P578TACROLIMUS 0.1% OINTMENT FOR INTERTRIGO

M. Chapman, MD, Joanne Brown, Dartmouth-Hitchcock Medical Center,Lebanon, NH, United States; Gregory Linowski, Fujisawa Healthcare, Inc.

Intertrigo is a combination of inflammatory conditions of the skin folds. Infection,contact dermatitis, moisture, and mechanical irritation all contribute to theinflammatory process. Obesity may also be a contributing factor. The inframammaryareas, axillae, abdominal folds, and crural folds are the most common sites affected.Treatment can be difficult and is aimed at all contributing factors. Even if infection islimited, the inflammatory component of intertrigo may persist.

Topical steroids can improve the symptoms and appearance of the eruption,however, long-term use is limited in those patients who have a recurrent, chroniccourse. Therefore, we proposed the use of tacrolimus 0.1% ointment twice daily for6 weeks in patients with non-infected intertrigo.

Patients applied tacrolimus twice daily. If there was infection present, patients wereexcluded or the infection was treated first, then were allowed to enroll. If clearancewas obtained prior to completion at 6 weeks, patients were allowed to decreasedosing frequency to once a day or as needed. All patients received drug. There wasno placebo. Patients were evaluated at 1, 3, and 6 weeks after initiating treatment.

Nine of the 10 patients completed the study and 11 areas were treated (one patienttreated axillae and crural folds). A single patient withdrew from the study because ofirritation and discomfort during the first week of application. Ten of 11 (91%) sitescleared at the end of 6 weeks of treatment according to both patient and physiciansassessments. Seven of 11 (64%) sites cleared at 3weeks. Three of 11 sites cleared at 1week. All but one patient showed some improvement at 1 week. There were noserious adverse events, no infections, and no unpredicted side effects.

Tacrolimus 0.1% ointment appears to be a safe and extremely effective treatment fornon-infected intertrigo. Burning is the most common side effect. Improvement israpid.

Dr. Chapman is a consultant and speaker and has performed clinical trials forFujisawa Healthcare, Inc.

P580THE CONTACT SENSITIZATION POTENTIAL OF TOPICAL FORMULATIONSCONTAINING KETOCONAZOLE 2% AND DESONIDE 0.05% ALONE AND INCOMBINATION

Brian Beger, BS, Anita Highton, MD, Robert Legendre, MS, Barrier Therapeutics,Inc., Princeton, NJ, United States

Objective: The primary objective of this trial was to evaluate the contactsensitization potential of a new formulation of ketoconazole 2% gel, desonide0.05% gel, ketoconazole 2% with desonide 0.05% gel, vehicle gel, and ketoconazole2% cream.

Methods: This trial used a single-center, randomized, double-blind, within subjectdesign. The trial consisted of a 3-week induction period where study medicationswere applied under occlusive patches on Monday, Wednesday, and Friday andremoved at the following visit (48 hours for patches applied on Monday andWednesday; 72 hours for patches applied on Friday); a 2-week rest period duringwith no patches applied; a challenge period where a single patch of each studymedication was applied and removed 48 hours later. During the challenge periodskin reactions were graded using a 5-point (0-4) scale within 15 minutes and 24 and48 hours after patch removal. The skin reaction grades during the challenge periodwere used to determine the study medication’s contact sensitization potential. Theinvestigator also gave a blinded clinical impression of the contact sensitizationpotential of each study medication.

Results: Two hundred thirty subjects enrolled and 23 prematurely withdrew fromthe trial. 73.9% (170/230) of the subjects were female. 61.7% of the subjects statedtheir ethnicity as African American, 36.5% white, 3% Native American, and 0.4% (1subject) Other. The mean age was 46 years (18-82 years) for the females and 43 years(18-67 years) for males. Challenge period skin reaction grades showed no grades of 3or 4 for desonide 0.05% and ketoconazole 2% with desonide 0.05% gels, vehicle andketoconazole 2% gels each had one test site with a grade 4, and ketoconazole 2%cream had six sites with a grade of 3 and two with a grade of 4. The investigator’sclinical impression was that none of the study medications were contact sensitizers.Seven subjects reported 12 non-serious adverse events none of whichwas related tothe study medications.

Conclusions: None of the study medications were considered contact sensitizersbased on the skin reaction grades or the investigator’s clinical impression. It isinteresting that the new formulation of ketoconazole 2% gel had only one test sitewith a grade of 4 while ketoconazole 2% cream had the most test sites (eight) withskin reaction grades of 3 or 4. None of the study medications were responsible forany adverse events.

Dr. Highton, Mr. Legendre, and Mr. Beger are employees of Barrier Therapeutics, Inc.

This research is 100% sponsored by Barrier Therapeutics, Inc.

P581THE IRRITATION POTENTIAL OF TOPICAL FORMULATIONS CONTAININGKETOCONAZOLE 2% AND DESONIDE 0.05% ALONE AND IN COMBINATION

Brian Beger, BS, Anita Highton, MD, Robert Legendre, MS, Barrier Therapeutics,Inc., Princeton, NJ, United States

Objective: The objective of this trial was to evaluate the irritation potential of a newformulation of ketoconazole 2% gel, desonide 0.05% gel, ketoconazole 2% withdesonide 0.05% gel, vehicle gel, ketoconazole 2% cream, and a positive control (0.5%sodium lauryl sulfate).

Methods: This trial used a single-center, randomized, double-blind, positive control,within subject design to evaluate the irritation potential of the study medicationsfollowing application under occlusive patches for 21 consecutive days. Irritationwas scored on a five-point (0-4) scale. The Cumulative Irritation Index (CII), the ratioof the total irritation score for a study medication divided by the maximum possibletotal irritation score, was calculated for each studymedication. The investigator gavea blinded clinical impression of the irritation potential of each study medication.

Results: Thirty subjects were enrolled and one withdrew from the trial prematurely.66.7% (20/30) of the subjects were female. 80% of the subjects were white and 20%were African American. The mean age was 53 years (21-74 years) for females and52.6 years (37-78 years) for males. The CII for the study medications was: desonide0.05% gel = 0.023; ketoconazole 2% with desonide 0.05% gel = 0.031; ketoconazole2% gel = 0.057; vehicle gel = 0.063; ketoconazole 2% cream = 0.270; and positivecontrol = 0.675. The investigator’s clinical impression of the irritation potential ofthe study medications corresponded with the CII with desonide 0.05% andketoconazole 2% with desonide 0.05% gels considered slightly irritating, ketocona-zole 2% gel somewhat irritating, vehicle gel and ketoconazole 2% cream irritatingand the positive control extremely irritating. No deaths or serious adverse eventswere reported and two subjects reported 5 non-serious adverse events that were notrelated to the study medications.

Conclusions: The results of this study differentiate the irritation potential of thestudy medications. Based on the CII the study medications, ranked from least tomost irritating were: desonide 0.05% gel\ ketoconazole 2% with desonide 0.05%gel \ ketoconazole 2% gel \ vehicle gel \ ketoconazole 2% cream \ positivecontrol. It is interesting that the new formulation of ketoconazole 2% gel was lessirritating than the ketoconazole 2% cream as based on both the CII and theinvestigator’s clinical impression. None of the study medications were responsiblefor any adverse events.

Dr. Highton, Mr. Legendre, and Mr. Beger are employees of Barrier Therapeutics, Inc.

This research is 100% sponsored by Barrier Therapeutics, Inc.

J AM ACAD DERMATOL P61

P579TELANGIECTASIA MACULARIS ERUPTIVA PERSTANS RAPIDLYPROGRESSING TO SYSTEMIC MASTOCYTOSIS

Periasamy Balasubramaniam, MBBS, MD, Fiona Lewis, MD, Worcestershire RoyalHospital, Worcester, England; Alistair Sawers, MD, Department of Haematology,Worcestershire Royal Hospital, Worcester, England

Mastocytosis is an uncommon disorder in which abnormal mast cell proliferate andinfiltrate various organs. The skin is the commonest organ involved and thepresenting features can be varied. Telangiectasia macularis eruptiva perstans(TMEP) is a rare form of cutaneous mastocytosis and usually has a prolonged,indolent course. We report a case of TMEP rapidly progress to systemicmastocytosis.

A 39-year-old woman presented with a 4-year history of a macular rash pre-dominantly affecting the trunk and proximal part of the limbs. Apart from milditching she had no other symptoms. She had a past medical history of irritable bowelsyndrome with occasional diarrhea. On examination there were widespreaderythematous macules measuring 2 mm to 6 mm in size, in a symmetricaldistribution. Telangiectasia were seen on the surface of the lesions. Darier’s signwas negative. Routine investigations were normal but a skin biopsy confirmedexcess mast cells around the dermal vessels with mild vasodilatation. Antihistaminesand disodium cromoglicate provided little benefit and she was lost to follow-up.

One year later she presented with weight loss, tiredness, and generalized painparticularly affecting her back. Systemic mastocytosis was suspected and confirmedby bone marrow trephine biopsy which showed mast cell infiltration with focalfibrosis and osteosclerosis. She had an elevated serum tryptase at 187 mcg/l (normal2-14 mcg/l).

She was started on subcutaneous alpha interferon in combination with cortico-steroids. After 6 months, her rash persisted though her general symptoms improved.A repeat trephine bone marrow biopsy at this point showed no change.

Cutaneous mastocytosis, presenting as urticaria pigmentosa, is predominantlya disorder of childhood with a good prognosis. TMEP is a rare form of cutaneousmastocytosis and generally affects adults. All adult onset cutaneous mastocytosisshould be investigated for systemic involvement. There is no specific treatment butit should be targeted to block the mediators’ effects and reduce the mast cell load inaffected organs. Commonly used medications include antihistamines, sodiumcromoglicate and H2 blockers. Interferon alpha has produced mixed results. Bonemarrow transplant and treatment with drugs like imatinib mesylate are in theirinfancy.

Nothing to disclose.

MARCH 2005