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Objective: To assess the safety and efficacy of 4 concentrations of tazarotene cream in the treatment of facial photodamage., Design: Prospective weekly multicenter, investigator-masked, randomized, parallel-group study., Setting: University hospitals and clinical research centers., Patients: Three hundred forty-nine subjects with facial photodamage., Intervention: Daily topical application of tazarotene cream (0.01%, 0.025%, 0.05%, and 0.1%) compared with its vehicle and with 0.05% tretinoin emollient cream., Results: Tazarotene cream and tretinoin cream significantly improved mottled hyperpigmentation and fine wrinkles. At week 24, treatment success rates based on global responses were 67% (39 of 58 subjects) with 0.1% tazarotene, 52% (30 of 58 subjects) with 0.05% tazarotene, 36% (21 of 58 subjects) with 0.025% tazarotene, 41% (24 of 59 subjects) with 0.01% tazarotene, 55% (32 of 58 subjects) with 0.05% tretinoin, and 22% (13 of 58 subjects) with vehicle. Local adverse events, although more frequent with tazarotene at higher concentrations, were generally mild to moderate., Conclusions: Tazarotene in a cream formulation is safe and is associated with positive changes in the treatment of photodamaged facial skin.

The possibility that there is an increased risk of melanoma in patients with psoriasis treated with psoralen-UV-A (PUVA) therapy has raised concern on the part of physicians and patients about the long-term safety of this treatment. In response to this concern, the National Psoriasis Foundation sponsored a workshop at which invited participants with expertise in PUVA therapy, psoriasis treatment, melanoma and nonmelanoma skin cancer, and epidemiological and clinical trials were asked to develop a consensus on the following 3 issues: the risk of long-term adverse effects of PUVA therapy with emphasis on nonmelanoma and melanoma skin cancer; the guidelines for physicians and patients for selection and use of PUVA therapy with consideration of the risk-benefit ratio of this treatment compared with the risk-benefit ratios of alternative treatments; and the directions for further evaluation of the long-term effects Of PUVA therapy.

Objective: To determine the safety and efficacy of topically applied tazarotene gel in the treatment of mild to moderate psoriatic plaques., Design: Two multicenter, double-blind, randomized studies of 6- and 8-week duration, with an 8-week follow-up in the second study., Setting: Medical center outpatient dermatology services., Participants: One hundred fifty-three adults with 2 bilateral target plaques on the trunk, legs, or arms., Interventions: Vehicle gel or 0.01% and 0.05% tazarotene gel administered twice daily to 45 patients (study A), or 0.05% and 0.1% tazarotene gel administered either once or twice daily to 108 patients (study B)., Main Outcome Measures: Treatment success and plaque elevation, scaling, and erythema vs time., Results: The 0.01% tazarotene gel showed minimal efficacy. Applications of 0.05% and 0.1% tazarotene gels administered once or twice daily, resulted in significant improvements in plaque elevation, scaling, erythema, and overall clinical severity as early as 1 week. Treatment success rates (defined as > 75% improvement from baseline) were 45% with 0.05% tazarotene gel vs 13% with vehicle gel after 6 weeks of treatment (P < .05; study A) and ranged from 48% to 63% with the various tazarotene treatment regimens after 8 weeks of treatment (study B). These improvements were evident at the 8-week follow-up. Treatment-related adverse effects were generally limited to mild or moderate local irritation and were less frequent with the treatment regimen administered once daily., Conclusion: The 0.05% and 0.1% tazarotene gels demonstrated significant efficacy in the treatment of mild to moderate psoriatic plaques that persisted after cessation of treatment.

Objective: To examine the safety and efficacy of photodynamic therapy using topical 5-aminolevulinic acid (ALA) and red light to treat actinic keratoses (AKs)., Design: Actinic keratoses were treated with topical ALA (concentrations of 0%, 10%, 20%, or 30%) under occlusion for 3 hours. Before photodynamic therapy, sites were examined for fluorescence. Sites were irradiated with an argon pumped dye laser (630 nm) at fluences of 10 to 150 J/cm2., Setting: Academic medical center., Patients: Forty patients with 6 clinically typical, previously untreated AKs per patient., Main Outcome Measure: Complete resolution and decrease in lesion area of the AK relative to baseline evaluated at weeks 1, 4, 8, and 16., Results: Three hours after ALA administration, lesions showed moderate red fluorescence. Cutaneous phototoxic effects, localized erythema and edema, peaked at 72 hours. Patients experienced mild burning and stinging during light exposure. Eight weeks after a single treatment using 30% ALA, there was total clearing of 91% of lesions on the face and scalp and 45% of lesions, on the trunk and extremities. No significant differences were observed in clinical responses with treatment using 10%, 20%, or 30% ALA. All concentrations of ALA were more effective than treating AKs with vehicle and light., Conclusions: Topical photodynamic therapy with ALA is an effective treatment of typical AKs. Complete clearing of nonhypertrophic AKs can be achieved with 10%, 20%, or 30% ALA that is easily tolerated by the patient. Lesions on the face and scalp are more effectively treated than lesions on the trunk and extremities. Hypertrophic AKs did not respond effectively.

Methotrexate is an effective and convenient treatment for severe psoriasis whose use is limited by the development of hepatic fibrosis and cirrhosis in a small number of patients. The mechanism of hepatotoxicity is unknown, but it is believed to be the result of intracellular polyglutamation and prolonged retention of methotrexate within the cell. Piritrexim isethionate is a lipid-soluble antifolate that has a mechanism of action similar to that of methotrexate. Since it is not polyglutamated, piritrexim could be effective in the treatment of psoriasis without the associated long-term hepatotoxicity. A 12-week phase I/II clinical trial of severe chronic plaque psoriasis assessed the safety and efficacy of oral piritrexim therapy. Based on experience gained from oncologic trials, each patient received a twice-daily dosage for 5 consecutive days every 2 weeks. Dosages ranged from 25 to 100 mg twice a day. Improvement in both lesion scores and percentage of body involvement was significant at a dose of 50 mg or more twice daily. Fifteen of 19 patients who completed 12 weeks of therapy demonstrated greater than 50% improvement in lesion scores. Improvement was limited by recrudescence of lesions over the 9-day rest period. Adverse experiences were minimal and dose related. Piritrexim is efficacious in the treatment of psoriasis.

A questionnaire that was mailed to 510 randomly selected dermatologists in the United States surveyed their use of three systemic chemotherapeutic agents for the treatment of psoriasis during the two-year period of 1973 to 1974. Methotrexate was used by 52% of the surveyed dermatologists, while hydroxyurea and azaribine were used by 10% and 2%, respectively. Seventy-five percent of the dermatologists who used methotrexate treated ten or fewer psoriatic patients with this drug. Multiple dose therapy with methotrexate divided over a period of 36 hours each week was the preferred schedule of 66% of the dermatologists. Liver biopsy specimens and creatinine clearance tests were obtained for only 17% and 35% of patients, respectively, prior to initiating methotrexate therapy. The estimated number of dermatologist-treated psoriatics nationwide receiving methotrexate is 25,000.

The effects of 28 different antiproliferative agents applied topically to normal and hyperproliferative hairless mouse skin were studied. Epidermal cell hyperproliferation was induced by an essential fatty acid-deficient diet or by irradiation with short-wavelength ultraviolet (UV) energy. Epidermal DNA synthesis was measured by hydroxyapatite column chromatography. We compared the effects of these drugs used on normal and hyperproliferative hairless mouse skin with clinical responses in patients with psoriasis treated using the same topical preparations. For most of the drugs tested, the normal and essential fatty acid-deficient mouse model effects showed a good correlation with clinical responses seen in treated patients with psoriasis. The short-wavelength UV energy-treated mouse model effects showed a poorer clinical correlation, perhaps partially caused by wide variations in DNA synthetic rates encountered in the epidermis in this model.

In five patients with annular tinea corporis, the tritated thymidine labeling indexes were determined in the rim, center, and intermediate areas of the lesion and compared with normal skin. Labeling indexes at the rim were much higher than those of normal skin (mean, 4.2 times). Labeling indexes elsewhere in the lesion were not significantly different from those of normal skin. Histologic examination showed epidermal thickening in all areas of the lesion as compared with normal skin. This study suggests that there is an increased epidermal turnover at the rim of annular dermatophytosis that may be important in the pathophysiology and morphogenesis of such lesions.

In an attempt to evaluate and improve the Goeckerman treatment of psoriasis, combinations of tar and ultraviolet (UV) light were studied. The effects of UV irradiation alone, of curde coal tar (CCT) ointment alone, and of UV irradiation with 1% CCT ointment and with 6% CCT ointment on psoriatic lesions were compared. The combinations of 1% CCT ointment with UV irradiation and of 6% CCT ointment with UV irradiation were found to be equally effective. The combination of UV irradiation with ointment had little effect on psoriatic lesions. In most cases, the combination of 1% CCT ointment and UV irradiation was superior to high-concentration (6%) tar ointment without UV irradiation. This study suggests that UV light is an important component of the Goeckerman treatment ant that tar and UV irradiation are superior to tar alone.

In 1974, we conducted a randomized survey of dermatologists to determine trends in the use of chemotherapeutic agents for psoriasis. The present survey updates and extends the earlier one to include phototherapy, photochemotherapy, and other modalities being used in the treatment of psoriasis too extensive or severe for topical agents alone. Questionnaires were sent to approximately 20% of dermatologists nationwide and also to all training/research programs. Results of the survey include: (1) approximately 523,000 patients with psoriasis were treated by dermatologists in 1984, and 30% of these were severe enough to require more than topical care; (2) the majority of dermatologists use ultraviolet B (71%) and methotrexate (58%), while 36% use psoralen and ultraviolet A; (3) creatinine clearance rates and liver biopsy specimens are being obtained for approximately half of methotrexate-treated patients; and (4) of those physicians using methotrexate, most (74%) use weekly divided orally administered methotrexate doses.

The mouse vaginal assay was modified to study mechanisms of drug action in epithelial cells in relation to the cell cycle. An evaluation of the labeling index, mitotic index, and the percent labeled mitoses in the vaginal epithelium was used to determine the site of drug action in the cell cycle. Systemic absorption from the vaginal epithelium was also monitored by these same measurements in rectal mucosa. Thirty drugs was tested; 17 showed cell kinetic perturbations in the vaginal mucosa and four of these had both vaginal (local) and rectal (systemic) effects. Thirteen drugs had no effect, suggesting inadequate concentration, penetration, duration of drugs exposure, or lack of biochemical action. These 30 drugs were tested in concentrations and vehicles also used for topical screening in psoriatic patients. Only 15 of the 30 drugs tested in this model predicted the clinical results.