A randomized trial of the efficacy of a new micronized formulation versus a standard formulation of isotretinoin in patients with severe recalcitrant nodular acne.

BACKGROUND: Isotretinoin is very frequently the drug of choice for the management of severe recalcitrant nodular acne. Recently, a new micronized and more bioavailable formulation of isotretinoin has been developed that permits once-daily administration in lower doses than usually used with standard isotretinoin (Accutane), regardless of whether it is taken with or without food. OBJECTIVE: Our purpose was to determine whether micronized isotretinoin and standard isotretinoin are clinically equivalent. METHODS: In this multicenter, double-blind, double-dummy study, 600 patients with severe recalcitrant nodular acne were treated with either 0.4 mg/kg of micronized isotretinoin once daily without food (n = 300) or 1.0 mg/kg per day of standard isotretinoin in two divided doses with food (n = 300). Lesion counts were monitored over 20 weeks. RESULTS: Both treatment groups in this well-controlled clinical trial experienced an equivalent reduction in the number of total nodules (facial plus truncal). In addition, an equivalent proportion of patients achieved 90% clearance of the total number of nodules. Both formulations had similar results for other efficacy variables. CONCLUSION: Once-daily use of the micronized and more bioavailable formulation of isotretinoin under fasted conditions is clinically equivalent to the standard twice-daily formulation under fed conditions in the treatment of severe recalcitrant nodular acne.

Safety of a new micronized formulation of isotretinoin in patients with severe recalcitrant nodular acne: A randomized trial comparing micronized isotretinoin with standard isotretinoin.

BACKGROUND: Isotretinoin is a very effective drug for treating severe recalcitrant nodular acne. A new micronized formulation of isotretinoin has been shown to be clinically equivalent to standard isotretinoin with improved bioavailability and minimal food effect. The safety profile of the micronized formulation has not been described previously. OBJECTIVE: The objective of this article is to report the incidence and intensity of adverse events found in a comparative, double-blind efficacy study that showed clinical equivalence of the new micronized formulation of isotretinoin and the standard isotretinoin formulation (Accutane). METHODS: Six hundred patients with severe recalcitrant nodular acne were treated with micronized isotretinoin (n = 300) under fasted conditions or standard isotretinoin (n = 300) under fed conditions. One cohort received single daily doses of 0.4 mg/kg of micronized isotretinoin without food and the other cohort received 1.0 mg/kg per day of standard isotretinoin in two divided doses with food. Adverse events were monitored during 20 weeks of drug therapy. RESULTS: The proportion of adverse events in most body systems was generally lower in patients receiving micronized isotretinoin than in those receiving standard isotretinoin. CONCLUSION: Micronized isotretinoin appears to have a safety profile similar to that of standard isotretinoin and to carry a lower risk of mucocutaneous events and hypertriglyceridemia.

Concurrent application of tretinoin (retinoic acid) partially protects against corticosteroid-induced epidermal atrophy.

Cutaneous atrophy arising from prolonged use of potent topical corticosteroids has long been a concern. Thus, it would be advantageous to find an agent which protects against atrophy produced by corticosteroids but at the same time does not impair their anti-inflammatory effects. Recent work shows that topical all-trans retinoic acid (tretinoin) prevents skin atrophy in mice treated with topical corticosteroids, but such studies have not been performed in humans. We performed an 8-week clinical, histological and biochemical study to test the ability of tretinoin to enhance efficacy and inhibit atrophogenicity of topical corticosteroids, when used in the treatment of psoriasis. In each of 20 psoriasis patients, one plaque, and its perilesional skin, was treated once daily with betamethasone dipropionate and tretinoin 0.1%, and one plaque, and its perilesional skin, treated with once daily betamethasone dipropionate and tretinoin vehicle. There was no difference in the speed or degree of improvement in plaques treated with either the topical corticosteroid/tretinoin combination or with corticosteroid alone. Light microscopy revealed a 19% reduction in epidermal thickness, in corticosteroid-treated perilesional skin, as compared with a slight (1%) increase in corticosteroid/tretinoin-treated perilesional areas (P = 0.067). Western blot analysis showed a 55% reduction in procollagen I aminopropeptide in perilesional skin treated corticosteroid alone, as compared with a 45% reduction in corticosteroid/tretinoin-treated perilesional skin. These data indicate that the addition of tretinoin does not impair the efficacy of a topical corticosteroid, in the treatment of psoriasis, and partially ameliorates epidermal atrophy produced by the topical corticosteroid.

Topical tretinoin (retinoic acid) treatment for liver spots associated with photodamage.

BACKGROUND: The hyperpigmented lesions commonly called liver spots distress patients, in part because such lesions are associated with aging. We investigated their treatment with topical 0.1 percent tretinoin (retinoic acid). METHODS: Fifty-eight patients completed a 10-month randomized, double-blind study in which they applied either 0.1 percent tretinoin (n = 28) or vehicle (n = 30) cream daily to the face, upper extremities, or both. Fifteen patients who responded well were than randomly assigned to continue tretinoin therapy or use vehicle alone for six more months. Patients were evaluated by physical examination every month and by analysis of biopsy specimens of lesions obtained at base line and at the end of the 10-month trial. RESULTS: After one month of treatment the patients treated with tretinoin had significant lightening of hyperpigmented lesions as compared with the patients who received vehicle (P less than 0.002). After 10 months, 20 (83 percent) of the 24 patients with facial lesions who were treated with tretinoin had lightening of these lesions, as compared with 8 (29 percent) of the 28 patients with facial lesions who received vehicle. The results for lesions of the upper extremities were similar. As compared with vehicle, tretinoin caused a significant decrease in the degree of epidermal pigmentation and increases in the degree of compaction of stratum corneum, thickness of the granular cell layer, and epidermal thickness. Reductions in epidermal pigmentation evident on histologic analysis were significantly correlated with the degree of clinical lightening of lesions (r = -0.53, P less than 0.0001). During the 6-month follow-up study, specifically identified lesions that had disappeared during the first 10 months of tretinoin treatment did not return in any patient, and six of seven patients who continued to use tretinoin had further improvement. CONCLUSIONS: Topical 0.1 percent tretinoin significantly improves both clinical and microscopical manifestations of liver spots; these lesions do not return for at least six months after therapy is discontinued.

Comparison of minimal phototoxic dose and skin type for determining initial UVA dose in oral liquid methoxsalen photochemotherapy for the treatment of psoriasis.

Twenty-five patients with extensive psoriasis were randomly assigned into one of three groups, each receiving 0.5 mg/kg of oral liquid methoxsalen photochemotherapy followed 1 h later by exposure to long-wave ultraviolet light (UVA). The sole difference between the three groups was the method used to determine the initial UVA dose, which was either based on skin type, 25% of the minimal phototoxic dose (MPD), or 50% of the MPD. All patients were treated in the Phototherapy Unit at the Massachusetts General Hospital. Data were obtained until reaching the endpoint of clearance. At clearance, the results of the number of treatments required to clear, final UVA dose, cumulative UVA dose, and side effects were tabulated, compared, and analyzed for each of the three groups. The 25% and 50% MPD groups required a mean of 15.0 +/- 1.7 and 13.4 +/- 1.9 treatments to clear, respectively, as compared to the skin type group, which needed an average of 17.6 +/- 2.5 treatments. The mean final UVA dose was 7.4 +/- 0.9 J/cm2 and 8.4 +/- 1.4 J/cm2 for the 25% and 50% MPD groups, respectively, in contrast to 11.6 +/- 1.4 J/cm2 for the skin type group. The mean cumulative UVA dose at clearance for the 25% and 50% MPD groups was 79 +/- 16 J/cm2 and 87 +/- 27 J/cm2, respectively, versus 136 +/- 30 J/cm2 for the skin type group. The comparisons between the individual MPD groups and the skin type group did not achieve statistical significance with the exception of a marginally significant difference in final dose between the skin type group and the 25% MPD group (p = 0.06). However, the results of the two MPD groups were then pooled and the mean final (7.9 +/- 0.8 J/cm2) and cumulative (83 +/- 15 J/cm2) UVA doses were significantly (p = 0.04) and marginally significantly (p = 0.07) lower than the respective means of the skin type group. The number of treatments to clear, although lower in the pooled MPD groups (14.2 +/- 1.3) than in the skin type group, did not attain statistical significance (p = 0.19). Our data suggest that the MPD measurement may be superior to the skin-typing system when calculating the initial UVA dose in oral liquid methoxsalen photochemotherapy for the treatment of psoriasis.

An unusual presentation of fixed cutaneous sporotrichosis: a case report and review of the literature.

Sporotrichosis is extremely rare in infants. This report describes an 84-day-old girl with fixed cutaneous sporotrichosis, presumably transmitted by a cat. A rapid, complete response to a low dose of oral potassium iodide therapy was attained. To our knowledge, this is the youngest reported patient with sporotrichosis, as well as the lowest effective daily dose of potassium iodide.