Efficacy, safety and tolerability of topical terbinafine nail solution in patients with mild-to-moderate toenail onychomycosis: results from three randomized studies using double-blind vehicle-controlled and open-label active-controlled designs.

BACKGROUND: Terbinafine nail solution (TNS) was developed for the treatment of onychomycosis. OBJECTIVE: To assess the efficacy of TNS vs. vehicle and amorolfine 5% nail lacquer. METHODS: Subjects with mild-to-moderate toe onychomycosis (25% to ≤75% nail-involvement, matrix uninvolved) were randomized to receive either TNS or vehicle in two double-blind studies, and to TNS or amorolfine in an active-controlled, open-label study. Primary endpoint was complete cure (no residual clinical involvement and negative mycology) at week 52. Secondary endpoints were mycological cure (negative mycology defined as negative KOH microscopy and negative culture) and clinical effectiveness (≤10% residual-involvement and negative mycology) at week 52. RESULTS: Complete cure was not different between TNS vs. vehicle and amorolfine. Mycological cure was higher with TNS vs. vehicle, as was clinical effectiveness with TNS vs. vehicle, and TNS and amorolfine were not different for secondary efficacy endpoints. Patients achieving mycological cure had a better clinical outcome, and efficacy was improved in subjects with milder disease. Post hoc analysis suggests that nail thickness is an important prognostic factor. Moreover, mycological cure may require 6 months of treatment regimen while complete cure and clinical effectiveness may be achievable only after 10 months. A simulation study suggests that longer treatment duration would have resulted in higher complete cure with TNS vs. vehicle. Study treatments were well-tolerated. CONCLUSION: Primary efficacy objectives were not met in the studies reported herein. Possible reasons for failure to achieve significant outcomes include insufficient length of treatment; stringency of primary endpoint and severity of nail involvement of study population.

Addition of topical pimecrolimus to once-daily mid-potent steroid confers no short-term therapeutic benefit in the treatment of severe atopic dermatitis; a randomized controlled trial.

BACKGROUND: Combination therapy with pimecrolimus cream 1%, a topical calcineurin inhibitor (TCI), and fluticasone propionate cream 0.05% (FP), a mid-potency topical corticosteroid, may have a synergistic effect for treatment of atopic dermatitis (AD) because their mechanism of action differs. OBJECTIVES: To assess the efficacy of concomitant pimecrolimus twice daily/FP once daily vs. vehicle twice daily/FP once daily in patients with severe AD. METHODS: An exploratory, 2-week, double-blind, randomized, within-patient study was conducted (n = 45). Two target areas of similar severity, size and location were assessed. Assessments included the modified Eczema Area and Severity Index (0-12 scale) (primary variable), localized investigator global assessment (0-4 scale) and Patients' Self-Assessment of Disease Severity (0-4 scale). RESULTS: Data for all variables were similar for the TCI/FP and vehicle/FP treatments. CONCLUSIONS: The efficacy observed for treatment of severe AD flares with this TCI/FP combination regimen was equivalent to that of vehicle/FP.

Tissue penetration by ertapenem, a parenteral carbapenem administered once daily, in suction-induced skin blister fluid in healthy young volunteers.

The penetration of 1 g of intravenous ertapenem once daily for 3 days in suction-induced skin blisters was evaluated. Ten forearm blisters were formed (n = 12) 12 h prior to the last dose. Concentrations of ertapenem in blister fluid exceeded 4 micro g/ml (the MIC at which 90% of the isolates tested are eliminated) for the entire dosing interval. The area under the concentration-time curve for 0 to 24 h ratio of blister fluid to plasma was 61% (90% confidence interval, 56, 65%) suggesting good blister penetration.

The safety of calcitriol 3 microg/g ointment. Evaluation of cutaneous contact sensitization, cumulative irritancy, photoallergic contact sensitization and phototoxicity.

Vitamin D analogues are widely used for the treatment of psoriasis. A new topical formulation of calcitriol (3 microg/g ointment) has been shown to be effective in the treatment of stable plaque-type psoriasis. This paper reports the results of four separate studies designed to evaluate specific local-safety parameters: cumulative irritancy, cutaneous contact sensitization, potential photoallergic contact sensitization and phototoxicity. Calcitriol 3 microg/g ointment was classified as non-irritant when compared to calcipotriol, tacalcitol and white petrolatum. Petrolatum and tacalcitol were slightly irritant and calcipotriol moderately irritant. No sensitization was observed with calcitriol 3 microg/g ointment. With regard to phototoxic potential, sites treated with calcitriol 3 microg/g ointment or vehicle ointment were less irritated than those treated with white petrolatum or those that were untreated. Using standard photoallergenicity testing methodology, there were no skin reactions of a photoallergic nature to the study material. These studies showed that calcitriol 3 microg/g ointment is a well-tolerated treatment for stable plaque-type psoriasis.

Eumovate (clobetasone butyrate) 0.05% cream with its moisturizing emollient base has better healing properties than hydrocortisone 1% cream: a study in nickel-induced contact dermatitis.

BACKGROUND: The emollient base of a topical corticosteroid, through its moisturizing properties, can be a useful treatment adjunct. OBJECTIVE: To compare the healing properties of Eumovate trade mark (clobetasone butyrate) 0.05% cream with its emollient base, hydrocortisone 1% cream and with no treatment. METHODS: A single-centre, double-blind, intra-individual, comparative study that involved 18 volunteers with nickel-induced contact dermatitis. Following a positive patch test to nickel, sub-therapeutic amounts (10 micro l = 3 mg cm(-2)) of each of the treatments were applied twice daily for seven days to each of the four test sites. RESULTS: In terms of the primary endpoint, a physician's global assessment after 7 days of treatment, clobetasone butyrate (CB) 0.05% cream showed a significantly better response than hydrocortisone (HC) 1% cream (78% vs 39%, difference -0.4, 95% CI -0.7 to -0.1; p = 0.046) or no treatment (78% vs 28%, difference -0.5, 95% CI -0.9 to -0.1; p = 0.016). CB 0.05% cream also showed a better response than its emollient base (78% vs 56%), though statistical significance was not achieved. In terms of moisturizing effects, there was no difference in transepidermal water loss (TEWL) between CB 0.05% cream and its emollient base. CB 0.05% cream treated sites did, however, have significantly lower values (i.e. were more moisturized) than untreated sites (difference -8.5, 95% CI -12.0 to -4.86; p < 0.001) or HC 1% treated sites (difference -7.1, 95% CI -11.0 to -3.4; p < 0.001). In terms of skin blanching activity, as expected the steroid-based creams achieved lower colorimetric values than the emollient base cream. CONCLUSIONS: These results from experimentally induced skin inflammation indicate that CB 0.05% (as Eumovate 0.05% cream) has both more effective anti-inflammatory activity and better moisturizing properties than hydrocortisone 1% cream and that these effects are in part due to its efficient emollient base.

[Determination of acceptability of 2 cutaneous estradiol gels, in a dose of 1.5 mg daily]. / Appréciation de l'acceptabilité de deux gels d'estradiol cutané, à la dose d'1,5 mg par jour.

OBJECTIVE: The aim was to compare acceptability of a percutaneous 0. 1% estradiol gel (Gel A, Estreva(R) Gel, Laboratoire Théramex, Monaco) to that of an 0.06% estradiol gel (Gel B, Oestrodose(R), Laboratoires Besins-Iscovesco) in its new formulation and packaging. MATERIAL AND METHODS: This randomized, crossed, simple-blind study was carried out in 48 volunteer healthy postmenopausal women. The volunteers applied on one forearm 1.5 mg/day of cutaneous estradiol in the form of either gel, according to randomized allocation, for four days without free period between the two therapeutic periods. The application and drying times of the two gels were measured during the first application; gel subjective women assessment was collected at the beginning and at the end of the study. RESULTS: Mean application and drying times with Gel A are significantly reduced, compared to Gel B (p=0.0259 and p=0.0001, respectively) with drying time 61% shorter; these data are confirmed by subjective women evaluation. The two gels are not significantly different regarding several criteria as consistency, ease of application and sensation of lasting stickiness. However, a significant difference is found in favour of Gel A on the following items: practicality of application (p=0.007), ease of penetration (p<0.001), quantity of gel to apply (p<0.001) after the first application. After four days of administration, a same significant difference is observed concerning practicality of the gel (p=0.0078), duration of use (p<0. 001), packaging, women opinion on the gel (p=0.022) and the product, gel and packaging (p<0.001). At the end of the study, gel A utilization is considered by women more practical (p=0.001) with an easier application (p<0.001) and less restricting while applying (p=0.001), compared to Gel B; 72.9% of women prefer the Gel A and 12. 5% of women prefer the Gel B. CONCLUSION: A better acceptability of the 0.1% estradiol gel and of its packaging compared to that of the 0.06% estradiol gel in this new formulation and packaging is observed in this study.

Primary cutaneous pleomorphic small T-cell lymphoma. A review of 11 cases. The French Study Group on Cutaneous Lymphomas.

BACKGROUND AND DESIGN: Cutaneous pleomorphic small T-cell lymphoma is a rare, recently recognized lymphoma, different from mycosis fungoides and Sézary syndrome. Only a few cases have been reported and no treatment modalities have been defined. We reviewed the clinical, histologic, immunohistochemical, molecular biologic, and follow-up data of 11 primary cutaneous pleomorphic small T-cell lymphomas. RESULTS: The lesions presented as red purplish nodules, tumors, or plaques. The infiltrate consisted of small pleomorphic lymphoid cells without epidermotropism in nine patients and with a propensity to infiltrate the dermis and subcutaneous fat. Most cases were CD4+/CD8-. A T-cell clone was detected in the skin lesions of nine patients tested. The mean follow-up was 70.1 months and the median follow-up was 20 months. Ten patients are alive with three having persistent lesions. Interferon alfa-2a induced partial or complete remissions in five patients. Interferon alfa-2a combined with a regimen containing doxorubicin chlorhydrate induced a complete remission in a patient suffering a relapse after cyclophosphamide and interferon alone. CONCLUSIONS: Cutaneous pleomorphic small T-cell lymphoma is a well-defined type of low-grade cutaneous lymphoma with favorable prognosis. Interferon and/or chemotherapy are the treatment of choice in patients with large tumor burden.