January/February 2012 • Volume 10 • Issue 1 - SKINmed Journal

EDITORIAL 

Modesty and the Skin: Why They Shouldn’t Mix 

Campbell and Parish 

COMMENTARY 

Origin and Evolution of Syphilis: Drifting Myth 

Sehgal, Verma, Chatterjee, Chaudhuri, Chatterjee, and Rasool 

ORIGINAL CONTRIBUTIONS 

A New Paradigm in the Treatment of Kerions: 

Treat the Inflammation 

Dolder, O’Neill, O’Brien, Ross, Allen, and Allen 

Pityriasis Rubra Pilaris: Evolution of Challenges in 

Promising Treatment Options 

Sehgal, Srivastava, and Verma 

REVIEW 

The Role of Surgical Debridement in Healing of 

Diabetic Foot Ulcers 

Gordon, Lebrun, Tomic-Canic, and Kirsner 

CORE CURRICULUM 

Cutaneous Tuberculosis: A Diagnostic Dilemma 

Sehgal, Verma, Bhattacharya, Sharma, Singh, and Verma 

DEPARTMENTS 

COSMETIC SCIENCE 

Repelling Insects With Safe and Effective 

Alternatives to DEET 

Epstein 

January/February 2012 • Volume 10 • Issue 1 

PERILS OF DERMATOPATHOLOGY 

It’s Not Just Who You Are, It’s Also Where You Are: 

The Cutaneous Leiomyosarcoma Dilemma 

Tumer, Castilla, and Lambert 

INFECTIOUS DISEASE CAPSULE 

It May Be Vulgar, but It Isn’t a Bad Word 

Saunders, Herchline, and Bernstein 

CASE STUDIES 

Unusually Severe Case of Dermatosis Neglecta 

Turrentine, Blalock, and Davis 

Fixed-Drug Eruption Caused by Ashwagandha 

(Withania somnifera): A Widely Used Ayurvedic Drug 

Sehgal, Verma, and Bhattacharya 

Chronic Lymphocytic Leukemia Revealed by a 

Granulomatous Zosteriform Eruption 

Trojjet, Hammami, Zaraa, Bouzguarrou, Joens, 

Haouet, Osman, and Mokni 

CORRESPONDENCE 

Mycobacterium marinum Cutaneous Infection 

With Sporotrichoid Distribution Treated With 

Azithromycin Monotherapy 

Rallis, Falidas, and Stavropoulos

DIFFERIN ® (adapalene) LOTION, 0.1%— 

THE ONLY RETINOID IN A LOTION FORMULATION 

ON THE JOB 

WITH GENTLE EFFICACY 1 

RESULTS PATIENTS WANT IN A FORMULATION THAT DOES THE WORK— 

PRESCRIBE DIFFERIN ® LOTION, 0.1% TODAY! 

* A 12-week, multicenter, randomized, double-blind, parallel-group study of patients 12 to 18 years of age with acne vulgaris (N=1075). 

† The most frequent adverse event reported was dryness. Erythema, stinging/burning, and scaling may also occur. 1 

Important Safety Information 

Differin ® Lotion, 0.1% is indicated for the topical treatment of acne vulgaris in patients 12 years and older. A thin fi lm of 

Differin ® Lotion, 0.1% should be applied once per day to the face and other areas of the skin affected by acne. In clinical 

trials, the most common adverse event (>1%) reported with use of Differin ® Lotion, 0.1% was mild to moderate skin dryness. 

Erythema, scaling, stinging and burning may also occur. Excessive exposure to sunlight and sunlamps should be avoided 

during treatment, and use of sunscreen products and protective clothing is recommended. Concomitant use of drying or 

irritating topical products (like products containing resorcinol, salicylic acid or sulfur) should be used with caution. Instruct 

patients to avoid the eyes, lips and mucous membranes when applying Differin ® Lotion, 0.1%, and not to apply to areas 

that have been depilated with wax products. Differin ® Lotion, 0.1% has not been tested in pregnant or nursing women, 

or with the elderly. Pregnancy Category C. 

www.differin.com/HCP 

Please see Brief Summary 

of Prescribing Information 

on adjacent page. 

58.2% MEDIAN TOTAL LESION COUNT 

REDUCTION BY WEEK 12 1 * 

TOLERABILITY PROFILE SIMILAR TO 

DIFFERIN ® (adapalene) CREAM, 0.1% 1† 

AVAILABLE IN AN EASY-TO-USE 

PUMP DISPENSER

DIFFERIN ® 

Rx only 

(adapalene) Lotion 0.1% 

For Topical Use Only 

Not For Oral, Ophthalmic, or Intravaginal Use. 

BRIEF SUMMARY 

INDICATIONS AND USAGE 

DIFFERIN Lotion is a retinoid product indicated for the topical treatment of 

acne vulgaris in patients 12 years and older. 

CONTRAINDICATIONS 

None. 

WARNINGS AND PRECAUTIONS 

Ultraviolet Light and Environmental Exposure: Avoid exposure to sunlight 

and sunlamps. Wear sunscreen when sun exposure cannot be avoided. 

Erythema, scaling, dryness, and stinging/burning may occur with use of 

DIFFERIN Lotion. 

ADVERSE REACTIONS 

Dry skin of mild to moderate severity was the most frequently reported 

(≥ 1%) treatment related adverse event. Erythema, scaling, dryness, 

burning/stinging were also seen during treatment. 

DRUG INTERACTIONS 

Concomitant use of topical products with a strong drying effect can increase 

skin irritation. Use with caution, especially in using preparations containing 

sulfur, resorcinol, or salicylic acid in combination with DIFFERIN Lotion. Wax 

depilation should not be performed on treated skin. 

Pregnancy 

Pregnancy Category C. There are no well-controlled trials in pregnant women 

treated with DIFFERIN Lotion. Therefore, DIFFERIN Lotion should be 

used during pregnancy only if the potential benefit justifies the potential risk 

to the fetus. Animal reproduction studies have not been conducted with 

DIFFERIN Lotion. Furthermore, such studies are not always predictive of 

human response. 

Human Data 

In clinical trials involving DIFFERIN Lotion, 0.1% in the treatment of acne 

vulgaris, women of childbearing potential initiated treatment only after a 

negative pregnancy test. Two women became pregnant while using DIFFERIN 

Lotion, 0.1%. One patient delivered a healthy full term baby and the other 

patient electively terminated her pregnancy. 

Animal Data 

No teratogenic effects were observed in rats treated with oral doses of 0.15 

to 5.0 mg adapalene/kg/day, up to 25 times (mg/m2 /day) the maximum 

recommended human dose (MRHD) of 2 grams of DIFFERIN Lotion. 

However, teratogenic changes were observed in rats and rabbits when treated 

with oral doses of ≥ 25 mg adapalene/kg/day representing 123 and 246 times 

MRHD, respectively. Findings included cleft palate, microphthalmia, 

encephalocele and skeletal abnormalities in rats; and umbilical hernia, 

exophthalmos and kidney and skeletal abnormalities in rabbits. 

Dermal teratology studies conducted in rats and rabbits at doses of 0.6- 

6.0 mg adapalene/kg/day [25-59 times (mg/m2 ) the MRHD] exhibited no 

fetotoxicity and only minimal increases in supernumerary ribs in both species 

and delayed ossification in rabbits. 

Systemic exposure (AUC 0-24h) to adapalene at topical doses 

(6.0 mg/kg/day) in rats represented 101 times the exposure to adapalene in 

patients with acne treated with DIFFERIN Lotion applied to the face, chest 

and back (2 grams applied to 1000 cm² of acne-involved skin). 

Nursing Mothers 

It is not known whether adapalene is excreted in human milk following 

use of DIFFERIN Lotion. Because many drugs are excreted in human milk, 

caution should be exercised when DIFFERIN Lotion is administered to a 

nursing woman. 

Pediatric Use 

Safety and effectiveness of DIFFERIN Lotion in pediatric patients under the 

age of 12 have not been established. 

Geriatric Use 

Clinical studies of DIFFERIN Lotion did not include sufficient numbers of 

subjects aged 65 and over to determine whether they respond differently 

from younger subjects. 

Carcinogenesis, Mutagenesis, Impairment of Fertility 

No carcinogenicity, mutagenicity and impairment of fertility studies were 

conducted with DIFFERIN Lotion. 

Carcinogenicity studies with adapalene have been conducted in mice at 

topical doses of 0.4, 1.3, and 4.0 mg/kg/day (1.2, 3.9, and 12 mg/m²/day), 

and in rats at oral doses of 0.15, 0.5, and 1.5 mg/kg/day (0.9, 3.0, and 

9.0 mg/m 2 /day). In terms of body surface area, the highest dose levels are 

9.8 (mice) and 7.4 times (rats) the MRHD of 2 grams of DIFFERIN Lotion. 

In the rat study, an increased incidence of benign and malignant 

pheochromocytomas in the adrenal medulla of male rats was observed. 

No photocarcinogenicity studies were conducted with adapalene. However, 

animal studies have shown an increased tumorigenic risk with the use 

of pharmacologically similar drugs (e.g. retinoids) when exposed to UV 

irradiation in the laboratory or sunlight. Although the significance of these 

findings to humans is not clear, patients should be advised to avoid or 

minimize exposure to either sunlight or artificial irradiation sources. 

Adapalene did not exhibit mutagenic or genotoxic effects in vitro (Ames test, 

Chinese hamster ovary cell assay, mouse lymphoma TK assay) or in vivo 

(mouse micronucleus test). 

In rat oral studies, 20 mg adapalene/kg/day (120 mg/m 2 /day; 98 times the 

MRHD based on mg/m 2 /day comparison) did not affect the reproductive 

performance and fertility of F 0 males and females, or growth, development 

and reproductive function of F 1 offspring. 

PATIENT COUNSELING INFORMATION 

• Apply a thin film of DIFFERIN Lotion to the affected areas of the skin once 

daily, after washing gently with a mild soapless cleanser. Dispense a nickel 

size amount of DIFFERIN Lotion (3-4 actuations of the pump) to cover the 

entire face. Avoid application to the areas of skin around eyes, lips and 

mucous membranes. DIFFERIN Lotion may cause irritation such as 

erythema, scaling, dryness, stinging or burning. 

• Advise patients to cleanse the area to be treated with a mild or soapless 

cleanser; pat dry. Apply DIFFERIN Lotion to the entire face or other 

acne affected areas as a thin layer, avoiding the eyes, lips and mucous 

membranes. 

• Exposure of the eye to this medication may result in reactions such as 

swelling, conjunctivitis and eye irritation. 

• Patients should be advised not to use more than the recommended amount 

and not to apply more than once daily as this will not produce faster 

results, but may increase irritation. 

• Advise patients to minimize exposure to sunlight including sunlamps. 

Recommend the use of sunscreen products and protective apparel 

(e.g., hat) when exposure cannot be avoided. 

• Moisturizers may be used if necessary; however, products containing alpha 

hydroxy or glycolic acids should be avoided. 

• This medication should not be applied to cuts, abrasions, eczematous, or 

sunburned skin. 

• Wax depilation should not be performed on treated skin due to the 

potential for skin erosions. 

• This product is for external use only. 

Marketed by: 

GALDERMA LABORATORIES, L.P., Fort Worth, Texas 76177 USA 

Manufactured by: 

Galderma Production Canada Inc., Baie d’Urfé, QC, H9X 3S4 Canada 

Made in Canada. 

GALDERMA is a registered trademark. 

P51503-0 

Revised: March 2010 

Reference: 1. Data on file. Galderma Laboratories, L.P. 

Galderma is a registered trademark. 

©2010 Galderma Laboratories, L.P. 

Galderma Laboratories, L.P. 

14501 N. Freeway 

Fort Worth, TX 76177 

DIFF-113 Printed in USA 09/10 

www.differin.com/HCP

EDITORIAL 

2 

TABLE OF CONTENTS 


Modesty and the Skin: Why They Shouldn’t Mix ................................................................................................ 6 

Caren Campbell, BA; Lawrence Charles Parish, MD, MD (Hon) 

COMMENTARY 

Origin and Evolution of Syphilis: Drifting Myth .................................................................................................. 8 

Virendra N. Sehgal, MD; Prashant Verma, MD; Kingshuk Chatterjee, MBBS; Anita Chaudhuri, MD; Gautam Chatterjee, MS; Farhan Rasool, MBBS 

ORIGINAL CONTRIBUTIONS 

REVIEW 

A New Paradigm in the Treatment of Kerions: Treat the Inflammation ............................................................. 14 

Sarah E. Dolder, MD; Brendan J. O’Neill, MD; Meghan M. O’Brien, MD; Amy S. Ross, MD; Robert A. Allen, MD; Herbert B. Allen, MD 

Pityriasis Rubra Pilaris: Evolution of Challenges in Promising Treatment Options ............................................. 18 

Virendra N. Sehgal, MD; Govind Srivastava, MD; Prashant Verma, MD 

The Role of Surgical Debridement in Healing of Diabetic Foot Ulcers .............................................................. 24 

Katherine A. Gordon, BS; Elizabeth A. Lebrun, MD; Marjana Tomic-Canic, PhD; Robert S. Kirsner, MD, PhD 


Cutaneous Tuberculosis: A Diagnostic Dilemma ............................................................................................. 28 

Virendra N. Sehgal, MD; Prashant Verma, MD; Sambit N. Bhattacharya, MD; Sonal Sharma, MD; Navjeevan Singh, MD; Nishant Verma, MD 

Self-Test Review Questions (p. 34) 

DEPARTMENTS 


Howard A. Epstein, PhD, Section Editor 

Repelling Insects With Safe and Effective Alternatives to DEET ....................................................................... 36 

Howard A. Epstein, PhD 


W. Clark Lambert, MD, PhD, Section Editor 

It’s Not Just Who You Are, It’s Also Where You Are: The Cutaneous Leiomyosarcoma Dilemma ......................... 40 

Gizem Tumer, MD; Carmen F. Castilla, BS; W. Clark Lambert, MD, PhD 


Jack M. Bernstein, MD, Section Editor 

It May Be Vulgar, but It Isn’t a Bad Word......................................................................................................... 42 

David Saunders, MD;Thomas Herchline, MD; Jack M. Bernstein, MD 

CASE STUDIES 

Vesna Petronic-Rosic, MD, MSc, Section Editor 

Unusually Severe Case of Dermatosis Neglecta .............................................................................................. 46 

Jake E. Turrentine, BS; Travis W. Blalock, MD; Loretta S. Davis, MD 

Fixed-Drug Eruption Caused by Ashwagandha (Withania somnifera): A Widely Used Ayurvedic Drug ................ 48 

Virendra N. Sehgal, MD; Prashant Verma, MD; Sambit N. Bhattacharya, MD

3 

TABLE OF CONTENTS 


Chronic Lymphocytic Leukemia Revealed by a Granulomatous Zosteriform Eruption ....................................... 50 

Sondes Trojjet, MD; Houda Hammami, MD; Inès Zaraa, MD; Alia Bouzguarrou, MD; Meriem Joens, MD; Slim Haouet, MD; 

Amel Ben Osman, MD; Mourad Mokni, MD 


Mycobacterium marinum Cutaneous Infection With Sporotrichoid Distribution Treated With 

Azithromycin Monotherapy ............................................................................................................................ 54 

Efstathios Rallis, MD, PhD; Evangelos Falidas, MD; Panagiotis Stavropoulos, MD, PhD 

ABOUT OUR JOURNAL 

SKINmed: Dermatology for the Clinician®, print ISSN 1540-9740, online 

ISSN 1751-7125, is published bimonthly by Pulse Marketing & Communications, 

LLC, located at 4 Peninsula Avenue, Sea Bright, NJ 07760. 

Printed in the USA. 

Disclaimer: The Publisher, Editors, and Editorial Board cannot be held 

responsible for errors or any consequences arising from the use of information 

contained in this journal; the views and opinions expressed herein 

do not necessarily reflect those of the Publisher, Editors, and Editorial 

Board, neither does the publication of advertisements constitute any endorsement 

by the Publisher, Editors, and Editorial Board of the products 

or services advertised. The Publisher, Editors, Editorial Board, Reviewers, 

Authors, and Affiliated Agents shall not be held responsible or in any way 

liable for the continued accuracy of the information or for any errors, 

inaccuracies, or omissions of any kind in this publication, whether arising 

from negligence or otherwise, or for any consequences arising thereafter. 

Copyright: © 2012 Pulse Marketing & Communications, LLC. All rights 

reserved. No part of this publication may be reproduced, stored, or transmitted 

in any form or by any means without the prior permission in writing 

from the Publisher. Requests should be addressed to the Permissions 

Editor at: Pulse Marketing & Communications, LLC, 4 Peninsula Avenue, 

Sea Bright, NJ 07760. 

Abstracting & Indexing: The journal is indexed in Index Medicus/ 

MEDLINE and Embase. 

To submit a manuscript for peer review, send as an e-mail attachment 

to the Editor in Chief at lparish@skinmedjournal.com. Please 

visit www.skinmedjournal.com for Information for Authors. 

EDITORIAL DIRECTOR 

Sarah D. Staats 

sstaats@skinmedjournal.com 

PUBLISHER 

Art Kalaka 

PRESIDENT 

Arthur Kalaka 

akalaka@skinmedjournal.com 

Editorial 

MEDIA WEB DIRECTOR 

Joan Osgoodby 

joan@skinmedjournal.com 

Publishing 

Corporate 

GENERAL COUNSEL 

Marianne Mckenzie 

mmckenzie@skinmedjournal.com 

COPYEDITOR 

Elizabeth Holcomb 

eholcomb@skinmedjournal.com 

ASSOCIATE PUBLISHER 

James R. Adams 

jadams@skinmedjournal.com 

CHIEF EXECUTIVE OFFICER 

Jo-Ann Kalaka-Adams 

jadams@skinmedjournal.com 

Pulse Marketing & Communications, LLC 

4 Peninsula Avenue • Suite 401 • Sea Bright, NJ 07760 

Tel (732) 747-6525 • Fax (732) 747-7010

William Abramovits, MD 

Dallas, TX 

Mohamed Amer, MD 

Cairo, Egypt 

Robert L. Baran, MD 

Cannes, France 

Anthony V. Benedetto, DO 

Philadelphia, PA 

Brian Berman, MD, PhD 

Miami, FL 

Jack M. Bernstein, MD 

Dayton, OH 

Sarah Brenner, MD 

Tel Aviv, Israel 

Joaquin Calap Calatayud, MD 

Cadiz, Spain 

Henry H.L. Chan, MB, MD, PhD, FRCP 

Hong Kong, China 

Noah Craft, MD, PhD, DTMH 

Torrance, CA 

Ncoza C. Dlova, MBChB, FCDerm 

Durban, South Africa 

Richard L. Dobson, MD 

Mt Pleasant, SC 

William H. Eaglstein, MD 

Palo Alto, CA 

Boni E. Elewski, MD 

Birmingham, AL 

Charles N. Ellis, MD 

Ann Arbor, MI 

January/February 2012 EDITORIAL BOARD 


Gibbstown, NJ 

Ibrahim Hassan Galadari, MD, PhD, FRCP 

Dubai, United Arab Emirates 

Anthony A. Gaspari, MD 

Baltimore, MD 

Michael Geiges, MD 

Zurich, Switzerland 

Michael H. Gold, MD 

Nashville, TN 

Lowell A. Goldsmith, MD, MPH 

Chapel Hill, NC 

Aditya K. Gupta, MD, PhD, FRCP(C) 

London, Ontario 

Seung-Kyung Hann, MD, PhD 

Seoul, Korea 

Roderick J. Hay, BCh, DM, FRCP, FRCPath 

London, UK 

Tanya R. Humphreys, MD 


Camila K. Janniger, MD 

Englewood, NJ 

Abdul-Ghani Kibbi, MD 

Beirut, Lebanon 

Andrew P. Lazar, MD 

Highland Park, IL 

EDITOR IN CHIEF 

Lawrence Charles Parish, MD, MD (Hon) 


W. Clark Lambert, MD, PhD 

Newark, NJ 

Vesna Petronic-Rosic, MD, MSc 

Chicago, IL 

DEPUTY EDITORS 

EDITORIAL BOARD 

4 

Larry E. Millikan, MD 

Meridian, MS 

Marcia Ramos-e-Silva, MD, PhD 

Rio de Janeiro, Brazil 

Jasna Lipozencic, MD, PhD 

Zagreb, Croatia 

Eve J. Lowenstein, MD, PhD 

New York, NY 

George M. Martin, MD 

Kihei, HI 

Marc S. Micozzi, MD, PhD 

Bethesda, MD 

George F. Murphy, MD 

Boston, MA 

Oumeish Youssef Oumeish, MD, FRCP 

Amman, Jordan 

Joseph L. Pace, MD, FRCP 

Naxxar, Malta 

Art Papier, MD 

Rochester, NY 

Johannes Ring, MD, DPhil 

Munich, Germany 

Roy S. Rogers III, MD 

Rochester, MN 

Donald Rudikoff, MD 

New York, NY 

Robert I. Rudolph, MD 

Wyomissing, PA 

Vincenzo Ruocco, MD 

Naples, Italy 

Jennifer L. Parish, MD 


Noah S. Scheinfeld, MD, JD 

New York, NY 

Virendra N. Sehgal, MD 

Delhi, India 

Charles Steffen, MD 

Oceanside, CA 

Alexander J. Stratigos, MD 

Athens, Greece 

James S. Studdiford III, MD 


Robert J. Thomsen, MD 

Los Alamos, NM 

Julian Trevino, MD 

Dayton, OH 

Snejina Vassileva, MD, PhD 

Sofia, Bulgaria 

Daniel Wallach, MD 

Paris, France 

Michael A. Waugh, MB, FRCP 

Leeds, UK 

Wm. Philip Werschler, MD 

Spokane, WA 

Joseph A. Witkowski, MD 


Ronni Wolf, MD 

Rechovot, Israel

A New Tretinoin Therapy 

From Triax Pharmaceuticals 

©2010 Triax Pharmaceuticals, LLC. All Rights Reserved. Printed in USA TX-0610-02 

%

January/February 2012 Volume 10 • Issue 1 

EDITORIAL 

Modesty and the Skin: Why They Shouldn’t Mix 

Caren Campbell, BA; 1 Lawrence Charles Parish, MD, MD (Hon) 2 

Some years ago, the American Cancer Society first 

mounted a campaign against modesty to publicize the 

need for breast examinations. All too often, women 

were not only too embarrassed to let their physicians fully 

examine their chests, but they were also reluctant to perform 

self-examination. 

This was not the case of the young woman who presented with 

a black lesion on her right breast. She was concerned about the 

peculiarity of the lesion since its appearance 2 months prior 

(Figure). Fortunately, modesty did not play a role in her situation. 

The lesion was quickly excised and proved to be a level 

3 melanoma. How many other patients are not so fortunate to 

have appropriate removal and treatment before it is too late? 

CANCER SCREENING 

Americans should be well informed on the importance of early 

detection in skin cancer. Much emphasis has been placed on this 

concept; however, while patients may be attuned to the idea of 

cancer screening for other body systems, they do not grasp the 

concept of the full body scan. This diagnostic procedure, needless 

to say, cannot be accomplished in a proper fashion without 

disrobing, but many patients are reluctant to do so. 

As any seasoned clinician can attest, melanomas and nonmelanoma 

skin cancers can be found in any area of the body from the 

breasts to the soles. They do not avoid the genitalia, let alone the 

intertriginous areas. Curiously, primary cutaneous melanomas in 

hidden anatomic sites are thicker than those in visible sites, likely 

because of a delay in diagnosis. 1,2 Additionally, the problem may 

be compounded by UV radiation from indoor tanning. Many a 

tanner disrobes completely to obtain his or her money’s worth at 

the tanning parlor but is reluctant to have the dermatologist see 

most of the body. 

MODESTY AT WORK 

Let’s reflect upon the skin examination. Isn’t its purpose to 

find anything that might create a problem? The reason for the 

procedure is to examine visually every skin surface. The act of 

wearing any clothing only serves to hinder and prolong the 

examination. 

Modesty is a behavior, manner, or appearance intended to avoid 

impropriety or indecency. During a physical examination, modesty 

is not serving to avoid impropriety or indecency. It is a false 

modesty. Much like the modesty panel underneath a desk or 

nude-colored hosiery worn by women, it is a social construct. 

The impropriety and judgment felt by the patient and others is 

also created by society. 

The subject of modesty has been examined in detail in other 

disciplines. For example, one such study on modesty sought to 

explore the role that culture played, finding that some perspectives 

on modesty are accounted for by culture, while others are 

not. 3 Modesty was found to be driven by maturity/age, religion/ 

culture, or esteem/upbringing. For the maturity-driven group, 

modesty did not play a role in the health care setting, while the 

religiously/culturally driven group felt modesty should be considered 

in a health care setting. (Disrobing in this setting was not 

an issue.) Most interestingly, the esteem-driven group posed the 

greatest challenge to health care providers, as this group felt it 

stressful and uncomfortable to undress in the health care setting 

and would likely avoid screening for reasons of modesty. 

Although not formally studied, one realizes that body image plays 

a large role in patient modesty. Patients worry that as the physician 

examines their skin they are secretly being judged on their lingerie 

or less-than-ideal body weight. Here, the truth hurts—the clinicians 

are doing their job—to screen the patient for skin cancer. 

There are many papers detailing ways to protect patient modesty, 4–8 

but just as important as the patient’s comfort is the necessity to perform 

a thorough examination. The most obvious way to accomplish 

an appropriate examination to detect malignancy, including 

the scalp, oral cavity, genitals, and nails, would be disrobing. 9 

The patient may wear a gown to cover surfaces not being examined. 

An alternative involves the patient disrobing one quadrant at a 

time. It is both curious and unfortunate when a patient requests a 

full body scan but only permits limited views of the skin. 

From the Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA; 1 and the Department of Dermatology and Cutaneous 

Biology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA2 Address for Correspondence: Lawrence Charles Parish, MD, MD (Hon), 1760 Market Street, Suite 301, Philadelphia, PA 19103 

• E-mail: larryderm@yahoo.com 

SKINmed. 2012;10:6–7 6 

© 2012 Pulse Marketing & Communications, LLC

January/February 2012 

Figure. A level 3 melanoma found on the right breast. 

REFLECTIONS 

When reflecting upon the situation, the role of modesty in 

prophylactic screening is raised. What stands out is a lack of compliance 

in both breast and colon cancer screening due to modesty. 

10,11 If patients are unwilling to undergo cancer screening 

developed for the sole purpose of early detection and prevention, 

we can only conclude that modesty should be considered 

dangerous to their health. 

Skin self-examination is one method that might prove an 

alternative for those too modest to allow yearly examination 

of the entire skin’s surface. Self-examination taught to 

both patient and partner improves self-efficacy for patients. 12 

SKINmed. 2012;10:6–7 

7 

EDITORIAL 

Partnering with those trusted by the patient might improve 

detection and outcomes for patients too modest for frequent 

skin examination. 

Isn’t there an old adage: Modesty killed the cat? 

REFERENCES 

1 Nagore E, Oliver V, Moreno-Picot S, Fortea JM. Primary cutaneous melanoma 

in hidden sites is associated with thicker tumours—a study of 829 

patients. Eur J Cancer. 2001;37:79–82. 

2 Hemo Y, Gutman M, Klausner JM. Anatomic site of primary melanoma 

is associated with depth of invasion. Arch Surg. 1999;134:148–150. 

3 Andrews CS. Defining and exploring modesty in Jewish American 

women. J Relig Health. 2010. http://www.springerlink.com.proxy1.lib. 

tju.edu:2048/content/r666v2x100160487/. Accessed April 23, 2011. 

4 Baillie J. Making a difference to the patient experience. Health Estate. 

2010;64:48–50, 52–55. 

5 Wehbe-Alamah H. Bridging generic and professional care practices for 

Muslim patients through use of Leininger’s culture care modes. Contemp 

Nurse. 2008;28:83–97. 

6 Yosef ARO. Health beliefs, practice, and priorities for health care of Arab 

Muslims in the United States. J Transcult Nurs. 2008;19:284–291. 

7 Roberts KS. Providing culturally sensitive care to the child bearing Islamic 

family. Adv Neonatal Care. 2002;2:222–228. 

8 Lawrence P, Rozmus C. Culturally sensitive care of the Muslim patient. 

J Transcult Nurs. 2001;12:228–233. 

9 Craft N, Fox LP, Goldsmith LA. VisualDx: Essential Adult Dermatology. 

Philadelphia, PA: Lippincott Williams & Wilkins; 2010. 

10 Denberg TD, Melhado TV, Coombes JM, et al. Predictors of nonadherence 

to screening colonoscopy. J Gen Intern Med. 2005;20:989–995. 

11 Parsa P, Kandiah M, Abdul Rahman H, Zulkefli NM. Barriers for breast 

cancer screening among Asian women: a mini literature review. Asian 

Pac J Cancer Prev. 2006;7:509–514. 

12 Robinson JK, Stapleton J, Turrisi R. Relationship and partner moderator 

variables increase self-efficacy of performing skin self-examination. 

J Am Acad Dermatol. 2008;58:755–762. 

HISTORICAL DIAGNOSIS & TREATMENT 

Diagnosis and treatments have advanced over the past century. This feature depicts conditions from a 

collection of steroptic cards published in 1910 by The Stereoscopic Skin Clinic, by Dr. S. I. Rainforth. 

(continued on page 12) 

Modesty and the Skin: Why They Shouldn’t Mix


COMMENTARY 

Origin and Evolution of Syphilis: Drifting Myth 

Virendra N. Sehgal, MD; Prashant Verma, MD; Kingshuk Chatterjee, MBBS; Anita Chaudhuri, MD; 

Gautam Chatterjee, MS; Farhan Rasool, MBBS 

The venereal form of treponematosis, caused by the spirochete Treponema pallidum, plagued every major city in the preantibiotic era. 

“Civilization means syphilization,” was an idea touted by Richard von Krafft-Ebing in the late 19th, and early 20th centuries that the 

effects of modern life make men more susceptible to syphilis and other diseases. Christopher Columbus was thought of as an importer of 

syphilis to Europe. Because his serendipitous voyages to the New World initiated the process of Spanish colonization, which foreshadowed 

general European colonization of the New World, it is difficult to rule out the cultural and political animosity created by Columbus and 

his men. These recent revelations are intriguing and may create dialogue that may subsequently challenge the age-old theory of “East to 

West” spread of venereal syphilis. This contribution warrants the continuation of study in this direction, taking into account skeletal studies 

that utilized radiocarbon dating technique and the phylogenetic analysis of the bacterial strains, offering a possible consensus on the origin 

and evolution of syphilis. 

Syphilis, a treponemal disease, has undergone discernible 

metamorphosis in its natural history. The diverse clinical 

manifestations of syphilis are known to masquerade as 

a spectrum of clinical entities, earning itself the reputation of 

being the great imitator. 1 Syphilis was even mentioned in Act 3 

of Timon of Athens 2 by William Shakespeare: 

Live loathed and long, 

Most smiling, smooth, detested parasites, 

Courteous destroyers, affable wolves, meek bears, 

You fools of fortune, trencher-friends, time’s flies, 

Cap and knee slaves, vapours, and minute-jacks! 

Of man and beast the infinite malady 

Crust you quite o’er! What, dost thou go? 

Soft! take thy physic first—thou too—and thou;— 

Stay, I will lend thee money, borrow none. 

The name for syphilis is derived from Fracastorius’ 1530 epic 

poem in three parts, Syphilis sive morbus gallicus (“Syphilis or 

The French Disease”), about a shepherd boy named Syphilus 

who insulted the sun god of Haiti and was punished by that 

god with a horrible disease. The poem suggests using mercury 

and “guaiaco” as a cure. 3,4 Oil of guaiac is a fragrance used in 

soap, originating from the Palo Santo, sacred tree in Ecuador, 

which provides an essential oil that heals both body and spirit. 5 

Syphilis, with its antiquity, has carried social stigma. In order 

to avoid the cultural embarrassment, countries attempted “to 

pass the buck to others.” 6 Accordingly, variations in its nomenclature 

were likely; the English and the Germans called it the 

“French disease”; the French called it the “Neapolitan sickness”; 

the Russians, the “Polish sicknes”; the Poles, the “German 

sickness”; Flemish, Dutch, Portuguese, and North Americans 

called it the “Spanish sickness” or “Castilian sickness”; and 

the Japanese, the “Canton rash” or “Chinese ulcer.” The term 

Great pox was used for 2 centuries to differentiate syphilis from 

Smallpox. 7 

Christopher Columbus, the great Italian voyager, whose precise 

date of birth is only speculated, 8 left on his first voyage 

at the age of 41 years (1492–1493). His journey initiated the 

process of Spanish colonization, which foreshadowed the general 

European colonization of the “New World.” 9 The idea that 

“Civilization is Syphilization” has historically stamped Columbus 

as the importer of syphilis to Europe. 10 The current contribution 

attempts to review the more recent archeological reports, 

dendrochronologic findings, and radiocarbon dating studies in 

order to clarify the development of the disease. The origin and 

evolution of syphilis is currently unknown 11 and may continue 

to puzzle researchers until a plausible consensus is developed. 

From the Dermato-Venereology (Skin/VD) Center, Sehgal Nursing Home, Panchwati, Delhi; Department of Dermatology and STD, University 

College of Medical Sciences, and Associated Guru Teg Bahadur Hospital, Shahdara, Delhi; Department of Dermatology, Burdwan Medical 

College and Associated Hospital, Burdwan; Apollo Nursing Home, Burdwan; Skin Institute and School of Dermatology, Greater Kailash New 

Delhi, India 

Address for Correspondence: Virendra N. Sehgal MD, Dermato-Venerology (Skin/VD) Center, Sehgal Nursing Home, A/6 Panchwati, 

Delhi 110 033 India • E-mail: drsehgal@ndf.vsnl.net.in 




HYPOTHESIS OF THE ORIGIN OF SYPHILIS 

THE UNITARIAN THEORY 

Hudson 12 has been credited with the unitarian theory, which 

claims that treponemal diseases originating from one form, 

free-living treponemes in the mud, ultimately evolve into 

human saprophytes. “Yaws” appears to have first evolved in 

Central Africa, from where it spread to engulf the east and 

north, probably attributable to the importation of slaves to 

Egypt in 30th century BCE. 13,14 Yaws eventually spread to the 

Arabian Peninsula and the valleys of the Tigris and Euphrates 

rivers, where it was called Bejel. 15 Dissemination of yaws into 

Europe followed, peaking in the 8th century CE, when the 

Crusades made the slave trade from Africa more popular by 

transporting slaves for work to other countries. 16,17 The Crusades 

moved from Europe to the Holy Land between the 11th 

and 14th centuries. 

It was between the 17th and 19th centuries that a series of 

yaws-like diseases, the endemic syphilis, and pinta were identified 

in individuals who had a poor rural background and overcrowded 

living conditions. Endemic syphilis prevailed as the 

Spirocolon of Greece, the hills of Bosnia, the Pian of Nerac 

in South-West France, the Button scurvy of Ireland, the Sibbens 

of Scotland, the Radseyege of Scandinavia, Siti of Gambia, 

Therlijevo of Croatia, Njovera of Zimbawe, Frenjak of 

the Balkans, and nonvenereal endemic syphilis, Bejel disease. 

The Dithmarsh evil of Jutland and Schlesweig-Holstein is yet 

another entity. All of these diseases, including yaws, were considered 

to be a consequence of either direct or indirect social 

contact, affecting all age groups. Children and family members 

were the most susceptible. 

The histories of Button scurvy and Sibbens have also been documented. 

18,19 These entities have been defined and classified into 

endemic syphilis or treponarids, and are considered to be a form 

of yaws modified by climatic conditions, clothing customs, and 

even the sharing of drinking utensils. This seems plausible due to 

the fact that yaws was later shipped via slaves from West Africa 

to the West Indies. In addition, some treponemes adapted to 

the conditions by thriving in the moist and warm areas of the 

body and by mutating into more lethal organisms. The latter 

was acquired by sexual contact and expressed as syphilis in the 

contemporary context. 

In the absence of any viable means to control the transmission 

of treponemes, the advent of soap in the Arab peninsula and 

Europe in the 7th and the 14th century, respectively, and its 

widespread use was acknowledged as a possible mode for the 

reduced survival of treponemes in treponarids. 


9 

COMMENTARY 

NONUNITARIAN THEORY 

An African origin hypothesis developed, with endemic treponemes 

originally acquired from apes, brought back to Europe by 

the Portuguese during the Age of Exploration. 6 

Another theory for the post-1492 syphilis outbreak mentions 

the role of a human immunodeficiency virus–like immunosuppressive 

agent causing an uncharacteristically severe variant of 

syphilis, lues maligna. 

PRE-COLUMBIAN PERCEPTION 

The perception that treponemal infection existed in the pre- 

Columbian civilization, which is now the southwestern part of 

the United States, was documented by the lesions indicative of 

treponematosis in a burial site found in the central Great House 

of Chaco Canyon, Pueblo Bonito, New Mexico, an epicenter of 

a broad culture system that spanned the Four Corners regions, in 

contrast to numerous reports available from New World skeletal 

burial remains. This is an interesting revelation, which may open 

a venue for future workup. 20–24 

COLUMBIAN THEORY 

It is speculated that treponematoses was absent in Europe 

in the pre-Columbian era25 until the 13th century CE, when 

yaws appeared as a possible result of slave trading. 26 Berbers and 

Moors, from North and North-West Africa, established themselves 

in Southern Europe, mostly in Spain, in the 15th century. 

Half a century prior to Columbus’ first voyage (1492–1493), 

Spanish and Portuguese sailors already competed with more 

extensive journeys down the West coast of Africa and encouraged 

the migration of the Africans. 

Despite the efforts for quarantines, yaws spread to the European 

continent. According to the Columbian theory, venereal syphilis 

appears to have been brought from the New World and joined 

so-called endemic syphilis. An outbreak of the epidemic resurfaced 

upon the return of Columbus and his men from the New 

World. A similar presentation of the disease was identified in the 

indigenous people of the New World as well as in the members 

of Columbus’ crew. The epidemic in the earliest years, popularly 

called the Morbus gallicus, may have been the combination of 

2 diseases; the newly arrived sexually acquired venereal syphilis 

and the old socially acquired endemic syphilis forms of yaws. 19 

The changes in clinical presentation, particularly in the first half 

of the 16th century, might be the result of expanding influences 

of the Renaissance, including improved personal hygiene. 

Others explain the devastating Morbus gallicus as the relatively 

benign venereal syphilis of the New World, afflicting people with 

no previous contact with the condition and producing more 

Origin and Evolution of Syphilis


obvious signs and symptoms, both the views commensurate 

with the Columbian theory. Accordingly, the arguments for and 

against the Columbian theory are listed below. 

• Syphilis, as one form of pathologic treponematosis, has a 

skeletal signature. Rothschild demonstrated that the osseotype 

characteristics of syphilis were absent in specimens 

from pre-Columbian Europe, Africa, and Asia. 27 

• The sailors with Columbus in 1493 were said to have 

brought the disease back to Spain. The Spanish fleet, when 

they fought for King Alfonso II against the French forces of 

Charles VIII of France in 1494–1495, heavily infected the 

people of Naples. The illness spread rapidly around Europe 

and mercenaries, who in 1496 joined Perkin Warbeck in 

Scotland and with the support of James IV of Scotland, 

invaded England, bore both arms and the grandgore (Old 

French; grand gorre: grand = great + gore = syphilis), as it 

was then called. In 1497, the Minutes of the Town Council 

of Edinborough (Phil. Trans. XLII. 421) recognized: “This 

contagious sickness call it the Grandgore.” 28 

• The osseous evidence documents the presence of syphilis 

in Hispanola, where Columbus landed. Columbus’ crew 

had the opportunity and means to contract and spread this 

venereal disease. 27 

• In the work “Tractado contra el mal serpentino,” written 

in 1510 and published in 1539, Ruy Diaz de Isla had 

been thought to have cured, during the travel of return in 

Europe, many members of the crew of Columbus, affections 

from certain luetic manifestations, and thought that 

the new disease was imported from Hispanola. This view 

was supported by Bartolomè de Las Casas. 29 

• The absence of evidence for congenital transmission of 

the disease in pre-1492 North America suggests that this 

treponemal disease was not the same venereal form we 

know today. 30 

CONTEMPORARY SCENARIO 

Several archeologic studies have taken cognizance of phylogenetically 

diverse material at different geographic locations and have 

gathered together enough evidence to suggest that the disease 

existed in Europe, long before the birth of Columbus (October 

31, 1451–May 20, 1506). 31 The osseotype characteristics of 

syphilis are absent in specimens from pre-Columbian Europe, 

Africa, and Asia. 32 

A study was conducted on approximately 240 skeletons exhumed 

at the site of a medieval friary in Hull. The skeletons were mostly 

of Augustinian friars, Mendicants serving the local poor, and seamen 

and prostitutes. Of the 245 well-preserved skeletons found, 


10 

COMMENTARY 

207 were relatively complete. Many were buried in wooden 

coffins, prepared from the wood brought from the Baltic 

countries. Dendrochronologic examination indicated that the 

trees had fallen between 1340 and 1369. The interpretation of the 

findings was, therefore, found to be confusing. Three skeletons 

showed more variable and more widespread bony lesions. One 

of these three, number 1216, was that of a man aged between 

25 and 35 years. He showed signs of syphilitic stigmata; thickening 

with areas of localized disease of thigh bones, sabre-like 

thickening of shin bones, perforation of the palate, and erosion 

of the skull’s frontal bone, a condition called caries sicca. 

Caries sicca, a bony finding from gummatous syphilis has been 

described as “The only reliable and pathognomonic lesion of 

syphilis….” 33 Other findings are of variable reliability. 34 

Carbon-dating of the skeleton showed it to have lived sometime 

between 1300 and 1420, corresponding to about a century 

before Columbus’ first voyage in 1492 to 1493. Three paleopathologists 

opined on the skeleton number 1216. Charlotte 

Roberts recognized it as treponemal disease but could not distinguish 

among them, 35 while Rothschild suggested that the 

population frequency of skeletal involvement was too high for 

treponemal disease. Secondly, the pattern of disease in the Hull 

site is classic for yaws. It matches in all details the reports of skeletal 

findings in yaws and is quite different than those for syphilis. 

Much of what was diagnosed as disease appeared taphonomic. 36 

George Armalegos, with extensive experience in viewing New 

World, pre-Columbian bones allegedly showing changes due to 

syphilis, was impressed but wanted the confirmation in terms of 

quantity rather than quality. 

Support for the existence of venereal syphilis in pre-Columbian 

Europe comes from Dr Mattie Hennenberg 37 and his wife 

based on the examination of 300 Greek skeletons buried in a 

southern Italian port in 600 BCE, with the claim that many 

of them showed changes similar to those of the Hull friary 

skeletons, indicative of syphilis; however, taphonomy could be 

a confounder. The term taphonomy (from the Greek taphos 

[τα´ φος] meaning burial and nomos [vóμoς] meaning law) was 

introduced to paleontology in 1940 by Russian scientist Ivan 

Efremov to describe the study of the transition of remains, parts, 

or products of organisms from the biosphere to the lithosphere, 

that is a creation of fossil assemblages. 38 

Hennenberg, a dental specialist, claimed that the upper central 

incisor teeth from two skeletons showed “grooves,” proof of 

congenital syphilis. A second “dig” of old bones from a port near 

Pompeii offers similar bony findings. Recent research based on 

exhumed human skeletons from a cemetery at an East London 

church, St Mary Spital, identified rough patches on skulls and 



limbs of some of the skeletons, pointing toward a syphilitic origin 

for such findings. This study scores over its predecessors in terms of 

executing radiocarbon dating of the exhumed samples, estimated 

to be 95% accurate. Brian Connell, an expert from the Museum 

of London who studied the bones, opined that the skeletons were 

buried before the Columbus voyage. He said “We’re confident that 

Christopher Columbus is simply not a feature of the emergence, 

and timing of the disease in Europe.” 39 Two of the syphilitic skeletons 

unearthed from the site were from 1200–1250, while the 

other 5 were from 1250–1400, preceding Columbus’ birth. They 

were buried with coins and other objects that helped the experts 

corroborate the radiocarbon dating results. 11,39 

The Unitarian hypothesis, based on skeletal morphology data, 40 

has recently been challenged by analysis of the molecular evolution 

of the tpr C, D, I, K, G, and J genes in the pathogenic genus 

Treponema. 41 The elusive outcome of past research warrants future 

exploration. The advent of phylogenetic systematic analysis may 

prove beneficial in exploring the veracity of the findings. It is that 

field of biology that deals with identifying and understanding the 

evolutionary relationships among the many different kinds of life 

on earth, both living (extant) and dead (extinct). 

Evolutionary theory states that similarity among individuals or species 

is attributable to common descent or inheritance from a common 

ancestor. Thus, the relationships established by phylogenetic 

systematics often describe a species’ evolutionary history and, hence, 

its phylogeny, the historical relationships among lineages or organisms 

or their parts, such as their genes. 42 This modality was made 

use of to analyze the data from 21 genetic regions examined in 26 

geographically disparate strains of pathogenic Treponema. 43 Of all 

the strains examined, the venereal syphilis–causing strains originated 

most recently and were more closely related to yaws-causing 

strains from South America than to other nonvenereal strains. 

Old World yaws–causing strains occupied a basal position on the 

tree, indicating that they first arose in human history, and a simian 

strain of Treponema pallidum was found to be indistinguishable 

from them. These results lend support to the Columbian 

theory of syphilis’ origin, while suggesting that the nonsexually 

transmitted subspecies arose earlier in the Old World. In yet 

another study, 44 using an integrative phylogenetic and paleopathologic 

approach, syphilis seems to have emerged in the time 

span between 5000 years before present (yBP) and 16,500 yBP, 

in the Americas, because the resulting evolutionary rate is compatible 

with those observed in other bacteria; however, these 

studies relied on 2 bacterial isolates from individuals with alleged 

yaws from a site where antibiotic treatment of yaws had altered 

the picture. It is unclear what disease was present in the two 

isolates on which they based their studies. The suggested time 

span for origin of syphilis of 5000 to 16,500 yBP is still debat- 


11 

COMMENTARY 

able, especially in view of skeletal evidence supporting origin 

2000 to 1800 yBP. In contrast, if the claims of pre-Columbian 

venereal syphilis outside the Americas are taken into account, 

the place of origin remains unresolved. 

REFERENCES 

1 King A, Nicol C, Rodin P, eds. Yaws: endemic syphilis: Bejel: Pinta. In: 

Venereal Diseases. 4th ed. London, England: Balliere Tindall; 1980: 

333–345. 

2 Soellner R. Timon of Athens: Shakespeare’s Pessimistic Tragedy. Columbus: 

Ohio State University Press; 1979. 

3 Baumgartner L, Fulton JF. A Bibliography of the Poem Syphilis Sive Morbus 

Gallicus, by Girolamo Fracastoro of Verona. New Haven, CT: Yale 

University Press; 1935:157–159. 

4 Opdyke DL. Bulnesia sarmientoi. Food Cosmet Toxicol. 1974;12:905 

5 Essential Oils Desk Reference. 4th ed. Orem, UT: Essential Science Publishing; 

2007. 

6 Rothschild BM. History of syphilis. Clin Infect Dis. 2005;40: 

1454–1463. 

7 Heymann WR. The history of syphilis. J Am Acad Dermatol. 2006;54: 

322–323. 

8 Dunn O, Kelly J. The Diario of Christopher Columbus’s First Voyage 

to America 1492–1493. Norman, OK: University of Oklahoma Press; 

1991:333–343. 

9 Stokes JH, Beerman H, Ingraham MR. Modern Clinical Syphilology. 

Philadelphia, PA: WB Saunders; 1945:1120–1121. 

10 Miller H. Secrets of the Dead. London, England: Channel 4 Books: Mac- 

Millan; 2000:149–184. 

11 Morton R, Rashid S. “The syphilis enigma”: the riddle resolved? Sex 

Transm Inf. 2001;77:322–324. 

12 Hudson EH. Non-Venereal Syphilis: A Sociological and Medical Study of 

Bejel. Edinburgh and London: E & S Livingstone; 1958. 

13 Hackett CJ. On the origin of the human treponematosis. Bull World 

Health Organ. 1963;29:7–41. 

14 Scott HH. The influence of the slave trade in the spread of tropical diseases. 

Transcr R Soc Trop Med Hygiene. 1943;38:169. 

15 Wedad M. Is Bejel, Yaws? (In Arabic). Bagdad, Iraq: Government 

Press; 1936. 

16 Hudson EH. Treponematosis and African slavery. Br J Vener Dis. 

1964;40:43–52. 

17 Major RH. “Prince Henry the Navigator”: A Life. New Haven, CT: Yale 

University Press; 2000. 

18 Morton RS. The buttons scurvy of Ireland. Br J Vener Dis. 1964;40: 

271–274. 

19 Morton RS. A clinical look at the morbus gallicus. Eur J Sex Transm Dis. 

1985;2:133–140. 

20 Marden K, Ortner DJ. A case of treponematosis from pre-Columbian 

Chaco Canyon, New Mexico. Int J Osteoarchaeol. 2011;21:19–31. 

21 Lahr MM, Bowman JE. Paleopathology of the Kechipawan site: health and 

disease in a southwestern Pueblo. J Archaeol Sci. 1992;19:639–654. 

22 Ortner DJ, Tuross N, Stix AI. New approaches to the study of disease in archaeological 

New World populations. Human Biology. 1992;64:337–360. 

23 Verano JW. Advances in the paleopathology of Andean South America. 

J World Prehistory. 1997;11:237–268. 

24 Baker BJ, Armelagos GJ. The origin and antiquity of syphilis: paleopathological 

diagnosis and interpretation. Curr Anthropol. 1988;29:703–738. 

25 Rothschild BM, Coppa A, Petrone PP. “Like a virgin”: absence of rheumatoid 

arthritis and treponematosis, good sanitation and only rare gout in 

Italy prior to the 15th century. Reumatismo. 2004;56:61–66. 



26 Rothschild C, Rothschild BM. Patterns of periosteal reaction in England 

from Roman through Elizabethan epochs. J Paleopath 1995;7:130. 

27 Rothschild BM. History of syphilis. Clin Infect Dis. 2005;40:1454–1463. 

28 Pearce JMS. A note on the origins of syphilis. J Neurol Neurosurg Psychiatry. 

1998;64:542. 

29 Di Cicco CO. History of syphilis. J Eur Acad Dermatol Venereol. 

2005;19:1–11. 

30 Dutour O, Palfi G, Berato J, Brun JP. The Origin of Syphilis in Europe: Before 

or After 1493? Toulon: Centre Archéologique du Var; 1995. 

31 Stirland, A. Evidence for pre-Columbian treponematosis in Medieval Europe. 

In: L’Origine de la Syphilis en Europe Avant ou après 1493? Dutour 

O, Palfi G, Berato J, Brun JP, eds. Toulon, France: Centre Archéologique 

du Var; 1995:109–115. 

32 Anderson T, Arcini C, Anda S, Tangerud A, Robertsen G. Suspected 

endemic syphilis (treponarid) in sixteenth-century Norway. Med Hist. 

1986;30:341–350. 

33 Virchow RLK. Beitrag zur geschichte der lues. Arch Dermatol. 1896;2:1–9. 

34 Lahr MM, Bowman JE. Palaeopathoogy of Kechipawan Site: health and 

disease in a south western pueblo. J Archeolog Sci. 1992;19:639–654. 

35 Roberts C, Millard A, Pearson G, Macpherson C, Nowell G. The origin 

and mobility of people with venereal syphilis buried in Hull, England in 

HISTORICAL DIAGNOSIS & TREATMENT: SYCOSIS (continued from page 7) 

SYNONYMS: ACNE SYCOSIS; SYCOSIS BARBAE, SEU MENTI; 

SYCOSIS NON PARASITICA; MENTAGRA; FOLLICULITIS 

BARBAE, SEU PILORUM. 

Sycosis is a chronic inflammatory disease of hairy parts of the 

skin characterized by tubercles, papules and pustules, each of 

which is pierced invariably by the shaft of a hair. In the great 

majority of cases the disease is limited to the region of the 

beard in men, though it may occur on the eyebrows, scalp, 

axillae and pubes. On the face it starts usually as one or more 

ill defined patches and may remain confined in certain areas or 

spread so as to include in time the whole bearded region. The 

disease does not extend to non-hairy parts. The lesions may 

be discrete and relatively few in number, or, in very severe 

cases, so numerous and closely set as to form almost continuous 

patches of infiltration. The inflammation starts in the walls 

of the hair follicles and the first surface manifestations are papules 

or tubercles situated at the orifices, with a hair passing 

through each little elevation. The papules and tubercles soon 

change into pustules. Occasionally in old patches, pustules 

develop about the hairs without preceding papulation. The pustules 

exhibit slight tendency to rupture, but the inflammatory 

exudate often escapes alongside the hairs from the mouths of 

the follicles and dries to form small crusts. When the lesions 

are closely set one crust may cover the openings of several 

follicles. The removal of such a crust does not expose a raw, 

oozing surface, but tears the top off a number of pustules. The 

amount of crusting is never very great. Burning and tension are 

usually the only subjective symptoms complained of. At the onset 

of an attack traction on the hairs which issue from inflamed 

follicles causes considerable pain, but later the root sheaths 

become swollen with pus and the hairs loosen and may be 

easily extracted. At times they fall out spontaneously. The hair 

loss is seldom permanent, though in some cases the thinning 


12 

COMMENTARY 

the late medieval period. Poster presented at: the 18th Paleopathology 

Association European Meeting, Vienna, Austria; 2010. 

36 Rothschild BM. History of syphilis. Clin Infect Dis. 2005;40:1454–1463. 

37 Henneberg RJ, Henneberg M. Possible occurrence of treponematosis 

in the ancient Greek colony of Metaponto. Am J Phys Anthropol. 1995 

(suppl 163):107–108. 

38 Efremov IA. Taphonomy: a new branch of paleontology. Pan-Am Geol. 

1940;74:81–93. 

39 Columbus Didn’t Sail Syphilis Back to Europe. Medieval Archives Illuminating 

the Dark Ages for the Digital World. Sci Technol. Oct 27, 2010. 

40 Hudson EH. Treponematosis and man’s social evolution. Am Anthropol. 

1965;67:885–901. 

41 Gray RR, Mulligan CJ, Molini BJ, et al. Molecular evolution of the tprC, D, 

I, K, G, and J genes in the pathogenic genus Treponema. Mol Biol Evol. 

2006;23:2220–2233. 

42 Hillis DM, Moritz C, Mable BK, eds. Molecular Systematics. 2nd ed. 

Sunderland, MA; Sinauer Associates: 1996 

43 Harper KN, Ocampo PS, Steiner BM, et al. On the origin of the treponematoses: 

a phylogenetic approach. PLoS Negl Trop Dis. 2008;2:e148. 

44 de Melo FL, de Mello JC, Fraga AM, et al. Syphilis at the crossroad of 

phylogenetics and paleopathology. PLoS Negl Trop Dis. 2010;4:e575. 

of the beard is quite noticeable. Untreated the disease persists 

indefinitely. Periods of quiescence alternate with exacerbations 

and the outbreak of acute symptoms is as a rule without any 

apparent cause. Sycosis on the upper lip, which is a favorite 

location, is often associated with chronic rhinitis. The nasal 

secretion may be the cause of the sycosis or the sycosis by 

extension may affect the vibrissae and cause the Schneiderian 

membrane to become swollen and exquisitely sensitive. Sycosis 

sometimes develops from eczema of the bearded region. 

The disease is feebly contagious and in not infrequently transmitted 

by the barber shop razor. The pyogenic staphylococci 

are invariably present in the pus. 

DIAGNOSIS: Numerous pustules pierced by hairs are almost 

pathognomonic of the disease. Trichophytosis barbae begins 

as a scaling spot and later produces a lumpy condition of 

the skin; from every node many hairs project and these may 

be twisted, split or broken. The spores are easily found with 

the microscope. In pustular eczema the pustules are not so 

accurately located about the hairs, the crusting is greater and 

the crusts cover raw, oozing surfaces. The disease spreads 

readily to non-hairy parts. Itching is severe. 

TREATMENT: Epilation is the most essential part of the treatment. 

Each day all the hairs in a given area of the affected 

region should be extracted. Pasta zinci Lassar, N. F., is to be 

applied plentifully and kept as constantly as possible in close 

contact with the skin. In very obstinate cases with thickening 

of the skin the amount of salicylic acid may be increased to 

10-15 per cent. Exposures to the X-rays carried to the point 

of producing a slight erythema and falling of the hair, have a 

brilliant curative effect, but every precaution must be observed 

not to cause dermatitis actinica. 


ABSTRACT 


ORIGINAL CONTRIBUTION 

A New Paradigm in the Treatment of Kerions: 

Treat the Inflammation 

Sarah E. Dolder, MD; Brendan J. O’Neill, MD; Meghan M. O’Brien, MD; Amy S. Ross, MD; 

Robert A. Allen, MD; Herbert B. Allen, MD 

Kerions result from a massive delayed-type hypersensitivity reaction to a dermatophyte. Treatment traditionally has been directed primarily 

toward the dermatophyte. The authors propose, however, that inflammation should be the initial target of treatment. Clinical findings and 

treatment outcomes for two patients with kerions, treated with short courses of anti-inflammatory agents, are presented. Earlier studies 

showing minimal effects with corticosteroid treatment of kerions may have had design flaws. The anti-inflammatory treatment of kerions 

is both safe and effective and permits the duration of therapy to be shortened dramatically. (SKINmed. 2012;10:14–16) 

We present two patients with kerions who are representative 

of more than 3 dozen similar patients 

seen in more than 2 decades of observation in our 

clinic. Recognizing that kerions are delayed-type hypersensitivity 

(DTH) reactions, 1 we treated all our patients with short courses of 

anti-inflammatory agents, and all had resolution of their lesions. 

CASE 1 

Patient 1 was a 7-year-old African American boy who was taking 

oral cephalexin for a cultured methicillin-sensitive Staphylococcus 

aureus markedly crusted, boggy, alopectic tumefaction on the left 

lateral scalp that was associated with markedly enlarged postauricular 

and posterior cervical nodes. He had taken the antibiotic for 

2 weeks without any resolution. A fungal culture obtained from a 

scaling scalp site distant from the kerion was positive for Trichophyton 

tonsurans, and the diagnosis was kerion. He was treated with 

two drops (94 mg) of saturated solution of potassium iodide (SSKI) 

three times daily2,3 and 2.5% selenium shampoo twice weekly. 4 Two 

weeks later, the crusting, swelling, and adenopathy had resolved, 

and 2 months later the hair had regrown without scarring. 

CASE 2 

Patient 2 was a 9-year-old African American boy who had been 

treated with adequate doses of griseofulvin for 4 weeks for a 

crusted, nodular, alopectic plaque on the posterior scalp (Figure 1) 

along with a markedly enlarged posterior cervical node. Bacterial 

and fungal cultures were negative. The clinical diagnosis was 

kerion, and treatment with prednisolone 1 mg/kg/d and selenium 

sulfide shampoo was instituted. Three weeks later, the plaque 

had cleared and new hair started to regrow (Figure 2). Within 

2 months, the hair had completely regrown without scarring. 

DISCUSSION 

Kerion formation is the inflammatory extreme of tinea capitis, 

producing a large, painful, crusted plaque on the scalp, often with 

purulent discharge and cervical lymphadenopathy. Kerions are 

the result of a massive DTH reaction to a dermatophyte. 1 Positive 

DTH skin tests, lesional histopathology, and immunofluorescence 

studies are all consistent with this concept, 1,5,6 proposed originally 

by Birt and Wilt7 in 1954 and later supported by Rasmussen and 

Ahmed. 8 Inasmuch as the kerion is an immunologic event, this 

helps explain why antibiotics, whether antibacterial or antifungal, 

are ineffective (in spite of positive cultures) and why all our 

patients responded to anti-inflammatory treatment with complete 

resolution of the kerions and subsequent regrowth of hair. 

Treatment of kerions has been directed primarily toward the 

underlying dermatophyte, often with protracted courses of griseofulvin; 

however, we believe the inflammation, rather than the 

infection, should be the initial focus of kerion treatment. The 

clinical findings and treatment outcomes for our two patients 

with kerion treated with short courses of anti-inflammatory 

agents are representative and exactly similar to the other patients 

with kerion seen in our clinic. 

From the Department of Dermatology, Drexel University College of Medicine, Philadelphia, PA 

Address for Correspondence: Herbert B. Allen, MD, Department of Dermatology, Drexel University College of Medicine, 219 North Broad 

Street, Philadelphia, PA 19107 • E-mail: hallen@drexelmed.edu 




Figure 1. Case 2: Kerion before treatment shows crusted 

pustular plaque on posterior scalp with significant lymphadenopathy. 

Figure 2. Case 2: Kerion shows total resolution 2 weeks after 

treatment with prednisone. 


In patients treated prior to 2001, we saw complete resolution 

in kerions treated with SSKI in 22 of 25 patients within 2 to 4 

weeks. This is similar to the resolution of kerions alluded to by 

Dobson 2 and was also similar to the resolution routinely seen 

in sporotrichosis. 9 The three patients who did not respond to 

SSKI (2 did not take it due to the taste, and 1 had worsening 

of his “id” reaction) had rapid clearance on prednisolone. After 

2001, when SSKI became scarce because of the threat of nuclear 

attacks and dirty bombs, we shifted to prednisolone and noted 

complete response to treatment in 15 of 15 patients. With both 

treatment protocols, the kerions cleared and the patients’ hair 

subsequently regrew without scarring. 

Two prospective randomized, controlled studies by other investigators 

have examined the treatment of kerions with oral doses of corticosteroids. 

10,11 Neither demonstrated a difference in the management 

of kerion between using oral corticosteroids plus griseofulvin vs griseofulvin 

alone. These findings are contrary to our observations that all 

our patients responded to short courses of anti-inflammatory agents 

and are also contrary to oral corticosteroids being recommended for 

kerions that present simultaneously with “id” eruptions, 12 as well as 

in situations in which the kerion becomes “inflamed.” 13 In addition, 

John Kenney (personal communication, 1983), who treated this 

disease in many children, routinely included oral corticoids in his 

regimen for kerions and saw results similar to ours. 

We believe the findings by some investigators 11 demonstrate the 

natural resolution of kerions. Similarly, findings in another study 10 

may also show the natural resolution; moreover, their treatment 

protocol, which included untapered prednisone at a maximum 

dose of 30 mg/d for only 10 days, in our opinion, may have been 

insufficient. 14 

We believe untreated kerions require 3 to 6 months to resolve. 

Many case reports consistent with this concept have been published. 

15–17 In one of our patients, who preferred not to take 

prednisolone and was treated with griseofulvin alone, the kerion 

took 4 months to resolve. In contrast, patients treated with antiinflammatory 

treatment responded rapidly. 

CONCLUSIONS 

Based on our observations, we believe the addition of prednisolone 

to the treatment of kerions is safe and allows the duration of therapy 

to be dramatically shortened. Adjunctive therapy with selenium 

sulfide shampooing remains useful, 4 and griseofulvin may 

be continued if scaling from tinea capitis remains after the kerion 

resolves. 18 Further studies would help resolve the differences in the 

prospective trials compared with the clinical observations. 


Treatment of Kerions


REFERENCES 


1 Arenas R, Toussaint S, Isa-Isa R. Kerion and dermatophytic granuloma. 

Mycological and histopathological findings in 19 children with 

inflammatory tinea capitis of the scalp. Int J Dermatol. 2006;45: 

215–219. 

2 Dobson RL. In: Dobson RL, ed. Yearbook of Dermatology. Chicago, IL: 

Yearbook Publishers; 1979:124. 

3 Sterling JB, Heymann WR. Potassium iodide in dermatology: a 19th century 

drug for the 21st century—uses, pharmacology, adverse effects, 

and contraindications. J Am Acad Dermatol. 2000;43:691–697. 

4 Allen HB, Honig PJ, Leyden JJ, McGinley KJ. Selenium sulfide: adjunctive 

therapy for tinea capitis. Pediatrics. 1982; 69:81–83. 

5 Woodfolk JA, Platts-Mills TA. The immune response to dermatophytes. 

Res Immunol. 1998;149:436–445; discussion 522–523. 

6 Woodfolk JA. Allergy and dermatophytes. Clin Microbiol Rev. 2005;18: 

30–43. 

7 Birt AR, Wilt JC. Mycology, bacteriology, and histopathology of suppurative 

ringworm. AMA Arch Derm Syphilol. 1954;69:441–448. 

8 Rasmussen JE, Ahmed AR. Trichophytin reactions in children with tinea 

capitis. Arch Dermatol. 1978;114:371–372. 

9 Sandhu K, Gupta S. Potassium iodide remains the most effective 

therapy for cutaneous sporotrichosis. J Dermatol Treat. 2003;14: 

200–202. 

10 Honig PJ, Caputo GL, Leyden JJ, et al. Treatment of kerions. Pediatr 

Dermatol. 1994;11:69–71. 

11 Hussain I, Muzaffar F, Rashid T, et al. A randomized, comparative trial of 

treatment of kerion celsi with griseofulvin plus oral prednisolone vs. griseofulvin 

alone. Med Mycol. 1999;37:97–99. 

12 Alvarez MS, Silverberg NB. Tinea capitis. In: Kelly AP, Taylor SC, 

eds. Dermatology for Skin of Color. New York, NY: McGraw Hill; 

2009:253. 

13 Tinea capitis. In: James WD, Berger TG, Elston DM, eds. Andrews’ 

Diseases of the Skin: Clinical Dermatology. 10th ed. Philadelphia, PA: 

Elsevier; 2006:298. 

14 Pomeranz AJ, Sabnis SS. Tinea capitis: epidemiology, diagnosis and 

management strategies. Paediatr Drugs. 2002;4:779–783. 

15 Van Rooij P, Detandt M, Nolard N. Trichophyton mentagrophytes of rabbit 

origin causing family incidence of kerion: an environmental study. 

Mycoses. 2006;49:426–430. 

16 Schauder S. Itraconazole in the treatment of tinea capitis in children. 

Case reports with long-term follow-up evaluation. Review of the literature. 

Mycoses. 2002;45:1–9. 

17 Gibbon KL, Goldsmith P, Salisbury JA, Bewley AP. Unnecessary surgical 

treatment of fungal kerions in children. BMJ. 2000;320:696–697. 

18 Allen HB, Honig PJ. Scaling scalp diseases in children. Clin Pediatr 

(Phila). 1983;22:374–377. 


Treatment of Kerions

ONE PRESCRIPTION. 

TWO POWERFUL EFFECTS. 

The power to calm inflammatory acne 

Inflammation is an important aspect in the 

pathophysiology of acne 1 

Both laboratory and clinical studies document the 

anti-inflammatory effects of minocycline 1 

TM 

CALMING 

WIPES 

(30 WIPES) 

Complementary T 3 Calming Wipes 

Soothing and alcohol-free — 

part of a complete approach 

to acne treatment 

+ 

The only pelletized form of Minocycline available... 

A dual approach to acne care 

The power to eradicate P acnes 

Significant reduction in P acnes—even up to 3 weeks 

after discontinuation 2 

A decrease in P acnes can lead to a drop in 

pro-inflammatory cytokines and reduced inflammation1 Minimal resistance in an in vitro study 

—The majority of tetracycline-resistant P acnes 

were cross-resistant to doxycycline—but sensitive 

to minocycline* 3 

The most common adverse events associated with MINOCIN are nausea, vomiting, and diarrhea. CNS adverse effects may include 

dizziness, vertigo, and headache. 

Important Information 

The most common adverse events associated with MINOCIN are nausea, vomiting, and diarrhea. Central nervous system adverse events including 

light-headedness, dizziness, or vertigo have been reported with minocycline therapy, but are generally transient in nature. Other adverse events 

include tinnitus, headache, sedation, and skin pigmentation, particularly on the face and mucous membranes. MINOCIN is contraindicated in persons 

who have shown hypersensitivity to any of the tetracyclines or to any of the components of the product formulation. WARNING: MINOCIN Pellet- 

Filled Capsules, like other tetracycline-class antibiotics, can cause fetal harm when administered to a pregnant woman. The use of drugs of the 

tetracycline class during tooth development (last half of pregnancy, infancy, and childhood to the age of 8 years) may cause permanent 

discoloration of teeth (yellow-gray-brown). Concurrent use of tetracyclines may render oral contraceptives less effective. 

References: 1. SapadinAN,Fleischmajer R.Tetracyclines:nonantibiotic properties and their clinical implications.JAmAcad Dermatol. 2006;54(2):258-265. 2. Leyden JJ,McGinley KJ,KligmanAM.Tetracycline and minocycline 

treatment.Arch Dermatol. 1982;118(1):19-22. 3. Hubbell CG,Hobbs ER,RistT,White JW Jr.Efficacy of minocycline compared with tetracycline in treatment of acne vulgaris.Arch Dermatol.1982;118(12):989-992. 

*In vitro activity does not necessarily correlate to in vivo activity. 

©2010 Triax Pharmaceuticals, LLC All rights reserved. Printed in USA. MN-0810-280 

For more information, go to www.minocin-kit.com

ABSTRACT 



Pityriasis Rubra Pilaris: 

Evolution of Challenges in 

Promising Treatment Options 

Virendra N. Sehgal, MD; 1 Govind Srivastava, MD; 2 Prashant Verma, MD3 Pityriasis rubra pilaris is an uncommon inflammatory dermatosis that is well recognized across the globe. Erythroderma is a common 

presentation. A precise diagnosis of pityriasis rubra pilaris is based on morphologic features and is classified into 6 types: classic adult 

onset (type I), atypical adult (type II), classic juvenile (type III), circumscribed juvenile (type IV), atypical juvenile (type V), and human 

immunodeficiency virus–associated (type VI). Several conventional systemic and/or topical treatments are currently in use. Largely, their 

results are unsatisfactory and limited by long-term toxicity. The authors investigate the efficacy of a wide spectrum of drugs by examining 

historical (archive) and promising (modern) treatment modalities for the treatment of pityriasis rubra pilaris. (SKINmed. 2012;10:18–23) 

Pityriasis rubra pilaris (PRP) comprises a group of chronic 

disorders that demonstrate circumscribed follicular 

keratosis with palmoplantar keratoderma. Both familial 

and acquired forms have been recognized. The former is 

infrequent and usually occurs in childhood. The bimodal or 

trimodal distribution usually involves a peak case incidence 

in the first and second decades of life, 1,2 and it affects both 

men and women. Its etiology and management has remained a 

challenge. Occasionally, PRP is associated with other diseases, 

and it was speculated that the disorder might be the result 

of an abnormal immune response to some antigenic stimuli. 

Familial occurrence of the disease might point to genes that 

predispose the individual to develop the disorder after certain 

precipitating events. The occurrence of PRP in patients with 

the human immunodeficiency virus (HIV)/AIDS is a topic of 

recent debate. 3 

METHODS 

Medline/PubMed (1936–2010) was searched using the terms 

“PRP” and “treatment.” Accordingly, this contribution outlines 

the published reports on the topic, with the objective to 

focus on the evolution and challenges of promising treatment 

options. 

CLINICAL CRITERIA/CLASSIFICATION 

Management of PRP varies according to the type, extent, and age 

at onset of the disease. Thus, an understanding of the classification 

of the disease offers insight into individualizing treatment. 

Griffiths1 classified PRP into 6 types according to the age at onset, 

behavior, clinical appearance, and prognosis (Table I). Classic 

adult-onset PRP (type I) shows the characteristic generalized 

rash with palmo-plantar keratoderma, whereas atypical adultonset 

PRP (type II) is chronic, with ichthyosiform and lamellar 

scales on the palms and soles and alopecia of varying degrees. The 

association of PRP and HIV infection has recently been identified 

as type VI PRP, and most of the cases have been reported in 

young heterosexual/homosexual men. It is characterized by nodulocystic 

and lichen spinulosus–like lesions, with poor prognosis 

and resistance to treatment. 2 Another classification5 divides the 

disease into 4 types based only on physical findings (Table II); 

however, Griffiths1 classification continues to be the mainstay in 

practice for delineating the disease. 

CHALLENGES AND PROMISING TREATMENTS 

HISTORICALLY (ARCHIVE) IMPORTANT MODALITIES 

The diagnosis and treatment of PRP have always been a source 

of great interest. At present, there is no acclaimed treatment 

From the Dermato Venereology (Skin/VD) Center, Sehgal Nursing Home, Panchwati, Azadpur, Delhi, India; 1 the Skin Institute and School of 

Dermatology, Greater Kailash, New Delhi, India; 2 Department of Dermatology, and STD University College of Medical Sciences and Associated 

Guru Teg Bahadur Hospital, Shahdara, Delhi, India3 Address for Correspondence: Virendra N. Sehgal MD, Dermato Venerology (Skin/VD) Center, Sehgal Nursing Home, A/6 Panchwati, Delhi, 

110 033, India • E-mail: drsehgal@ndf.vsnl.net.in 



January/February 2012 �� 

Table I. Pityriasis Rubra Pilaris: Griffiths Clinical Classification 

CLINICAL TYPE LESIONS’ DISTRIBUTION NATURAL COURSE PERCENTAGE OF CASES 

�� 55 

�� 5 

�� 10 

�� 25 

�� 5 

�� 

�� 

�� 

��- 

�� 

��- 

�� 

�� 

�� 

��- 

�� 

�� 

�� 

�� 

PROMISING (MODERN) MODALITIES 

�� 

�� 

�� 

�� 

��- 

�� 

�� 15–18 

�� 8 

�� - 

�� 

�� 

Table II. Pityriasis Rubra Pilaris: Piamphongsant and Akaraphant Classification 5 

TYPES 

168 PATIENTS 

ADULTS CHILDREN 

CLINICAL FEATURES 

�� 22 � �� 

�� 25 �� 

�� 

��- 

�� 

�� 

�� 

�� - 

�� 

�� 

�� 

�� - 

�� 

�� 

�� 21 �� 28 ��- 

�� 

RETINOIDS/VITAMIN A DERIVATIVES 

��21�� - 

��- 

�� 

�� 

�� 

�� 11 21 �� 

�� 

�� 

�� 20 �� 

�� 10 � �� 

SKINmed. 2012;10:18–23 �� 

��


�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 35 

IMMUNOSUPPRESSIVE THERAPY 

�� 

��- �� 

�� 

�� 

��31�� 

�� 

�� 

�� 32��- ��33 PHOTOTHERAPY 

�� 

�� 21� �� 

�� 

�� 

�� 28 

TOPICAL THERAPY 

�� 

�� 

��- �� 

�� 8 ��- 

�� 

��38 ��- ��8��10 ��11� �� 12 and 

��13�� 

�� 

�� 

BIOLOGICS 

�� 

�� 

�� 

Table III. Pityriasis Rubra Pilaris: Challenges and Promising Treatment—Historical (Archive) Importance 

AUTHOR(S) YEAR(S) RECOMMENDED DRUG(S) DOSAGE RESPONSE/RESULT PATIENTS 

�� 

�� 

�� 

�� 

�� ´�� Good �� 

�� 8 �� 

�� 


�� 

�� 

�� 

��10 �� Good – 

��11 �� – �� – 

��12 �� 

��- 

�� 

�� 

�� 13 �� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

–


Table IV. Pityriasis Rubra Pilaris (PRP): Challenges and Promising Treatment—Modern Modalities 

AUTHOR(S) YEAR RECOMMENDED DRUG(S) DOSAGE RESPONSE/RESULT PATIENTS 

�� - 

�� 

– – – 

��30 �� – 

��31 �� Good �� 

�� 2000 �� 

�� 

�� 

�� 

��25 �� 

�� 

�� 

�� 

�� 

�� - 

�� 

�� 28 2000 �� 

�� 

�� 

�� 21 2000 �� 

�� 

�� 

�� 

�� 

�� 

�� – 

�� 2005 �� – �� – 

�� - 

�� 

�� 2 /mo on 

�� 

�� 

�� 

�� 

��50 �� – �� – 

�� - 

�� 

– �� – 

�� 

�� 

�� 2008 �� 

�� 2008 �� 

�� 2008 �� 

�� 2008 �� 

�� 2008 �� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

��20 �� 


�� 

– 

Continued »


�� 35 �� 

�� 

�� 

�� 2010 ��a 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

��- 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

��- 

��- 

�� 

�� 

�� 

�� 

�� 

�� 

��- 

�� 

FIVE-YEAR VIEW 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

��- 

��- 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

��- 

�� 

�� 

��- 

�� 

�� 

�� 

��- 

�� 

REFERENCES 

�� 

�� 

�� 

1 Griffiths WA. Pityriasis rubra pilaris–an historical approach. 2. Clinical 

features. Clin Exp Dermatol. 1976;1:37–50. 

2 Sehgal VN, Srivastava G, Dogra S. Adult onset pityriasis rubra pilaris. 

Indian J Dermatol Venereol Leprol. 2008;74:311–321. 

3� �� laris 

and human immunodeficiency virus infection. Br J Dermatol. 

1995;133:990–993. 

4� �� 

and HIV infection: a part of the spectrum of HIV-associated follicular 

syndrome. Br J Dermatol. 1995;135:818–819. 

5 Piamphongsant T, Akarphant R. Pityriasis rubra pilaris: a new proposed 

classification. Clin Exp Dermatol. 1994;19:134–138. 

6 Petter MF. Pityriasis rubra pilaris, with particular reference to vitamin 

medication and dietary control. Penn Med J. 1936;39:864–866. 


�� 

�� 

a �� 

�� b �� 

�� 

�� 

��


7 Gunther S, Alston W. Follicular keratoses. Pilot studies of serum level of 

vitamin A and liver function tests during administration of retinoic acid in 

hyperkeratosis follicularis et parafollicularis (Kyrle’s disease), pityriasis 

rubra pilaris, and keratosis follicularis (Darier’s disease). Dermatologica. 

1973;147:274–283. 

8 Ayres S Jr, Mihan R, Scribner MD. Synergism of vitamin A and 

��Cutis. 1979;23:600–603, 689–690. 

9� �� 

diseases. J Am Acad Dermatol. 1981;5:222. 

10� ��Arch 

Dermatol Syphilol. 1941;43:42–61. 

11� �� ence 

in therapy with carotene and vitamin A. Arch Dermatol Syphilol. 

1943;48:288–296. 

12 Webster JR, Falk AB. Pityriasis rubra pilaris; clinical and laboratory 

observation on combined treatment with corticotropin and vitamin A. 

AMA Arch Dermatol Syphilol. 1952;65:685–700. 

13 Irgang S. Pityriasis rubra pilaris responsive to ascorbic acid. Australas J 

Dermatol. 1968;9:211–217. 

14� �� 

drugs as possible therapeutic agents. Arch Dermatol. 1965;92:428–430. 

15� �� 

rubra pilaris. Arch Dermatol. 1981;117:749–750. 

16� �� 

the retinol binding protein. Br J Dermatol. 1981;104:253–256. 

17� �� 

13-cis-retinoic acid (isotretinoin). J Am Acad Dermatol. 1982;6:710–715. 

18� ��riasis 

rubra pilaris: unapproved use. Int J Dermatol. 2006;45:1238–1240. 

19� �� 

pilaris with calcipotriol. Br J Dermatol. 1994;130:675–678. 

20 Vergilis-Kalner IJ, Mann DJ, Wasserman J, Petronic-Rosic V, Tsoukas MM. 

Pityriasis rubra pilaris sensitive to narrow band-ultraviolet B light therapy. 

J Drugs Dermatol. 2009;8:270–273. 

21 Kirby B, Watson R. Pityriasis rubra pilaris treated with acitretin and 

��Br J Dermatol. 2000;142:376–377. 

22 Hanke CW, Steck WD. Childhood-onset pityriasis rubra pilaris treated with 

��Cleve Clin Q. 1983;50:201–203. 

23 Wetzig T, Sticherleng M. Juvenile pityriasis rubra pilaris: successful 

treatment with cyclosporine. Br J Dermatol. 2003;149:202–203. 

24 Usuki K, Sekiyama M, Shimada T, et al. Three cases of pityriasis rubra 

pilaris successfully treated with cyclosporine A. Dermatology. 

2000;200:324–327. 

25� �� 

pilaris. Arch Dermatol. 1985;121:105–106. 

26� �� 

rubra pilaris responsive to triple anti-retroviral therapy. Br J Dermatol. 

1999;140:931–934. 

27 Bonomo RA, Kormam N, Nagashima-Wholen I, et al. Pityriasis rubra 

pilaris–an unusual cutaneous complication of AIDS. Am J Med Sci. 

1997;314:118–121. 

28� �� 

radiation and acitretin therapy as a treatment option for pityriasis rubra 

pilaris. Br J Dermatol. 2000;142:574–575. 

29� �� 

for the treatment of erythrodermic pityriasis rubra pilaris. Arch Dermatol. 

1999;135:475–476. 

30� ��Aust J 

Dermatol. 1966;8:183–185. 

31 Hunter GA, Forbes IJ. Treatment of pityriasis rubra pilaris with azathioprine. 

Br J Dermatol. 1972;87:42–45. 

32 Wetzig T, Sticherling M. Juvenile pityriasis rubra pilaris: successful 

treatment with ciclosporin. Br J Dermatol. 2003;149:202–203. 

33� �� 

pilaris with calcipotriol. Br J Dermatol. 1994;130:675–678. 

34� ��- 

�� Clin 

Exp Dermatol. 2004;29:244–246. 

35� �� 

therapeutic agents in pityriasis rubra pilaris. J Dtsch Dermatol Ges. 

2010;8:354–356. 

36� ��ment 

of pityriasis rubra pilaris with pimecrolimus cream 1%. J Drugs 

Dermatol. 2007;6:340–342. 

37� ��scribed 

pityriasis rubra pilaris to topical tazarotene treatment. Pediatr 

Dermatol. 2008;25:125–126. 

38 Raza N, Bari AU, Dar NR. Juvenile onset classical pityriasis rubra pilaris: 

every patient may not require systemic therapy. J Coll Physicians Surg 

Pak. 2007;17:564–565. 

39� �� 

�� Acta Derm Venereol. 

2007;87:552–553. 

40� �� 

pilaris with etanercept. J Am Acad Dermatol. 2008;59:113–114. 

41� �� 

rubra pilaris. Br J Dermatol. 2008;158:642–644. 

42 Barth D, Harth W, Treudler R, et al. Successful treatment of pityriasis 

�� 

J Dtsch Dermatol Ges. 2009;7:1071–1073. 

43� �� 

treatment for adult-onset pityriasis rubra pilaris: case report and review 

of the literature on biologic therapy. J Am Acad Dermatol. 2008;59: 

65–70. 

44� �� 

��J Eur Acad Dermatol Venereol. 

2008;22:117–118. 

45 Garcovich S, Di Giampetruzzi AR, Antonelli G, Garcovich A, Didona B. 

Treatment of refractory adult-onset pityriasis rubra pilaris with TNFalpha 

antagonists: a case series. J Eur Acad Dermatol. 2010;24: 

881–884. 

46� �� 

of pityriasis rubra pilaris with adalimumab treatment. Clin Exp Dermatol. 

2009;35:e155–e156. 

47� ��mumab. 

Arch Dermatol. 2009;145:99–101. 

48 Kerr AC, Ferguson J. Type II adult-onset pityriasis rubra pilaris successfully 

treated with intravenous immunoglobulin. Br J Dermatol. 

2007;156:1055–1056. 

49� ��Clin Exp Dermatol. 

1991;16:181–184. 

50� �� 

pilaris with combination eternacept and acitretin therapy. Arch Dermatol. 

2007;143:1597–1599. 


��


REVIEW 

The Role of Surgical Debridement in Healing 

of Diabetic Foot Ulcers 

Katherine A. Gordon, BS; Elizabeth A. Lebrun, MD; Marjana Tomic-Canic, PhD; Robert S. Kirsner MD, PhD 

ABSTRACT 

A critical question in the treatment of chronic wounds is whether and when debridement is needed. The three most common chronic 

wounds are the diabetic foot ulcer (DFU), the venous leg ulcer, and the pressure or decubitus ulcer. Surgical debridement, aimed at removing 

necrotic, devitalized wound bed and wound edge tissue that inhibits healing, is a longstanding standard of care for the treatment 

of chronic, nonhealing wounds. Debridement encourages healing by converting a chronic nonhealing wound environment into a more 

responsive acute healing environment. While the rationale for debridement seems logical, the evidence to support its use in enhancing 

healing is scarce. Currently, there is more evidence in the literature for debridement for DFUs than for venous ulcers and pressure ulcers; 

however, the studies on which clinicians have based their rationale for debridement in DFUs possess methodologic flaws, small sample 

sizes, and bias. Thus, further studies are needed to develop clinical evidence for its inclusion in treatment protocols for chronic wounds. 

Here, the authors review the scientific evidence for debridement of DFUs, the rationale for debridement of DFUs, and the insufficient data 

supporting debridement for venous ulcers and pressure ulcers. (SKINmed. 2012;10:24–26) 

A 

question commonly encountered when treating chronic 

wounds is whether and when debridement is needed. 

The 3 most common chronic wounds are the diabetic 

foot ulcer (DFU), the venous leg ulcer, and the pressure or decubitus 

ulcer. The former 2 chronic wounds have been more extensively 

studied. Using DFU as an example, certainly the question 

is of importance, considering that an estimated 15% of the 170 

million people currently with diabetes mellitus will develop a 

foot ulcer during their lifetime. 1,2 

The multifactor etiology of DFUs includes peripheral vascular disease 

along with sensory, motor, and autonomic neuropathy. 3 DFUs 

are a major cause of morbidity and mortality due to increased 

amputations, infections, and hospitalizations in diabetic patients. 4 

At first glance it would seem to be a rather simple question. 

Surgical debridement is a longstanding standard of care for 

DFUs, aimed at removing necrotic, devitalized wound bed and 

wound edge tissue that inhibits healing. Such tissue includes 

hyperkeratotic epidermis (callus) and necrotic dermal tissue, 

foreign debris, and harmful bacterial elements. 5 Various debridement 

methods exist, including surgery, wet-to-dry dressings, 

biosurgery (ie, maggots), enzyme preparations, polysaccharide 

beads or paste dextranomer polysaccharide, and hydrogels. 3 This 

contribution focuses on surgical debridement. 

Debridement encourages healing by converting a chronic 

nonhealing wound environment into a more responsive acute 

healing environment. 6 Debridement is included in multiple 

guidelines for the care of DFUs, including the American Diabetes 

Association, the American College of Foot and Ankle 

Surgeons, and the Wound Healing Society; however, herein lies 

the issue: while the rationale for debridement seems logical, the 

evidence to support its use in enhancing healing is scarce. 

REVIEW OF CURRENT LITERATURE 

Many studies on which clinicians have based their rationale for 

debridement possess methodologic flaws, small sample sizes, 

and bias. 3 A recent paper7 systematically reviewed 5 published 

clinical trials that investigated surgical debridement of DFUs 

to enhance healing. 5,8,9 These clinical trials were found to be 

defective in their methodology, statistically insignificant, or 

lacking in definitive scientific evidence for surgical debridement 

in the treatment of DFUs. 7 In addition, most existing studies 

are not randomized clinical trials optimized to test the relationship 

between debridement of DFUs and wound healing. 

A focused, well-designed study is needed, therefore, to elucidate 

the effect of surgical debridement on the healing status of 

chronic wounds. 

From the Department of Dermatology & Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL 

Address for Correspondence: Robert S. Kirsner, MD, PhD, Department of Dermatology & Cutaneous Surgery, University of Miami Miller 

School of Medicine, 1600 NW 10th Avenue, RMSB, Room 2023-A, Miami, FL 33136 • E-mail: rkirsner@med.miami.edu 




SCIENTIFIC EVIDENCE FOR DFU DEBRIDEMENT 

The biological and molecular basis for debridement has been 

investigated in several studies. 10,11 Molecular and histologic analyses 

of biopsies from the nonhealing edge of a chronic wound 

have been suggested to validate the use of debridement. 10 

Keratinocytes become activated following wounding and are key 

players in restoring the epidermal barrier during wound healing. 12 

Keratinocytes and fibroblasts at the nonhealing edges of chronic 

wounds were shown to exhibit not only a pathogenic phenotype 

detrimental to healing but also a slowed migratory capacity. 10–13 In 

chronic wounds, the keratinocytes multiply at a higher rate than 

usual (hyperproliferation), yet they are unable to migrate into the 

wound as would be normally expected. 10–13 Basically, keratinocytes 

on a chronic wound edge are capable of proliferating but are 

unable to migrate properly. 12 These nonhealing keratinocytes of the 

chronic wound edge are marked by induction of c-Myc and nuclearization 

of β-catenin, which may contribute to the inhibition of 

migration. 10–12 Many clinicians visually identify this nonhealing 

phenotype as a “callus,” indicating the need for removal to facilitate 

wound healing. 14 Debridement seems to be a reasonable solution 

to the problem of nonmigratory tissue in the margins of chronic 

wounds. Researchers suggest that debridement will be effective if 

unresponsive cells are surgically removed, and cells responsive to 

wound healing signals and topical agents are optimized. 11 

RATIONALE FOR DEBRIDEMENT OF DFUS 

The benefits of debridement include removal of bacteria, 

senescent cells, and hyperproliferative nonmigratory tissue and 

stimulation of growth factor activity. 15 

Bacterial burden in a wound likely impedes healing, 16 as greater 

bacterial load and certain types of bacteria have been shown 

to reduce healing responses. 17,18 Bacteria in chronic wounds 

stimulate a prolonged inflammatory response with a concomitant 

release of free oxygen radicals and various lytic enzymes, 

ultimately causing tissue damage. 19 In addition, biofilms, which 

are communities of bacteria and other organisms embedded 

in an extrapolysaccharide matrix within the wound bed, show 

increased resistance to antimicrobial agents and to the host 

immune system. 20,21 Debridement is an effective way to remove 

bacterial burden and biofilms from nonhealing wounds. 

Additionally, growth factors are reduced in chronic wounds, 

including platelet-derived growth factor, fibroblast growth factor, 

epidermal growth factor, and transforming growth factor 

β. 22 Dead tissue within chronic wounds, which is removed by 

surgical debridement, is unreceptive to growth factors. 23 In addition, 

the bleeding and platelet activation caused by debridement 

stimulates the production of blood-borne growth factors, further 

promoting wound healing. 24 


25 

REVIEW 

Senescent cells have markedly decreased proliferation and protein 

production. 17 Chronic wound fibroblasts are less receptive to 

growth factor stimuli, 25 making these wounds less likely to heal 

or respond to treatments. 26 Overall, debridement removes both 

the hyperproliferative edge and the senescent cells of the chronic 

wound, thus allowing the remaining cells to undergo normal 

proliferation, migration, response to treatment, and healing. 

DEBRIDEMENT AND VENOUS ULCERS 

Another example of a chronic wound is venous ulcer. Venous insufficiency 

is the most common cause of lower-extremity ulcers and 

accounts for the development of approximately 1 million venous 

ulcers in patients in the United States with venous insufficiency. 27 

There are many theories for the mechanism of venous ulcer development, 

including pericapillary fibrin cuff deposition, abnormalities 

of the fibrinolytic system, trapping of growth factors by macromolecules 

in the dermis, and leukocyte plugging in the vessels of the lower 

extremities. 28–30 The treatment modalities for venous ulcers include 

bed rest with leg elevation31 ; compression therapy32 ; aspirin33 ; pentoxifylline34 

; skin grafting, 35 including cultured epidermal autografts 

and allografts36,37 ; superficial venous surgery38 ; and debridement. 17,39 

The data supporting debridement for venous ulcers are even 

more sparse than for DFUs. The role of debridement in the 

treatment of venous ulcers has not been proven, although it is 

used as a standard of care. 39 One controlled, prospective cohort 

study involving 53 patients for 12 months evaluated sharp 

debridement in combination with standard treatment regimens 

for nonhealing venous leg ulcers. 40 The study group contained 

ulcers that had slough, nonviable tissue and no granulation tissue, 

while the control group had ulcers with 15% to 20% granulation 

tissue without slough or nonviable tissue. Although they 

failed to reach statistical significance, the authors concluded that 

sharp debridement was effective at initiating the healing process. 

They found a 6-cm 2 reduction in the mean surface area of the 

study group ulcers, compared with a 1-cm 2 reduction in the 

control group in the first 4 weeks (P = .02). 40 

Clinical experience also dictates that venous ulcers are commonly 

more difficult to debride than most DFUs, and it is more 

time-consuming for the clinician to achieve viable tissue margins 

in these cases; therefore, chronic venous ulcers, much like DFUs, 

are in need of evidence-based standardized treatment plans. 

DEBRIDEMENT AND PRESSURE ULCERS 

The most common cause of chronic wounds is the pressure 

ulcer. While the rationale for debridement is excellent as part 

of standard care when treating pressure ulcers, given the multiple 

comorbidities coexistent in patients with pressure ulcers, 

the data supporting debridement for pressure ulcers are the least 

substantial of the 3 common chronic wounds. 

Surgical Debridement in DFUs


CONCLUSIONS 

Surgical debridement, despite the need for better data, is part of 

standard care in the treatment of chronic, nonhealing wounds, 

with better evidence for DFUs than for venous ulcers. Some may 

be concerned that debridement may create a new portal of entry 

for bacterial organisms, but studies have shown that the rate of 

infection does not increase in debrided wounds. 40 Debridement is 

relatively safe and convenient in the outpatient setting, but studies 

validating the effects on healing continue to be limited. While 

debridement continues to be a mainstay of treatment, further 

studies are needed to develop clinical evidence for its inclusion 

in treatment protocols for chronic wounds. Ideally, a randomized 

controlled trial would provide the necessary data for future 

evidence-based practice in the treatment of chronic wounds. 

REFERENCES 

1 Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: 

estimates for the year 2000 and projections for 2030. Diabetes 

Care. 2004;27:1047–1053. 

2 American Diabetes Association. Consensus development conference 

on diabetic foot wound care: April 7–8, 1999; Boston, MA. Adv Wound 

Care. 1999;12:353–361. 

3 Edwards J, Stapley S. Debridement of diabetic foot ulcers. Cochrane 

Database Syst Rev. 2010;(1):CD003556. 

4 Margolis DJ, Kantor J, Berlin JA. Healing of diabetic neuropathic foot 

ulcers receiving standard treatment. A meta-analysis. Diabetes Care. 

1999;22:692–695. 

5 Cardinal M, Eisenbud DE, Armstrong DG, et al. Serial surgical 

debridement: a retrospective study on clinical outcomes in chronic lower 

extremity wounds. Wound Repair Regen. 2009;17:306–311. 

6 Golinko MS, Joffe R, Maggi J, et al. Operative debridement of diabetic 

foot ulcers. J Am Coll Surg. 2008;207:e1–e16. 

7 Lebrun E, Tomic-Canic M, Kirsner RS. The role of surgical debridement in 

healing of diabetic foot ulcers. Wound Repair Regen. 2010;18:433–438. 

8 Steed DL, Donohoe D, Webster MW, Lindsley L. Effect of extensive 

debridement and treatment on the healing of diabetic foot ulcers. 

Diabetic Ulcer Study Group. J Am Coll Surg. 1996;183:61–64. 

9 Piaggesi A, Schipani E, Campi F, et al. Conservative surgical approach 

versus non-surgical management for diabetic neuropathic foot ulcers: a randomized 

trial. Diabet Med. 1998;15:412–417. 

10 Piaggesi A, Viacava P, Rizzo L, et al. Semiquantitative analysis of the 

histopathological features of the neuropathic foot ulcer: effects of pressure 

relief. Diabetes Care. 2003;26:3123–3128. 

11 Saap LJ, Falanga V. Debridement performance index and its correlation 

with complete closure of diabetic foot ulcers. Wound Repair Regen. 

2002;10:354–359. 

12 Brem H, Stojadinovic O, Diegelmann RF, et al. Molecular markers in 

patients with chronic wounds to guide surgical debridement. Mol Med. 

2007;13:30–39. 

13 Stojadinovic O, Brem H, Vouthounis C, et al. Molecular pathogenesis 

of chronic wounds: the role of beta-catenin and c-myc in the inhibition 

of epithelialization and wound healing. Am J Pathol. 2005;167:59–69. 

14 Tomic-Canic M, Ayello EA, Stojadinovic O, Golinko MS, Brem H. 

Using gene transcription patterns (bar coding scans) to guide wound 

debridement and healing. Adv Skin Wound Care. 2008;21:487–492; 

quiz 493–494. 

15 Morasso MI, Tomic-Canic M. Epidermal stem cells: the cradle of epidermal 

determination, differentiation and wound healing. Biol Cell. 

2005;97:173–183. 


26 

REVIEW 

16 Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: a 

systematic approach to wound management. Wound Repair Regen. 

2003;11 suppl 1:S1–S28. 

17 Zacur H, Kirsner RS. Debridement: rationale and therapeutic options. 

Wounds. 2002;14(suppl E):2E–7E. 

18 Bucknall TE. The effect of local infection upon wound healing: an experimental 

study. Br J Surg. 1980;67:851–855. 

19 Robson MC, Stenberg BD, Heggers JP. Wound healing alterations caused 

by infection. Clin Plast Surg. 1990;17:485–492. 

20 Robson MC, Heggers JP. Surgical infection. II. The beta-hemolytic 

streptococcus. J Surg Res. 1969;9:289–292. 

21 Serralta VW, Harrison-Balestra C, Cazzaniga AL, Davis SC, Mertz 

M. Lifestyles of bacteria in wounds: presence of biofilms? Wounds. 

2001;13:29–34. 

22 Kerstein MD, Reis ED. Current surgical perspectives in wound healing. 

Wounds. 2001;13:53–58. 

23 Mulder GD, Vande Berg JS. Cellular senescence and matrix metalloproteinase 

activity in chronic wounds. Relevance to debridement and new 

technologies. J Am Podiatr Med Assoc. 2002;92:34–37. 

24 Hunt TK, Hopf H, Hussain Z. Physiology of wound healing. Adv Skin 

Wound Care. 2007;13(2 suppl):6–11. 

25 Hasan A, Murata H, Falabella A, et al. Dermal fibroblasts from venous 

ulcers are unresponsive to the action of transforming growth factor-beta 

1. J Dermatol Sci. 2007;16:59–66. 

26 Margolis DJ, Berlin JA, Strom BL. Which venous leg ulcers will heal with 

limb compression bandages? Am J Med. 2000;109:15–19. 

27 Valencia IC, Falabella A, Kirsner RS, Eaglstein WH. Chronic venous insufficiency 

and venous leg ulceration. J Am Acad Dermatol. 2001;44: 

401–421; quiz 422–424. 

28 Falanga V, Eaglstein WH. The “trap” hypothesis of venous ulceration. 

Lancet. 1993;341:1006–1008. 

29 Browse NL, Burnand KG. The cause of venous ulceration. Lancet. 

1982;2:243–245. 

30 Thomas PR, Nash GB, Dormandy JA. White cell accumulation in dependent 

legs of patients with venous hypertension: a possible mechanism for trophic 

changes in the skin. Br Med J (Clin Res Ed). 1988;296:1693–1695. 

31 Abu-Own A, Scurr JH, Coleridge Smith PD. Effect of leg elevation on 

the skin microcirculation in chronic venous insufficiency. J Vasc Surg. 

1994;20:705–710. 

32 Blair SD, Wright DD, Backhouse CM, Riddle E, McCollum CN. 

Sustained compression and healing of chronic venous ulcers. BMJ. 

1988;297:1159–1161. 

33 Layton AM, Ibbotson SH, Davies JA, Goodfield MJ. Randomised trial of 

oral aspirin for chronic venous leg ulcers. Lancet. 1994;344:164–165. 

34 Jull AB, Waters J, Arroll B. Pentoxifylline for treating venous leg ulcers. 

Cochrane Database Syst Rev. 2002;(1):CD001733. 

35 Douglas WS, Simpson NB. Guidelines for the management of 

chronic venous leg ulceration. Report of a multidisciplinary workshop. 

British Association of Dermatologists and the Research Unit of the 

Royal College of Physicians. Br J Dermatol. 1995;132:446–452. 

36 Limova M, Mauro T. Treatment of leg ulcers with cultured epithelial 

autografts: treatment protocol and five year experience. Wounds. 

1995;7:170–180. 

37 Phillips TJ, Kehinde O, Green H, Gilchrest BA. Treatment of skin ulcers 

with cultured epidermal allografts. J Am Acad Dermatol. 1989;21(2 pt 

1):191–199. 

38 Olivencia JA. Subfascial endoscopic ligation of perforator veins (SEPS) in 

the treatment of venous ulcers. Int Surg. 2000;85:266–269. 

39 de Araujo T, Valencia I, Federman DG, Kirsner RS. Managing the patient 

with venous ulcers. Ann Intern Med. 2003;138:326–334. 

40 Williams D, Enoch S, Miller D, et al. Effect of sharp debridement using 

curette on recalcitrant nonhealing venous leg ulcers: a concurrently 

controlled, prospective cohort study. Wound Repair Regen. 

2005;13:131–137. 

Surgical Debridement in DFUs


Tuberculosis (TB) is a common disease worldwide, 1 

and its clinical incidence has been impacted by the 

emergence of the human immunodeficiency virus 

(HIV), increased transmigration from endemic countries, 

and its transmission in health care facilities, prisons, homeless 

shelters, and other crowded settings. 2–5 TB is largely an airborne 

infection; however, skin manifestations may be caused 

by hematogenous spread or the contiguity from latent and/or 

active foci of infection. Primary inoculation, although uncommon, 

is another known mode of transmission. HIV infection, 

intravenous drug abuse, diabetes mellitus, immunosuppressive 

therapy, malignancies, end-stage renal disease, and infancy may 

predispose to TB. Although cutaneous TB (CTB) is a well- 

recognized clinical entity, it often poses a diagnostic dilemma 

for physicians 6 ; therefore, it is important to perform a careful 

review of clinical presentations in each patient, which may prove 

predictive of its diagnosis. 7,8 

CLASSIFICATION 

The most widely accepted CTB classification is based on the 

route of infection. 6,9 Exogenous inoculation occurs after the 

direct inoculation of Mycobacterium tuberculosis into the skin of a 

person who is susceptible to infection (vide infra). This may cause 

TB verrucosa cutis (TBVC), TB chancre, and some cases of lupus 

vulgaris (LV), whereas endogenous infection is caused by either 

lymphatic or hematogenous spread or a contiguous extension. 

Occasionally, lymphatic spread is seen in LV. Hematogenous 

spread, on the other hand, is responsible for acute miliary TB, 

metastatic tubercular abscess, gummatous TB, papulonecrotic 

tuberculid (PNT), and lupus vugaris. Contiguous extension 


Virendra N. Sehgal, MD, Section Editor 

Cutaneous Tuberculosis: A Diagnostic Dilemma 

Virendra N. Sehgal, MD; 1 Prashant Verma, MD; 2 Sambit N. Bhattacharya, MD; 2 Sonal Sharma, MD; 3 

Navjeevan Singh, MD; 3 Nishant Verma, MD 4 

Cutaneous tuberculosis continues to be one of the most difficult conditions to diagnose. It is a challenge particularly in developing 

countries due to the lack of resources. The authors define the classification and clinical manifestations considered predictive of its diagnosis. 

from the underlying lesion is a characteristic feature of both 

scrofuloderma and TB cutis orificialis (TBCO). 

In attempt to embellish the preceding classification, it has been 

divided into multibacillary and paucibacillary variants based on 

the bacterial load. The former is recognized by the characteristic 

morphology of the organism in the tissue sections stained 

with Ziehl-Neelsen method, complemented by in vitro recovery 

of M tuberculosis, while sparse bacilli on histological examination 

and rare in vitro culture isolation 2 identify the latter. 

Unfortunately, it is difficult to distinguish the organisms in 

paucibacillary TB. 

CLINICAL FEATURES 

Although the prevalence of CTB accounts for 1.5% of all cases 

of TB, it is, nevertheless, important to consider the entity when 

patients present with a suggestive clinical morphology. CTB has 

many forms, including multibacillary and paucibacillary CTB, 

which are defined in detail below. 

MULTIBACILLARY CTB 

TB CHANCRE/INOCULATION TB 

Tuberculous chancre (primary inoculation TB) is a variant of 

multibacillary CTB that results from direct introduction of 

mycobacteria into the skin or mucosa of an individual who neither 

had tubercular infection in the past nor was immunized 

with Bacille Calmette-Guérin (BCG). Trauma also facilitates the 

entry of the organism into the skin. 10,11 

Face and other exposed areas are vulnerable sites of introduction. 

The organism multiplies in tissue macrophages and migrates to 

From the Dermato-Venereology (Skin/VD) Center, Sehgal Nursing Home, Panchwati, Delhi; 1 the Departments of Dermatology and STD2 and 

Pathology, 3 University College of Medical Sciences and Associated Guru Teg Bahadur Hospital, Delhi; and the Department of Microbiology, 

Maulana Azad Medical College and Associated Chacha Nehru Bal Chikitsalaya, Delhi, 4 India 

Address for Correspondence: Virendra N. Sehgal, MD, Dermato-Venerology (Skin/VD) Center, Sehgal Nursing Home, A/6 Panchwati, Delhi 

110 033 India • E-mail: drsehgal@ndf.vsnl.net.in 




regional lymph nodes. An inflammatory papule develops in 2 

to 4 weeks after inoculation that breaks down into a firm, nonhealing, 

shallow, nontender, undermined ulcer with a granulomatous 

base. Painless regional lymphadenopathy is a cardinal 

sign, appearing after about 3 to 8 weeks. Numerous bacilli are 

demonstrable at the inoculation site and regional lymph node. 

The ultimate ulceroglandular lesion is a “mirror image” of the 

Ghon’s complex. Its clinical course varies according to the hostimmune 

response. 12 

The primary lesion heals with scarring after 1 to 3 months; 

however, with a less effective host-immune response, the bacterial 

load remains high, and healing may be delayed up to 

12 months. Regional nodes may suppurate, erode, and perforate 

the surface of overlying skin, resulting in scrofuloderma. Latent 

foci of infection may persist at the site and progress to either 

LV or TBVC despite evident tuberculin sensitivity. Hematogenous 

dissemination of mycobacteria from skin can result in TB 

at other sites, particularly bones or joints, or progress to acute 

miliary disease with poor outcome. 

SCROFULODERMA (TB COLLIQUATIVE CUTIS) 

Scrofuloderma (TB colliquative cutis) is the most common 

form of CTB in children. It results from the direct extension 

from an underlying TB focus, such as a regional lymph node 

or infected bone or joint, to the overlying skin. Lesions present 

as firm, painless, subcutaneous, red-brown nodules overlying an 

infected focus, which gradually enlarge and suppurate, forming 

ulcers and sinus tracts that drain watery, purulent, and/or caseous 

material. The ulcers heal with typical puckered scarring. 13 

TB CUTIS ORIFICIALIS 

The lesions associated with TBCO are frequently characterized 

by erythematous, edematous nodules, and/or plaques. Painful 

central ulceration covered by necrotic pseudomembranous 

material with an irregular border is apparent. Constitutional 

symptoms of TBCO include fever, malaise, weight loss, and 

night sweats. The oral mucosa and tongue are the most commonly 

afflicted sites. 2 The exact mechanism resulting in TBCO 

is unknown; however, ingestion of bacilli in sputum from active 

pulmonary TB, hematogenous and lymphatic spread, and direct 

spread from adjacent organs has been alleged, 14 with ingestion 

of bacilli in sputum being the most accepted mode. 15 There has 

been a reported case of isolated perianal TB without pulmonary 

or gastrointestinal involvement. 16 

DISSEMINATED MILIARY TB 

Disseminated miliary TB is characterized by a wide dissemination 

of M tuberculosis in the body and shows a distinctive 


pattern of millet-sized, multiple, tiny lesions on chest x-ray, 

distributed throughout the lung fields. It may hematogenously 

infect any number of organs including the lungs, liver, and 

spleen in patients with advanced TB. There is a systemic failure 

of the cell-mediated immune system that allows and facilitates 

the spread of infection, resulting in rapid deterioration 

and death. 4,17,18 Certain events, infections, and medications 

that suppress the body’s cell-mediated immune system may 

precipitate this infection. Although miliary TB is rare and 

well known for its occurrence in children, it is an increasingly 

serious infection in immunosuppressed patients, such as those 

infected with HIV and those on long-term oral corticosteroid 

therapy or other immunosuppressive therapies for organ 

transplant or inflammatory and autoimmune conditions. 

Cutaneous skin lesions associated with miliary TB consist of 

small, erythematous to violaceous papules or pustules with 

hemorrhagic necrosis and umbilication affecting a substantial 

portion of the body. Healing is indicated by the presence of 

atrophic, depressed scars surrounded by a brownish, hyperpigmented 

halo. 

METASTATIC TUBERCULOUS ABSCESSES (GUMMA) 

Metastatic tuberculous abscesses (gumma) may either arise 

from the breakdown of an old healed tubercle that still has 

live organisms or in immunocompromised individuals. 2,4 

Accordingly, it is usually seen in malnourished children and 

immunosuppressed adults. 6 Single or multiple, nontender, fluctuant 

nodules develop, forming draining sinuses and abscesses 

(Figure 1). Nodules may occur at any location without specific 

predominance. 

Figure 1. Metastatic tuberculous abscesses (gumma): a 

single, nontender, fluctuant nodule, draining sinus is apparent. 


Cutaneous Tuberculosis

PAUCIBACILLARY CTB 


TB VERRUCOSA CUTIS 

TBVC occurs after direct inoculation of M tuberculosis into the 

skin of previously infected individuals. It manifests as a painless, 

solitary, purplish or brownish red warty plaque that may extend 

peripherally, causing central atrophy, or form fissures that exude 

pus or keratinous material (Figure 2). It is often accompanied by 

lymphadenopathy. Skin lesions may evolve and persist for years, 

although spontaneous resolution may also occur. Response to 

treatment is favorable. 6,19 

LUPUS VULGARIS 

LV is a chronic and progressive form of CTB that is widely 

described as the most common form. Lesions occur on normal 

skin as a result of direct extension from underlying deeper TB 

focus, by lymphatic or hematogenous spread, after primary inoculation 

or BCG vaccination, or in scars of old scrofuloderma. 20 

Lesions are typically small, solitary, nodular, sharply defined, 

and reddish brown with a gelatinous consistency. “Apple-jelly” 

nodules present on the head and neck of individuals in Western 

Figure 2. Tuberculosis verrucosa cutis illustrating verrucous, 

hyperkeratotic fissured lesions. 


Figure 3. Lupus vulgaris: well-circumscribed plaque, 

displaying coalesce of discrete, red-brown papules, elevated 

verrucous border, and central atrophy. 

countries, while lesions on the lower extremities or buttocks 

are present in individuals in tropical and subtropical areas. It 

has several clinical variations such as classic plaque or keratotic 

hypertrophic, ulcerative, and vegetating. The plaque type begins 

as discrete, red-brown papules that coalesce and form plaques 

with a slightly elevated verrucous border and central atrophy 

(Figure 3). Persistent lesions may damage underlying tissue and 

ulcerate, causing severe disfigurement and an increased risk of 

skin cancer. 21 

TUBERCULIDS 

The relationship between tuberculids and TB is a subject of continuing 

debate. They are generalized exanthems with a moderate 

to high degree of host immunity to TB. Patients are usually in 

good health and show (1) positive tuberculin skin test results; 

(2) inactive tuberculous involvement of viscera or lymph nodes; 

(3) negative staining and culture for pathogenic mycobacteria 

in affected tissue; and (4) skin lesions that heal with remission 

or treatment of TB. Its morphological variations include lichen 

scrofulosorum (LS), 22 erythema induratum of Bazin (EIB), 

and PNT. 

Tuberculids may be classified into 2 groups: (1) true tuberculids, 

and (2) facultative tuberculids. M tuberculosis plays a major 

etiologic role in the former, while it is one of several possible 

etiologic agents in the latter. Tuberculids were once believed to 

be a result of hypersensitivity to the presence of mycobacterial 

antigens within a host of previously acquired immunity to TB; 

however, most are now known not to be uniquely caused by 

M tuberculosis. PNT and LS are still widely accepted as true 

tuberculids and EIB as a facultative tuberculid. 22 




Figure 4. Lichen scrofulosorum: multiple, small, grouped, 

firm, perifollicular, lichenoid papules and/or plaques. 

LICHEN SCROFULOSORUM 

LS is an eruption of multiple, small, grouped, asymptomatic, 

firm, perifollicular, lichenoid papules and/or plaques (Figure 

4), most often affecting children or young adults, that progresses 

and subsides within weeks to months without scarring. 

4,23 An association between LV, caries of the spine, LS, 24 

and its unusual occurrence in pulmonary TB25 has been 

described in the past. 

ERYTHEMA INDURATUM OF BAZIN 

EIB is a TB-associated panniculitis that presents with multiple, 

painful, recurring, ulcerated nodules that affect the legs of 

women. 4,6 Pre-existing vascular disease may predispose patients 


31 


to lesions during exposure to cold weather. Lesions are chronic, 

slow to resolve (if at all), and result in atrophic hyperpigmented 

scarring after several months (Figure 5). Although patients show 

TB skin hypersensitivity, acid-fast bacilli (AFB) are rarely identified. 

A study from Spain demonstrated that about 10% of cases 

were positive for M tuberculosis using polymerase chain reaction 

(PCR). 26 A case series and literature review revealed that organisms, 

such as Mycobacterium bovis and Mycobacterium marinum, 

may also be involved in the etiology of EIB, although no 

evidence of such was found during the investigation. It was 

suggested that EIB has diverse etiologies with varying pathogenesis, 

leading to similar histological changes, and the cases 

analyzed may not have had an infectious etiology (suggesting a 

facultative tuberculid picture). 27 

PAPULONECROTIC TUBERCULID 

Papulonecrotic tuberculid occurs as a chronic and recurrent symmetric 

eruption of necrotizing skin papules appearing in clusters 

and healing with varioliform scars (Figure 6). Tubercle bacilli are 

difficult to demonstrate, but patients typically have an internal 

focus of TB and are tuberculin sensitive, and skin lesions resolve 

after anti-TB therapy. TB DNA has been detected in these 

lesions using PCR amplification reactions. 28 Lesions appear on 

the exterior aspects of extremities, knees, elbows, buttocks, and 

lower trunk in a symmetric distribution, often in clusters. Individual 

lesions are asymptomatic, small, dusky red papules with 

a central punctum or crust. Involution is common after 6 to 8 

weeks. 29 

DIAGNOSIS 

Diagnosis of CTB is based on relative and absolute criteria, in 

addition to supportive immunologic evidence. 30 

Figure 5. Erythema induratum occupying the lower leg. Figure 6. Papulonecrotic tuberculid. 


RELATIVE DIAGNOSIS 


CARDINAL MORPHOLOGIC FEATURES (VIDE SUPRA) 

A characteristic history of evolution of the disease is distinct 

in re-infection and re-activation. In re-infection, a history 

of primary infection or BCG vaccination must be obtained. 

The latter forms an important component of the immunization 

program in some countries, including India, and may be 

identified by a BCG vaccination scar at the insertion point on 

the left deltoid. In re-activation, on the other hand, a history 

of TB, established by clinical and/or investigative procedures, 

followed by cure and an asymptomatic period on completion 

of specific anti-tubercular therapy. Often, the only evidence 

of past infection may be pulmonary scarring and calcification 

visible on radiography. Subsequently, any event that lowers 

the cell-mediated immunity may re-activate the condition, 

resulting in its relapse. 

MANTOUX TEST 

A positive Mantoux test indicates the cell-mediated skin hypersensitivity 

to tuberculin. The response in re-infection may be 

higher as compared with that in re-activation TB. This in vivo 

test correlates well with the migratory index of lymphocytes to 

tuberculin antigen, assayed through leukocyte migration inhibition 

test. A strongly positive reaction, however, indicates 

active TB. It has only a limited diagnostic application in countries 

where the infection is highly prevalent and BCG forms an 

integral part of the immunization program and the majority of 

adults are tuberculin positive; nevertheless, it may be a useful 

adjunct in developed countries. 

Microscopic examination of the tissue section may depict a 

tuberculoid and tuberculous granuloma. The former, characterized 

by a focal accumulation of epithelioid cells, a few giant 

cells, and surrounding mantle of mononuclear cells, is a relative 

parameter encountered in LV and TBVC. It also demonstrates 

caseation necrosis in the center. It may be possible to demonstrate 

AFB on Fite’s stain. This granuloma fulfills an absolute 

criterion for diagnosis of TB and typifies scrofuloderma. 

ABSOLUTE DIAGNOSIS 

An absolute diagnosis consists in the demonstration of AFB on 

Ziehl-Neelsen’s staining of the smear, prepared from material 

from lesions. The colonies should be further subjected to biochemical 

and pigment production tests to confirm M tuberculosis. 

Recovery of M tuberculosis on inoculation of material from 

lesions into guinea pigs. 

In an effort to achieve universal access to high-quality diagnosis 

and ultimate patient-centered treatment as envisaged by World 


Health Organization (WHO), it is important to be aware of the 

diagnostic modalities thus far available in the global arena. 31 

NONTUBERCULOUS MYCOBACTERIA 

Physicians should be aware of nontuberculous mycobacteria 

(NTMB) in the current context, because they are environmental 

organisms capable of causing chronic disease in humans worldwide. 

The prevalence of NTMB disease is steadily increasing and 

has emerged in previously unrecognized populations. They, too, 

are a diagnostic challenge. 32 TB verrucosa cutis–like lesions may 

be caused by M bovis. 33 

ATYPICAL MYCOBACTERIOSIS 

Mycobacterium avium-intracellulare (MAI) is now a wellestablished 

cause of cervical lymphadenitis, simulating scrofuloderma, 

especially in the pediatric age group in the developed 

world. 34 In addition, LV-like morphology may also be encountered 

following primary MAI infection. 35 

HIV INFECTION AND CTB 

HIV-infected patients are vulnerable to contract TB. 36 TB may present 

as a rapidly progressive disease in immunosuppressed patients. 

Miliary TB is common and may be associated with cutaneous 

manifestations. 37 Disseminated CTB may show a high yield of 

mycobacterium from an unusual dermatitis in this group. Despite 

the dissemination of the organism, the diagnosis of TB may be difficult. 

38,39 In addition, atypical presentations of oesophago-pleurocutaneous 

and pleuro-cutaneous fistula may be seen. 40,41 

In addition to the decrease in tuberculin reactivity, atypical 

chest radiographic patterns are common. Biopsy and aspirates 

of peripheral and regional lymph nodes, liver, and bone marrow 

provide the highest yield and are used for early diagnosis. 42 

Co-lesional acquired immunodeficiency syndrome– associated 

cutaneous Kaposi’s sarcoma and M tuberculosis–associated 

granulomatous inflammation have recently been documented. 43 

Tuberculous gumma, new-onset cervical lymphadenopathy, and 

worsening of the pre-existing lymphadenitis, yet another highrisk 

immune reconstitution inflammatory syndrome, has previously 

been described. 44 

CONCLUSIONS 

Reviewing the prevalence and variations in the clinical expression 

of CTB across the globe may assist in evolving a uniform 

pattern of the disease vital for a core curriculum. The comprehension 

of the text is, therefore, crucial in developing treatment 

strategy through the recommendations of WHO. WHO 

believes that the same treatment regimen for pulmonary and/or 

extrapulmonary TB should be used. 45 



REFERENCES 


1 Sehgal VN, Wagh SA. The history of cutaneous tuberculosis. 

Int J Dermatol. 1990;29:666–668. 

2 Bravo FG, Gotuzzo E. Cutaneous tuberculosis. Clin Dermatol. 

2007;25:173–180. 

3 Fariña MC, Gegundez MI, Piqué E, et al. Cutaneous tuberculosis: a 

clinical, histopathologic, and bacteriologic study. J Am Acad Dermatol. 

1995;33:433–440. 

4 MacGregor RR. Cutaneous tuberculosis. Clin Dermatol. 1995;13:245–255. 

5 Bhutto AM, Solangi A, Khaskhely NM, et al. Clinical and epidemiological 

observations of cutaneous tuberculosis in Larkana, Pakistan. Int J Dermatol. 

2002;41:159–165. 

6 Barbagallo J, Tager P, Ingleton R, et al. Cutaneous tuberculosis: diagnosis 

and treatment. Am J Clin Dermatol. 2002;3:319–328. 

7 Regnier S, Ouagari Z, Perez ZL, et al. Cutaneous miliary resistant tuberculosis 

in a patient infected with human immunodeficiency virus: case 

report and literature review. Clin Exp Dermatol. 2009;34:e690–e692. 

8 Rai VM, Shenoi SD, Gowrinath. Tuberculous gluteal abscess coexisting 

with scrofuloderma and tubercular lymphadenitis. Dermatol Online J. 

2005;11:14. 

9 Lai-Chong JE, Perez A, Tang V, et al. Cutaneous manifestations of tuberculosis. 

Clin Exp Dermatol. 2007;32:461–466. 

10 Glickman FS, Price E. Primary inoculation complex (tuberculous chancre). 

Arch Dermatol. 1969;100:646–647. 

11 Ara M, Seral C, Baselga C, et al. Primary tuberculous chancre caused by 

Mycobacterium bovis after goring with a bull’s horn. J Am Acad Dermatol. 

2000;43:535–537. 

12 Mataix J, Botella R, Herrero A, et al. Tuberculous primary complex of the 

skin. Int J Dermatol. 2008;47:479–481. 

13 Kiliç A, Gül U, Soylu S, et al. Scrofuloderma: a forgotten disease? 

Skinmed. 2007;6:303–304. 

14 Sharma MP, Bhatia V. Abdominal tuberculosis. Indian J Med Res. 

2004;120:305–315. 

15 Ichihashi K, Katoh N, Takenaka H, et al. Orificial tuberculosis: presenting 

as a refractory perianal ulcer. Acta Derm Venereol. 2004;84:331–332. 

16 Akgun E, Tekin F, Ersin S, et al. Isolated perianal tuberculosis. Neth J 

Med. 2005;63:115–117. 

17 Sehgal VN, Sharma S, Verma P, et al. Disseminated cutaneous tuberculosis 

an atypical presentation of re-infection (secondary) tuberculosis in 

an immuno-competent individual. Am J Dermatopathol. 2011. Sep 13. 

[Epub ahead of print] 



report and literature review. Clin Exp Dermatol. 2009;34:e690–e692. 

19 Afshar K, Mundi M. Tuberculosis verrucosa cutis. Mayo Clin Proc. 

2004;79:1562. 

20 Marcoval J, Servitje O, Moreno A, et al. Lupus vulgaris. Clinical, histopathologic, 

and bacteriologic study of 10 cases. J Am Acad Dermatol. 

1992;26:404–407. 

21 Akoglu G, Karaduman A, Boztepe G, et al. A case of lupus vulgaris successfully 

treated with antituberculous therapy despite negative PCR and 

culture. Dermatology. 2005;211:290–292. 

22 Frankel A, Penrose C, Emer J. Cutaneous tuberculosis: a practical 

case report and review for the dermatologist. J Clin Aesthet Dermatol. 

2009;2:19–27. 

23 Singal A, Bhattacharya SN. Lichen scrofulosorum: a prospective study of 

39 patients. Int J Dermatol. 2005;44:489–493. 

24 Sehgal VN, Srivastava G, Sharma VK. Lupus vulgaris, caries of the spine 

and lichen scrofulosorum—an intriguing association. Clin Exp Dermatol. 

1987;12:280–282. 


33 


25 Seghal VN, Chander R, Logani K. Lichen scrofulosorum: an unusual 

expression of pulmonary tuberculosis in a child. J Eur Acad Dermatol 

Venereol. 1995;4:71–74. 

26 Vieites B, Suárez-Peñaranda JM, Pérez Del Molino ML, et al. Recovery of 

Mycobacterium tuberculosis DNA in biopsies of erythema induratum— 

results in a series of patients using an improved polymerase chain reaction 

technique. Br J Dermatol. 2005;152:1394–1396. 

27 Bayer-Garner IB, Cox MD, Scott MA, et al. Mycobacteria other than 

Mycobacterium tuberculosis are not present in erythema induratum/ 

nodular vasculitis: a case series and literature review of the clinical and 

histologic findings. J Cutan Pathol. 2005;32:220–226. 

28 Quirós E, Bettinardi A, Quirós A, et al. Detection of mycobacterial DNA 

in papulonecrotic tuberculid lesions by polymerase chain reaction. J Clin 

Lab Anal. 2000;14:133–135. 

29 Freiman A, Ting P, Miller M, et al. Papulonecrotic tuberculid: a rare form 

of cutaneous tuberculosis. Cutis. 2005;75:341–346. 

30 Sehgal VN. Cutaneous tuberculosis. Dermatol Clin. 1994;12:645–653. 

31 The Regional Strategic Plan for TB Control 2006–2015. World Health 

Organization, Regional Office for South-East Asia, World Health 

House, Indraprastha Estate, Mahatma Gandhi Road, New Delhi 

110002, India. 

32 Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: 

diagnosis, treatment, and prevention of non tuberculous mycobacterial 

diseases. Am J Respir Crit Care Med. 2007;175:367–416. 

33 Wolff K, Tappeiner G. Mycobacterial diseases: tuberculosis and 

atypical mycobacterial infection. In: Fitzpatrick TB, Eisen AZ, Wolff 

K, eds. Dermatology in General Medicine. 3rd ed. New York, NY: 

McGraw Hill; 1987:2152–2170. 

34 Starke JR. Management of nontuberculous mycobacterial cervical adenitis. 

Pediatr Infect Dis J. 2000;19:674–675. 

35 Kullavanijaya P, Sirimachan S, Surarak S. Primary cutaneous infection 

with Mycobacterium avium intracellulare complex resembling 

lupus vulgaris. Br J Dermatol. 1997;136:264–266. 

36 Starke JR. Tuberculosis. In: Jenson HB, Baltimore RS, eds. Pediatric 

Infectious Diseases: Principles and Practices. Philadelphia, PA: WB 

Saunders; 2002:396–419. 

37 Sharma SK, Mohan A, Sharma A, et al. Miliary tuberculosis: new insights 

into an old disease. Lancet Infect Dis. 2005;5:415–430. 



report and literature review. Clin Exp Dermatol. 2009;34:e690-e692. 

39 Corbett EL, Crossley I, De Cock KM, et al. Disseminated cutaneous 

Mycobacterium tuberculosis infection in a patient with AIDS. Genitourin 

Med. 1995;71:308–310. 

40 Arif M. Oesophago-pleuro-cutaneous fistula in an HIV-positive patient. 

Braz J Infect Dis. 2010;14:183–185. 

41 Gulinelli A, Toledo DO, Coelho-Neto AP, et al. Parasternum pleuralcutaneous 

fistula in a severely immunosuppressed HIV-positive patient. 

Braz J Infect Dis. 2010;14:183–185. 

42 Shafer RW, Kim DS, Weiss JP, Quale JM. Extrapulmonary tuberculosis 

in patients with human immunodeficiency virus infection. Medicine 

(Baltimore). 1991;70:384–397. 

43 Ramdial PK, Sing Y, Subrayan S, et al. Granulomas in acquired 

immunodeficiency syndrome-associated cutaneous Kaposi sarcoma: 

evidence for a role for Mycobacterium tuberculosis. J Cutan Pathol. 

2010;37:827–834. 

44 Sharma SK, Dhooria S, Barwad P, et al. A study of TB-associated 

immune reconstitution inflammatory syndrome using the consensus 

case-definition. Indian J Med Res. 2010;131:804–808. 

45 World Health Organization. Treatment of tuberculosis guidelines. 

Treatment of extrapulmonary TB and of TB in special situations. 

4th ed. Geneva 27, Switzerland; 2009: 95–99. 



SELF-TEST REVIEW QUESTIONS 

34 

Volume 10 • Issue 1 


Instructions: For each of the following numbered questions, choose the most appropriate lettered response(s) Unless directed to choose only one lettered 

response, all, some, or none of the responses may be correct. 

1) Exogenous inoculation, due to the direct inoculation of Mycobacterium 

tuberculosis into the skin of a person who is susceptible 

to infection, may be responsible for: (Answer as 

many as apply.) 

a. acute military tuberculosis. 

b. gummatous tuberculosis. 

c. lupus vulgaris. 

d. papulo-necrotic tuberculid. 

e. tuberculous chancre. 

f. tuberculosis verrucosa cutis. 

2) Exogenous inoculation, due to the direct inoculation of Mycobacterium 

tuberculosis into the skin of a person who has 

been previously infected but is susceptible to infection, is 

most likely to be responsible for: (Choose the single best 

response.) 

a. acute military tuberculosis. 

b. gummatous tuberculosis. 


d. papulo-necrotic tuberculid. 

e. tuberculous chancre. 

f. tuberculosis verrucosa cutis. 

3) Which of the following is widely described as the most common 

form of cutaneous tuberculosis? (Choose the single best 

response.) 

a. Acute military tuberculosis 

b. Gummatous tuberculosis 

c. Lupus vulgaris 

d. Papulo-necrotic tuberculid 

e. Tuberculous chancre 

f. Tuberculosis verrucosa cutis 

4) The most accepted mode of development of tuberculosis 

cutis oroficialis is: (Choose the single best response.) 

a. direct spread from adjacent organs. 

b. hematogenous spread. 

c. ingestion of bacilli in sputum. 

d. lymphatic spread. 

e. exogenous inoculation due to the direct inoculation of 

Mycobacterium tuberculosis into the skin/mucosa of a 

person who is susceptible to infection. 

5) “Apple-jelly” nodules present on the head and neck of individuals 

in Western countries are most characteristic of: (Choose 

the single best response.) 

a. erythema induratum of Bazin. 

b. lichen scrofulosorum. 


d. papulonecrotic tuberculid. 

e. tuberculosis verrucosa cutis. 

ANSWERS TO SELF-TEST REVIEW QUESTIONS: 

1) c, e, f; 2) f; 3) c; 4) c; 5) c 

From the Departments of Pathology and Dermatology, UMDNJ-New Jersey Medical School, Newark, NJ 

Address for Correspondence: W. Clark Lambert, MD, PhD, Room C520 MSB, UMDNJ-NJMS, 185 South Orange Avenue, Newark, NJ 07101 

• E-mail: lamberwc@umdnj.edu 

RESTLESS LEG SYNDROME 

Drugs that may cause restless leg syndrome (RLS) 

Alcohol Haldol Prozac Topamax 

Caffeine Iron Remeron Ultram 

Celexa Klonopin Risperdal Zoloft 

Dilantin Neurotin Seroquel Zyprexa 

Elavil Paxil 

Adapted from Litt, JZ. Curious, Odd, Rare, and Abnormal Reactions to Medications. Fort Lee, 

NJ: Barricade Books; 2009:107. 


Arnika Forte ® 

SPEED THE HEALING 

Arnika Forte ® 

The New Gold Standard 

for treating bruising, 

swelling, pain 

� 

� 

� 

1st and only combination 

of Arnica Montana 30x and 

Bromelain 

One convenient capsule 

twice a day 

All natural, safe, 

physician - formulated 

Speed the healing time 

from bruising, swelling and 

pain after surgery or dermal 

filler injections 

To Order Call 484-568-0306



Howard A. Epstein, PhD, Section Editor 

Repelling Insects With Safe and Effective 


In addition to the annoying itch that results from biting 

insects, insect-borne diseases, including Lyme disease, 

encephalitis, Rocky Mountain spotted fever, and West Nile 

virus, are all causes of concern for many individuals who wish to 

enjoy the outdoor environment during the warmer months of the 

year. The military of various nations experienced the same problems 

and have conducted much research in developing repellents 

to protect their soldiers. The Indian Army used oils of citronella, 

camphor, and paraffin as repellents. These agents were effective 

for limited periods and therefore the search for more effective 

repellents continued. In 1953, N, N-diethyl-m-toluamide 

(DEET) was discovered (Figure 1). As of 2007, it was estimated 

that 15 million people in the United Kingdom, 78 million people 

in the United States, and 200 million people globally use 

DEET each year. 1 Over the years, as cases of insect-borne diseases 

continued to be reported in the news, so has the use of 

DEET. Reports of adverse reactions associated with DEET have 

increased with its use. 

HEALTH-RELATED ISSUES AND 

CONSUMER CONCERNS 

In 2004, the Oregon State University (OSU) Agricultural Experiment 

Station issued a press release entitled “OSU Scientist Gives 

Safety Tips for Use of DEET Against Mosquitoes & West Nile 

Virus.” In the release, Dr Damiel Sudakin, an assistant professor 

at OSU’s Department of Environmental and Molecular Toxicology 

and toxicologist at the Agricultural Experiment Station was quoted 

as expressing concern that hundreds of adverse reactions, most commonly 

affecting the skin, are reported each year. The majority of 

these adverse reactions occur when DEET is overused or misused. 2 

In 2009, Science Daily published a paper entitled “Popular Insect 

Repellent DEET Is Neurotoxic.” 3 The contribution referenced a 

study that concluded that DEET is not simply a behavior-modifying 

chemical, but also inhibits the activity of a key central nervous system 

enzyme, acetylcholinesterase, in both insects and mammals. 4 


In 2004, the Agency for Toxic Substances & Disease Registry issued 

a report on the health effects of DEET in humans. The report mentioned 

6 cases of DEET ingestion, 3 led to death after ingestion 

of 15 mL to 50 mL of 47.5% to 95% DEET filled in bottles. In 

2 of these cases, the individuals drank an unspecified amount of 

alcohol. In the third case, the individual ingested an unspecified 

number of pills with 50 mL of DEET. In yet another case, a woman 

ingested 15 mL to 25 mL of 95% DEET and was admitted to a 

hospital with right and left atrial enlargement that returned to normal 

within 24 hours. This woman survived with no further cardiac 

abnormalities. 5 From 1961 to 2002, the Agency reported 8 deaths 

related to DEET exposure, 3 resulting from deliberate ingestion, 

and 2 following dermal exposure to DEET. The remaining 3 cases 

were girls aged 17 months, 5 years, and 6 years. All 3 children were 

described as having “heavy, frequent, or nightly applications of 

DEET.” The 6-year-old had congenital ornithine carbamoyl transferase 

deficiency, which may have contributed to her death. 5 Two 

other reported cases involved 2 men, aged 27 and 30 years, who 

developed severe psychological effects from exposure to DEET. In 

both cases, the men recovered after hospitalization. 5 

MILITARY AND GOVERNMENT PERSONNEL: 

DERMAL EFFECTS OF DEET EXPOSURE 

Unique cutaneous side effects were reported in 15 soldiers who 

applied military-issued DEET repellents. One soldier applied a 

33% DEET repellent to his skin without washing it off at bedtime. 

He developed a vesiculobullous eruption, which cleared after 

14 days. Another soldier who went to bed without removing 

DEET applied to his skin woke up 8 hours later complaining of 

a burning sensation and skin eruptions. A 10-day treatment with 

corticosteroids cleared the condition. Other soldiers reported 

burning skin and erythema after application of 50% DEET 

solution applied just before bedtime. Three soldiers were referred 

to treatment by a dermatologist: 2 of the soldiers developed a 

permanent scar and 1 required corrective surgery. 5 

From EMD Chemicals Inc, Gibbstown, NJ 

Address for Correspondence: Howard A. Epstein, PhD, EMD Chemicals Inc, One International Plaza, Suite 300, Philadelphia, PA 19113 • 

E-mail: howard.epstein@merckgroup.com 




O 

N 

Figure 1. DEET CAS 

134–62–3. 

Other controlled studies in which DEET was applied to 63 volunteers 

with a gauze pad soaked in DEET determined that DEET 

should be washed from skin prior to sleeping directly related to the 

irritant effects of DEET. 5 Additional studies involving 143 National 

Park Service employees at Everglades National Park resulted in 36 

of the workers having adverse health effects to the applied DEET. 

The effects included skin or mucous membrane irritation, transient 

numb or burning lips, dizziness, disorientation, and difficulty in 

concentration. Headache and nausea were also reported. 5 

MULTIPLE CASE STUDIES OF DEET EXPOSURE 

An analysis of phone calls to poison control centers in the United 

States from 1985 to 1989 represented more than 6 million human 

exposures to a variety of chemicals. Of these, 9086 were related to 

DEET. Of the DEET-related calls, 54% of patients had no symptoms 

at the time of the call and 40% had symptoms thought 

to be related to DEET exposure. The most commonly reported 

exposure was inhalation of DEET or spray into the eyes. These 

exposures were more likely to cause adverse reactions compared 

with cases in which small quantities of DEET were ingested. Of 

the individuals with symptoms, 88% did not require medical 

attention, 35% had minor skin irritation, and 1% experienced 

disorientation or brief seizures. There was a reported death from 

deliberate consumption of an 8-oz bottle of DEET. Children 

were not more likely to develop side effects than adults. 5 

CASE REPORTS OF CHILD EXPOSURES 

During 1961 to 2002, 14 of the 17 reported cases of significant 

DEET toxicity were in children younger than 8 years. The most 

frequently reported symptoms of DEET toxicity in children 

were lethargy, headaches, tremors, involuntary movements, seizures, 

and convulsions. 5 The common route of exposure in children 

is frequently dermal or accidental ingestion. Adverse effects 

have been reported in an 18.5-month child who was sprayed 

with 20% DEET daily for 3 months and a 6-year-old who was 

sprayed with 15% DEET on 10 occasions. Generally, children 

recover from exposure. In 1989, there were 4 cases of children 

ages 3 to 7 years and a 29-year-old man having generalized 


37 


seizures associated with the dermal application of DEET, with 

fewer than 3 applications. 5 

ALTERNATIVES TO DEET 

Picaridin, 1-piperidine carboxylic acid-2(2-hydroxxyethyl)-1methpropylester 

(Figure 2) was developed by Bayer in the 1980s. 

It is a synthetic molecule chemically based on the active agent 

in pepper (Piper sp). Picaridin was first registered with the US 

Environmental Protection Agency (EPA) in 2001 and entered 

the market in 2005. Picaridin has a favorable safety profile, most 

likely because the compound has not been as commercially 

available for as long as DEET, and therefore there is far less information 

regarding adverse reactions. 

The first report of a contact allergy during commercial use was 

reported in 2005, in which a 39-year-old man experienced an 

itchy erythematous reaction to a spray a few hours after application 

to the skin. 1 Australian soldiers evaluated 19.2% Picaridin 

compared with 35% DEET in a gel formulation, with significantly 

more soldiers reporting mild discomfort and irritation 

with the use of the DEET gel. Published studies indicate that 

Picaridin may be as effective as DEET. There are variations in 

repellent efficacy depending on species of insect and levels of 

use. The literature reports that Picaridin is aesthetically more 

“elegant” than DEET in various formulations. 1 It is registered 

for use on the human body and clothing to repel biting flies, 

ticks, chiggers, fleas, and mosquitoes. 6 

NATURAL AND EFFECTIVE ALTERNATIVES 

IR3535, [3-(N-acetyl-N-butyl)aminopropionic acid ethyl ester] 

(Figure 3) has been marketed by Merck KGaA, Darmstadt, 

Germany, for the past 30 years. It was registered by the US EPA 

in 1999. IR3535 is unique in that it is classified as a biopesticide 

repellent. DEET and Picaridin are classified as conventional 

insect repellent pesticides. The EPA defines a biopesticide as a 

pesticide derived from natural materials including animal, plant, 

bacteria, and minerals. Canola oil and baking soda have pesticidal 

applications and are considered biopesticides. 7 Biochemical 

pesticides are naturally occurring substances that control pests 

N 

O 

C O 

CH 2 

Me 

CH 2 

CH 

Figure 2. Picaridin, 

Chemical Abstracts 

Service registry number 

119515–38–7. 

Et 

OH 

O O 

Figure 3. Ethyl butylacetylaminopropionate 

(IR3535), Chemical 

Abstracts Service registry 

number 52304–36–6. 


N O


by nontoxic mechanisms. The EPA has established a special 

committee to determine the most appropriate classification 

based on established criteria. 7 

Biopesticides are usually less toxic than conventional pesticides. 

They generally affect only the target pest and closely 

related organisms compared with broad-spectrum conventional 

pesticides that may affect other organisms including birds and 

mammals. 7 IR3535 received this classification because it is functionally 

identical to naturally occurring b-alanine. It is a substituted 

B amino acid that contains 98% 3-(N-acetyl-N-butyl) 

aminopropionic acid, ethyl ester as an active ingredient and 2% 

inert ingredients. The end groups are not likely to contribute 

to toxicity and it acts to control the target pest via a nontoxic 

mode of action. 7 In various studies, IR3535 has been shown to 

be as effective as DEET. As with Picaridin the formulation, level 

of repellent, and species of insect may be a factor with respect 

to repellent efficacy. 1 IR3535 is also reported to be more cosmetically 

elegant than DEET when evaluated in various human 

Table I. Comparative Toxicology Data for IR3535, 7,8 Picaridin, 9 and DEET 10 


38 


studies. As of publication in 2007, the authors of Insect Repellents: 

Principles, Methods, and Uses claim there were no reported 

adverse reactions to IR3535. 1 IR3535 is registered for use as an 

insect repellent against mosquitoes, deer ticks, body lice, and 

biting flies. The formulated products are applied directly to skin. 

The low toxicity data for IR3535 implies that there is reasonable 

certainty of no harm for the general population, as well as subgroups 

including infants and children. 7 

REVIEW OF TOXICITY DATA FOR DEET, 

PICARIDIN, AND IR3535 

Tables I and II review toxicological data obtained from various 

sources. Regarding safety classification, the World Health 

Organization (WHO) classification for IR3535 is hazard class 

U, indicating that the compound is unlikely to present acute 

hazard in normal use. 8 The WHO classified Picaridin as class III, 

indicating a slight hazard. 9,11 DEET was also designated as class 

III by the WHO. 12,13 

TEST IR3535 PICARIDIN DEET REPORTED DOSE 

Acute toxicity oral rat (lethal dose, 50%) >5000 2236 2170 mg/kg body weight 

Acute dermal toxicity rabbit or rat (lethal dose, 50%) >3000 >2000 4280 mg/kg body weight 

Acute inhalation (lethal dose, 50%) >5.1 >4.3 NA mg/L 

Eye irritation in rabbit Irritating to eye Moderate irritant Irritating 

Skin sensitization in guinea pig No No No 

Dermal sensitization human (NOEL) No No No mg/kg/d 

Subchronic dermal rat (NOEL) 3000 200 300 mg/kg/d 

Developmental rat (oral) 1000 400 250 mg/kg/d 

Ames test (Salmonella typhimurium) Nonmutagenic Nonmutagenic Nonmutagenic 

Micronucleus assay Nonmutagenic Nonmutagenic Nonmutagenic 

Abbreviations: DEET, N, N-diethyl-m-toluamide; NA, not applicable; NOEL, no observed effect level. Higher scores indicate lower potential 

for toxicity. 

Table II. Information From Various EPA Fact Sheets5,7,9 EPA FACT SHEET CLASS IR3535 PICARIDIN DEET 

Acute inhalation toxicity IV IV IV 

Primary dermal irritation IV IV III 

Acute oral IV III III 

Acute dermal III III III 

Primary eye II III III 

Abbreviations: DEET, N, N-diethyl-m-toluamide; EPA, Environmental Protection Agency. Category I, very highly or highly toxic; category 

II, moderately toxic; category III, slightly toxic; category IV, practically nontoxic. 

Alternatives to DEET


CONCLUSIONS 

Insect repellents are more effective at higher concentrations. In 

addition to the level of actives in the formulation, the degree 

of efficacy may be related to the species of insect to be repelled. 

Another factor is proper use of the repellent. When there is 

concern that label directions for use may not be properly followed, 

the best option is to suggest the compound with the 

least hazard risk. The WHO notes that classification criteria are 

guide-points intended to supplement but never substitute for 

special knowledge, sound clinical judgment, or experience with 

a compound. 13 

REFERENCES 

1 Debboun M, Frances SP, Strickman D, eds. Insect Repellents: Principles, 

Methods, and Uses. Boca Raton, FL: CRC Press; 2006. 

2 Gewin V. OSU scientist gives safety tips for use of DEET against 

mosquitoes & West Nile virus. http://extension.oregonstate.edu/news/ 

release/2004/08/osu-scientist. Accessed June 24, 2011. 

3 Science Daily. Popular insect repellant DEET is neurotoxic. http://www. 

sciencedaily.com/releases/2009/08/090804193230.htm. Accessed 

June 24, 2011. 

4 Corbel V, Stankiewicz M, Pennetier C, et al. Evidence for inhibition of 

cholinesterases in insect and mammalian nervous systems by the insect 

repellant deet. BMC Biology. 2009;7:47. 

5 Agency for Toxic Substances & Disease Registry Division of Toxicology 

and Environmental Medicine. Health Effects in Humans: DEET (N,N- 

Diethyl-meta-toluamide). Atlanta, GA: Agency for Toxic Substances and 

Disease Registry; December 6, 2004. http://www.atsdr.cdc.gov/consultations/deet/health-effects.html. 

Accessed July 12, 2011. 

VINTAGE LABEL 

Courtesy of BuyEnlarge, Philadelphia, PA 


39 


6 National Pesticide Information Center. Picaridin Technical Fact Sheet. 

Corvalis, OR: Oregon State University; March 2009. http://npic.orst. 

edu. Accessed July 14, 2011. 

7 United States Environmental Protection Agency. Pesticides: Regulating 

Pesticides. 3-[N-Butyl-N-acetyl]-aminopropionic acid, ethyl ester (113509) 

Technical Document. Washington, DC: United States Environmental Protection 

Agency; February 1999. http://.epa.gov/opp00001/biopesticides/ 

ingredients. Accessed July 13, 2011. 

8 World Health Organization. Specifications and Evaluations for Public 

Health Pesticides. Ethyl Butylacetylaminopropionate also known as 

IR3535 3-(N-acetyl-N-butyl) aminopropionic acid ethyl ester. Geneva, 

Switzerland: World Health Organization; February 2006. htt://www.who. 

int/quality/en/. Accessed July 12, 2011. 

9 United States Environmental Protection Agency. EPA New Pesticide Fact 

Sheet Picaridin. Washington, DC: United States Environmental Protection 

Agency; May 2005. http://www.epa.gov/opprd001/factsheets/. 

Accessed July 12, 2011. 

10 United States Environmental Protection Agency. Reregistration 

Eligibility Decision (RED) DEET. Washington, DC: United States Environmental 

Protection Agency; September 1998. EPA738-R-010. 

11 World Health Organization. Specifications and Evaluations for Public Health 

Pesticides. Icaridin, 1-piperidinecarboxylic acid 2-(2-hydroxxxyethyl)-1methylpropylester 

also known as isobutyl piperidine carboxylate. Geneva, 

Switzerland: World Health Organization; October 2004. http://www.who. 

int/quality/en/. Accessed July 12, 2011. 

12 World Health Organization. International Program on Chemical Safety PCS 

INCHEM. Data Sheet on Pesticide No. 80 DEET. Geneva, Switzerland: 

World Health Organization. WHO/VBC/DS/87.80. http://www.inchem. 

org/documents/pds/pds/pest80. Accessed June 24, 2011. 

13 World Health Organization. IPCS, IOMC. The WHO Recommended 

Classification of Pesticides by Hazard and Guidelines to Classification 

2009. Geneva, Switzerland: World Health Organization; 2010. 

http://www.who.int/ipcs/publications/pesticides_hazard. Accessed 

July 12, 2011. 

Alternatives to DEET




It’s Not Just Who You Are, It’s Also Where You Are: 

The Cutaneous Leiomyosarcoma Dilemma 

Gizem Tumer, MD; Carmen F. Castilla, BS; W. Clark Lambert, MD, PhD 

“To understand a name you must be acquainted with the particular of which it is a name.”—Bertrard Russell 

Leiomyosarcoma of the skin is a rare soft tissue neoplasm 

of smooth muscle origin. Treatment and prognosis of 

this lesion are dependent on its depth, with deep soft tissue 

tumors carrying a significantly worse prognosis and requiring 

more extensive surgery than cutaneous ones. It is essential 

that all physicians involved know this. It is also critical that the 

dermatopathologist report the depth of a leiomyosarcoma in 

order for the clinician to render appropriate therapy. Failure to 

report the location of this neoplasm and/or failure to comprehend 

the prognostic significance of this information, can lead to 

inappropriate therapy and increased morbidity in patients. 

CLASSIFICATION 

Three classifications of smooth muscle tumors of the skin have 

been described1 : 

• Atypical smooth muscle tumor of the dermis (purely dermal 

lesion); 

• Cutaneous leiomyosarcoma (dermal lesion with minimal 

extension into the subcutis); 

• Subcutaneous leiomyosarcoma. 2 

Microscopically, the cutaneous leiomyosarcoma lesion involves 

the dermis and focally, the subcutis. It is composed of bluntended, 

cigar-shaped fusiform neoplastic spindle cells with eosinophillic 

cytoplasm forming fascicles and bundles. 2–5 This neoplasm 

may appear in two different architectural patterns: a fasciculated 

growth pattern and a pilar-type architectural pattern (Figure 1 and 

Figure 2). The latter generally represents a low-grade neoplasm 

showing histologic features suggestive of pilar leiomyoma with the 

addition of a variable degree of cytological atypia and mitoses. 2 

CLINICAL FINDINGS 

Cutaneous leiomyosarcomas typically follow an indolent clinical 

course. Local recurrence does occur; however, distant metastasis 

is uncommon and mortality related to tumor progression 

is unusual. 2,6–10 In contrast to cutaneous leiomyosarcoma, 

subcutaneous leiomyosarcoma presents as a larger mass of a 

higher grade. Although still superficially located above the fascia, 

the local recurrence rate and metastatic rate of subcutaneous 

leiomyosarcoma is closer to the more ominous deep soft tissue 

leiomyosarcoma. 5,6,11 

Based on the differences in their prognoses, investigators proposed 

the term atypical intradermal smooth muscle neoplasm 

instead of cutaneous leiomyosarcoma to highlight the benign 

nature of cutaneous leiomyosarcoma vs the more aggressive 

soft tissue leiomyosarcoma and subcutaneous leiomyosarcoma. 

The same group also argued that grading primary dermal atypical 

smooth muscle neoplasms is inappropriate given the fact 

that the only prognostic predictor is margin status at the time of 

excision and no other reliable prognostic factor has been identified. 

5 While we respect these investigators’ opinion, we believe 

that thus terming such lesions is a bit like a tail wagging the 

dog. We believe it is more sensible to name a tumor in the most 

logical way based on its histological features, and subsequently 

to note if some subset of these lesions has a different prognosis. 

TREATMENT 

Treatments for cutaneous and deep soft tissue leiomyosarcoma 

differ significantly. Unlike deep soft tissue leiomyosarcoma, 

which requires extensive surgery, the standard treatment for 

cutaneous leiomyosarcoma and subcutaneous leiomyosarcoma is 

wide local excision, with margins ranging from 2 cm to 5 cm. 12,13 

Mohs’ micrographic surgery (MMS) has also been used for cutaneous 

leiomyosarcomas. This technique can be beneficial as it 

provides the ability to examine all margins as the lesion is excised 

while sparing normal tissue. 9 At this time, only a few small studies 

investigating MMS have been reported and further studies 

are required to investigate this technique. 13–16 

From the Departments of Dermatology and Pathology, UMDNJ-New Jersey Medical School, Newark, NJ 

Address for Correspondence: W. Clark Lambert, MD, PhD, Room C520 MSB, UMDNJ-NJMS, 185 South Orange Avenue, Newark, NJ 07103 

• E-mail: lamberwc@umdnj.edu 




Figure 1. Subcutaneous skin biopsy of tumor cells composed 

of cigar-shaped spindle cells with mitotic figures (black arrows) 

(hematoxylin-eosin stain, original magnification ×20). 

OBSERVATIONS 

Due to the increased risk of metastasis and the worse prognosis of 

subcutaneous leiomyosarcoma, an analysis of the subcutaneous 

tissue is crucial when the diagnosis of cutaneous leiomyosarcoma 

is made. Undergrading of the tumor may occur if a shave biopsy 

is utilized to diagnose the lesion. 

In contrast to deep soft tissue leiomyosarcomas, which may 

require extensive surgery, overly aggressive treatment or mutilating 

surgeries are not warranted in cutaneous leiomyosarcoma. 

The standard of care for cutaneous leiomyosarcoma remains 

wide excisional biopsy; however, recent studies have shown benefits 

to using MMS. 

The dermatopathologist must report the depth of the tumor 

and the closest distance from the margin in order to provide the 

best therapeutic approach. The clinician must then understand 

the significance of this interpretation. Failure to distinguish and 

report the exact depth of this neoplasm or a failure of the clinician 

to understand the significance of this information may lead 

to inappropriate and aggressive treatment with excess morbidity. 

REFERENCES 

1 Hornick JL, Fletcher CD. Criteria for malignancy in nonvisceral smooth 

muscle tumors. Ann Diagn Pathol. 2003;7;60–66. 

2 Massi D, Franchi A, Alos L, et al. Primary cutaneous leiomyosarcoma: 

clinicopathological analysis of 36 cases. Histopathology. 2010;56: 

251–262. 


41 


Figure 2. Spindle cell lesion with areas of mitosis (arrowheads). 

3 Mentzel T. Sarcomas in the skin of the elderly. Clin Dermatol. 

2011;29:80–90. 

4 De Giorgi V, Sestini S, Massi D, et al. Superficial cutaneous leiomyosarcoma: 

a rare, misleading tumor. Am J Clin Dermatol. 2008;9:185–187. 

5 Kraft S, Fletcher CD. Atypical intradermal smooth muscle neoplasms: 

clinicopathologic analysis of 84 cases and a reappraisal of cutaneous 

“leiomyosarcoma.” Am J Surg Pathol. 2011;35:599–607. 

6 Svarvar C, Böhling T, Berlin O, et al. Clinical course of nonvisceral 

soft tissue leiomyosarcoma in 225 patients from the Scandinavian 

Sarcoma Group. Cancer. 2007;109:282–291. 

7 Brown MD. Recognition and management of unusual cutaneous tumors. 

Dermatol Clin. 2000;18:543–552. 

8 Ikari Y, Tokuhashi I, Haramoto I, et al. Cutaneous leiomyosarcoma. 

J Dermatol. 1992;19:99–104. 

9 Swanson PE, Stanley MW, Scheithauer BW, Wick MR. Primary cutaneous 

leiomyosarcoma: a histological and immunohistochemical study 

of 9 cases, with ultrastructural correlation. J Cutan Pathol. 1988;15: 

129–141. 

10 Fields JP, Helwig EB. Leiomyosarcoma of the skin and subcutaneous 

tissue. Cancer. 1981;47:156–169. 

11 Massi D, Franchi A, Alos L, Cook M. Primary cutaneous leiomyosarcoma: 

clinicopathological analysis of 36 cases. Histopathology. 2010;56: 

251–262. 

12 Tsut Sumido A, Yoshida T, Yamamoto Y, Itoh T. Management of superficial 

leiomyosarcoma: a retrospective study of 10 cases. Plast Reconst 

Surg. 2005;116:8–12. 

13 Humphreys TR, Finkelstein DH, Lee JB. Superficial leiomyosarcoma treated 

with Mohs micographic surgery. Dermatol Surg. 2004;30:108–112. 

14 Starling J 3rd, Coldiron BM. Mohs micrographic surgery for the treatment 

of cutaneous leiomyosarcoma. J Am Acad Dermatol. 2011;64: 

1119–1122. 

15 Huether MJ, Zitelli JA, Brodland DG. Mohs micographic surgery for 

the treatment of spindle tumors of the skin. J Am Acad Dermatol. 

2001;44:656–659. 

16 Annest NM, Grekin SJ, Stone MS, Messingham MJ. Cutaneous leiomyosarcoma: 

a tumor of the head and neck. Dermatol Surg. 2007;33:628–633. 

It’s Not Just Who You Are



Jack M. Bernstein, MD, Section Editor 

It May Be Vulgar, but It Isn’t a Bad Word 

�� 1,2 �� 2 Jack M. Bernstein, MD 1,2 

A 

�� 

�� 

�� 

�� 

�� 

��- 

�� 

�� 

��- 

�� 

�� 

�� 

�� - 

�� 

�� and 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 4 �� 

��- 

�� 3 �� 

��- 

�� 

�� 4 �� 

�� 1 

DIAGNOSIS 

��- 

�� 

��- 

��- 

�� 

��4�� 

��4�� 

�� 

�� 

�� 

�� 

��- 

��1 �� 

�� 

��2�� 

��3�� 

��1 TREATMENT 

�� 

�� 

�� 

�� 

�� 

CLINICAL MANIFESTATIONS 

�� 

�� 

��8�� Mycobacterium 

tuberculosis�� 

��3 CONCLUSIONS 

�� 

�� 

��- 

�� 

From the Department of Veterans Affairs Medical Center, Dayton, OH, 1 and the Department of Medicine, Wright State University School of 

Medicine, Dayton, OH2 Address for Correspondence: Jack M. Bernstein, MD, Research (151), VA Medical Center, 4100 West Third Street, Dayton, OH 45428 

�� 


��


Figure 1. �� 


�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 


43 

�� 


�� 

�� 

�� 

�� 

�� 

REFERENCES 

1 �� 

��J Am Acad Dermatol. 

�� 

2 �� 

��Dermatology in General 

Medicine.�� 

3 �� 

��Int J Tuberc Lung Dis.�� 

4 �� 

�� 

�� Int J Dermatol.�� 

5 �� 

�� Int J Dermatol.�� 

6 �� 

�� 

MMWR Recomm Rep.�� 

7 �� 

�� JAMA.� �� 

�� 

8 �� 

N Engl J Med.�� 

��

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

��


The term dermatosis neglecta was originally coined in 

1995 when three cases of an “unwashed dermatosis” 

were presented by L. Poskitt and colleagues. 1 

In all cases, the patients committed what Poskitt described 

as “acts of omission” by failing to wash their skin in the 

affected areas. The resulting hyperpigmented, hyperkeratotic 

dermatosis resolved by vigorously washing with soap and 

water or, in severe areas, by applying 5% salicylic acid in 

aqueous cream twice daily. Our patient had a severe case that 

responded well to salicylic acid followed by routine washing. 

Because the patient was subsequently lost to follow-up, we were 

unable to evaluate hair regrowth. 

Periodic shedding of the outermost cellular layers is an essential 

component of normal keratinocyte development. In the 

stratum corneum, protein-rich, lipid-depleted keratinocytes 

are the “bricks” that are held together by hydrophobic intercellular 

membranes and desmosomes, making up the “mortar.” 2,3 

Genetic defects in this system—either in the keratinocytes themselves 

or their intercellular molding—can lead to abnormal retention 

of stratum corneum, causing disorders such as ichthyosis 

vulgaris and recessive X-linked ichthyosis. Ichthyosis vulgaris 

is caused by defective profilaggrin, a keratinocyte protein, and 

CASE STUDY 

Vesna Petronic-Rosic, MD, MSc, Section Editor 

Unusually Severe Case of Dermatosis Neglecta 

Jake E. Turrentine, BS; Travis W. Blalock, MD; Loretta S. Davis, MD 

An 18-year-old black woman with cerebral palsy was admitted for evaluation of an intrathecal baclofen pump site infection. The dermatology 

service was consulted for treatment suggestions of a presumed diagnosis of chronic tinea capitis. Three courses of oral griseofulvin during 

the past 2 years failed to resolve the patient’s chronic scalp dermatosis. Scalp lesions first began about 2 years earlier after hospitalization for 

placement of an intrathecal baclofen pump. The patient was unable to care for her scalp due to her cerebral palsy, and her mother interpreted 

the scalp condition as infectious. No routine shampoo care, scalp care, or topical treatment was performed for more than 1½ years. 

The mother felt that touching the patient’s scalp might cause pain and noted that the majority of her time was spent concentrating on more 

critical medical issues. Physical examination revealed coalescing hyperkeratotic plaques extending dorsally from the anterior hairline to the 

occipital scalp with small flecks of keratinous debris throughout the remaining hair (Figure 1). The plate-like plaques were devoid of hair, 

except at a few fissures where a few tufts of hair emerged. No cervical lymph nodes were appreciated on palpation. Treatment was initiated 

with compresses consisting of large warm water–soaked towels 4 times daily. Three times a day, a nursing staff applied 5% salicylic acid in 

olive oil to the scalp under a shower cap for approximately 1 hour. Over the following 2 days, a significant reduction in keratinous debris 

was appreciated. Within 2 weeks, the bulk of the plaques had been removed (Figure 2). At 6-week follow-up, the underlying scalp showed 

areas of fibrosis and possible scarring with a few emerging tufts of hair. On the basis of history and response to treatment with salicylic acid 

and routine scalp care, the patient was diagnosed with an unusually severe case of dermatosis neglecta. 

recessive X-linked ichthyosis is caused by a deficiency in steroid 

sulfatase, an enzyme in the intercellular domain. 4 These genetic 

abnormalities of adherent stratum corneum illustrate the importance 

of regular shedding of superficial keratinocyte layers. 

Dermatosis neglecta represents a failure to cleanse adequately a 

particular area of skin, leading to the buildup of adherent hyperpigmented 

scales. Thus, dermatosis neglecta can be understood 

as a self-induced “defect” in normal keratinocyte shedding that 

causes abnormal accumulation of cellular layers and debris. Dermatosis 

neglecta typically occurs in an area of hyperesthesia or 

prior trauma where the patient refuses to scrub the skin. 5 Also, 

as in our patient, dermatosis neglecta can develop in situations 

where a patient is unable to properly care for an area of skin 

because of physical or mental disability. 

A similar condition described in the literature is terra firma forme 

dermatosis (TFFD), which is a disorder of unknown etiology characterized 

primarily by disordered keratinization. 6–8 In TFFD, the 

classic clinical finding is a dark, dirty-looking, slightly raised hyperkeratotic 

skin lesion that is completely asymptomatic. Cases of 

TFFD respond to 70% isopropyl alcohol rubs but not to cleansing 

with normal soap and water; therefore, TFFD can be distinguished 

From the Division of Dermatology, Medical College of Georgia, Augusta, GA 

Address for Correspondence: Travis W. Blalock, MD, Medical College of Georgia, Division of Dermatology, 1004 Chafee Avenue, Augusta, 

GA 30904 • E-mail: tblalock@mcg.edu 




Figure 1. Crusted, plate-like plaques on the scalp at initial 

presentation. 

clinically from dermatosis neglecta by the lack of response to normal 

washing and, of course, the absence of historical clues of neglect. 

Given its rapid response to inexpensive and simple treatment, 

dermatosis neglecta should be considered in the evaluation of 

a pigmented, hyperkeratotic skin lesion. If identified, a skin 

biopsy can often be avoided. Physicians should always inquire 

about skin care habits when gathering history about an unexplained 

skin lesion and should review and recommend normal 

skin hygiene, when a patient fails to respond to a full course of 

standard therapy for an alternate diagnosis. 

REFERENCES 

1 Poskitt L, Wayte J, Wojnarowska F, Wilkinson JD. “Dermatosis neglecta”: 

unwashed dermatosis. Br J Dermatol. 1995;112:827–829. 


VINTAGE LABEL 


47 

CASE STUDY 

Figure 2. Almost complete resolution of scalp plaque following 

2 weeks of therapy. 

2 Elias PM. Epidermal lipids, barrier function, and desquamation. J Invest 

Dermatol. 1983;80:44s–49s. 

3 Williams ML. Ichthyosis: mechanisms of disease. Pediatr Dermatol. 

1992;9:365–368. 

4 Elias PM, Crumrine D, Rassner U, et al. Basis for abnormal desquamation 

and permeability barrier dysfunction in RXLI. J Invest Dermatol. 

2004;122:314–319. 

5 Lucas JL, Brodell RT, Feldman SR. Dermatosis neglecta: a series of case 

reports and review of other dirty-appearing dermatoses. Dermatol Online 

J. 2006;12:5. 

6 Akkash L, Badran D, Al-Omari AQ. Terra firma forme dermatosis: case 

series and review of the literature. J Dtsch Dermatol Ges. 2009;7:102– 

107. 

7 Guarneri C, Guarneri F, Cannavo SP. Terra firma-forme dermatosis. Int J 

Dermatol. 2008;47:482–484. 

8 Raveh T, Gilead LT, Wexler MR. Terra firma forme dermatosis. Ann Plast 

Surg. 1997;39:542–545. 

Dermatosis Neglecta


CASE STUDY 

Fixed-Drug Eruption Caused by Ashwagandha 

(Withania somnifera): A Widely Used Ayurvedic Drug 

Virendra N. Sehgal, MD; Prashant Verma, MD; Sambit N. Bhattacharya, MD 

A 28-year-old man with decreased libido received ashwagandha in the usual daily dosage of 5 g for 10 days. During this period, he 

experienced a burning and/or itching sensation as well as discoloration of the skin/mucous membrane confined to the penis. He had a 

similar type of eruption at the same site 6 months prior while taking ashwagandha. Examination of the skin surface was conspicuous and 

marked by the presence of a dusky, erythematous, oval, eroded plaque of 3 cm, affecting the glans penis and prepuce (Figure). The drug 

was withdrawn and topical 0.05% clobetasol propionate cream was administered along with cetrizine dihydrochloride, an H 1 -receptor 

blocker, 10 mg daily for 1 month. There was a perceptible amelioration of the lesion, resulting in residual greyish white pigmentation. He 

was prescribed oral drug provocation with 1 g of ashwagandha powder. Within 12 hours, a flare-up developed at the earlier site, confirming 

the causality. 

Fixed-drug eruption, one of the most well-recognized 

adverse drug reactions, is characterized by a peculiar, 

sudden onset of round and/or oval, edematous, dusky 

red macules/plaques on the skin and/or mucous membranes 

accompanied by burning and/or itching. 1 Several drugs 

have been incriminated in its causation, the details of which 

have been specifically recounted in a recent comprehensive 

review. 2 Ashwagandha belongs to an alternative system of 

medicine and has a long medicinal history. It is an innocuous 

agent that has not been associated with any cutaneous drug 

reactions to date. Fixed-drug eruption following the use of 

ashwagandha is an uncommon occurence; hence, the current 

report. 

Ashwagandha literally means “horse smell” (ashwa = horse, 

gandha = smell), for its wet roots smell similar to horse’s urine. 

Withania somnifera, also known as ashwagangha, Indian ginseng, 

winter cherry, ajagandha, kanaje hindi, and samm al 

ferakh, the offending indigenous drug, is derived from a plant 

in the Solanaceae or nightshade family. 3 It is a beautiful, delicate 

plant native to India, Pakistan, and Sri Lanka. It is considered 

the king of herbs among ayurvedic medicines. It has 

a medicinal history of 4000 years and is a well-accepted, vital 

drug in Ayurveda and Indian traditional medicine. 4 It has 

been conventionally used for calming the mind and relieving 

weakness, nervous exhaustion, and arthritis. In addition, it 

is used for building sexual energy. Ashwagandha root is said 

to be beneficial in people who do physical labor or exercise 

a lot, helping the body adapt to physical stress. In addition, 

its paste is recommended for external use in the treatment 

of carbuncles, ulcers, and nondescript swellings. Bedsores and 

wounds are also amenable to topical application of ashwagandha 

leaves. 

CONCLUSIONS 

Ashwagandha is said to possess anti-inflammatory, anti-tumor, 

antistress, antioxidant, immunomodulatory, hemopoeitic, and 

rejuvenating effects. 5 In addition, it is thought to exert a positive 

influence on the endocrine, cardiopulmonary, and central 

nervous systems. 6 Ashwagandha’s mechanism of action is still 

speculative, and toxicity studies have revealed it to be a safe compound. 

7–9 

REFERENCES 

1 Sehgal VN, Bhattacharya SN, Verma P. Physiopathology of adverse cutaneous 

drug reactions—applied perceptions: Part I. Skinmed. In press. 

2 Sehgal VN, Srivastava G. Fixed drug eruption (FDE): changing scenario 

of incriminating drugs. Int J Dermatol. 2006;45:897–908 

3 Winters M. Ancient medicine, modern use: Withania somnifera and its potential 

role in integrative oncology. Altern Med Rev. 2006;11:269–277. 

From the Dermato-Venereology (Skin/VD) Center, Sehgal Nursing Home, Panchwati-Delhi, India; the Department of Dermatology and STD, 

University College of Medical Sciences and Guru Teg Bahadur Hospital, Shahdara, Delhi, India 

Address for Correspondence: Virendra N. Sehgal, MD, Dermato-Venereology (Skin/VD) Center, Sehgal Nursing Home, A/6 Panchwati, 

Delhi 110 033, India • E-mail: drsehgal@ndf.vsnl.net.in 




Figure. Fixed-drug eruption affecting the glans and prepuce 

of the penis. 

VINTAGE LABEL 


CASE STUDY 

4 Rasool M, Varalakshmi P. Protective effect of Withania somnifera root 

powder in relation to lipid peroxidation, antioxidant status, glycoproteins 

and bone collagen on adjuvant-induced arthritis in rats. Fundam Clin 

Pharmacol. 2007;21:157–164. 

5 Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic 

use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 

2000;5:334–346. 

6 Sehgal VN, Srivastava G. Traditional/ayurvedic pharmacotherapy of skin 

diseases. Skinmed. 2010;8:282–284. 

7 Behl PN, Arora RB, Srivastava G. Traditional Indian Dermatology Concept 

of Past and Present. 1st ed. New Delhi, India: SISD Publication; 1992. 

8 Behl PN, Srivastava G. Herbs Useful in Dermatological Therapy. 2nd ed. 

New Delhi, India: CBS Publishers; 2004. 

9 Sehgal VN, Grangwani OP. Fixed drug eruptions: a study of 

epidemiological, clinical and diagnostic aspects of 89 cases from India. 

J Dermatol. 1988;15:50–54. 


Fixed-Drug Eruption Caused by Ashwagandha


CASE STUDY 

Chronic Lymphocytic Leukemia Revealed by a 

Granulomatous Zosteriform Eruption 

Sondes Trojjet, MD; 1 Houda Hammami, MD; 1 Inès Zaraa, MD; 1,2 Alia Bouzguarrou, MD; 1 Meriem Joens, MD; 1 

Slim Haouet, MD; 2,3 Amel Ben Osman, MD; 1,2 Mourad Mokni, MD1,2 A 70-year-old woman presented with an atypical erythematopapular zosteriform eruption of 3 weeks’ duration. The patient had no history 

of previous vesicular eruption. She developed a painful burning sensation on the neck. Clinical examination revealed a cluster of small 

erythematous firm papules and plaques in a zosteriform distribution on the left ear, face, neck, and shoulder (Figure 1A). The lesions were 

unilateral and did not cross the midline. Multiple cervical and axillary lymph nodes were palpable. Laboratory tests revealed an increase 

in white blood cells of 25,000/mm 3 , with 17,910/mm 3 lymphocytes and a normal range of hemoglobin, platelets, creatinine, and liver 

enzymes. Erythrocyte sedimentation rate was 87 mm. Blood smear results showed small, morphologically mature lymphocyte cells. In 

immune phenotyping, lymphocyte cells co-express CD5 and B-cell–surface antigens CD19 and CD23, as well as a restriction of kappa 

immunoglobulin light chains. The cells were CD22-, CD79b-, CD38-, CD10-, CD25- and FMC7-. Computed thoracoabominal tomography 

revealed cervical, mediastinal, abdominal, and pelvic adenopathy confirming the diagnosis of B-cell chronic lymphocytic leukemia 

(B-CLL) stage B. Histology of a skin biopsy from a papule showed a dense nodular granulomatous infiltrate in the dermis (Figure 2A). 

The infiltrate contained epithelioid and giant cells surrounded by lymphocytes and plasma cells. Small monomorphic lymphocytes without 

mitotic figures predominated (Figure 2B). The epidermis was irregularly thickened. Immunohistology revealed a polymorphous infiltrate 

with a phenotype of reactive T lymphocytes (CD3, CD5 positive) (Figure 2C), B lymphocytes (CD20 positive) (Figure 2D). Epithelioid 

and giant cells were positive for CD68 (Figure 2E). A latent herpes zoster infection with granulomatous reaction at the site of zoster lesions 

was highly suspected as the patient reported a unilateral burning sensation without a history of vesicular zosteriform eruption. She received 

treatment with intravenous acyclovir 10 mg/kg every 8 hours. The papular lesions resolved markedly (60%) on macular plaques at the end 

of the treatment. Following topical treatment with corticosteroids, the lesions healed completely within 4 weeks (Figure 1B). Concerning 

leukemia, our patient was monitored without therapy by the hematologist. 

Various cutaneous lesions may appear at sites of prior 

herpes zoster infection, such as annular granuloma, sarcoidal 

granuloma, granulomatous vasculitis, Kaposi’s 

sarcoma, and pseudolymphoma. 1 These cutaneous lesions may 

appear immediately after resolving vesicular lesions or at varying 

times after the acute eruption. We describe in this report an 

unusual case of a granulomatous zosteriform eruption revealing 

a B-cell chronic lymphocytic lymphoma. 

Our patient is of special interest because she presented with a 

granulomatous eruption arising after a probable latent zoster revealing 

B-CLL. Unfortunately, varicella-zoster virus DNA detection 

was not performed in our case. 

Granulomatous reactions and specific infiltrations at sites 

of resolved cutaneous herpes zoster lesions in patients with 

B-CLL have been described as a rare clinical event. 2,3 The 

cause of granulomatous reactions caused by varicella- 

zoster virus remains to be elucidated. 4 Type III and type 

IV hyper sensitivity reaction, 5 isotopic response, 6,7 and viral 

etiologies 2 are thought to be possible provoking factors. 

A study of granulomatous reactions associated with herpes 

zoster lesions for the presence of varicella-zoster virus 

genome using the polymerase chain reaction suggested 

that varicella-zoster virus DNA is detected in cases where 

eruption occurred immediately in the wake of resolving 

vesicular herpes zoster lesions. 2 In this case, differential 

diagnosis includes specific cutaneous infiltrates with 

neoplastic B cells. The clinical resolution of the lesions after 

treatment with acyclovir and topical steroids confirms the 

benign nature of the granulomatous infiltration. 

From the Department of Dermatology, La Rabat Hospital, Tunis Tunisia; 1 the Faculté de Médecine de Tunis, Tunis El Manar University, Tunis, Tunisia; 2 

and the Department of Pathology, La Rabta Hospital, Tunis, Tunisia3 Address for Correspondence: Ines Zaraa, MD, Dermatology Department, La Rabta Hospital, Jabbari, Bab Saadoun, Tunis, 1007 Tunisia 

• E-mail: inesrania@yahoo.fr 



January/February 2012 CASE STUDY 

Figure 1A. Clustered erythematous papules and plaques on 

right neck and shoulder. 

Figure 1B. Healing of clustered erythematous papules and 

plaques within 4 weeks. 

CONCLUSIONS 

An atypical zosteriform eruption should alert dermatopathologists 

to the possibility of an associated hematological dyscrasia, 

mainly B-CLL. 

Figure 2A. Histology of skin papule showing a dense nodular 

granulomatous infiltrate in the dermis (hematoxylin and eosin 

stain, original magnification ×40). 

Figure 2B. Granulomatous infiltrate containing small mature 

lymphocytes with no significant atypia, epithelioid, or giant cells 

(hematoxylin and eosin stain, original magnification ×100). 

REFERENCES 

1 Requena L, Kutzner H, Escalonilla P, et al. Cutaneous reactions at 

sites of herpes zoster scars: an expanded spectrum. Br J Dermatol. 

1998;138:161–168. 


Chronic Lymphocytic Leukemia

January/February 2012 CASE STUDY 

Figure 2C. The majority of infiltrating cells staining positively 

with the pan–T-cell marker CD3 (CD 3 staining [Novocastra, 

Newcastle upon Tyne, UK], original magnification ×40). 

Figure 2D. The infiltrating cells staining positively with the 

pan–B-cell marker CD20 (CD 20 staining [DakoCytomation, 

Glostrup, Denmark], original magnification ×40). 

VINTAGE LABEL 


Figure 2E. Epithelioid and giant cells staining positive with 

CD68 (CD 68 staining [DakoCytomation, Glostrup, Denmark], 

original magnification ×40). 

2 Serfling U, Penneys NS, Zhu WY, et al. Varicella-zoster virus DNA in 

granulomatous skin lesions following herpes zoster. A study by the polymerase 

chain reaction. J Cutan Pathol. 1993;20:28–33. 

3 Wakelin SH, Young E, Kelly S, Turner M. Transient leukaemia cutis in 

chronic lymphocytic leukaemia. Clin Exp Dermatol. 1997;22;148–151. 

4 Cerroni L, Zenahlik P, Kerl H. Specific cutaneous infiltrates of 

B-cell chronic lymphocytic leukemia arising at the site of herpes 

zoster and herpes simplex scars. Cancer. 1995;76: 

5 

26–31. 

Gibney MD, Nahass GT, Leonardi CL. Cutaneous reactions following 

herpes zoster infections: report of three cases and a review of the 

literature. Br J Dermatol. 1996;134:504–509. 

6 Schena D, Barba A, Chieregato C. Granulomatous folliculitis as a manifestation 

of post-herpetic isotopic response. J Eur Acad Dermatol Venereol. 

2001;15:473–475. 

7 Ruocco V, Ruocco E, Ghersetich I, et al. Isotopic response after herpesvirus 

infection: an update. J Am Acad Dermatol. 2002;46:90–94. 


Chronic Lymphocytic Leukemia

Grand Wailea, Maui • February 4–8, 2012 

Register Now for the 8th Annual Conference! 

February 4–8, 2012 Grand Wailea : Maui, Hawaii 

Plan to attend the 8th Annual Maui Derm Conference! “Cutting 

edge, a great blend of science and clinical medicine and a world 

class faculty” describe Maui Derm 2012. Our faculty will share with 

you the most important developments in medical and cosmetic 

dermatology vital to your practice. Our live patient demonstration 

workshops in lasers, Botulinum Toxin A and fi llers have set 

the standard for “hands on” workshops. Our format has been 

specifi cally designed to allow optimal time for discussion with our 

faculty.We are certain that you will fi nd this to be an outstanding 

and memorable educational event that you will not want to miss. 

Put Maui Derm on your calendar for 2012! 

Featured Lectures 

Hot Topics • Cases for the Panel • 

Seminars • Workshops • Basic Science 

Medical Dermatology: Basic Science, Hot Topics, Cases for 

the Panel, Point:Counterpoint, Seminars, “How I Do It” 

Cutaneous Oncology • Acne/Rosacea • Pediatric Dermatology • Infectious Diseases 

Psoriasis • Skin of Color • Life Threatening Dermatoses • Master’s CPC • Offi ce 

Surgery • Practice Management 

Cosmetic Dermatology: From Basic Science to Case Based 

Discussion and “How I Do It” 

Botulinum Toxin A and Fillers • Lasers • Sclerotherapy 

“Lunch with the Faculty” – 

Controversial Topics, Case-based Discussions 

Interactive Workshops 

Small Group, Live Patient, Hands-On Demonstrations: Botulinum Toxins/Fillers, 

Sclerotherapy 

2012 Faculty * 

Matthew Avram, MD 

Neal Bhatia, MD 

Andrew Blauvelt, MD 

Valerie Callender, MD 

Joel Cohen, MD 

Lawrence Eichenfi eld, MD 

Rebecca Fitzgerald, MD 

Keith T. Flaherty, MD 

Sheila Friedlander Fallon, MD 

Ilona Frieden, MD 

Michael Gold, MD 

Mitchel Goldman, MD 

Pearl Grimes. MD 

Derek Jones, MD 

Arthur Kavanaugh, MD 

Suzanne Kilmer, MD 

David Laub, MD 

Philip LeBoit, MD 

Craig Leonardi, MD 

Stuart Maddin, MD 

Ashfaq Marghoob, MD 

Chairman: 

Dr. George Martin 

20 

12 

Sam Moschella, MD 

Stuart Nelson, MD 

Kevin Pinski, MD 

Phoebe Rich, MD 

Ted Rosen, MD 

E. Vic Ross, MD 

Alan Shalita, MD 

Ava Shamban, MD 

Daniel Siegel, MD 

Eggert Stockfl eth, MD 

Bruce Strober, MD, PhD 

Neil Swanson, MD 

James Treat, MD 

Hensin Tsao, MD 

Sandy Tsao, MD 

Guy Webster, MD, PhD 

Wm. Philip Werschler, MD 

John Zone, MD 

* Subject to Change 

MAUI DERM 2012 

HAS SPECIAL/REDUCED RATES AT THE 

Grand Wailea and the Wailea Marriott 

For more details, visit our website at 

www.acmd-derm-hawaii.com


MYCOBACTERIUM MARINUM CUTANEOUS 

INFECTION WITH SPOROTRICHOID DISTRIBUTION 

TREATED WITH AZITHROMYCIN MONOTHERAPY 

To the Editor: 

Mycobacterium marinum is an aerobic, waterborne mycobacterium 

commonly found in nonchlorinated water in a worldwide 

distribution. It is also the most common atypical Mycobacterium 

to cause infection in humans. Infection is not transmittable 

from person to person, and skin infections due to M marinum 

are rare. 1 

There is no established treatment of choice for M marinum 

infection, probably because it is a multidrug-resistant species. 

Its treatment has been based primarily on personal experience 

without the benefit of large studies. 2 To our knowledge, this is 

the first case of cutaneous M marinum infection treated with 

azithromycin monotherapy. 

A 52-year-old-woman, a cleaning worker in our hospital, was 

referred to our department because of the appearance of red 

nodules on the left palm and left forearm in a sporotrichoid 

distribution (Figure 1). She mentioned that the first lesion 

appeared on her hand 6 months previously and new lesions 

gradually appeared and increased in number and size during this 

period. She also reported a private fish aquarium usually cleaned 

by her without using hand protection. The remainder of her 

medical history was unremarkable. 

Figure 1. Mycobacterium marinum skin infection of the left 

palm with sporotrichoid distribution on the left forearm. 


Routine laboratory tests including human immunodeficiency 

virus test were within normal limits. The patient underwent 

surgical skin biopsy of the nodule of the forearm, and histologic 

examination revealed the presence of tuberculoid structures with 

neutrophils and macrophages (Figure 2). Results from periodic 

acid-Schiff and Ziehl-Neelsen stains were negative. Cultures taken 

from the lesions were negative for bacilli or atypical mycobacteria. 

Chest and right hand radiological evaluations were normal. The 

patient reported an episode of headache after doxycycline intake, 

a ciprofloxacin-associated morbilliform eruption, and frequent 

gastrointestinal symptoms after drug administration. She told 

us she could receive azithromycin without a problem; therefore, 

we decided to try azithromycin 500 mg (tabs Zinfect 

500 mg, Verisfield, Athens, Greece) 3 times a week for 2 months 

and re-evaluation. To our surprise, complete clinical cure was 

obtained after 8 weeks of treatment (Figure 3). No relapse has been 

observed after 10 months of follow-up. 

M marinum infection, also called “fish tank granuloma,” 

“aquarium granuloma,” or “swimming pool granuloma” seems to 

represent an opportunistic disease and occurs after approximately 

2 weeks of direct (traumatic) inoculation of the organism either 

from fish fins and bites or from the handling of aquariums. 1 

Solitary red-to-violaceous plaques or nodules with an overlying 

crust or verrucous and/or ulcerate surface is a common clinical 

presentation in immunocompetent patients. Inflammatory 

Figure 2. Histologic examination revealed the presence of 

tuberculoid structures (hematoxylin and eosin stain, original 

magnification ×100). 




nodules, abscesses with a sporotrichotic type of distribution, 

followed by nodular lymphangitis can develop in severely immunosuppressed 

patients. 3 Over a period of months, involvement 

of deeper soft tissues (tenosynovitis, arthritis, bursitis, and/or 

osteomyelitis of the underlying bone) may be life- threatening. 4 

Lesions may be either painful or painless. Lung involvement, 

disseminated infection, and bacteremia have been rarely 

reported. 1 

The organism can be isolated from the lesion as well as from 

infected fish or aquariums; however, in clinical practice, 

diagnosis remains largely presumptive based on clinicohistologic 

features. Histopathologic examination usually reveals a nonspecific 

inflammatory infiltrate. 1 

Treatment of M marinum infections is challenging. In superficial 

cutaneous infections, minocycline, clarithromycin, doxycycline, 

Figure 3. Complete clearance of the lesions was achieved 

after 8 weeks of azithromycin treatment. 

55 


trimethoprim sulfamethoxazole, and ciprofloxacine as monotherapy 

are usually effective treatment options. In severe infections, 

a combination of rifampicin and ethambutol seems to be 

the recommended regimen. Surgical treatment is usually unnecessary, 

and where it should be performed must be cautiously 

determined. 1,2 

Azithromycin shows good response in vitro against other than 

Mycobacterium tuberculosis mycobacteria. There is only one 

case of M marinum infection in a patient who underwent lung 

transplantation successfully treated with surgical removal of the 

lesions and a 12-month administration of a combination of 

azithromycin and ethambutol. 5 

Azithromycin seems to be a promising option to treat M marinum 

skin infections, although, further studies—or at least cases—are 

needed to establish the effectiveness of the drug. 

REFERENCES 

FORMULARY OF DR GEORGE C. ANDREWS 

Nail Bleach 

Oxalic acid Gm xxx 

Distilled water 2000 cc 

Perfume Qs ad 

The above may be irritating—ingredients should be on 

poison label with a word of caution. 

Submitted by Douglas D. Altchek, MD, New York, NY 

1 Rallis E, Koumantaki-Mathioudaki E. Treatment of Mycobacterium 

marinum cutaneous infections. Expert Opin Pharmacother. 2007;8: 

2965–2978. 

2 Edelstein H. Mycobacterium marinum skin infections. Report of 

31 cases and review of the literature. Arch Intern Med. 1994;154: 

1359–1364. 

3 Bartralot R, Garcia-Patos V, Sitjas, et al. Clinical patterns of cutaneous 

nontuberculous mycobacterial infections. Br J Dermatol. 

2005;152:727–734. 

4 Wu TS,Chiu CH,Su LH et al. Mycobacterium marinum infection in Taiwan. 

J Microbiol Immunol Infect. 2002;35:42–46. 

5 Torres F, Hodges T, Zamora MR. Mycobacterium marinum infection 

in a lung transplant recipient. J Heart Lung Transplant. 2001;20: 

486–489. 

—Efstathios Rallis, MD, PhD, Department of Dermatology, Veterans 

Administration Hospital (NIMTS), Athens, • E-mail: efrall@otenet.gr; 

Evangelos Falidas, MD, 1st Department of General Surgery, Veterans 

Administration Hospital (NIMTS), Athens; Panagiotis Stavropoulos, MD, 

PhD, Department of Dermatology, University of Athens, “A.Syggros” 

Hospital, Athens, Greece

THE Aesthetic Show 

of the Year 

Register with Promo Code TAS3AD: 

�� 

�� 

��Aesthetic TV 

World-Class Faculty 

Pre-Show Educational Sessions 

Advanced Hands-On Training 

THE Aesthetic Awards 

Patient Tx Workshops 

TM 

To register visit www.aestheticshow.com or call + 1 (949) 830-5409

CANCUN CANCUN 2012 

2012 

January 31st to February 4th 

Cancun Quintana Roo, Mexico 

www.WCOCD2012.com 

info@WCOCD2012.com 

+ (52 55) 5531- 0865 

+ (52 55) 5203- 6454 

Abstract submission deadline: 

October 30th, 2011

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

�� 

��

Locoid Lipocream ® Cream, 0.1% Rx Only 

(hydrocortisone butyrate 0.1% cream) 

For Topical Use Only 

BRIEF SUMMARY 

INDICATIONS AND USAGE 

Locoid Lipocream is a topical corticosteroid indicated for: relief of the inflammatory 

and pruritic manifestations of corticosteroid-responsive dermatoses in adults and 

the treatment of mild to moderate atopic dermatitis in patients 3 months to 18 years 

of age. 

WARNINGS AND PRECAUTIONS 

Reversible hypothalamic-pituitary-adrenal (HPA) axis suppression may occur, with 

the potential for glucocorticosteroid insufficiency. Consider periodic evaluations for 

HPA axis suppression if Locoid Lipocream is applied to large surface areas or used 

under occlusion. If HPA axis suppression is noted, reduce the application frequency, 

discontinue use, or switch to a lower potency corticosteroid. 

Systemic effects of topical corticosteroids may also include manifestations of 

Cushing’s syndrome, hyperglycemia, and glucosuria. 

Pediatric patients may be more susceptible to systemic toxicity due to their larger 

skin surface-to-body-mass ratios. 

Initiate appropriate therapy if concomitant skin infections develop. 

Discontinue use if irritation develops. 

ADVERSE REACTIONS 

The most common adverse reactions (>1%) are HPA axis suppression and 

application site reactions. 

The following additional local adverse reactions have been reported infrequently 

with topical corticosteroids, and they may occur more frequently with the use of 

occlusive dressings and higher potency corticosteroids. These reactions included: 

irritation, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, 

allergic contact dermatitis, secondary infection, skin atrophy, striae, miliaria and 

telangiectasia. 

USE IN SPECIFIC POPULATIONS 

Pregnancy 

Pregnancy Category C. Corticosteroids have been shown to be teratogenic in 

laboratory animals when administered systemically at relatively low dosage levels. 

Some corticosteroids have been shown to be teratogenic after dermal application 

in laboratory animals.There are no adequate and well-controlled studies in 

pregnant women. Therefore, Locoid Lipocream should be used during pregnancy 

only if the potential benefit justifies the potential risk to the fetus. 

Please refer to full prescribing information for detailed information regarding 

systemic embryofetal development studies. 

Nursing Mothers 

Systemically administered corticosteroids appear in human milk and could 

suppress growth, interfere with endogenous corticosteroid production, or cause 

other untoward effects. It is not known whether topical administration of 

corticosteroids could result in sufficient systemic absorption to produce detectable 

quantities in human milk. Because many drugs are excreted in human milk, caution 

should be exercised when Locoid Lipocream is administered to a nursing woman. 

Pediatric Use 

Safety and efficacy in pediatric patients below 3 months of age have not been 

established. 

Because of higher skin surface-to-body-mass ratios, pediatric patients are at a 

greater risk than adults of HPA axis suppression when they are treated with topical 

corticosteroids. They are therefore also at a greater risk of glucocorticosteroid 

insufficiency after withdrawal of treatment and of Cushing’s syndrome while on 

treatment. 

Eighty-six (86) pediatric subjects (5 months to less than 18 years of age) with 

moderate to severe atopic dermatitis affecting at least 25% of body surface area 

(BSA) treated with Locoid Lipocream three times daily for up to 4 weeks were 

assessed for HPA axis suppression. The disease severity (moderate to severe 

atopic dermatitis) and the dosing regimen (three times daily) in this HPA axis study 

were different from the subject population (mild to moderate atopic dermatitis) and 

the dosing regimen (two times daily) for which Locoid Lipocream is indicated. 

Five of the 82 evaluable subjects (6.1%) demonstrated laboratory evidence of 

suppression, where the sole criterion for defining HPA axis suppression was a 

serum cortisol level of less than or equal to 18 micrograms per deciliter after 

cosyntropin stimulation. Suppressed subjects ranged in age from 5 months to 

16 years and, at the time of enrollment, had 25% to 95% BSA involvement. These 

subjects did not develop any other signs or symptoms of HPA axis suppression. 

At the first follow up visit, approximately one month after the conclusion of 

treatment, cosyntropin stimulation results of all subjects had returned to normal, 

with the exception of one subject. This last subject recovered adrenal function by 

the second post treatment visit, 65 days post-treatment. 

Cushing’s syndrome, linear growth retardation, delayed weight gain, and 

intracranial hypertension have also been reported in pediatric patients receiving 

topical corticosteroids. Manifestations of adrenal suppression in pediatric patients 

include low plasma cortisol levels to an absence of response to ACTH stimulation. 

Manifestations of intracranial hypertension include bulging fontanelles, headaches, 

and bilateral papilledema. 

Geriatric Use 

Clinical studies of Locoid Lipocream did not include sufficient numbers of subjects 

aged 65 and over to determine whether they respond differently from younger 

subjects. 

Carcinogenesis, Mutagenesis, Impairment of Fertility 

No studies were conducted to determine the photococarcinogenic or dermal 

carcinogenic potential of Locoid Lipocream. 

Hydrocortisone butyrate revealed no evidence of mutagenic or clastogenic 

potential based on the results of two in vitro genotoxicity tests (Ames test and 

L5178Y/TK + mouse lymphoma assay) and one in vivo genotoxicity test (mouse 

micronucleus assay). 

No evidence of impairment of fertility or effect on mating performance was 

observed in a fertility and general reproductive performance study conducted in 

male and female rats at subcutaneous doses up to and including 1.8 mg/kg/day 

(0.7X maximum topical human dose [MTHD]). Mild effects on maternal animals, 

such as reduced food consumption and a subsequent reduction in body weight gain, 

were seen at doses ≥0.6 mg/kg/day (0.2X MTHD). 

PATIENT COUNSELING INFORMATION 

Patients using Locoid Lipocream should receive the following information 

and instructions: 

Apply a thin layer to the affected skin two or three times daily for corticosteroidresponsive 

dermatoses in adults. Consult with your physician to determine if 

treatment is needed beyond 2 weeks. Apply a thin film to the affected skin areas 

two times daily for atopic dermatitis in patients 3 months of age and older. 

Safety of Locoid Lipocream in pediatric patients has not been established beyond 4 

weeks of use. 

Rub in gently. 

Avoid contact with the eyes. 

Do not bandage, otherwise cover, or wrap the affected skin area so as to be 

occlusive unless directed by your physician. 

Do not use Locoid Lipocream in the diaper area, as diapers or plastic pants may 

constitute occlusive dressings. 

Do not use Locoid Lipocream on the face, underarms, or groin areas unless 

directed by your physician. 

If no improvement is seen within 2 weeks, contact your physician. 

Do not use other corticosteroid-containing products while using Locoid Lipocream 

without first consulting your physician. 

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled 

Room Temperature]. Protect from freezing. Keep out of the reach of children. 

Manufactured for: Triax Pharmaceuticals, LLC 

Cranford NJ 07016 

By: Ferndale Laboratories, Inc. 

Ferndale MI 48220 

Locoid Lipocream is a registered trademark of 

Astellas Pharma Europe BV licensed to 

Triax Pharmaceuticals, LLC. 

Marketed and Distributed By: 

Triax Pharmaceuticals, LLC 

Cranford NJ 07016 

www.Locoid.com 

131B301 

Rev 11/09

Now younger eczema 

patients have something 

to smile about 

Now approved for use in children 

down to 3 months of age 

The power of an ointment with the elegance of a cream 

Locoid Lipocream is indicated for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses, 

including the treatment of mild to moderate atopic dermatitis in patients 3 months of age and older. 

Safety and effectiveness in pediatric patients below 3 months of age have not been established. 

Reversible HPA axis suppression may occur, with the potential for corticosteroid insufficiency. Consider periodic evaluations for HPA 

axis suppression if applied to large surface areas or used under occlusion . Systemic effects of topical corticosteroids may also include 

manifestations of Cushing’s syndrome, hyperglycemia, and glucosuria. Pediatric patients may be more susceptible to systemic toxicity 

due to their large skin surface-to-body-mass ratios. Initiate appropriate therapy if concomitant skin infection develops. Discontinue use 

if irritation develops. Please see full Prescribing Information on adjacent page. Visit us at www.locoid.com 

(hydrocortisone butyrate 0.1%) Cream 

©2010 Triax Pharmaceuticals, LLC. All rights reserved. Locoid is a registered trademark of Astellas Pharma Europe B.V. licensed to Triax Pharmaceuticals, LLC. LOC-0410-01

January/February 2012 • Volume 10 • Issue 1 - SKINmed Journal

Create successful ePaper yourself

Delete template?

Save as template?