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Background: Doxepin applied topically by itself or in combination with triamcinolone acetonide is a safe and effective treatment for atopic dermatitis. Objective: We evaluated the pharmacokinetic profile of doxepin and desmethyldoxepin after topical application of doxepin hydrochloride 5% cream alone or in combination with 0.025% triamcinolone acetonide (doxepin/TAC). Methods: Twenty-four subjects with atopic dermatitis received either doxepin or doxepin/TAC cream 4 times daily for 7 days in a randomized, double-blind, controlled trial. Serum samples were obtained and pharmacokinetic parameters estimated from the dose-normalized serum concentrations of doxepin and desmethyldoxepin. Efficacy and adverse experiences were determined by physician and subject evaluations. Results: Pharmacokinetic parameters (K e , t 1/2 and AUC) calculated in 9 subjects (doxepin/TAC = 4 subjects, doxepin=5 subjects) with detectable serum concentrations were similar for both groups. Pruritus relief and lessening of pruritus severity were significantly greater with doxepin/TAC than doxepin alone. Conclusion: Topically applied doxepin is safe and effective therapy for pruritus. (J Am Acad Dermatol 1999;41:209-14.)

Treatment-related changes in hyperpigmentation are difficult to quantify with visible light photography, especially when the changes are subtle.Our purpose was to determine the utility and reliability of fluorescence photography to measure changes in mottled and diffuse hyperpigmentation.Thirty-two subjects, with mildly to moderately photodamaged skin, completed a 36-week, double-blind, vehicle-controlled study of tretinoin cream 0.025%. Clinical evaluation of hyperpigmentation as well as standard flash photographs and fluorescence photographs were obtained at baseline and week 36.The fluorescence photographs were evaluated blindly and yielded macule counts that decreased significantly from baseline in tretinoin-treated subjects compared with vehicle-treated subjects (31% vs 11% decrease; p = 0.02). Diffuse hyperpigmentation, as evaluated from the fluorescence photographs, decreased 16% from baseline for tretinoin-treated subjects and increased 5% for vehicle-treated subjects (p0.01). No significant differences in mottled or diffuse hyperpigmentation were observed between groups through clinical evaluation.Fluorescence photography is a noninvasive method that is sensitive in the evaluation and quantification of distribution and changes of mottled and diffuse hyperpigmentation.

I. Dicken CH, Carrington SG, Winkelmann RK. Generalized granulomaannulare. Arch DermatolI969;99:556-63. 2. Mobacken H, Gisslen H, Johannisson G. Granuloma annulare:cortisone-glucose tolerancetest in a non-diabetic group. Acta Derm Venereal (Stockh) 1970;50:440-4. 3. Williamson DM, Dykes JRW. Carbohydrate metabolism in granuloma annulare. J InvestDermatol 1972;58:400-4. 4. BlohmeG, MobackenH, WaldenstromJ. Early insulinresponseto glucoseinjectedintravenously in patientswith 10calizedgranulomaannulare. ActaDerm Venereal(Stockh) 1974;54:259-63. 5. Haim S, Friedman-BirnbaumR, Shafir A, et al. Generalized granulomaannulare: relationshipto diabetes mellitus as revealed in 8 cases. Br J DermatoI1970;83:302-5. 6. Hammond R, DyessK, Castro A. Insulin productionand glucosetolerancein patients with granuloma annulare. Br J DermatoI1972;87:540-7. 7. Andersen BL, VerdichJ. Granuloma annulare and diabetes mellitus. Clin Exp Dermatol 1979;4:31-7. 8. Muhlemann MF, Williams DDR. Localized granuloma Briefcommunications 663

• Background and Methods.— Because acne is androgen dependent, antiandrogen therapy might improve the condition. Inocoterone acetate (RU 882) is a nonsteroidal antiandrogen that binds to the androgen receptor and has antiandrogenic activity in animal models. To test its topical effect on acne, 126 male subjects with facial acne completed a 16-week, multicenter, double-blind study in which the twicedaily application of a 10% solution of inocoterone was compared with vehicle solution. Baseline and monthly examinations included acne lesion counts and general and endocrine laboratory tests. Results.— Inflammatory papules and pustules showed greater reduction in the inocoterone-treated subjects than in the subjects treated with vehicle. This difference achieved statistical significance by week 12 (24% reduction vs 10%) and week 16 (26% reduction vs 13%) and, with longitudinal analysis, throughout the course of the study. Global assessments and changes in comedo counts and sebum excretion rates were not significantly different between the groups. No serious adverse reactions were encountered. Conclusions.— In this double-blind study of 126 male subjects with acne, a topical solution of the antiandrogen inocoterone, compared with vehicle, produced a modest but statistically significant reduction in the number of inflammatory acne lesions. ( Arch Dermatol. 1992;128:1197-1200)

A prospective, randomized, double-blind, placebo-controlled multicentre study assessed the clinical efficacy and safety of pulsed electromagnetic limb ulcer therapy (PELUT) in the healing of recalcitrant, predominantly venous leg ulcers. The portable device was used at home for 3 h daily during this 8-week clinical trial as an adjunct to a wound dressing. Wound surface area, ulcer depth and pain intensity were assessed at weeks 0, 4 and 8. At week 8 the active group had a 47.7% decrease in wound surface area vs. a 42.3% increase for placebo (P < 0.0002). Investigators' global evaluations indicated that 50% of the ulcers in the active group healed or markedly improved vs. 0% in the placebo group, and 0% of the active group worsened vs. 54% of the placebo group (P < 0.001). Significant decreases in wound depth (P < 0.04) and pain intensity (P < 0.04) favouring the active group were seen. Patients whose ulcers improved significantly after 8 weeks were permitted to continue double-blind therapy for an additional 4 weeks. Eleven active and one placebo patient continued therapy until week 12, with the active treatment group continuing to show improvement. There were no reports of adverse events attributable to this device. We conclude that the PELUT device is a safe and effective adjunct to non-surgical therapy for recalcitrant venous leg ulcers.

Low-dose cyclosporine therapy for severe plaque psoriasis is effective. Most side effects can be controlled by patient monitoring, with appropriate dose adjustment or pharmacologic intervention, or both, if indicated. Prevention or reversibility of laboratory and chemical abnormalities may be achieved by discontinuation of therapy after the induction of clearing. However, relapse occurs rapidly on discontinuation. Maintenance therapy with cyclosporine after induction has not been fully evaluated.Our purpose was to compare a regimen of 3.0 mg/kg per day of oral cyclosporine with placebo in maintaining remission or improvement in patients with psoriasis.After a 16-week unblinded induction phase in which 181 patients received cyclosporine, 5.0 mg/kg per day (an increase up to 6.0 mg/kg per day and a decrease to 3.0 mg/kg per day were allowed, if required, to achieve efficacy or tolerability, respectively), those patients showing a 70% decrease or more in involved body surface area (BSA) entered the 24-week maintenance phase and were randomly assigned to either placebo, cyclosporine, 1.5 mg/kg per day, or cyclosporine, 3.0 mg/kg per day. Patients were considered to have had a relapse when BSA returned to 50% or more of the prestudy baseline value. Clinical efficacy, adverse effects, and laboratory values were monitored regularly throughout both study phases.During induction, cyclosporine at approximately 5.0 mg/kg per day produced a reduction in BSA of 70% or more in 86% of the patients. During maintenance, the median time to relapse was 6 weeks in both the placebo and cyclosporine 1.5 mg/kg per day groups, but was longer than the 24-week maintenance period in the 3.0 mg/kg per day group (p0.001 vs placebo). By the end of the maintenance period, 42% of the patients in the 3.0 mg/kg per day cyclosporine group had a relapse compared with 84% in the placebo group. Changes in laboratory values associated with the higher induction dosage generally exhibited partial or complete return toward mean prestudy baseline values during the maintenance phase, with the greatest degree of normalization in the placebo group.Cyclosporine, 3.0 mg/kg per day, adequately and safely maintained 58% of patients with psoriasis for a 6-month period after clearing of their psoriasis with doses of approximately 5.0 mg/kg per day.

Background: Quantification of acne remains a challenge. It may be difficult to identify lesions by standard flash photography. Previous studies have shown that foci of light in fluorescence photographs correspond to high protoporphyrin IX production by Propionibacterium acnes in open comedones, follicles, and inflammatory lesions. Objective: Our purpose was to study the utility of fluorescence photography for evaluation of acne. Methods: Forty subjects with mild to moderate acne vulgaris were randomly selected to apply either clindamycin 1% topical solution or vehicle twice daily. Counts of acne lesions and flash and fluorescence photographs were obtained at baseline, and at 4, 8, and 12 weeks. Results: At 12 weeks, the treatment group had a larger percentage change in open comedones, less fluorescence in all areas assessed, and a larger percent decrease in fluorescence than the vehicle group. Conclusion: Fluorescence photography appears to be a useful tool to chart the course of acne treatment.

Background: Multiple immunologic abnormalities such as impaired T-cell function, elevated serum IgE level, and increased interleukin 4 production have been demonstrated in patients with atopic dermatitis. Objective: As part of a 12-week, multicenter, double-blind, placebo-controlled clinical trial, we evaluated the safety and efficacy of thymopentin (Timunox) as an adjunctive treatment in patients with severe atopic dermatitis. Methods: Thirty-nine patients at least 2 years old with severe atopic dermatitis on a minimum of 20% of their cutaneous surface area were randomly selected to receive either thrice-weekly subcutaneous injections of thymopentin, 50 mg, or placebo. Use of triamcinolone 0.1% or hydrocortisone 1.0% cream and oral antihistamines were permitted during this trial. Results: After 12 weeks, thymopentin-treated patients had significantly greater improvement than those receiving placebo. No thymopentin-related adverse events occurred. Conclusion: Thymopentin may be a safe effective adjunct to therapy in patients with severe atopic dermatitis.

Tretinoin administered topically in 0.1% concentration has been shown to improve the wrinkling and irregular pigmentation of photoaged skin.The purpose of this study was to assess the safety and efficacy of various concentrations of tretinoin in a new emollient cream base in the treatment of photoaged skin.Three concentrations of tretinoin (0.05%, 0.01%, and 0.001%) in a new emollient cream formulation were compared with vehicle in a 24-week, double-blind, randomized, multicenter study of 296 subjects with photodamaged facial skin.Tretinoin emollient cream 0.05% gave a significantly better global response to therapy than vehicle (p less than 0.001), with 68% of subjects exhibiting improvement at the end of therapy, compared with 43% of subjects in the vehicle group. An excellent or good response was found in 26% of subjects treated with tretinoin emollient cream 0.05% versus 11% of vehicle-treated subjects. Fine wrinkling, mottled hyperpigmentation, and roughness were more improved in subjects who received tretinoin emollient cream 0.05% than in vehicle-treated subjects (p less than 0.05). No significant difference was found between vehicle and tretinoin emollient cream 0.01% or 0.001%. Histologic examination showed increases in epidermal and granular layer thickness, decreased melanin content and compaction of the stratum corneum after therapy with tretinoin emollient cream 0.05% or 0.01%. Mild to moderate skin reactions, such as erythema, peeling, and burning, were the most common side effects and, although most prevalent in the group using the 0.05% concentration, generally did not limit tretinoin use.Tretinoin emollient cream 0.05% appears to be safe and effective in the treatment of photodamaged skin.