affected by psoriatic balanitis a uniform pattern consisting of dilated and tortuous capillaries with a typical bushy, homogenous aspect in all examined fields (Figure 6.20–6.22). This pattern histologically corresponded to dilated, elongated, and tortuous capillary loops in the papillary dermis. In the six cases of nonpsoriatic balanitis, no bushy pattern was observed, and the presence of dilated, linear, and irregularly distributed capillaries, without any peculiar aspect, was evident (Figure 6.23). In conclusion, VD seems to hold promise as a tool that can potentially improve the clinical diagnosis of psoriatic balanitis through the evaluation of superficial vascular structures, thus avoiding skin biopsy. This might be particularly useful in those cases in which psoriatic lesions located in typical body areas or elsewhere in the body are missing. It should be remarked that VD examination must be performed with the epiluminescence technique and that particular care is needed while applying the contact to the skin with a minimal pressure in order to avoid vessels blanching.

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REFERENCES 1. Buechner SA. Common skin disorders of the penis. BJU Int 2002; 9: 498–506. 2. Palamaras I, Hamill M, Sethi G, Wilkinson D, Lamba H. The usefulness of a diagnostic biopsy clinic in a genitourinary medicine setting: recent experience and a review of the literature. J Eur Acad Dermatol Venereol 2006; 20: 905–10. 3. De Angelis R, Bugatti L, Del Medico P, Nicolini M, Filosa G. Videocapillaroscopic findings in the microcirculation of the psoriatic plaque. Dermatology 2002;204:236–9. 4. Bull RH, Bates DO, Mortimer PS. Intravital video-capillaroscopy for the study of the microcirculation in psoriasis. Br J Dermatol 1992; 91: 343–5. 5. Rosina P, Zamperetti MR, Giovannini A, Girolomoni G. Videocapillaroscopy in the differential diagnosis between psoriasis and seborrheic dermatitis of the scalp. Dermatology 2007; 214: 21–4. 6. Micali G, Nardone B, Scuderi A, Lacarrubba F. Video­ dermatoscopy enhances the diagnostic capability of palmar and/or plantar psoriasis. Am J Clin Dermatol 2008; 9: 119–22. 7. Lacarrubba F, Nasca MR, Micali G. Videodermatoscopy enhances diagnostic capability in psoriatic balanitis. J Am Acad Dermatol, in press.

6.1e Scalp psoriasis Paolo Rosina

Videocapillaroscopy (VCP) allows morphological and functional analysis of microcirculation at all cutaneous sites, including the scalp. Psoriasis capillary changes determine a specific vascular pattern: capillaries are enlarged, elongated, and tortuous and look like a bush or clew.(1–4) This pattern is already visible with hand-held dermatoscope (Figure 6.24) but are better valuable with a greater magnification using videodermatoscopy or videocapillaroscopy (Figure 6.25). Psoriasis and seborrheic dermatitis can be difficult to differentiate, especially when lesions are confined to the scalp.

The lesions of seborrheic dermatitis may closely resemble clinically those of psoriasis. Their distribution is generally different, but when lesions are confined to the scalp and are long standing, even histology may hardly differentiate the two conditions. Distinction of seborrheic dermatitis from psoriasis is obviously relevant for the long-term prognosis, but it may be particularly important in patients with arthritis symptoms. In fact, the presence of skin psoriasis is the most relevant criteria for the diagnosis of psoriatic arthritis, and deciding whether erythematous scaly plaques on the scalp are psoriasis or seborrheic dermatitis may change the interpretation of the rheumatic symptoms. An important difference between psoriasis and seborrheic dermatitis could be the microvasculature changes, which are constantly present and characteristic in psoriasis.(5, 6) In a recent study we employed videocapillaroscopy (VCP) to compare capillary morphology, distribution, and density in psoriasis and seborrheic dermatitis of the scalp to use for differential diagnosis.(1) VCP was performed using an optical probe (Videocap 200R DS Medica, Milano, Italy) on histologyconfirmed scalp lesions of 30 patients with chronic plaque psoriasis, 30 patients with seborrheic dermatitis, and 30 healthy subjects. Scalp psoriasis presented a homogeneous pattern with tortuous and dilated capillaries (appearing as bushes or clews) and a completely disarranged microangioarchitecture (Figure 6.26). The capillary loops have identical “bushy” morphology

Figure 6.24  Tortuous capillary loops visible with hand-held dermatoscope (x10).

Figure 6.25  Videocapillaroscopic appearance of capillary loops in lesional scalp psoriasis (x100).

Figure 6.26  Homogeneous psoriatic pattern with tortuous and dilated capillaries (appearing as bushes or clews) and a completely disarranged microangioarchitecture (x100).

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rosina

Figure 6.27  Capillary loops with “bushy” morphology in psoriasis (x200).

Figure 6.29  Mildly tortuous capillaries and only isolated “bushy” in seborrheic dermatitis (x200).

Figure 6.28  Lesional scalp seborrheic dermatitis with a conserved local microangioarchitecture similar to healthy scalp skin (x100).

Figure 6.30  Normal scalp skin of healthy subject (x100).

in all scalp locations (Figure 6.27). In contrast, scalp seborrheic dermatitis presented a multiform pattern, with mildly tortuous capillaries and only isolated bushy, and mildly dilated capillaries (Figure 6.28 and 6.29), with a conserved, local micro­ angioarchitecture similar to healthy scalp skin (Figure 6.30). The diameter of capillary bush of scalp psoriasis is much greater than in scalp affected by seborrheic dermatitis or normal scalp skin of healthy subjects. In seborrheic dermatitis, mean diameter of capillary bush was similar to that of the scalp of healthy subjects. Capillary loop density was similar in all conditions. Normal looking skin of patients with both dermatitis did not show significant changes compared to normal skin of healthy subjects.

In conclusion, VCP demonstrated that psoriasis exhibit homo­­ geneously tortuous and dilated capillaries, confirming previous findings, and it could be a useful and noninvasive method for differentiating psoriasis and seborrheic dermatitis, especially when the scalp is the only site affected.

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References 1. Rosina P, Zamperetti MR, Giovannini A, Girolomoni G. Videocapillaroscopy in the differential diagnosis between psoriasis and seborrheic dermatitis of the scalp. Dermatology 2007; 214: 21–4. 2. Hern S, Mortimer PS. Visualization of dermal blood vessels––capillaroscopy. Clin Exp Dermatol 1999; 24: 473–8.

scalp psoriasis 3. De Angelis R, Bugatti L, Del Medico P. Videocapillaroscopic findings in the microcirculation of the psoriatic plaque. Dermatology 2002; 204: 236–9. 4. Braverman IM, Yen A. Ultrastucture of the capillary loops in the dermal papillae of psoriasis. J Invest Dermatol 1977; 68: 53–60.

5. Braun-Falco O, Heilgermeir GP, Lincke-Plewig H. Histo­­ patho­logical differential diagnosis of psoriasis vulgaris and seborrheic eczema of the scalp. Hautarzt 1979; 30: 478–83. 6. Hern S, Stanton AWB, Mellor RH et al. In vivo quantification of the structural abnormalities in psoriatic microvessels before and after pulsed dye laser treatment. Br J Dermatol 2005; 152: 505–11.

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6.2 Clear cell acanthoma

Francesco Lacarrubba, Orazia D’Agata, Federica Dall’Oglio, and Giuseppe Micali

Clear cell acanthoma (CCA) is a usually solitary benign epidermal tumor first described by Degos in 1962.(1) The mean age of onset is about 52 years, with equal frequency in men and women.(2–5) It clinically appears as a dome-shaped, sharply circumscribed, reddish papule, variable in size from 5 to 20 mm; a peripheral scaling collarette is characteristic, but not always present (Figure 6.31–6.32). CCA occurs frequently on the lower extremities, but other anatomic sites (trunk, upper extremities) have been reported. Multiple lesions (from 2 up to 400) are rarely encountered; the rate between solitary and multiple CCA is estimated to be 1:9–1:15.(2–6) Ichthyosis and varicose veins are the most frequent associated findings. The etiology is not well understood; although some authors

Figure 6.32  Close-up clinical view of a CCA: reddish, sharply circumscribed papule with a peripheral scaling collarette.

Figure 6.31  Multiple CCAs of the legs (arrows).

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suggest that the lesion may represent a benign epithelial neoplasm, others consider the disease as a localized reactive inflammatory dermatosis (pseudotumor).(2–5) The differential diagnosis of single and/or multiple CCA includes several conditions, such as histiocytomas, seborrheic keratoses, basal-cell carcinomas, pyogenic granulomas, syringomas, hidradenomas, leiomyomas, fibromas, perifolliculomas, disseminated granuloma annulare, lichen planus, and sarcoidosis. The diagnosis of CCA is usually confirmed by histologic examination, showing in the epidermis acanthosis, papillomatosis, and a sharply demarcated epidermal proliferation of keratinocytes with a clear and slightly larger cytoplasm and a positive PAS stain. In the superficial dermis, enlarged capillaries in the papillae are evident. In 2001, Blum et al. reported a single case of CCA and first described a characteristic dermoscopic vascular pattern at X20 magnification, consisting of “partly homogeneous, symmetrically or bunch-like arranged, pinpoint-like capillaries”.(7) Histo­pathologically this pattern corresponded to dilated, tortuous capillaries within markedly elongated dermal papillae. Although the authors stated that a similar pattern could also be seen in psoriatic plaques, after removal of the scales, and considering that both entities possessed similar histopathologic features, they concluded that the dermatoscopic examination might anyway be of help to differentiate CCA from other skin tumours.(7) Successively, Bugatti et al. reported six cases of CCA characterized by this psoriasis-like vascular findings on dermatoscopy (8);

clear cell acanthoma

Figure 6.33  VD examination of CCA: presence of symmetrical, homogeneous pinpoint-like vascular structures with a pearllike disposition (X30).

Figure 6.35  VD examination of CCA: presence of symmetrical, homogeneous pinpoint-like vascular structures arranged in a net-like pattern (X30).

Figure 6.34  VD examination of CCA: presence of symmetrical, homogeneous pinpoint-like vascular structures with a pearl-like disposition (X30).

Figure 6.36  VD examination of CCA: presence of symmetrical, homogeneous pinpoint-like vascular structures arranged in a net-like pattern (X30).

they observed that the dotted vessels were regularly distributed in a reticular array; moreover, they detected the presence of a squamous surface with translucid collarette as an additional characteristic dermatoscopic finding. The authors concluded that the psoriasis-like pattern of CCA would appear to provide further evidence of a neoangiogenetic inflammatory process rather than a neoplastic one for CCA formation.(8) Zalaudek et al. stated that dermoscopic features of CCA are different from those of psoriasis (9) as, in their experience, in CCA the dotted vessels are linearly arranged as pearls on a line, whereas in psoriasis they are homogeneously and regularly distributed throughout the entire lesion. Therefore, in their

opinion, these pearl-like vessels represent a peculiar dermoscopic pattern of CCA.(9) In the same year, we studied the videodermatoscopic pattern of multiple CCAs in a single patient (10), with all of them showing the same pattern: symmetrical and homogeneous pinpoint-like vascular structures throughout the entire lesion. The pearl-like vessels disposition, at least in a portion of each lesion, was always present (Figure 6.33–6.34), whereas the presence of a net-like pattern was a frequent but not constant finding (Figure 6.35–6.36). At higher magnification (X200), each vascular structure appeared to have a bush-like aspect (Figure 6.37).

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lacarrubba, d'agata, dall'oglio and micali rubra pilaris and some variants of contact dermatitis) characterized by epidermal proliferation and dermal capillaries dilation, thus implying the need for additional diagnostic criteria. Differential diagnosis from psoriasis is particularly relevant in the case of multiple CCAs. Other cutaneous conditions, such as warts, actinic, and seborrhoeic keratoses; Bowen’s disease, squamous cell carcinoma; hypopigmented Spitz nevus; melanoma; and melanoma metastasis may sometimes show pinpoint-like vessels. In these instances, however, a correct evaluation of anamnestic and clinical features, along with additional dermatoscopic features, will help to address the correct diagnosis. In conclusion, VD may improve the clinical diagnosis of single or multiple CCAs, ruling out clinically similar disorders that do not show the same features of CCA. Figure 6.37  A detail at high-magnification depicting the bushlike aspect of pinpoint-like capillaries in CCA (X200).

Figure 6.38  The VD pattern of CCA corresponds to the histological aspect of regularly elongated rete ridges and enlarged capillaries in the dermal papillae. The VD pattern of CCA corresponds to the histologic aspect of regularly elongated rete ridges and enlarged capillaries in the dermal papillae (Figure 6.38). For this reason, the dermatoscopic pattern of CCA resembles that of psoriasis and, possibly, of other psoriasiform disorders (such as pityriasis

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REFERENCES   1. Degos R, Delort J, Civatte J, Baptista P. Tumeur épidermique d’aspect particulier: acanthome à cellules claires. Ann Dermatol Syphiligr 1962; 89: 361–71.   2. Trau H, Fisher BK, Schewach-Millet M. Multiple clear cell acanthomas. Arch Dermatol 1980; 116: 433–4.   3. Bonnetblanc JM, Delrous JL, Catanzano G, Licout A, Roux J. Multiple clear cell acanthoma. Arch Dermatol 1981; 117: 1.   4. Innocenzi D, Barduagni F, Cerio R, Wolter M. Disseminated eruptive clear cell acanthoma: a case report with review of the literature. Clin Exp Dermatol 1994; 19: 249–53.   5. Wilde JL, Meffert JJ, McCollough ML. Polypoid clear cell acanthoma of the scalp. Cutis 2001; 67: 149–51.   6. Burg G, Wursch TH, Fah J, Elsner P. Eruptive hamartomatous clear-cell acanthomas. Dermatology 1994; 189: 437–9.   7. Blum A, Metzler G, Bauer J, Rassner G, Garbe C. The dermatoscopic pattern of clear cell acanthoma resembles psoriasis vulgaris. Dermatology 2001; 203: 50–2.   8. Bugatti L, Filosa G, Broganelli P, Tomasini C. Psoriasis-like dermoscopic pattern of clear cell acanthoma. J Eur Acad Dermatol Venereol 2003; 17: 452–5.   9. Zalaudek I, Hofmann-Wellenhof R, Argenziano G. Dermoscopy of clear-cell acanthoma differs from dermoscopy of psoriasis. Dermatology 2003; 207: 428. 10. Lacarrubba F, de Pasquale R, Micali G. Videodermatoscopy improves the clinical diagnostic accuracy of multiple clear cell acanthoma. Eur J Dermatol 2003; 13: 596–8.

6.3 HPV infections

Pompeo Donofrio and Maria Grazia Francia

Human papillomaviruses (HPV) are DNA viruses that infect basal epithelial (cutaneous or mucosal) cells. There is international consensus that “high-risk” genotypes, including genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 and 66, can lead to cervical cancer and are associated with other mucosal anogenital and head and neck cancers.(1) Infections with other genotypes, termed “low-risk,” can cause benign or low-grade cervical tissue changes and genital warts (condylomata acuminata), which are growths of cervix, vagina, vulva and anus in women and penis, scrotum and anus in men.(1) Early HPV infection may be accompanied by mild changes of the epithelium that are detectable only using virological and/or cytological techniques, allowing an early treatment. HPV genital infection is considered to be the most prevalent sexually transmitted disease in the US and Europe, affecting 1–2 percent of the sexually active population between 15 and 49 years of age.(1) Genital HPV infection is primarily transmitted by genital skin-to-skin contact, usually but not necessarily during sexual intercourse. HPV infection can occur at any age and has been reported in healthy young children. Dermatoscopy of the genital region may be called as penovulvoscopy. This technique allows the recognition of some morphological patterns that can be observed in both physiological or pathological conditions of the genital area. Digital peno-vulvoscope allows enlargement of images with the use of special algorithms, defined “digital filters” or curves of color, in order to improve the visibility of the vascular pattern of the genital area, not provided by the natural contrast present in other cutaneous districts due to its notable vascularization. (2) Particular optics provided polarized light, allowing to avoid improper chromatic variations toward the red, typical of the genital mucosa. The vascular pattern that may be observed in external anogenital warts has a dotted aspect that can be defined as “mosaic like” (Figure 6.39). This pattern in progress of HPV infection is probably due to the local production of nitric oxide from the papillomaviruses, with consequent vasodilatation of the capillary handles. Such pattern, which may be observed at X10–X40 magnification (Figure 6.40), is constituted by short capillary handles perpendicular to the cutaneous surface (Figure 6.41) that dermoscopically appear as sting red in color and elegantly distributed.(2) The mosaic-like vascular pattern may be frequently observed in the apparently unaffected perilesional area (Figure 6.42), where, in the following weeks, the onset of new lesions may be observed (subclinical infection).(3)

Figure 6.39  Anogenital warts: The vascular pattern that may observed assumes a punctiform aspect that can be defined as “mosaic like” in appearance (X20).

Figure 6.40  Anogenital warts: punctiform vascular pattern at X40 magnification (X20). Differential diagnosis Pearly Papules In the male patients, the pearly papules located in the glans crown represent a frequent, but not pathological, condition. (4) They present at X20 magnification a characteristic vascular pattern: The handle that serves every single papilla originates from the base, reaches the apex of the papilla, and then refolds again toward the base, showing a hairpin-like appearance (Figure 6.43).

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donofrio and francia

Figure 6.41  The dotted pattern is constituted by short capillary handles perpendicular to the cutaneous surface, which dermoscopically appear sting red in color and elegantly distributed (X20).

Figure 6.42  Anogenital warts: the vascular “mosaic-like” pattern is frequently observed also in the perilesional areas (X40).

they appear as yellowish reliefs of the diameter of 1–2 mm. At peno-vulvoscopy observation, they show a characteristic, vascular, “garland-like” appearance, whose “bows” seemed to wind the yellowish lobules of the spots without crossing them. In every case, these ectopic glands do not require any treatment.

Figure 6.43  Vascular hairpin pattern in pearly papules (X20). Fordyce spots These physiological formations may commonly be observed on the skin of the penis and on the prepuce and are considered isolated sebaceous glands not connected to follicles. In women, they are frequently seen on the labia minora. Clinically

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References 1. Ljubojevic´ S, Lipozencic´ J, Grgec DL et al. Human papilloma virus associated with genital infection. Coll Antropol 2008; 32(3): 989–97. 2. Micheletti L, Bogliatto F, Lynch PJ. Vulvoscopy: review of a diagnostic approach requiring clarification. J Reprod Med 2008; 53(3): 179–82. 3. Bleeker MC, Hogewoning CJ, Voorhorst FJ et al. HPVassociated flat penile lesions in men of a non-STD hospital population: less frequent and smaller in size than in male sexual partners of women with CIN. Int J Cancer 2005; 113(1): 36–41. 4. Hogewoning CJ, Bleeker MC, van den Brule AJ et al. Pearly penile papules: still no reason for uneasiness. J Am Acad Dermatol 2003; 49(1): 50–4.

6.4 Venular malformations (port wine stain type) Francisco Vázquez-López

The value of dermoscopy for further evaluating venular malformations (VM) has been proposed.(1) Venular malformations (or capillary vascular malformations) are congenital, low-flow, vascular abnormalities of the dermal capillaries. VM affect 0.3%–0,5% of newborns with equal prevalence in male and female patients. They may have a genetic basis, tend to be present at birth, and grow with age. VM are initially flat and smooth (macular) but nodules may develop with time. The color varies from pink, red, to deep purple. VM may be part of syndromes such as Sturge-Weber and Klippel-Trenaunay. Very rarely, VM may present late onset in adolescents and adults, usually caused by trauma. VM are characterized by ectatic vessels with flattened endothelium, most of them situated in the papillary dermis and upper part of the reticular dermis, but may be located deeper. The origin of VM is unclear, possibly being a result of vascular channel developmental defects or segmental deficiency of autonomic inervation of postcapillary venules.(2, 3) VM are being classified according to their color and location. In addition, the recent introduction of noninvasive image techniques such as dermoscopy or videodermoscopy has allowed the analysis of the capillary composition, that is, the type of the capillary involved (4–8) (Figures 6.44–6.57), which may be related to prognosis. By means of these devices, a better understanding of the morphology of the vessels involved can be obtained in daily practice, and rapidly, without the risk of injury to the patient and without additional cost, revealing significant vascular structures hidden in the standard visual inspection. By means of dermoscopy, the vessels are visualized

Figure 6.44  Clinical view of a flat, partially treated, long-standing venular malformation (VM) of the forehead.

because of the red blood cells filling and passing through them. Therefore, it is important to avoid excessive pressure on the lesion when performing this procedure, which causes occlusion

Figure 6.45  Dermoscopy of this VM reveals a superficial pattern of VM, showing scattered type 1 ectatic vessels (red, rounded vessels) with a variable size (original magnification: X10). This pattern has been related to the superficial capillary loops of the papillae. Round vessels may be pinpointed or globular according to their size. Largest structures are similar to “red lagoons”.

Figure 6.46  Dermoscopy of VM showing type 1, round capillaries in greater number. The contrast with the surrounding normal skin is well evident. Some authors describe this pattern as a better response to laser therapy. The main prognostic factors are the depth and diameter of capillaries of VM (original magnification: X10).

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vzquez-lpez

Figure 6.47  Dermoscopy of VM showing numerous type 1 round vessels, disclosing a variable size (dotted, globular, and similar to lagoons) (original magnification: X10).

Figure 6.49  Dermoscopy of the former lesion reveals a type 2 vascular pattern, devoid of round type 1 vessels. Tortuous, thin, linear vessels configured in an irregular network are demonstrated. Type 2 linear vessels are thought to correspond to the subepidermal, horizontal, vascular plexus of the dermis (original magnification: X10).

Figure 6.48  Clinical view of a VM located on the thigh. and lack of visualization of the vessels if nonpolarized dermoscopy is applied or when taking dermoscopic photographs with skin contact. Several authors (1, 4, 7) have described two types of vessels in VM with videodermoscopy: type 1 (superficial papillary vessels) and type 2 (deeper subpapillary vessels). Mixed and undefined vascular patterns can also be observed. Digital videodermoscopy allows a higher magnification of vessels involved and the ability to record and compare the digital images, but similar structures can also be revealed with stereomicroscope (4) and pocket dermoscope.(6) Type I vessels are seen as red and sharp structures having a round to oval shape and a variable size (termed as dotted, pinpointed, or globular, according to their size) (Figures 6.44–6.47). They have been correlated to ectatic capillary loops of the papillae.(5)

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Figure 6.50  Dermoscopy of the border of same lesion (higher degree of magnification), where the contrast between VM vessels and the surrounding normal skin can be better appreciated. Type 1 round vessels are not seen. In contrast, type 2 subpapillary vessels are seen as red, linear structures, showing a variable tortuosity, thickness, and sharpness and forming irregular networks (Figures 6.48–6.56). Type 2 linear vessels have been correlated to the horizontal subepidermal vascular plexus.(5) In addition a gray-whitish veil has also been reported related to the deeper vessels of the lower reticular dermis.(4) According to videodermoscopy, VM have been predominantly classified into type 1 (superficial) or type 2 (deep) patterns (Figures 6.44–6.50). In addition, mixed and undefined patterns (5, 7) can also be observed (Figures 6.51– 6.58). Nevertheless, a clear correlation between dermoscopic

venular malformations

Figure 6.51  Clinical view of a VM located on the leg. Figure 6.53  Dermoscopy of the same lesion, with a higher degree of magnification after applying digital zoom to the attached camera. Round, dotted vessels are easily demonstrated in conjunction to linear vessels.

Figure 6.52  Dermoscopy of this lesion revealed not only a predominantly type 2 vascular pattern (linear vessels) but also scattered, well-defined, dotted, type 1 vessels (X10). and histological observations has not been found by some authors.(4) A correlation between these patterns and anatomical location has been reported. VM located in the dermatome V3, neck, and trunk showed mainly a type 1 pattern, whereas lesions located on dermatome V2 and extremities showed mainly a type 2 or a mixed pattern.(5) Round vessels, either as an isolated finding or in a mixed pattern, have been found in most VM in some studies.(4) Round vessels of VM may appear quite small and as tiny dots (especially in children) or large, globular structures. The largest globules, previously described as “red lagoons,” are characteristic of hemangiomas. Lagoons or lacunae appear small, deeply red in color, sharply demarcated, varying in size, as oval to round structures and appear either as tightly clustered or as loosely scattered. They may or may not be located within round- to oval-shaped red patches. Lagoons of hemangiomas are secondary to both proliferation and ectasia of the vessels involved, whereas round

vessels of vascular malformations represent only a vascular dilatation devoid of proliferation (Figures 6.59–6.64). Dermoscopy offers, therefore, new clinical insights into VM. Interestingly, it has been proposed that these findings may have a prognostic significance.(1, 4, 5) The current standard treatment of VM is the pulsed-dye laser, although a complete lightening of the lesion is rare. Dermoscopic findings in VM may help to predict the outcome of the therapy. The response of VM to laser treatment is believed to be dependent on several factors, which may be related to partial damage of some vessels, persistence of lesions, or neovascularization after therapy. 1. Therapy of VM and clinical data (color, location, size of VM, age of patients).(9–11) - The color of VM (pink, red, purple) has been found to be predictive of response to treatment, with purple and red lesions tending to respond better than the pink ones. - Location: Certain sites for VM respond better to laser treatment. Lesions on the distal extremities and medial face tend to do less well than lesions on the lateral face or trunk. As regards the dermatomal distribution of VM, those involving V2 respond less well than those located on V1 and V3. 2. Therapy of VM and histological data: depth and diameter of the capillaries of VM.(12, 13) A number of studies have established the importance of capillary depth and diameter in determining the response of VM to laser treatments. It seems that the response of an untreated VM to laser treatment will be dependent on the range of depths and

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vzquez-lpez

Figure 6.54  Clinical view of a VM located on the cheek. The lesion has been previously treated with laser. Blanched areas are well evident.

Figure 6.56  Dermoscopy of the same lesion with a higher degree of magnification. Tortuous linear vessels and globular vessels are demonstrated herein, despite the previous therapy.

Figure 6.55  Dermoscopy (low magnification) revealed herein a mixed pattern with linear, tortuous, short, and arboriform vessels, and also round, globular vessels (original magnification: X10).

Figure 6.57  Long-standing VM of the face, partially masked by a cosmetic camouflage, and partially treated with electrodessication. At this phase, lesions may become darker, violaceous, thicker, and may develop blebs, in contrast with the patient of the Figure 6.44.

diameters of capillaries comprising the lesion. Deeper vessels with a small diameter are those responding less well. 3. Therapy of VM and dermoscopic data. Dermoscopic data provide information related to the morphology of the vessels involved, which has been related to their depth. The presence of type 2 vessels (1, 5, 7) and gray-whitish veil (4) has been related to deeper vessels and with less response to the treatment; meanwhile type 1 round vessels were related to superficial vessels, and hence, a better response to therapy. A clear correlation between dermoscopic and histological

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observations has not been found by all authors (4), who found the presence of a gray-whitish veil hiding the inferior structures as the most significant feature related to prognosis. Recently, a videomicroscope that is capable of determining morphology, depth, and diameter of capillaries (depth-measuring videomicroscope, DMV) has been developed and applied for evaluating VM (8). This tool is similar to a traditional video microscope, but it facilitates better visualization of vessel depth and diameter in the dermis. This device allows individual capillaries to be imaged and their depth and diameter to be calculated.

venular malformations

Figure 6.58  Dermoscopy of the former lesion revealed an undefined pattern, with a deep purplish background; red lagoons; and a delicate, whitish network (original magnification: X10).

Figure 6.59  Clinical image showing a patient with a prominent midline “salmon patch” VM of the neck, which are classified separately from lateral Port Wine stains. According to the results obtained with this device (8) and also according to the previous histological results (12, 13), it seems that the small, deeply located vessels are more resistant to the laser treatment and tend to remain uncoagulated. The outcome of VM therapy will most likely depend on the depth and size of the deeper vessels. Deep vessels may be revealed only after clearing the superficially located type 1 capillaries by four or five dye laser treatments, which previously obscured them.(8) As regards correlations between these different clinical, histological, and dermoscopic parameters of VM, a controversy exists between different studies; however, only a few authors corroborate the correlations between these parameters, (5)

Figure 6.60  Dermoscopy of this lesion revealed a homogeneous, type 1, globular vascular patterns, devoid of linear vessels (original magnification: X10). Perifollicular areas seem to be uninvolved. Perifollicular white halos are an unspecific and peculiar dermoscopic finding, which may be observed in both melanocytic and nonmelanocytic skin lesions.(15)

Figure 6.61  Dermoscopy of an acquired hemangioma. Hema­ ngiomas are characterized by lagoons or lacunae, which are red to blue-red or blue-black to maroon in color, appear round to oval in shape, and as sharp structures, either tightly clustered or loosely scattered throughout the lesion (original magnification: X10). Lagoons are a result of the proliferation of dilated venules, whereas VM present only vascular ectasia. while most others are of the impression that such correlations might not be possible.(8, 9) 4. Other factors (8, 9, 14) It must be taken into account that other factors may play a role in the response of VM to laser treatment, in addition to capillary

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vzquez-lpez

Figure 6.62  Dermoscopy of acquired angioma serpiginosum revealing multiple, scattered, sharp lagoons (original magnification: X10).

Figure 6.64  Dermoscopy of this lesion reveals tightly clustered, red, globular vessels and blue lagoons (original magnification: X10). These structures are related to the vessel ectasia and not to vascular proliferation.

linear type 2 vessels), are related to the depth of the vessels involved.(1,5,7) In addition, videodermoscopy is also helpful in deciding more accurately when to end the treatment because it objectively shows when a VM becomes resistant to further treatments (persistence of small and deep vessels). It is also helpful for demonstrating this to patients and their parents by means of an objective image. Moreover, it has been speculated that videomicroscopy may facilitate in the future the development of newer pulseddye lasers to treat VM more efficiently, as pulse duration and wavelength could be matched to measured vessel diameter and depth, respectively. Figure 6.63  Clinical view of a patient with a mixed vascular malformation on the arm with prominent, deep component, which is different from venular malformations. depth and diameter or the dermoscopic vessel type, such as the flow through these capillaries, and the amount of competing chromophores within the skin, such as melanin or the thickness of the skin. In sum, dermoscopy and videodermoscopy serve to further evaluate VM on a non-invasive basis. In conjunction with the clinical examination, this device improves the understanding of the morphology of the vessels involved, which may have a prognostic significance. It can be applied in most settings, without additional cost for demonstrating significant vascular structures that are hidden in the standard visual inspection; for some authors, these vascular structures (round type 1 and

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REFERENCES   1. Motley RJ, Lanigan SW, Katugampola GA. Videomicroscopy predicts outcome in treatment of port-wine stains. Arch Dermatol 1997; 133: 921–2.   2. Meghan FS, Glick SA, Hirsch RJ. Laser treatment of pediatric vascular lesions: Port wine stains and hemangiomas. J Am Acad Dermatol 2008; 58: 261–85.   3. Garzon MC, Huang JT, Enjolras O, Frieden IJ. Vascular malformations: Part I. J Am Acad Dermatol 2007; 56: 353–70.   4. Procaccini EM, Argenziano G, Staibano S, Ferrara G, Monfrecola G. Epiluminescence microscopy for port-wine stains: pretreatment evaluation. Dermatology 2001; 203: 329–32.   5. Eubanks LE, McBurney EI. Videomicroscopy of port-wine stains: correlation of location and depth of lesion. J Am Acad Dermatol 2003; 48: 984–5.

venular malformations   6. Vázquez-López F, Manjón-Haces JA, Vázquez-López AC, Pérez-Oliva N. The hand-held dermatoscope improves the clinical evaluation of port-wine stains. J Am Acad Dermatol 2003; 48: 984–5.   7. Sevila A, Nagore E, Botella-Estrada R et al. Videomicroscopy of venular malformations (port-wine stain type): prediction of response to pulsed dye laser. Pediatr Dermatol 2004; 21: 589–96.   8. Sivarajan V, Mackay IR The depth measuring videomicroscope (DMV): a non-invasive tool for the assessment of capillary vascular malformations. Lasers Surg Med 2004; 34: 193–7.   9. Sivarajan V, MacKay IR. The relationship between location, color, and vessel structure within capillary vascular malformations. Ann Plast Surg 2004; 53(4): 378–81. 10. Renfro L, Geronemus RG. Anatomical differences of portwine stains in response to treatment with the pulsed dye laser. Arch Dermatol 1993; 129(2): 182–8. 11. Nguyen CM, Yohn JJ, Huff C et al. Facial port wine stains in childhood: prediction of the rate of improvement as

12.

13.

14.

15.

a function of the age of the patient, size and location of the port wine stain and the number of treatments with the pulsed dye (585 nm) laser. Br J Dermatol 1998; 138: 821–5. Onizuka K, Tsuneda K, Shibata Y, Ito M, Sekine I. Efficacy of flashlamp-pumped pulsed dye laser therapy for port wine stains: clinical assessment and histopathological characteristics. Br J Plast Surg 1995; 48: 271–9. Fiskerstrand EJ, Svaasand LO, Kopstad G et al. Laser treatment of port wine stains: therapeutic outcome in relation to morphological parameters. Br J Dermatol 1996; 134: 1039–43. Nagore E, Requena C, Sevila A et al. Thickness of healthy and affected skin of children with port wine stains: potential repercussions on response to pulsed dye laser treatment. Dermatol Surg 2004; 30: 1457–61. Vázquez-López F, Más-Vidal A, Sánchez-Martín J, PérezOliva N, Argenziano G. Perifollicular white halo: a dermoscopic subpattern of melanocytic and non melanocytic skin lesions. Arch Dermatol (in press).

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6.5 Bowen’s disease

Leonardo Bugatti, Giorgio Filosa, and Alessandra Filosa

Bowen’s disease (BD) is an intraepidermal (in situ) squamouscell carcinoma clinically presenting as a slowly enlarging sharply demarcated erythematous plaque with a crusting and scaling surface (Figure 6.65a). Resemblance with psoriasis or dermatitis classically leads to a delay in the correct diagnosis. It predominantly affects older female patients, and in about three-quarters of the cases, it is located on the lower limbs. Lesions are usually solitary but may be multiple in 10%–20% of patients. Unusual sites or variants include pigmented, subungual/periungual, palmar, genital, perineal, and verrucous BD. Most studies suggest a risk of tumoral progression to be about 3%–5% for classic BD. Reported relevant etiological factors are irradiation (solar, photochemiotherapy, radiotherapy), long-term arsenic exposure, immunosuppression, and oncogenic HPV (mainly 16, 18 subtypes). Development of ulceration is usually a sign of invasive carcinoma. Histopathologically, BD is characterized by acanthotic epidermis with elongation and thickening of rete ridges, with convoluted and dilated papillary vessels. Throughout the epidermis, the cells lie in complete disorder, resulting in a “windblown appearance.” Many cells are highly atypical, showing large hyperchromatic nuclei with conspicuous nucleoli and abundant cytoplasm. Another common feature is the presence of occasional, individually atypical, keratinized cells (Figure 6.65b). The border between epidermis and dermis appears sharp and the basement membrane remains intact. The upper dermis shows a moderate amount of chronic inflammatory infiltrate, which sometimes adopts a lichenoid distribution. Several dermoscopic features of BD have been described (Table 6.1). The most peculiar and common findings for this (a)

Table 6.1  Dermoscopic Features of Bowen’s Disease. • Multicomponent global pattern • Atypical vascular structures (dotted/glomerular) • Scaly surface • Pseudonetwork • Irregular, structureless, diffuse pigmentation • Patchy distribution of small, brown globules • Focal/multifocal hypopigmentation • Blue-whitish veil • Peppering/white areas • Hemorrhages

tumor seem to be multicomponent global pattern (90%– 100%), atypical vascular structures (86.6%–100%) and scaly surface (64.2–90%).(1, 2) The presence of vascular structures on the surface of the tumor is consisting mainly of dotted vessels (50%) irregularly distributed in clusters, but linear, arborizing, bushy, and hairpinlike vessels can also be found (Figure 6.66, 6.67). Dotted vessels histopathologically correlate with dilated tortuous capillaries of middle reticular dermis progressing to the top of the papillae. Higher magnification can disclose a distinctive type of vascular structures, namely, “glomerular vessels,” characterized by highly convoluted tortuous capillaries mimicking the glomerular apparatus of the kidney (Figure 6.68). Some authors prefer to keep dotted vessels as distinct from glomerular vessels, as the latter are usually larger in size, often looped, and regularly arranged in a patchy distribution (Figure 6.69a, 6.69b).(2, 3) Glomerular morphology has also been described for severe venous stasis.(4) (b)

Figure 6.65  (a) Sharply demarcated erythemato-desquamative plaque. (b) Epidermal acanthosis with a number of highly atypical keratinocytes often with features of dyskeratosis (ematoxylin-eosin, at x100 magnification).

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bowens disease (a)

Figure 6.66  Brownish pseudonetwork, dotted and linear vascular structures (original magnification, x10).

Figure 6.67  Dotted vascular structures, scaly surface, hemorrhages (original magnification, x10).

Figure 6.68  Multicomponent global pattern, irregular diffuse structureless pigmentation, dotted (glomerular) vascular pattern, and scaly surface (original magnification, x10).

(b)

Figure 6.69  (a) Dotted vascular structures and multifocal hypo­pigmentation (original magnification, x10). (b) Magnified detail of Figure 6.69a. Tortuous capillaries with glomerular, hairpin, bushy morphology. A variety of peculiar vascular structures can be recognized under dermoscopic examination, and though not specific, they have a diagnostic significance.(5) Atypical (or polymorphous) vascular pattern has been described as red structures irregularly distributed outside areas of regression in melanocytic lesions, showing three features: (i) linear, irregular vessels; (ii) dotted or pinpoint, regularly shaped vessels; and( iii) milky red globules. (6, 7) Kreusch has given a thorough morphological illustration of the vascular component of skin tumors and has suggested an algorithm for the diagnosis based on dermoscopic vascular patterns.(8) The recognition of distinctive vascular structures enhances the diagnostic range of dermoscopy, especially when the classic pigmented structures are lacking.(9) It can be speculated that vascular morphology is consistent with a process of tumoral neoangiogenesis in BD. Video­ capillaroscopic studies might better describe the vascular structures involved in BD and other cutaneous neoplasias.

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bugatti, filosa, and filosa

Figure 6.70  Dotted vascular structures, scaly surface, hemorrhages (original magnification, x10).

Figure 6.72  Pseudonetwork and irregular, structureless diffuse pigmentation (original magnification, x10).

Figure 6.71  Scaly surface, irregular diffuse pigmentation, and patchy distribution of globules (original magnification, x10).

dermopathologic examination. The false atypical pigmented network may be created by the thickening of the rete ridges due to deposits of melanin within the tumoral cells in the dermal papillae.(12) Dotted vessels can commonly be found in melanocytic tumors, sometimes of seborrheic keratoses and other skin diseases, such as psoriasis, warts, clear-cell acanthoma, and dermatofibroma. In most cases of psoriasis, red-dotted globules are homogenously distributed over the entire surface, whereas dotted vessels in warts are distinctive for a pale halo of keratinization. (13) Dotted vessels in clear-cell acanthoma are often arranged uniformly like pearls in a line with a psoriasiform appearance. (14) In dermatofibromas, dotted vessels may be either centrally located or diffuse throughout the lesion, together with other accompanying features, such as globular structures, scarlike white patch, and peripheral fine network.(15) Dotted vessels are reported to be a frequent finding in amelanotic melanoma, especially in early thin lesions. In this case, the concurrence of a white to pinkish veil and a small amount of residual, light-brown pigmentation may contribute to the diagnosis.(16–18) Dermoscopy has also been proposed as a valuable tool for monitoring of nonsurgical treatment of BD, where the disappearance of vascular structures may indicate adequate treatment.(12) In conclusion, multicomponent global pattern, vascular component (dotted vessels or “glomerular” subtype morphology) and scaly surface represent valuable dermoscopic clues to the diagnosis of BD. However, further studies are needed to assess the specificity and sensitivity of these dermoscopical criteria in differentiating BD from other pigmented and nonpigmented skin tumors.(1, 2, 19)

The degree of scaling may vary according to different factors, such as body location, environmental conditions, topical pretreatment, and type of lubricant used to minimize surface reflection. The greater thickness of the corneal layer in acral skin gives rise to heavier scaling. (Figure 6.70) (10) BD is generally scarcely pigmented, although pigmented structures can be detected, especially in the unusual form of heavily pigmented BD, such as the presence of pseudonetwork (10–35.7%), irregular structureless diffuse pigmentation (64.2–80%), and small brown globules (64.2–90%).(1, 2) The pigmented globules are usually smaller than those associated with melanocytic lesions and follow a regular patchy distribution over the lesion (Figure 6.71). In heavily pigmented BD pseudonetwork or reticular pigmentation, sometimes simulating atypical network, can be the main dermoscopic criterion lacking other, well-expressed, standard criteria (Figure 6.72). (11) This should bring to the prompt removal of the lesion for

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references   1. Bugatti L, Filosa G, De Angelis R. Dermoscopic observation of Bowen’s disease. J Eur Acad Dermatol Venereol 2004; 18: 572–4.

bowens disease   2. Zalaudek I, G.Argenziano, B.Leinweber et al. Dermoscopy of Bowen’s disease. Br J Dermatol 2004; 150: 1112–6.   3. Zalaudek I, Di Stefani A, Argenziano G. The specific dermoscopic criteria of Bowen’s disease JEADV 2006; 20: 341–62.   4. Vaquez-Lopez F, Kreusch J, Marghoob AA. Dermoscopic semiology: further insights into vascular features by screening a large spectrum of nontumoral skin lesions. Br J Dermatol 2004; 150: 226–31.   5. Kreusch J, Koch F. Characterization of vascular patterns in skin tumors by incident light microscopy. Hautartz 1996; 47: 264–72.   6. Stolz W, Landthaler M, Falco OB et al. Color Atlas of Dermatoscopy 2nd ed. Oxford: Blackwell Publishing; 2002.   7. Argenziano G, Fabbroncini G, Carli P et al. Clinical and dermoscopic criteria for the preoperative evaluation of cutaneous melanoma thickness. J Am Acad Dermatol 1999; 40: 61–8.   8. Kreusch JF. Vascular patterns in skin tumors. Clin Dermatol 2002; 20: 248–54.   9. Argenziano G, Zalaudek I, Corona R et al. Vascular structures in skin tumors. A dermoscopy study. Arch Dermatol 2004; 140: 1485–9. 10. Bugatti L, Filosa G, De Angelis R. The specific dermoscopical criteria of Bowen’s disease. J Eur Acad Dermatol Venereol 2007; 21: 700–1.

11. Stante M, De Giorgi V, Massi D et al. Pigmented Bowen’s disease mimicking cutaneous melanoma: clinical and dermoscopic aspects. Dermatol Surg 2004; 30: 541–4. 12. Hu C, Chiu H, CHEN G et al. Dermoscopy as a diagnostic and follow-up tool for pigmented Bowen’s disease on acral region. Dermatol Surg 2008; 34: 1248–53. 13. Vasquez-Lopez F, Kreuscj J, Marghoob AA. Dermoscopic semiology: further insights into vascular features by screening a large spectrum of nontumoral skin lesions Br J Dermatol 2004; 150: 226–31. 14. Bugatti L, Filosa G, Broganelli P, Tomasini C. Psoriasis-like dermoscopic pattern of clear cell acanthoma. J Eur Acad Dermatol Venereol 2003; 17: 452–5. 15. Zaballos P, Puig S, Llambrich A, Malvehy J. Dermoscopy of dermatofibromas: a prospective morphological study of 412 cases. Arch Dermatol 2008; 144: 75–83. 16. Pizzichetta MA, Talamini R, Stanganelli I et al. Amelanotic/ hypomelanotic melanoma: clinical and dermoscopic features. Br J Dermatol 2004; 150: 1117–24. 17. Bono A, Maurichi A, Moglia D et al. Clinical and dermatoscopic diagnosis of early amelanotic melanoma. Melanoma Res 2001; 11: 491–4. 18. Zalaudek I, Argenziano G, Kerl H et al. Amelanotic/ Hypomelanotic melanoma––is dermatoscopy useful for diagnosis? J Dtsch Dermatol Ges 2003; 1: 369–73. 19. J. Hernández-Gil J, Fernández-Pugnaire MA, SerranoFalcón C et al. Clinical and dermoscopic features of pigmented Bowen disease. Actas Dermosifiliogr 2008; 99: 419–27.

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6.6 Pyogenic granuloma Pedro Zaballos Diego

PYOGENIC GRANULOMA Pyogenic granuloma is a relatively common, benign, vascular lesion of the skin and mucous membranes whose exact cause is unknown. This misnamed entity is neither infectious nor granulomatous and, therefore, some authors prefer the term lobular capillary hemangioma to describe these lesions because of the histologic findings. Pyogenic granuloma is relatively common and it is especially frequent in children and young adults.(1–3) It represents 0.5% of all skin nodules in children.(4) The typical lesion appears as a papule or polyp with a glistening surface, which bleeds easily. Sites of predilection include the gingiva, lips, mucosa of the nose, face, and extremities (mainly the fingers). Pyogenic granuloma with satellitosis, a subcutaneous subtype, a intravenous subtype, and a disseminated variant have been described in literature. The gingival lesion developed during pregnancy termed epulis gravidorum is considered a variant of this tumor. A few reports of lesions developing in a preexisting nevus flammeus or spider angioma exist. The exact etiopathogenesis of this condition is unknown. It has been thought to be a reactive, hyperproliferative, vascular response to a variety of stimuli, such as infective organisms, penetrating injury, hormonal factors, and retinoid therapy. Pyogenic granulomas usually develop at the site of a preexisting injury, where they evolve rapidly over a period of weeks to a maximun size and then shrink in a fibroma that can regress within a few months. The histopathologic findings in all variants of pyogenic granuloma are similar. Early lesions resemble granulation tissue, that is, numerous capillaries and venules with

Figure 6.73  The characteristic dermoscopic pattern of pyogenic granuloma is made up of a reddish homogeneous area surrounded by a white collarette. We can also observe superficial scales and “white rail” bands (instead of lines) that intersect the lesion (X10).

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plump endothelial cells arrayed radially toward the skin surface (usually eroded, ulcerated, and covered with scabs) amidst an edematous stroma containing a mixed inflammatory infiltrate. The matured polypoid lesion exhibits a fibromyxoid stroma separating the lesion into a lobular pattern. Each lobule is composed of aggregations of capillaries and venules with plump endothelial cells. In this stage, reepithelialization of the surface and a peripheral collarette of hyperplastic adnexal epithelium may be noted, with less inflammatory infiltrates present and disappearance of edema of the stroma. Older lesions tend to organize and partly fibrose and, in time, pyogenic granuloma resolves into fibroma.(1–4) Although the clinical diagnosis of pyogenic granuloma is rather easy, in some instances the differentiation from other benign and malignant tumors, such as amelanotic melanoma, is difficult to determine. In 38 % of one case series (5), the clinical diagnosis of pyogenic granuloma proved to be wrong. Misdiagnosis documented in medical literature include keratoacanthoma, squamous-cell carcinoma, basal-cell carcinoma, inflamed seborrhoeic keratosis, common warts, melanocytic nevus, Spitz nevus, amelanotic melanoma, metastasic carcinoma, Kaposi´s Sarcoma, and true hemangiomas among others.(1–6) Dermoscopy may be helpful in the recognition of pyogenic granulomas.(7, 8) The results of one study where 13 pyogenic granulomas were collected and evaluated reveal that a reddish homogeneous area surrounded by a white collarette is the most frequent dermoscopic finding in pyogenic granulomas (Figures 6.73–6.75 and 6.77).(7) This pattern was identified in 84.6% of

Figure 6.74  Another characteristic pyogenic granuloma with a reddish homogeneous area surrounded by a white collarette. We can also see scales and ulceration (X10).

pyogenic granuloma

Figure 6.75  Figure shows the characteristic dermoscopic pattern in a pyogenic granuloma located on a upper lip (X10).

Figure 6.76  Pyogenic granuloma that shows a reddish homogeneous area and “white rail” lines that intersect the lesion. This is a pediculated lesion, and, in these cases, it is difficult to see the white collarette on polarized contact dermoscopy. We can also see a scale in the left part of the lesion and an area of ulceration in the upper part (X10). pyogenic granulomas of the study. Other dermoscopic structures that were found were “white rail” lines (Figures 6.73 and 6.76) that intersect the lesion in 30.7% of cases and ulceration in 46.1% of pyogenic granulomas (Figures 6.74 and 6.76). The histopathologic correlation of the reddish homogeneous area may be attributed to the presence of numerous small capillaries or proliferating vessels that are set in a myxoid stroma of pyogenic granulomas. The white collarette corresponds to the hyperplastic adnexal epithelium that partially or totally embraces the lesion at the periphery of most pyogenic granulomas. The

Figure 6.77  Figure shows the characteristic pattern of pyogenic granuloma (a reddish homogeneous area surrounded by a white collarette), but there are several vascular structures. In these cases, it is important to remove the lesions in order not to misdiagnose an amelanotic melanoma (X10).

Figure 6.78  An atypical dermoscopic image of pyogenic granuloma with a central area of ulceration and polymorphous/atypical vessels (linear irregular, hairpin, and glomerular vessels). The lesion should be excised in order not to misdiagnose an amelanotic melanoma (X10). white lines similar to a double rail that intersect the lesion in some pyogenic granulomas may correspond histologically to the fibrous septa that surround the capillary tufts or lobules in more advanced cases. Finally, pyogenic granulomas are frequently eroded and crusted and may bleed very easily. This feature may explain the hemorrhagic crusts or ulceration that we can observe in some cases of pyogenic granulomas. Occasionally, we can observe different vascular structures like

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zaballos

Figure 6.79  Figure shows a dermoscopic image of an amelanotic melanoma previously diagnosed clinically as a pyogenic granuloma. Under dermoscopy, we can observe polymorphous/ atypical vessels, irregularly shaped depigmentation (white lines and structures), brown dots or globules irregular in size and distribution, and light-brown, structureless areas of more than 10% of the area of the lesion (X10). dotted vessels, telangiectasias, glomerular vessels, hairpin vessels, linear-irregular vessels, and polymorphous/atypical vessels (Figures 6.77 and 6.78). In our opinion, all cases of pyogenic granulomas with vascular structures should be excised in order not to misdiagnose an amelanotic melanoma. Dermoscopic differential diagnosis between pyogenic granuloma and other vascular lesions, such as angiomas and angiokeratomas, and other pigmented lesions, such as basal-cell carcinoma, Spitz nevus, and amelanotic melanoma, should be considered.(7, 9) Regarding other vascular lesions, the dermoscopic hallmark of most hemangiomas is the presence of red lacunas, which are characterized by well-demarcated, round to oval, red or reddish-blue areas and correspond histopathologically to dilated, blood-filled vessels in the papillary dermis. Lacunas commonly vary in size and color within a given lesion and may be either tightly clustered or loosely scattered throughout.(10) They are often located on a background of a red, red-bluish, or red-whitish homogeneous area. In a recent study, 6 dermoscopic structures were observed in at least 50% of the solitary angiokeratomas (11): dark lacunas (93.8%), whitish veil (90.6%), erythema (68.8%), peripheral erythema (53.1%), red lacunas (53.1%), and hemorrhagic crusts (53.1%). The structure “dark lacunas” is the most frequent dermoscopic finding in solitary angiokeratomas and represents the most valuable criteria for correctly diagnosing this vascular tumor with a sensitivity of 93.8% and a specificity of 99.1%.(11) “Dark lacunas,” like red lacunas, also represent dilated vascular spaces in the upper dermis and their dark violaceous, blue, or black color corresponds to vascular spaces that are partially or completely thrombosed. It is important to note that the pattern composed of “dark

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lacunas plus whitish veil” was determined to be the most common pattern in solitary angiokeratomas. Another vascular tumor whose dermoscopic image has been described in the literature is targetoid hemosiderotic hemangioma.(12, 13) Although patients usually describe cyclic changes and, therefore, the dermoscopic appearance is changing, most cases show a pattern composed of a central area with reddish or dark lacunas surrounded by a reddish, violaceous, or brownish homogeneous pigmentation. Nodular basal-cell carcinoma and amelanotic melanoma may be also included in the differential diagnosis of a reddish tumor. The dermoscopic criteria for basal-cell carcinoma (14) include lack of features of a melanocytic lesion and the presence of at least one of the following criteria: large gray-blue ovoid nests, multiple blue-gray globules, maple leaf–like areas, spoke-wheel areas, arborizing telangiectasias, and ulceration. When these tumors are ulcerated they may resemble pyogenic granulomas because ulceration has been also described in 46.1% of pyogenic granulomas in one study.(7) However, none of the other specific dermoscopic criteria of basal-cell carcinoma has been described in pyogenic granulomas and the peripheral white collarette is not a characteristic of basal-cell carcinomas. Regarding amelanotic melanoma, in a recent study (15), the most positive predictors of amelanotic and hypomelanotic melanoma were multiple blue-gray dots, irregularly shaped depigmentation, brown dots or globules irregular in size or distribution, 5 to 6 colors, predominant central vessels, red-blue color, and peripheral, light-brown, structureless areas of more than 10% of the area of the lesion. Although Menzies et al. did not include any pyogenic granuloma in their study, all these features were significant, positive predictors of melanoma, compared with benign melanocytic lesions and nonmelanocytic lesions of the study. As for vascular features, the most predictive for melanoma were central vessels, hairpin vessels, milky red–pink areas, more than 1 shade of pink, a combination of dotted and linear irregular vessels, and linear, irregular vessels as the predominant vessel type. Milky red-pink areas are defined as larger areas than globules of fuzzy or unfocused milky-red color usually corresponding to an elevated part of the lesion.(16) It is important to note that, in some pyogenic granulomas, the “white rail” lines that intersect the lesion in 30.7% of cases (7) could divide the total reddish homogeneous area in structures similar to milky red–pink areas. Moreover, occasionally, we have found several vascular structures (dotted vessels, telangiectasias, glomerular vessels, hairpin vessels, linear-irregular vessels, and polymorphous/atypical vessels) in some pyogenic granulomas. However, none of the 105 amelanotic and hypomelanotic melanomas of the study of Menzies et al.(16) showed a peripheral white collarette. In our opinion, according to this study, all cases of reddish tumor with characteristic dermoscopic structures of pyogenic granulomas (a total reddish homogeneous area surrounded by a white collarette), including those with more than one shade of pink and/or vascular structures (mostly having predominantly central vessels, milky red pink areas not surrounded by white-rail lines and

pyogenic granuloma polymorphous/atypical vessels), should be excised in order not to misdiagnose an amelanotic melanoma (Figure 7.69). REFERENCES   1. Mooney MA, Janninger CK. Pyogenic granuloma. Cutis 1995; 55: 133–6.   2. Pagliai KA, Cohen BA. Pyogenic granuloma in children. Pediatric Dermatology 2004; 21: 10–3.   3. Requena L, Sangueza OP. Cutaneous vascular proliferation. Part II. Hyperplasias and benign neoplasms. J Am Acad Dermatol 1997; 37: 887–919.   4. Grimalt R, Caputo R. Symmetric pyogenic granuloma. J Am Acad Dermatol 1993; 29: 652.   5. Rowe L. Granuloma pyogenicum. AMA Arch Dermatol 1958; 78: 341–7.   6. Elmets CA, Ceilley RI. Amelanotic melanoma as a pyogenic granuloma. Cutis 1980; 25: 164–7.   7. Zaballos P, Llambrich A, Cuellar F, Puig S, Malvehy J. Dermoscopic findings in pyogenic granuloma. Br J Dermatol 2006; 154: 1108–11.   8. Zaballos P, Salsench E, Puig S, Malvehy J. Dermoscopy of pyogenic granulomas. Arch Dermatol 2007; 143: 824.   9. Wolf IH. Dermoscopic Diagnosis of Vascular lesions. Clin Dermatol 2002; 20: 273–5.

10. Argenziano G, Soyer HP, Chimenti S et al. Dermoscopy of pigmented skin lesions: results of a consensus meeting via the Internet. J Am Acad Dermatol 2003; 48: 679–93. 11. Zaballos P, Daufí C, Puig S et al. Dermoscopy of solitary angiokeratoma: a morphological study. Arch Dermatol 2007; 143: 318–25. 12. Sahin MT, Demir MA, Gunduz K, Ozturkcan S, TürelErmertcan A. Targetoid haemosiderotic haemangioma: dermoscopic monitoring of three cases and review of the literatura. Clin Exp Dermatol 2005; 30: 672–6. 13. Morales-Callaghan AM, Martinez-Garcia G, AragonesesFraile H, Miranda-Romero A. Targetoid hemosiderotic hemangioma: clinical and dermoscopical findings. J Eur Acad Dermatol Venereol 2007; 21: 267–9. 14. Menzies SW, Westerhoff K, Rabinovitz H et al. Surface microscopy of pigmented basal cell carcinoma. Arch Dermatol 2000; 136: 1012–6. 15. Menzies SW, Kreusch J, Byth K et al. Dermoscopic evaluation of amelanotic and hypomelanotic melanoma. Arch Dermatol 2008; 144: 1120–7. 16. Argenziano G, Zalaudek I, Corona R et al. Vascular structures in skin tumors. A dermoscopy study. Arch Dermatol 2004; 140: 1485–9.

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7.1

Lichen ruber planus Francisco Vázquez-López

Lichen planus is a subacute or chronic dermatosis characterized by violaceous papules that may coalesce into plaques. Postinflammatory hyperpigmentation may appear, being troublesome for the patients if it is long standing. Histologically, active papules of lichen planus show (a) hyperkeratosis, (b) focal hypergranulosis, (c) irregular acanthosis, (d) damage to the basal cell layer, and (e) band-like dermal infiltrate in close approximation to the epidermis.(1) The surface of lichen planus lesions shows clinically pathognomonic white lines or dots in a variable configuration (Wickham striae, WS), which recall those observed in the oral mucosa. The histological correlate of WS is a compact orthokeratosis above the zones of wedge-shaped hypergranulosis and acanthosis, centered around acrosyringia and acrotrichia.(1, 2) Wickham striae cannot always be recognized in the standard visual inspection. They are rendered more evident by painting the lesions with oil and by examining them with a magnifying lens. The use of dermoscopy improves and facilitates this maneuver, allowing an easier and rapid recognition of WS in clinical practice. Therefore, dermoscopy improves the clinical diagnosis of lichen ruber planus in patients with active lesions.(3–5) Dermoscopy also serves for monitoring the evolution of LP lesions and for evaluating the type of postinflammatory hyperpigmentation, which may present a prognostic significance.(6) The usual precautions must be taken in order to prevent nosocomial infections if contact, nonpolarized dermoscopy is performed on eroded lesions. By means of dermoscopy, the vessels are visualized because of the red blood cells fulfilling and passing through them. Therefore, it is also important to avoid excessive pressure on the lesion when performing this procedure, which may cause blanching and lack of visualization of the vessels if nonpolarized dermoscopy is applied or when taking photographs with skin contact.

Figure 7.1  Clinical view of a patient with active, well-developed, violaceous papules and plaques of lichen ruber planus located on the arms.

DERMOSCOPIC APPEARANCE AND EVOLUTION OF THE LESIONS OF LICHEN PLANUS 1. Initial LP lesions (round, pink papules): Initial papules of LP show round, small Wickham Striae (WS) with a central yellow-brown dot. WS are visualized as pearly whitish, opaque structures. WS can be observed with both polarized and nonpolarized dermoscopes. Polarized dermoscopes allows for better recognition of deeper structures (vasculature, dermal pigment, fibrosis) but for worse recognition of the superficial layers of the epidermis. Structures such as the milia cysts of seborrheic keratoses and the blue-white veil associated with orthokeratosis may be harder to

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Figure 7.2  Dermoscopy with low magnification of the same patient. A polygonal network of pathognomonic, white, Wickham Striae surrounded by red capillaries is shown in active LP lesions. Vascular structures are seen because they are filled with red cells (original magnification: X10). In order to prevent their occlusion it is important to avoid an excessive pressure over the lesions if nonpolarized dermoscopy is performed. appreciate with this device.(7) In LP lesions, polarized dermoscopes serve for accurately demonstrating WS, specially of its contour, but WS appear less uniform, with variations in the intensity of the color, which gives

lichen ruber planus

Figure 7.3  Dermoscopy of active LP lesions (digitally zoomed images). The Wickham Striae contours show broad ramifications, which become a reticular configuration in the largest lesion. WS are surrounded by radial capillaries. The magnification of the dermoscopic images obtained with Dermlite Foto can be increased by means of the digital zoom of the attached camera.

Figure 7.5  Dermoscopy of LP papules (digitally zoomed images). The WS presents herein thin projections of the border (“comblike” appearance), intermingled with well-defined radial capillaries. These are the most characteristic vascular finding of LP, but round vessels (globular/dots) can also be seen.

Figure 7.4  Dermoscopy of active LP lesions (digitally zoomed images). WS can be revealed with both polarized and nonpolarized dermoscopes. In LP lesions, polarized dermoscopes serve for accurately demonstrating WS, but they appear speckledlike, less uniform, showing variations in the intensity of the color. With nonpolarized dermoscopes WS appear more uniform, compact, and pearly whitish.

Figure 7.6  Dermoscopy of LP lesions showing radial, linear capillaries. Round vessels can also appear but are less characteristic (original magnification: X10).

a more speckled and “unfocused-like” appearance. With nonpolarized dermoscopes WS appear more focused, compact, and uniformly pearly whitish. In addition to the WS, peripheral capillaries become progressively more evident in LP lesions. The initial yellow-brown area of some LP papules could correspond to vacuolar

alterations of basal keratinocytes and to spongiosis in the spinous zone.(1) 2. Mature LP lesions (violaceous papules or plaques) (Figures 7.1–7.8). Mature LP lesions remain isolated or become confluent in reticular networks. WS become polymorphic and show projections of the border, which are visualized as thin spikes (“comb-like” projections) or as broad arboriform ramifications. In this phase, the central yellow-brown area disappears and prominent peripheral linear, radial capillaries surround the WS

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vzquez-lpez

Figure 7.7  Clinical view of an active lichen planus plaque.

Figure 7.9  Clinical view of long-standing annular LP of the axillary region.

Figure 7.8  Dermoscopy of this plaque revealed round and linear WS configured in a well-developed white, polygonal network, most prominent in the periphery, and outlined by radial capillaries. Some WS show yellow-brown areas (original magnification: X10).

Figure 7.10  Dermoscopy (high degree of digital zoom magnification) reveals herein a granular pigment deposition in the border of the previous annular LP lesion.

contour, intermingled with the projections of the border. Less characteristic round vessels can also be seen. Several types of pearly white WS can be recognized:

lesions show pigmented structures, with or without WS devoid of capillaries, according to their duration and the intensity of the inflammatory process. 4. Annular lichen ruber planus. This type of configuration appears most commonly in the groin and axillary area. Dermoscopy of the active border shows WS, capillaries, or pigmented structures according to their duration (Figures 7.9, 7.10). 5. Hypertrophic lichen planus appear as thickened, hyperkeratotic plaques on anterior legs. These lesions may show under dermoscopy comedo-like structures filled with yellow plugs or round corneal structures (“corn pearls”) in addition to WS and vascular findings (Figure 7.11).

(a) (b) (c) (d) (e)

Round WS Linear WS Arboriform WS Reticular WS Annular WS

3. Evolved LP lesions: These lesions show WS with decreasing, less prominent peripheral vessels. Pigmented structures begin to appear surrounding the WS contour. Long-standing

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lichen ruber planus

Figure 7.11  Dermoscopy of long-standing LP plaque (high degree of digital zoom), showing “corn pearls.” Comedo-like structures filled with yellow plugs or round, yellow corneal structures (corn pearls) can appear within some LP lesions over time.

Figures 7.13  Dermoscopy of pigmented LP lesions. Granular pigment consists of fine or coarse, grey-blue or brown round dots or globules. They outline the WS contour in recognizable patterns, such as the “ashy-holes,” showing granules clustered into round “holes” surrounded by round WS. A striking “sewing machine-like” regular distribution of clusters of pigment outlining the WS contour can also be recognized. Pigment granules first surround the WS and finally are an isolated finding (original magnification: X10).

Figure 7.12  Dermoscopy of long-standing pigmented LP lesions, revealing granular pigment outlining the contour of polygonal WS (original magnification: X10). Nonatrophic ashy or brown LP macules may present with dermoscopy a homogeneous, structureless, light-brown pattern, or a granular pigmentation. This last pattern seems to persist longer and corresponds to pigment-laden dermal melanophages.

Figures 7.14  Higher magnification of this lesion. The “ashy-holes” and a “sewing machine-like” distribution of pigment granules are well evident.

6. Postinflammatory hyperpigmentation of LP (ashy dermatosis, lichen planus pigmentosus, dyscromic and pig­ mented actinic lichen planus, and lichen planus with hyperpigmentation). Discolorations related to LP may present a long evolution, which is disturbing for patients. Different dermoscopic patterns of nonatrophic, macular, pigmented LP may be related to prognosis (6) (Figures 7.12–7.17).

Ashy or brown macules secondary to lichen planus may present with dermoscopy: (a) Homogeneous, structureless, lightbrown areas devoid of granularity. This type of pigmentation seems to present a shorter course. (b) Granular pigmentation, which corresponds to pigment-laden dermal melanophages. This pattern seems to persist longer when large amounts of granules are present. Granular pigment consists of fine or coarse, gray-blue or brown, clustered, round dots or globules,

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vzquez-lpez

Figure 7.15  Clinical view of ashy dermatosis related to lichen planus.

Figure 7.18  Dermoscopy of a psoriatic plaque (original magnification: X10), revealing multiple, uniformly sized and distributed rounded vessels (dots/globules). The color of the surrounding background may vary from pink to deep red.

FIgure 7.16  Dermoscopy of the same ashy LP lesions. Pigment granules are located herein within homogeneous brown discolorations (original magnification: X10).

Figure 7.19  Dermoscopy of plaque psoriasis (center of the lesion). A high degree of digital zoom reveals that these apparently rounded vessels are indeed convoluted, “coiled” curvilinear capillaries. within or without light-brown discolorations. They outline the WS contour in recognizable patterns such as follows:

Figure 7.17  Coarse and fine gray-blue and brown globules are better visualized in the previous lesion by increasing the magnification with zoom (Dermlite Foto).

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(a) “Ashy-holes”. Pigment granules are seen in greater amounts in rounded, depressed areas that appear centrally within some rounded WS. (b) “Sewing machine” pigment distribution. The clusters of pigment granules outline the WS contour in a striking regular distribution. Plaque psoriasis (PP) and lichen planus (LP) are well differentiated clinically. Nevertheless, dermoscopy may be helpful

lichen ruber planus to prognosis. In addition, dermoscopy may be used herein for investigative and teaching purposes.

Figure 7.20  Dermoscopy of plaque psoriasis (periphery of the lesion). The capillary loops are less coiled at the margins of the plaques (high degree of digital zoom). for discriminating between them in special instances, such as in atypical patients or when LP coexist with PP.(3, 8) As described above, LP is characterized by a network of whitish striae, which are always absent in plaque psoriasis. In contrast, PP shows multiple, uniformly sized and distributed round vessels (globular/dotted), surrounded by a colored background (pink to red) (9–10) (Figure 7.18). Nevertheless, by increasing the degree of magnification (stereomicroscope, video microscope) they are really seen as curvilinear, twisted, or convoluted vessels (Figures 7.19–7.20). The subpapillary horizontal vascular plexus is not seen with any magnification, being hidden by the epidermal hyperplasia, unless an atrophy secondary to topical steroid treatment develops.(11) In sum, dermoscopy, in conjunction with clinical examination, is a very useful and low-cost tool for diagnosing LP in most settings. It improves the recognition of pathognomonic structures (Wickham striae) and allows the recognition of different patterns of postinflammatory pigmentation likely related

REFERENCES   1. Ragaz A, Ackerman AB. Evolution, maturation, and regression of lesions of lichen planus. New observations and correlations of clinical and histologic findings. Am J Dermatopathol 1981; 3: 5–25.   2. Rivers JK, Jackson R, Orizaba M. Who was Wickham and what are his striae? Int J Dermatol 1986; 25: 611–3.   3. Vázquez-López F, Alvarez-Cuesta C, Hidalgo-García Y, Pérez-Oliva N. The handheld dermatoscope improves the recognition of Wickham striae and capillaries in Lichen planus lesions. Arch Dermatol 2001; 137: 1376.   4. Vázquez-López F, Manjón-Haces JA, Maldonado-Seral C et al. Dermoscopic features of plaque psoriasis and lichen planus: new observations. Dermatology 2003; 207: 151–6.   5. Vázquez-López F, Gómez-Díez S, Sánchez J, Pérez-Oliva N. Dermoscopy of active lichen planus. Arch Dermatol 2007; 143: 1092.   6. Vázquez-López F, Maldonado-Seral C, López-Escobar M, Pérez-Oliva N. Dermoscopy of pigmented lichen planus lesions. Clin Exp Dermatol 2003; 28: 554–5.   7. Pan Y, Gareau DS, Scope A et al. Polarized and nonpolarized dermoscopy: the explanation for the observed differences. Arch Dermatol 2008; 144: 82–9.   8. Zalaudek I, Argenziano G. Dermoscopy subpatterns of inflammatory skin disorders. Arch Dermatol 2006; 142: 808.   9. Vazquez-López F, Marghoob A, Kreusch J. Other uses of dermoscopy. In: Marghoob AA, Braun RP, Kopf AW, eds. Atlas of Dermoscopy. London, Taylor & Francis, 2005: 299–306. 10. Vázquez-López F, Zaballos P, Fueyo-Casado A, SánchezMartín J. A dermoscopy subpattern of plaque-type psoriasis: red globular rings. Arch Dermatol 2007; 143: 1612. 11. Vázquez-López F, Marghoob AA. Dermoscopic assessment of long-term topical therapies with potent steroids in chronic psoriasis. J Am Acad Dermatol 2004; 51: 811–3.

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7.2 Urticaria and urticarial vasculitis Francisco Vázquez-López

Dermoscopy may be of great help for the study of common urticaria and similar disorders, such as urticarial vasculitis and may be used for differentiating between them on a noninvasive basis in most settings. The usual precautions must be taken in order to prevent nosocomial infections if contact, nonpolarized dermoscopy is performed or when taking photographs with skin contact. Recognition of vascular structures is fundamental for evaluating lesions of urticaria. Vessels are visualized because of the red blood cells fulfilling and passing through them. Therefore, it is important to avoid excessive pressure on the lesion when performing this procedure, which may cause occlusion and lack of visualization of the vessels, if nonpolarized dermoscopy is applied or when taking contact photographs. Common urticaria (CU) is characterized by the acute or chronic appearance of transient, recurrent wheals. Histologically, urticaria is characterized by dermal or subcutaneous edema and a sparse or dense perivascular lymphocytic infiltrate, intermingled with neutrophils and eosinophils.(1, 2) Dermoscopy of CU serves to reveal the transiently dilated superficial dermal capillaries of the lesions (3) (Figures 7.21–7.26). Urticaria vasculitis (UV) presents episodes of urticaria often associated with arthralgia and abdominal pain and rarely with glomerulonephritis. The individual lesions tend to persist longer than common wheals (1–3 days). They may reveal faint purpura and resolve with residual discoloration. The degree of clinical purpura in UV is variable. Purpuric areas may be minimal and unapparent by means of the standard visual inspection, requiring biopsy for diagnosis. Dermoscopy serves herein

Figure 7.22  Polarized dermoscopy (low magnification) of a wheal (CU), disclosing a well-circumscribed, oval area, with a red network of linear vessels (original magnification: X10).

Figure 7.23  Dermoscopy with greater magnification, disclosing an irregular red network of linear vessels, which corresponds to transiently dilated, horizontally oriented dermal capillaries.

Figure 7.21  Clinical appearance of transient lesions (wheals) of common urticaria (CU) in a patient with vitiligo.

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for improving their recognition, as a first-line screening tool (4, 5) (Figures 7.27–7.30). Histologically, UV disclose fibrinoid deposits in the vessels walls, nuclear dust, neutrophilic infiltrates, and slight-to-moderate extravasation of erythrocytes. For differentiating between CU and UV lesions, nuclear dust and dermal hemorrhage have been considered the most specific differential criteria for UV.(1, 2)

urticaria and urticarial vasculitis

Figure 7.24  Dermoscopy of the same lesion after increasing the degree of magnification. The magnification of the dermoscopic images obtained with Dermlite Foto can be increased by means of the digital zoom of the attached camera, although with reduction of the image quality if it is excessive.

Figure 7.26  Dermoscopy of a CU lesion, showing a red network of linear vessels. In addition, sharp, red, round vessels can be recognized along their course. This vascular finding must be differentiated from true purpuric structures (original magnification: X10). vessels). Round vessels may be dotted/punctate/pinpointed, or globular according to their size, although this differentiation may be difficult to make. Linear vessels may appear as simple or as arboriform structures, with a defined or a blurred contour, and may form networks (Figures 7.22–7.24). Dermoscopic purpuric structures may be mainly of two types:

Figure 7.25  A peripheral red network of linear vessels surrounding a central negative area are shown in a CU lesion. The vessels were obscured by a prominent edema (original magnification: X10). Common urticaria and urticarial vasculitis clinically overlap, and biopsy is required for differentiation between them. This discrimination is important because UV may be a cutaneous manifestation of an underlying connective tissue disease. Dermoscopy, in conjunction with history and clinical examination, may be very useful for discriminating between them in daily practice. Dermoscopic differentiation between CU and UV requires the knowledge of both vascular and purpuric structures.(3–5) Dermoscopic vascular findings observed at standard magnification (x10 fold) may be seen as round (vertically oriented papillary vessels) or as linear structures (horizontal subpapillary

(a) Homogeneous, structureless purpura. It is observed in noninflammatory forms of dermal hemorrhage (vessel-wall dysfunction or trauma; degeneration of the supporting stroma; coagulation-fibrinolytic disorders, infective organisms) (e.g., senile purpura) (Figure 7.31) (b) Round purpuric dots/globules (PG), derived from perivascular hemorrhage. PG are associated with diverse purpuric inflammatory processes (pigmented purpuric dermatoses, arthropods reactions, viral and drugs reactions, leucocytoclastic vasculitis, infective organisms) (Figure 7.32). Purpuric globules are blurred and appear within a purpuric background and later within orange-brown patches. The color of the background surrounds PG but may obscure them if it is prominent or when tissue necrosis appears. (c) Other purpuric patterns that may be recognized include purpuric/black dots of subcorneal purpura and hemorrhagic crusts. Under dermoscopy, the lesions of common urticaria (CU) reveal a process of transient vasodilatation of dermal capillaries, without presenting other structures. According to the previous basic semiology, the wheals of CU disclose under dermoscopy a red, reticular network of linear vessels (Figures 7.21–7.26). This

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vzquez-lpez

Figure 7.27  Clinical picture of a patient with urticarial vasculitis (UV). The lesions do not show clinically purpuric areas, but UV may be suspected after screening with dermoscopy.

Figure 7.28  Polarized dermoscopy of a lesion of UV revealing blurred purpuric globules (PG). Lesions of UV with slight hemorrhage may also show a surrounding linear network of vessels (original magnification: X10). These PG may be clinically unapparent. dermoscopic pattern corresponds histologically with ectatic subpapillary vessels, horizontally oriented. Linear vessels may be associated with dotted vessels (Figure 7.26). Red lines may surround structureless, negative areas devoid of vascular findings in some lesions (Figure 7.25), representing areas where vessels have been obscured by a prominent edema (negative areas). Purpuric structures are not observed in CU, and red lines disappear after making a pressure on the lesion. In contrast to CU, lesions of UV characteristically show more or less prominent and numerous blurred, round purpuric structures or globules (PG). PG may appear or not appear

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Figure 7.29  Clinical image of a patient with urticarial vasculitis. Lesions consist of pruriginous, raised, urticariform plaques, but showing well-evident, numerous pethechiae. In this case, the degree of dermal hemorrhage is so severe that it is clinically evident even without dermoscopy.

Figure 7.30  Dermoscopy of the previous lesion. Purpuric globules within purpuric patches: They can be demonstrated by using dermoscopy with low magnification and also in a clinical basis (original magnification: X10). within purpuric or orange-brown patches (Figures 7.27–7.30). Recognition of PG allows easy differentiation with CU. In addition to purpuric dots/globules, lesions of UV with slight hemorrhage may reveal linear vessels (Figure 7.28). These purpuric structures correspond histologically with the presence of vasculitis and are associated with perivascular extravasation and degradation of red blood cells. The degree of dermal hemorrhage in UV lesions is variable. Dermoscopy may be of great value for the screening of lesions with minimal purpuric areas

urticaria and urticarial vasculitis

Figure 7.31  Dermoscopy of a noninflammatory form of purpura. A homogeneous, structureless purpuric patch devoid of other findings is shown (original magnification: X10).

Figure 7.32  Dermoscopy of inflammatory purpura. A lesion of leucocytoclastic vasculitis is shown, disclosing multiple, numerous, blurred, purpuric globules. Some of them are located within yellow-brown patches (original magnification: X10).

(Figures 7.27, 7.28), although purpura can be clinically evident in some severe cases (Figures 7.29, 7.30). Dermoscopic red lines and purpuric globules are not specific to urticaria and urticarial vasculitis, respectively. However, their recognition will help in discriminating between them, with the presence of PG in urticaria lesions being indicative of an underlying vasculitis. These structures are easily recognizable even by nonexpert observers and after minimal training. Dermoscopic purpuric structures of UV must be differentiated only from round vessels, which are occasionally present in CU (Figure 7.26), and from crusted erosions rarely seen in CU. Round vessels are red, well demarcated, and are located along linear vessels, whereas the purpuric globules are blurred, irregular, and not related to the vessels. In addition, the ectatic vessels of CU disappear after making a pressure on the lesion while purpuric structures of UV lesions do not blanch. In sum, dermoscopy, in conjunction with history and standard clinical examination, may serve as a first-line screening tool for discriminating between common urticaria and urticaria vasculitis on a noninvasive and low-cost basis in daily

practice. This discrimination is based on an unspecific feature (purpuric globules) but which is rendered highly specific for UV when both diseases are confronted. REFERENCES 1. Ackerman AB. Histologic diagnosis of inflammatory skin diseases. Baltimore: Williams and Wilkins; 1997. 2. Peteiro C, Toribio J. Incidence of leukocytoclastic vasculitis in chronic idiopathic urticaria. Study of 100 cases. Am J Dermatopathol 1989; 11: 528–33. 3. Vázquez-López F, Kreusch J, Marghoob AA. Dermoscopic semiology: further insights into vascular features by screening a large spectrum of nontumoral skin lesions. Br J Dermatol 2004; 150: 226–31. 4. Vázquez-López F, Maldonado-Seral C, Soler-Sánchez T, Perez-Oliva N, Marghoob AA. Surface microscopy for discriminating between common urticaria and urticarial vasculitis. Rheumatology 2003; 42: 1079–82. 5. Vazquez-López F, Marghoob A, Kreusch J. Other uses of dermoscopy. In: Marghoob AA, Braun RP, Kopf AW, eds. Atlas of Dermoscopy. London, Taylor & Francis, 2005: 299–306.

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7.3

Disorders of collagen tissues Paolo Rosina

In normal conditions or in primary Raynaud’s phenomenon (RP), the normal nailfold videocapillaroscopic (VCP) pattern shows a regular disposition of the capillary loops along the nail-bed (Figure 7.33). By contrast, in subjects suffering from secondary RP, one or more alterations in the VCP findings (architectural disorganization, enlarged loops, giant capillaries, microhemorrhages, reduction of capillary density, angiogenesis, avascular areas, etc.) should suggest a connective tissue disease (Figure 7.34 and 7.35).

Figure 7.35  Irregular capillaries distribution with few giant capillaries and avascular area in scleroderma “late” pattern (x100).

Figure 7.33  Regular disposition of the capillary loops along the nail bed (x100).

Figure 7.36  Giant capillary and hemorrhage visible with handheld dermatoscope (x10).

Figure 7.34  Videocapillaroscopic appearance of giant capillary loop (x200).

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Patients initially diagnosed as having primary RP may shift to secondary during the follow-up. VCP analysis twice a year can early detect the transition to a secondary form in patients showing at the beginning a normal pattern or not-specific nailfold capillary abnormalities.(1) In patients affected by systemic sclerosis (SSc), the most typical nail-fold VCP pattern of microangiopathy, the socalled scleroderma pattern (SP), is commonly observed. It is characterized by irregularly enlarged capillaries, giant

disorders of collagen tissues

Figure 7.37  Giant capillary and hemorrhage visible with videocapillaroscope (x100).

Figure 7.38  Tortuous and “bushy” capillaries in discoid lupus erythematosus visible with hand-held dermatoscope (x10). capillaries (capillary diameter >50 micron of both arteriolar and venular branches), microbleedings, reduced capillary number with avascular areas, capillary architecture disorganization, as well as ramified capillaries. The giant capillary is pathognomonic of the scleroderma pattern. Three distinct NVC patterns of microangiopathy have been described in SSc patients: “early,” “active,” and “late,” which do not normally coexist at the same time. Early SP is characterized by irregularly enlarged capillaries, a few giant capillaries and hemorrhages; capillary architecture is almost regular without significant loss of capillaries. In the active pattern frequent giant capillaries and hemorrhages may be observed and mild loss of capillaries and capillary architecture disorganization with a few ramified capillaries. Severe loss of capillaries with few giant capillaries, avascular areas, capillary architecture

Figure 7.39  Completely disarranged microangioarchitecture with loss of capillaries and marked angiogenesis in discoid lupus erythematosus (x200).

Figure 7.40  Vessel tortuosity with partial respect of normal reticular pattern in subacute lupus erythematosus (x200). disorganization, and ramified capillaries are typical abnormalities of late SP.(2) Nail-fold VC helps to staging the patient affected by SSc and provides prognostic information. In fact, scleroderma patterns are related to disease subset and disease severity, affecting different sites as peripheral circulation, skin, heart, and lung. Scleroderma patients with late VC pattern show an increased risk to have an active disease and to be affected by a moderate/severe skin or visceral involvement, compared with patients with early and active patterns.(3) The VC features observed in dermatomyositis and in undifferentiated connective tissue disease are generally reported as being of the “scleroderma-like pattern.” Nail-fold capillary microscopy can be performed with various optical instruments such as videocapillaroscope,

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rosina videodermatoscope, stereomicroscope, ophthalmoscope, and also hand-held dermatoscope.(4) The simplest and most direct way to carry out an approximate evaluation of skin microcirculation conditions is the hand-held dermatoscope (Figure 7.36). It is relatively easy to recognize certain features of microvascular involvement in systemic sclerosis (giant capillaries, microbledding, etc.), although sensitivity is limited by the low level of magnification possible (Figure 7.37). In cutaneous discoid lupus erythematous, tortuous and irregular “bushy” capillaries are already visible with hand-held dermatoscope (Figure 7.38), but in advanced lesions, a completely disarranged microangioarchitecture with loss of capillaries (avascular areas) and marked angiogenesis are better observed with VC (Figure 7.39). In subacute lupus erythematosus, polygon irregularities and vessel tortuosity with partial respect of normal reticular pattern are observed (Figure 7.40). This vascular pattern

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can be used in differential diagnosis when cutaneous manifestation of lupus erythematosus clinically resemble psoriasis. References 1. Cutolo M, Grassi W, Matucci Cerinic M. Raynaud’s fenomenon and the role of capillaroscopy. Arthritis Rheum 2003; 48: 3023–30. 2. Cutolo M, Pizzorni C, Sulli A. Capillaroscopy. Best Pract Res Clin Rheumatol 2005; 19: 437–52. 3. Caramaschi P, Canestrini S, Martinelli N et al. Scleroderma patients nailfold videocapillaroscopic patterns are associated with disease subset and disease severity. Rheumatology 2007; 46: 1566–9. 4. Bergman R, Sharony L, Schapira D, Nahir MA, BalbirGurman A. The handheld dermatoscope as a nail-fold capillaroscopic instrument. Arch Dermatol 2003; 139: 1027–30.

7.4 Rosacea

Paolo Rosina

Rosacea is a common dermatosis affecting 10% to 20% of the middle-aged population, especially among fair-skinned subjects. Rosacea primarily involves the cutaneous microcirculation of the central part of the face. Several etiologic factors and pathogenetic mechanisms have been proposed. Age and exposure to environmental factors, in particular ultraviolet light, are probably causing initial dermal modification in susceptible individuals. There is a general agreement that rosacea is primarily a vascular disorder characterized by persistent small-vessel dilatation and angiogenesis, increased vascular permeability and vascular hyperreactivity which results in flushing, teleangiectases, papules pustules, and phyma.(1, 2) The National Rosacea Society Expert Committee has proposed a classification and staging of rosacea defining four subtypes (erythematotelangiectatic, papulopustular, phymatous, and ocular) and one variant (granulomatous rosacea) and a grading system based on clinical score.(3) There are currently no objective measures or laboratory tests for assessing and monitoring the severity of rosacea, which rests only on clinical judgment. Some studies on rosacea have considered skin-color changes as a surrogate measurement of vessel changes. The majority of the trials evaluating erythema and teleangiectasia have utilized subjective methods of color measurement and vessel changes. The development of instrumental techniques is obviously important for a more reproducible disease assessment and may allow a more rigorous comparisons between studies, especially on drug efficacy.

Figure 7.42  Reddish background in erythematotelangiectatic rosacea (x100).

Figure 7.43  Larger polygons with thickened vessel walls in rosacea (x100).

Figure 7.41  Videocapillaroscopic images of normal facial skin (x100).

(4, 5) Capillaroscopy is widely used on nail-fold region to diagnose and monitor rheumatologic diseases and has been considered superior to indirect technique (e.g., laser Doppler) for the clinical investigation of cutaneous microcirculation in various skin disease.(6) We used the videocapillaroscopic technique to evaluate qualitative and quantitative microvessels alterations of facial rosacea and compared them with those of seborrheic dermatitis.(1) Our results indicate that videocapillaroscopy may represent a valid adjunctive method in the early identification and measurement of erythematotelangiectatic rosacea.

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rosina

Figure 7.44  Neoangiogenesis and polygonal net in rosacea (x100).

Figure 7.46  Marked polygon irregularities and pink background in seborrheic dermatitis (x100).

Figure 7.45  Teleangiectases and larger Rosacea vessel in rosacea (x200).

Figure 7.47  Vessel tortuosity in seborrheic dermatitis (x100).

Thirty patients with erythematoteleangiectatic rosacea were compared with 30 age- and sex-matched patients with facial seborrheic dermatitis and 30 healthy control subjects, using an optical probe (Videocap 200R DS Medica, Milano, Italy) at x100 and x200 magnifications. Parameters analyzed on the cheek area were background color and morphological (polygons irregularity, vessel tortuosity, neoangiogenesis) and quantitative parameters (polygon perimeter, mean diameter of teleangiectases and vessels). A regular polygonal net represents the normal distribution of the cutaneous microcirculation on the cheek, with capillary loops projected at the inner and outer part of the polygons (Figure 7.41). Patients with rosacea showed a reddish background due to the extended vessel dilatation of the subpapillary plexus

(Figure 7.42). In contrast, healthy subjects and patients with seborrheic dermatitis displayed a pink background. Characteristic alterations of skin vessels were observed in facial rosacea, with a pattern distinct from that of facial seborrheic dermatitis. In particular, rosacea showed neoangiogenesis and significantly larger polygons with thickened vessel walls (Figure 7.43 and 7.44), more prominent teleangiectases, and larger mean vessel diameter (Figure 7.45), compared to seborrheic dermatitis. Seborrheic dermatitis displayed more polygon irregularities and vessel tortuosity (Figure 7.46 and 7.47). For all the morphological and quantitative parameters investigated, no substantial differences were noted between male and female patients. In some subjects videocapillaroscopy was repeated at least twice, with an interval of 48 hours between the first and the second videocapillaroscopic examination.

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rosacea Erythema was slightly changing, but vessel characteristics did not change significantly from day 1 of the treatment, in single individuals. In contrast, no alterations were found in the nail-fold region, suggesting that rosacea specifically affects the facial microvasculature. In conclusion, facial rosacea was found to present characteristic alterations of skin vessels, with a pattern distinct from that of facial seborrheic dermatitis. In particular, neoangiogenesis, larger polygons, more prominent teleangiectases, and larger vessels diameter was observed only in rosacea, whereas seborrheic dermatitis displayed polygon irregularities and vessel tortuosity. Videocapillaroscopy is a noninvasive and easily repeatable technique that can disclose specific and measurable vessel alterations and may represent a valid adjunctive method in the early diagnosis and measurement of erythematotelangiectatic rosacea.

References 1. Rosina P, Zamperetti MR, Giovannini A, Chieregato C, Girolomoni G. Videocapillaroscopic alterations in erythematotelangiectatic rosacea. J Am Acad Dermatol 2006; 54: 100–4. 2. Crawford GH, Pelle MT, James WD. Rosacea: I. Etiology, pathogenesis, and subtype classification. J Am Acad Dermatol 2004; 51: 327–41. 3. Wilkin J, Dahl M, Detmar M et al. Standard classification of rosacea: report of the National Rosacea Society Expert Committee on the classification and staging of rosacea. J Am Acad Dermatol 2004; 50: 907–12. 4. Bamford JTM, Gessert CE, Renier CM. Measurement of the severity of rosacea. J Am Acad 2004; 51: 697–703. 5. Carpentier PH. New techniques for clinical assessment of the peripheral microcirculation. Drugs 1999; 58: 17–22. 6. Hern S, Mortimer PS. Visualization of dermal blood vessels— capillaroscopy. Clin Exp Dermatol 1999; 24: 473–8.

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7.5

Molluscum contagiosum Pedro Zaballos Diego

MOLLUSCUM CONTAGIOSUM Molluscum contagiosum (MC) is a disease caused by a poxvirus of the Molluscipox virus genus that produces a cutaneous, mucosal, benign, self-limited papular eruption of multiple, umbilicated, cutaneous tumors. It was first described and later assigned its name by Bateman in the beginning of the nineteenth century. Though generally thought to infect only humans, case reports of the virus occurring in other animals have been published. There are four main subtypes of molluscum contagiosum virus (MCV): MCV I, MCV II, MCV III, and MCV IV. There is no apparent relationship between viral subtype, morphology, or anatomical distribution. However, there appears to be marked geographical variation in the distribution of subtypes. This disease is transmitted primarily through direct skin contact with an infected individual. Fomites and sexual transmission have been suggested as another source of infection. The MCV can be found worldwide with a higher distribution in tropical areas and has a higher incidence in children, sexually active adults, and those who are immunodeficient. The average incubation time is between 2 and 7 weeks with a range extending to 6 months. Clinically, MC produces a papular eruption of multiple umbilicated lesions (Figures 7.48 and 7.49). The morphology of an individual lesion is a dome-shaped papule, flesh colored or pearly, with an umbilicated center. Lesions vary in size from 1 to 10 mm, although occasionally giant lesions are seen. The papules may become inflamed spontaneously or after trauma and present atypically in size, shape, and color. The lesions are often grouped in small

Figure 7.49  Molluscum contagiosum on a face of an adult.

Figure 7.50  Figure shows the typical pattern of molluscum contagiosum (central, poliglobular, white-yellowish amorphous structure and peripheral crown of vessels) (X10).

Figure 7.48  Clinical image of a typical case of molluscum contagiosum in a child.

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areas but may also become widely disseminated. Any cutaneous surface may be involved, but favored sites include the axillae, the antecubital and popliteal fossae, and the crural folds in children. Autoinoculation is common. MC in adults affects the groin, genital area, thighs, and lower abdomen and is often acquired sexually. Histologically, MC exhibits epidermal hyperplasia producing a crater filled with huge, up to 35 microns, eosinophilic to basophilic intracytoplasmatic inclusions that

molluscum contagiosum

Figure 7.51  Another typical dermoscopic image of molluscum contagiosum (X10).

Figure 7.52  Figure shows central, poliglobular, white-yellowish, amorphous structure surrounded by a peripheral crown of vessels with reddish globules and areas of erythema (X10).

Figure 7.53  Figure shows two pearly, waxy, dome-shaped papules located on the nose of a 76-year-old man that were clinically diagnosed as basal-cell carcinomas. However, the dermoscopic image of both lesions shows the characteristic pattern of molluscum contagiosum (a central, poliglobular, white-yellowish, amorphous structure and a peripheral crown of vessels) (X10). are called molluscum bodies or Henderson–Patterson bodies. MC is a self-limited disease, which, left untreated, will eventually resolve itself in immunocompetent hosts but may be protracted in atopic and immunocompromised individuals. Most of the common treatments consist of various means to traumatize the lesions. Antiviral and immune-modulating treatments have recently been added to the options.(1–5) The clinical diagnosis of MC is usually easy, mainly in pediatric patients, because they are normally quite characteristic in appearance. However, MC may be occasionally confused with other tumors, particularly those found in adulthood.(6) In these cases, dermoscopy discloses additional information to improve

our diagnosis.(6–10) Dermoscopically, MC displays a characteristic pattern composed of the presence of a poliglobular whiteyellowish amorphous structure in the center of the lesions with a surrounding crown of linear, fine, and sometimes blurred vessels, some of them branching, which do not usually cross the center of the lobules (Figures 7.50–7.53).(6–10) In some cases, we can also observe curvilinear vessels that form a peripheral, reddish, ring-like structure that encircle the poliglobular, white-yellowish structures, and, in more rare cases, we can see arborizing vessels (Figure 7.54), comma vessels, red globules, and dotted vessels. A central pore or umbilication could be an additional feature in some cases. The histopathological correlation of central,

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zaballos many other skin lesions with high confidence. Zaballos et al. (7) published an atypical case of a 67-year-old woman with two 5-mm, pearly, waxy, dome-shaped papules of 7-month duration, one located on the thorax and the other on the back, which were clinically diagnosed as basal-cell carcinomas and, dermoscopically, as MC because they presented this characteristic pattern.

Figure 7.54  Atypical case of molluscum contagiosum. Dermoscopic image shows isolated, peripheral, white-yellowish globules (asterisks) and arborizing vessels throughout the lesion (X10). aggregated, white-yellowish globules could be the lobulated, endophytic epidermal hyperplasia with intracytoplasmic inclusion bodies, also known as molluscum or Henderson–Paterson bodies. The crown of vessels or “red corona” corresponds histopathologically to dilated vessels in the dermis and is characteristic of MC. Vazquez-Lopez et al. (8) evaluated and classified the dermoscopic vascular structures seen in 33 nontumoral dermatoses and found this vascular structure in 10 of 15 patients with MC. However, these crown vessels are not solely limited to MC, we can also find these vascular structures in sebaceous hyperplasia.(11) However, the recognition of this pattern (a central, poliglobular, white-yellowish, amorphous structure and a peripheral crown of vessels) is very helpful in the clinical diagnosis of MC, above all in adulthood, and allows us to differentiate these disease from

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REFERENCES   1. Diven DG. An overview of poxviruses. J Am Acad Dermatol 2001; 44: 1–14.   2. Brown ST, Nalley JF, Kraus SJ. Molluscum contagiosum. Sex Transm Dis 1981; 8: 227–34.   3. Hanson D, Diven DG. Molluscum contagiosum. Dermatol Online J 2003; 9: 2.   4. Gottlieb SL, Myskowki PL. Molluscum contagiosum. Int J Dermatol 1994; 33: 453–61.   5. Valentine CL, Diven DG, Treatment modalities for molluscum contagiosum. Dermatol Ther 2000; 13: 285–9.   6. Morales A, Puig S, Zaballos P, Malvehy J. Dermoscopy of Molluscum contagiosum. Arch Dermatol 2005; 141: 1644.   7. Zaballos P, Ara M, Puig S, Malvehy J. Dermoscopy of molluscum contagiosum: a useful tool for clinical diagnosis in adulthood. J Eur Acad Dermatol Venereol 2006; 20: 482–3.   8. Vázquez-López F, Kreusch J, Marghoob AA. Dermoscopic semiology: further insights into vascular features by screening a large spectrum of nontumoral skin lesions. Br J Dermatol 2004; 150: 226–31.   9. Zalaudek I, Argenziano G, Di Stefani A et al. Dermoscopy in general dermatology. Dermatology 2006; 212: 7–18. 10. Zalaudek I, Giacomel J, Cabo H et al. Entodermoscopy: a new tool for diagnosing skin infections and infestations. Dermatology 2008; 216: 14–23. 11. Zaballos P, Ara M, Puig S, Malvehy J. Dermoscopy of sebaceous hyperplasia. Arch Dermatol 2005; 141: 808.

7.6 Sebaceous hyperplasia Pedro Zaballos Diego

SEBACEOUS HYPERPLASIA Sebaceous hyperplasia is the most common proliferative abnormality of the sebaceous glands. It most often presents on the face of older adults, particularly males. The forehead and cheeks are predominantly affected and occasionally diffuse facial involvement occurs. Other less common sites include the mouth, nose, upper arms, chest, areola, penis, and vulva. Sebaceous hyperplasia lesions begin to appear in the fifth or sixth decade of person´s life and continue to appear into later life. However, premature or familial cases have been reported in which younger individuals are affected with multiple lesions, suggesting a genetic predisposition. Lesions may occur individually, in groups, or as a sheet of papules. The classic appearance of sebaceous hyperplasia on physical examination reveals whitish-yellow or skin-colored, normally umbilicated, papules that are soft and vary in size from 2 to 9 mm. Rarely reported variants have included a giant form, a linear or zosteriform arrangement, a diffuse form, and a familial form. Juxtaclavicular beaded lines are an additional variant characterized by closely placed papules arranged in parallel rows. Sebaceous hyperplasia significantly increases in transplant patients, particularly males following heart and renal transplantation, and this may be related to therapy with cyclosporin A. Sebaceous hyperplasia has been reported in association with internal malignancy in the setting of Muir–Torre syndrome but alone does not signify a predisposition to cancer or represent a

Figure 7.56  Characteristic dermoscopic image of sebaceous hyperplasia (X10).

Figure 7.57  Another dermoscopic image of sebaceous hyperplasia (X10).

Figure 7.55  Typical dermoscopic image of sebaceous hyperplasia with aggregated white-yellowish globules in the center of the lesion (“cumulus sign”) with surrounding crown of vessels. We can also observe brownish globular structures with ring-like appearance in the center of the lesion (X10).

sign of Muir–Torre syndrome. Sebaceous hyperplasia has no direct association with malignant degeneration and is not a cause of morbidity, except perhaps related to cosmesis and, therefore, is often found incidentally upon examination. Clinically, the primary entities that must be included in the differential diagnosis of sebaceous hyperplasia are basal-cell carcinoma, fibrous papule of the face, milia, molluscum contagiosum, and other adnexal tumors.(1, 2) Sebaceous hyperplasia is frequently clinically misdiagnosed as basal-cell carcinoma.(3) Some papules

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zaballos

Figure 7.58  “Bonbon Toffee sign” is the association of a central umbilication surrounded by cumulus sign. We can also see a peripheral crown of vessels, characteristic of this tumor (X10).

Figure 7.60  Large sebaceous hyperplasia. Figure shows aggregated white-yellowish globules and groups of orderly, bending, scarcely branching vessels located throughout the lesion (X10).

Figure 7.59  Another sebaceous hyperplasia with the “Bonbon Toffee sign” (central umbilication surrounded by aggregated whiteyellowish globules) and peripheral crown of vessels (X10).

Figure 7.61  Figure shows the characteristic dermoscopic pattern of a sebaceous hyperplasia located on the penis (X10).

may be associated with characteristics similar to this malignant tumor, such as telangiectasia, and dermoscopy may be useful as a noninvasive tool to distinguish between nodular basal-cell carcinoma and sebaceous hyperplasia, reducing unnecessary surgery. Dermoscopically, sebaceous hyperplasia shows a pattern composed of the presence of aggregated white-yellowish globules in the center of the lesions with a surrounding crown of vessels (Figures 7.55–7.61).(3–7) The central aggregated white-yellowish structures or globules, showing a sharp difference from surrounding skin, were defined by Bryden et al. (3) as “cumulus sign,” a descriptive sign, because these structures resemble the cumulus clouds and correspond histopathologically to hyperplastic sebaceous glands. Bryden et al. (3) and Oztas et al. (5) observed these

structures in 100% of the sebaceous hyperplasias of their studies. These aggregated yellowish globules are not limited solely to sebaceous hyperplasia and may also be seen in some molluscum contagiosum, nevus sebaceous of Jadassohn, and sebaceous adenoma. (7–9) Sometimes, the ostium of the gland is visible as a small crater or umbilication in the center of these yellowish structures. Oztas et al. (5) named the association of the central umbilication surrounded by cumulus sign as “Bonbon Toffee sign” and found this pattern in 80% of sebaceous hyperplasias (Figures 7.58 and 7.59). Regarding vascular structures that we can find at the periphery of sebaceous hyperplasias, the most common ones are the “crown vessels” (Figures 7.55–7.60).(3–7) These vascular structures have been defined as groups of orderly, bending, scarcely branching

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sebaceous hyperplasia vessels located along the border of the lesion.(10) These vessels may extend toward the center but do not usually cross it. They are very common in sebaceous hyperplasias, but we can find these vessels in some lesions of molluscum contagiosum. Argenziano et al. (10) found crown vessels in 83.3% of sebaceous hyperplasias, and Oztas et al. (5) found crown vessels in 86.7% of cases. Other vascular structures that we can observe are arborizing vessels in 16.7% of cases according to Argenziano et al.(10) Sebaceous hyperplasia is frequently clinically misdiagnosed as basal-cell carcinoma and arborizing telangiectasias are among the characteristic criteria of this tumor. However, none of the other specific criteria of BCC (11) (blue globules; large, blue-gray, ovoid nests; leaf-like areas; spoke-wheel structures; and ulceration) have beeen found in sebaceous hyperplasias, and aggegrated white-yellowish globules are not typical in BCC. Brown dots and globules, some of them with ring-like appearance and milia-like cysts, are less common features that we can see in few sebaceous hyperplasias. REFERENCES   1. Lazar AJF, McKee PH. Tumors and related lesions of the sebaceous glands. In: McKee PH, Calonje E, Granter SR eds. Pathology of the Skin with Clinical Correlations. China: Elsevier Mosby; 2005.   2. Simpson NB, Cunliffe WJ. Disorders of the sebaceous glands. In: Burns T, Breathnach S, Cox N, Griffiths C eds. Rook´s Textbook of Dermatology. Oxford: Blackwell Publishing Ltd; 2004.

  3. Bryden AM, Dawe RS, Fleming C. Dermatoscopic features of benign sebaceous proliferation. Clin Exp Dermatol 2004; 29: 676–7.   4. Zaballos P, Ara M, Puig S, Malvehy J. Dermoscopy of sebaceous hyperplasia. Arch Dermatol 2005; 141: 808.   5. Oztas P, Polat M, Oztas M, Alli N, Ustun H. Bonbon toffee sign: a new dermatoscopic feature for sebaceous hyperplasia. J Eur Acad Dermatol Venereol 2008; 22: 1200–2.   6. Zalaudek I, Argenziano G, Di Stefani A et al. Dermoscopy in general dermatology. Dermatology 2006; 212: 7–18.   7. Kim NH, Zell DS, Kolm I, Oliviero M, Rabinovitz HS. The dermoscopic differential diagnosis of yellow lobularlike structures. Arch Dermatol 2008; 144: 962.   8. Morales A, Puig S, Zaballos P, Malvehy J. Dermoscopy of Molluscum contagiosum. Arch Dermatol 2005; 141: 1644.   9. Zaballos P, Ara M, Puig S, Malvehy J. Dermoscopy of molluscum contagiosum: a useful tool for clinical diagnosis in adulthood. J Eur Acad Dermatol Venereol 2006; 20: 482–3. 10. Argenziano G, Zalaudek I, Corona R et al. Vascular structures in skin tumors: a dermoscopy study. Arch Dermatol 2004; 140: 1485–9. 11. Menzies SW, Westerhoff K, Rabinovitz H et al. Surface microscopy of pigmented basal cell carcinoma. Arch Dermatol 2000; 136: 1012–6.

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7.7

Pigmented purpuric dermatoses Pedro Zaballos Diego

PIGMENTED PURPURIC DERMATOSES Pigmented purpuric dermatoses (PPD), also called purpura simplex or chronic capillaritis, is the generic term for a variety of chronic conditions characterized by orange/brown pigmentation (due to hemosiderin deposition likened to cayenne pepper), interspersed with fine-point purpura (due to extravasated red blood

Figure 7.64  A more advanced stage of pigmented purpuric dermatosis (Schamberg´s disease) where the red-brownish patches predominate (X10).

Figure 7.62  Characteristic dermoscopic image of PPD (Schamberg´s disease). Pattern composed of irregular, round to oval, red dots, globules, and patches, with a red-brownish or red-coppery, diffuse, homogeneous pigmentation in the background (X10).

Figure 7.65  Figure shows the presence of irregular, round to oval, red dots, globules, and patches, with a red-brownish or red-coppery, diffuse, homogeneous pigmentation in the background in a case of a pigmented, purpuric, lichenoid dermatosis of Gougerot and Blum. In the image, we can also observe a network of brownish to gray interconnected lines (X10).

Figure 7.63  Another characteristic area in the same patient where we can also find vascular structures (X10).

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cells).(1–3) PPD typically occurs on the lower limbs (Figures 7.62–7.68) in a symmetrical distribution and often shows a benign and self-limited, although chronic, course. The etiology of PPD is unknown. Gravidity and increased venous pressure are

pigmented purpuric dermatoses

Figure 7.66  Figure shows the presence of round to oval, red dots and globules and scales, with a red-brownish or red-coppery, diffuse, homogeneous pigmentation in the background in a case of Eczematoid-like purpura of Doucas and Kapetanakis (X10).

Figure 7.67  Presence of round to oval, red dots, globules, and patches, with a scanty, red-brownish, diffuse, homogeneous pigmentation in the background in a case of Majocchi´s disease (X10). important localizing factors in many cases and triggering factors such as drugs, chemical ingestions, food additives, infections, or underlying hematologic/internal diseases have been described.(1–3) PPD have traditionally been divided into five clinical entities: progressive, pigmented, purpuric dermatosis or Schamberg´s disease; purpura annularis telangiectodes or Majocchi´s disease; pigmented, purpuric, lichenoid dermatosis of Gougerot and Blum; eczematoid-like purpura of Doucas and Kapetanakis; and lichen aureus. (1–3) Schamberg´s disease (Figures 7.62–7.64) is characterized by usually asymptomatic, chronic, and persistent purpura and

Figure 7.68  Figure shows the characteristic dermoscopic pattern of PPD (lichen aureus) with irregular, round to oval, red dots, globules, and patches, with a red-brownish or red-coppery, diffuse, homogeneous pigmentation in the background. In the image we can also observe a network of brownish to gray interconnected lines, mainly in the upper part of the lesion (X10).

petechiae with conspicuous pigmentation located predominantly on the lower limbs. In Majocchi´s disease (Figure 7.67), the lesions tend to be reddish annular macules located on the lower limbs and associated with telangiectases. Patients with pigmented, purpuric, lichenoid dermatosis of Gougerot and Blum (Figure 7.65) developed lichenoid papules in addition to purpuric lesions, most often on the legs. Eczematoid-like purpura of Doucas and Kapetanakis (Figure 7.66) or itching purpura has many similarities to Schamberg´s disease but is generally more extensive, develops more rapidly, and is characterized by a persistent, intense itch. Finally, lichen aureus (Figure 7.68) is a localized variant of PPD that is characterized by the appearance of sudden-onset, limited lichenoid papules in association with purpuric lesions, located commonly on the lower limbs, and occasionally on the trunk and the face. There are other more unusual presentations that include the itching purpura of Loewenthal, linear, granulomatous, quadrantic, transitory, and familial forms.(1–3) All these disorders may show overlapping clinical and histological features. Indeed, under dermoscopic examination, all forms of PPD show similar findings.(4–6) The dermoscopic pattern associated with PPD is the presence of irregular, round to oval, red dots, globules, and patches, with a red-brownish or red-coppery, diffuse, homogeneous pigmentation in the background (Figures 7.62–7.68). The histopathological correlation of the red-brownish or red-coppery background may be the presence of the dermal infiltrate of lymphocytes and histiocytes, extravasated red blood cells, and hemosiderin-laden macrophages. The irregular red dots, globules, and patches, which were not blanched by compression, can also correspond histologically to the extravasation of red

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zaballos blood cells and to the increased number of blood vessels, some of which are dilated and swollen. In some cases, some gray dots and a network of brownish to gray interconnected lines (Figures 7.65 and 7.68) can be observed that correlate histopathologically to hemosiderin-laden macrophages (gray dots) and the presence of hyperpigmentation of the basal-cell layer and incontinentia pigmenti in the upper dermis (network-like structure) related to some lichenoid infiltrates. This characteristic pattern of PPD could be useful to distinguish them from other diseases such as angioma serpiginosum and venous stasis dermatitis. Numerous small, relatively well-demarcated, round to oval red lacunas without the brownish background were determined with dermoscopy in angioma serpiginosum (7–9), and the presence of glomerular vessels and a scaly surface is the characteristic pattern of venous stasis dermatitis.(10, 11) However, this is not a pathognomonic pattern and the presence of red dots, globules, and patches, with a red-brownish pigmentation in the background is not solely limited to PPD, as we can find a similar pattern in other diseases also. Vázquez-López et al. found a pattern composed of purpuric or reddish dots and globules in a patchy, orange-brown background in two cases of urticaria vasculitis (12) and also described a similar pattern composed of reddish or brownish globules in diffuse brownish areas in some cases of pigmented lichen planus.(13) REFERENCES   1. Cox NH, Piette WW. Purpura and microvascular occlusion. In: Burns T, Breathnach S, Cox N, Griffiths C eds. Rook´s Textbook of Dermatology. Oxford: Blackwell Publishing Ltd; 2004.   2. Superficial and deep perivascular inflammatory dermatoses. In: McKee PH, Calonje E, Granter SR eds. Pathology of the Skin with Clinical Correlations. China: Elsevier Mosby; 2005.

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  3. Sardana K, Sarkar R, Sehgal VN. Pigmented purpuric dermatoses: an overview. Int J Dermatol 2004; 43: 482–8.   4. Zaballos P, Puig S, Malvehy J. Dermoscopy of pigmented purpuric dermatoses (lichen aureus): a useful tool for clinical diagnosis. Arch Dermatol 2004; 140(10): 1290–1.   5. Zalaudek I, Ferrara G, Brongo S, Giorgio CM, Argenziano G. Atypical clinical presentation of pigmented purpuric dermatosis. J Dtsch Dermatol Ges 2006; 4: 138–40.   6. Zalaudek I, Argenziano G, Di Stefani A et al. Dermoscopy in general dermatology. Dermatology 2006; 212: 7–18.   7. Ohnishi T, Nagayama T, Morita T et al. Angioma serpiginosum: a report of 2 cases identified using epiluminescence microscopy. Arch Dermatol 1999; 135: 1366–8.   8. Kalisiak MS, Haber RM. Angioma serpiginosum with linear distribution: case report and review of the literatura. J Cutan Med Surg 2008; 12: 180–3.   9. Ilknur T, Fetil E, Akarsu S et al. Angioma serpiginosum: dermoscopy for diagnosis, pulsed dye laser for treatment. J Dermatol 2006; 33: 252–5. 10. Zaballos P, Salsench E, Puig S, Malvehy J. Dermoscopy of venous stasis dermatitis. Arch Dermatol 2006; 142: 1526. 11. Vázquez-López F, Kreusch J, Marghoob AA. Dermoscopic semiology: further insights into vascular features by screening a large spectrum of nontumoral skin lesions. Br J Dermatol 2004; 150: 226–31. 12. Vázquez-López F, Fueyo A, Sánchez-Martín J, PérezOliva N. Dermoscopy for the screening of common urticaria and urticaria vasculitis. Arch Dermatol 2008; 144: 568. 13. Vázquez-López F, Maldonado-Seral C, López-Escobar M, N Pérez-Oliva. Dermoscopy of pigmented lichen planus lesions. Clin Exp Dermatol 2003; 28: 554–64.

7.8 Actinic porokeratosis Pedro Zaballos Diego

ACTINIC POROKERATOSIS Porokeratosis is a clonal disorder of keratinization clinically characterized by sharply demarcated, atrophic, annular lesions with a distinct keratotic edge corresponding histologically to the presence of the cornoid lamella, a column of parakeratotic cells extending through the stratum corneum. The patophysiology of this disease is due to a clonal hyperproliferation of atypical keratinocytes that leads to the formation of the cornoid lamella, which expands peripherally and forms the raised boundary between abnormal and normal keratinocytes. Several risk factors for the development of porokeratosis have been identified; these factors include genetic inheritance, ultraviolet radiation, and immunosuppression. The formation of squamous or basal-cell carcinomas has been reported in all forms of porokeratosis, although the degree of premalignant potential is controversial. Five clinical variants of porokeratosis are recognized: classic porokeratosis of Mibelli, disseminated superficial actinic porokeratosis (DSAP), porokeratosis palmaris et plantaris disseminata, linear porokeratosis, and punctate porokeratosis.(1–3) DSAP is the most common presentation, with lots of lesions of up to 10 mm, predominantly in sun-exposed sites in middleaged individuals in their third or fourth decade of life, especially those with sun-sensitive skin. DSAP is 3 times as likely to develop in women than in men. The tendency to develop these lesions is inherited as an autosomical dominant. Multiple, annular, keratotic lesions that develop predominantly on the extensor

Figure 7.70  Figure shows a peripheral white-brownish track and a central, whitish, homogeneous area. We can also observe peripheral vascular structures in some areas (X10).

Figure 7.71  Figure shows a peripheral white track and a central, whitish, homogeneous area, with dotted vessels, red globules, and a delicate pigment network (X10).

Figure 7.69  Typical dermoscopic image of actinic porokeratosis with a peripheral “white track” that demarcates a central, red-whitish, homogeneous area with dotted vessels and scales (X10).

surfaces of the legs and the arms characterize DSAP. The lesion begins as a 1–3 mm conical papule, reddish or brownish in color, which contains a keratotic plug that expands to a sharp, slightly raised, keratotic ring, producing a plaque of 10 mm or more. The skin within the ring is usually somewhat atrophic and mildly reddened or hyperpigmented. In a few cases, the center of the area becomes inflamed, covered by thick hyperkeratosis, or even

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zaballos

Figure 7.72  Another example of actinic porokeratosis with a peripheral white track and a central area with dotted vessels and red globules (X10).

Figure 7.74  Figure shows a peripheral white track with a central scaly surface (X10).

Figure 7.73  Figure shows a peripheral white track with different kind of vessels (X10).

Figure 7.75  In this case of actinic porokeratosis, the epithelium toward the center was acanthotic and because of that we can observe a verrucous surface in the center of the lesion (X10).

ulcerated and crusted. They are usually asymptomatic, but they may itch slightly. The lesions of DSAP are easily mistaken for actinic keratoses, with which they may coexist, and psoriasis. There is a nonactinic form of disseminated, superficial porokeratosis after organ transplantation, renal failure, HIV infection, or in association with other causes of immunosuppression that may have a generalized distribution of identical lesions, sparing the palms and the soles.(1–3) Dermoscopically, porokeratosis reveals a whitish annular structure called “white track” located at the periphery of the lesion, with a brownish pigmentation on the inner side and with a double white track in some areas (Figures 7.69–7.75).(4–7) The color of this annular structure could be yellowish or light brown in rare cases. This single or double white track is characteristic of porokeratosis

and corresponds histopathologically to the cornoid lamella. Although nonpathognomonic, the cornoid lamella is the most histopathologic, distinctive feature of the various types of porokeratosis and consists of a thin column of tightly packed parakeratotic cells within a keratin-filled epidermal invagination. The papillary dermis beneath the cornoid lamella contains a moderately dense, lymphocytic infiltrate and dilated capillaries. Therefore, we can observe brownish pigmentation on the inner side of the white track and a peripheral vascularization. Liquefactive degeneration of the basal layer of the epithelium is sometimes present and occasionally provokes melanophagia, and, in these cases, we can observe some blue-gray coarse granules. White track demarcates a central, lightwhitish, homogeneous area with different kind of vessels (red dots and globules, linear-irregular vessels, or telangiectasias) (Figures

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actinic porokeratosis 7.69–7.73) that are more easily observed because of the presence of atrophic epithelium in the center of the porokeratosis.(4–7) The epithelium toward the center may be of normal thickness or even acanthotic and because of this we can observe, in less common cases, an intense white homogeneous area or even a verrucous surface (Figures 7.74 and 7.75) . Other uncommon structures that we can see in the center of the porokeratosis are delicate pigment network or brown globules, some of them with a ring-like appearance. The lesions of DSAP are possibly mistaken for actinic keratoses, with which they may coexist, and psoriasis. Four essential dermoscopic features were observed in nonpigmented actinic keratosis that combined to produce the “strawberry pattern”: (a) erythema, revealing a marked, pink-to-red “pseudonetwork” surrounding the hair follicles; (b) white-to-yellow surface scale; (c) fine, linear-wavy vessels surrounding the hair follicles; and (d) hair follicle openings filled with yellowish keratotic plugs and/ or surrounded by a white halo.(8, 9) Although all the actinic keratosis of the study were located on the face, none of the lesions showed the characteristic peripheral “white track” of DSAP. The dermoscopic pattern associated with psoriasis is composed of multiple, uniformly sized, and distributed dotted vessels or red globules, together with a central surface scale.(10, 11) REFERENCES   1. Judge MR, Malean WHI, Munro CS. Disorders of keratinization. In: Burns T, Breathnach S, Cox N, Griffiths C eds. Rook´s Textbook of Dermatology. Oxford: Blackwell Publishing Ltd; 2004.

  2. Shumack SP, Commens CA. Disseminated superficial actinic porokeratosis: a clinical study. J Am Acad Dermatol 1989; 20: 1015–22.   3. Sasson M, Krain AD. Porokeratosis and cutaneous malignancy. A review. Dermatol Surg 1996; 22: 339–42.   4. Delfino M, Argenziano G, Nino M. Dermoscopy for the diagnosis of porokeratosis. J Eur Acad Dermatol Venereol 2004; 18: 194–5.   5. Zaballos P, Puig S, Malvehy J. Dermoscopy of disseminated superficial actinic porokeratosis. Arch Dermatol 2004; 140(11): 1410.   6. Panasiti V, Rossi M, Curzio M, Bruni F, Calvieri S. Disseminated superficial actinic porokeratosis diagnosed by dermoscopy. Int J Dermatol 2008; 47: 308–10.   7. Vargas-Laguna E, Nagore E, Alfaro A et al. Monitoring the evolution of a localized type of porokeratosis using [dermatoscopy]. Actas Dermosifiliogr 2006; 97: 77–8.   8. Zalaudek I, Giacomel J, Argenziano G et al. Dermoscopy of facial nonpigmented actinic keratosis. Br J Dermatol 2006; 155: 951–6.   9. Peris K, Micantonio T, Piccolo D, Fargnoli MC. Dermoscopic features of actinic keratosis. J Dtsch Dermatol Ges 2007; 5: 970–6. 10. Vázquez-López F, Manjón-Haces JA, Maldonado-Seral C et al. Dermoscopic features of plaque psoriasis and lichen planus: new observations. Dermatology 2003; 207: 151–6. 11. Zalaudek I, Argenziano G, Di Stefani A et al. Dermoscopy in general dermatology. Dermatology 2006; 212: 7–18.

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7.9 Xanthomatous lesions

Filomena Mandato, Maurizio Biagioli, and Pietro Rubegni

Xanthomatous lesions of the skin manifest as typically yellowish, sometimes tending to orange or blue, macules (flat xanthomas), papules (eruptive xanthomas), nodules (tuberous xanthomas), or tendon infiltrations (tendon xanthomas).(1) Their histology is characterized by accumulation of xanthomatous cells (macrophages) containing lipids responsible for their color. Sometimes they are idiopathic, but they are more commonly encountered in patients with internal diseases, especially with high cardiovascular risk.(2) As xanthomatous lesions often indicate the concomitance of secondary or acquired hyperlipidemia, these patients should undergo analysis of lipid profile. In other cases, fortunately rare, a syndrome is involved (Table 7.1).(3–6) Xanthomization indicates a gradual process of accumulation of lipids in tumoral lesions such as histiocytomas (Figure 7.76) or inflammatory sequelae such as lipid necrobiosis, foreign body reaction, histiocytosis X, erythema elevatum diutinum, and leprosy scars. Xanthelasms––These are the most frequent xanthelomatous lesions (Figure 7.77). They manifest as yellowish papules, usually arranged symmetrically at the internal canthus of the eye, on the upper eyelids, and sometimes on the lower ones. If untreated, they may join up to form plaques that need to be removed to avoid ectropion.(7–8) Tuberous xantoma––These lesions are hard, yellowish, slowly evolving nodules, often surrounded by an erythematous halo. They are generally located symmetrically in pressure regions (elbows, knees, and ankles). Table 7.1  Syndromes Associated with Skin Xanthomas. Syndrome

Clinical symptoms and signs

Necrobiotic xanthoma

Purplish inflammatory plaques and nodules with a xanthomatous central area (chest and periorbital), associated with paraproteinemia in 80% of cases, may be associated with other hematological disorders but nondyslipidemia. Montgomery Papular xanthomas of the skin (neck, folds, disseminated xanthoma periorbital, and perioral) and mucosa (pharynx, larynx) associated with diabetes insipidus in 30% of cases. Cerebrotendinous Rare autosomal dominant hereditary xanthomatosis disease characterized by xanthelasmas, tendon xanthomas, and tuberous xanthomas. Young patients also have mental retardation, progressive spasticity, cataracts, and high cardiovascular risk. The disorder is caused by diffuse deposition of cholesterol and cholestanol.

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Figure 7.76  Solitary rethiculohistiocytoma. Dermoscopy reveals branched and linear vessels predominantly at the periphery of the lesion on an orange-yellow background (X10). Eruptive papular xantoma––These are small, inflammatory-like papules that erupt on elbows or knees and are sometimes itchy. Initially red, the papules veer to yellowish and may unite to form tuberous/eruptive xanthomas.(9) Palmar, striated xanthochromia––This skin disease present with yellowish, infiltrative maculopapules in the digital and palmar folds. It is a pathognomonic sign of hereditary dysbetalipoproteinemia, usually responsive to fibrates treatment and a diet low in fats and carbohydrates. Diffuse, flat, normolipidemic xanthomas––These large, yellowish, papular plaques with well-defined borders occur

xanthomatous lesions

Figure 7.77  Xanthelasma. Dermoscopy reveals only yellow background (X10).

Figure 7.79  Juvenile xanthogranuolma. The dermoscopic pattern is characterized by orange-yellow background with “clouds” of paler yellow deposits. Moreover, branched and linear vessels running from the periphery to the center of the lesions are present (X10).

on the face, trunk, neck, elbows, and folds (10–11) (Figure 7.78). They are not associated with dyslipidemia and may be idiopathic. Juvenile xanthogranuloma––This is the most frequent non-Langerhans histiocytosis and consists of hard, yellow to orange papule or nodule with clear borders, usually on the face or neck (Figure 7.79).(12–13) It is more frequent in children but possible also in adults. It may be isolated or eruptive and micro- (0.2–0.5 cm) or macro- (1–3 cm) nodular.

Figure 7.78  Diffuse,flat,normolipidemicxanthomas.Dermoscopic examination shows only pale yellow deposits (X10).

Dermoscopic aspects of xanthomatous lesions Xanthomatous lesions show similar patterns under the dermoscope (Figure 7.76–7.79).(14) There is always a yellowish background that may veer from pale yellow to orange (sunset color).

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mandato, biagioli, and rubegni Most contain randomly disposed linear and branched vessels. (15) A word of warning: during dermoscopic examination, undue pressure of the dermoscope on the skin may limit blood flow to the lesion and prevent observation of the vascular component.(16–17) Apart from these two features, xanthomas have no other dermoscopic characteristics, though some lesions may show other details. For example, brownish globules and dots of hemosiderin, detected by the pathology lab, were recently observed in reticulohistiocytoma. The same authors also proposed dermoscopic analysis of a xanthomized dermofibroma revealing peripheral delicate pigment network that is usually seen in typical dermatofibromas, corresponding to hyperplastic epidermis with basal hyperpigmentation.(18) References   1. De Schaetzen V, Richert B, De La Brassinne M. Les xanthomes. Rev Med Liege 2004; 59: 46–50.   2. Crook M. Xanthelasma and cardiovascular risk. Int J Clin Pract 2008; 62: 178–9.   3. Fernández-Herrera J, Pedraz J. Necrobiotic xanthogranuloma. Semin Cutan Med Surg 2007; 26: 108–13.   4. Shah KC, Poonnoose SI, George R, Jacob M, Rajshekhar V. Necrobiotic xanthogranuloma with cutaneous and cerebral manifestations. Case report and review of the literature. J Neurosurg 2004; 100: 1111–4.   5. Kumakiri M, Sudoh M, Miura Y. Xanthoma disseminatum. Report of a case, with histological and ultrastructural studies of skin lesions. J Am Acad Dermatol 1981; 4: 291–9.   6. Romero JO, Callejón JR, Alonso G. Cerebrotendinous xanthomatosis. Neurologia 2008; 23: 530–1.   7. Rohrich RJ, Janis JE, Pownell PH. Xanthelasma palpebrarum: a review and current management principles. Plast Reconstr Surg 2002; 110: 1310–4.

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  8. Singla A. Normolipemic papular xanthoma with xanthelasma. Dermatol Online J 2006; 12(3): 19.   9. Merola JF, Mengden SJ, Soldano A, Rosenman K. Eruptive xanthomas. Dermatol Online J 2008; 14: 10. 10. Breier F, Zelger B, Reiter H, Gschnait F, Zelger BW. Papular xanthoma: a clinicopathological study of 10 cases. J Cutan Pathol 2002; 29: 200–6. 11. Caputo R, Passoni E, Cavicchini S. Papular xanthoma associated with angiokeratoma of Fordyce: considerations on the nosography of this rare non-Langerhans cell histiocytoxanthomatosis. Dermatology 2003; 206: 165–8. 12. Shoo BA, Shinkai K, McCalmont TH, Fox LP. Xanthogranulomas associated with hematologic malignancy in adulthood. J Am Acad Dermatol 2008; 59: 488–93. 13. Satter EK, Gendernalik SB, Galeckas KJ. Diffuse xanthogranulomatous dermatitis and systemic Langerhans cell histiocytosis: a novel case that demonstrates bridging between the non-Langerhans cell histiocytosis and Langerhans cell histiocytosis. J Am Acad Dermatol 2008; 60: 841–8. 14. Cavicchini S, Tourlaki A, Tanzi C, Alessi E. Dermoscopy of solitary yellow lesions in adults. Arch Dermatol 2008; 144: 1412. 15. Palmer A, Bowling J. Dermoscopic appearance of juvenile xanthogranuloma. Dermatology 2007; 215: 256–9. 16. Rubegni P, Mandato F, Fimiani M. Juvenile Xanthogranuloma: dermoscopic pattern. Dermatology 2008; 218: 380. 17. Rubegni P, Mandato F, Mourmouras V, Miracco C, Fimiani M. Xanthomatous papule in a child. Clin Exp Dermatol, paper in press. 18. Zaballos P, Puig S, Llambrich A, Malvehy J. Dermoscopy of dermatofibromas: a prospective morphological study of 412 cases. Arch Dermatol 2008; 144: 75–83.

8

Dermatoscopy in cosmetic applications Warren Wallo

Dermatoscopy can be a great visual help in monitoring skin changes during treatment. Accuracy and reproducibility in positioning of skin sites over time can be achieved through (A)

documentation of skin landmarks. Color, resolution, lighting, and magnification standards should be recorded to assure precision and reproducibility of measurements.(1) (B)

Figure 8.1  Xerotic skin on the lower leg, before (A) and after 14 days’ treatment (B) with oatmeal-containing moisturizer. Imaging shows dramatic visual improvements in skin textural properties, including dryness and flaking after 2 weeks, using the oatmealcontaining skin-protectant lotion (100x) (from reference 2, by permission of Johnson & Johnson Consumer Companies, Inc. (J&JCCI); J.Nebus). (A)

(B)

Figure 8.2  (Continued)

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wallo (C)

(D)

(E)

(F)

Figure 8.2  Dermatoscopy is valuable when studying moisturization in skin of color: (A, D) baseline, (B, E) Day 1, and (C, F) Day 14, in two patients (A-C and D-F). Images show visible improvements in the appearance of skin ash and scale in skin of color patients, as well as visible improvements in skin textural lines as early as Day 1. There was continued visible improvement in skin ash at Day 14 (20x) (from reference 3, by permission of J&JCCI; G. Smith).

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videodermatoscopy in cosmetic applications (A)

(B)

(C)

(D)

Figure 8.3  The appearance of ashy skin (A, baseline) was greatly improved after treatment with a regimen consisting of twice daily topical application of an oatmeal-containing moisturizer and an exfoliating scrub containing oatmeal used on a weekly basis by an African-American female (B, 1 day; C, 7 days; D, 14 days). The presence of a hypopigmented mark can be useful in locating the exact positioning for subsequent imaging. The exact same hair follicles can also be located, and the growth of hairs can be a compelling indication of the reproducibility of this technique (20x). (from reference 5, by permission of J&JCCI; G. Smith) Xerosis and Ashy Skin In dry skin (xerosis), the corneocytes are disorderly arranged and their borders project above the surface, producing a visually dull appearance. By using the dermatoscope in cross-polarization, we enhance the visualization of the lifted coenocytes’ edges and skin flakes, which will appear white. This technique can be used to view at high magnification the improvement in skin dryness. After moisturization, the skin appears smoother and the white flakes disappear.(2) (Figure 8.1) In skin of color, the presence of fine scaliness (ash) and flakes is more apparent because of its contrast with darker skin.(1)

Clinical studies have used digital dermatoscopy to monitor the improvement of ashy skin in darker skin types after applications of an oatmeal-containing moisturizer. Dermatoglyphics and dryness were visibly less apparent as early as Day 1 and continued to improved at Day 14.(3) (Figures 8.2 and 8.3) Postinflammatory Hyperpigmentation (PIH) Skin inflammation alters the activity of melanocytes and may lead to pigmented macules and patches lasting long after the inflammation is gone (postinflammatory hyperpigmentation). Because melanosomes in dark skin can produce large quantities of melanin, PIH is

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wallo (A)

(B)

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Figure 8.4  Documenting postinflammatory hyperpigmentation (PIH) over time with dermatoscopy: (A) baseline, (B) 4 weeks, and (C) 8 weeks. With careful attention to detail, PIH marks, on the lower legs of African-American females, were followed over time, as seen in this patient. The value of dermatoscopy is clearly demonstrated for assessing changes in pigmentation and documenting changes over time and with treatment (Captured at 12x / further cropped and enlarged for publication by 5x (therefore overall mag 60x)) (from reference 5, by permission of J&JCCI; G. Smith).

most prevalent in darker skin types, and it is the cause of significant complaints by patients, especially with acne and pseudofolliculitis barbae (PFB).(4) Dermatoscopy, in cross-polarization mode, can be used to beautifully document the changes in melanin pigmentation over time and with treatment.(5) (Figure 8.4) Pseudofolliculitis Barbae (PFB) PFB is an inflammatory condition frequently affecting people of darker skin color with tightly coiled hair. The cause of PFB

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is usually the penetration of shaved hair into adjacent skin. (6) The outcome is often the formation of an inflammatory papule at the site of the in-grown hair, followed by postinflammatory hyperpigmentation. Dermatoscopy in cross-polarization mode is extremely helpful in identifying the extrafollicular skin penetration of hair and in treatment follow-up.(5) (Figure 8.5) Dermatoscopy has also been used in the clinical practice to show patients the in-growing of hair corresponding to individual papules and to enhance compliance in treatment.(7)

videodermatoscopy in cosmetic applications (A)

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Figure 8.5  Dermatoscopy of facial acne on African-American males with pseudofolliculitis barbae (PFB). Dermatoscopy was used to illustrate (A) (20X) normal skin, and various examples of the spectrum of PFB symptoms, including (B) (20X) cheek area with skin dryness around follicle; (C) (100X) site of recurring PFB; and (D) (100X) PFB lesion with extrafollicular penetration (from reference 5, by permission of J&JCCI; J. Woodruff).

Trichostasis Trichostasis spinulosa is a follicular condition in which pores retain fascicles of hair embedded in sebaceous material. This is more prominent on the centrofacial region of adult and older individuals and appears as dark pores.(8) Owing to the clear contrast between the dark-brown, clogged follicles and the surrounding skin color, videodermatoscopy and epiluminescence have been used to investigate the removal of trichostatic impactions with the use of pore strips.(9) Acne Lesions Acne consists of noninflammatory (comedones) and inflammatory lesions (papules, pustules, and nodules). In mild acne, patients are often concerned with the appearance and evolution of individual papules and pustules. They often purchase

acne-spot treatments to selectively target those lesions. The ability to accurately capture images of individual lesions is, therefore, important to study their evolution with treatment. Several studies have used digital dermatoscopy to demonstrate the efficacy of topical formulations to quickly improve papules and pustules in acne.(10) (Figure 8.6). Conclusion Dermatoscopy represents an extremely valuable tool to monitor skin conditions under magnification and standardized lighting settings. The ability of epiluminescence to visualize subsurface pigment has enabled researchers to detect details not appreciated by the naked eye. Furthermore, digitization of images has allowed the archiving of images and dramatically helped dermatologists in the monitoring of lesions and skin treatments.

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wallo (A)

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Baseline

8 hours

24 hours

Figure 8.6  Dermatoscopy of a target acne lesion before and after treatment with a 2% salicylic acid product: (A) baseline, (B) 8 hours, and (C) 24 hours. Acne target lesions can be followed using dermatoscopy, offering the opportunity to observe and measure changes in size and redness over time (12X) (from reference 10, by permission of J&JCCI; D. Miller).

References   1. Wallo W, Smith G, Luedtke M, Kurtz ES. Micro-imaging of skin with innovating methodology: Valuable for Skin of color. Poster presented at: 62nd AAD Meeting; February 6–11, Washington, DC, 2004: P278.   2. Nebus J, Wallo W, Kurtz E. Alleviating itchy, extra dry skin with an oatmeal, skin protectant lotion. J Am Acad Dermatol 2006; 54: AB53.   3. Nebus JA, Smith G, Kurtz ES, Wallo W. Alleviating dry, ashen skin in patients with skin of color. Poster presented at: 62nd AAD Meeting; February 6–11, Washington, DC, 2004: P294.   4. Baumann L, Rodriguez D, Taylor SC, Wu J. Natural considerations for skin of color. Cutis 2006; 78: 2–19.   5. Wallo W, Woodruff J, Smith G, Kurtz ES. Documentation of cutaneous conditions important in skin of color with innovative imaging approaches. J Am Acad Dermatol 2005; 52: 89.

  6. Garcia-Zuazaga J. Pseudofolliculitis barbae: review and update on new treatment modalities. Mil Med 2003; 168: 561–4.   7. Chuh A, Zawar V. Epiluminescence dermatoscopy enhanced patient compliance and achieved treatment success in pseudofolliculitis barbae. Australas J Dermatol 2006; 47: 60–2.   8. Pagnoni A, Kligman AM, el Gammal S, Stoudemayer T. Determination of density of follicles on various regions of the face by cyanoacrylate biopsy: correlation with sebum output. Br J Dermatol 1994; 131: 862–5.   9. Pagnoni A, Kligman AM, Stoudemayer T. Extraction of follicular horny impactions of the face by polymers. Efficacy and safety of a cosmetic pore-cleansing strip (Biore’). J Dermatol Treat 1999; 10: 47–52. 10. Coret C, Chantalat J, Miller D, Kurtz E. Fast-acting treatment of mild to moderate acne lesions by a novel 2% salicylic acid microgel complex. J Am Acad Dermatol 2006; 54: AB18.

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Index

Page references in italics refer to tables. acetic acid 22 acne lesions 125 actinic keratosis 117 actinic porokeratosis 115–17 albendazole 22–3 alopecia areata 33–5, 40 dystrophic hair 34–5 yellow dots 33–4 alopecia areata incognita dystrophic hairs 36 short regrowing hairs 35–6 yellow dots 35 amelanotic melanoma 88 analogue videodermoscopy 2 androgenetic alopecia (AGA) 43 hair diameter diversity 32–3 peripilar signs 33 secondary signs 33 angiogenesis and psoriasis 52 anogenital warts 73 ashy skin 123 Auspitz sign 58 balanitis 64 benzyl alcohol 21 benzyl benzoate 21 Bowen’s disease dermoscopic features of 82, 83 detection of 84 brittle nails 47 butter/margarine/mayonnaise 22 capillaroscopy 103 carbaryl 21 chronic capillaritis 112 cicatricial alopecias 37 citronella 22 clear cell acanthoma (CCA) definition 70 dermoscopic features of 71 diagnosis of 70 videodermatoscopy of 72 collagen tissues, disorders of 100–2

common urticaria (CU) 96, 97–8, 99 congenital triangular alopecia 37 contact incident light dermoscope 3–4 cosmetic applications, videodermatoscopy in 121–2, 126 acne lesions 125 postinflammatory hyperpigmentation (PIH) 123–4 pseudofolliculitis Barbae (PFB) 124 trichostasis spinulosa 125 xerosis and ashy skin 123 cotrimoxazole 23 crab lice 9, 17–18 crotamiton 21 crusted scabies see Norwegian scabies cyclosporine 54 data storage 4 dermatological digital image management, database software for 4 dermatomyositis 47 dermatoscopy 1, 2 alopecia 40–2 scabies 12–13 alopecia areata see alopecia areata alopecia areata incognita see alopecia areata incognita androgenetic alopecia (AGA) 32–3 cicatricial alopecias 37 congenital triangular alopecia 37 discoid lupus erythematosus (DLE) 39 folliculitis decalvans (FD) 40 lichen planopilaris (LPP) 37–8 trichotilomania 37 xanthomatous lesions 119–20 pyogenic granuloma 48–9 tungiasis 29–30 venular malformations 75–6, 77 warts 49 Dermo-Image 4 dermoscopy see dermatoscopy diffuse, flat, normolipidemic xanthomas 118–19 digital dermoscopy analysis, instruments for 5 digital videodermoscopy 2–3 dimethicone 21 discoid lupus erythematosus (DLE) 38–9, 102

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index disseminated superficial actinic porokeratosis (DSAP) 115–16, 117 distal subungual onychomycosis (DSO) 47 epidermal hyperplasia 52 epiluminescence microscopy 1, 11, 25 epimeres 25 epulis gravidorum 86 eruptive papular xantoma 118 erythematotelangiectatic rosacea 103, 104 folliculitis decalvans (FD) 39–40 frontal fibrosing alopecia 41 glomus tumor 49 hair loss alopecia areata 33–5 alopecia areata incognita 35–6 androgenetic alopecia (AGA) 32–3 congenital triangular alopecia 37 dermoscopy in the differential diagnosis of alopecia 40–3 discoid lupus erythematosus (dle) 38–9 folliculitis decalvans (fd) 39–40 lichen planopilaris (lpp) 37–8 normal scalp 31–2 scarring alopecia 37 therapeutic monitoring of hair loss with videodermatoscopy 43 trichotilomania 36–7 head lice clinical features 8 diagnosis of 9, 16 differential diagnosis 9 epidemiology 8 pathogenesis 8 videodermatoscopy 16–17 hemangiomas 88 Henderson–Paterson bodies 106–7, 108 human papillomaviruses (HPV) 73–4 definition 73 differential diagnosis Fordyce spots 74 pearly papules 73–4 hypomelanotic melanoma 88 hyponychium dermoscopy 45, 46 Imagestore for Healthcare 4 indomethacin 23 infantile scabies 8 ivermectin 21, 23 juvenile xanthogranuloma 119

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kerosene/gasoline/petroleum distillates 22 lacunas 88 levamisole 23 lichen aureus 113 lichen planopilaris (LPP) 37–8 lichen planus annular lichen ruber planus 92 definition 90 evolved LP lesions 92 hypertrophic lichen planus 92 initial LP lesions 90–1 mature LP lseions 91–2 postinflammatory hyperpigmentation of LP 93–5 lindane 21–2 lobular capillary hemangioma 86 Majocchi’s disease 113 malathion 22 melanocyte activation 50 melanocytic hyperplasia 49, 50, 51 melanonychia 49 distal edge of the nail plate dermoscopy 50 hyponychium and proximal nail-fold dermoscopy 50 intraoperative dermoscopy 52 melanocyte activation 49 melanocytic hyperplasia 49–50 nail plate dermoscopy of 50 Micro-Hutchinson’s sign 45, 50 Mirror Software 4 molluscipox virus 106 molluscum bodies 106–7, 108 molluscum contagiosum (MC) 106–8 clinical diagnosis of 107 epidermal hyperplasia 106–7 molluscum contagiosum virus (MCV) 106 Muir–Torre syndrome 109 nail bed melanoma 50 nail disease 45 brittle nails 47 dermoscopic examination 45 dermoscopy of hyponychium 45 distal edge of the nail plate, dermoscopy of 45 intraoperative dermoscopy 45–6 melanonychia 49–51 nail plate dermoscopy 45 nail tumors 48 glomus tumor 49 onychomatrichoma 48 onychopapilloma 48

index pyogenic granuloma 48–9 warts 49 onychomycosis 47 proximal nail fold dermoscopy 45 psoriasis 46 subungual hemathoma 47–8 nail matrix melanoma 49 nail matrix nevi 49 nail matrix psoriasis 46 nail plate dermoscopy 45 brittle nails and 47 glomus tumor and 49 onychomatrichoma and 48 onychomycosis and 47 onychopapilloma and 48 psoriasis and 46 subungual hematomas and 48 nail tumors 48 glomus tumor 49 onychomatrichoma 48 onychopapilloma 48 pyogenic granuloma 48–9 warts 49 National Rosacea Society Expert Committee 103 nits 9, 16 nonpsoriatic balanitis 66 Norwegian scabies 8 onychomatrichoma 48 onychomycosis 47 onychopapilloma 48 optical dermoscope 2 oral ivermectin 23 palmar, striated xanthochromia 118 palmoplantar psoriasis 61–3 pediculosis crab lice 9 head lice 8–9 therapeutic monitoring with videodermatoscopy 25–6 videodermatoscopy 16–18 pediculosis capitis see head lice pediculosis pubis infestation see crab lice Pediculus humanus capitis 8, 16 peno-vulvoscopy 73, 74 perifollicular erythema 37 permethrin 22 petrolatum (petroleum jelly) 22 phototricogram 43 Phthirus pubis 17 pigmented purpuric dermatoses (PPD) 112–14 clinical entities of 113 dermoscopic examination of 113–14 occurrence of 112

plaque psoriasis 53, 67, 94–5 phases of 57–8 stages of clinical polymorphism 58–60 early steady-state phase 58 initial phase 58 intermediate phase 58 late steady-state phase 59 phase of resolution 59–60 porokeratosis clinical variants of 115–16 dermoscopic features of 116 risk factors of 115 postinflammatory hyperpigmentation (PIH) 123–4 proximal nail-fold dermoscopy 45, 46 proximal subungual onychomycosis (PSO) 47 pseudofolliculitis barbae (PFB) 124 psoriasis 46 angiogenesis and 52 definition 52, 57 histopathological correlations of 57–60 palmoplantar 61–3 psoriatic balanitis 64–6 scalp 67–8 therapy monitoring 53–5 vascular patterns in 53 videocapillaroscopy in 52 videodermatoscopy in 52–3 see also plaque psoriasis psoriatic balanitis 64–6 Pthirus pubis 9 pubic lice 18, 25 purpura simplex 112 pyogenic granuloma 48–9, 89 clinical diagnosis of 86 dermoscopy in recognition of 86–7 with vascular structures 87–8 pyrethrins 22 Raynaud’s phenomenon (RP) 100 rosacea 103–5 symptoms of 104 videocapillaroscopic technique and 103 Sarcoptes scabiei 7, 25 scabies 7 biologic cycle 7 clinical features 7–8 dermoscopic diagnosis of 12 diagnosis 8 differential diagnosis 8 epidemiology 7 therapeutic monitoring with videodermatoscopy 26–8 transmission 7 videodermatoscopy and 11–14

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index scalp atrophy 39 scalp pruritus 9 scalp psoriasis 67–8 scarring alopecia 37 Schamberg’s disease 113 scleroderma 47 scleroderma pattern (SP) 100–1 scraping versus high magnification videodermatoscopy (VD) 11–12 sebaceous hyperplasia appearance of 109 dermoscopic features of 110 diagnosing 109–10 vascular structures 110–11 seborrheic dermatitis 9, 16, 53, 67, 68, 103, 104, 105 softwares for assessment and diagnosis 4–5 subacute lupus erythematosus 102 subungual hematomas 47–8 sulfur 22 systemic lupus erythematosus (SLE) 47 systemic sclerosis (SSc) 100, 101 tea tree oil 22 teledermatology 1, 13 therapeutic monitoring of parasitoses with videodermatoscopy scabies 25–6 pediculosis 26–8 therapy of scabies and pediculosis 20 alternative unproven remedies 22 natural products 22 nit combs 20 pediculosis 20 scabies 20 systemic treatment 22–3 topical treatment 21–2 TNF-α 52, 55 topical corticosteroids 22 Tricho-scan 5 trichostasis spinulosa 125 trichotilomania 36–7 tuberous xantoma 118

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tunga penetrans 29 tungiasis 29–30 urticaria 96 urticarial vasculitis (UV) 96 dermoscopic purpuric structures, types of 97–8 lesions of 99 vascular endothelial growth factor (VEGF) 52 venular malformations 75–80 clinical data and therapy of 78 definition 75 dermoscopic data and therapy of 78–80 dermoscopy of 75–6, 77, 80 histological data and therapy of 78 vessels in 76–7 videocapillaroscopy collagen tissues and 100 in psoriasis 52–3 scalp psoriasis and 67 videodermatoscopy (VD) 1, 2, 14, 20 analogue 2 clear cell acanthoma (CCA) 72 contact, noncontact and polarized 3–4 cosmetic applications 121–6 digital 2–3 palmoplantar psoriasis 61–3 pediculosis and 16–18 pediculosis capitis 16–17 phthiriasis pubis 17–18 psoriasis 52–3 psoriatic balanitis 64–5 scabies 8 therapeutic monitoring of hair loss with 43 venular malformations 76–7, 80 videodermoscopy see videodermatoscopy white superficial onychomycosis (WSO) 47 Wickham striae 90, 91, 92, 95 xanthelasms 118 xanthomatous lesions 118–20 xanthomization 118 xerosis 123

Dermatology About the book Dermatoscopy has increasingly been taken up in dermatology practice as a non-invasive technique for the differential diagnosis of pigmented skin lesions. However, there are further uses for dermatoscopy in several dermatologic conditions in terms of diagnosis, prognostic evaluation, and monitoring response to treatment. There is also the technique of videodermatoscopy – employing the use of digital systems that ensure high magnifications – in addition to the dermatoscopy that conventionally refers to manual devices. This book aims to advance knowledge of these extended clinical applications for enhanced visualization and digital imaging using manual dermatoscopy or videodermatoscopy, beyond the usual indication of cutaneous pigmented lesions. This will serve as an important yet relatively simple aid to a dermatologist’s daily office practice. Contents Introduction * Equipment * Scabies and Pediculosis: Biologic Cycle and Diagnosis * Videodermatoscopy and Scabies * Videodermatoscopy and Pediculosis * Therapy of Scabies and Pediculosis: Potential and Pitfalls * Therapeutic Monitoring of Parasitoses with Videodermatoscopy * Tungiasis * Hair Loss * Nail Diseases * Psoriasis: Vascular Pattern under Videodermatoscopy Observation * Psoriasis: Histopathological Correlations * Palmo-plantar Psoriasis * Psoriatic Balanitis * Scalp Psoriasis * Clear Cell Acanthoma * HPV Infections * Venular Malformations (Port Wine Stain Type) * Bowen’s Disease * Pyogenic Granuloma * Lichen Ruber Planus * Urticaria and Urticarial Vasculitis * Disorders of Collagen Tissues * Rosacea * Molluscum Contagiosum * Sebaceous Hyperplasia * Pigmented Purpuric Dermatoses * Actinic Porokeratosis * Xantomatous Lesions * Dermatoscopy in Cosmetic Applications

About the editors Giuseppe Micali, MD, is Professor and Chairman at the Department of Dermatology, AOU Policlinico-Vittorio Emanuele, Catania, Italy Francesco Lacarrubba, MD, is Researcher at the Department of Dermatology, AOU Policlinico-Vittorio Emanuele, Catania, Italy

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