American Academy of Dermatology
63rd Annual Meeting
February 18-22, 2005
New Orleans, LA
Production and publication
of this supplement made possible
by a grant from
Journal of the American Academy of
DERMATOLOGYM arch 2005 • Volume 52 • Number 3
Copyright Ó 2005 by the American Academy of Dermatology, Inc.
Jeffrey D. Bernhard, MD
Thomas G. Cropley, MD
Karen Wiss, MD
55 Lake Avenue North
Worcester, MA 01655
Michael E. Bigby, MD
Andrew Blauvelt, MD
Jean L. Bologonia, MD
New Haven, Connecticut
Luis A. Diaz, MD
Chapel Hill, North Carolina
Jane M. Grant-Kels, MD
Mark Lebwohl, MD
New York, New York
Donald J. Miech, MD
Ginat W. Mirowski, MD
Scott A. Norton, MD
Elise Olsen, MD
Durham, North Carolina
Army S. Paller, MD
Stuart J. Salasche, MD
Martin A. Weinstock, MD
Providence, Rhode Island
J. Graham Smith, Jr, MD
Richard L. Dobson, MD
Charleston, South Carolina
POSTER DISCUSSION SESSIONS
Production and publication of this supplement made possible by
a grant from Abbott Immunology
PDS 491—Psoriasis P1
PDS 492—Lasers in Dermatology P3
PDS 493—Acne P4
PDS 494—Infections and Anti-ineffectives P6
PDS 495—Pediatrics P8
Art, History, and Humanities of Dermatology P33
Basic Science P36
Clinical Dermatology and Other Cutaneous Disorders P41
Connective Tissue Diseases P65
Dermatitis (Atopic) P66
Dermatitis (Contact and Allergic Irritant) P75
Digital/Electronic Technology P97
Continued on page 2A
March 2005 VOLUME 52 NUMBER 3
JOURNAL OF THE AMERICAN ACADEMY OF
Statements and opinions expressed in the articles and communications herein are those of the author(s)
and not necessarily those of the Editor(s), publisher, or Academy, and the Editor(s), publisher, and Acad-
emy disclaim any responsibility or liability for such material. Neither the Editor(s), publisher, nor the Acad-
emy guarantees, warrants, or endorses any product or service advertised in this publication, nor do they
guarantee any claim made by the manufacturer of such product or service.
Education and Teaching in Dermatology P99
Epidemiology and Health Services Administration P102
Hair and Nail Disorders P111
Immunodermatology and Blistering Disorders P115
Infection (Bacterial) P117
Infection (Fungal) P121
Infection (Viral, including AIDS) P131
Internal Medicine Dermatology P134
Lymphoma, Cutaneous/Mycosis Fungoides P137
Melanoma and Pigmented Lesions P143
Nonmelanoma Skin Cancer P147
Pediatric Dermatology P151
Photobiology, Phototherapy, and Photosensitivity Diseases P157
Pigmentary Disorders and Vitiligo P167
Psoriasis and Other Papulosquamous Disorders P171
Skin Anatomy, Embryology, and Physiology P205
Surgery (Cosmetic) P205
Surgery (Dermatologic) P206
Surgery (Laser) P208
Wound Healing and Ulcers P210
Author Index 214
Subject Index 223
2A MARCH 2005 J AM ACAD DERMATOL
POSTER DISCUSSION SESSION 491—PSORIASIS
ETANERCEPT THERAPY IN PSORIASIS PATIENTS WITH UNDERLYING
Erin Allen, MD, Yadira Hurley, MD, Saint Louis University, St. Louis, MO, United
States; Craig Leonardi, MD, Central Dermatology, St. Louis, MO, United States
Few systemic therapies exist for patients with moderate to severe psoriasis and
hepatitis C. Patients who require systemic treatment of their skin disease are at
increased risk for hepatotoxicity with oral retinoids and methotrexate. Cyclosporine
is relatively contraindicated because of its immunosuppressive effects. Pho-
totherapy is usually the preferred treatment modality; however, its use is frequently
limited by inconvenience. Furthermore, psoriasis can worsen when interferon
therapy is used to treat the hepatitis C virus (HCV) infection, presumably because of
a shift in the Th1 population of CD4 cells. Tumor necrosis factor (TNF)-a contributes
to the pathogenesis of chronic viral hepatitis. Elevated levels of TNF-a are found in
serum and liver tissue samples from patients with hepatitis C and correlate with
elevated serum aminotransferases as well as histopathologic liver damage. TNF-a,
among other cytokines, also plays a role in psoriasis. Given the role of TNF in both
diseases, it is rational to use an anti-TNF therapy. Etanercept neutralizes the
proinﬂammatory effects of TNF by preventing TNF-a and TNF-b from binding to
their receptors. Etanercept may therefore offer a new therapeutic option for
patients with extensive psoriasis and HCV. We present a case series of 5 psoriasis
patients with underlying HCV who were treated with etanercept and report liver
transaminases, viral load, and psoriasis response. In general, etanercept therapy was
well tolerated, with most patients experiencing decreased HCV viral loads.
All authors have participated in clinical trials for etanercept. Drs. Hurley and
Leonardi have also participated in trials for other biologic therapies. Dr. Leonardi is
on the advisory boards of Amgen, Centocor, Genentech, and Serono, and he has
received grant support from Amgen and Genentech.
COMPARISON OF BIOLOGIC THERAPIES FOR THE TREATMENT OF
William Abramovits, MD, Texas Dermatology Research Institute, Dallas, TX,
United States; Lisa Stevenson, BA, MS II
This is an improved and updated version of the highly covered poster (from AAD
2004) comparing the 5 biologics (adalimumab, alefacept, efalizumab, etanercept,
and inﬂiximab) currently indicated for psoriasis and psoriatic arthritis. The brand
names will be removed to comply with AAD Guidelines.
The cost of therapy for each of the biologics is adjusted for the current year, and new
data on the more recently approved indications are presented in a very objective
William Abramovits, MD, has received research support and/or is a consultant
and/or lecturer for the following: Abbott Laboratories, Allergan, Inc., Amgen, Inc.,
Astralis, Inc., Berlex, Inc., Biogen Idec, Bradley Pharmaceuticals, Brymill
Cryogenics, Centocor, Inc., Collagenex Pharmaceuticals
Connetics Corporation, Corixa Corporation, Dermik Laboratories, Doak
Dermatologics Ferndale Laboratories, Inc., Fujisawa Healthcare, Inc., Galderma,
GlaxoSmithKline, IDEC Corporation, Ligand Pharmaceuticals, Medicis,
Novartis Pharmaceuticals, Otsuka Pharmaceutical, Inc., Protein Design Labs, Serono
Synta Pharma, and 3M Pharmaceuticals.
CESSATION OF CYCLOSPORINE THERAPY BY TREATMENT WITH
ETANERCEPT IN PATIENTS WITH SEVERE PSORIASIS
Paul Yamauchi, MD, PhD, Nicolas Lowe, MD, Clinical Research Specialists,
Santa Monica, CA, United States; Supin Koo, PhD, Amgen, Thousand Oaks, CA,
This case series includes 8 patients (5 females, 3 males) who presented with severe
plaque psoriasis. The average Psoriasis Area and Severity Index (PASI) score was
22.1. One patient also had psoriatic arthritis. Patient ages ranged from 23 to 61 years
(mean 40.2). Cyclosporine therapy (200 mg twice daily) was initiated in an effort to
obtain a rapid improvement in symptoms, and patients were examined every 4
weeks to monitor their progress. Blood pressure, complete metabolic panels,
complete blood cell counts, and lipid panels were measured once a month during
cyclosporine therapy. On average, the patients achieved PASI score improvement of
50% to 75% within 4 to 6 weeks of initiating cyclosporine. The most common
adverse events with cyclosporine therapy were fatigue (n = 5), arthralgia (n = 3),
hirsutism (n = 2), and myalgia (n = 3). One patient had flu-like symptoms (fever,
chills, arthralgia, and myalgia) for 1 week after starting cyclosporine. No hyperten-
sion or nephrotoxicity was noted. Once a PASI 50 to 75 response was achieved,
treatment with etanercept (50 mg/wk) was initiated to assist in tapering patients off
cyclosporine. (The recommended starting dose of etanercept for adult patients is
a 50-mg dose given twice weekly [administered 3 to 4 days apart] for 3 months
followed by a reduction to a maintenance dose of 50 mg/wk.) After 2 to 4 weeks of
combination therapy, the dose of cyclosporine was reduced by 100 mg/d for 2 to 4
weeks until the patients were maintained on 100 mg/d of cyclosporine for at least 2
to 4 weeks. The cyclosporine dose was then reduced to 100 mg every other day for 2
to 4 weeks, at which point the cyclosporine therapy was discontinued and patients
were maintained on etanercept monotherapy. Clinical improvements were main-
tained throughout the tapering period and for at least 12 weeks after cyclosporine
discontinuation. The patient who had psoriatic arthritis had improvement of joint
pain with cyclosporine therapy, and that improvement was maintained with
etanercept monotherapy. There was no additional toxicity when etanercept was
added to cyclosporine therapy or when patients received etanercept monotherapy.
No patients experienced serious adverse events. All 8 patients were successfully
tapered off cyclosporine therapy by the addition of etanercept treatment.
Dr. Yamauchi is a consultant, principal investigator, and speaker for Amgen but has
no proprietary interest in the company. Dr. Lowe is a member of the Speakers
Bureau for Amgen. Dr. Koo is an employee of Amgen.
Writing support and poster production provided by Immunex Corporation,
a wholly owned subsidiary of Amgen Inc., and by Wyeth Research.
MAINTENANCE OF EFFICACY AND SAFETY WITH CONTINUOUS
EFALIZUMAB THERAPY IN PATIENTS WITH MODERATE TO SEVERE
CHRONIC PLAQUE PSORIASIS: FINAL PHASE IIIb STUDY RESULTS
Alice Gottlieb, MD, UMDNJ—Robert Wood Johnson Medical School, New
Brunswick, NJ, United States; Kenneth Gordon, MD, Loyola University Medical
Center, Maywood, IL, United States; Tiffani Hamilton, MD, Atlanta Dermatology,
Vein & Research Center, LLC, Alpharetta, GA, United States; Craig Leonardi, MD,
Saint Louis University School of Medicine, St. Louis, MO, United States
Efalizumab inhibits multiple key T-cell events in psoriasis pathogenesis. An ongoing
open-label, phase IIIb study is evaluating up to 3 years of efalizumab therapy for
patients with moderate to severe chronic plaque psoriasis. Patients who achieved
$50% improvement in Psoriasis Area and Severity Index (PASI-50) or a static
Physician Global Assessment of mild, minimal, or clear after 12 weeks relative to
baseline could enroll in the maintenance treatment phase and receive up to 33
additional months of continuous efalizumab therapy. During maintenance treat-
ment, separate analyses were performed in 3-month segments using 3 different
patient populations: intent-to-treat (ITT; n = 339), maintenance group (all patients
who were eligible for and entered the maintenance therapy phase; n = 290), and as-
treated (n varies because of discontinuations). At week 12, 41% and 13% of patients
achieved PASI-75 and PASI-90, respectively. At month 30, PASI-75 responses were
50% in the ITT population, 58% in the maintenance group, and 78% in the as-treated
population (n = 159). PASI-90 responses at month 30 were 29% for ITT, 34% for
maintenance group, and 45% for as-treated patients (n = 159). No new common
($5% of patients) adverse events emerged during continuous long-term therapy.
There was no evidence of a trend toward an increasing rate of clinically significant
adverse events with continued therapy. The rate of withdrawal from the study
during any given 3-month segment was low and steady during maintenance therapy.
Up to 30 months of continuous efalizumab therapy maintained efficacy and
a favorable safety profile, providing patients with the potential for continuous
control of psoriasis. This is the longest continuous time period that any group of
psoriasis patients has been followed on a biologic therapy. The final study results,
representing 36 months of continuous efalizumab therapy, will be presented.
100 percent sponsored by Genentech, Inc.
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
MARCH 2005 J AM ACAD DERMATOL P1
SUSTAINED IMPROVEMENTS IN PATIENT-REPORTED OUTCOMES IN
PSORIATIC ARTHRITIS PATIENTS TREATED WITH ETANERCEPT
Philip Mease, MD, Seattle Rheumatology Associates, Seattle, WA, United States;
Alice Gottlieb, MD, PhD, UMDNJ—Robert Wood Johnson Medical Center, New
Brunswick, NJ, United States; J. Michael Woolley, PhD, Amgen Inc., Thousand
Oaks, CA, United States; Meleana Dunn, MS
Objective: To evaluate patient-reported outcomes of psoriatic arthritis patients
taking etanercept in an open-label extension study for up to 2 years.
Methods: Two hundred ﬁve patients originally participated in a 24-week, double-
blind, placebo-controlled study of etanercept 50 mg weekly versus placebo. The
study was then followed by a maintenance phase for up to 24 weeks, where patients
were kept on their blinded drug and after that, an open-label extension phase (48
weeks) where all patients (originally on placebo or originally on etanercept)
received etanercept 25 mg twice weekly. Patient-reported outcomes collected in the
trial included the Health Assessment Questionnaire (HAQ) and Short-Form 36 (SF-
36). Norm-based scoring was used for scoring the SF-36. Data on patient-reported
outcomes for up to 2 years were reported.
Results: There were 169 patients (81originally on placebo; 88 originally on
etanercept) in the open-label extension study. At baseline, the mean HAQ disability
index (HAQ DI) was 1.1 for both groups of patients (etanercept and placebo); the SF-
36 physical component summary (PCS) was 35.8 for etanercept patients and 35.7
for placebo patients; and the SF-36 mental component summary (MCS) was 50.9 for
etanercept patients and 48.4 for placebo patients, indicating signiﬁcant impairment
in functional status and physical health but approximately normal mental health. At
the start of the open-label phase, mean HAQ DI improvement from baseline was 0.7
for etanercept patients and 0.1 for placebo patients; PCS scores improved by 10.9 for
etanercept patients versus 1.0 for placebo patients and MCS scores improved by 2.8
for etanercept patients versus 0.4 for placebo patients. During the open-label phase,
patients who were originally on etanercept continued to show sustained improve-
ments in their patient-reported outcomes, whereas patients originally on placebo
and switched to etanercept in the open-label phase showed substantial improve-
ments. After 96 weeks of combined double-blind, maintenance, and open-label
treatment, etanercept patients (n = 61) reported a mean improvement of HAQ DI
of 0.7, a mean PCS improvement of 12.6, and a mean MCS improvement of 1.4.
Conclusions: Psoriatic arthritis patients taking etanercept had signiﬁcant and
clinically meaningful improvements in their functional status and health-related
quality of life as demonstrated by the HAQ and SF-36. These improvements were
sustained for up to 2 years.
Dr. Mease receives grant support from Amgen for conducting clinical trials and is
a consultant for and a member of the speakers bureau for Amgen.
Research funded by Immunex Corporation, a wholly owned subsidiary of Amgen
Inc., and by Wyeth Research.
ADALIMUMAB IN PSORIATIC ARTHRITIS: 24-WEEK RESULTS OF A PHASE
Philip Mease, MD, University of Washington School of Medicine, Seattle, WA,
United States; Dafna Gladman, MD, University of Toronto, Toronto, ON, Canada;
Christopher Ritchlin, MD, University of Rochester, Rochester, NY, United States;
Mark Weinberg, MD, Abbott Laboratories, Abbott Park, IL, United States
Introduction: Tumor necrosis factor (TNF) is present in increased concentrations in
the joints and skin of patients with psoriatic arthritis (PsA). Effective therapeutic
approaches would simultaneously impact the pathophysiology in both areas.
Objective: To evaluate the efﬁcacy and safety over 24 weeks of 40-mg adalimumab
administered subcutaneously every other week (eow) compared with placebo in
patients with active PsA.
Methods: In this phase III, placebo-controlled, double-blind study, adult patients
were enrolled if they had active PsA and had failed nonsteroidal anti-inﬂammatory
drug therapy. Screening for active and latent tuberculosis was performed. Patients
were stratiﬁed by methotrexate use and degree of psoriasis. Efﬁcacy and safety
evaluations were performed at baseline and throughout the study, including the PASI
in patients with[3% body surface area involvement, and the ACR response criteria.
Results: Baseline characteristics for the 313 patients were well matched between
study arms and were consistent with active PsA (mean 6 SD; PASI 7.9 6 6.7,
duration of Ps 17.2 6 12.3 y, PsA 9.5 6 8.5 y); 50% were taking concomitant
methotrexate and 69 patients per group were eligible for PASI evaluation. Of those
enrolled, 289 completed the 24-week study (92% from each arm). Response was
rapid, with 36% of patients receiving adalimumab achieving a PASI 50 response after
4 weeks of therapy, compared with 7% of placebo patients. Week 12 PASI 50/75/90
responses (%) were 71, 48, 30 for adalimumab, and 14, 4, 0 for placebo. Week 24
results were 74, 60, 41 and 13, 1, 0, respectively. Week 24 ACR 20/50/70 responses
(%) were 56, 39, 23 for adalimumab, and 15, 6, 1 for placebo. These PASI and ACR
results were statistically signiﬁcant (P .001 adalimumab vs. placebo). Adverse
events (AE) and serious AE (SAE) observed were similar to those reported in
adalimumab rheumatoid arthritis trials. The number of patients with any AE was 121
(80%) and 130 (80%) for adalimumab- and placebo-treated patients, respectively, and
5 (3%) and 7 (4%) for any SAE, respectively. Most commonly reported ($5%) AE from
either group were URI, injection site reaction, nasopharyngitis, liver function test
elevations, hypertension, PsA and Ps aggravated, arthralgia, and diarrhea.
Conclusions: Adalimumab treatment, 40 mg eow, was effective in treating the signs
and symptoms of PsA. Treatment was well tolerated, with a similar safety proﬁle as
that observed in patients with rheumatoid arthritis.
Financial relationships with Abbott Laboratories: Dr. Mease writes research grants,
receives consulting fees, and in on the Abbott Laboratories speaker’s bureau.
Dr. Gladman is a clinical investigator for and it on the advisory board of Abbott
Laboratories. Dr. Ritchlin writes research grants for Abbott Laboratories.
Dr. Weinberg is employed by Abbott Laboratories.
Abbott Laboratories supported this study and the printing of this poster.
LONG-TERM USE OF ALEFACEPT: EFFICACY AND OFF-TREATMENT
RESPONSES IN PATIENTS WHO HAVE RECEIVED MULTIPLE COURSES OF
Alan Menter, MD, Baylor University Medical Center, Dallas, TX, United States;
Diane Baker, MD, Allergy, Asthma, and Dermatology Research Center, Lake
Oswego, OR, United States; Harold Farber, MD, Harold F. Farber, MD and
Associates, Clinical Research, Philadelphia, PA, United States; Mark Lebwohl, MD,
Mt. Sinai School of Medicine, New York, NY, United States
Alefacept is a fully human LFA-3/IgG1 fusion protein that inhibits T-cell activation
and stimulates apoptosis of memory (CD45RO+) T cells, which have been
implicated in psoriasis pathogenesis. Alefacept is the ﬁrst biologic agent approved
for the treatment of adult patients with chronic plaque psoriasis. The safety and
efﬁcacy of alefacept, administered as a once-weekly injection for 12 weeks followed
by a 12-week observation period, are well documented for 1 and 2 courses of
therapy. In clinical trials, patients treated with alefacept 15 mg intramuscularly once
weekly for 12 weeks had signiﬁcant improvements in psoriasis, with 33% and 57%
achieving a $75% or $50% reduction in PASI (PASI 75 and PASI 50), respectively. A
second 12-week course of alefacept increased these response rates to 43% and 69%,
respectively. Further analysis of the data indicates that patients who respond during
the ﬁrst course of therapy have an 80% likelihood of achieving at least the same, if
not greater, response with a second course of therapy. Patients who achieve 50%
improvement after one course have an approximately 40% chance of achieving
a PASI 50 with the second course. A small percentage of patients who had little to no
beneﬁt, deﬁned as25% improvement from baseline PASI, with one course achieve
PASI 50 during or after the second course of alefacept therapy. As part of the clinical
development program of alefacept, patients who completed phase 2 and 3 studies
were eligible to participate in open-label extension studies to determine the safety
and efﬁcacy of repeated courses of alefacept. A cohort of patients has received up to
9 courses of therapy over 4.5 years. Data from these extension studies will be pooled
to determine repeat response rates and incremental beneﬁt with multiple courses of
alefacept. Analysis of multiple-course data shows that patients’ response with
additional treatment to alefacept is incrementally beneﬁcial regardless of response
to initial treatment. Additionally, no tachyphylaxis was observed throughout
multiple courses of alefacept therapy.
Dr. Menter has received research support and consultancies from Biogen Idec, Inc.
Supported by Biogen Idec Inc.
LONG-TERM SAFETY AND EFFICACY OF ADALIMUMAB IN THE TREATMENT
OF MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS
Richard Langley, MD, Dalhousie University, Halifax, NS, Canada; Craig Leonardi,
MD, Central Dermatology, St. Louis, MO, United States; Darryl Toth, MD, Probity
Medical Research, Windsor, ON, Canada; Diana Chen, MD, Abbott Laboratories,
Abbott Park, IL, United States
Background: Psoriasis is an immune-mediated disorder characterized by inﬂamma-
tion and thickening of the epidermis causing thick scaly plaques on the skin.
Previously reported data demonstrated adalimumab is efﬁcacious in the treatment of
plaque psoriasis. Adalimumab is a fully human, monoclonal IgG1 antibody against
Objective: To evaluate the long-term safety and efﬁcacy of adalimumab in the
treatment of moderate to severe chronic plaque psoriasis.
Methods: Patients with moderate to severe plaque psoriasis enrolled in a 12-week,
double-blind, placebo-controlled study (M02-528) and were randomized to one of
three treatment arms: (1) adalimumab 80 mg subcutaneous (sc) at week 0 followed
by 40 mg sc every other week (eow) beginning at week 1; (2) adalimumab 80 mg sc
at week 0 and 1 followed by 40 mg sc weekly starting at week 2; and (3) placebo
weekly beginning at week 0. Patients who completed this initial trial were eligible to
continue in a 48-week extension trial (M02-529) that remained blinded through
the ﬁrst 12 weeks. In the extension trial, patients who received adalimumab
during the initial study continued their assigned doses. Patients on placebo received
80 mg the ﬁrst week, and 40 mg eow thereafter. After week 12 in the extension
study, patients who had a Psoriasis Area and Severity Index (PASI) response 50%
increased to weekly dosing for at least 8 weeks. The primary analysis of the
extension study was the percentage of patients achieving a PASI response $75% at
week 12. Safety and efﬁcacy information was collected throughout the study.
Results: One hundred forty-eight patients at 18 sites in the US and Canada enrolled
in the initial study. One hundred thirty-seven patients completed week 12 and
continued in the extension study. Of these, 43 patients were in the adalimumab 40
mg eow arm, 47 were in the weekly arm, and 47 were in the placebo/40 mg eow
arm. Patients were predominantly male (70.1%) and white (89.8%) with a mean age
of 44 years (range 20-86). At entry into the initial study, mean duration of psoriasis
was 19.4 years, mean PASI score was 15.7, and mean BSA was 27.2%. At week 12 of
the extension study (24 weeks of continuous treatment with adalimumab), 67% of
patients in the eow arm and 77% of patients in the weekly arm achieved a $ PASI 75
response. A PASI 90 response or better was achieved in 44% and 66% of patients in
the eow and weekly treatment arms, respectively. Additional efﬁcacy and safety data
through week 48 will be presented.
Drs. Langley, Leonardi, and Toth are primary investigators for Abbott Laboratories.
Dr. Chen is employed by Abbott Laboratories.
100 percent sponsored by Abbott Laboratories
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
P2 J AM ACAD DERMATOL MARCH 2005
POSTER DISCUSSION SESSION 492—
LASERS IN DERMATOLOGY
COMPARATIVE STUDY OF PULSED DYE AND EXCIMER LASERS IN
TREATMENT OF PSORIASIS
Saleem Taibjee, MBChB, Seau-Tak Cheung, MBChB, Laube Simone; Sean Lanigan,
MBBS, MD, Lasercare Clinics, Birmingham, England
Background and objectives: This is the ﬁrst comparative study of the pulsed dye laser
(PDL) and excimer laser in plaque psoriasis treatment.
Methods: We conducted a within-patient controlled prospective trial of treatment of
localized plaque psoriasis with the PDL and excimer laser. Twenty-two adult patients
with localized plaque psoriasis (mean total body Psoriasis and Area Severity Index
score [PASI] = 7.1) were recruited. Five patients were followed up to 1 year.
Primary outcome measures:
1. Change in modified PASI from baseline to end of treatment for excimer and PDL
2. Comparison of PSI changes in laser-treated and control plaques.
3. Clinical rating of response to treatment (CRT) for excimer and PDL plaques.
4. Comparison of CRT in laser-treated and control plaques.
5. Time to relapse.
Results: Mean improvement in PASI was 4.7 (standard deviation [SD] 2.1) with
excimer and 2.6 (SD 2.2) with PDL, respectively. Mean PASI improvement was
greater in excimer than PDL (P.001) or control plaques (P.001). CRT indicated
14 patients responded better with excimer than PDL, 1 patient better with PDL, and
in 7 patients there was no difference. There were statistically significant differences
in CRT comparing excimer with control (P .001), PDL with SA (P = .004), and
excimer with PDL (P = .001). 8 patients showed complete clearance with excimer,
with both mean and median time to clearance 8.5 weeks (range 4-12 weeks),
equivalent to 17 treatments. Four of these patients were followed up to 1 year,
1 patient relapsing at 1 month, and 1 patient at 6 months and 2 patients remaining
clear. Four patients completely cleared with PDL, requiring a mean of 3 treatments
(range 2 to 4). 2 of these patients were followed up to 1 year, both remaining clear.
Despite common side effects including blistering and hyperpigmentation, patient
satisfaction was high.
Conclusions: Both the excimer and PDL are useful treatments for localized plaque
psoriasis. Although excimer laser was on average more efﬁcacious, a subset of
patients may respond better to PDL. Long-term remission in treated psoriatic
plaques is achievable with both lasers.
No conﬂict of interest other than sponsorship of current research study.
The research study is 100% sponsored by Candela Laser Corporation.
INVESTIGATION OF THE MECHANISM OF NONABLATIVE PULSED-DYE
LASER THERAPY IN ACNE VULGARIS AND PHOTOREJUVENATION
Edward Seaton, Akaterina Charikida, Paul Seldon, Anthony Chu, Department of
Dermatology, Imperial College, London, England
Nonablative laser and light therapies are advocated for photorejuvenation and,
increasingly, acne. Collagen up-regulation occurs after laser therapy, but the
molecular mechanism of this is as yet unclear. Photodestruction of P acnes or
injury to sebaceous glands have been proposed as possible mechanisms of laser in
acne. We investigated the mechanism of nonablative pulsed dye laser therapy, which
has reported efficacy in both acne and photorejuvenation. (wavelength 585 nm,
pulse duration 350 s, fluence 2.5 J/cm2
) We examined the effect of full-face laser
therapy on P acnes colonization density, sebum production and cutaneous cytokine
and collagen production. P acnes density was assessed before and 24 hours after
laser using a scrub-wash technique, with serial dilution and anaerobic culture.
Sebum was collected before and 2, 4, 8, and 12 weeks after laser using lipid
absorbent tape applied to the forehead for 1 hour. Volumetric sebum output was
quantified by photometric computerized analysis. Immediate effects of laser on
production of tumor growth factor (TGF)-a, IL-1a, IL-1aRa, IL-10, procollagen I, and
TNF-a mRNA species were assessed using semiquantitative RT-PCR. RNA was
obtained from skin biopsy specimens at 0, 3, and 24 hours after laser therapy in 8
volunteers. Mean P acnes colonization density was 168,100 cfu/cm2
therapy and 234,200 cfu/cm2
after 24 hours (P = .074; n = 15). Sebum production
at 0, 2, 4, 8, and 12 weeks after laser therapy was respectively 114.0, 114.9, 128.6,
120.1, and 118 nL/cm2
/h. (P [ .05). TGF-a mRNA concentrations at 3 and 24 hours
after laser irradiation were 152.4% (P = .173) and 510.1% (P = .018) with respect to
baseline. Messenger RNA concentrations of IL-1a, IL-1aRa, IL-10, procollagen I, and
TNF-a did not alter significantly in 24 hours. The pathogenesis of acne is
multifactorial, involving increased sebum production, P acnes colonization and
inflammation. Nonablative laser therapy does not reduce P acnes colonization
density or alter sebum production, but induces a fivefold increase in TGF-a mRNA
within 24 hours of treatment. TGF-a is a highly potent growth inhibitor of
lymphocytes, keratinocytes, and macrophages, and blocks stimulation of lympho-
cytes by IL-1. It is produced in wounded skin and stimulates fibroplasia and healing.
We suggest that early up-regulation of TGF-a and the likely subsequent cytokine
cascade is of central importance in both nonablative photorejuvenation and the
inhibition of acne inflammation.
Funded by Euphotonics Limited, the laser manufacturer. The manufacturer has no
inﬂuence on the content of this submission.
EFFICACY OF COMBINATION RED INFRARED LIGHT THERAPY IN FACIAL
Bruce Russell, MD, Advanced Laser Derm Surgery Clinic, PC, Beaverton, OR,
Purpose: To evaluate the safety and utility of combination continuous-wave red and
infrared light for facial rejuvenation.
Statement of research design: Sixteen patients were enrolled and treated. Thrice-
weekly sessions of 830 nm light at 20 minutes continued for 2 weeks, then followed
up with alternating 633- and 830-nm sessions (twice weekly). No topical therapy
was permitted. Photographs were taken before treatment and at each session, along
with 1-, 2-, and 6-month follow-up photographs. Biopsy specimens obtained before
and after treatment were submitted for histologic evaluation.
Summary of results: Improvement was scored for pore size, ﬁne lines, redness, scars,
and dyschromia. All patients had some degree of improvement in one or more
parameters, with best results noted for textural issues. Pigment was less predictable.
Histologic evaluation of biopsy specimens taken before and after treatment shows
evidence of new collagen deposition, telangiectasia reduction, and changes in the
rete ridge pattern. No complications were noted.
Conclusion: Alternating 830- and 633-nm light treatments with continuous-wave
sources shows both textural and color improvements in this small study. Further
work elucidating optimal parameters and dosages of light is necessary and currently
under way, which will provide important information, including durability data.
Nothing to disclose.
PULSED DYE LASER FOR THE TREATMENT OF BASAL CELL CARCINOMA
Keyvan Nouri, MD, Maria Patricia Rivas, MD, Christopher Ballard, BSc, George
Elgart, MD, University of Miami School of Medicine, Department of Dermatology
and Cutaneous Surgery, Miami, FL, United States
Background: Basal cell carcinomas (BCCs) are the most common malignant tumor of
the skin, accounting for approximately 900,000 new cases annually. Surgical and
nonsurgical treatment options available to the BCC patient include Mohs surgery,
cryosurgery, curettage and electrodesiccation, radiotherapy, topical 5-ﬂuorouracil,
imiquimod, and photodynamic therapy. The disadvantage of most treatments is the
high risk of scarring, induced pain, and an increased healing time allowing greater
opportunity for infection. The role of pulsed dye laser (PDL) for treatment of BCC
has not been well studied.
Objective: The purpose of this study was to determine the efﬁcacy of the PDL as
a treatment modality for removal of well-deﬁned noduloulcerative BCCs.
Methods: A total of 7 patients with 9 BCCs were enrolled in this study. Treatment of
the BCC was done using a PDL with the following speciﬁcations: a single 450-s
pulse with 585-nm wavelength, 7-mm spot size, and 9.0 J energy. The lesion along
with a 4-mm border of normal skin were treated. After 1 month, when complete
healing had occurred, cosmetic evaluation of the carcinoma site followed by
excision and histologic evaluation was done.
Results and conclusion: Our results show that the PDL is not effective for the
treatment of BCC.
Nothing to disclose.
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
MARCH 2005 J AM ACAD DERMATOL P3
COMPARISON OF THE EFFECTS OF THE PULSED DYE LASER 585 AND 595
IN THE TREATMENT OF NEW SURGICAL SCARS
Keyvan Nouri, MD, Maria Patricia Rivas, MD, Lauren Singer, BSc, George Elgart,
MD, University of Miami School of Medicine, Department of Dermatology and
Cutaneous Surgery, Miami, FL, United States
Background: Prior studies have shown that the pulsed dye laser (PDL) is effective in
improving the vascularity, color, height, texture and pliability of scars. In previous
studies we have demonstrated improvement in the quality and appearance of the
scar when using the 585-nm PDL immediately after the removal of sutures.
Objective: The objective of this study was to document the effect of 595 nm and to
see whether it is better or equally effective as the 585-nm laser in improving scarring
Methods: A total of 14 patients with 19 scars were enrolled in this study. Scars were
divided randomly into three equal ﬁelds using the central ﬁeld always as the control
region. One third received 450-s 585 nm PDL treatment using 10-mm spot size at
3.5 J. The middle third received no treatment, while the other third received 450-s
595 nm PDL treatment using 10-mm spot size at 3.5 J. The three sections were
mapped and recorded. The patient received treatment immediately after the sutures
were removed from the wound and then monthly for 3 months.
Results and conclusion: Our results show that both 585- and 595-nm PDLs cause
a signiﬁcant improvement of the scar compared with the control. However, there is
no signiﬁcant difference between 585- and 595-nm PDL for the treatment of new
Nothing to disclose.
SELECTIVE PHOTOTHERMOLYSIS OF BLOOD VESSELS FOLLOWING FPDL
TREATMENT IN VIVO
Philipp Babilas, MD, Department of Dermatology, University Hospital, University
of Regensburg, Regensburg, Germany; Gal Shaﬁrstein, MD, PhD, Department of
Otolaryngology, University of Arkansas, Little Rock, AK, United States; Wolfgang
Ba¨umler, MD, PhD, Michael Landthaler, MD, PhD, Department of Dermatology,
University Hospital, University of Regensburg, Regensburg, Germany
Laser therapy is the standard treatment for vascular lesions like port-wine stains
(PWS). The ﬂashlamp-pumped pulsed dye laser (FPDL) with a wavelength of 585 nm
and a pulse duration of 0.45 millisecond is mainly used. However, successful
treatment relies on the laser light absorbed by the endogenous chromophore
hemoglobin and is unsatisfying for many lesions. The goal of this work is to
investigate the effects of the FPDL on blood vessels regarding vessel diameter in vivo
and to correlate the experimental results with the predictions of a mathematical
model. The dorsal skinfold chamber model in hamsters (n = 18) was used for
monitoring the vascular effects of FPDL treatment (l = 585 nm; pulse duration: 0.45
ms; fluence: 6 J/cm2
). Diameters of vessels (n = 3394; ranging from 2 to 186 m)
marked with FITC-dextran (molecular weight 150,000) were measured using
intravital fluorescence microscopy before and 15 minutes, 1 hour, and 24 hours
after irradiation. Histology was taken 1 hour and 24 hours after therapy and tissue
sections were stained with hematoxylin-eosin, NBTC, or CD31. The in vivo results
were correlated with the predictions of a mathematical model based on the finite
element method. FPDL treatment revealed a less pronounced effect on smaller
blood vessels as the number of unperfused vessels increases with increasing
diameter (2-30 m). Overall, 87.1 % of the vessels with a diameter ranging from 30 to
100 m were unperfused at 15 minutes following FPDL treatment lasting up to the
end of the observation time. The correlation of the observed with the calculated
reduction of perfused vessels was in agreement as the corresponding graphs
showed a similar distribution. Histology indicated that 1 hour following treatment,
thermal damage induced immediate coagulation restricted to the irradiated area,
whereas at 24 hours a higher degree of tissue damage not restricted to the irradiated
area was observed. This indicates a delayed biologic response contributing to the
extent of laser-tissue interaction. The experimental results obtained in this model
can be described by a mathematical model. The lack of efficacy regarding the
destruction of smaller vessels (2-25 m) may explain the lack of complete PWS
blanching response in the clinical setting. According to the experimental model, this
is very likely because of the low hematocrit in these vessels.
Nothing to disclose.
HISTOLOGICAL CLEARANCE OF PATCH-STAGE MYCOSIS FUNGOIDES WITH
THE 308 NM EXCIMER LASER
Edward Upjohn, MBBS, Rodney Sinclair, MBBS, Philip Lane, MBBS, Peter Foley,
MD, BS, Skin and Cancer Foundation of Victoria, Melbourne, Australia
Introduction: Mycosis fungoides (cutaneous T-cell lymphoma) is a malignancy of
skin homing T cells. Skin-directed therapies include narrowband ultraviolet B (UVB)
therapy, psoralen plus ultraviolet A therapy, electron beam therapy, bis-chloro-
ethylnitrosyurea (BCNU), and topical nitrogen mustard. These therapies induce
remission and can also be curative; they may, however, also be inconvenient and
carry particular side effects. The xenon chloride (XeCl) laser delivers high-fluence
308 nm light. This wavelength is close to that of narrowband UVB (311-313 nm). It is
thought that the laser will have greater efficacy than narrowband UVB in the
treatment of dermatologic disease because of its ability to deliver greater fluencies.
Improved safety is also a feature of the laser, as treatment areas can be specifically
targeted and unaffected skin spared from UV irradiation.
Methods: Eight patients with patch-stage mycosis fungoides were recruited. All
other treatments had been ceased before enrollment in this study. Treatments with
308-nm excimer laser were administered twice weekly for 10 weeks. The initial dose
was the minimal erythema dose for that patient and dosage was increased as
tolerated. Cumulative doses were recorded. Skin biopsy and photography were
performed before and after treatment, and clinical response was noted in each
Results: One patient withdrew. Six of the remaining 7 patients had a complete
clinical and histologic response. One patient had a partial response. The average
cumulative dose was 7.001 J/cm2
. Aside from expected hyperpigmentation, there
were no side effects or complications of treatment.
Conclusions: This pilot study suggests that the 308-nm excimer laser is a safe and ef-
fective treatment for patients with patch-stage mycosis fungoides. Ongoing follow-up
of these patients will help determine the duration of clinical response.
Nothing to disclose.
POSTER DISCUSSION SESSION 493—ACNE
PULSE-THERAPY WITH AZITHROMYCIN IN ACNE ROSACEA AND
PERIORAL DERMATITIS: AN OPEN STUDY
Caputo Ruggero, MD, Mauro Barbareschi, MD, Stefano Veraldi, MD, Institute of
Dermatologic Sciences, Milan, Italy
Introduction: Azithromycin has already demonstrated to be active in papulopustular
acne where it exerts a speciﬁc inhibitory effect on P acnes. Pulse-therapy with
azithromycin also showed to reduce significantly inflammation in acne areas.
Objectives: On the basis of this observation we carried out an open study to evaluate
the efﬁcacy of azithromycin in patients with two inﬂammatory face dermatosis as
acne rosacea and perioral dermatitis according to a pulsed therapeutic regimen.
Patients and methods: We enrolled 20 patients of both sexes, with ages ranging from
33 to 65 years (mean age 45) affected by acne-rosacea microbiologically negative for
Demodex and 20 female patients suffering from perioral dermatitis with ages
ranging from 16 to 34 years (mean age 20) microbiologically negative for Demodex
or Malassezia spp. The patients with rosacea were classified according to the
criteria of the ‘‘standard grading system for rosacea-global assessment subtypes.’’ The
scheduled treatment for each patients was oral azithromycin 500 mg/d for 3
consecutive days a week for a period ranging between 4 and 8 weeks. In any case
azithromycin was stopped at the eighth week.
Results: In acne rosacea 65% of patients had a clear reduction of clinical symptoms
after 4 weeks of treatment, 75% of patients after 6 weeks of treatment, and almost
90% of patients after 8 weeks of treatment. In perioral dermatitis 60% of patients had
a clear reduction of clinical symptoms after 4 weeks of treatment, 70% of patients
after 6 weeks of treatment, and 85% of patients after 8 weeks of treatment. Gastralgia
was the only side effect we found in two patients.
Conclusions: (1) Azithromycin showed clearly therapeutic effects in either acne
rosacea or perioral dermatitis; (2) clinical observations led us to conclude that
azithromycin has anti-inﬂammatory properties that could be useful in the treatment
of these dermatoses; and (3) the drug is not phototoxic and therefore may also be
used safely in summer.
Culic O, Erakovic V, Cepelak I, et al. Azithromycin-modulated neutrophil function
and circulating inflammatory mediators in healthy human subjects. Eur J
Wilkin J, Dahl M, Detmar M, et al. Standard grading system for rosacea: Report of
the National Rosacea Society Expert Committee on the classification and staging
of rosacea. J Am Acad Dermatol 2004;50:907-12.
Nothing to disclose.
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
P4 J AM ACAD DERMATOL MARCH 2005
TRETINOIN DOWN-REGULATES TOLL-LIKE RECEPTOR-2 EXPRESSION AND
Philip Liu, BS, Sarah Sharfstein, BS, Robert Modlin, MD, University of California at
Los Angeles, Los Angeles, CA, United States
Although treatment of acne with tretinoin (all-trans-retinoic acid) involves an
antiproliferative effect, there is evidence that it also exerts an anti-inflammatory
activity. We hypothesized that this anti-inflammatory activity was mediated by
regulation of toll-like receptors (TLRs) since TLR2 and its co-receptor CD14 is
expressed in acne lesions and is activated by Propionibacterium acnes, a bacterium
that contributes to the pathogenesis of acne. We found that treatment of primary
human monocytes with tretinoin led to the down-regulation of TLR2 and CD14
messenger (m)RNA but not TLR4 mRNA. Furthermore, tretinoin treatment of
monocytes decreased the cell surface expression of TLR2 and CD14, whereas the
expression of TLR4 remained constant. The ability of a TLR2 ligand and P acnes to
trigger monocyte cytokine release was decreased by pretreatment and cotreatment
with tretinoin. However, TLR4 activation of monocytes was affected by cotreatment
but not pretreatment with tretinoin. These data indicate that tretinoin exerts an anti-
inflammatory activity on monocytes via two pathways, one specifically affecting
TLR2/CD14 and one involving the TLR signaling pathway generally.
Dr. Modlin is currently a member of the Johnson Johnson Scientiﬁc Avisory Board.
DEBUNKING THE EXERCISE AND ACNE MYTH: A SINGLE-BLINDED
RANDOMIZED STUDY ON THE EFFECT OF EXERCISE-INDUCED
OCCLUSION ON TRUNCAL ACNE
Yolanda Agredano, BS, Stanford University School of Medicine, Mountain View,
CA, United States; Rebecca W. Short, MD, Alexa B. Kimball, MD, MPH, Stanford
Department of Dermatology, Stanford, CA, United States
Background: In 1975, Mills and Kligman coined the term acne mechanica to
describe a variant of acne vulgaris resulting from mechanical forces on the skin that
they found common in football players. The precise role of exercise and sweat
occlusion in this condition was left undefined, but a perception that exercise
influences acne has persisted.
Objective: To assess the effect of exercise-induced sweat occlusion on truncal acne.
Methods: Thirty physically active adolescent or adult males (mean age 23 years)
capable of breaking a sweat while exercising, with at least 10 inﬂammatory
acneiform lesions on the chest and/or back, were randomized with Research
Randomizer into one of three study groups for this 2-week, Institutional Review
Board-approved, single-blinded study. The study was powered at 90% with a two-
sided alpha of 0.05. Twenty-three subjects completed the study. One group did not
exercise (n = 7), and two groups broke a sweat in 100% cotton T-shirts 5 days per
week while exercising, with one of those groups showering within 1 hour of
exercise (n = 8), and the other showering 4 or more hours after exercising (n = 8).
Inflammatory acne lesions were counted by blinded investigators. Subjective stress
levels were assessed with the 14-item Perceived Stress Scale questionnaire both at
baseline and at the 2-week end visit. SPSS 12.0 was used to analyze the data.
Results: Change in acne from baseline to study end was similar among the 3 study
groups (analysis of variance [ANOVA] P = .956). Stress was similar among the 3
groups (ANOVA baseline P = .141, ANOVA study end P = .619). Change in acne did
not correlate with exercise parameters (number of days exercised, time spent
exercising, time of sweating during exercise, or the time interval between exercising
and taking a shower). Of the subjects in exercise groups, 83% of exercise days were
spent in noncontact activities.
Conclusion: Exercise-induced sweat occlusion does not have a signiﬁcant inﬂuence
on truncal acne.
Mills OH Jr, Kligman A. Acne mechanica. Arch Dermatol 1975;111:481-3.
Nothing to disclose.
MANAGEMENT OF PAPULOPUSTULAR ROSACEA WITH 2% POLYPHENONE
(GREEN TEA EXTRACT) IN A HYDROPHILIC CREAM: A PLACEBO-
CONTROLLED DOUBLE-BLIND STUDY
Tanweer Syed, MD, PhD, University of San Francisco, San Francisco, CA, United
States; Raza Aly, MD, PhD, University of California San Francisco, San Francisco,
CA, United States; Seyed Ali Ahmad, BS, University of California Berkeley,
Berkeley, CA, United States; Wendy Wong, MD, Syed Skin Care, Inc., San
Francisco, CA, United States
Objective: To evaluate the clinical efﬁcacy, tolerability, safety, and beneﬁcial effects
of 2% polyphenone-epigallocatechin gallate [EGCg]) incorporated in a hydrophilic
cream to cure papulopustular rosacea.
Methods: Preselected female subjects (n = 60), 25 to 50 years old, showing visible
signs of papules/pustules were sequentially randomized into two parallel groups. An
identical precoded tube containing 50 g (either active drug or placebo) was
allocated to each subject with instructions on how to topically apply the trial cream
twice a day for 4 weeks. Cure was defined as absence of clinical signs of
inflammation. Photographic and optical techniques were used both at the baseline
and on a weekly basis.
Results: By the end of the study, marked beneﬁcial improvement was observed in
both the groups. Code disclosure revealed that 2% polyphenone in a hydrophilic
cream yielded statistically signiﬁcantly higher reduction in mean inﬂammatory
lesion count than placebo. The most frequently assessed signs of rosacea were
papules/pustules (n = 23), erythema (n = 20), and telangiectasia (n = 17). Using
the investigator’s global assessment, therapeutic success in terms of a clear, minimal,
or mild result was documented in 70% of patients treated with 2% polyphenone
(-EGCg) cream (P .0001).
Conclusion: The study indicates that 2% polyphenone(-EGCg) in a hydrophilic
cream is safe, tolerable, and signiﬁcantly more beneﬁcial in contributing superior
clinical efﬁcacy than placebo to cure papulopustular rosacea in female subjects.
The primary author is a consultant.
75% of this study is sponsored by Syed Skin Care, Inc.
5% DAPSONE TOPICAL GEL: SAFETY AND EFFICACY WITH LONG-TERM
(1 YEAR) TREATMENT FOR ACNE VULGARIS
Janet Roberts, MD, NW Cutaneous Research Specialists, Portland, OR, United
States; Michael Maloney, MD, Cherry Creek Research, Inc., Denver, CO, United
States; Mark Ling, MD, PhD, MedaPhase, Inc., Newman, GA, United States; Anne
W. Lucky, MD, Dermatology Research Associates, Cincinnati, OH, United States
Objective: To evaluate the long-term safety and efﬁcacy of 5% dapsone topical gel
(DTG) in patients with acne vulgaris.
Methods: In this multicenter, open-label, noncomparative study, patients applied
DTG twice daily to acne-involved areas for up to 12 months. Assessments for safety
and efﬁcacy included adverse events (AEs), laboratory analyses, and acne lesion
Results: A total of 506 patients (12-77 years old) were enrolled and 340 patients
completed 12 months of treatment. The majority (80%) was white; 54% were
female. At baseline, mean total facial acne lesion count was 87 (48 inﬂammatory;
38.5 noninﬂammatory). The most commonly reported AEs, regardless of causality,
were headache (20%), common cold/nasopharyhgitis (15%), and pharyngitis (9%).
The most commonly reported application site AEs were dryness (3%), rash (3%), and
sunburn (2%). AEs were generally mild to moderate in severity, transitory, and rarely
(2.3%) led to treatment discontinuation. There was no increase in AEs or laboratory
abnormalities over time. Plasma levels of dapsone were low and remained low
throughout the study. Improvement in acne was observed by month 1 and
continued throughout the study: mean reduction from baseline to month 12 for
inﬂammatory, noninﬂammatory, and total lesion counts was 58.2%, 19.5%, and
Conclusions: DTG 5% appears to be safe and effective for the long-term treatment of
Sponsored by Fujisawa Healthcare, Inc. and Atrix Laboratories, Inc.
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
MARCH 2005 J AM ACAD DERMATOL P5
DAPSONE GEL 5% IS AN EFFECTIVE, SAFE, NOVEL TOPICAL TREATMENT
OF ACNE VULGARIS
David Wilson, MD, The Educational Research Foundation, Inc., Forest, VA,
United States; James Herndon, MD, Stephens and Associates, Carrollton,
TX, United States; David Whiting, MD, Dallas Associated Dermatologists,
Dallas, TX, United States; Alan Shalita, MD, State University of New York,
Brooklyn, NY, United States
Objective: To determine the efﬁcacy and safety of 5% dapsone topical gel (DTG) in
patients with acne vulgaris.
Methods: In this multicenter, double-blind, randomized study, patients at least 12
years of age with facial acne vulgaris applied DTG (n = 330) or vehicle gel (n = 166)
twice daily for 12 weeks. Evaluations for safety and efficacy included the Global
Acne Assessment Score, acne lesion counts, and adverse event incidence rates.
Results: Demographics and baseline disease characteristics were similar between
treatment groups; baseline severity was moderate for the majority (72%) of patients
with mean total lesion counts of 90 (DTG group) and 86 (vehicle group). Sig-
niﬁcantly greater responses were observed for the DTG group, compared with the
vehicle group for all efﬁcacy end points at week 12/end of treatment. Success
(Global Acne Assessment Score of 2 at end of treatment) was signiﬁcantly greater
for the DTG treatment group compared with the vehicle treatment group (26.7% vs
18.7%; P = .042). Treatment with DTG versus vehicle resulted in mean percent
reduction of 37.2% versus 26.6% for inflammatory, 27.5% versus 16.8% for
noninflammatory, and 32.0% versus 21.9% for total lesion counts, (all P .005).
The majority of treatment-related adverse events were application site reactions,
reported by fewer than 2% of patients, mild in severity, and not significantly different
between treatment groups.
Conclusions: Dapsone gel 5% represents a novel, effective, and safe topical therapy
for the treatment of acne vulgaris.
Sponsored by Fujisawa Healthcare, Inc. and Atrix Laboratories, Inc.
HIGH-RESOLUTION IMAGING EVALUATION OF ACNE
Theresa Chen, PhD, Neutrogena Skincare Institute, Los Angeles, CA, United
States; Georgios Stamatas, PhD, Johnson and Johnson Consumer and Personal
Products Worldwide, Skillman, NJ, United States; Huayi Dong, MS, I-Ting Wu, BS,
Neutrogena Skincare Institute, Los Angeles, CA, United States
Acne is a pleomorphic condition. An acne lesion has its beginning in the clogged
pores and follicles long before it becomes visible. The microcomedones, unseen by
eyes, have thus been appropriately referred to as ‘‘the invisible time bombs of acne.’’
Noninvasive methods that can detect acne lesions before they become visible and
also track the course of resolution should enhance understanding of acne etiology
and optimize treatment modality. Several high-resolution imaging methodologies,
including spectral imaging, have been developed and used to evaluate acne in its
visible and invisible states. Also evaluated were the effects of a spot treatment gel on
the dynamics of acne lesion resolution. Although the severity of placebo-treated or
untreated lesions worsened from baseline and peaked at 24 to 48 hours, the gel-
treated lesions showed rapid reduction of erythema, edema, and lesion size within 8
hours after the ﬁrst application. These results demonstrate the power of the imaging
techniques in studying acne and in evaluating acne treatment modality.
The authors are employed by the manufacturer of the products, Neutrogena
Corporation, or its corporate afﬁliate, Johnson and Johnson Consumer and Personal
100% sponsored by Neutrogena Corporation, a Johnson and Johnson Company
POSTER DISCUSSION SESSION 494—
INFECTIONS AND ANTI-INEFFECTIVES
INDUCERS OF EPITHELIAL ANTIMICROBIAL PEPTIDE EXPRESSION:
EXPLORING A NEW POTENTIAL CLASS OF DERMATOLOGIC
Michael Zasloff, MD, PhD, Georgetown University School of Medicine,
Washington, DC, United States; Otto Mills, PhD, Robert Woods Johnson
Medical School, New Brunswick, NJ, United States
Antimicrobial peptides are expressed on the epithelial surfaces of all animals, both
invertebrates, such as insects, and vertebrates, such as humans1
known peptides in human skin include the defensins (HBD1, HBD2, and HBD3) and
the cathelicidin LL-37. These peptides are broad-spectrum effectors active against
bacteria, fungi, and certain viruses and are believed to provide both anti-infective
defense as well as control over the species and number of organisms that normally
reside on the skin. All but HBD1 are inducible, generally after injury and exposure to
a microbial challenge. Considerable information has been gathered regarding the
pathways involved in induction and it is clear that both certain microbial
components as well as certain proinflammatory cytokines can induce the
expression of these peptides. In certain disorders, such as atopic dermatitis, recent
data have suggested that expression of several antimicrobial peptides are inhibited
by cytokines associated with the underlying atopic process, such as interleukins 4
and 13, in part explaining the superinfection accompanying eczema. Several years
ago we began a search for substances that could induce epithelial antimicrobial
peptide expression, exploring a universe of food substances and both pathogenic
and commensal organisms. As a result of this survey we discovered that the essential
amino acid, isoleucine was a potent inducer2
In this presentation we will describe
several of the other agents discovered to have inducing activity and discuss the
possible significance of these findings for the practice of dermatology.
1. Zasloff M. Nature 2002;415:389.
2. Fehlbaum, et al. Proc Nat Acad Sci 2000;197:12723.
Nothing to disclose.
THE EFFECT OF ITRACONAZOLE ON PATIENTS WITH ATOPIC DERMATITIS
OF THE HEAD AND UPPER TRUNK
Shemer Avner, MD, Nir Nathansohn, MD, Henri Trau, MD, C. Sheba Medical
Center, Tel Hashomer, Israel
Background: Atopic dermatitis usually affects the folds and upper trunk. Atopic
dermatitis of the upper trunk area responds less favorably to topical steroids
compared with the folds. Mycologic smears proved high concentrations of
Malassezia spp on the upper trunk of atopic dermatitis patients.
Purpose: To test whether itraconazole improves the skin condition of patients with
atopic dermatitis around the neck and upper trunk
Patients: Thirty adult patients with moderate to severe atopic dermatitis entered the
study. All had positive direct smear of Malassezia species on the upper trunk and
were instructed to apply only emollients 2 weeks before start of study on affected
areas. All patients were treated with bifonazole 1% and flucinonide 0.05% cream in
the morning and bifonazole 1% cream in the evening to all affected areas, while
taking oral itraconazole 200 mg/d for 2 weeks followed by 4 weeks of the topical
regimen only. Skin condition was assessed at weeks 2 and 6. Another 6-week
regimen was given to all patients whose skin condition on the head and upper trunk
was partially improved with the previous course, up to a total of 3 courses.
Results: Twenty-seven patients, aged 11 to 39 years (mean 24 years) completed the
study and 3 patients were lost to follow-up. Sixteen patients received 1 pulse (6
weeks) of treatment, 5 patients received 2 pulses, and 6 patients received 3 pulses.
At the end of the treatment, itraconazole effect on the head and upper trunk’s skin
was excellent in 7 of 27 patients (26%). For all patients responding ‘‘excellent’’ to
itraconazole, the skin of the upper trunk and head’s response to topical steroids was
poor (topical steroids either worsened the skin’s condition or did not help) (P.01).
No such relationship was noted between the response of the folds’ skin to topical
steroids and its response to itraconazole. Patients whose skin of the upper trunk was
improved by topical steroids only rarely benefited from the addition of itraconazole.
Patients’ age and duration of atopic dermatitis were not related to the response to
Conclusion: When the skin of atopic patients in the upper trunk and around the
neck does not respond well to topical steroids, itraconazole may induce an excellent
response, possibly by reducing the concentration of Malassezia yeasts.
Nothing to disclose.
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
P6 J AM ACAD DERMATOL MARCH 2005
ONE-DAY HIGH-DOSE VALACYCLOVIR REDUCES THE QUANTITY AND
DURATION OF HERPES SIMPLEX VIRUS-1 (HSV-1) SHEDDING AFTER
RECURRENT HERPES LABIALIS
Stan Gilbert, MD, University of Washington, Department of Medicine, Division of
Dermatology and Dermatology and Laser Center, N.W., Bellingham, WA, United
Background: Recurrent herpes labialis (RHL) is a common disorder affecting 20% to
40% of herpes simplex virus-1 (HSV-1) seropositive adults. Treatment with a 1-day
high-dose regimen of oral valacyclovir (VAL) has been shown to shorten the duration
of RHL episodes. Little is known, however, regarding the natural history or the
impact of treatment on the oral shedding of HSVassociated with RHL. Previous HSV-
1 shedding studies in relation to such outbreaks are rare and have relied mostly on
viral cultures. These have shown shedding lasting from 1 to 8 days. Other studies
have sampled subjects randomly for the presence of HSV-1 in saliva and have
reported asymptomatic shedding rates of 2% to 9%. Transmission of HSV to
seronegative individuals is suspected to occur during and between cold sore
outbreaks from such viral shedding. To our knowledge, this is the ﬁrst known study
designed using polymerase chain reaction (PCR) analysis to assess the impact of oral
VAL on the duration of HSV-1 shedding associated with episodes of RHL.
Design: This was a randomized, double-blind, placebo-controlled study in which 64
individuals with a history of RHL ([3 episodes/y) were followed through the course
of 1 outbreak. At the ﬁrst sign of prodrome, subjects took either four 500 mg (2 gm)
VAL caplets (n = 30) or 4 placebo caplets (n = 34). This dosing was repeated 12
hours later. PCR swabs were collected every 12 hours starting at the first sign of
prodrome and continuing thereafter for 10 days.
Results: The groups were similar with respect to demographics. The median number
of days on which shedding occurred was signiﬁcantly reduced with VAL treatment
compared with placebo (VAL 1.8, placebo 4.0; P = .003). The median proportion of
days of shedding was 17.5% for the VAL group and 40.0% for the placebo group
(P = .004). A comparison of the log HSV-1 DNA copies detected by PCR over time
(using the average area under the curve) showed that there was significantly
less shedding from the VAL-treated subjects compared with the placebo group
Conclusion: This study demonstrates that episodic use of high-dose 1-day oral VAL
can signiﬁcantly decrease the duration and quantity of HSV-1 shedding associated
with RHL. Decreased oral shedding may lead to lower transmission rates for oral-
oral, oral-genital, and oral-cutaneous spread of virus. Further studies are needed to
assess the impact of ongoing suppressive dosing on asymptomatic shedding rates
Dr. Gilbert is a member of the Valtrex Speakers Bureau for GSK and has been
a consultant to Novartis Pharmaceuticals.
Research supported 50% by Glaxo Smith Kline, printing costs covered by GSK.
IMIQUIMOD IN ORGAN TRANSPLANT PATIENTS
Claas Ulrich, MD, Tobias Schmook, MD, Eggert Stockﬂeth, MD, Michael Sachse,
MD, Department of Dermatology, Charite´, University of Berlin, Berlin, Germany
Background: Immunosuppression-related skin infections and epithelial malignan-
cies are a signiﬁcant problem in organ transplant patients. In addition to the
systemically impaired immune system, locally acting ‘‘immunosuppressants’’ such as
ultraviolet radiation or certain human papillomavirus (HPV)-encoded proteins
establish the basis for the signiﬁcantly increased dermatologic complications after
transplantation. Imiquimod as an immune response modiﬁer might offer a desirable
therapeutic option in the management of numerous noninvasive and early invasive
skin cancers such as actinic keratosis and basal cell carcinoma. Furthermore,
imiquimod is recommended for the treatment of genital warts and other HPV-
induced lesions. Because the action of imiquimod is restricted to the application
area, imiquimod might be an interesting alternative for the treatment of cutaneous
neoplasms and HPV-induced skin infections.
Methods: A single-center retrospective analysis of the efﬁcacy and the safety of
imiquimod was performed using medical records of organ transplant patients who
were treated for actinic keratosis (24 patients), basal cell carcinoma (7 patients),
Bowen’s disease (4 patients), bowenoid papulosis (3 patients), as well as genital
warts (4 patients) and common warts (23 patients).
Results: A total of 62 patients with imiquimod 5% cream treatment of different
malignant or neoplastic lesions was recorded. All patients were documented
throughout their therapy and speciﬁc cases are presented with clinical pictures
and the course of their therapy. Different dosing and application regimens of the
imiquimod cream are discussed, and the safety panel used to monitor possible
immunologic side effects of the therapy is presented.
Conclusions: In a dermatological department organ transplant patients remain
a delicate subgroup for whom effective treatment of preinvasive and early invasive
skin lesions represents a crucial challenge for long-term maintenance. This
cumulative summary of cases demonstrates possible indications and regimens for
safe and effective treatment of neoplastic as well as infective skin diseases in organ
transplant recipients using imiquimod 5% cream.
Nothing to disclose.
CANDIDA ALBICANS ALLERGENIC EXTRACT STIMULATES EXPRESSION OF
TOLL-LIKE RECEPTOR 2 AND TOLL-LIKE RECEPTOR 9 AND INCREASES
EXPRESSION OF TOLL-LIKE RECEPTOR 8 IN HUMAN
Robert Signore, DO, Dermatology, Private Practice, Tinley Park, IL, United States;
Luigina Romani, MD, PhD, University of Perugia, Perugia, Italy
Introduction: Candida albicans allergenic extract 1:1000 (CAE) has been used by
dermatologists for intralesional injection immunotherapy of verruca vulgaris and
plantar warts. However, its mechanism of action has not been fully elucidated. Toll-
like receptors (TLRs) are pattern recognition receptors which detect microbial
pathogens and are an important first line of defense of the innate immune system.
Objectives: To evaluate whether CAE might affect TLR expression on human
polymorphonuclear leukocytes (PMNs).
Methodology: Freshly isolated human PMNs were assessed for TLR expression by
reverse transcriptase-polymerase chain reaction (RT-PCR) upon exposure to
different concentrations of CAE.
Results: CAE induced the expression of TLR2 and TLR9 and increased the expression
of TLR8 in human PMNs.
Conclusion: This investigation demonstrates that CAE stimulates innate immunity
through TLR expression in human PMNs. We are unaware of any previous reports
demonstrating TLR expression by CAE. Further studies investigating whether CAE
might affect expression of human monocyte TLRs and cytokines are under way.
Nothing to disclose.
EXPANDING THE SPECTRUM OF ACTIVITY OF MUPIROCIN TO INCLUDE
GRAM-NEGATIVE BACTERIA USING CATIONIC STEROID ANTIBIOTICS
Paul Savage, PhD, Brigham Young University, Provo, UT, United States;
Satyanarayan Bhat, PhD, Stephen M. Milner, MD, DDS, Southern Illinois
University School of Medicine, Springﬁeld, IL, United States
Mupirocin is widely used in a variety of topical applications and has proven to be
very effective against most gram-positive bacteria. However, mupirocin is unable to
effectively traverse the outer membranes of gram-negative bacteria and conse-
quently is inactive against these organisms. In multiple cases, selective targeting of
gram-positive bacteria through use of mupirocin has increased the risk of
opportunistic infections by gram-negative bacteria. Because mupirocin has been
well studied in the clinical environment and is well used by the medical community,
it would be advantageous to broaden the spectrum of this antibiotic to include gram-
We have developed small molecules, termed cationic steroid antibiotics (CSAs), that
selectively associate with the outer membranes of gram-negative bacteria. These
compounds demonstrate higher afﬁnity for the disaccharide head group of lipid A
than does polymyxin B. Examples of CSAs do not display antibacterial behavior
alone. Nevertheless, by binding to lipid A in the outer membranes of gram-negative
bacteria, these CSAs render the membranes permeable and sensitize gram-negative
bacteria to hydrophobic antibiotics. This activity broadens the spectrum of activity
mupirocin to include gram-negative bacteria.
Against standard strains of gram-negative bacteria, the minimum inhibition concen-
trations (MICs) of mupirocin are very high. For example, against Escherichia coli
(25922) the MIC of mupirocin is [85 g/mL. To lower the MIC of mupirocin from
[85 to 1 g/mL, a clinically relevant concentration, requires only 1 g/mL of the
CSA. This behavior extends to other gram-negative bacteria including Pseudomonas
aeruginosa. Synergistic behavior of antibiotics can be quantified using fractional
inhibition concentrations (coefficients) (FICs). FIC values less than 0.5 are indicative
of synergism. The FIC values of mupirocin with the CSA are particularly low against
gram-negative bacteria. For example, the FIC of these two antibiotics with E coli is
0.04. Because the spectrum of activity of mupirocin is limited, complicating gram-
negative infections can arise. By making the outer membranes of gram-negative
bacteria permeable with low concentrations of CSAs, mupirocin becomes a much
broader spectrum antibiotic. This type of combination therapy may prove useful in
combating a range of multibiotic infections.
Nothing to disclose.
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
MARCH 2005 J AM ACAD DERMATOL P7
EFFICACY OF TERBINAFINE HYDROCHLORIDE NAIL LACQUER
FORMULATIONS IN A GUINEA PIG MODEL OF TRICHOPHYTON
Mohammad Hossain, MBBS, PhD, Mahmoud Ghannoum, PhD, Case Western
Reserve University, Cleveland, OH, United States; William Pﬁster, PhD, Ming Lu,
MD, PhD, NexMed (U.S.A.), Inc., Robbinsville, NJ, United States
Introduction: Currently available topical antifungal therapy is often not satisfactory
for the treatment of superﬁcial fungal infections, including onychomycosis.
Terbinaﬁne hydrochloride nail lacquer is a novel antifungal drug with dodecyl-2-
N,N-dimethylaminopropionate hydrochloride (DDAIP HCl), a biocompatible and
biodegradable permeation enhancer developed by NexMed (USA) Inc. In this study,
we evaluated the clinical and mycological efficacy of different preparations of the
Terbinafine HCl nail lacquer using a guinea pig model of Trichophyton menta-
Material and methods: The animal model used in this study is described in our
Briefly, following the IACUC Guidelines, guinea pig skin was abraded
under anesthesia. Each animal was inoculated with a cell suspension of T
mentagrophytes ATCC 24953 containing 1 3 10(7) T mentagrophytes conidia.
The experimental animals were divided into 11 groups, with 5 animals per group:
vehicle control; low DDAIP-treated; 1%, 5%, and 10% terbinafine HCl nail lacquer
(without DDAIP)-treated; 1% terbinafine HCl nail lacquer with low, moderate, and
high DDAIP-treated; 5% and 10% terbinafine HCl nail lacquer with low DDAIP-
treated; and an untreated control group. Evaluation of clinical and mycological
efficacy was performed 72 hours after completion of the 7-day treatment. Skin
samples were processed for histopathology and GMS stain.
Results: The infected, untreated control guinea pigs showed patches of hair loss and
ulcerated or scaly skin, and fungal invasion of hair roots. Vehicle-treated and low
DDAIP-treated groups did not show any signiﬁcant activities. All 3 concentrations of
terbinaﬁne (1%, 5%, and 10%) with or without DDAIP showed 100% mycological
efﬁcacy by hair root invasion test, unlike untreated controls. Clinical efﬁcacy of
terbinaﬁne 5% or 10% improved with addition of low DDAIP (47.4% and 73.8% vs
68.4% and 89.5%, respectively). No fungal elements were detectable in the treated
guinea pig skin.
Conclusion: Our in vivo studies demonstrate that addition of low DDAIP to
terbinaﬁne HCl Nail Lacquer formulations resulted in better clinical efﬁcacy in the
treatment of dermatophytosis. Thus DDAIP may enhance the efﬁcacy of terbinaﬁne
and warrant clinical investigation.
1. Ghannoum MA, et al. J Chemother 2004;16(2):139-44.
William R. Pﬁster, consultant
Mahmoud A. Ghannoum, consultant
Ming Q. Lu, consultant
Sponsored by NexMed, Inc.
EOSINOPHILIC FOLLICULITIS IN THE PRE- AND POSTANTIRETROVIRAL
ERAS: A RETROSPECTIVE STUDY
Jacqueline Dolev, MD, Priya Rajendran, Toby Maurer, MD, MPH, University of
California San Francisco, San Francisco, CA, United States
Introduction: HIV-associated eosinophilic folliculitis (EF) classically presents as
recurrent, pruritic, erythematous, or urticarial follicular papules located on the
upper body. EF develops in the setting of abnormal host immunity and is seen in
individuals with late-stage HIV disease and/or CD4 cell counts below 300 cells/mm3
Anecdotally, EF improves with antiretroviral therapy (ART). However, since the start
of the modern postantiretroviral era, marked by the introduction of protease
inhibitors (PIs), EF persists. It has been informally observed that the period of
immune reconstitution after ART initiation may indeed lead to EF. This is the first
study to compare the characteristics, natural history, and treatment of EF in the
preantiretroviral and postantiretroviral periods.
Methods: The San Francisco General Hospital pathology database was searched for
the ﬁrst 30 HIV-positive patients with biopsy-proven diagnoses of EF between June
30, 1994 and June 30, 1996 and the ﬁrst 30 patients between July 1, 1996 and
January 5, 2000. July 1, 1996 was used as the cut-off between pre-ARTand post-ART
era groups. Clinical course, laboratory values, and treatment were compared with
a 24-month follow-up period.
Results: The 57 eligible patients had a median age of 40 years and consisted of: 51
males, 6 females; 14 African Americans, 30 Caucasians, 8 Latinos, and 5 Asian/Paciﬁc
Islanders. The median CD4 cell count (within 80 days of EF diagnosis) was 66
, and the median nadir was 19 cells/mm3
. Sixty percent of all patients
were taking ART regardless of group, and 65% were on PI-containing regimens. The
rise in CD4 cell count (measured between nadir and current CD4 cell count) was
significantly different between ART-treated and naive patients (17.8 vs 85.2, P.05),
but current CD4 cell count and nadir were not significantly different (P = .17 and
P = .89, respectively). Nineteen of 20 patients were diagnosed as having EF within 6
months of starting PI-containing ART regimens (16 within 3 months), whereas 6 of
12 patients were diagnosed within 6 months of starting non-PI regimens.
Conclusions: Both the median CD4 cell count and nadir were well below 300
in our cohort. The rise in CD4 cell count and the marked majority of
patients developing EF within 6 months of ART initiation demonstrate that EF
occurred with immune reconstitution and most dramatically in patients on PI-
Nothing to disclose.
POSTER DISCUSSION SESSION 495—PEDIATRICS
ASYMPTOMATIC NEUROVASCULAR ANOMALIES IN PHACES SYNDROME:
FINDINGS ON SCREENING MRI AND MRA IN 5 CHILDREN
Kimberly Horii, MD, Children’s Mercy Hospital, Section of Dermatology, Kansas
City, MO, United States; Lisa Lowe, MD, Children’s Mercy Hospital Department of
Radiology, Kansas City, MO, United States; Daniel Church, MD, Children’s Mercy
Hospital Department of Radiology, Kansas City, MO, United States; Amy Nopper,
MD, Children’s Mercy Hospital Section of Dermatology, Kansas City, MO, United
Although arterial anomalies are a well-known feature of PHACE syndrome, the
clinical signiﬁcance of cerebral vascular anomalies as well as appropriate monitoring
recommendations remain unclear. We report 5 children (all female) with PHACE
syndrome with neurovascular anomalies noted on screening MRI and MRA studies
who thus far have had no apparent neurologic consequences.
Speciﬁc vascular anomalies present in this group of patients include ectasia/fusiform
dilatation of internal carotid artery (n = 2), persistent trigeminal artery (n = 2),
aneurysm of internal carotid artery (n = 1), absent left vertebral artery (n = 1),
absent A1 segment of anterior communicating artery (n = 1), absent posterior
communicating artery (n = 1), and abberant superior cerebellar artery (n = 1).
Of note, all ﬁndings were ipsilateral to the cutaneous hemangioma and 4 of the
5 patients had left-sided arterial anomalies. Three of these 5 patients also have
cerebellar anomalies including Dandy-Walker malformation and one patient had an
absent septum pellucidum. Other PHACE associations in this group of patients
include 3 patients with aortic hypoplasia and one with coarctation of the aorta, VSD,
ASD, and PDA. Several of the patients had ocular abnormalities, one with optic nerve
hypoplasia. Less commonly observed anomalies included a subglottic hemangioma
in one child.
Thus far, there have been no acute cerebrovascular events in our group of patients.
In those patients who have had repeat neuroimaging, the abnormalities appear to be
stable with the exception of one patient with slight interval increase in the size of
the tortuous dilated arteries.
We present this group of patients to increase awareness of neurovascular anomalies
in PHACE syndrome. Further study and collaboration is needed to obtain more
information regarding the expected prognosis of these vascular anomalies and to
identify speciﬁc ﬁndings which may be predictive of future complications.
Burrow PE, Robertson RL, Mulliken JB, et al. Cerebral vasculopathy and neurologic
sequelae in infants with cervicofacial hemangioma: report of eight patients.
Bhattacharya JJ, Luo CB, Alvarez H, et al. PHACES syndrome: a review of eight
previously unreported cases with late arterial occlusions. Neuroradiology
Nothing to disclose.
ACRODERMATITIS ENTEROPATHICA OCCURRING IN TWO SIBLINGS
Adam Esser, MD, Mayo Clinic Jacksonville, Jacksonville, FL, United States; Pearl
Kwong, MD, PhD, Nemours Children’s Clinic, Jacksonville, FL, United States
Acrodermatitis enteropathica is an autosomal recessive disorder that shares clinical
ﬁndings with nutritional zinc deﬁciency, and iatrogenic zinc deﬁciency associated
with total parenteral nutrition. Although clinical manifestations of acrodermatitis
enteropathica may have variations, classically patients exhibit perioriﬁcial and acral
dermatitis, alopecia, diarrhea, irritability, and depression. We present two siblings
with almost identical cutaneous eruptions consisting of a reticulated pattern of
erythema on the face and low serum zinc levels. Genetic mutations in the gene
SLC39A4 that encodes a protein similar to the zinc-iron regulated transporter-like
protein family believed to be involved in the absorption of zinc are discussed. Other
entities with similar clinical presentations including acrodermatitis acidemia and
cystic fibrosis are also discussed in the differential diagnosis of this distinctive
Nothing to disclose.
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
P8 J AM ACAD DERMATOL MARCH 2005
SKIN BARRIER DAMAGE: CAUSE OR CONSEQUENCE OF ATOPIC
Michael Cork, MD, University of Shefﬁeld Medical School and Shefﬁeld Children’s
Hospital, Shefﬁeld, UK
Conventional treatment for atopic dermatitis is based on the use of emollients to
alleviate dry skin, coupled with reactive use of topical corticosteroids (CS) for short-
term treatment of disease ﬂares. Studies of normal skin show that epidermal
thickness varies across the body, ranging from 31 to 637 m. The eyelid, scrotum,
and inguinal skin are the thinnest, and the back, palms, and soles are the thickest.
A very potent CS (clobetasol propionate) was shown to thin the epidermis,
compromising barrier homeostasis and stratum corneum integrity after 3 consec-
utive days’ application on healthy skin. This damage results from a marked reduction
of intercellular lamellae lipids and corneodesmosomes. Absorption of CS through
eczematous skin is up to 10-fold greater than through normal skin; in skin sites
where the stratum corneum is already very thin (face, neck, ﬂexures), absorption of
CS is signiﬁcantly increased. For example, Feldmann and Maibach demonstrated that
there was a 300-fold greater penetration of topical CS through the skin of the eyelids
than through the sole. Furthermore, in atopic dermatitis, there is a genetic
predisposition to a defective epidermal barrier. A defective skin barrier enhances
the penetration of allergens, leading to more ﬂares. The defective and steroid-
induced thinning of the barrier may explain why rebound and steroid addiction
occur more frequently in these areas.
Nothing to disclose.
ACQUIRED TUFTED ANGIOMA: A RARE VASCULAR LESION IN CHILDREN
Alexandra Zhang, MD, Emily Omura, MD, John Donahue, MD, Amy Theos, MD,
Department of Dermatology, University of Alabama at Birmingham, Birmingham,
AL, United States
Tufted angiomas are rare indolent slow-growing vascular tumors that typically arise
before 5 years of age. We report a 19-month-old white girl who presented with an 8-
month history of a slowly enlarging asymptomatic pink plaque below her navel. On
physical examination, there was a 5.0 by 10.0 cm, pink to violaceous, indurated
plaque below the umbilicus with peripheral hypertrichosis. Biopsy results of this
lesion showed multiple separated lobules of spindle cells within the dermis with
numerous mitoses but no cellular atypia. Small capillary-sized vascular lumina were
present within the lobules. There was no inﬂammation or edema to suggest
pyogenic granuloma. Immunostaining with S-100 to rule out a melanocytic lesion
and with CD31 to conﬁrm the vascular nature of the spindle cells was performed
and was consistent with a tufted angioma. Complete blood cell count was also
performed and revealed a normal platelet count, which excluded Kasabach-Merritt
syndrome. Because this is a benign lesion and the patient had no symptoms, no
treatment was planned. The characteristic clinical presentation, differential di-
agnosis, and histology of tufted angioma reviewed in this case are helpful in
promoting recognition and appropriate management of this rare vascular tumor.
Nothing to disclose.
IN VIVO EFFICACY AND SAFETY OF AN EXPERIMENTAL PEDICULICIDE
Nalini Kaul, PhD, Hill-Top Research Inc., Winnipeg, MB, Canada; K. G. Palma,
PhD, Piedmont Pharmaceuticals, Greensboro, NC, United States; A. Maric, BSc,
D. de Rocquigny, BSc, S. Silagy, MD, W. J. Lazer, MBA, Hill-Top Research Inc.,
Winnipeg, MB, Canada
Pediculosis capitis is the most prevalent worldwide parasitic infestation affecting
children and adults. Topical agents called pediculicides are used to treat head lice
infestations. There is growing concern that both over-the-counter and prescription
formula pediculicides are no longer effective because of noncompliance with
labeled instructions, and/or increasing resistance to these insectisides. Toxicity of
these pediculicides has become an issue due to overuse, based on inefﬁcacy of the
labeled rate. Despite advances, there is a need for better products as existing
therapies fail and lice remain potential vectors of disease for millions of people.
Thirty subjects were enrolled in the study using the experimental rinse containing
50% isopropyl myristate and 50% ST-cyclomethicone. Twenty-nine subjects com-
pleted the study. Evaluations were conducted at screening, baseline, days 7, 14, and
21 for efﬁcacy and follow-up for safety reasons. Erythema and edema were
monitored during the study for safety purposes. Any other safety concern was
noted during evaluations. Following evaluations, the test product was applied to
subject’s hair. The product was left on for 10 minutes, following which the hair was
rinsed with water and combed for 10 minutes to collect adult lice/nymphs. These
were held in the incubator for 24 hours to determine mortality. Subjects were
considered successes if they only required two or less treatments over the 21-day
evaluation period. If subjects had lice on day 21, they were then given the standard
course of therapy. Our results with the experimental pediculicide suggest product
effectiveness in treating lice infestations with no serious side effects. Based on the
ease of use (rinse-off), with no waiting period in between uses (compared to a 1- to 2-
week waiting period for others), ingredient safety (common cosmetic ingredients
versus insecticides) and its fast acting nature (10 minutes each time), this
experimental product appears to be an effective treatment modality.
Hill-Top Research may split cost with Piedmont laboratories for printing.
UTILIZATION OF MEDICAL-CARE SERVICES IN HEALTH-PLAN MEMBERS
WITH ATOPIC DERMATITIS INITIATING THERAPY WITH PIMECROLIMUS,
TACROLIMUS, OR TOPICAL CORTICOSTEROIDS
Thomas Delea, MS, Policy Analysis Inc. (PAI), Brookline, MA, United States;
Charles Makin, MS, Outcomes Reseach Center, Humana Inc., Louisville, KY,
United States; Jane Chang, MPH, Duke Clinical Research Institute, Duke
University Medical Center, Durham, NC, United States; J. Mark Jackson, MD,
University of Louisville, Department of Internal Medicine, Division of
Dermatology, Louisville, KY, United States
Objective: To compare medical care utilization in therapy-naive patients with atopic
dermatitis (AD) who initiated topical therapy with pimecrolimus (PIM), tacrolimus
(TAC), or corticosteroids (CS).
Methods: This was a retrospective, observational study using data from a health
insurance claims database from August 2000 through October 2003and represent-
ing approximately 2 million members. Study subjects included all members with
one or more prescriptions for PIM, TAC, or CS and a previous claim with a diagnosis
of AD. The date of the ﬁrst prescription for PIM, TAC, or CS was designated as the
‘‘index date’’; members were stratiﬁed into treatment groups based on index
prescription (PIM [6CS], TAC [6CS], and CS [only]). Those with less than 12
months of continuous enrollment before and after index were excluded. Utilization
of AD medications and number of ofﬁce visits with a diagnosis of AD in the 12
months after the index date were compared for patients initiating therapy with PIM
vs TAC and PIM vs CS using multivariate regression to adjust for differences in
pretreatment characteristics including age, gender, plan type, other skin conditions,
preindex medications (antibiotics, antihistamines, systemic immunotherapies), and
preindex ofﬁce visits.
Results: A total of 6373 members met study inclusion criteria, including 235, 171,
and 5967 who initiated therapy with PIM, TAC, and CS, respectively. Mean (SD) age
was 26 (20), 28 (22), and 43 (24) years respectively (P .001 for PIM vs CS). After
adjustment for pretreatment characteristics, members who initiated therapy with
PIM received fewer grams of CS in the follow-up period (adjusted mean 18.0 vs 39.5;
P .001) than those who initiated therapy with TAC. Among those who initiated
therapy with PIM, 1.2% subsequently received TAC, whereas 6.6% of those who
initiated with TAC subsequently received PIM (P =.002). Members who initiated
therapy with PIM had fewer office visits than those who initiated therapy with TAC
(adjusted mean 0.74 vs 1.02; P =.002), but more than those who initiated therapy
with CS (0.74 vs 0.43; P .001).
Conclusions: AD patients who initiated therapy with PIM used less CS, were less
likely to switch therapy, and had fewer ofﬁce visits than those who initiated with
TAC, but had more ofﬁce visits than those receiving CS only. Although this analysis
controlled for observed characteristics, information on severity of AD was unavail-
able, and the possibility of confounding must be recognized. Further research is
needed to conﬁrm results of this study.
Mr. Delea is a Senior Research Consultant at PAI, an independent contract research
organization that has received research funding for this and other projects from
Novartis. Mr. Makin is a Pharmacoeconomics and Outcomes Research Fellow at the
Humana Outcomes Research Center, which received consulting fees and data
acquisition fees for this project from PAI on behalf of Novartis. Ms. Chang is a Health
Economics and Outcomes Research Fellow at Novartis. Dr. Jackson has received
research, honoraria, and consulting support from Novartis.
100% sponsored by Novartis Pharmaceuticals.
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
MARCH 2005 J AM ACAD DERMATOL P9
STEROID-SPARING EFFECT OF AN EMOLLIENT IN THE TREATMENT OF
MILD TO MODERATE ATOPIC DERMATITIS IN CHILDREN
Philippe Msika, Nathalie Piccardi, Jean Christophe Choulot, Bernard
Chadoutaud, Laboratoires Expanscience, Epernon, France
The application of emollients is widely recommended as a ﬁrst-line therapy in atopic
dermatitis. It is safe and it improves quality of life of the children and their parents.
Additionally, it may allow application of a lesser amount of topical steroids during
crisis and thus prevent skin atrophy.
An emollient speciﬁcally formulated for atopic dermatitis has been studied. It
contains 2% of a patented sunﬂower oleodistillate, obtained by molecular distillation
and composed of 90% essential lipids (linoleic and oleic triglycerides), 5%
phytosterols (beta-sitosterol), and 1% vitamin E. It has been shown to statistically
increase the neosynthesis of cerebrosides, ceramides, and cholesterol when applied
on human skin explant. This emollient also contains a multi-lamellar system
composed by phytosphingosins E, cholesterol, and ceramides 3, 6, 1, mimicking
lipids of the stratum corneum.
A large multicenter study with 35 pediatricians including 175 atopic children
was conducted for a 3-week period. The children were divided into 5 groups:
A: desonide 0.05 %, 2 3 1 day; B: desonide 0.05%, 2 3 1 day + emollient 2 3
1 day; C: desonide 0.05%, 131 day; D: desonide 0.05%, 1 3 1 day + emollient 2 3 1
day; E: desonide 0.05%, 1 3 2 days + emollient 2 3 1 day. SCORAD score (SCORing
Atopic Dermatitis) has been calculated at J0, J7, and J21; quality of life was evaluated
at J0, J30. Preliminary results for 63 children show that the emollient improves
effacy of steroids (B vs A) with a decrease of the SCORAD score of 86% vs 70% and
improves quality of life (86% vs 64%). The emollient has a steroid-sparing effect: D vs
A (steroids 1 3 1 day + emollients vs steroid 2 3 1 day alone) shows similar results:
ÿ75% SCORAD score vs ÿ70%; E vs A (steroids one every other day + emollients vs
steroid 2 3 1 day alone) idem with ÿ73% vs ÿ70%.
In conclusion, our 3-week comparative study on atopic children found that this
emollient, containing a patented sunﬂower oleodistillate, can decrease the
frequency of application of a topical steroid by a factor of 4.
P. Msika, N. Piccardi and J. C. Choulot are all employees of Laboratoires
100% supported by Laboratoires Expanscience
EFFECTS OF DA-9102 ON ATOPIC DERMATITIS IN NC/NgA MICE
In-Ki Lee, MS, Miwon Son, PhD, Soon-Hoe Kim, PhD, Research Laboratories of
Dong-A Pharmaceutical Co., Ltd., Yongin, Korea; Kyu-Han Kim, MD, PhD,
Department of Dermatology, Seoul National University Hospital, Seoul, Korea
Atopic dermatitis is a chronic, itchy, inﬂammatory skin disease that usually develops
in early childhood. Although the origin of atopic dermatitis remains unclear, it has
been shown that both Th1 and Th2 cytokines play pathogenic roles in the
generation of atopic dermatitis. DA-9102 is an extract from Actinidia species
containing an immune-modulating activity for allergy-related disease. We have
examined whether DA-9102 suppresses the development of atopic dermatitis-like
skin lesions in NC/Nga mice. NC/Nga mice were given daily DA-9102 starting at 6
weeks of age. Drugs were orally administered to the mice. The efficacy of DA-9102 in
NC/Nga mice was judged by measurement of skin severity, scratching behavior, and
plasma immunoglobulin levels (IgE, IgG1, and IgG2a). Dermatitis developed in
control mice from 10 weeks of age continuously. However, oral administration of
DA-9102 (100 mg/kg) suppressed the development of dermatitis. The skin severity
score of the control group reached 5.3 6 2.0 at 13 weeks of age, whereas that of
DA-9102 was 2.7 6 1.3. The plasma IgE level increased gradually with age, and
treatment with DA-9102 reduced the plasma IgE level. The plasma IgE level was
3541.5 6 641.2 ng/mL for the control group but 1442.2 6 343.85 ng/mL for the DA-
9102-administered group after 7 weeks of administration (P .05). Oral adminis-
tration of DA-9102 also had an inhibitory effect on plasma IgG1 levels (control
group, 2617.5 6 358.9 g/mL; DA-9102-administered group, 1034.9 6 100.9
g/mL; P.01). However, the plasma IgG2a level was not affected. At the age of 13
weeks, we counted the amount of time scratching behaviors occurred during a 20-
minute period. The time of scratching decreased twofold after oral administration of
DA-9102. These observations suggest that DA-9102 can be expected to be a useful
drug for atopic dermatitis.
Nothing to disclose.
A META-ANALYSIS OF THE ANTI-INFLAMMATORY ACTIVITY OF
Robert Day, PhD, Marge Nighland, BSc, Johnson Johnson Consumer and
Personal Products Worldwide, Skillman, NJ, United States
The objective of this study was to analyze the integrated statistical analysis of the
inﬂammatory lesion data from the two pivotal double-blind, placebo-controlled
trials of tretinoin gel microsphere 0.04% to determine the efﬁcacy of tretinoin gel
microsphere 0.04% in the treatment of inﬂammatory lesions of acne vulgaris.
A total of 451 patients were randomized to tretinoin gel microsphere 0.04% or
vehicle. The statistical analysis included ITT/LOCF minus duplicate patients (19
patients) for the analyses combined across protocols.
Results of combined studies of tretinoin gel microsphere 0.04% demonstrate the
superiority of active drug over vehicle treatment in the reduction of inﬂammatory
lesions. At 12 weeks (end of study) tretinoin gel 0.04% had statistically signiﬁcant
reductions (P .00125) of 43.3% compared with 22.2% for vehicle. Treatment
superiority versus vehicle was consistently present at 2, 4, 6, 8, 10, and 12 weeks for
percent reduction in inflammatory lesions. Treatment superiority emerges as early
as week 2 with reductions of 14.8% for tretinoin gel microsphere 0.04% versus 0.5%
This meta-analysis conﬁrms that tretinoin gel microsphere 0.04% results in a rapid
reduction in inﬂammatory lesions in acne vulgaris as early as 2 weeks after
beginning treatment. Superior efﬁcacy is maintained throughout the 12-week
Management of acne—A report from a global alliance to improve outcomes in
acne. J Am Acad Dermatol 2003:49:??.
Dr. Day, Ms. Nighland, and Rachel Grossman are employees of Johnson Johnson.
Mark Van Buskirk received financial support from Johnson Johnson for statistical
100% sponsored by Johnson Johnson
A MULTI-CENTER, INVESTIGATOR-BLIND CLINICAL TRIAL TO ASSESS THE
SAFETY AND EFFICACY OF METRONIDAZOLE GEL 1% AS COMPARED TO
METRONIDAZOLE GEL VEHICLE AND METRONIDAZOLE CREAM 1% IN THE
TREATMENT OF ROSACEA
Karl Beutner, MD, PhD, Barry Calvarese, MS, Dow Pharmaceuticals Sciences,
Petaluma, CA, United States; Michael Graeber, MD, Galderma RD Inc,
Princeton, NJ, United States
Objectives: To show the noninferiority of metronidazole gel 1% to metronidazole
cream 1% in the treatment of rosacea, to show its superiority over its gel vehicle, and
to evaluate safety and tolerability of the treatments.
Methods: This was a multicenter, randomized, investigator-blind, active- and vehicle-
controlled, parallel comparison involving adult subjects of any race with rosacea.
Subjects applied metronidazole gel 1%, metronidazole cream 1%, or metronidazole
gel vehicle to the face once daily at bedtime for 10 weeks with evaluations at 2, 4, 7,
and 10 weeks after baseline. Evaluations included inﬂammatory lesion count for
forehead, chin, nose, right cheek, and left cheek at each visit and a blinded
assessment of the signs and symptoms of rosacea (Investigator’s Global Severity
Score; GSS). Primary efﬁcacy analysis variables were percent reduction from
baseline in inﬂammatory lesion counts at week 10 and percent of subjects rated
as successes (clear or almost clear) in the dichotomized Investigator’s GSS at week
10. For the week 10 analysis in the ITT population, the median reduction in
inﬂammatory lesion counts was 66.7% in the gel group, 58.3% in the cream group,
and 46.2% in the gel vehicle group. Based on the primary analysis of week 10 LOCF
data in the ITT population, metronidazole gel demonstrated superiority over its
vehicle (P .0001). The analysis of success rate showed that gel and cream had
a comparable and higher percentage of subjects for whom treatment was successful
(38.4% and 35.4%, respectively) compared with a success rate of 27.5% in the gel
vehicle group. Success was noted in a greater percentage of gel-treated subjects than
in the cream and gel vehicle groups beginning at week 4 and continuing through the
end of the study. Based on the primary analysis of week 10 data in the ITT
population, the gel demonstrated superiority over its vehicle (P = .006).
Local adverse events occurred in 6.5% of subjects in the gel group, in 6.3% of the
subjects in the cream group, and in 6.3% of the subjects in the gel vehicle group.
Treatment-related adverse events occurred in 16 subjects (2.9%) in the gel group, in
22 subjects (4.0%) in the cream group, and in 8 subjects (4.2%) in the gel vehicle
Conclusion: This clinical study demonstrated that metronidazole gel 1% had a higher
efﬁcacy rate than its cream formulation and its vehicle and was equally well
Dr. Beutner and Mr. Calvarese are employees of Dow Pharmaceutical Sciences.
Dr. Graeber is an employee of Galderma RD Inc.
Supported by Galderma RD Inc.
5.0 DTD YMJD2245_2283_proof 8 January 2005 9:43 pm
P10 J AM ACAD DERMATOL MARCH 2005