Jerome L. Shupack

Rediscovering thalidomide: a review of its mechanism of action, side effects, and potential uses.

Thalidomide, a hypnosedative drug introduced in the 1950s, has been used in a variety of dermatologic conditions during the past few decades. Although originally withdrawn from the world market on discovery of its teratogenic effect, it has since been selectively reintroduced for use in various disorders thought to have an autoimmune or inflammatory basis. A review of the literature focused on clinical uses of thalidomide in the treatment of dermatologic diseases was performed. Diseases for which thalidomide has been found effective include erythema nodosum leprosum, prurigo nodularis, actinic prurigo, discoid lupus erythematosus, aphthous stomatitis, Behçets syndrome, and graft-versus-host disease. Side effects such as teratogenicity and peripheral neuropathy remain its limiting factor. Thalidomide is a useful addition to the therapeutic armamentarium for treatment-resistant dermatoses as long as proper vigilance for adverse effects is maintained.

Cyclosporine consensus conference: With emphasis on the treatment of psoriasis ☆ ☆☆ ★

Cyclosporine has been in worldwide use for 15 years for patients who have undergone transplantation operations and is now being used to control inflammatory reactions in other organs (eg, joints, bowel, and skin). Neoral, a more consistently absorbed form of cyclosporine, has recently been approved by the Food and Drug Administration for the treatment of psoriasis. This report outlines the indications, contraindications, dosage recommendations, monitoring requirements, adverse events, drug interactions, interactions with other psoriasis treatments, and suggestions for cyclosporines use in rotational therapy.

Rediscovering mycophenolic acid: A review of its mechanism, side effects, and potential uses

Oral mycophenolic acid (MPA) therapy has been investigated in the treatment of moderate to severe psoriasis since the early 1970s and has been found to be both safe and effective. By inhibiting de novo purine biosynthesis, it functions as an antifungal, antibacterial, antiviral, and immunosuppressive agent. The recent availability of mycophenolate mofetil (MMF), a morpholinoester of MPA, has created renewed interest in the antipsoriatic properties of MPA. MMF is currently indicated for the prevention of organ rejection in transplant recipients and is used concomitantly with cyclosporine and corticosteroids. This review focuses on the pharmacology of MPA and MMF, studies of MPA in the treatment of psoriasis, and therapy with MMF. There is a potential application of MMF in the treatment of severe psoriasis and other inflammatory dermatoses, as well as topical MPA for the treatment of psoriasis.

Tretinoin emollient cream: a new therapy for photodamaged skin.

BACKGROUND Tretinoin administered topically in 0.1% concentration has been shown to improve the wrinkling and irregular pigmentation of photoaged skin. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION Tretinoin emollient cream 0.05% appears to be safe and effective in the treatment of photodamaged skin.

Once-weekly fluconazole (150, 300, or 450 mg) in the treatment of distal subungual onychomycosis of the fingernail.

BACKGROUND Onychomycosis is a prevalent infection of the nail caused primarily by dermatophytes. Fluconazole is active in vitro against the most common pathogens of onychomycosis, penetrates into the nail bed, and is clinically effective in the treatment of a wide variety of superficial fungal infections. OBJECTIVE The purpose of this study was to compare the efficacy and safety of three different doses of fluconazole (150, 300, and 450 mg) given orally once weekly to that of placebo in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. METHODS In this multicenter, double-blind study, 362 patients with mycologically confirmed onychomycosis were randomized to treatment with fluconazole, 150, 300, or 450 mg once weekly, or placebo once weekly for a maximum of 12 months. To enter the study, patients were required to have at least 25% involvement of the target nail with at least 2 mm of healthy nail from the nail fold to the proximal onychomycotic border. Patients who were clinically cured or improved at the end of treatment were further evaluated over a 6 month follow-up period. At both the end of therapy and the end of follow-up, clinical success of the target nail was defined as reduction of the affected area to less than 25% or cure. RESULTS At the end of therapy, 86% to 89% of patients in the fluconazole treatment groups were judged clinical successes as defined above compared with 8% of placebo-treated patients. Clinical cure (completely healthy nail) was achieved in 28% to 36% of fluconazole-treated patients compared with 3% of placebo-treated patients. Fluconazole demonstrated mycologic eradication rates of 47% to 62% at the end of therapy compared with 14% for placebo. The rates at the end of follow-up were very similar, indicating that eradication of the dermatophyte was maintained over the 6-month period. All efficacy measures for the fluconazole groups were significantly superior to placebo (p=0.0001); there were no significant differences between the fluconazole groups on these efficacy measures. The clinical relapse rate among cured patients over 6 months of follow-up was low at 4%. Fluconazole was well tolerated at all doses over the 12-month treatment period, with the incidence and severity of adverse events being similar between the fluconazole and placebo treatment groups. Mean time to clinical success in the fluconazole treatment groups was 6 to 7 months. This time frame may be used as a guideline for fluconazole treatment duration. CONCLUSION The results of this study support the use of fluconazole in the treatment of distal subungual onychomycosis of the toenail caused by dermatophytes. Doses between 150 to 450 mg weekly for 6 months were clinically and mycologically effective as well as safe and well tolerated.

A portable pulsed electromagnetic field (PEMF) device to enhance healing of recalcitrant venous ulcers: a double-blind, placebo-controlled clinical trial.

Summary A prospective, randomized, double‐bind, 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. Elevan 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.

Weekly low-dose methotrexate therapy for cutaneous sarcoidosis

Three patients with severe, treatment-resistant cutaneous sarcoidosis were treated with low-dose oral methotrexate on a weekly basis. Facial granulomas and ulcerations responded best. A response was apparent after several weeks of treatment, but 6 to 9 months were required to reach maximal effect.

Treatment of keratoacanthomas with oral 13-cis-retinoic acid.

KERATOACANTHOMAS are common cutaneous neoplasms that resemble squamous-cell carcinomas morphologically but behave in a biologically benign manner.1 A rare clinical manifestation of this neoplastic ...

Efficacy of topical sensitizers in the treatment of alopecia areata

It has been more than 2 decades since the first report of the use of dinitrochlorobenzene to induce hair growth in 2 patients with alopecia areata. Other topical sensitizers, namely squaric acid dibutylester and diphenylcyclopropenone, have been used with variable success. This article reviews the efficacy and safety of the use of topical sensitizers in the treatment of alopecia areata.

Clinical dose ranging studies with finasteride, a type 2 5α-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.