Treatments for Skin of Color E-Book

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Written to address conditions specifically associated with ethnic disparities in skin types, Treatments for Skin of Color, by Susan C. Taylor, Sonia Badreshia, Valerie D. Callender, Raechele Cochran Gathers and David A. Rodriguez helps you effectively diagnose and treat a wide-range of skin conditions found in non-white patients. Presented in an easy-to-use, templated format, this new reference encompasses medical dermatology and cosmetic procedures and provides you with evidence-based first and second line treatment options. Practical tips and other highlighted considerations minimize the risk of potential pitfalls. A dedicated section examines alternative therapies, some of which have cultural significance and may impact medical outcomes. An abundance of vivid color images and photos provide unmatched visual guidance for accurate diagnosis and treatment.

  • Get information not found in mainstream dermatology references. Essential medical dermatology and cosmetic procedures as well as evidence-based first and second line treatment options provide you with specific information to treat a full range of conditions found in skin of color.
  • Offer your patients the best care and avoid pitfalls. Evidence-based findings and practical tips equip you with the knowledge you need to recommend and discuss the most effective treatment options with your patients.
  • Broaden your understanding of complementary and alternative medicine (CAM) used by your patients. A special section examines the cultural significance and impact on medical outcomes caused by these alternative therapies.
  • Spend less time searching with easy-to-use, templated chapters focused on visual identification and diagnosis of diseases across all skin tones, and recommended treatment options.
  • Make rapid, confident decisions on diagnosis and treatment by comparing your clinical findings to the book’s extensive collection of 270 detailed illustrations.

Sujets

Livres
Savoirs
Medecine
Médecine
Acné rosacea
United States of America
Generalized granuloma annulare
Localized granuloma annulare
SAFETY
Oncology
Alopecia mucinosa
Systemic lupus erythematosus
Pseudopelade of Brocq
Myocardial infarction
Skin physiology
Photocopier
Acne
List of cutaneous conditions
Systemic autoimmune disease
Lupus erythematosus
Papulosquamous disorder
Lichen nitidus
Benignity
Resource
Medical procedure
Mycophenolate mofetil
Granuloma annulare
Laser surgery
Erythema nodosum
Bullous pemphigoid
Data analysis
Adverse event
Atopic dermatitis
Dermatitis
Alopecia totalis
Dyshidrosis
Mycosis fungoides
Melasma
Neoplasm
Lichen sclerosus
Hyperpigmentation
Chapter (books)
Dermatomyositis
Erythema multiforme
Nevus
Urticaria
Lichen planus
Benzoyl peroxide
Cutaneous conditions
Melanoma
Light therapy
Basal cell carcinoma
Azithromycin
Random sample
Psoriatic arthritis
Amyloidosis
Erythema
Glucocorticoid
Sulfonamide (medicine)
Physician assistant
Seborrhoeic dermatitis
Itch
Folliculitis
Granuloma inguinale
Chancroid
Biopsy
Hypersensitivity
Lesion
Sarcoidosis
Immunosuppressive drug
Clinical trial
Isotretinoin
Internal medicine
Alopecia
General practitioner
Alopecia areata
Keloid
Impetigo
Acne vulgaris
Dermatology
Acrochordon
Philadelphia
Melanocytic nevus
Diabetes mellitus
Infection
Vehicle
Data storage device
Radiation therapy
Privatization
Pediatrics
Mechanics
Infectious disease
Erythromycin
Chemotherapy
Alternative medicine
Cyclophosphamide
Pemphigus
Coral
Doxycycline
Acupuncture
Hydroquinone
Acanthosis nigricans
Shampoo
Méthotrexate
Blister
Vitiligo
Cortisone
Azathioprine
Electronic
Minocycline
Prednisone
Papule
Hair
Psoriasis
London
Copyright

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Publié par
Date de parution 08 février 2011
Nombre de lectures 1
EAN13 9781437736168
Langue English
Poids de l'ouvrage 3 Mo

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Treatments for Skin of Color
Susan C Taylor, MD
Assistant Clinical Professor of Dermatology, College of
Physicians and Surgeons, Columbia University, Society Hill
Dermatology, Phildelphia, PA, USA
Raechele Cochran Gathers, MD
Senior Staff Physician, Henry Ford Hospital, Multicultural
Dermatology Center, Detroit, MI, USA
Valerie D Callender, MD
Associate Professor of Dermatology, Howard University
College of Medicine, Washington DC, USA, Callender Skin
and Laser Center, Glenn Dale, MD, USA
David A Rodriguez, MD
Voluntary Associate Professor, Dermatology and Cutaneous
Surgery, University of Miami, Medical Director, Dermatology
Associates and Research, Coral Gables, FL, USA
Sonia Badreshia-Bansal, MD
Clinical Instructor, Department of Dermatology, University of
California San Francisco, Elite MD, Inc, Advanced
Dermatology, Laser, and Plastic Surgery Institute, Danville,
CA, USA
S a u n d e r sFront Matter
Treatments for Skinof Color
Susan C Taylor MD
Assistant Clinical Professor of Dermatology
College of Physicians and Surgeons
Columbia University
Society Hill Dermatology
Phildelphia, PA, USA
Sonia Badreshia-Bansal MD
Clinical Instructor
Department of Dermatology
University of California San Francisco
Elite MD, Inc
Advanced Dermatology, Laser, and Plastic Surgery Institute
Danville, CA, USA
Valerie D Callender MD
Associate Professor of Dermatology
Howard University College of Medicine
Washington DC, USA
Callender Skin and Laser Center
Glenn Dale, MD, USA
Raechele Cochran Gathers MD
Senior Staff Physician
Henry Ford Hospital
Multicultural Dermatology Center
Detroit, MI, USA
David A Rodriguez MDVoluntary Associate Professor
Dermatology and Cutaneous Surgery
University of Miami
Medical Director
Dermatology Associates and Research
Coral Gables, FL, USA
Edinburgh, London, New
York, Oxford, Philadelphia, St Louis, Sydney, Toronto
Acquisitions Editor: Claire Bonnett/Russell Gabbedy
Development Editor: Nani Clansey
Editorial Assistant: Poppy Garraway
Project Manager: Beula Christopher
Design: Charles Gray
Illustration Manager: Bruce Hogarth
Illustrator: Gillian Richards
Marketing Manager: Richard JonesCopyright
SAUNDERS is an imprint of Elsevier Inc.
© 2011, Elsevier Inc. All rights reserved.
No part of this publication may be reproduced or transmitted in any form or
by any means, electronic or mechanical, including photocopying, recording, or
any information storage and retrieval system, without permission in writing from
the publisher. Details on how to seek permission, further information about the
Publisher’s permissions policies and our arrangements with organizations such as
the Copyright Clearance Center and the Copyright Licensing Agency, can be found
at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under
copyright by the Publisher (other than as may be noted herein).
Notices
Knowledge and best practice in this 1eld are constantly changing. As new
research and experience broaden our understanding, changes in research
methods, professional practices, or medical treatment may become necessary.
Practitioners and researchers must always rely on their own experience and
knowledge in evaluating and using any information, methods, compounds, or
experiments described herein. In using such information or methods they should
be mindful of their own safety and the safety of others, including parties for
whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identi1ed, readers are
advised to check the most current information provided (i) on procedures
featured or (ii) by the manufacturer of each product to be administered, to verify
the recommended dose or formula, the method and duration of administration,
and contraindications. It is the responsibility of practitioners, relying on their
own experience and knowledge of their patients, to make diagnoses, to determine
dosages and the best treatment for each individual patient, and to take all
appropriate safety precautions.
To the fullest extent of the law, neither the Publisher nor the authors,
contributors, or editors, assume any liability for any injury and/or damage to
persons or property as a matter of products liability, negligence or otherwise, or
from any use or operation of any methods, products, instructions, or ideascontained in the material herein.
British Library Cataloguing in Publication Data
Treatments for skin of color.
1. Skin – Diseases – Treatment. 2. Pigmentation disorders – Treatment.
3. Human skin color.
I. Taylor, Susan C.
616.5′0089 – dc22
ISBN-13: 9781437708592
Library of Congress Cataloging in Publication Data
A catalog record for this book is available from the Library of Congress

Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
$




Preface
There are many complexities associated with selection of appropriate treatment
for cutaneous diseases. These complexities increase when selecting treatment for
patients with skin of color due to structural and functional di erences in their skin
and hair as well as di ering adverse event pro les. Treatment for Skin of Color is
an important resource that will allow the practicing clinician to quickly identify
evidence-based treatment options for their skin of color patients. The scope of the
book is extensive beginning with medical dermatology followed by follicular
disorders, tumors, cosmetics and concluding with alternative medicine. Each
therapy covered has been assigned an evidence level from A (the strongest
scienti c evidence) to E (anecdotal case reports) re ecting the amount of
published evidence available to support its use.
The truly outstanding authors of Treatment for Skin of Color, to whom I am
indebted, were chosen for this project based upon the strength of their clinical
skills, and their ability to educate and present information in an organized,
succinct and easily absorbable manner. The work of Drs. Rodriguez, Gathers,
Badreshia-Bansal, and Callender with diverse patient populations coupled with
their clinical research experience have allowed us to produce a unique resource.
When a question or therapeutic dilemma arises in a teaching clinic or private
o. ce setting, Treatment for Skin of Color is a quick reference for either the
dermatology resident or the more experienced clinician. Additionally, by
providing extensive references, it provides the rst step for a seamless in-depth
look into topics of interest.
Susan C. Taylor, MDList of Contributors
Sonia Badreshia-Bansal, MD, Clinical Instructor
Department of Dermatology
University of California San Francisco
Elite MD, Inc
Advanced Dermatology, Laser, and Plastic Surgery
Institute
Danville, CA, USA
Vivek Bansal, MD, Medical Director of Plastic Surgery
Elite MD, Inc
Advanced Dermatology, Laser, and Plastic Surgery
Institute
Danville, CA, USA
Valerie D. Callender, MD, Associate Professor of
Dermatology
Howard University College of Medicine
Washington DC, USA
Callender Skin and Laser Center
Glenn Dale, MD, USA
David Robert Crowe, MD, Dermatology Resident
Department of Dermatology
University of Cincinnati
Cincinnati, OH, USA
Erica Chon Davis, MD, Dermatology Research Fellow
Callender Skin and Laser Center
Glenn Dale, MD, USA
Vijay K. Garg, MD MNAMS, Professor and Head of
Department
Department of Dermatology
Maulana Azad Medical College
New Delhi, IndiaRaechele Cochran Gathers, MD, Senior Staff Physician
Henry Ford Hospital
Multicultural Dermatology Center
Detroit, MI, USA
Hugh Morris Gloster, Jr., MD, Professor of Dermatology
Director of Dermatologic Surgery and Mohs Surgery
University of Cincinnati
Cincinnati, OH, USA
Candrice R. Heath, MD, Physician
Children’s Healthcare of AtlantaAtlanta, GA, USA
Erica Mailler-Savage, MD, Clinical Instructor
Dermatology Department
University of Cincinnati
Cincinnati, OH, USA
Vivek Nair, MD, Senior Resident
Department of Dermatology
Maulana Azad Medical College
New Delhi, India
Vic A. Narurkar, MD FAAD, Chairman
Department of Dermatology
California Pacific Medical Center
San Fransisco, CA, USA
Janet L. Nelson, MS Lac, Practitioner of Asian Medicine
Elite MD, Inc
Advanced Dermatology, Laser, and Plastic Surgery
Institute
Danville, CA, USA
Ninad Pendharkar, MD, Dermatology Resident
Penn State, College of Medicine
Department of Dermatology
Milton S. Hershey Medical Center
Hershey, PA, USA
Crystal Y. Pourciau, MD MPH, Resident PhysicianDepartment of Dermatology
Henry Ford Hospital
Detroit, MI, USA
David A. Rodriguez, MD, Clinical Assistant Professor
University of Miami School of Medicine
Dermatology and Cutaneous Surgery
Miami, FL, USA
Rashmi Sarkar, MD MNAMS, Associate Professor
Department of Dermatology
Maulana Azad Medical College
New Delhi, India
Surabhi Sinha, MD MNAMS DNB, Senior Resident
Department of Dermatology
Maulana Azad Medical College
New Delhi, India
Sumayah J. Taliaferro, MD, Dermatologist
Private Practice
Metro Atlanta Dermatology
Atlanta, GA, USA
Matthew Joseph Turner, MD PhD, Dermatology Resident
Department of Dermatology
University of Cincinnati
Cincinnati, OH, USA
Janelle Vega, MD, Dermatology Resident
University of Miami Miller School of Medicine
Miami, FL, USAEvidence Levels
Each therapy covered has been assigned a letter from A (most evidence) to E
(least evidence) signifying the amount of published evidence available to support
its use. The following table shows the criteria used in making this classification.
A DOUBLE-BLIND STUDY
At least one prospective randomized, double-blind, controlled trial without
major design flaws (in the author’s view)
B CLINICAL TRIAL ≥ 20 SUBJECTS
Prospective clinical trials with 20 or more subjects; trials lacking adequate
controls or another key facet of design, which would normally be considered
desirable (in the author’s opinion)
C CLINICAL TRIAL
Small trials with fewer than 20 subjects with signi5cant design limitations, very
large numbers of case reports (at least 20 cases in the literature), retrospective
analyses of data
D SERIES ≥ 5 SUBJECTS
Series of patients reported to respond (at least 5 cases in the literature)
E ANECDOTAL CASE REPORTS
Individual case reports amounting to published experience of less than 5 casesA c k n o w l e d g e m e n t s
Each of us had the invaluable opportunity to collaborate with extraordinary
colleagues on various chapters of this book. We thank them for their expertise and
commitment to making this book a success.
We also thank Claire Bonnett of Elsevier Publishing who guided this project from
the very beginning and Nani Clansey and Beula Christopher for their assistance in
completing this extensive project.
Drs. Taylor, Badreshia-Bansal, Callender, Gathers, and Rodriguez


Introduction
Each day in dermatology practices and clinics throughout the United States,
we nd ourselves increasingly challenged as we attempt to select the most
appropriate treatments for our skin of color patients. Our challenges are two-fold.
First, in the United States, the number of individuals with skin of color has
increased signi cantly and continues to do so. Those who were previously
considered in the minority, by the year 2056 will become the majority of US
citizens. Thus, we are increasingly encountering skin of color patients including
those with more complicated and di( cult to treat dermatologic disorders.
Secondly, di) erences in the skin and hair of individuals with skin of color have
important implications regarding treatment selection, success and sequelae.
Treatment for Skin of Color is designed to assist and guide clinicians in the
selection of the best therapeutic options for their skin of color patients, assess the
likelihood of success, and educate regarding common and unexpected adverse
events.
Who is the patient that we are primarily addressing in Treatment for Skin of
Color? For the purposes of this book, we are de ning skin of color patients as those
who have Fitzpatrick Skin Phototypes IV through VI (Table 1). Thus, we are
concentrating on individuals with darker skin hues including patients with light
brown, brown and black skin tones as compared to patients with white skin tones.
Table 1 Fitzpatrick Skin Phototypes and Corresponding Color Hues
Type Description
Type I Always burns, never tans (white skin tones)
Type II Always burns, minimal tan (white skin tones)
Type III Burns minimally, tans moderately and gradually (white skin tones)
Type IV Burns minimally, tans well (light brown skin tones)
Type V Rarely burns, tans deeply (brown skin tones)
Type VI Never burns, tans deeply (dark brown/black skin tones)
Additionally, individuals of several racial and ethnic groups are highly
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represented in the group of patients with darker skin hues including those of
Southeast and South Asian, Latino or Hispanic, African, and Native American
descent. Although there is clearly variability in skin hue amongst individuals of
these racial and ethnic groups, many have darker skin hues.
Why is it important to distinguish skin of color patients from others when
considering treatment options? Fundamental structural and functional di) erences
exist between individuals with skin of color and those with white skin tones. These
di) erences may have a direct e) ect upon a clinician’s selection of appropriate
treatment as well as for the rate of success of the treatment and occurrence of
adverse e) ects. Key di) erences involve melanin content and pigmentation, brosis
and scarring, and tightly coiled hair and follicular disorders, to name just a few.
For example, facial seborrheic dermatitis is a common cutaneous disorder in
individuals of all skin types. However, because of the lability of melanocytes in
individuals with darker skin tones, post-in ammatory hypopigmentation is often
the presenting complaint in skin of color seborrheic dermatitis patients. In this
patient population, treatment considerations will include agents that
simultaneously treat the seborrheic dermatitis as well as the post-in ammatory
hypopigmentation such as lower potency corticosteroids or topical immune
modulators. Additionally, patients should be counseled that the pigmentary
alteration is temporary and does not represent the more serious disorder, vitiligo.
Furthermore, for patients with concomitant scalp seborrheic dermatitis, daily
shampooing is often not the most appropriate treatment given the tightly coiled
hair with low water content and increased fragility of this population. Rather, the
addition of daily topical treatment agents coupled with once weekly shampooing
often yields appropriate treatment results and avoids potential adverse events.
Often, adverse event pro les are di) erent in skin of color patients.
Consequently, the selection of treatment may vary. As an example, a disorder in
which liquid nitrogen is an accepted treatment for white skin hues may not be the
appropriate treatment for skin of color patients due to the sequelae of
hypopigmentation or depigmentation. Additionally, cosmetic procedures, such as
laser hair removal may need to be performed with a lower uence or a particular
laser may be required given the propensity of skin of color toward laser induced
hyperpigmentation.
Some disorders may occur at increased frequency or even exclusively in skin
of color patient populations. An important example is central centrifugal
cicatricial alopecia (CCCA). Whereas alopecia areata is covered in general
treatment books, central centrifugal cicatricial alopecia is usually not included.
CCCA appears to be responsible for more cases of scarring alopecia in African
American women as compared to all other forms of scarring alopecia combined.

>


For this disorder, understanding treatment selection, success and sequelae is
critically important. Treatment for Skin of Color will provide insight into these
types of disorders.
Likewise, there are di) erences in the occurrence of systemic disorders in
certain skin of color populations. Hypertension and diabetes a) ect individuals of
African and Latino descent disproportionately as compared to those of Caucasian
descent. One would expect increased dermatologic disorders related to these
disorders. Examples would include disorders such as drug-induced eruptions
which may present di) erently in skin of color patients, such as photodistributed
hyperpigmentation.
Finally, the de nition of treatment success may vary with skin of color
patients as compared to those of Caucasian descent. Skin of color patients may
view acne as unsuccessfully treated if post-in ammatory hyperpigmentation (PIH)
remains after papules, pustules and comedones have resolved. Therefore,
treatment of PIH is as important as treatment of the acne in skin of color
populations. Either the selection of topical agents that can simultaneously address
acne and PIH, or the simultaneous use of acne and PIH agents are required in this
population.
How should you use this book?
Treatment for Skin of Color is a great resource that should not be read once and
then led away in a bookcase. Rather, it should be kept near you in your practice
or clinic to be referred to on a daily basis. It will provide you with the most up to
date treatment recommendations and you will nd that it will be particularly
helpful as you navigate treatment dilemmas. In addition, under each disease, you
will nd two invaluable sections: Commonly Encountered Pitfalls in Skin of Color
and Special Management and Counseling Considerations. These sections provide
diagnostic pearls, examples of potential hindrances to achieving treatment goals
and how to avoid them, and effective ways to counsel your skin of color patient.
Organization of the book
Treatment for Skin of Color is organized into six easy to use sections. Pediatric
perspectives on treatment have been added at the end of certain sections.
• Medical dermatology
• Pigmentary disorders
• Follicular disorders including alopecia



• Tumors benign and malignant
• Cosmetics
• Alternative medicine.
In each section, treatment will be outlined speci cally with your skin of color
patients in mind. Additionally, each treatment will be evaluated and assessed
based upon the current evidence available in the literature. The evidence level
scale utilized in this book is one that you may be familiar with as it encompasses
five grades, A through E.
A Double blind, control trial
B Clinical trial involving more than 20 subjects
C Clinical trial involving fewer than 20 subjects
D Case series involving more than 5 subjects
E Anecdotal case reports involving fewer than 5 subjects.
As you will see, there is a relative paucity of data for the treatment of certain
diseases that occur in your skin of color patients. In recent years, the FDA has
required populations of diverse subjects in pivotal trials for new drugs and devices.
Existing clinical trials or case series that include skin of color patients, when
available, have been cited for each treatment. Nevertheless, there are many
disorders in which there are no clinical trials or case reports that include skin of
color subjects. In these instances, we rely on anecdotal case reports, the experience
of skin of color experts or experience with non-skin of color patients.
Unlike other books that provide a guide to treatment, we thought it important
to include a section on complementary and alternative medicine (CAM) because of
its importance to many skin of color populations. Even if you do not suggest or
prescribe to these particular treatments, the CAM section in this book will provide
a rm foundation for you to understand the fundamentals of these treatments. As
you will learn in this chapter, Americans spend $34 billion dollars annually on
complementary and alternative medicine. CAM’s use by adults with dermatologic
disorders in the US has been estimated at between 50% and 62%. It has been
estimated that in skin of color patients, 50% of Native Americans, 40% of Asians,
25% of Blacks and 25% of Hispanics utilize some form of CAM. This section will
provide insight and guide you as to treatments that your patients may already be
participating in.
We trust that you will nd Treatment for Skin of Color a valuable and trusted
resource. The treatment sections o) er rst-line, second-line and third-linerecommendations which will provide the entire scope of available therapeutic
options. We trust that Treatment for Skin of Color will allow you to select the most
effective and safest treatments for your skin of color patients.
Susan C Taylor, MDTable of Contents
Front Matter
Copyright
Preface
List of Contributors
Evidence Levels
Acknowledgements
Introduction
Part 1: Medical Dermatology
Chapter 1: Acneiform Disorders
Chapter 2: Bullous and Pustular Disorders
Chapter 3: Collagen Vascular Diseases
Chapter 4: Eczematous Disorders
Chapter 5: Granulomatous Disorders
Chapter 6: Hypersensitivity and Allergic Disorders
Chapter 7: Infectious Diseases
Chapter 8: Lichenoid Disorders
Chapter 9: Papulosquamous Disorders
Part 2: Pigmentary Disorders
Chapter 10: Hyperpigmented Disorders
Chapter 11: Hypopigmented Disorders
Part 3: Follicular Disorders and Alopecias
Chapter 12: Alopecias
Chapter 13: Follicular Disorders
Part 4: Tumors Benign and Malignant
Chapter 14: Benign TumorsChapter 15: Malignant Neoplasms
Part 5: Cosmetics
Chapter 16: Cosmetic Applications
Chapter 17: Cosmetic Treatments
Part 6: Complementary and Alternative Medicine
Chapter 18: An Overview of Complementary and Alternative Medicine
IndexPart 1
Medical Dermatology*
*
1
Acneiform Disorders
Sonia Badreshia-Bansal, Vivek Bansal
Acne 3
Acne vulgaris 3
Pomade acne 12
Steroid acne 13
Pediatric perspectives: Infantile acne 13
Pediatric perspectives: Neonatal acne (acne neonatorum) 14
Acne rosacea 14
Hidradenitis suppurativa 19
Perioral dermatitis 21
Acne
Acne vulgaris
1-4Acne vulgaris is a multifactorial disorder of the pilosebaceous unit. The
pathogenesis involves a complex interaction of multiple internal and external
factors. The four main factors that cause acne include excess sebum from increased
androgenic hormonal stimulation (especially at adrenarche), follicular epidermal
hyperkeratosis with subsequent plugging of the follicle, elevated P. acnes
1-4population, and subsequent in ammation. Medications that can precipitate
acneiform lesions include corticosteroids, lithium, some antiepileptics, and
5 6iodides. Genetic factors may also play a role.
Acne vulgaris is a common skin disease that a/ ects over 85% of people at some
time point. It is also an extremely common dermatological problem among ethnic
7patients and is found predominantly during adolescence. Acne may be present in
the 3rst few weeks and months of life while a newborn is still under the in uence
of maternal hormones and when the androgen-producing portion of the adrenal
8gland is disproportionately large. Neonatal acne resolves spontaneously.
Adolescent acne commonly begins prior to the onset of puberty, when the adrenal*
*
gland begins to produce and release higher levels of the androgen hormone.
However, acne is not limited to adolescence – 12% of women and 5% of men at 25
years of age have acne. By 45 years of age 5% of both men and women are still
7affected.
The diagnosis of acne is primarily clinical and may be characterized by
comedones, papules, pustules, nodules and cysts. Acne vulgaris a/ ects areas of the
skin more densely populated with sebaceous follicles, including the face, upper
chest, and back. A severe in ammatory variant of acne, acne fulminans, can be
associated with fever, arthritis, and additional systemic symptoms. Darker skin
types represent a particular clinical challenge for dermatologists treating acne due
to the higher risk of post-in ammatory hyperpigmentation (PIH), hypertrophic
scarring, and keloids (Fig. 1.1). Additionally, acne lesions may lead to permanent
scarring. Although the overall prognosis is good, acne can result in long-lasting
psychosocial impairment and physical scarring.
Figure 1.1 This African-American patient presents with active acne and PIH.
The di/ erential diagnosis of acne is extensive. During the neonatal period, it
includes transient sebaceous hyperplasia, miliaria, and Candida. In adolescence
and adulthood, appendageal tumors such as trichoepithelioma, trichodiscomas,
cysts, steatocystoma multiplex, and eruptive vellus hair cysts should be considered
in the di/ erential diagnosis. Bacterial folliculitis, pseudomonas folliculitis (if on the
lower trunk), rosacea, pseudofolliculitis barbae, acne keloidalis nuchae, perioral
dermatitis (if previously treated with topical corticosteroids), and steroid acne (if
treated with oral corticosteroids) may also be considered. Cultures of skin lesions to
rule out Gram-negative folliculitis are necessary when acne is unresponsive to
treatment or when improvement is not maintained with treatment.
As with all patients, therapy should be directed toward the known pathogenic
factors. The grade and the severity of the acne determines which of the following
treatments is most appropriate (Fig. 1.2). When using a topical or systemic
antibiotic, a benzoyl peroxide should be utilized in conjunction to reduce the
emergence of bacterial resistance. The patient’s skin color, skin type, and*
*
*
propensity for PIH can in uence choice of formulation of a topical regimen. The
ideal acne treatment for ethnic skin would speci3cally target the in ammatory
process as well as the resulting hyperpigmentation.
Acne algorithm.20,27-31Figure 1.2
There are several components to the treatment of mild acne including topical
retinoids, antibiotics and benzoyl peroxide. Topical retinoids, including tretinoin,
adaalene and tazarotene, are comedolytic, normalize follicular hyperkeratinization,
9-11and are anti-in ammatory. Retinoids may enhance the penetration of other
12topical products and medications. They are known to thin the stratum corneum,
13cause irritation, and increase the risk of sunburn. Therefore, the use of sunscreen
is essential. Short contact method and gradual titration may be attempted to*
*
*
*
*
14increase tolerance and minimize contact irritant dermatitis. Although topical
retinoids may result in improvement of PIH, the potential for irritation may
provoke further PIH. Each retinoid has unique characteristics. For example, the
synthetic retinoid, adapalene is light stable and resistant to oxidation by benzoyl
15peroxide. Finally, retinoids are known teratogens and contraceptive counseling
must be provided to women of childbearing age.
Benzoyl peroxide is an important bacteriostatic agent that exerts its a/ ect
through the interaction of oxidized intermediates with elements of bacterial cells. It
decreases in ammatory damage by inhibiting the release of reactive oxygen species
16from polymorphonuclear leukocytes. However, the risk of irritation with
subsequent PIH may occur. Benzoyl peroxide is most e/ ective when used in a
17-18combination as resistance to this agent has not been reported.
Topical antibiotics are helpful in controlling P. acnes colonization and its
proin ammatory mediators. The development of resistance is signi3cant when
antibiotics are used as monotherapy, and greatly lowered when used in
combination treatment with benzoyl peroxide. Clindamycin inhibits bacterial
protein synthesis by binding to the 50S ribosomal subunits, causing inhibition of
19peptide-bond formation. Clindamycin suppresses the complement-derived
chemotaxis of polymorphonuclear leukocytes in vitro, thereby reducing the
20potential for in ammation. Azelaic acid is a naturally occurring dicarboxylic
acid which inhibits growth of P. acnes, alters hyperkeratinization and may help to
21lighten PIH. Sodium sulfacetamide is a generally well tolerated topical antibiotic
22that restricts P. acnes growth. It is available in a 10% lotion in combination with
5% sulfur with tinted formulations available. Salicylic acids are widely used
overthe-counter products for their comedolytic and mild anti-inflammatory ability.
Moderate to severe in ammatory acne unresponsive to a topical combination
regimen will require systemic treatment. First-line antibiotic therapy with
tetracycline or its derivatives doxycycline and minocycline, suppress growth of P.
acnes and are anti-in ammatory. At this time, minocycline is felt to have less
antibiotic resistance but increased side e/ ects including nausea, vomiting,
23,24esophagitis, yeast infection, and sun sensitivity compared to tetracycline. In
addition, minocycline crosses the blood–brain barrier and increases susceptibility to
pseudotumor cerebri and also can cause a serum sickness-like reaction,
drug23,24induced lupus, or blue-black pigmentation. Erythromycin has the greatest
25amount of resistance. Other antibiotics reportedly useful include
trimethoprimsulfamethoxazole, and azithromycin. Hormonal therapies may be e/ ective in the
treatment of acne. When hyperandrogenism is suspected, especially in a female
patient with dysmennorhea or hirsutism, a hormonal evaluation including total and
free testosterone and DHEA sulfate should be performed. Oral contraceptive agents*
*
*
*
*
*
have been shown to be e/ ective in decreasing circulating free testosterone while
26spironolactone binds the androgen receptor and reduces androgen production.
Side e/ ects with spironolactone include breast tenderness, dysmennorhea, and
abnormalities in blood pressure.
Severe, scarring acne is best treated with the oral retinoid, 13-cis-retinoic acid.
Isotretinoin normalizes follicular hyperkeratinization and causes sebaceous gland
atrophy, thus reducing sebum production and producing an unfavorable
9environment for P. acnes. In patients with marked in ammatory acne, lower
starting doses may be indicated to prevent the induction of severe ares during the
283rst month of treatment. In cases of acne fulminans or initial retinoid induced
ares, prednisone may decrease the severity of the are and subsequent exuberant
granulation tissue formation. Potential adverse events are numerous and may
include generalized xerosis, eczematous dermatitis, and elevated triglycerides,
decreased night vision, arthralgias, myalgias, headache, depression, skeletal
hyperkeratosis, elevations in liver function tests or an abnormal blood count.
Teratogenicity is among the most serious adverse events and pregnancy should not
occur during or one month post-treatment with oral isotretinoin. Thorough
contraception counseling in females of child bearing age must be performed and
two forms of contraception must be used concomitantly.
Several other options may be used adjunctively which include comedone
extraction, intralesional injections, chemical peels, and photodynamic therapy.
Comedone extraction may improve responsiveness to prescribed comedolytic
agents, but in amed lesions should be avoided. For deep or in amed cysts,
intralesional corticosteroids can be e/ ective. Chemical peels with lipophilic
comedolytics such as salicylic acid, glycolic acid, and trichloracetic acid can
28decrease corneocyte cohesion.
The sequela of acne includes acne scarring and PIH which may be improved
after the active acne has been treated (Fig. 1.3). Options for acne scarring may
include dermabrasion, laser resurfacing, and soft tissue augmentation. PIH will
improve with time regardless of therapy. However, resolution can be hastened with
vigilant use of sunscreen along with topical skin lightening agents such as
hydroquinone, retinoic acid, kojic acid, soy, niacinamide, licorice extract, azelaic
acid, glycolic acid, salicylic acid, antioxidants such as vitamin C, as well as
20chemical peels and lasers.*
Figure 1.3 Asian patient with acne scarring and biopsy consistent with osteoma
cutis.
First-Line Therapies (For Mild to Moderate Acne Vulgaris)
Topical retinoids A
Topical benzoyl peroxide A
Topical salicylic acid A
Topical antibiotics A
Topical azelaic acid A
Topical sulfur D
Topical dapsone A
Oral antibiotics A
Combination therapy A
The mainstay of acne treatment includes a regimen that targets the four
pathogenic factors. There is strong evidence to support the use of retinoids and
benzoyl peroxide in every acne regimen. In addition, in mild to moderate acne,
topical and oral antibiotics can be considered to reduce the in ammatory
component found in ethnic skin which is felt to lead to PIH.
Adapalene in the treatment of African patients. Jacyk WK. J Eur Acad
Dermatol Venereol 2001; 15(Suppl 3):37–42.
To assess the eG cacy and safety of topical adapalene gel 0.1% as a treatment for
acne vulgaris in Black South African patients, an open-label study was performed*
*
*
*
*
*
*
*
*
over a 12-week period. In the 44 subjects completing the trial, adapalene gel 0.1%
showed clear eG cacy against both in ammatory and non-in ammatory lesions. In
two-thirds of cases, patients experienced reductions in both the number of
hyperpigmented macules and the density of hyperpigmentation. Adapalene gel
0.1% is an effective, well-tolerated topical therapy for Black patients.
A comparison of adapalene gel 0.1% vs tretinoin gel 0.025% in the
treatment of acne vulgaris in China. Tu P, Li GQ, Zhu XJ, Zheng J, Wong WZ. J
Eur Acad Dermatol Venereol 2001; 15(Suppl 3):31–36.
In this Chinese patient population, 150 patients with grade II-III acne vulgaris
were randomized to 8 weeks of daily treatment with either adapalene gel 0.1% or
tretinoin gel 0.025%. Both adapalene and tretinoin produced dramatic reductions
in total, in ammatory and non-in ammatory lesion counts, in the range of 69–
74% on average. More than 70% of patients in both groups had complete
clearance or marked improvement. In general, irritation was mild, but was more
common and more severe in the tretinoin group vs the adapalene group.
Tretinoin gel microspheres 0.04% versus 0.1% in adolescents and adults
with mild to moderate acne vulgaris: A 12-week, multicenter, randomized,
double-blind, parallel-group, phase IV trial. Berger R, Rizer R, Barba A, Wilson
D, Stewart D, Grossman R. Clin Ther. 2007 Jun; 29(6):1086–1097.
In this multicenter, double-blind, controlled, parallel-group, Phase IV
doseranging study, patients with facial acne were randomized to apply either tretinoin
gel 0.04% or 0.1% each night for 12 weeks in 156 patients (57.1% white, 19%
Black, 2% Asian, 18.6% Hispanic, 2% Native American, 1.3% Other). Both resulted
in e/ ective and similar reductions in in ammatory and nonin ammatory lesions,
likely from its action on the microcomedone, the precusor lesion of acne. However,
there was greater reduction in in ammatory lesions with the 0.1% concentration.
The 0.4% concentration resulted in fewer side e/ ects such as dryness during the
early phase of the treatment, but this was not found to be significant.
A multicenter, double-blind, randomized comparison study of the e4 cacy
and tolerability of once-daily tazarotene 0.1% gel and adapalene 0.1% gel
for the treatment of facial acne vulgaris. Webster GF, Guenther L, Poulin YP,
Solomon BA, Loven K, Lee J. Cutis 2002; 69(2 Suppl):4–11.
The efficacy and tolerability of tazarotene 0.1% gel and adapalene 0.1% gel over
12 weeks was compared in a multicenter, double-blind, randomized, parallel-group
study in 145 patients with mild-to-moderate facial acne vulgaris. Compared with
adapalene, treatment with tazarotene was associated with a signi3cantly greater
incidence of treatment success and signi3cantly greater reductions in overall
disease severity, non-in ammatory lesion count, and in ammatory lesion count.
However, adapalene demonstrated a superior tolerability pro3le, especially in the
early weeks of therapy. By the end of treatment, patients considered both*
treatments to be comparably well tolerated.
Although retinoids can improve PIH in ethnic patients, caution must be taken to
slowly titrate upward so as to avoid irritant contact dermatitis and subsequent PIH.
Comparison of 5ve antimicrobial regimens for treatment of mild to
moderate in6ammatory facial acne vulgaris in the community: randomised
controlled trial. Ozolins M, Eady EA, Avery AJ, Cunli/ e WJ, Po AL, O’Neill C.
Lancet 2004; 364(9452):2188–2195.
In this randomized, observer-masked trial, participants with facial and/or
truncal acne were allocated to one of 3ve antibacterial regimens. Of approximately
130 participants for each regimen, moderate or greater improvement at 18 weeks
was reported in about 55% of participants assigned either oral oxytetracycline or
oral minocycline plus topical placebo; in an average of 63% assigned topical
benzoyl peroxide or topical erythromycin and benzoyl peroxide in a combined
formulation plus oral placebo; and in an average of 63% assigned topical
erythromycin and benzoyl peroxide separately. Most improvement occurred in the
3rst 6 weeks. Di/ erences in eG cacy were small and, generally not statistically
signi3cant. In particular, modi3ed-release minocycline, the most expensive
regimen, was not found to be superior. Benzoyl peroxide alone was the most
coste/ ective regimen for mild to moderate facial acne and represents the best value
antimicrobial for first-line use if irritant potential is limited.
Comparison of the e4 cacy and safety of a combination topical gel
formulation of benzoyl peroxide and clindamycin with benzoyl peroxide,
clindamycin and vehicle gel in the treatments of acne vulgaris. Leyden JJ,
Berger RS, Dunlap FE, Ellis CN, Connolly MA, Levy SF. Am J Clin Dermatol 2001;
2(1):33–39.
Combined use of benzoyl peroxide with topical antibiotics has been shown to
decrease the emergence of antibacterial resistant species. To determine the eG cacy
and safety of a combination benzoyl peroxide plus clindamycin gel, a 10-week,
multicenter, double-blind trial of 480 patients with moderate to severe acne was
performed. Patients were randomized to receive twice-daily treatment with 5%
benzoyl peroxide plus 1% clindamycin, 5% benzoyl peroxide, 1% clindamycin, or
vehicle. Signi3cantly greater reductions in the number of in ammatory and total
lesions were demonstrated in patients using combination therapy compared with
those using any of its three individual components.
A novel gel formulation of 0.25% tretinoin and 1.2% clindamycin
phosphate: e4 cacy in acne vulgaris patients aged 12 to 18 years. Eichen3eld
LF, Wortzman M. Pediatr Dermatol. 2009 May-Jun; 26(3):257–261.
This was a subgroup analysis of a phase 3, 12-week, multicenter, double-blind,
randomized, placebo-controlled study that compared clindamycin/retinoic*

*
*

acid(CLIN/RA) gel, clindamycin phosphate, tretinoin, and vehicle in 1710 patients
aged 12–18 years old (23% non-Caucasian). CLIN/RA is signi3cantly more
e/ ective in reducing mean lesion counts for all types of lesions regardless of
baseline severity than vehicle, clindamycin, or tretinoin (p
Combination therapy is ideal to o er synergy in their mechanism of action. The
medications should penetrate the follicle without causing excessive tolerability
problems. The manufacturer of this dual product shows at least 90% of tretinoin
particles by count have sizes ≤20 µm and at least 50% have sizes ≤10 µm. In
addition, the gel contains a mixture of solubilized and crystalline tretinoin which may
impact tolerability by slowing the delivery of tretinoin.
Adapalene-benzoyl peroxide, a 5xed-dose combination for the treatment of
acne vulgaris: results of a multicenter, randomized double-blind, controlled
study. Thiboutot DM, Weiss J, Bucko A, Eichen3eld L, Jones T, Clark S;
Adapalene-BPO Study Group. J Am Acad Dermatol. 2007 Nov; 57(5):791–799.
This was a randomized, multicenter, double-blind, parallel group study
conducted at 36 centers in the United States in 517 patients 12 years and older.
Patients were 72% Caucasion, 11% Black, 13% Hispanic, 1% Asian, 3% other.
They were randomized in a 2 : 2 : 2 : 1 ratio to receive either adapalene-BPO gel,
adapalene gel, BPO gel, or gel vehicle for 12 weeks. The combination therapy
regimen consistently provided an additional decrease of in ammatory and
nonin ammatory lesions, with statistically signi3cant di/ erences in total lesion
counts observed as early as the 3rst postbaseline assessment with good tolerability.
Total acne lesions were reduced by 51%, in ammatory lesions by 63%, and
noninflammatory lesions by 51%.
Combination therapies are highly e ective. Retinoids are anticomedogenic,
antiin- ammatory, and enhance penetration. Adapalene is stable when combined with
BPO in the presence or absence of light. Adapalene and tretinoin have been shown to
induce a dose-dependent inhibition of toll-like receptor 2 in cultured human
monocytes. P acnes acts through the toll-like receptor 2 to induce the production of
proin- ammatory cytokines. There is likely a synergistic anti-in- ammatory action
where BPO kills P acnes and adapalene down-regulates the cell surface receptor that P
acnes uses to induce cytokine production.
Comparison of a salicylic acid cleanser and a benzoyl peroxide wash in the
treatment of acne vulgaris. Shalita AR. Clin Ther 1989; 11(2):264–267.
A 4-week crossover study to compare the eG cacy of an acne cleanser containing
2% salicylic acid with that of a 10% benzoyl peroxide wash was conducted in 30
patients with mild-moderate acne vulgaris. A review of four clinical studies and a
comedolytic assay attests to the eG cacy and safety of 0.5% and 2% solutions of
salicylic acid for the treatment of acne vulgaris. Interestingly, patients treated with
the salicylic acid cleanser for the 3rst 2 weeks showed a signi3cant improvement in
*
*
*

*
*
acne, but worsened during benzoyl peroxide therapy over the following 2 weeks. In
contrast, patients initially treated with the benzoyl peroxide wash for the 3rst 2
weeks continued to improve with salicylic acid cleanser over the next 2 weeks.
Utilizing combination therapy for ethnic skin. Taylor SC. Cutis 2007; 80(1
Suppl):15–20.
Combination therapy has become the gold standard for the management of acne,
particularly for moderate-to-severe cases. In an attempt to treat and prevent PIH,
subjects received combination clindamycin 1%-benzoyl peroxide (BPO) 5% topical
gel containing glycerin and dimethicone. Subjects were randomized to receive this
combination therapy in addition to either a tretinoin microsphere (RAM) gel at
concentrations of either 0.04% or 0.1% or adapalene gel 0.1%. There was a trend
toward better resolution of hyperpigmentation in the subjects receiving the
clindamycin-BPO topical gel in combination with RAM gel 0.04%. Retinoids have
anti-in ammatory activity while decreasing microcomedo formation resulting in
dual function for acne and PIH.
Early and aggressive treatment of acne and PIH while minimizing side e ects is
essential for successful treatment in ethnic skin.
Versatility of azelaic acid 15% gel in treatment of in6ammatory acne
vulgaris. Thiboutot D. J Drugs Dermatol 2008; 7(1):13–16.
Two randomized, multicenter, controlled clinical trials compared the e/ ects of
azelaic acid (AzA) 15% gel with either topical benzoyl peroxide 5% or topical
clindamycin 1%, using a twice-daily dosing regimen. AzA 15% gel resulted in a
70% median reduction of facial papules and pustules compared with a 77%
reduction with benzoyl peroxide 5% gel and a 63% reduction with clindamycin.
93.9% of physicians reported patient improvement after an average of 73.1 days.
The majority of patients were more satisfied with AzA than with previous therapies.
Azelaic acid represents a mild but e ective treatment option for active acne, the
maintenance phase of acne, and in reducing PIH due to its skin lightening properties.
Two randomized studies demonstrate the e4 cacy and safety of dapsone
gel, 5% for the treatment of acne vulgaris. Draelos ZD, Carter E, Maloney JM,
Elewski B, Poulin Y, Lynde C; United States/Canada Dapsone Gel Study Group. J
Am Acad Dermatol. 2007 Mar; 56(3):439.
Two 12-week, randomized, double-blind phase III studies were conducted under
identical protocols to evaluate the eG cacy and safety of twice daily dapsone 5%
gel monotherapy compared with a vehicle gel control in the treatment of acne
vulgaris in 3010 patients (72.9% Caucasian, 14% African American, 9.4%
Hispanic, Asian 2.2%, 1.6% other). Although clinical improvement was observed
with both in ammatory and nonin ammatory lesions, dapsone gel was particularly
e/ ective for in ammatory acne lesions. Reductions in in ammatory lesions*
7
*
occurred earlier, within 2 weeks, and were of greater magnitude by the end of
treatment. No signi3cant change in hemoglobin or other laboratory values, even
among the 44 patients with G6PD de3ciencies (glucose-6-phosphate
dehydrogenase) was noted.
Potential mechanisms of action of this sulfone medication in acne include
antiin- ammatory and antimicrobial properties such as direct inhibition of leukocyte
tra2 cking, inhibition of chemical mediators of in- ammation, and altered levels
and/or activity of propionibacteria located in the upper third of the follicles. Although
oral dapsone has been associated with adverse hematologic reactions especially in
G6PD, topical formulation has minimal systemic absorption. Although African
Americans are more likely to have G6PD de ciency, topical dapsone is considered a
safe and well tolerated option.
Topical therapy of acne vulgaris using 2% tea lotion in comparison with
5% zinc sulphate solution. Sharquie KE, Noaimi AA, Al-Salih MM. Saudi Med J
2008; 29(12):1757–1761.
This is a randomized, single-blinded comparative clinical trial in Iraq of 40
patients, ages 13–27 years. 2% tea lotion was statistically signi3cant in decreasing
the number of in ammatory lesions in acne vulgaris, while 5% zinc sulphate
solution was bene3cial, but did not reach a statistical signi3cance. 2% tea lotion
was felt to be a good alternative remedy in the treatment of acne vulgaris, and was
superior to topical 5% zinc sulphate solution.
Second-Line Therapies (or First-Line Therapies For Moderate to Severe
Acne Vulgaris)
Intralesional corticosteroid B
Oral antibiotics A
Oral contraceptive pills (if clinically hyperandrogenic) A
Antiandrogens (if clinically hyperandrogenic) B
Use of more aggressive treatment options including oral antibiotics in
conjunction with retinoids and benzoyl peroxide containing products has been
observed to be e/ ective in 3rst line therapies for moderate to severe acne or second
line therapy for mild to moderate acne. In addition, hormonal ares have been
treated e/ ectively with oral contraceptive pills and anti-androgenic agents.
Treatment of individual nodulocystic lesions with intralesional corticosteroids is
effective.Intralesional corticosteroids in the treatment of nodulocystic acne. Levine
RM, Rasmussen JE. Arch Dermatol 1983; 119(6):480–481.
Triamcinolone acetonide at a concentration of 0.63 mg/mL was as eG cacious as
the higher concentration of 2.5 mg/mL in the treatment of nodulocystic acne.
Lower concentrations of intralesional corticosteroids are e/ ective, while minimizing
side effects including skin atrophy. Intralesional steroid injections are most effective
as adjunctive treatment for nodulocystic acne when a more rapid response is
desired.
Lymecycline in the treatment of acne: an e4 cacious, safe and
coste: ective alternative to minocycline. Bossuyt L, Bosschaert J, Richert B,
Cromphaut P, Mitchell T, Al Abadie M. Eur J Dermatol. 2003 Mar-Apr; 13(2):130–
135.
A randomized, investigator masked UK study comparing lymecycline and
minocycline in two parallel groups of 134 patients with acne vulgaris was
conducted. Lymecycline 300 mg day is comparable to minocycline in terms of
percent decrease in lesion counts and slightly superior in terms of eG cacy
compared to lowered dose of lymecycline. Treatment with lymecycline was found
to be 4 times more cost-effective than with minocycline.
Doxycycline plus levamisole: combination treatment for severe
nodulocystic acne. Ansarin H, Savabynasab S, Behzadi AH, Sadigh N, Hasanloo
J. J Drugs Dermatol 2008; 7(8):737–740.
A double-blind, randomized, placebo-controlled trial in 60 Iranian patients with
severe and reclacitrant acne vulgaris were randomly administered oral levamisole
2.5 mg/kg/wk (up to 150 mg/wk) plus doxycycline 100 mg daily or 100 mg of
oral doxycycline daily and a placebo. This study is the 3rst clinical trial that
suggests levamisole as an effective and well tolerated new treatment for severe acne
vulgaris.
Optimizing use of oral antibiotics in acne vulgaris. Del Rosso JQ, Kim G.
Dermatol Clin 2009; 27(1):33–42.
For moderate to severe facial or truncal disease, the most common oral
antibiotics for treating acne vulgaris are the tetracycline derivatives, although
macrolide agents such as erythromycin have also been used extensively. Due to
increased resistance, eG cacy of oral tetracycline and erythromycin has markedly
diminished, leading to increased use of doxycycline, minocycline, and other agents,
such as trimethoprim/sulfamethoxazole and azithromycin. Oral azithromycin has
been reported to be e/ ective in treating acne vulgaris in four open and two
investigator-blinded clinical trials, inclusive of 187 subjects and 341 subjects,
respectively, using various treatment regimens. Most commonly used regimens
included intermittent dosing schedules, such as three 250 mg doses per week,7
because of a long terminal half-life of 68 hours.
Despite documentation of widespread global prevalence of antibiotic-resistant P
acnes, topical and oral antibiotics that have been used extensively over several
years, such as topical clindamycin, oral minocycline, and oral doxycycline,
continue to show efficacy in acne vulgaris.
These oral treatments are most appropriately used in combination with a topical
regimen containing benzoyl peroxide and a topical retinoid.
Trimethoprim/sulfamethoxazole may be associated with adverse reactions that are
uncommon but potentially severe, including toxic epidermal necrolysis (TEN) and
Stevens-Johnson syndrome (SJS), primarily within the rst 1 to 2 months after
initiation of therapy, and hematologic reactions, including agranulocytosis,
hrombocytopenia, and pancytopenia, when used in high doses or preexisting folic acid
deficiency or megaloblastic hematopoiesis.
Low-dose adjunctive spironolactone in the treatment of acne in women: a
retrospective analysis of 85 consecutively treated patients. Shaw JC. J Am
Acad Dermatol 2000; 43(3):498–502.
Spironolactone, an established androgen receptor blocker, is successful in
treating adult women with acne, but side e/ ects are common at the doses reported
in published studies to date. 85 women with acne were treated with low dose
spironolactone at 50–100 mg/day, administered either as single-drug therapy or as
an adjunct to standard therapies for a maximum of 24 months. Clearing or marked
improvement of acne occurred in 66% of patients treated with low doses of
spironolactone while 27% showed partial improvement, and 7% showed no
improvement.
Anti-androgenic therapy using oral spironolactone for acne vulgaris in
Asians. Sato K, Matsumoto D, Iizuka F, Aiba-Kojima E, Watanabe-Ono A, Suga H.
Aesthetic Plast Surg 2006; 30(6):689–694.
Spironolactone (initial dose, 200 mg/day) was administered orally to 139
Japanese patients (116 females and 23 males) with severe, recurring, or
widespread acne. Most female patients exhibited excellent improvement over 20
weeks, although some discontinued treatment because of menstrual disturbances or
other reasons. The treatment was less eG cacious for the males than for the females,
and because gynecomastia developed in three male patients, spironolactone
treatment for males was stopped. Drug eruptions and edema in the lower
extremities were seen in three patients. Hormonal anti-androgenic treatments can
inhibit sebum production and acne. Obtaining this race-speci3c information is
important because Caucasians and Asians respond differently to hormone therapy.
Despite its proven e2 cacy, other hormonal anti-androgenic treatments have
limitations. For instance, cyproterone acetate is potentially carcinogenic, but is still*
*
*
widely used for severe acne in many countries. Flutamide is also restricted due to its
hepatotoxicity.
Norgestimate and ethinyl estradiol in the treatment of acne vulgaris: a
randomized, placebo-controlled trial. Redmond GP, Olson WH, Lippman JS,
Kafrissen ME, Jones TM, Jorizzo JL. Obstet Gynecol 1997; 89(4):615–622.
A prospective study of 250 women (84% white, 11% black, 1.7% oriental, 3.4%
hispanic) were enrolled in a multicenter, randomized, double-blind,
placebocontrolled clinical trial with moderate acne vulgaris. Subjects received either 3
consecutive weeks of active triphasic oral contraceptive treatment followed by 1
week of inactive drug for 6 months or 4 weeks of placebo tablets. Oral
contraceptive group was better than placebo for in ammatory lesions, total lesions,
and investigator’s global assessment. Free testosterone decreased signi3cantly and
sex hormone-binding globulin increased signi3cantly in the oral contraceptive
group thereby reducing the androgen stimulus in acne pathogenesis.
A combined oral contraceptive containing 3-mg drospirenone/20-microg
ethinyl estradiol in the treatment of acne vulgaris: a randomized,
doubleblind, placebo-controlled study evaluating lesion counts and participant
self-assessment. Lucky AW, Koltun W, Thiboutot D, Niknian M, Sampson-Landers
C, Korner P. Cutis 2008; 82(2):143–150.
This study compared the eG cacy of a low-dose combined oral contraceptive
containing 3-mg drospirenone and 20-microg ethinyl estradiol administered in a
24-day active pill/4-day inert pill (24/4) regimen and placebo in 534 women with
moderate acne vulgaris. Greater reduction was noted from baseline to end point in
individual lesion counts (papules, pustules, open and closed comedones) compared
with placebo, but did not affect nodule count.
E: ectiveness of norgestimate and ethinyl estradiol in treating moderate
acne vulgaris. Lucky AW, Henderson TA, Olson WH, Robisch DM, Lebwohl M,
Swinyer LJ. J Am Acad Dermatol 1997; 37(5 Pt 1):746–754.
To evaluate the eG cacy of a triphasic combination oral contraceptive compared
with placebo in the treatment of moderate acne vulgaris, 257 healthy female
subjects (82% Caucasian, 9.1% Black, 2.7% Oriental, 5.5% Hispanic, 0.9% Other)
with moderate comedonal or in ammatory acne vulgaris were enrolled in a
multicenter, randomized, double-blind, placebo-controlled clinical trial. Each
month for 6 months, subjects received either 3 weeks of the oral contraceptive
containing 0.035 mg of ethinyl estradiol combined with the triphasic regimen of
norgestimate followed by 7 days of inactive drug. The mean decrease in
in ammatory lesion count was 62.0% and the mean decrease in total lesion count
was 53.1% in the oral contraceptive group.*
7
Third-Line Therapies (or First Line Therapies For Severe Acne Vulgaris)
Oral isotretinoin A
The most e/ ective medication in the treatment of severe or resistant acne is oral
isotretinoin. However, the close monitoring required can be a limiting factor for
patients and the increased regulation of the medication can be a barrier to
physicians wishing to prescribe it.
Roaccutane treatment guidelines: results of an international survey.
Cunli/ e WJ, van de Kerkhof PC, Caputo R, et al. Dermatology 1997; 194(4):351–
357.
Twelve dermatologists from several countries reviewed the surveys of 1000
patients. 55% of patients had severe nodular cystic acne or severe in ammatory
acne resistant to conventional treatment and 45% of patients had either moderate
or mild acne which was either recalcitrant, scarring or psychologically distressing.
Treatment was initiated at daily doses of 0.5 mg/kg and increased to 1.0 mg/kg,
with the aim of achieving a cumulative dose of > 100–120 mg/kg. Mucocutaneous
side e/ ects occur frequently but were manageable while severe systemic side
e/ ects were rarely problematic (2%). Signi3cant cost savings when treating acne
patients with oral isotretinoin as compared to other treatment modalities were
further proven in this study.
This study highlights the important role that oral isotretinoin plays not only in
patients with severe disease but also in patients with less severe acne, especially if
there is scarring and signi cant psychological stress associated with their disease. Acne
patients should, when appropriate, be prescribed isotretinoin early in their condition to
prevent further scarring.
Other therapies
Acne
• Chemical peels
• Photodynamic therapy
• Blue and red light
• Nonablative lasers
• Comedone extraction• Microdermabrasion
Acne scarring
• Surgery:
– Subcision, punch grafts, dermabrasion
• Lasers:
– Ablative – CO , erbium, radiofrequency fractional resurfacing2
– Nonablative – Nd:YAG, IPL, fractional photothermolysis, diode, Er:YAG
• Chemical peels:
– Superficial depth: glycolic, salicylic acid
– Medium depth: Jessner’s, TCA 35%
– Deep peel: Focal trichloracetic acid 95–100%
Keloid scarring
• Silicone gel sheeting
• Intralesional corticosteroids
• Nonablative lasers
• Surgical excision
• Radiation
Post-inflammatory hyperpigmentation
• Topicals:
– Lightening agents (see Chapter 10)
– Azelaic acid
– Retinoids
– Sunscreens
• Chemical peels
• Lasers
Insight into skin lightening cosmeceuticals for women of color.
BadreshiaBansal S, Draelos ZD, J Drugs Dermatol 2007; 6(1):32–39.
This article highlights the research behind several common skin lightening
cosmeceuticals addressing their advantages and disadvantages. Commercially
available products are discussed with mechanisms of action including phenolic and
non-phenolic compounds with tyrosinase inhibition, inhibition of melanosome
transfer, antioxidants, and increased skin turnover. Their synergistic role with*
*
*
*
*
*
*
*
*
*
sunscreens and corrective cosmetic camou age that are available over the counter
are addressed.
Commonly encountered pitfalls
Acne is the number one reason that the African-American population consults a
32dermatologist. Acne vulgaris displays histological and clinical di/ erences in
33people with skin of color compared with Caucasians. Di/ erences may include a
trend toward greater P. acnes density and di/ erences in sebaceous gland size and
34activity. In skin of color acne patients, acne is primarily in ammatory.
Surprisingly comedonal lesions in Blacks display marked in ammation and points
towards a subcategory of in ammatory comedonal acne which may predispose to
PIH. This may be important when selecting appropriate therapy. Of the available
topical treatments, benzoyl peroxide is e/ ective as an anti-in ammatory. Retinoids
act on both the comedonal and in ammatory components of acne and have skin
lightening properties. However, a commonly encountered pitfall with these agents
is the occurrence of an irritant contact dermatitis. It is important that
dermatologists minimize epidermal irritation when treating skin of color because of
the risk of either PIH or postin ammatory hypopigmentation. In Dakar, Senegal,
acne patients are commonly treated with benzoyl peroxide and a topical retinoid
4for their more advanced disease. It is important to note that the use of alternative
medicine occurs frequently, particularly in Asian populations, where increasing
5PIH can occur.
The family of tetracyclines are useful in the treatment of acne in skin of color but
they are not without adverse events which can lead to common pitfalls. The
tetracycline family of antibiotics are useful in the treatment of acne in skin of color
as they are anti-in ammatory. However, they are not without adverse events which
can lead to pitfalls. Although minocycline has been used safely in this population,
it has been reported to cause a drug hypersensitivity syndrome that can resemble
35infectious mononucleosis, as well as fatalities in the ethnic population. In
addition, minocycline can induce generalized dark brown to gray discolorations or
dark blue-black macules (localized at sites of in ammation) on the lower legs or
sun exposed areas. Doxycycline is an e/ ective treatment, but has photosensitizing
properties.
Acne patients with ethnic skin are at an increased risk for developing
postin ammatory hyperpigmentation and keloidal scarring. Treatment approaches for
acne in darker skin patients must balance early aggressive intervention with the
selection of eG cacious and non-irritating agents. For most patients, a combination
of topical retinoids, and topical or oral antibiotics, with hydroquinone to control
hyperpigmentation, will be successful. For patients with sensitive skin, topical
agents in lower concentrations and with cream vehicles are preferred. While PIH*
*
*
tends to gradually disappear over time, it is the number one complaint among acne
patients with darker skin tones. PIH should be treated aggressively with a
combination of sunblock, hydroquinone, retinoid, chemical peels, and
microdermabrasion, when appropriate. Caution must be taken when treating ethnic
skin with ablative or nonablative lasers and super3cial or deep chemical peels due
to the high risk of further PIH, scarring, and permanent hypopigmentation. Keloid
scarring secondary to acne can be treated with pressure, silicone gels, intralesional
coritcosteroids, surgery, laser treatment or radiation therapy. However, keloids
treated with surgical excision can have rates of recurrence as high as 50%.
Special management & counseling considerations
Successful management of acne in ethnic patients can be achieved with early
initiation of an appropriate combination drug regimen coupled with good patient
compliance. Topical medications, such as retinoids, may be used safely and
e/ ectively to treat acne in skin of color patients. Dryness and irritation can be
minimized by counseling patients to use retinoids initially in lower concentrations
with every other day application in addition to daily use of a hydrating agent.
Patients should also be instructed to treat their skin gently, avoiding scrubbing and
picking of acne lesions. Mild, non-abrasive cleansers, non-comedogenic
moisturizers and cosmetics are preferred. Moisturizers treat the dry skin and
prevent irritant contact dermatitis that may commonly occur. In addition, use of
cocoa butter, a comedogenic agent, is very common among Black patients and
should be avoided. For best results, clinicians should manage the entire grooming
regimen of the skin and hair of their ethnic patients. Patients should be advised to
avoid comedogenic hair and scalp preparations that can cause or exacerbate acne.
32Sunscreen use has been found to be scarce in ethnic patients. Chemical
sunscreens have a higher likelihood of exacerbating acne and causing contact
dermatitis. Physical sunblocks containing micronized zinc oxide or titanium
dioxide are preferred for best protection, especially with coexisting post
in ammatory hyperpigmentation. The administration of a skin bleaching agent
combined with a photoprotective agent for application in the morning, instead of
hydrating cream, is acceptable to patients, improves compliance, and is effective.
Additionally, acne may be improved by controlling hormones and in ammation,
both of which may be in uenced by diet. Concurrent with standard anti-acne
therapy, a trial of discontinuing all dairy products and high glycemic foods should
be stopped for at least 6 months to evaluate the e/ ect, since it is thought to
contribute to elevations in growth factors and hormones that cause acne. Vitamin A
supplementation may help reduce plugging of pores in de3cient individuals, while
foods containing ω-3 essential fatty acids (EFAs) may help to control
36-42inflammation. Individualized care and close monitoring is required.References
1 Norris JF, Cunliffe WJ. A histological and immunocytochemical study of early acne
lesions. Br J Dermatol. May 1988;118(5):651-659.
2 Thiboutot D, Gilliland K, Light J, Lookingbill D. Androgen metabolism in sebaceous
glands from subjects with and without acne. Arch Dermatol. Sep
1999;135(9):10411045.
3 Pochi PE, Strauss JS. Sebaceous gland activity in black skin. Dermatol Clin. Jul
1988;6(3):349-351.
4 Kim J, Ochoa MT, Krutzik SR, Takeuchi O, Uematsu S, Legaspi AJ, et al. Activation
of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J
Immunol. Aug 1 2002;169(3):1535-1541.
5 Weiss JS. Current options for the topical treatment of acne vulgaris. Pediatr Dermatol.
1997;14:480-488.
6 Goulden V, McGeown CH, Cunliffe WJ. The familial risk of adult acne: a comparison
between first-degree relatives of affected and unaffected individuals. Br J
Dermatol. Aug 1999;141(2):297-300.
7 Krowchuk DP, Lucky AW. Managing adolescent acne. Adolesc Med. 12(2), 2001 Jun.
8 Katsambas AD, Katoulis AC, Stavropoulos P. Acne neonatorum: a study of 22 cases.
Int J Dermatol. 1999 Feb;38(2):128-130.
9 Gollnick H, Cunliffe W, Berson D, Dreno B, Finlay A, Leyden JJ, et alGlobal Alliance
to Improve Outcomes in Acne. Management of acne: a report from a Global
Alliance to Improve Outcomes in Acne. J Am Acad Dermatol. 2003;49(suppl
1):S1S37.
10 Thielitz A, Helmdach M, Röpke EM, Gollnick H. Lipid analysis of follicular casts
from cyanoacrylate strips as a new method for studying therapeutic effects of
antiacne agents. Br J Dermatol. 2001;145:19-27.
11 Verschoore M, Bouclier M, Czernielewski J, Hensby C. Topical retinoids: their uses
in dermatology. Dermatol Clin. 1993;11:107-115.
12 Mills OHJr, Kligman AM. Treatment of acne vulgaris with topically applied
erythromycin and tretinoin. Acta Derm Venereol. 1978;58:555.
13 Halder RM, Brooks HL, Callender VD. Acne in ethnic skin. Dermatol Clin. 2003
Oct;21(4):609-615. vii
14 Embil K, Nacht S. The Microsponge Delivery System (MDS): a topical delivery
system with reduced irritancy incorporating multiple triggering mechanisms for
the release of actives. J Microencapsul. 1996 Sep–Oct;13(5):575-588.
15 Martin B, Meunier C, Montels D, Watts O. Chemical stability of adapalene and
tretinoin when combined with benzoyl peroxide in presence and in absence of
visible light and ultraviolet radiation. Br J Dermatol. 1998;139(suppl 52):8-11.16 Cove H, Holland KT. The effect of benzoyl peroxide on cutaneous micro-organisms
in vitro. J Appl Bacteriol. 1983;54:379-382.
17 Cunliffe WJ, Holland KT. The effect of benzoyl peroxide on acne. Acta Derm
Venereol. 1981;61(3):267-269.
18 Bojar RA, Cunliffe WJ, Holland KT. The short-term treatment of acne vulgaris with
benzoyl peroxide: effects on the surface and follicular cutaneous microflora. Br J
Dermatol. 1995;132:204-208.
19 Crawford WW, Crawford IP, Stoughton RB, Cornell RC. Laboratory induction and
clinical occurrence of combined clindamycin and erythromycin resistance in
Corynebacterium acnes. J Invest Dermatol. 1979 Apr;72(4):187-190.
20 Badreshia-Bansal S, Draelos ZD. Insight into skin lightening cosmeceuticals for
women of color. J Drugs Dermatol. 2007;6(1):32-39.
21 Webster G. Combination azelaic acid therapy for acne vulgaris. J Am Acad
Dermatol. 2000 Aug;43(2 Pt 3):S47-S50.
22 Gupta AK, Nicol K. The use of sulfur in dermatology. J Drugs Dermatol.
2004;3:427431.
23 Espersen F. Resistance to antibiotics used in dermatological practice. Br J Dermatol.
1998;139:4-8.
24 Ochsendorf F. Minocycline in acne vulgaris: benefits and risks. Am J Clin Dermatol.
2010;11(5):327-341.
25 Eady EA, Jones CE, Tipper JL, Cove JH, Cunliffe WJ, Layton AM. Antibiotic
resistant propionibacterium in acne: need for policies to modify antibiotic usage.
BMJ. 1993;306:555.
26 Kurokawa I, Danby FW, Ju Q, Wang X, Xiang LF, Xia L, et al. New developments
in our understanding of acne pathogenesis and treatment. Exp Dermatol. 2009
Oct;18(10):821-832.
27 Zaenglein AL, Thiboutot DM. Expert Committee Recommendations for Acne
Management. Pediatrics. 2006 Sep;118(3):1188-1199.
28 Quarles FN, Brody H, Johnson BA, Badreshia S. Chemical peels in richly pigmented
patients. Dermatol Ther. 2007 May–Jun;20(3):147-148.
29 Badreshia S, Verma S. Laser and light modalities in the treatment of acne vulgaris.
The CSI Journal of Cosmetic Dermatology. Feb 2006;Vol 1:5-9.
30 Davis EC, Callender VD. A Review of acne in ethnic skin pathogenesis, clinical
manifestations, and management strategies. J Clin Aesthet Dermatol. 2010
April;3(4):24-38.
31 Quarles FN, Johnson BA, Badreshia S, Vause SE, Brauner G, Breadon JY, et al. Acne
vulgaris in richly pigmented patients. Dermatol Ther. 2007
May–Jun;20(3):122127.
32 Poli F. Acne on pigmented skin. Int J Dermatol. 2007;46(Suppl 1):39-41.*
33 Taylor SC, Cook-Bolden F, Rahman Z, Strachan D. Acne vulgaris in skin of color. J
Am Acad Dermatol. 2002;46(2 Suppl Understanding):S98-S106.
34 Paul Kelly, Susan C. Taylor Dermatology for Skin of Color Chapter 12. The Structure
and Function of Skin of Color, Sonia Badreshia-Bansal and Susan C Taylor. New York:
McGraw-Hill; 2009.
35 Tsuruta D, Someda Y, Sowa J, Kobayashi H, Ishii M. Drug hypersensitivity
syndrome caused by minocycline. J Cutan Med Surg. 2006;10(3):131-135.
36 Koldovsky O. Hormones in milk. Vitam Horm. 1995;50:77-149.
37 Hoyt G, Hickey MS, Cordain L. Dissociation of the glycaemic and insulinaemic
responses to whole and skimmed milk. Br J Nutr. 2005;93:175-177.
38 Charakida A, Charakida M, Chu AC. Double-blind, randomized, placebo-controlled
study of a lotion containing triethyl citrate and ethyl linoleate in the treatment of
acne vulgaris. Br J Dermatol. 2007;157:569-574.
39 Treloar V, Logan AC, Danby FW, Cordain L, Mann NJ. Comment on acne and
glycemic index. J Am Acad Dermatol. 2008;58:175-177.
40 Namazi MR. Further insight into the pathomechanism of acne by considering the
5alpha-reductase inhibitory effect of linoleic acid. Int J Dermatol. 2004;43:701.
41 Danby FW. Acne and iodine: reply. J Am Acad Dermatol. 2007;56:164-165.
42 Danby FW. Diet and acne. Clin Dermatol. 2008;26:93-96.
Pomade acne
Pomades are comedogenic cosmetic and hair dressings used commonly to style
African American hair. Pomades are oil-based products used to improved hair
manageability, straighten curly hair or to mold hair into various shapes. The oils in
pomades can cause follicular plugging, setting the stage for formation of
comedones. In addition, other ingredients in pomades may irritate skin,
contributing to in ammation. African Americans are common users of pomades,
oils, or ointments to style or improve the manageability of their hair, which may
lead to forehead, temple or scalp acne, called pomade acne or acne cosmetica (Fig.
1.4). Pomade acne usually consists of comedones, papules, and pustules. One study
1showed half of Blacks with acne used hair oil or pomade.Figure 1.4 Pomade acne on the forehead.
Treatment of pomade acne requires discontinuing or minimizing pomade use
and substituting with silicone-based hair products. If a pomade is used to decrease
scalp dryness, it should be applied 2.5 cm (1 inch) behind the hairline. When used
to style or improve hair manageability, the pomade should be applied only to the
distal ends of the hair to avoid contact with the scalp and hairline. Pomade acne
will gradually clear if it is discontinued or if no contact is made with the skin.
However, if pomade acne persists, it should be treated as described above for acne
vulgaris.
Reference
1 Taylor SC, Cook-Bolden F, Rahman Z, Strachan D. Acne vulgaris in skin of color. J
Am Acad Dermatol. 2002;46(2 Suppl Understanding):S98-106.
Steroid acne
Steroid acne presents as monomorphous papulo-pustules located predominantly on
the trunk, extremities and face. Characteristically, it appears after the
administration of topical or systemic corticosteroids, including intravenous and
inhalation therapy. The eruption usually resolves after discontinuation of the
corticosteroid and, in addition, may respond to the usual acne treatment regimens.
In some African and Asian immigrant groups, use of corticosteroid-containing fade
creams is common and acne is increasingly observed in adults using these
depigmenting agents (Fig. 1.5). Discontinuation of the corticosteroid will lead to
resolution of the acne.

Figure 1.5 (A) Steroid acne resulting from long-term topicalclobetasol use. (B)
and (C) Steroid containing fade creams.
Pediatric perspectives: Infantile acne
Candrice R Heath
First-Line Therapies*
Observation (mild cases) C
Infantile acne: a retrospective study of 16 cases. Hello M, Prey S,
LéautéLabrèze C, et al. Pediatr Dermatol 2008; 25(4):434–438.
In this retrospective review of 16 cases (11 boys and 5 girls), the cheeks were the
primary site of involvement. Cystic lesions were reported in 25% of the patients.
Information regarding treatment was available for 15 patients; 3 of 15 resolved
without treatment, 4 were treated with benzoyl peroxide, 5 with topical antibiotics
and 7 with topical retinoids. Oral medications were used in 8 patients: 4 with zinc
salts, 2 with macrolides and 2 with isotretinoin. The disease duration was between
9 and 42 months. Of the 8 patients who reached adolescence at the time of the
review, only one developed severe adolescent acne. Of the 16 total cases reviewed,
9 reported scarring, generally atrophic.
Isotretinoin is only approved for children 12 years and older with nodulocystic acne,
though there have been reports in the literature of use in younger age groups for
recalcitrant cases.
Second-Line Therapies
Benzoyl peroxide (inflammatory acne) C
Tretinoin (comedonal acne) C
Topical antibiotic (erythromycin or clindamycin) C
Adapalene gel 0.1% C
A clinical and therapeutic study of 29 patients with infantile acne. Cunli/ e
WJ, Baron SE, Coulson IH. Br J Dermatol 2001; 145(3):463–466.
In this retrospective review of 29 patients (24 boys and 5 girls) with infantile
acne, 24% of the cases were mild, 62% were moderate and 14% of the cases were
severe. In ammatory acne occurred in 59% of the cases, while comedonal lesions
in 17%, nodular lesions in 7% and a mixture of lesions was seen in 17%. The
patients with mild acne were treated successfully with benzoyl peroxide,
erythromycin and topical retinoids. All of the infants with moderate acne
responded well with a combination of oral erythromycin and topical treatment,
except 2 infants. The two erythromycin resistant cases were treated with
trimethoprim. The majority of the infants treated with oral antibiotics were treated
with oral therapy for 18 months or less. However 38% of the infants treated with*
oral antibiotics required over 24 months of treatment. The acne lasted between 6
and 40 months. One case was treated successfully with a 4-month course of
isotretinoin. Five of the 29 patients were left with residual scarring.
Topical acne medications should be used very sparingly on the skin of infants to
avoid irritation.
Adapalene gel 0.1% in the treatment of infantile acne: an open clinical
study. Kose O, Koç E, Arca E. Pediatr Dermatol 2008; 25(3):383–386.
12 patients were treated with adapalene gel 0.1% once per day for 16 weeks.
Clearance of lesions was achieved in 4 patients after 3 months of treatment and the
remaining 8 patients cleared in 4 months. There was no residual scarring, however
at a one-year follow-up evaluation, 3 patients had a few mild lesions.
Third-Line Therapies
Oral antibiotics (erythromycin) C
Oral tetracycline is not recommended in children under 8 years old due to decreased
bone growth and tooth staining.
Pediatric perspectives: Neonatal acne (acne neonatorum)
Candrice R Heath
Although predominately a disease of adults and adolescents, acne may occur in
newborns and infants. The acne that presents in newborns and infants is more
common in males. Hyperactivity of the sebaceous glands stimulated by androgens
has been the implicated cause of acne in both boys and girls in this group. Open
and closed comedones predominate, but other in ammatory lesions may occur as
well. Neonatal acne appears within the 3rst few weeks of life. While infantile acne
occurs in infants between 3 months and 6 months of age. When infantile acne
occurs, it usually persists and may be severe.
First-Line Therapies
Observation C
Daily Cleansing with Gentle Soap
Acne neonatorum: a study of 22 cases. Katsambas AD, Katoulis AC,7
*
*
Stavropoulos P. Int J Dermatol 1999; 38(2):128–130.
22 patients (18 males and 4 females) with acne neonatorum were evaluated. The
average age of onset was 3 weeks, with an average duration of 4 months. The
cheeks were involved in 81.8% of the cases. Papules and pustules were the
predominant lesion type in 72.7% and only 22.7% of the patients had comedones.
A family history of acne was present in 3 cases. 18 patients were treated with a
regimen of daily cleansing with soap and water. Benzoyl peroxide 5% gel was used
in 3 patients and 1 patient was treated with benzoyl peroxide 5% gel combined
with topical clindamycin alcohol solution. Though this is a self-limiting disorder,
treatments hastened resolution.
Neonatal acne occurs within the rst few weeks of life while infantile acne usually
does not occur until 3 to 6 months of age.
Acne rosacea
Rosacea is a common skin disease characterized by vascular hyper-reactivity,
facial ushing, erythema, and telangiectasias. The pathogenesis appears to be
multifactorial. Demodex mites, normal inhabitants of the human hair follicle, are
found in greater numbers in rosacea patients and are thus theorized to play a role
1-3in its pathogenesis. However, more studies are needed to conclusively determine
i f Demodex truly is pathogenic. Also, inconclusive evidence suggests that
Helicobacter pylori (H. pylori) is associated with the etiology of rosacea, as
4,5increased levels of H. pylori antibodies have been detected. However, many of
the studies were not controlled.
Rosacea is most common in middle aged fair skinned individuals, but it can also
be seen in individuals of any skin type.Data on the incidence of rosacea in di/ erent
racial groups is variable and generally lacking. Rosacea appears to be more
common in light skinned and Asian populations and less common in people who
have darker skin. However, in ethnic skin, the diagnosis can be obscured due to
skin hue, causing rosacea to appear more hyperpigmented and less erythematous in
darker patients with resulting misdiagnosis. Although it is considered to be rare
6among Black patients, it may be more common than believed to be in the past.
There are four main subtypes of rosacea: vascular rosacea characterized by
ushing and persistent central erythema (Fig. 1.6); papulopustular rosacea
characterized by central facial papules or pustules; phymatous rosacea with
thickened, irregular, nodular skin, (referred to as rhinophyma when the nose is
involved, Fig. 1.7); and ocular rosacea characterized by burning, stinging, or the
sensation of a foreign body in the eye. Patients may present with one or a
combination of symptoms and signs such as facial burning and stinging, edema,
erythematous plaques, dryness, ocular manifestations, or phymatous changes.*
*
*
Extrafacial involvement may occur on the neck and the upper chest. Common
rosacea triggers include hot and/or cold temperatures, wind, hot drinks, ca/ eine,
exercise, spicy food, alcohol, stress, topical products that irritate the skin and
decrease the stratum corneum barrier, or medications that cause ushing. Rosacea
fulminans (pyoderma faciale) is a rare complication characterized by the
development of nodules and abscesses with sinus tract formation accompanied by
systemic signs. A rare caseating granulomatous variant of rosacea, called lupus
miliaris disseminatus faciei, can manifest with in ammatory red-brown or
eshcolored papules distributed symmetrically across the upper part of the face,
particularly around the eyes and the nose.
Figure 1.6 Rosacea with persistent central erythema in an Asian woman.
Figure 1.7 Rhinophyma in an Indian man.
Unlike with acne vulgaris, patients with rosacea generally do not report oily skin*
*
*
but instead they experience dryness and peeling. The absence of comedones and
lack of scarring is another helpful distinguishing feature from acne vulgaris. Other
cutaneous disorders that mimic rosacea include polycythemia vera, connective
tissue diseases (e.g. lupus erythematous, dermatomyositis, mixed connective tissue
disease), perioral dermatitis, seborrheic dermatitis, photosensitivity, mastocytosis,
neuroendocrine tumor such as pheochromocytoma or carcinoid, long-term
application of topical steroids, anticancer agents such as epidermal growth factor
receptor inhibitor (Fig. 1.8), contact dermatitis, and photosensitivity. Clues to an
endocrinopathy include tachycardia, hypertension, sweats, hot flashes, or diarrhea.
Figure 1.8 Skin eruption induced by an epidermal growth factor receptor
inhibitor
(Courtesy of Emmy Graber MD, Dave Adams MD, and Diane Thiboutot MD; Department
of Dermatology, Penn State Milton S. Hershey Medical Center).
Rosacea is a challenging disease to treat and there are very few large well
controlled studies. Additionally, vasodilation, a key component of rosacea, is
unresponsive to therapy. However, avoiding triggers described above may help
7-9with symptoms. Sunblock may have an e/ ect on vasodilatation since exposure
to ultraviolet radiation leads to destruction of collagen and the surrounding
10,11supportive connecting tissue, which contributes to vasodilation. Topical
therapy includes the use of metronidazole for in ammatory rosacea with resulting
slow, gradual response. Azelaic acid has been helpful in reducing erythema.
Sodium sulfacetamide, as an adjunct to therapy, may improve severe disease. A
combination of topical and oral therapy usually provides the best results for initial
ares. Oral therapy consists of the tetracycline class of antibiotics administered
over several weeks with a gradual taper for initial ares. Other options may include*
*
*
*
*
*
*
trimethoprim/sulfamethoxazole and cipro oxacin but these may be limited by cost
and resistant micro-organisms. In the most severe cases of rosacea with resistant
in ammatory lesions and nodules or rhinophyma, isotretinoin therapy may be
required. Persistent erythema may respond best with vascular lasers, which are the
mainstay of rosacea therapy. Cosmetic improvement of rhinophyma may be
produced by mechanical dermabrasion, surgical shave techniques, CO laser or hot2
loop recontouring. Anecdotal evidence indicates treatment of rosacea with
medications including beta-blockers, clonidine, naloxone, ondansetron, and
selective serotonin reuptake inhibitors may improve cutaneous flushing.
First-Line Therapies
Oral antibiotics A
Topical antibiotics A
Topical metronidazole A
Topical azelaic acid A
Laser surgery B
There is evidence to support the use of topical metronidazole and azelaic acid in
the maintenance of rosacea. For acute, in ammatory ares, oral antibiotics in
combination with topical agents will result in improvement. Finally, laser therapy
may help diminish the erythema associated with rosacea, but care must be
exercised when treating ethnic patients.
American Acne & Rosacea Society rosacea medical management
guidelines. Del Rosso JQ, Baldwin H, Webster G, American Acne & Rosacea
Society. J Drugs Dermatol 2008; 7(6):531–533.
The pharmacologic agents discussed are inclusive of those that are
FDAapproved based on phase 3 pivotal trials. The mainstay of treatment for
in ammatory lesions has been oral antibiotics, but topical metronidazole also may
be e/ ective. Antibiotics are more e/ ective for in ammatory lesions than for
erythema and telangiectasia. Isotretinoin may be e/ ective for in ammatory lesions,
edema and rhinophyma and in some resistant cases, but its use is limited by side
effects and teratogenecity.
E4 cacy and safety of azelaic acid (15%) gel as a new treatment for
papulopustular rosacea: results from two vehicle-controlled, randomized
phase III studies. Thiboutot D, Thiero/ -Ekerdt R, Graupe K. J Am Acad Dermatol
2003; 48(6):836–845.*
*
*
*
*
Two multicenter, double-blind, randomized, parallel-group, vehicle-controlled
studies were conducted enrolling 665 subjects (92.5% Caucasian, 0.75% African
American, 5.75% Hispanic, 0.25% Asian, 0.75% Asian) with moderate
papulopustular rosacea. Azelaic acid 15% gel yielded statistically signi3cantly
higher reductions in mean in ammatory lesion count with improvement in
erythema and therapeutic success as compared to placebo within 12 weeks of
treatment. In vitro investigations indicate that azelaic acid may exert an
antiin ammatory e/ ect by scavenging or reducing the generation and/or release of
proin ammatory reactive oxygen species by neutrophils (much like the e/ ect of
tetracyclines in rosacea).
Randomized placebo-controlled trial of metronidazole 1% cream with
sunscreen SPF 15 in treatment of rosacea. Tan JK, Girard C, Krol A, Murray HE,
Papp KA, Poulin Y, Chin DA, Jeandupeux D. J Cutan Med Surg 2002; 6(6):529–
534.
120 patients with moderate to severe rosacea were enrolled in a randomized,
placebo-controlled, double-blind study. Study cream was applied twice daily to the
entire face over a 12-week period. Treatment with metronidazole 1% cream with
SPF 15 sunscreen resulted in significant improvement in inflammatory lesion count,
erythema and telangiectasia scores, and investigator and patient global assessment
scores compared with baseline and placebo.
Rosacea patients are prone to irritation, including from ingredients found in
sunscreen. It is preferable to use physical blockers containing zinc oxide or titanium
dioxide and/or ones that contain dimethicone or cyclomethicone to reduce possible
contact dermatitis.
Combined e: ect of anti-in6ammatory dose doxycycline (40-mg
doxycycline, usp monohydrate controlled-release capsules) and
metronidazole topical gel 1% in the treatment of rosacea. Fowler JF Jr. J
Drugs Dermatol 2007; 6(6):641–645.
This 16-week, randomized, double-blind, placebo-controlled study of an
antiin ammatory dose of doxycycline plus topical metronidazole gel 1% for mild to
moderate rosacea is presented. At week 12, metronidazole was discontinued and
patients continued on either placebo or doxycycline. Combination therapy
signi3cantly reduced in ammatory lesion counts as early as week 4 and through
week 12 compared to topical metronidazole 1% gel monotherapy.
Long-pulsed (6-ms) pulsed dye laser treatment of rosacea-associated
telangiectasia using subpurpuric clinical threshold. Jasim ZF, Woo WK,
Handley JM. Dermatol Surg 2004; 30(1):37–40.
To examine the e/ ect of long-pulsed PDL at subpurpuric clinical threshold in the
treatment of rosacea-associated telangiectasia, 12 patients with rosacea-associated*
telangiectasia were recruited into the study. The 595-nm PDL at a pulse duration of
26 ms was titrated up to a uence between 7 and 9 J/cm to produce immediate
purpura lasting only a few seconds. Pretreatment cooling was achieved by cryogen
spray. Patients were evaluated 6–8 weeks after one PDL treatment. Two of 12
patients had more than 75% improvement, another two had 50–75%
improvement, and 3ve had 25–50% improvement. Overall, 9 (75%) of 12 patients
had more than 25% improvement after a single treatment of PDL. None of the
patients reported lasting post-treatment purpura or complications.
Caution must be taken when treating ethnic skin, especially with lasers containing
cryogen spray due to possible risk of hyperpigmentation or hypopigmentation.
Second-Line Therapies
Topical calcineurin inhibitors A
Topical sulfur C
Topical antibiotics A
Oral antibiotics (ampicillin, metronidazole) A
Supporting evidence of treatment with topical immunomodulators, benzoyl
peroxide, and oral antibiotics has been varied.
Pimecrolimus 1% cream for the treatment of steroid-induced rosacea: an
8-week split-face clinical trial. Lee DH, Li K, Suh DH. Br J Dermatol 2008;
158(5):1069–1076.
This investigator-blided, split-face study evaluated the eG cacy and safety of
pimecrolimus 1% cream for the treatment of steroid-induced rosacea. Patients
applied pimecrolimus 1% cream twice daily to a randomly allocated half face for
the 3rst 2 weeks, and then applied pimecrolimus 1% cream to both sides of the
face for 6 more weeks. After 1 week of application, a statistically signi3cant
improvement in erythema was observed. Asian subjects (type IV) were included in
the study but no mention was made regarding demographics. Some patients
developed hyperpigmentation as papules and pustules resolved. This was most
common in ethnic patients and was considered to be PIH.
E2 cacy of pimecrolimus for the treatment of steroid induced rosacea is debated.
Other case reports have concluded that rosaceiform eruption could be aggravated after
tacrolimus or pimecrolimus treatment.
Combination sodium sulfacetamide 10% and sulfur 5% cream with
sunscreens versus metronidazole 0.75% cream for rosacea. Torok HM,*
*
Webster G, Dunlap FE, Egan N, Jarratt M, Stewart D. Cutis 2005; 75(6):357–363.
In an investigator-blinded, randomized, parallel-group study at 6 sites, after 12
weeks of treatment with sodium sulfacetamide 10% and sulfur 5% cream with
sunscreens, there was a signi3cantly greater percentage reduction in in ammatory
lesions compared with metronidazole 0.75% cream, as well as a signi3cantly
greater percentage of subjects with improved erythema. Seven subjects had poor
tolerance to the sodium sulfacetamide 10% and sulfur 5% cream with sunscreens,
possibly caused by a sulfa drug allergy.
Double-blind, randomized, vehicle-controlled clinical trial of once-daily
benzoyl peroxide/clindamycin topical gel in the treatment of patients with
moderate to severe rosacea. Breneman D, Savin R, VandePol C. Int J Dermatol
2004; 43(5):381–387.
This 12-week, double-blind, vehicle-controlled, randomized, prospective,
parallel-group study in 53 patients with moderate to severe rosacea showed a
di/ erence in favor of benzoyl peroxide/clindamycin by the third week of treatment
as compared to placebo. Severity scores for erythema, papules/pustules, and
ushing/blushing decreased more with benzoyl peroxide/clindamycin than with
vehicle. Application site reactions were reported in 14% of patients.
Caution must be taken in skin of color with topical agents that can cause irritant
contact dermatitis, and subsequent post-inflammatory hyperpigmentation.
Comparison of e4 cacy of azithromycin vs doxycycline in the treatment of
rosacea: a randomized open clinical trial. Akhyani M, Ehsani AH, Ghiasi M,
Jafari AK. Int J Dermatol 2008; 47(3):284–288.
A randomized, open clinical trial was conducted in Iran to compare the eG cacy
of azithromycin with doxycycline in 77 rosacea patients who were randomized to
receive either azithromycin 500 mg three times weekly (on Monday, Wednesday,
and Saturday) in the 3rst month, 250 mg three times weekly in the second month,
and 250 mg twice weekly (on Tuesday, and Saturday) in the third month. The
other group was given doxycycline 100 mg/day for the three months. Clinical
assessment was made at baseline, at the end of 3rst, second, third, and 3fth months
after treatment. Statistically signi3cant improvement was obtained with both
drugs. In the azithromycin group, 4 patients had diarrhea, while epigastric burning
was seen in 2 patients using doxycycline. This study indicates that azithromycin is
at least as effective as doxycycline in the treatment of rosacea.
Third-Line Therapies
Topical retinoids
Oral antibiotics: trimethoprim/sulfamethoxazole, ciprofloxacin*
Oxymetazoline
Photodynamic therapy
Demodex eradication: topical permethrim, oral ivermectin
H. pylori eradication
Oral isotretinoin
Topical steroid
Ketoconazole
Bifonazole
Ondansetron
Spironolactone
Octreotide
Commonly encountered pitfalls
The various forms of rosacea are more common than once believed in ethnic skin.
The caseating granulomatous variant may be more common in Asian or Black
patients and acne rosacea may be more common in Black patients than previously
thought. However, rhinophyma has remained relatively uncommon in Japanese
12-15and reported in only 3 cases in African-Americans. Ocular rosacea in Black
patients has been found to range from blepharitis and conjunctival hyperemia to
sight-threatening problems such as corneal neovascularization, thinning,
16ulceration, and perforation.
Treating rhinophyma is diG cult due to the technical challenges of producing a
good cosmesis. In Japan, almost all cases are located to the lower half of the nose,
which is treated by full-thickness excision followed by application of either skin
13grafts or direct closure. Laser therapy and dermabrasion, a commonly used
treatment in the US for rhinophyma, should be used with caution in ethnic patients
since risk of scarring and pigment dyschromias are high.
Special management & counseling considerations
Combination therapy with mild skin care products, vigilant use of sunblock, and
maintenance medical therapy as well as vascular lasers may optimize treatment
results. As discussed, care must be taken to avoid irritant contact dermatitis and
post-in ammatory hyperpigmentation. The daily use of broad-spectrum sunblock is
recommended for all patients, including ethnic patients in whom sunscreen use islow. A sunscreen that protects against both ultraviolet A and ultraviolet B rays
should be selected. Physical blockers with micronized titanium dioxide and/or zinc
oxide are well tolerated in ethnic skin but may produce a temporary white or
purple skin hue. Green tinted sunscreens or cosmetics can provide coverage of
erythema if present in patients with lighter skin hues. Patients should be
encouraged to avoid astringents, toners, menthols, camphor, waterproof cosmetics
requiring solvents to be removed, or products containing sodium lauryl sulfate
which can irritate the skin. Dietary modulation should aim at avoidance of triggers.
References
1 Erbağci Z, Ozgöztaşi O. The significance of Demodex folliculorum density in rosacea.
Int J Dermatol. 1998;37(6):421-425.
2 Forton F, Seys B. Density of Demodex folliculorum in rosacea: a case control study
using standardized skin-surface biopsy. Br J Dermatol. 1993;128(6):650-659.
3 Bonnar E, Eustace P, Powell FC. The Demodex mite population in rosacea. J Am
Acad Dermatol. 1993;28(3):443-448.
4 Rebora A, Drago F, Picciotto A. Helicobacter pylori in patients with rosacea. Am J
Gastroenterol. 1994;89(9):1603-1604.
5 Utaş S, Ozbakir O, Turasan A, Utaş C. Helicobacter pylori eradication treatment
reduces the severity of rosacea. J Am Acad Dermatol. 1999;40(3):433-435.
6 Rosen T, Stone MS. Acne rosacea in blacks. J Am Acad Dermatol. 1987;17(1):70-73.
7 Jansen T, Plewig G. Rosacea: classification and treatment. J R Soc Med.
1997;90:144-150.
8 Wilkin JK. Flushing reactions: consequences and mechanisms. Ann Intern Med.
1981;95:468-476.
9 Guarrera M, Parodi A, Cipriani C, Divano C, Rebora A. Flushing in rosacea: a
possible mechanism. Arch Dermatol Res. 1982;272:311-316.
10 Wilkin JK. Rosacea. Pathophysiology and treatment. Arch Dermatol.
1994;130:359362.
11 Plewig G, Jansen T. Rosacea. In: Freedberg IM, Eisen AZ, Wolff K, et al, editors.
Dermatology in General Medicine. 5th ed. New York, NY: McGraw-Hill Health
Professions Division; 1999:785-794.
12 Koffi-Aka V, Kouassi AA, D’Horpock FA, Boka NJ, Ehouo F. [Rhinophyma in a black
African]. Rev Laryngol Otol Rhinol (Bord). 2002;123(2):109-110.
13 Furukawa M, Kanetou K, Hamada T. Rhinophyma in Japan. Int J Dermatol.
1994;33(1):35-37.
14 Allah KC, Kossoko H, Yéo S, Richard Kadio M, Assi Djè Bi Djè V. [Rhinophyma in a
black African male patient]. Rev Stomatol Chir Maxillofac. 2009
Dec;110(6):347349.*
*
15 Khoo CT, Saad MN. Rhinophyma in a negro: case report. Br J Plast Surg. 1980
Apr;33(2):161-163.
16 Browning DJ, Rosenwasser G, Lugo M. Ocular rosacea in blacks. Am J Ophthalmol.
1986;101(4):441-444.
Hidradenitis suppurativa
Hidradenitis suppurativa (HS) results from rupture of the hair follicle into the
surrounding dermis, which leads to in ammation and subsequent abscess
1formation. A familial form with autosomal dominance inheritance has been
described. HS occurs around puberty and women are three times more likely to
develop HS than men. It is common in Europeans and African-Americans.
HS is a debilitating disease characterized by chronic in amed, swollen, painful
nodules and sterile abscesses in apocrine gland-bearing sites including the axillae,
groin, and inframmamary areas. Over time, recurrent boils lead to a hallmark of
the disease, draining sinus tracts, 3stulae, and subsequent hypertrophic scars (Fig.
1.9, Fig. 1.10). Often patients are aZ icted with acne, pilonidal cysts, and scalp
2folliculitis, giving rise to the term follicular occlusion triad. Exacerbating factors
include being overweight, cigarette use, and moisture. Several complications can
occur including scarring, contracture at the sites of lesions, urethral or rectal
3stulas, squamous cell carcinomas, anemia secondary to chronic infection, and
3lymphedema from chronic inflammation and scarring.
Figure 1.9 Severe hidradenitis supparativa
(Courtesy of Dave Adams MD, Department of Dermatology, Penn State Milton S. Hershey
Medical Center).*
Figure 1.10 Hidradenitis supparativa affecting the axilla
(Courtesy of Dave Adams MD; Department of Dermatology, Penn State Milton S. Hershey
Medical Center).
Several treatments have been tried with varied success. Weight reduction,
limiting friction and moisture from sweating by employing maneuvers such as
wearing loose undergarments, using absorbent powders, antiseptic soaps, and
topical aluminum chloride, are somewhat helpful. In early lesions, topical and
intralesional corticosteroids or topical antibiotics such as clindamycin have proven
to be bene3cial. In acute cases, oral antibiotics may be necessary as a short- or
long-term treatment option. Culture of exudates often reveal staphylococci,
streptococci, pseudomonas, and/or anaerobic bacteria. Female patients presenting
with HS should be screened for underlying polycystic ovary syndrome (PCOS) and
insulin resistance. In severe cases, the best results occur with radical excision with
primary closure or grafts. Although extensive surgery is usually considered the most
e/ ective curative therapy, there is little experience with this approach, with most
being reports from European studies. An alternative has been the use of ablative
laser treatment with secondary intention healing or radiation treatment. Systemic
retinoids may reduce ares but have not been a reliable cure. Acitretin may have
better results as compared to isotretinoin. Systemic corticosteroids often lead to
dramatic improvement but results are not sustained upon discontinuation. Topical
antibacterials containing benzoyl peroxide may be helpful to prevent or diminish
relapses. Individual lesions are slow to heal, usually with drainage of pus.
Remissions may last months to years and recurrences are common with progressive
scarring and sinus tracts.
First-Line Therapies*
*
Antibiotics A
Surgical excision B
Topical treatment of hidradenitis suppurativa with clindamycin.
Clemmensen OJ. Int J Dermatol 1983; 22(5):325–358.
This double-blind trial evaluated the eG cacy of topical clindamycin in
hidradenitis in 27 patients over 3 months. Clindamycin was superior to placebo.
However, no di/ erence was found for in ammatory nodules and abscesses at the
second and third month evaluation. Topical clindamycin may be helpful prior to
radical surgery or spontaneous remission.
Combination therapy with clindamycin and rifampicin for hidradenitis
suppurativa: a series of 116 consecutive patients. Gener G, Canoui-Poitrine F,
Revuz JE, Faye O, Poli F, Gabison G, Pouget F, Viallette C, Wolkenstein P,
BastujiGarin S. Dermatology. 2009; 219(2):148–154.
This retrospective study evaluated the eG cacy of a combination of systemic
clindamycin (300 mg twice daily) and rifampicin (600 mg daily) in the treatment
of patients with severe HS which was given for 10 weeks with success. The
proposed mechanism of action was the antibacterial and anti-in ammatory e/ ects
of the two antibiotic agents. No data regarding long-term follow-up and recurrence
was reported. This treatment regimen was aimed at being suspensive only,
therefore, a maintenance treatment with tetracyclines or zinc gluconate was
prescribed at the conclusion of the 10-week regimen.
Topical clindamycin versus systemic tetracycline in the treatment of
hidradenitis suppurativa. Jemec GB, Wendelboe P. J Am Acad Dermatol 1998;
39(6):971–974.
46 patients with hidradenitis suppurativa were treated in a double-blind, double
dummy controlled trial. Systemic therapy with tetracyclines 1 g daily did not
produce better results than topical therapy with clindamycin twice daily after a
minimum of 3 months of treatment. Abscesses were reduced during the 3rst 3
months of treatment. Nodules only appeared to be reduced in number after 3
months of treatment. The time course suggests that nodules may be precursors to
abscesses.
Surgical treatment of hidradenitis suppurativa: a retrospective study of 93
cases. Bordier-Lamy F, Palot JP, Vitry F. Ann Dermatol Venereol 2008;
135(5):373–379.
Of 93 French patients followed for a mean of 30 months, 209 anatomical sites
were operated on with curative intent, using either limited or wide excision. The
disease had been present for an average of 7.6 years before surgical treatment, with7
onset 7 years earlier in women. Surgery required hospitalization for an average
duration of 6.6 days, caused complications in 21% of cases and was often
perceived as diG cult. Relapse in the operated areas occurred in 33% of cases and
this was more frequent after limited excision. Nevertheless, 74% of patients were
ultimately satis3ed with their surgical treatment and most regarded surgery as the
only e/ ective therapy. Wide excision remains the mainstay of therapy in extensive
forms of hidradenitis suppurativa.
Surgical treatment of hidradenitis suppurativa: a 10-year experience.
Kagan RJ, Yakubo/ KP, Warner P, Bemard P, Grange F. Surgery 2005;
138(4):734–740.
This study attempted to determine which factors have the greatest impact on
outcome in order to develop an operative treatment algorithm. An algorithm for
operative treatment was developed based on the extent of involvement, chronicity,
and comorbid conditions. 57 patients had an average duration of symptoms of 6.7
years. 92 operative procedures were performed, 50% involved the axilla, 36%
involved the perineum, and 14% involved the inguinal region. Excision and
primary closure was used for localized disease and wide excision with or without
skin grafting was used for di/ use disease. De3nitive treatment involves excision of
the involved apocrine tissue and should be individualized based on the stage and
location of the disease.
Total surgical excision may be required in the gluteal region to prevent further
complications including abscess, sinus tract formation, stulization, and scarring. A
multidisciplinary team approach is necessary and the patients often require an
extensive hospital stay with aggressive wound care management.
Surgical treatment of hidradenitis suppurativa with gentamicin sulfate: a
prospective randomized study. Buimer MG, Ankersmit MF, Wobbes T,
Klinkenbijl JH. Dermatol Surg 2008; 34(2):224–247.
A prospective randomized study was performed showing gentamicin sulfate was
useful in the surgical treatment of hidradenitis suppurativa. In the 76 patients in
the study, gentamicin after primary excision of hidradenitis suppurativa reduced
the number of complications 1 week post-operatively, including dehiscence,
infection, and seroma. Furthermore, in 65% of the patients treated with
gentamicin, the wound was completely healed within 2 months. No e/ ect on the
long-term recurrence rate was noted.
Second-Line Therapies
Oral corticosteroids E
Oral isotretinoin B
7



Hormonal therapy B
Radical surgery B
Severe vulval apocrine acne successfully treated with prednisolone and
isotretinoin. Fearfield LA, Staughton RC. Clin Exp Dermatol 1999; 24(3):189–192.
A case of a 34-year-old woman with severe vulval apocrine acne was successfully
treated initially with prednisolone and then maintained with long-term isotretinoin.
Long-term treatment with isotretinoin may be more successful than a 4–6 month
treatment regime.
Long-term results of isotretinoin in the treatment of 68 patients with
hidradenitis suppurativa. Boer J, van Gemert MJ. J Am Acad Dermatol 1999;
40(1):73–76.
This retrospective study assessed low-dose isotretinoin for 4–6 months in the
treatment of 68 patients with mild-to-severe HS. In 23.5% of patients, the condition
completely cleared during initial therapy and 16.2% maintained their
improvement during the follow-up period. Treatment was more successful in the
milder forms of HS. Monotherapy with isotretinoin for patients with HS usually has
a limited therapeutic effect.
However, another recent study found no e ect or even worsening with use of oral
isotretinoin. It seems unclear if isotretinoin, which a ects sebaceous glands would
have an e ect on apocrine glands involved in HS. The limited therapeutic e ect may
be due to absence of signi cant sebaceous gland involvement in HS, as measured by
sebum excretion rates and histopathologic observation.
Hidradenitis suppurativa in 64 female patients: retrospective study
comparing oral antibiotics and antiandrogen therapy. Kraft JN, Searles GE. J
Cutan Med Surg 2007; 11(4):125–131.
As HS has been linked to a hyperandrogenic state, this retrospective study
examined its association with PCOS. In 64 female HS patients, the prevalence of
PCOS was 38.1%. Antiandrogen therapy was superior to oral antibiotic therapy.
Female patients presenting with HS should be considered for screening of underlying
PCOS and insulin resistance.
A double-blind controlled cross-over trial of cyproterone acetate in
females with hidradenitis suppurativa. Mortimer PS, Dawber RP, Gales MA. Br
J Dermatol 1986; 115(3):263–268.
Ethinyloestradiol 50 micrograms/cyproterone acetate 50 mg in a reverse
sequential regimen was compared with ethinyloestradiol 50 micrograms/norgestrel
500 micrograms in 24 female patients. Both treatments produced substantial
improvement in disease activity. 12 patients cleared and have remained disease
free for 18 months, 5 patients improved, four remained unchanged, while two
deteriorated. Cyproterone acetate was not more e/ ective than combination
therapy, and both gave a similar reduction in free androgen index.
Cyproterone has been e ective in some cases but high doses may be necessary which
may raise safety issues.
Third-Line Therapies
Laser (CO , Nd:Yag, Laser lipolysis)2
Photodynamic therapy
Immunosuppressants
Infliximab
Etanercept
Cyclosporine
Adalimumab
Dapsone
Botulinum toxin
Electrosurgery
Zinc
Granulocyte colony stimulating factor
Commonly encountered pitfalls
Controversy exists whether African-Americans have a di/ erence in the size,
4number, and morphology of apocrine glands. African-Americans have been found
to have a higher incidence of HS than those of European descent. Ingrown hairs
may be a predisposing factor. Care must be taken with excision of lesions of HS due
to the high risk of hypertrophic or keloidal scarring. Radical surgical excision may
be limited in this patient population in whom keloid scarring is frequent. Further
studies are required in ethnic populations.
Special management & counseling considerations
Unfortunately, none of the treatment modalities have a high success rate. It is
important to note that cases of squamous cell carcimoma have been reported in
longstanding HS. Despite its low incidence, squamous cell carcinoma remains the
most serious complication and patients with darker skin are not exempt.*
References
1 Balik E, Eren T, Bulut T, Büyükuncu Y, Bugra D, Yamaner S. Surgical approach to
extensive hidradenitis suppurativa in the perineal/perianal and gluteal regions.
World J Surg. 2009 Mar;33(3):481-487.
2 Deschamps ME, Payet S, Tournadre A, Soubrier M, Souteyrand P, D’Incan M.
[Efficacy of infliximab in the treatment of follicular occlusion triad]. Ann Dermatol
Venereol. 2010 Aug–Sep;137(8–9):546-550.
3 Tanaka A, Hatoko M, Tada H, Kuwahara M, Mashiba K, Yurugi S. Experience with
surgical treatment of hidradenitis suppurativa. Ann Plast Surg. 2001;47:636-642.
4 Paul Kelly, Susan C. Taylor Dermatology for Skin of Color Chapter 12. The Structure and
Function of Skin of Color, Sonia Badreshia-Bansal and Susan C Taylor. New York:
McGraw-Hill; 2009.
Perioral dermatitis
Perioral dermatitis is a chronic papulo-pustular and eczematous facial dermatitis
which occurs primarily in women. The etiology of perioral dermatitis is unknown.
However, the use of topical steroids of any strength on the face often precedes the
manifestation of the disease. Many patients abuse topical corticosteroid
preparations, so reassurance and education regarding discontinuation of steroid is
essential. Cosmetics, moisturizers, drooling, and toothpaste have also been
1-5implicated in the etiology.
Characteristic skin lesions are grouped perioral, perinasal, or perioribital red
follicular papules, papulovesicles, and/or papulopustules, and is often termed
periori3cial dermatitis. Skin of color patients can, in addition, present with
hyperpigmentation or hypopigmentation. Perioral dermatitis can resemble other
conditions including rosacea and acne vulgaris.
Anti-in ammatory agents such as antibiotics and topical immunomodulators
may help hasten resolution. The tetracycline class of antibiotics decreases the
chemotactic response of neutrophils, inhibits granuloma formation, and inhibits
protein kinase C. Photodynamic therapy has also been reported to be helpful in
small clinical studies.
First-Line Therapies
Discontinuation of corticosteroids B
Antibiotics BPerioral dermatitis: etiology and treatment. Bendl BJ. Cutis 1976;
17(5):903–908.
95 patients with perioral dermatitis showed consistent clearing of the eruption
with oral tetracycline in combination with a topical sodium
sulfacetamide-sulfurhydrocortisone lotion. When compared to 50 control patients, there were highly
signi3cant quantitative di/ erences. Lubricating and moisturizing products play a
part in the etiology of perioral dermatitis.
The use of topical agents containing hydrocortisone is not recommended for
treatment of perioral dermatitis.
Topical cosmetics and perioral dermatitis. Dirschka T, Weber K, Tronnier H.
J Dtsch Dermatol Ges 2004; 2(3):194–199.
75 patients with perioral dermatitis and 125 randomly selected control patients
were compared, including history of atopic dermatitis. There were signi3cant
di/ erences between the patient and control group in morning skin care regimens
including the use of day creams. 25% of patients used topical corticosteroids which
were initiated after the onset of the rash. There was a correlation also with history
of atopic diseases. A possible interaction between external factors, such as
cosmetics, and intrinsic factors, such as atopic dermatitis appears to contribute to
perioral dermatitis, perhaps by subclinical repetitive irritation and overwhelming
the reparative capacity of the epithelial barrier function.
Critical appraisal of reports on the treatment of perioral dermatitis. Weber
K, Thurmayr R. Dermatology 2005; 210(4):300–307.
There were consistent results on a variety of therapeutic trials regarding
treatment of perioral dermatitis. The most common and consistent treatment
guidelines included use of oral tetracycline as 3rst line agents, topical antibiotics
and metronidazole as second line, and to a lesser extent, recommending no therapy
with only spontaneous resolution. The discontinuation of topical corticosteroids and
cosmetics is thought to be important. Perioral dermatitis is thought to be
selflimited because it spontaneously clears in most patients within approximately 3
months.
Second-Line Therapies
Topical corticosteroids E
Topical sulfur E
Topical metronidazole B
Topical calcineurin inhibitors B*
*
Photodynamic therapy B
Topical azelaic acid D
Oral isotretinoin E
Topical therapy for perioral dermatitis. Bikowski JB. Cutis 1983; 31(6):678–
682.
Six patients with perioral dermatitis were successfully treated with a combination
of erythromycin topical solution twice a day and topically applied hydrocortisone
valerate cream. Hydrocortisone valerate cream, when used in a controlled, tapered
regimen, seems to prevent acute rebound are of perioral dermatitis from previous
high-potency steroid use or abuse.
Low-potency topical corticosteroid in cases of exacerbation (if there is any) during
the first 2 weeks after initiation of therapy may be used.
The multifunctionality of 10% sodium sulfacetamide, 5% sulfur emollient
foam in the treatment of in6ammatory facial dermatoses. Draelos ZD. J Drugs
Dermatol. 2010 Mar; 9(3):234–236.
This uncontrolled, observational, prospective, open-label, single site, eight-week
study enrolled 24 subjects (8 with rosacea, 8 with seborrheic dermatitis, 8 with
acne vulgaris) to evaluate the safety and eG cacy of this novel foam formulation. At
8 weeks, statistically signi3cant improvement was seen in all conditions. Perioral
dermatitis may have been overlapped with some of these subjects. Sodium
sulfacetamide possesses anti-in ammatory and antibacterial properties while sulfur
is a nonspecific antibacterial and antifungal.
Topical metronidazole in the treatment of perioral dermatitis. Veien NK,
Munkvad JM, Nielsen AO, Niordson AM, Stahl D, Thormann J. J Am Acad
Dermatol 1991; 24(2 Pt 1):258–260.
In a prospective, double-blind, randomized, multicenter trial, 108 patients were
treated with twice-daily 1% metronidazole cream or tetracycline 250 mg orally
twice daily over 8 weeks. Oral tetracycline was signi3cantly more e/ ective than
topical metronidazole.
Perioral dermatitis in children – clinical presentation,
pathogenesisrelated factors and response to topical metronidazole. Boeck K, Abeck D,
Werfel S, Ring J. Dermatology 1997;195(3):235–238.
This study investigated perioral dermatitis in children and the possible
pathogenetic mechanisms to response with topical metronidazole 1% cream in 7
children. Pretreatment with topical corticosteroids, skin prick test with a panel of
six common aeroallergens, and screening for gastrointestinal colonization withCandida albicans was performed. In all but one child, topical corticosteroids had
been used in the face prior to the 3rst presentation. An association with atopy or
intestinal Candida colonization was not found. In all children, skin lesions resolved
after 3–6 months and they remained symptom free for 2 years.
A randomized, double-blind, vehicle-controlled study of 1% pimecrolimus
cream in adult patients with perioral dermatitis. Schwarz T, Kreiselmaier I,
Bieber T, Thaci D, Simon JC, Meurer M. J Am Acad Dermatol 2008; 59(1):34–40.
A multicenter, randomized, double-blind, parallel-group study was performed in
112 adult patients with perioral dermatitis treated with pimecrolimus cream 1%
twice daily or pimecrolimus vehicle until clearance was achieved up to 4 weeks.
After 8 days of treatment, 40% of the patients treated with pimecrolimus
experienced a marked improvement in their skin symptoms compared with 10% in
the vehicle group, with no rebound over 8 weeks.
Photodynamic therapy for perioral dermatitis. Richey DF, Hopson B. J Drugs
Dermatol 2006; 5(2 Suppl):12–16.
A split-face 21-patient study was conducted in which one side of the face was
treated 4 times weekly with aminolevulinic acid photodynamic therapy (ALA-PDT).
A protocol of 30-minute ALA incubation with blue light activation was used while
the other side was treated with topical clindamycin. 66.7% of patients completed
the study. The side treated with ALA-PDT achieved a mean clearance of 92.1%
compared to 80.9% for the clindamycin-treated side. More studies are needed to
confirm these results and to elucidate the mechanism of action.
Perioral dermatitis with histopathologic features of granulomatous
rosacea: successful treatment with isotretinoin. Smith KW. Cutis. 1990 Nov;
46(5):413–415.
A young woman with granulomatous perioral dermatitis failed standard
therapies. Her eruption cleared after a 20 week treatment of oral isotreinoin.
Isotertinoin is only indicated for long-standing and refractory forms of perioral
dermatitis.
Commonly encountered pitfalls
Ethnic patients are more likely to use topical bleaching agents on the face which
may contain high potency corticosteroids, thus increasing their incidence of
perioral dermatitis. All lightening creams should be assessed by the clinician,
especially from Asian or African countries where lightening creams are more likely
to be adulterated with potent corticosteroids. In the United States, lightening
creams purchased in beauty supply stores should likewise be carefully evaluated.
Discontinuation of lightening agents which contain potent corticosteroids is the
treatment of choice, though a rebound phenomenon can occur. A taper of topical*
steroids may be considered.
Special management & counseling considerations
Since many cases are associated with the use of topical corticosteroids, withdrawal
of this medication is the most important strategy, despite initial ares. In ethnic
patients, as previously stated, use of bleaching agents should be discontinued if
they are suspected of containing high potency corticosteroids. Patients should be
advised to discard the bleaching agent as they may be tempted to reuse if
uncomfortable symptoms associated with a rebound flare occur.
References
1 Manders SM, Lucky AW. Perioral dermatitis in childhood. J Am Acad Dermatol.
1992;27:688-692.
2 Cohen HJ. Perioral dermatitis. J Am Acad Dermatol. 1981;4:739-740.
3 Ferlito TA. Tartar-control toothpaste and perioral dermatitis. J Clin Orthod.
1992;26:43-44.
4 Kalkoff KW, Buck A. Etiology of perioral dermatitis. Hautarzt. 1977;28:74-77.
5 Held E, Ottevanger V, Petersen CS, Weismann K. Perioral dermatitis in children
under steroid inhalation therapy. Ugeskr Laeger. 1997;159:7002-7003.$
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Bullous and Pustular Disorders
Janelle Vega, David A. Rodriguez
Bullosis diabeticorum 25
Bullous pemphigoid 26
Impetigo 29
Infantile acropustulosis 32
Pemphigus foliaceus 33
Pemphigus vulgaris 35
Bullosis diabeticorum
Bullosis diabeticorum (BD) is a relatively rare cutaneous complication of diabetes
mellitus, characterized by the spontaneous development of tense bullae that may range
up to several centimeters in size. BD usually arises on previously normal skin
particularly on acral areas with the feet the most common location, (Fig. 2.1), followed
by the lower legs, hands and forearms. The blister is lled with clear, sterile uid with a
1thick consistency. Patients report rapid onset, with lesions often appearing ‘overnight.’
2The lesions of BD heal without scarring in most cases.#
Figure 2.1 Bullosis diabeticorum. A tense blister on the palm as well as desquamation
at sites of previous bullae.
(From Bolognia; Dermatology 2e; Mosby, copyright Elsevier 2008.)
Diabetes mellitus is a common disease of individuals with skin of color, particularly
those of Latin and African American decent. Although 30% of diabetic patients develop
cutaneous manifestations of their disorder, BD occurs much less commonly, with an
3,4incidence of 0.16% per year in one series. Patients may have more than one episode
5during their lifetime. In some cases, the development of BD heralds the onset of
6diabetes or insulin resistance. The cause of BD is unknown, but it has been observed in
7patients with diabetic microangiopathy, neuropathy, nephropathy, and retinopathy.
Therapy
There are no studies regarding appropriate therapy for BD; some articles suggest that
lesions will spontaneously resolve within 2–6 weeks; however, others suggest local care
including de-roofing and treatment with antibiotics when necessary.
Incidence of bullosis diabeticorum – a controversial cause of chronic foot
ulceration. Larsen K, Jensen T, Karlsmark T, Holstein PE. Int Wound J 2008; 5(4):591–
596.
This single-center retrospective case series included 25 patients with BD; collectively,
they experienced 35 episodes with 93 total bullae. The authors recommend de-roo ng
and drainage of the bullae, then the application of a non-adherent gauze. Patients were
followed, received regular foot care and wore special shoes. Patients that had what
appeared to be an infection were treated with appropriate antibiotics.
Commonly encountered pitfalls
Although much of the literature suggests that spontaneous resolution is the rule, some
case series have reported subsequent chronic ulcers, osteomyelitis, and even amputation@
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8following bullosis diabeticorum. Careful observation and close follow-up of these
patients are required. Patients without a history of diabetes who are present with a
4lesion similar to BD should be fully evaluated for an existing endocrinopathy.
Special management & counseling considerations
In a study of the prevalence of diabetes in di erent ethnic groups, the authors found a
signi cantly higher prevalence of BD in Hispanics, which was statistically signi cantly
higher than in Blacks, and higher than Asians and Caucasian patients (Hispanics
9334/1000; Blacks 296/1000; Asians 243/1000; Whites 184/1000). Therefore, the
prevalence of BD in clinical practice may be higher depending on the population one is
treating.
References
1 Derighetti M, Hohl D, Krayenbühl BH, Panizzon RG. Bullosis diabeticorum in a newly
discovered type 2 diabetes mellitus. Dermatology. 2000;200(4):366-367.
2 Aye M, Masson EA. Dermatological care of the diabetic foot. Am J Clin Dermatol.
2002;3(7):463-474.
3 Bernstein JE, Medenica M, Soltani K, Griem SF. Bullous eruption of diabetes mellitus. Arch
Dermatol. 1979;115:324-325.
4 Larsen K, Jensen T, Karlsmark T, Holstein PE. Incidence of bullosis diabeticorum – a
controversial cause of chronic foot ulceration. Int Wound J. 2008;5(4):591-596.
5 Basarab T, Munn SE, McGrath J, Russell JR. Bullosis diabeticorum. A case report and
literature review. Clin Exp Dermatol. 1995;20:218-220.
6 Lopez PR, Leicht S, Sigmon JR, Stigall L. Bullosis diabeticorum associated with a
prediabetic state. South Med J. 2009 May 7. [Epub ahead of print]
7 Anand KP, Kashyap AS. Bullosis diabeticorum. Postgrad Med J. 2004;80(944):354.
8 Tunuguntla A, Patel KN, Peiris AN, Zakaria WN. Bullosis diabeticorum associated with
osteomyelitis. Tenn Med. 2004;97:503-504.
9 McBean AM, Li S, Gilbertson DT, Collins AJ. Differences in diabetes prevalence,
incidence, and mortality among the elderly of four racial/ethnic groups: whites, blacks,
hispanics, and asians. Diabetes Care. 2004;27(10):2317-2324.
Bullous pemphigoid
Bullous pemphigoid (BP) is an autoimmune blistering disorder equally a ecting male
and female patients between the ages of 60 and 80 years. IgG autoantibodies target
hemidesmosomal proteins (BP230 [BPAg1] and BP180 [BPAg2]) and result in tense,
1uid lled vesicles (Fig. 2.2). Often, the early phase of BP is urticarial, and patients
may initially present with erythematous pruritic plaques, which evolve over time to form
bullae. Common sites of involvement include exural areas such as axillae, antecubital
fossae, inner thighs, groin, lower trunk, and lower legs. The one year mortality for BP is#
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23%; however, when BP patients were matched with controls for age and comorbidities,
there was no signi cant di erence in mortality. It is likely that BP does not confer
increased mortality to these patients, and mortality results from disease-independent
2factors.
Figure 2.2 Bullous pemphigoid. Classic presentation with multiple bullae arising on
normal and erythematous skin. Several of the bullae have ruptured leaving circular
erosions.
(Courtesy Dr. Henry Lim.)
First-Line Therapy
Systemic corticosteroids A
Topical corticosteroids A
Patients with mild to moderate disease can be treated initially with high potency
topical corticosteroids and systemic corticosteroids may be added if they are
3uncontrolled. The need for high dose corticosteroids has not been established, and may
confer an increased adverse event pro le. Therefore, the dosage of corticosteroids may
begin at 0.5–0.75 mg/kg/day.
Treatment of bullous pemphigoid with prednisolone only: 0.75 mg/kg/day
versus 1.25 mg/kg/day. A multicenter randomized study. Morel P, Guillaume JC.
Annales de Dermatologie et Vénéréologie 1984; 111:925–928.
In this randomized, multicenter study, patients received either 0.75 mg/kg/day or
1.25 mg/kg/day of prednisolone. There was no signi cant di erence in clearance of
lesions at 21 or 51 days with the two dosage regimens. However, there were more deaths
in the 1.25 mg/kg/day group.
A comparison of oral and topical corticosteroids in patients with bullous#
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pemphigoid. Joly P, Roujeau JC, Benichou J, Picard C, Dreno B, Delaporte E and the
Bullous Diseases French Study Group. N Engl J Med 2002; 346(5):321–327.
This multicenter, non-blinded, randomized trial of 341 participants who were
randomized to receive potent topical corticosteroids (clobetasol propionate: 40g/d), or
prednisone (1 mg/kg/d) for severe disease [>10 new blisters/day]; or 0.5 mg/kg/d for
moderate disease [<10 new="" _blisters2f_day5d_29_.="" even="" in="" patients=""
with="" severe="" _disease2c_="" survival="" was="" higher="" for="" those=""
using="" topical="" steroids="" _28_7625_29_="" versus="" on="" oral=""
_28_5825_2c_="" or="" _0.442c_="" _9525_="" ci="" _0.24e28093_0.8329_.=""
disease="" control="" achieved="" within="" 3="" weeks="" _9925_="" of="" the=""
receiving="" _9125_="">
Second-Line Therapy
Topical tacrolimus D
Azathioprine A
Mycophenolate mofetil A
Tetracycline and nicotinamide C
Several case reports have demonstrated success of topical tacrolimus in the treatment
of both localized and generalized BP. Its addition has allowed for tapering of
prednisone. Topical tacrolimus may be a good therapeutic option for patients who
cannot use topical steroids, do not improve with their use, or for patients with facial
4lesions. One limitation to this therapy is its high cost particularly when compared to
the price of topical corticosteroids.
Topical tacrolimus is a useful adjunctive therapy for bullous pemphigoid. Chu
J, Bradley M, Marinkovich MP. Arch Dermatol 2003; 139:813–815.
This case series of two patients describes a 70-year-old woman on multiple
medications including doxycycline, niacinamide, mycophenolate mofetil and prednisone
(60 mg/d). Physicians were unable to taper prednisone without signi cant are of the
BP. Topical tacrolimus was added, and after 2 weeks, the area of application was clear
of lesions. Over the next 4 weeks, she was weaned to 20 mg/d of prednisone without a
are. The second patient was a 58-year-old man, on multiple medications including
prednisone (20 mg/d), tetracycline, and niacinamide was also able to be tapered o of
prednisone three weeks after topical tacrolimus was added to the therapeutic regimen.
The addition of an immunosuppressive agent to a therapeutic regimen that includes
an oral corticosteroid, allow the dosage of the corticosteroid to be reduces or
discontinued, thus reducing possible adverse event from the corticosteroid.
A comparison of oral methylprednisolone plus azathioprine or mycophenolate$
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mofetil for the treatment of bullous pemphigoid. Beissert S, Werfel T, Frieling U,
Böhm M, Sticherling M, Stadler R, et al. Arch Dermatol 2007; 143(12):1536–1542.
In this prospective, multicenter, randomized, non-blinded clinical trial, patients were
randomized to receive methylprednisolone (0.5 mg/kg/day) and azathioprine or
mycophenolate mofetil. Clinical remission was achieved faster in patients in the
azathioprine group (23.8 ± 18.9 days vs 42.0 ± 55.3 days), and lower total doses of
methylprednisolone were used overall in this group (4967.0 ± 12 190.7 mg vs 5754.0
± 9692.8 mg). Higher adverse e ects were seen in the azathioprine group, with 24% of
patients experiencing grade 3 or 4 adverse e ects vs 17% of patients in the
mycophenolate mofetil group. There was decreased liver toxicity in the mycophenolate
mofetil group.
Nicotinamide and tetracycline therapy of bullous pemphigoid. Fivenson DP,
Breneman DL, Rosen GB, Hersh CS, Cardone S, Mutasim D. Arch Dermatol 1994;
130:753–758.
In this randomized, non-blinded trial, a total of 20 patients were randomized to
receive prednisone versus tetracycline (500 mg po qid) and nicotinamide (500 mg po
tid). Only 18 of the 20 enrolled were treated, and 6 of these were randomized to the
prednisone group. There were two complete responders in the tetracycline and
nicotinamide group versus one complete responder in the prednisone group. At
10month follow-up, there were only 5 participants able to be reached in the tetracycline
group, all of whom were disease free after tapering. In the prednisone group, three
patients were reached at follow-up, all of whom had ares on a steroid taper. Severe
side e ects in the prednisone group included death secondary to sepsis and in the
tetracycline group included transient renal failure in patients with impaired renal
function at the start of the trial.
Third-Line Therapy
Methotrexate C
Intravenous immunoglobulin (IVIg) C
Rituximab E
Low-dose methotrexate is a treatment option for BP patients who are able to tolerate
the treatment or for those who have coexisting psoriasis. It has been demonstrated that
methotrexate confers no difference in mortality as compared to prednisone alone.
A retrospective analysis of patients with bullous pemphigoid treated with
methotrexate. Kjellman P, Eriksson H, Berg P. Arch Dermatol 2008; 144(5):612–616.
This was a retrospective study of 138 patients with bullous pemphigoid who received
either methotrexate (median weekly dosage 5 mg/week), prednisone, methotrexate and@
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prednisone, or topical glucocorticoids alone. Mild adverse e ects occurred with
methotrexate including gastrointestinal tract irritation, transient alveolitis, anemia, and
increasing liver enzymes. There was a trend toward decreased mortality in the patients
on low dose methotrexate, and no signi cant di erence in survival in all groups.
Twoyear remission in the methotrexate alone group was better than the methotrexate plus
prednisone group, and there were no clinical remissions in the prednisone alone group.
No randomized controlled trials have been performed on the use of IVIg in BP, but a
consensus statement summarized the available data up until 2003 which seems
5promising. It may be helpful to add IVIg when a patient has failed 6 weeks of
prednisone at 1 mg/kg/day, and has failed therapy even with the addition of
immunosuppressive agents for 10–12 weeks. Other indications for treatment are patients
with severe side e ects on corticosteroids or immunosuppressive agents or with
contraindications to these agents. The addition of an immunosuppressive agent and IVIg
may help resolution of BP by decreasing the burden of circulating autoantibodies,
according to one case report.
Intravenous immunoglobulin therapy for patients with bullous pemphigoid
unresponsive to conventional immunosuppressive treatment. Ahmed AR. J Am
Acad Dermatol 2001; 45:825–835.
In this case series of 15 patients with severe BP refractory to high dose corticosteroids
and immunosuppressive agents, requiring multiple hospitalizations, the patients
received IVIg at 2 g/kg per cycle. All patients achieved remission, even after IVIg was
discontinued. Time to e ectiveness was a mean of 2.9 months and patients were treated
for a mean of 24.4 months with IVIg. Oral prednisone was tapered over time.
The response to rituximab therapy, a CD 20 monoclonal antibody targeted at B cells,
has been mixed, and although e ective in some patients, deaths have been associated
6with its use.
Rituximab in autoimmune bullous diseases: mixed responses and adverse
effects. Schmidt E, Seitz CS, Benoit S, Bröcker EB, Goebeler M. Br J Dermatol 2007;
156(2):352–356.
In this case series, 2 of the 7 patients had BP and were treated with intravenous
2rituximab weekly for one month at a dose of 375 mg/m . One of the patients was a
2year-old boy who developed a prolonged hypogammaglobulinemia and required
parenteral feeding; the other patient died of nosocomial pneumonia. These patients had
partial and complete remission of the BP.
Commonly encountered pitfalls
BP has an urticarial phase, which is commonly misdiagnosed as urticaria. It is important
to include BP in the di erential diagnosis of urticarial-like lesions. If treating an elderly
patient with urticaria, it is also helpful to warn them if the lesions become blisters, that
7immediate reevaluation by their physician is required.@
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Special management & counseling considerations
Patients with bullous pemphigoid tend to be older and have more comorbidities. It may
be prudent, wherever possible, to use the least toxic therapy (i.e. topical corticosteroids)
to avoid any unwanted side e ects. Mortality in this age group is high, and it is not
desirous to add therapies that further increase it.
References
1 Suárez-Fernández R, España-Alonso A, Herrero-González JE, Mascaró-Galy JM. [Practical
management of the most common autoimmune bullous diseases]. Actas Dermosifiliogr.
2008;99(6):441-455.
2 Parker SR, Dyson S, Brisman S, Pennie M, Swerlick RA, Khan R, et al. Mortality of bullous
pemphigoid: an evaluation of 223 patients and comparison with the mortality in the
general population in the United States. J Am Acad Dermatol. 2008;59(4):582-588.
3 Khumalo N, Kirtschig G, Middleton P, Hollis S, Wojnarowska F, Murrell D. Interventions
for bullous pemphigoid. Cochrane Database Syst Rev 2005; (3):CD002292.
4 Ko MJ, Chu CY. Topical tacrolimus therapy for localized bullous pemphigoid. Br J
Dermatol. 2003;149:1079-1081.
5 Czernik A, Bystryn JC. Improvement of intravenous immunoglobulin therapy for bullous
pemphigoid by adding immunosuppressive agents: marked improvement in depletion
of circulating autoantibodies. Arch Dermatol. 2008;144(5):658-661.
6 Hertl M, Zillikens D, Borradori L, Bruckner-Tuderman L, Burckhard H, Eming R, et al.
Recommendations for the use of rituximab (anti-CD20 antibody) in the treatment of
autoimmune bullous skin diseases. J Dtsch Dermatol Ges. 2008;6(5):366-373.
7 Brodell LA, Beck LA. Differential diagnosis of chronic urticaria. Ann Allergy Asthma
Immunol. 2008;100(3):181-188.
Impetigo
Impetigo, a super cial infection of the skin, is the most common cause of bacterial
1infections in children. It is extremely contagious and can be transmitted by
person-toperson contact as well as via fomites. Children with diseases that disrupt the epidermal
2,3barrier, such as atopic dermatitis, are especially prone to impetigo. Atopic dermatitis
is a disorder that occurs frequently in children with skin of color (Fig. 2.3). The bullous
form of impetigo accounts for about one-third of cases, and is sometimes referred to as
pyoderma. This form is almost always a result of Staphylococcus aureus infection, due to
its ability to produce exfoliative toxins (ET-A, ET-B), which cleave cell-to-cell adhesions,
4specifically, desmoglein 1. Occasionally, bullous impetigo can be caused by β-hemolytic
5streptococcus pyogenes. Although bullae may appear anywhere on the skin, moist
intertriginous areas on the trunk are the most common location. Lesions often resolve
over several days.#
@
Figure 2.3 Impetigo. Widespread impetigo in a Filipino child.
(From Johnson, Moy, White: Ethnic Skin – Medical and Surgical, Mosby, copyright Elsevier
1998.)
Although lesions may clear on their own, failure to treat impetigo appropriately can
result in a variety of complications including septicemia, guttate psoriasis,
staphylococcal scalded skin syndrome, and acute post-streptococcal glomerulonephritis
6(APGN). APGN is a feared complication, which can occur in as many as 5% of cases of
7streptococcal bullous impetigo.
First-Line Therapy
Mupirocin A
Fusidic Acid A
Retapamulin A
Topical antibiotics are the rst-line therapy for impetigo when the patient has limited
involvement, and is otherwise well. Mupirocin, fusidic acid and retapamulin are superior
to other topical antibiotics, and have minimal side e ects given their route of
administration. Additionally, the antibiotic concentration is highest in the area intended
for treatment, and topical antibiotics are generally less expensive than oral antibiotics.
There is a paucity of high-quality trials evaluating the best therapy for patients with
impetigo; however, there are meta-analyses that demonstrate that topical antibiotics are
at least better than placebo, and evidence suggests that they may be superior to oral#
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8,9antibiotics, in uncomplicated cases.
Mupirocin is the rst line of treatment for impetigo in the United States. The
mechanism of action of mupirocin, a derivative of Pseudomonas uorescens, is the
inhibition of transfer-RNA synthetase. A short course of 3–7 days is e ective utilizing
two to three times daily dosing. However, it is important to note that treatment for
10,11longer than 10 days should be avoided to prevent bacterial resistance.
Mupirocin resistance. Patel JB, Gorwitz RJ, Jernigan JA. Clin Infect Dis 2009 Sep;
49(6): 935–941.
Low levels of resistance have emerged against mupirocin, especially in strains of
methicillin-resistant Staphylococcus aureus (MRSA). This is related to its widespread use
in the general population for skin infections, as well as to the use of mupirocin for
elimination of nasal carriage of MRSA.
Topical mupirocin treatment of impetigo is equal to oral erythromycin therapy.
Mertz PM, Marshall DA, Eaglstein WH, Piovanetti Y, Montalvo J. Arch Dermatol 1989;
125:1069–1073.
This investigator-blinded study of 75 impetigo patients with Staphylococcus aureus,
Streptococcus pyogenes, or both, used topical mupirocin applied three times daily or oral
erythromycin ethylsuccinate (30–50 mg/kg per day). Mupirocin treatment produced
similar clinical results to oral erythromycin and was superior in the eradication of S.
aureus, including antibiotic-resistant S. aureus. This study proved topical mupirocin to
be a safe and effective alternative to oral antibiotic therapy in the treatment of impetigo.
Fusidic acid, which is not available in the United States, is an antibiotic derived from
Fusidium coccineum that inhibits bacterial protein synthesis by interfering with ribosome
12function. Resistance patterns to this topical antibiotic are also emerging.
Fusidic acid cream in the treatment of impetigo in general practice: a double
blind randomised placebo controlled trial. Koning S, van Suijlekom-Smit LWA,
Nouwen JL, Verduin CM, Bernsen RMD, Oranje AP, et al. BMJ 2002; 324:203–206.
This double-blind, randomized, placebo-controlled trial of fusidic acid cream in
combination with povidone-iodine shampoo is compared to placebo. Patients in the
fusidic acid group had a 55% clinical cure rate versus only 13% in the placebo group
(OR 12.6, 95% confidence interval [5.0–31.5]).
A newly approved topical antibiotic for impetigo is retapamulin 1% cream, which has
13been shown to be superior to placebo in clinical trials. The treatment course is similar
to mupirocin (BID × 5 days). This antimicrobial is derived from Clitopilus
passeckeraianus, and functions by inhibiting the 50S subunit of the bacterial ribosome,
which ultimately inhibits protein synthesis. Although other antibiotics function against
10the 50S subunit, the mechanism of retapamulin is novel. The bene t of the drug also
lies in its success against strains of Staphylococcus aureus that are resistant to fusidic
acid, methicillin and mupirocin. It has been shown in trials to be as e ective as fusidic
14acid and oral cephalexin in the treatment of impetigo. Its recent development and@
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15unique mechanism of action makes bacterial resistance intrinsically more unlikely.
E cacy and safety of retapamulin ointment as treatment of impetigo:
randomized double-blind multicentre placebo-controlled trial. Koning S, van der
Wouden JC, Chosidow O, et al. Br J Dermatol 2008; 158(5):1077–1082 [Epub 2008 Mar
13].
In this randomized, double-blind, multicenter study retapamulin was tested vs
placebo in a total of 213 patients. Retapamulin ointment had a success rate of 84.6% in
contrast to placebo, which had a success rate of 52.1% (p
Topical retapamulin ointment (1%) twice daily for 5 days versus oral
cephalexin twice daily for 10 days in the treatment of secondarily infected
dermatitis: results of a randomized controlled trial. Parish LC, Jorizzo JL, Breton JJ,
Hirman JW, Scangarella NE, Shawar RM, et al. J Am Acad Dermatol 2006; 55:1003–
1013.
This is a randomized, double-blind, double-dummy, non-inferiority trial, evaluating
the e cacy and safety of retapamulin ointment 1% BID for 5 days in the treatment of
secondarily infected dermatitis vs cephalexin 500 mg BID for 10 days. The study yielded
results demonstrating that retapamulin was just as e ective as cephalexin both clinically
(85.9% vs 89.7% respectively) and in terms of microbiologic clearance (87.2% vs
91.8%). Of note is the fact that participants preferred topical treatment. The study
concludes that topical retapamulin is just as e ective in the treatment of secondary
infected dermatitis as oral cephalexin.
Second-Line Therapy
Oral antibiotics B
When bullous impetigo is extensive, treatment with oral antibiotics may be a more
practical option for patients. The oral route should also be considered if infection is
complicated by systemic symptoms such as fever. It is important to be familiar with
resistance patterns of Staphylococci in one’s community when deciding on an oral
antibiotic. If no methicillin resistance is suspected or culture shows methicillin sensitive
Staphylococcus aureus (MSSA), β-lactamase resistant penicillins, macrolides and 1st or
2nd generation cephalosporins (Gram-positive activity) are all viable treatment options.
Treatment duration should span 10 days; the dosing varies according to the medication
(see Table 2.1).
Table 2.1 Oral therapy for impetigoThird-Line Therapy
Erythromycin B
Erythromycin should be used as third-line therapy because of gastrointestinal side
effects, and studies that demonstrate that it may be inferior to topical mupirocin.
Topical mupirocin treatment of impetigo is equal to oral erythromycin therapy.
Mertz PM, Marshall DA, Eaglstein WH, Piovanetti Y, Montalvo J. Arch Dermatol 1989;
125:1069–1073.
This investigator-blinded study of 75 impetigo patients with Staphylococcus aureus,
Streptococcus pyogenes, or both, used topical mupirocin applied three times daily or oral
erythromycin ethylsuccinate (30–50 mg/kg per day). Mupirocin treatment produced
similar clinical results to oral erythromycin and was superior in the eradication of S.
aureus, including antibiotic-resistant S. aureus. This study proved topical mupirocin to
be a safe and effective alternative to oral antibiotic therapy in the treatment of impetigo.
Commonly encountered pitfalls
As with all contagious conditions, crowded living areas, low-income housing, impaired
access to health care, lack of appropriate sanitation and homelessness will increase a
patient’s risk of developing impetigo. Therefore, it is imperative to maintain a high index
16of suspicion in these patients. The risk for acquiring community-acquired
methicillinresistant Staphylococcus aureus (CA-MRSA) is increased in these same conditions. Thus,
in treating some patients with ethnic skin, it is crucial to obtain cultures of bullous
17lesions or treat presumptively for CA-MRSA.
Special management & counseling considerations
MRSA infection is an increasing problem in the treatment and management of
dermatologic diseases. Infection with resistant strains should be treated according to the
Infectious Disease Society of America (IDSA) practice guidelines. For CA-MRSA,
doxycycline, minocycline, and trimethoprim-sulfamethoxazole are viable treatment
options, whereas for more serious infection, systemic therapy with vancomycin,\
18linezolid, clindamycin or daptomycin can be employed. Tigecycline is a new
glycylcycline antibiotic that has shown e cacy comparable with that of vancomycin
19and can be used in hospital settings.
Simple practices such as handwashing and general good hygiene have also been
20shown to decrease transmission of impetigo.
References
1 Darnstadt GL. Cutaneous bacterial infections. In: Behrman RE, Kliegman RM, Jenson HB,
editors. Nelson textbook of pediatrics. Philadelphia: WB Saunders; 2000:2028-2030.
2 Kiken DA, Silverberg NB. Atopic dermatitis in children, part 1: epidemiology, clinical
features, and complications. Cutis. 2006;78(4):241-247.
3 Koning S, Verhagen AP, van Suijlekom-Smit LW, Morris A, Butler CC, van der Wouden JC.
Interventions for impetigo. Cochrane Database Syst Rev 2004; CD003261.
4 Amagai M, Matsuyoshi N, Wang ZH, Andl C, Stanley JR. Toxin in bullous impetigo and
staphylococcal scalded-skin syndrome targets desmoglein 1. Nat Med.
2000;6:12751277.
5 Lin JJ, Wu CT, Hsia SH, Chiu CH. Bullous impetigo: a rare presentation in fulminant
streptococcal toxic shock syndrome. Pediatr Emerg Care. 2007;23:318-320.
6 Hedrick J. Acute bacterial skin infections in pediatric medicine: current issues in
presentation and treatment. Pediatr Drugs. 2003;5(Suppl 1):35-46.
7 Oumeish I, Oumeish OY, Bataineh O. Acute bacterial skin infections in children. Clin
Dermatol. 2000;18:667-678.
8 George A, Rubin G. A systematic review and meta-analysis of treatments for impetigo. Br
J Gen Pract. 2003;53:480-487.
9 Mertz PM, Marshall DA, Eaglstein H, Piovanetti Y, Montalvo J. Topical mupirocin
treatment of impetigo is equal to oral erythromycin therapy. Arch Dermatol.
1989;125:1069-1073.
10 Gelmetti C. Local antibiotics in dermatology. Dermatol Ther. 2008;21(3):187-195.
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daily for 10 days in the treatment of secondarily infected dermatitis: results of a
randomized controlled trial. J Am Acad Dermatol. 2006;55:1003-1013.#
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2005;366(9481):225-233.
Infantile acropustulosis
Recurrent, acral pruritic, vesiculopustules during infancy characterizes this rare
disorder. It is most commonly seen in boys with skin types IV–VI. The onset of lesions is
1within the rst 6 months of age which regress within 1–2 weeks, and recur monthly.
The frequency of recurrence and duration of lesions wanes until they resolve, usually
around 3 years of age. Infantile acropustulosis most commonly occurs on the palms and
soles, dorsa of hands and feet (Fig. 2.4), and between the digits. Rarely, these lesions
occur in an axial distribution. Although this disease resolves spontaneously, extreme
pruritus causes signi cant discomfort, di culty sleeping, and excoriations, which can
2become secondarily infected.
Figure 2.4 Infantile acropustulosis with multiple pustules on the foot of an African-@
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American child.
(Courtesy of Valarie Callander, MD.)
First-Line Therapies
Topical corticosteroids B
Oral antihistamines E
Studies have shown that medium to high potency corticosteroids for a brief time are
safe and e ective in treating pruritus. If needed, the corticosteroids can be used with
3wet wraps to help increase their e cacy. Supplementation with oral antihistamines,
4usually at sedating doses, is also e ective in alleviating the symptoms. Although the
pustules are sterile, treatment with oral antibiotics has been reported to be helpful, likely
due to their anti-in ammatory properties. Secondarily infected lesions should be treated
with antibiotics and topical antibiotics are usually adequate.
Infantile acropustulosis revisited: history of scabies and response to topical
corticosteroids. Mancini AJ, Frieden IJ, Paller AS. Pediatr Dermatol 1998; 15(5):337–
341 [PubMed PMID: 9796580].
This is a retrospective study of 21 patients diagnosed with infantile acropustulosis, in
which the history of scabies and prior treatment for scabies was analyzed. In 14 of 21
patients, there was a history of scabies, but only 2 of whom had evidence of scabies on
microscopic analysis. All patients were treated with topical corticosteroids ranging from
class I to VI with no adverse events.
Second-Line Therapies
Dapsone D
Dapsone, a potent inhibitor of neutrophil chemotaxis, at a dose of 2 mg/kg/day, is
thought to be the most e ective oral medication for infantile acropustulosis, but should
be reserved for cases refractory to treatment. Potential severe side e ects including
aplastic anemia, methemoglobinemia, and peripheral motor neuropathy precludes
widespread use. There have been no randomized controlled trials, and support for its use is
5,6basis of multiple case series and case reports.
Atypical acropustulosis in infancy. Truong AL, Esterly NB. Int J Dermatol 1997;
36(9):688–691.
A 20-month-old girl with lesions on the feet, extending to the legs, chest and scalp,