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DERMATOLOGY

  1. 1. ISSN 0190-9622 Poster Abstracts 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 Abbott Immunology Journal of the American Academy of DERMATOLOGYM arch 2005 • Volume 52 • Number 3 supplement to
  2. 2. (pagesp1-232)NO.3VOL.52march2005JOURNALoftheAMERICANACADEMYOFDERMATOLOGY
  3. 3. Copyright Ó 2005 by the American Academy of Dermatology, Inc. Editor Jeffrey D. Bernhard, MD Deputy Editors Thomas G. Cropley, MD Karen Wiss, MD Editorial Office University of Massachusetts Medical School 55 Lake Avenue North Worcester, MA 01655 508-856-2583 E-mail: melissa.derby@ umassmed.edu Assistant Editors Michael E. Bigby, MD Boston, Massachusetts Andrew Blauvelt, MD Bethesda, Maryland Jean L. Bologonia, MD New Haven, Connecticut Luis A. Diaz, MD Chapel Hill, North Carolina Jane M. Grant-Kels, MD Farmington, Connecticut Mark Lebwohl, MD New York, New York Donald J. Miech, MD Marshfield, Wisconsin Ginat W. Mirowski, MD Indianapolis, Indiana Scott A. Norton, MD Bethesda, Maryland Elise Olsen, MD Durham, North Carolina Army S. Paller, MD Chicago, Illinois Stuart J. Salasche, MD Tucson, Arizona Martin A. Weinstock, MD Providence, Rhode Island Founding Editor J. Graham Smith, Jr, MD Mobile, Alabama Editor Emeritus 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 Acne P10 Aging/Geriatrics P26 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 Dermatopathology P80 Dermatopharmacology/Cosmeceuticals P83 Digital/Electronic Technology P97 Continued on page 2A March 2005 VOLUME 52 NUMBER 3 SUPPLEMENT TO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY 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. 1A
  4. 4. Education and Teaching in Dermatology P99 Epidemiology and Health Services Administration P102 Genodermatoses P109 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 Contents continued 2A MARCH 2005 J AM ACAD DERMATOL
  5. 5. POSTER DISCUSSION SESSION 491—PSORIASIS P1 ETANERCEPT THERAPY IN PSORIASIS PATIENTS WITH UNDERLYING HEPATITIS C 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. P2 COMPARISON OF BIOLOGIC THERAPIES FOR THE TREATMENT OF PSORIASIS 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 way. 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, Genentech, Inc. GlaxoSmithKline, IDEC Corporation, Ligand Pharmaceuticals, Medicis, MedImmune, Inc. Novartis Pharmaceuticals, Otsuka Pharmaceutical, Inc., Protein Design Labs, Serono Synta Pharma, and 3M Pharmaceuticals. P3 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, United States 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. P4 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 Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm MARCH 2005 J AM ACAD DERMATOL P1
  6. 6. P5 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. P6 ADALIMUMAB IN PSORIATIC ARTHRITIS: 24-WEEK RESULTS OF A PHASE III STUDY 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. P7 LONG-TERM USE OF ALEFACEPT: EFFICACY AND OFF-TREATMENT RESPONSES IN PATIENTS WHO HAVE RECEIVED MULTIPLE COURSES OF THERAPY 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. P8 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 TNF. 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 Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm P2 J AM ACAD DERMATOL MARCH 2005
  7. 7. POSTER DISCUSSION SESSION 492— LASERS IN DERMATOLOGY P9 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 plaques. 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. P10 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 before laser 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. P11 EFFICACY OF COMBINATION RED INFRARED LIGHT THERAPY IN FACIAL REJUVENATION Bruce Russell, MD, Advanced Laser Derm Surgery Clinic, PC, Beaverton, OR, United States 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. P12 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 Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm MARCH 2005 J AM ACAD DERMATOL P3
  8. 8. P13 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 conditions. 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 surgical scars. Nothing to disclose. P14 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. P15 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 patient. 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 P16 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. Bibliography Culic O, Erakovic V, Cepelak I, et al. Azithromycin-modulated neutrophil function and circulating inflammatory mediators in healthy human subjects. Eur J Pharmacol 2002;450:277-89. 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 Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm P4 J AM ACAD DERMATOL MARCH 2005
  9. 9. P17 TRETINOIN DOWN-REGULATES TOLL-LIKE RECEPTOR-2 EXPRESSION AND FUNCTION 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. P18 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. Bibliography Mills OH Jr, Kligman A. Acne mechanica. Arch Dermatol 1975;111:481-3. Nothing to disclose. P19 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. P20 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 counts. 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 49.0%, respectively. Conclusions: DTG 5% appears to be safe and effective for the long-term treatment of acne vulgaris. Sponsored by Fujisawa Healthcare, Inc. and Atrix Laboratories, Inc. 5.0 DTD Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm MARCH 2005 J AM ACAD DERMATOL P5
  10. 10. P21 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. P22 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 Products Worldwide. 100% sponsored by Neutrogena Corporation, a Johnson and Johnson Company POSTER DISCUSSION SESSION 494— INFECTIONS AND ANTI-INEFFECTIVES P23 INDUCERS OF EPITHELIAL ANTIMICROBIAL PEPTIDE EXPRESSION: EXPLORING A NEW POTENTIAL CLASS OF DERMATOLOGIC THERAPEUTICS 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 The principal 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. References 1. Zasloff M. Nature 2002;415:389. 2. Fehlbaum, et al. Proc Nat Acad Sci 2000;197:12723. Nothing to disclose. P24 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 itraconazole. 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 Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm P6 J AM ACAD DERMATOL MARCH 2005
  11. 11. P25 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 States 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 (P .001). 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 and transmission. 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. P26 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. P27 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 POLYMORPHONUCLEAR LEUKOCYTES 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. P28 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- negative bacteria. 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 Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm MARCH 2005 J AM ACAD DERMATOL P7
  12. 12. P29 EFFICACY OF TERBINAFINE HYDROCHLORIDE NAIL LACQUER FORMULATIONS IN A GUINEA PIG MODEL OF TRICHOPHYTON MENTAGROPHYTES DERMATOPHYTOSIS 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- grophytes dermatophytosis. Material and methods: The animal model used in this study is described in our publication.1 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. Reference 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. P30 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 cells/mm3 , 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 cells/mm3 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- containing regimens. Nothing to disclose. POSTER DISCUSSION SESSION 495—PEDIATRICS P31 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 States 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. Bibliography Burrow PE, Robertson RL, Mulliken JB, et al. Cerebral vasculopathy and neurologic sequelae in infants with cervicofacial hemangioma: report of eight patients. Radiology 1998;207:601-7. Bhattacharya JJ, Luo CB, Alvarez H, et al. PHACES syndrome: a review of eight previously unreported cases with late arterial occlusions. Neuroradiology 2004;46(3):227-33. Nothing to disclose. P32 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 disease. Nothing to disclose. 5.0 DTD Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm P8 J AM ACAD DERMATOL MARCH 2005
  13. 13. P33 SKIN BARRIER DAMAGE: CAUSE OR CONSEQUENCE OF ATOPIC DERMATITIS? 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. P34 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. P35 IN VIVO EFFICACY AND SAFETY OF AN EXPERIMENTAL PEDICULICIDE RINSE 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. P36 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 Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm MARCH 2005 J AM ACAD DERMATOL P9
  14. 14. P37 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 Expanscience. 100% supported by Laboratoires Expanscience P38 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. Acne P100 A META-ANALYSIS OF THE ANTI-INFLAMMATORY ACTIVITY OF TRETINOIN GEL 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% for vehicle. 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 treatment period. Bibliography 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 services. 100% sponsored by Johnson Johnson P101 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 group. 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 tolerated. 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 Š YMJD2245_2283_proof Š 8 January 2005 Š 9:43 pm P10 J AM ACAD DERMATOL MARCH 2005

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