Laboratory induction and clinical occurrence of combined clindamycin and erythromycin resistance in Corynebacterium acnes.

Corynebacterium acnes strains cross-resistant to clindamycin and erythromycin were observed following long-term selection or mutagenic treatment in the laboratory. Similar strains were found among clinical isolates from patients using clindamycin or erythromycin topically in the treatment of acne vulgaris. Clindamycin resistance was never observed in the absence of resistance to macrolides or other lincosaminides. It is suggested that this resistance may result from an alteration of the 50S ribosomal subunit.

Multicenter study comparing 0.05% gel formulations of desoximetasone and fluocinonide in patients with scalp psoriasis.

A double-blind, multicenter study was conducted to evaluate and compare the safety and efficacy of desoximetasone gel 0.05% and fluocinonide gel 0.05% in patients with scalp psoriasis. One hundred twenty-five patients were enrolled in this randomized, parallel-group trial. Responses based on clinical assessment in 123 patients showed that the desoximetasone gel formulation is a safe and effective treatment for psoriasis of the scalp. Although efficacy appears equivalent to that of fluocinonide gel 0.05% in treating psoriasis of the scalp, desoximetasone appears to be slightly better tolerated and better accepted cosmetically.

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.

Correlation of the vasoconstriction assay and clinical activity in psoriasis.

A large group of glucocorticosteroid formulations were assayed by the vasoconstriction test in normal skin sites and paired comparison studies in patients with psoriasis. Excellent correlation between the vasoconstriction assay and selected paired comparison studies occurred in 20 of 23 instances. In three instances, involving two glucocorticosteroid formulations tested, correlation was absent. The vasoconstrictor assay is an inexpensive and reliable method for screening glucocorticosteroid formulations for clinical activity in psoriasis.

Anemia of azaribine in the treatment of psoriasis.

Azaribine is an effective agent in the treatment of psoriasis. In this investigation the extent of clinical dermatologic remission appeared to correlate with the degree of metabolic block induced by 6-azauridylic acid, as quantitated by the urinary excretion of orotic acid and orotidine, and the development of anemia. Following azaribine therapy there was a coordinate rise of the specific activities of erythrocyte orotate phosphoribosyltransferase and orotidine-5'-monophosphate decarboxylase. There was no correlation between the pretreatment activity of these enzymes and the clinical response to azaribine. The anemia of azaribine therapy was mile and of a megaloblastic type. Uridine effectively corrected the azaribine-induced anemia, but led to exacerbation of the patients' psoriasis. Following uridine therapy there was a reduction in the urinary excretion of orotic acid and orotidine, presumable reflecting end-product inhibition or repression of the first steps of a repeated pyrimidine biosynthesis.

A clinical screening program for topical chemotherapeutic drugs in psoriasis.

In this national, multicenter cooperative study, a standardized drug screening program was designed and evaluated to test the clinical effectiveness of 30 topically applied chemotherapeutic drugs to psoriasis. Appropriate concentrations and vehicles for topical administration were selected with regard to clinical testing consisted of a double-blind application of test agents to psoriatic plaques under occlusion daily for up to nine days. Drugs known to be topically active in psoriasis, eg, thiotepa, fluorouracil, and betamethasone valerate, were easily detected in the clinical protocol, confirming the validity of this topical drug screening program. Seven drugs produced substantial clinical improvement with evidence of clearing; nine drugs produced slight improvement; 14 drugs had no effect. No systemic toxid reactions occurred. This screen should be useful to test other potential antipsoriatic drugs and to evaluate potential animal model screens for their predictive values with the same drugs.

Comparison of amcinonide ointment 0.1 percent twice daily and fluocinonide ointment 0.05 percent three times daily in the treatment of psoriasis.

Thirty-nine patients with psoriasis were treated either with amcinonide ointment 0.1 percent twice a day or with fluocinonide ointment 0.05 percent three times a day in a two-week, randomized, parallel-group, double-blind study. The severities of the skin lesions at baseline and at weekly intervals and the overall improvement at weekly intervals were evaluated by the investigator and the patient. The skin lesions improved significantly (p less than or equal to 0.01) over their condition at baseline, with good overall improvement attained by both treatment groups within one week. Both treatments were well tolerated. Amcinonide ointment 0.1 percent applied twice a day was found to be as effective and acceptable to patients as was fluocinonide ointment 0.05 percent applied three times a day in the treatment of psoriasis.

A comparison of clobetasol propionate 0.05 percent ointment and an optimized betamethasone dipropionate 0.05 percent ointment in the treatment of psoriasis.

A multicenter, double-blind study compared the effectiveness of two highly potent topical corticosteroids in patients with moderate to severe signs of psoriasis. Left/right paired comparisons of clobetasol propionate ointment 0.05 percent, and an optimized formulation of betamethasone dipropionate ointment 0.05 percent, were made in 130 patients with roughly symmetrical psoriatic lesions. The ointments were applied by the patients twice daily, without occlusion, for two weeks. Both drugs were shown to be highly effective and were well tolerated. Significantly more patients showed greater improvement on the side treated with clobetasol propionate. Follow-up evaluation two weeks after the treatment period showed statistically significant (p less than 0.001) longer remissions resulting from the use of clobetasol propionate.

New cream vehicle for flurandrenolide.

New methods are now available to help select vehicles for topical corticosteroids. In the development of a new cream vehicle for flurandrenolide, the goal was a cream base with optimal solubility for release of the drug, minimal irritation potential, and no sensitizing preservatives. Vasoconstriction tests make selection much more scientific, and a newer method for such testing is described in detail. Irritation testing then helped determine the vehicle concentration that was least irritating. Final studies included double-blind comparisons with the previous formulation in the treatment of psoriatic patients.

Double-blind comparison of topical 1 percent clindamycin phosphate (Cleocin T) and oral tetracycline 500 mg/day in the treatment of acne vulgaris.

An eight week double-blind study comparing 1 percent clindamycin phosphate (Cleocin T) applied topically with tetracycline 500 mg a day taken orally was conducted in fifty subjects. Topically applied 1 percent clindamycin phosphate was found to be superior to oral tetracycline at six weeks as judged by patient evaluation and reduction of papules. There was a consistent trend favoring clindamycin phosphate at the other visits but the difference was not significant. The use of topically applied 1 percent clindamycin phosphate seems to be a logical alternative to the use of oral tetracycline.

The effect of alclometasone dipropionate cream 0.05% on the hypothalamic-pituitary-adrenal axis of normal volunteers.

In an open study of ten evaluable normal volunteers, 30 g of alclometasone dipropionate cream 0.05% was applied to 80% of body surface each morning and evening for 21 days. A plastic body suit effectively occluded the treated area for 12 hours/day. As demonstrated by continued normal levels of 8 a.m. plasma cortisol and 24-hour urinary 17-hydroxysteroid and free cortisol, no suppression of the hypothalamic-pituitary-adrenal axis occurred. Local adverse reactions were mild and transient.

Clinical trials of topical corticosteroids in psoriasis: correlations with the vasoconstrictor assay.

It would be desirable to develop an alternative system to clinical studies to evaluate the potency of generic topical corticosteroids and of new formulations of existing innovator corticosteroids. The vasoconstrictor assay is a reliable method for testing potency; however, its results do not always agree with clinical studies. Psoriasis offers an ideal clinical model to evaluate corticoid potency because the ability to perform within-patient comparisons of the treatment of bilateral lesions permits meaningful comparisons with a relatively small sample size. The results of bilateral comparisons in psoriasis agreed with those of the vasoconstrictor assay in 20 of 23 comparisons of active agents and in numerous comparisons of active corticosteroids with a placebo. Eczematous dermatoses do not lend themselves well to bilateral paired comparison studies and therefore require parallel treatment studies with relatively large sample sizes to produce statistically significant comparisons.

Topical clobetasol-17-propionate: review of its clinical efficacy and safety.

Clobetasol-17-propionate, the most potent of currently available topical steroids as predicted by the vasoconstrictor assay, has just been approved in the United States. In psoriasis, it has proved significantly more effective than class II steroids and as or more effective than the only marketed class I steroid. In the more steroid-responsive eczemas, the superior efficacy of clobetasol is also apparent, but less striking. Clobetasol prolongs remission rates, making intermittent treatment schedules feasible and minimizing inherent potential steroid side effects. Clobetasol may also be useful in the treatment of a myriad of other skin conditions. A review of the pharmacology, efficacy, and side effects of this addition to our dermatologic armamentarium is presented here.

Six-month controlled study of effect of desoximetasone and betamethasone 17-valerate on the pituitary-adrenal axis.

Twenty-two patients were treated with desoximetasone emollient cream 0.25% twice daily without occlusion for 6 months. Patients applied the medication to approximately one-third of their body over psoriatic lesions. Corticosteroid plasma cortisol values decreased to below normal limits in nine patients before the 6-month study was terminated. In four of these the plasma cortisol spontaneously returned to normal despite therapy; in four other patients, however, the plasma cortisol was still suppressed at the end of 5 months of continual therapy but returned to normal within 7 days of discontinuation of the medication. In one patient, lost to further follow-up at 5 1/2 months of therapy, the trend at the fourth month was an increase in plasma cortisol to within one unit of normal range. Betamethasone 17-valerate 0.1% cream applied twice daily did not suppress plasma cortisol in twenty-three patients similarly tested. The clinical response to desoximetasone emollient cream was significantly better than to betamethasone valerate cream. This study closely approximates the way in which many patients with steroid-responsive dermatoses use potent topical steroids, namely over a long time period and without occlusion.

Plasma complement and histamine changes in atopic dermatitis.

Fifteen patients with atopic dermatitis were investigated to evaluate the total of complement and histamine. In five patients total serum complement haemolytic activity (CH50) was significantly decreased as was the haemolytic activity of complement components C2 (C2H50) and C3 (C3H50). By counter immunoelectrophoresis split products of C3 were detected. There was no evidence for alternative pathway activation or the presence of an activator of the alternative pathway. In three patients plasma histamine concentrations were elevated. The intensity of the complement and histamine changes observed seemed to be correlated to the severity of the disease.