Clinical dose ranging studies with finasteride, a type 2 5alpha-reductase inhibitor, in men with male pattern hair loss.

BACKGROUND: Androgenetic alopecia is a common condition of adult men. Finasteride, a type 2 5alpha-reductase inhibitor, decreases the formation of dihydrotestosterone from testosterone. OBJECTIVE: Two separate clinical studies were conducted to establish the optimal dose of finasteride in men with this condition. METHODS: Men from 18 to 36 years of age with moderate vertex male pattern hair loss received finasteride 5, 1, 0.2, or 0.01 mg/day or placebo based on random assignment. Efficacy was determined by scalp hair counts, patient self-assessment, investigator assessment, and assessment of clinical photographs. Safety was assessed by clinical and laboratory measurements and by analysis of adverse experiences. RESULTS: Efficacy was demonstrated for all end points for finasteride at doses of 0.2 mg/day or higher, with 1 and 5 mg demonstrating similar efficacy that was superior to lower doses. Efficacy of the 0.01 mg dose was similar to placebo. No significant safety issues were identified in the trials. CONCLUSION: Finasteride 1 mg/day is the optimal dose for the treatment of men with male pattern hair loss and was subsequently identified for further clinical development.

Finasteride in the treatment of men with androgenetic alopecia. Finasteride Male Pattern Hair Loss Study Group.

BACKGROUND: Androgenetic alopecia (male pattern hair loss) is caused by androgen-dependent miniaturization of scalp hair follicles, with scalp dihydrotestosterone (DHT) implicated as a contributing cause. Finasteride, an inhibitor of type II 5alpha-reductase, decreases serum and scalp DHT by inhibiting conversion of testosterone to DHT. OBJECTIVE: Our purpose was to determine whether finasteride treatment leads to clinical improvement in men with male pattern hair loss. METHODS: In two 1-year trials, 1553 men (18 to 41 years of age) with male pattern hair loss received oral finasteride 1 mg/d or placebo, and 1215 men continued in blinded extension studies for a second year. Efficacy was evaluated by scalp hair counts, patient and investigator assessments, and review of photographs by an expert panel. RESULTS: Finasteride treatment improved scalp hair by all evaluation techniques at 1 and 2 years (P < .001 vs placebo, all comparisons). Clinically significant increases in hair count (baseline = 876 hairs), measured in a 1-inch diameter circular area (5.1 cm2) of balding vertex scalp, were observed with finasteride treatment (107 and 138 hairs vs placebo at 1 and 2 years, respectively; P < .001). Treatment with placebo resulted in progressive hair loss. Patients' self-assessment demonstrated that finasteride treatment slowed hair loss, increased hair growth, and improved appearance of hair. These improvements were corroborated by investigator assessments and assessments of photographs. Adverse effects were minimal. CONCLUSION: In men with male pattern hair loss, finasteride 1 mg/d slowed the progression of hair loss and increased hair growth in clinical trials over 2 years.

Mometasone furoate 0.1%-salicylic acid 5% ointment versus mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis: a multicenter study.

Topical corticosteroids and keratolytics are both used widely in the management of patients with psoriasis. A combination of the two types of agents may provide enhanced relief. The purpose of this study was to compare the efficacy and safety of the combination ointment mometasone furoate 0.1% plus salicylic acid 5% with that of mometasone furoate 0.1% ointment in the treatment of moderate-to-severe psoriasis vulgaris. A total of 408 patients were enrolled in this controlled, randomized, double-masked, parallel-group, multicenter comparison. Patients applied either mometasone furoate-salicylic acid ointment or mometasone furoate ointment alone to target lesions twice daily for 21 days. Severity of erythema, induration, and scaling were scored at baseline and at days 4, 8, 15, and 22. An evaluation of overall change in disease status of all treated lesions was performed at each follow-up visit. Adverse events were also monitored and scored, including signs of skin atrophy. Beginning on day 8, the combination of mometasone furoate-salicylic acid was significantly more effective than mometasone furoate alone, as indicated by the mean percentage of improvement in total disease scores, mean total disease sign scores, and the individual score for scaling. Similarly, the combination was more effective beginning on day 15, as indicated by the global evaluation of overall clinical response and individual scores for erythema and induration. Both treatments were well tolerated. Mometasone furoate-salicylic acid ointment provides more effective treatment of moderate-to-severe psoriasis than does mometasone furoate ointment alone and is safe and well tolerated.

A multicenter, placebo-controlled, double-blind study of intermittent therapy with itraconazole for the treatment of onychomycosis of the fingernail.

BACKGROUND: Onychomycosis is the most frequent cause of nail disease and represents 30% of all mycotic infections of the skin. OBJECTIVE: Our purpose was to compare the effectiveness and tolerability of intermittent dosing of itraconazole ("pulse therapy") with placebo in fingernail onychomycosis. METHODS: Seventy-three patients with clinically and mycologically diagnosed fingernail onychomycosis were randomly selected to receive itraconazole, 200 mg twice daily, or placebo for the first week of each month for 2 consecutive months; patients were observed for 19 weeks. Seventy-one patients received the study medication and were included in the safety analysis. Efficacy of treatment was evaluated in 46 patients. RESULTS: A significantly greater proportion of itraconazole-treated patients than placebo-treated patients achieved clinical success (77% vs 0%), mycologic success (73% vs 13%), and overall success (68% vs 0%). No itraconazole-treated patient had a clinical or mycologic relapse during the follow-up period. Ten itraconazole-treated patients (28%) and nine placebo-treated patients (26%) had adverse events. Three patients discontinued treatment for safety reasons. CONCLUSION: Pulse therapy with itraconazole for 2 consecutive months produces significantly greater clinical, mycologic, and overall success than placebo. Short-term itraconazole pulse therapy for fingernail onychomycosis is effective and well tolerated.

Cutaneous involvement in chronic myelomonocytic leukemia.

BACKGROUND: Chronic myelomonocytic leukemia has been associated with various nonspecific cutaneous manifestations. Rarely has the leukemia been reported to directly affect the skin. METHODS: This case documents the progression of a patient who ultimately developed chronic myelomonocytic leukemia, by clinical examination, hematologic parameters, dermatopathology, and bone marrow pathology. RESULTS: The skin showed nonspecific cutaneous involvement, progressing to specific leukemic lesions parallel with increasing systemic and hematologic involvement. CONCLUSIONS: Chronic myelomonocytic leukemia can manifest with lesions of leukemia cutis. The possibility of nonspecific cutaneous involvement in the preleukemic phase exists.

Androgenetic alopecia in the female. Treatment with 2% topical minoxidil solution.

BACKGROUND: Women generally regard their hair loss as socially unacceptable and go to great measures to conceal their problem. In some cases, the negative self-image brought about by hair loss may be the basis of psychiatric illness. The purpose of this study was to evaluate a 2% topical minoxidil solution (Rogaine/Regaine, The Upjohn Co, Kalamazoo, Mich) for the treatment of female androgenetic alopecia. A 32-week, double-blind, placebo-controlled trial was conducted in 11 US centers. Three hundred eight women with androgenetic alopecia were enrolled. Two hundred fifty-six of these women completed the trial. A refined photographic technique was used to objectively determine the number of nonvellus hairs regrown. RESULTS: After 32 weeks of treatment, the number of nonvellus hairs in a 1-cm2 evaluation site was increased by an average of 23 hairs in the 2% minoxidil group and by an average of 11 hairs in the placebo group. The 95% confidence interval for the difference in mean hair count change between the treatment groups was 5.9 to 17.5 hairs. The investigators determined that 13% in the minoxidil-treated group had moderate growth and 50% had minimal growth. This compared with 6% and 33%, respectively, in the placebo-treated group. Similarly, 60% of the patients in the 2% minoxidil group reported that they had new hair growth (20% moderate, 40% minimal) compared with 40% (7% moderate, 33% minimal) of the patients in the placebo group. No evaluations of dense hair growth were reported for either treatment group. No clinically significant changes in vital signs were observed and no serious or unexpected medical events were reported. CONCLUSIONS: Topical minoxidil was significantly more effective than placebo in the treatment of female androgenetic alopecia.

Papulonecrotic tuberculid secondary to disseminated Mycobacterium avium complex.

BACKGROUND: Papulonecrotic tuberculid is a rarely reported cutaneous reaction to the mycobacterium bacillus. It is most often encountered in association with tuberculosis. The clinical and histologic picture of the entity is a distinctive one, but the etiology of the disease process is uncertain. Therapy directed against the causative organism is dramatically successful. METHODS: A 35-year-old white man with AIDS was referred to the Dermatology clinic for evaluation of a widespread skin eruption. The skin lesions were biopsied for histopathology and culture. From the cutaneous cultures Mycobacterium avium complex (MAC) organisms were grown. RESULTS: We report the first case of papulonecrotic tuberculid manifestation in an AIDS patient with disseminated MAC. Unusual features seen in this case include the predominance of pruritic eschars rather than asymptomatic papules and the confirmation by special stains of mycobacterium organisms within the skin biopsy. Papulonecrotic tuberculid has not been previously associated with either MAC or AIDS. CONCLUSIONS: Papulonecrotic tuberculid should be a diagnostic consideration in immunocompromised patients with MAC whose clinical and histologic features are compatible with this rare entity.

Sepsis associated with Norwegian scabies in patients with acquired immunodeficiency syndrome.

A review of the literature reveals that of the eight reported cases of patients with acquired immunodeficiency syndrome acquiring Norwegian scabies, three of these have been complicated by sepsis. We describe such a patient who contracted sepsis from Pseudomonas aeruginosa. We propose that the fissures often seen in severe cases of Norwegian scabies may serve as a port of entry for bacteria, thus placing these patients at a high risk for sepsis. We also believe that empiric antibiotic treatment is justified in these patients and that the choice of agent should be based on the institution's bacterial flora profile.

Antifungals: oral and topical.

This article discusses the mechanism of action, pharmacokinetics, and clinical efficacy of allylamine and triazole antifungal agents, griseofulvin, imidazoles, and clotrimazole.

Treatment-resistant alopecia areata. Response to combination therapy with minoxidil plus anthralin.

Combination therapy with 5% minoxidil plus 0.5% anthralin was used to treat 51 patients with severe treatment-resistant alopecia areata. History of a cosmetically inadequate response to one or both drugs used as a single agent was present in 50 of the 51 patients. Therapy was relatively well tolerated except by 1 patient who developed a severe irritant reaction and was dropped from the study. Mild to moderate irritant dermatitis was seen in all remaining patients. Cosmetic response was seen in 5 (11%) of 45 patients who completed the 6-month study. Cosmetic response was maintained in 4 (80%) of 5 patients who continued treatment for as long as 84 weeks. All responders had evidence of hair regrowth by week 12. The rapidity and extent of hair regrowth were greater with combination therapy than with either drug used as a single agent. Serum and 24-hour urinary minoxidil determinations showed enhanced systemic minoxidil absorption, which was probably secondary to the irritant dermatitis in some patients; however, no clinical evidence of a systemic minoxidil effect was found. These data suggest that combination therapy using drugs with probable different mechanisms of action may provide a synergistic effect in alopecia areata.

The therapeutic use of topical minoxidil.

Topical minoxidil is a trichogenic agent that stimulates the hair follicle via the vasoactive metabolite minoxidil sulfate without any evidence of antiandrogen activity or an effect on the immune system. Less than 5% of the applied dose is absorbed. The therapeutic effect on hair regrowth is demonstrated for androgenetic alopecia in males and females, by a computer-assisted image analysis counting technique of nonvellus hairs from a photographic print. Patients with severe alopecia areata respond poorly to topical minoxidil treatment. The most common adverse reactions are limited to irritant and allergic contact dermatitis on the scalp. The use of retinoic acid with topical minoxidil has been disappointing relative to the increase in systemic exposure. The value of topical minoxidil as an adjunct for the hair transplant procedure and its effect on hair loss from chemotherapy are being evaluated.

Topical minoxidil for androgenetic alopecia: optimizing the chance for success by appropriate patient selection.

Cosmetically acceptable hair growth was achieved in 18 (32%) of 56 balding male subjects during a 12-month study using 2 or 3% topical minoxidil. The criteria for successful hair regrowth devised from those subjects were: (1) no baldness greater than a Hamilton pattern IV; (2) a balding vertex area smaller than 10 cm in diameter, and (3) a balding process of less than 5 years' duration. Frontotemporal hair loss did not respond to treatment and in fact progressed in severity, despite the twice-daily applications of minoxidil. In a subsequent study of 91 subjects who met these three criteria, 51 (56%) subjects achieved cosmetically acceptable hair growth after 1 year using 2% topical minoxidil (Regaine; registered trade mark of The Upjohn Company) twice daily.

Oral isotretinoin therapy for familial Muir-Torre syndrome.

Two representative cases of familial Muir-Torre syndrome are presented. Multiple benign sebaceous neoplasms in both cases and a solitary keratoacanthoma in one were successfully treated with oral isotretinoin. Low-dose maintenance therapy has stabilized the cutaneous manifestations in the two patients, and no new epithelial neoplasms have appeared. This report emphasizes (1) the rationale for the use of isotretinoin in the Muir-Torre syndrome and (2) the potential for a familial pattern of inheritance and a possible association with the cancer family syndrome. It speculates on the prevention of future internal malignancies in Muir-Torre syndrome patients by maintenance oral isotretinoin treatment.

Congenital unilateral punctate porokeratosis.

A 16-year-old girl with congenital unilateral punctate porokeratosis is described. The clinical and histopathologic findings are presented. The various clinical forms of porokeratosis and the differential diagnosis of this type of lesion are discussed. To our knowledge, this is the first case of congenital unilateral punctate porokeratosis to be reported.