A comparative trial of two retinoids commonly used in the treatment of acne vulgaris.

BACKGROUND: Topical retinoids are highly effective treatments for acne vulgaris. The various formulations and concentrations available allow physicians to tailor therapies to individual patient's needs and minimize the cutaneous irritation that is often observed with the use of these drugs. OBJECTIVE: To compare the efficacy and safety of tretinoin gel microsphere 0.1% with adapalene gel 0.1% in the treatment of acne vulgaris. METHODS: A 12-week double-blind study was conducted, and patients were evaluated at baseline and at weeks 2, 3, 4, 6, 8, 10, and 12. RESULTS: Although the two drugs displayed similar efficacy in the resolution of acne lesions at 12 weeks, a significantly greater reduction in the number of comedones was seen at week 4 among patients treated with tretinoin gel microsphere (p = 0.047). Patients receiving tretinoin gel microsphere had an increased incidence of dryness (weeks 8 and 10) and peeling (weeks 3, 6, 8, and 10) compared with those patients treated with adapalene gel, but the two groups were comparable with respect to erythema, burning/stinging, and itching. CONCLUSION: Both drugs have similar efficacy in the resolution of acne lesions but tretinoin gel microsphere may result in a faster onset of action in the reduction of comedones compared to adapalene.

Ketoconazole 2% shampoo in the treatment of tinea versicolor: a multicenter, randomized, double-blind, placebo-controlled trial.

BACKGROUND: Tinea versicolor is a common superficial fungal infection caused by a lipophilic yeast. This chronically recurring opportunistic infection is especially prevalent in tropical and semitropical regions. The topical short-term application of ketoconazole 2% shampoo may provide effective and safe therapy for tinea versicolor. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of a single application (1 day) versus three daily applications (3 days) of ketoconazole 2% shampoo versus placebo shampoo in the treatment of mycologically confirmed tinea versicolor. METHODS: Three hundred twelve patients were included in the primary analyses for this 31-day study. Global evaluation scores were measured on days 10 and 31 with a 5-point scale (1 = healed to 5 = worsening), and a cellophane tape test was done at baseline and days 3, 10, and 31. Efficacy was assessed by clinical response, defined as both a global evaluation score of 1 (healed) and a negative cellophane tape test on day 31. Signs and symptoms of tinea versicolor (scaling, itching, erythema, hypopigmentation, hyperpigmentation) also were evaluated at baseline, day 10, and day 31 with a 4-point scale (0 = absent to 3 = severe). RESULTS: Both regimens of ketoconazole shampoo were significantly (P < .001) more effective than placebo for rate of clinical response, global evaluation scores, and mycologic outcomes (cellophane tape test). The clinical response rates at day 31 were 73%, 69%, and 5% for the 3-day ketoconazole, 1-day ketoconazole, and placebo groups, respectively. The difference in the efficacy of the two ketoconazole treatment regimens was not statistically significant. There were no significant differences between any of the treatment groups in the number of patients who experienced adverse events. No serious adverse events occurred and no patient withdrew from the trial prematurely because of an adverse event. CONCLUSION: Ketoconazole 2% shampoo, used as a single application or daily for 3 days, is safe and highly effective in the treatment of tinea versicolor.

Long-term safety of cyclosporine in the treatment of psoriasis.

BACKGROUND AND DESIGN: Cyclosporine has proved to be highly effective in the treatment of psoriasis. However, cyclosporine is potentially toxic. Side effects include renal toxic effects, hypertension, and an increased risk of malignant neoplasm. The toxicity of cyclosporine is dose-related, yet the safe duration of treatment is undefined. We studied the hospital records of all patients with psoriasis treated with cyclosporine at Saint Louis Hospital, Paris, France, between January 1, 1987, and December 31, 1993. In total, 122 patients treated for 3 to 76 months were evaluated. RESULTS: The percentage of patients who discontinued treatment because of side effects rose from a mean +/- SD of 14% +/- 2.4% at 12 months to 41% +/- 6.7% at 48 months. An increase in serum creatinine levels to more than 30% above the baseline value occurred in 53 patients after a median treatment time of 23 months. Hypertension developed in 29 patients after a median treatment time of 53 months. Three initial patient characteristics--age older than 50 years (P = .04), initial diastolic pressure higher than 75 mm Hg (P = 0.5), and serum creatinine levels more than 100 mumol/L (1.1 mg/dL) (P = .02, log rank test)--predicted discontinuation of cyclosporine because of side effects. CONCLUSIONS: The risk of cyclosporine-induced toxic effects increases with age of the patient and with preexisting hypertension or high serum creatinine levels. The data suggest that the incidence of side effects increases with time. Thus, cyclosporine is not an acceptable long-term monotherapy for psoriasis.

A novel therapeutic approach to psoriasis with combination calcipotriol ointment and very low-dose cyclosporine: results of a multicenter placebo-controlled study.

BACKGROUND: Recent advances in the treatment of psoriasis include both the topical vitamin D analogue calcipotriol and cyclosporine. Combined treatments have been sought to decrease the incidence of side effects while maintaining efficacy in the treatment of severe chronic plaque psoriasis. OBJECTIVE: The objective of this study was to evaluate the efficacy and safety of the combination of 2 mg/kg/day of cyclosporine with calcipotriol ointment (50 micrograms/gm) in the treatment of severe plaque psoriasis. METHODS: Sixty-nine patients were randomly selected for this double-blind, multicenter study to receive cyclosporine (2 mg/kg/day) combined with calcipotriol ointment (50 micrograms/gm) or cyclosporine (2 mg/kg/day) combined with placebo ointment (vehicle of calcipotriol) for a 6-week period. RESULTS: Complete clearing or 90% improvement in Psoriasis Area and Severity Index score occurred in 50.0% of patients in the calcipotriol/cyclosporine group in comparison with 11.8% of patients treated with placebo/cyclosporine (p = 0.0019). The confidence interval for the difference ranged from 17.8% to 58.7%. No difference was found between the two groups with respect to side effects. CONCLUSION: The calcipotriol/cyclosporine combination was more effective than placebo/cyclosporine. Further studies are needed to establish the long-term efficacy and safety profile of this combination therapy.

Studies of the effect of cyclosporine in psoriasis in vivo: combined effects on activated T lymphocytes and epidermal regenerative maturation.

Cyclosporine (CSA) decreases lymphokine synthesis and keratinocyte proliferation in vitro, but its in vivo mechanism of action in treating recalcitrant psoriasis is incompletely understood. Ten psoriasis patients were treated with CSA (2-7.5 mg/kg/d) with clinical improvement in nine of 10 patients. Skin biopsies before and after 1-3 months of CSA treatment were studied for evidence of immune and keratinocyte activation using immunoperoxidase and Northern blotting analysis. The number of activated, IL-2 receptor+ T cells in plaques after CSA treatment was reduced in all patients by a mean of 60%. Seven of 10 patients showed a decrease in keratinocyte HLA-DR expression; five of seven showed a decrease in gamma-IP-10 immunoreactivity, suggesting a decline in gamma interferon levels in plaques after CSA therapy. We studied the effect of CSA treatment in vivo on TGF-alpha, IL-6, and keratin K16 expression, three markers of keratinocyte growth activation. Expression of keratinocyte TGF-alpha and IL-6, which are elevated in active psoriatic epidermis, did not change in these patients after CSA treatment. The majority of patients (five of eight) continued to express the hyperproliferative keratin K16 after CSA treatment. Our results suggest that the predominant direct mechanism of action of Cyclosporine in vivo is a diminution of T-cell activation in plaques, with attendant decreased lymphokine production.

Hypertriglyceridemia in patients with psoriasis treated with cyclosporine.

Eight patients received cyclosporine at doses of 2.0 to 7.5 mg/kg/day. Seven of these patients had increased fasting plasma triglyceride levels with cyclosporine therapy compared with pretreatment values, which peaked after 1 month of therapy. Four patients experienced elevations in fasting triglycerides, over the upper limits for age- and sex-matched controls, which were at least two times higher than their baseline values. It was striking that all four of these patients had previously had hypertriglyceridemia while using etretinate and three of these patients had preexisting hypertriglyceridemia before both etretinate and cyclosporine therapy. Triglyceride elevation did not correlate with cyclosporine levels. Thus cyclosporine, similar to etretinate, unmasks a latent tendency for mild to moderate hypertriglyceridemia. Fasting triglyceride levels should be monitored during cyclosporine therapy, especially after 1 to 2 months of use, and in patients with preexisting increased triglycerides and/or a history of etretinate use.

Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes.

Psoriasis is a common papulosquamous skin disease. The histopathology is characterized by epidermal hyperplasia and inflammation. Recent studies suggest that keratinocyte proliferation and inflammation in psoriasis are manifestations of the same underlying pathological process. Interleukin 6 (IL-6), a cytokine that is a major mediator of the host response to tissue injury and infection, is produced by both keratinocytes and leukocytes in culture. IL-6 expression was studied in psoriatic plaques by immunoperoxidase staining with two different polyclonal anti-recombinant IL-6 antisera and by in situ nucleic acid hybridization with IL-6 cRNA probes. Epidermal and dermal cells in active psoriatic plaques from 35 psoriasis patients stained heavily for IL-6 as compared with nonlesional skin and with plaques after treatment with antimetabolic and antiinflammatory agents. Absorption of the anti-recombinant IL-6 antisera with purified fibroblast-derived IL-6 or with recombinant IL-6, but not bovine serum albumin, removed the immunostaining. Increased levels of IL-6 were detected in the plasma of patients with active psoriasis (mean 3 ng/ml) by using two different bioassays. IL-6 production by proliferating keratinocytes was suggested by IL-6-specific immunostaining in cultured normal and psoriatic keratinocytes and by the detection of mRNA specific for IL-6 in psoriatic epidermis by in situ hybridization. IL-6 stimulated the proliferation of cultured, normal human keratinocytes as assessed by two different assays. Thus, IL-6 could directly contribute to the epidermal hyperplasia seen in psoriatic epithelium as well as affect the function of dermal inflammatory cells.

The development of scales to measure social support for diet and exercise behaviors.

The purpose of this study was to develop measures of perceived social support specific to health-related eating and exercise behaviors. In Study I, specific supportive and nonsupportive behaviors were identified through interviews with 40 individuals making health-behavior changes. In Study II, items derived from the interviews were administered to 171 subjects. Support from family and friends was assessed separately for both diet and exercise habits. Meaningful factors were identified for each of the four scales, and some factors were similar for family and friend scales. Both test-retest and internal consistency reliabilities were acceptable, and six factors can be used as subscales. Social support scales were correlated with respective self-reported dietary and exercise habits, providing evidence of concurrent criterion-related validity. A measure of general social support was not related to the specific social support scales or to reported health habits. These scales are among the first measures of social support behaviors specific to dietary- and exercise-habit change.