Tazarotene cream versus adapalene cream in the treatment of facial acne vulgaris: a multicenter, double-blind, randomized, parallel-group study.

A multicenter, double-blind, randomized, parallel-group trial compared tazarotene 0.1% cream with adapalene 0.1% cream, once daily for 12 weeks, in 173 patients with facial acne vulgaris. Tazarotene was associated with a significantly greater incidence of patients achieving 50% or greater global improvement (77% vs. 55%, P < or = .01), and a significantly greater reduction in comedo count (median of 68% vs. 36%, P < or =.001, compared with adapalene. A significant between-group difference in baseline inflammatory lesion count precluded a comparison of efficacy against inflammatory acne. The most common adverse events were dryness, peeling/flaking, itching, redness/erythema, burning, and facial irritation with comparable incidences of each between groups. Mean peeling and burning levels were milder with adapalene, though were trace or less in both groups throughout. There were no significant between-group differences in the incidence of patients discontinuing due to lack of efficacy or adverse events. Tazarotene cream offers significantly greater efficacy and comparable tolerability to adapalene cream.

The effect of the menstrual cycle on acne.

Acne is a common disease with an underlying hormonal basis; however, there has never been a study to determine the ways in which the different stages of the menstrual cycle affect acne in women. Four hundred female participants, aged 12 to 52 years, were questioned whether their acne got worse before, during, or after their menstrual period and also asked whether it was unrelated to the menstrual period. Their age, severity of acne, ethnicity, and oral contraceptive use were also recorded. Overall 177 of 400 (44%) of those interviewed experienced premenstrual flares of their acne. Severity of acne, ethnicity, and oral contraceptive use did not affect the premenstrual flare rate. Women older than 33 years had a higher rate of premenstrual flares relative to women aged 20 to 33 years (P =.03 by chi(2) analysis). We concluded that almost half of all women experience premenstrual flares of their acne. Premenstrual flares may be more common in older women.

Isotretinoin dosing: past, present, and future trends.

Isotretinoin is the treatment of choice for severe nodulocystic acne. It represents the sole agent that effectively addresses all of the pathophysiological factors in the production of acne. Dosing recommendations are based on European trials that included patients with nonacne skin disease, which requires higher doses of isotretinoin for clearance. In this article, the authors relate their extensive experience with dosing regimens for acne as well as discuss recommendations for length of therapy.

The integral role of topical and oral retinoids in the early treatment of acne.

This article will review the rationale for early use of topical retinoids alone or in combination with topical antimicrobials in light of the pathogenesis of microcomedones and later lesions. Knowledge of the pathogenic processes in acne vulgaris has risen dramatically over the last three decades. It is now widely accepted that acne is the result of four distinct processes: increased proliferation, cornification, and shedding of follicular epithelium; increased sebum production; colonization of the follicle with Propionibacterium acnes; and induction of inflammatory responses by bacterial antigens and cell signals. Clinical focus of disease management has shifted toward earlier treatment targeting these fundamental processes. Elimination of microcomedones, the precursor to all subsequent lesions, would optimize acne therapy by preventing the later inflammatory stages of disease. With the exception of oral isotretinoin, no single first-line agent addresses all pathogenic mechanisms. Topical retinoids have comedolytic and in some cases anti-inflammatory effects, but have no direct impact on P. acnes. Thus treatment with a combination of topical retinoid and topical antimicrobial is warranted. The former can also enhance penetration of the latter by increasing microcomedonal extrusion. In selecting a combination, one must consider efficacy, cost, and likelihood of compliance. Once thought to be effective primarily for treating comedones, topical retinoids have also been demonstrated to be effective in reducing inflammatory lesions. The activity of a topical retinoid combined with an antimicrobial agent has been shown to clear more lesions and to clear them more rapidly than antimicrobial therapy alone. Topical retinoids are also used effectively to maintain remissions.

Tazarotene gel is safe and effective in the treatment of acne vulgaris: a multicenter, double-blind, vehicle-controlled study.

Retinoids reverse the abnormal pattern of keratinization seen in acne vulgaris. Tazarotene is the first of a novel family of topical receptor-selective acetylenic retinoids. This study evaluates the safety and efficacy of topical tazarotene 0.1% and 0.05% gels, in comparison to vehicle gel, applied once daily for 12 weeks, in the treatment of mild-to-moderate facial acne vulgaris. A total of 446 patients with facial acne vulgaris were enrolled, and 375 patients, ranging in age from 14 to 44 years, were evaluable in this multicenter, double-blind, randomized study. In comparison to vehicle gel, treatment with tazarotene 0.1% gel resulted in significantly greater reductions in noninflammatory and total lesion counts at all follow-up visits, and inflammatory lesion counts at Week 12. Tazarotene 0.05% gel resulted in significantly greater reductions in noninflammatory and total lesion counts than vehicle gel at Weeks 8 and 12. At Week 12, treatment success rates were 68% and 51% for tazarotene 0.1% and 0.05%, respectively (40% for vehicle gel). Tazarotene gel was an effective, safe, and generally well-tolerated therapy for the treatment of acne vulgaris.

Finasteride in the treatment of men with frontal male pattern hair loss.

BACKGROUND: Finasteride, a specific inhibitor of type II 5alpha-reductase, decreases serum and scalp dihydrotestosterone and has been shown to be effective in men with vertex male pattern hair loss. OBJECTIVE: This study evaluated the efficacy of finasteride 1 mg/day in men with frontal (anterior/mid) scalp hair thinning. METHODS: This was a 1-year, double-blind, placebo-controlled study followed by a 1-year open extension. Efficacy was assessed by hair counts (1 cm2 circular area), patient and investigator assessments, and global photographic review. RESULTS: There was a significant increase in hair count in the frontal scalp of finasteride-treated patients (P < .001), as well as significant improvements in patient, investigator, and global photographic assessments. Efficacy was maintained or improved throughout the second year of the study. Finasteride was generally well tolerated. CONCLUSION: In men with hair loss in the anterior/mid area of the scalp, finasteride 1 mg/day slowed hair loss and increased hair growth.

Androgen receptor polymorphisms (CAG repeat lengths) in androgenetic alopecia, hirsutism, and acne.

BACKGROUND: The androgen receptor (AR) is a structurally conserved member of the nuclear receptor superfamily. The amino-terminal domain is required for transcriptional activation and contains a region of polyglutamine encoded by CAG trinucleotide repeats. In humans, the number of CAG repeats is polymorphic. Expansion of CAG repeats in the AR has clinical implications for human disease. OBJECTIVE: Androgens influence androgenetic alopecia (AGA), hirsutism, and acne; the polymorphisms in CAG repeat length may affect the clinical course of patients with these cutaneous disorders. The purpose of this study is to test for an association between these disorders and CAG repeat length. METHODS: We analyzed normal lymphocyte genomic DNA from a total of 48 men and 60 women. The CAG repeat region of the AR was amplified by polymerase drain reaction (PCR) and the products were sized on polyacrylamide gels. RESULTS: In normal men and women controls, a range of 12 to 29 trinucleotide repeats was found, with men having 22 +/- 4 (M 6 SD), women 21 +/- 3. Men with AGA had 19 +/- 3, whereas women with AGA had 17 +/- 3. Men with acne had 21 +/- 3, whereas women had 20+/- 3; men with AGA and acne had 18 +/- 4; and women with hirsutism had 16 +/- 3. Women with a combination of at least two disorders also had 16 +/- 3 trinucleotide repeats. CONCLUSION: associated with the development of androgen-mediated skin disorders in men and women. These data suggest that CAG-repeat length in AR may affect androgen mediated gene expression in hair follicles and sebaceous glands in men and women with these androgenic skin disorders.

Clinical aspects of acne.

Acne vulgaris may present in a wide variety of clinical forms depending on the type, number and severity of the predominant lesion. Thus there may be mild, moderate or severe comedonal or inflammatory acne, the latter with many subtypes. Furthermore, the number and extent of the lesions do not necessarily predict the response to therapy, and patients may also be categorized as therapeutically responsive or therapeutically refractory. Finally, there may be alterations in the clinical manifestations and therapeutic response depending on the distribution of the lesions, age of the patient and provoking or complicating factors.

Clinical efficacy and safety comparison of adapalene gel and tretinoin gel in the treatment of acne vulgaris: Europe and U.S. multicenter trials.

BACKGROUND: Adapalene is a new chemical entity that exhibits tretinoin-like activities in the terminal differentiation process. OBJECTIVE: We evaluated a dose range effect of two concentrations of adapalene gel as acne treatment and compared adapalene 0.1% gel with tretinoin 0.025% gel in the treatment of acne patients in two large multicenter studies. METHODS: Multicenter, investigator-masked, parallel group studies including 89 acne patients in the dose range study and 591 patients in the concurrent controlled studies were conducted. RESULTS: Adapalene gel 0.1% was significantly more effective in treating acne lesions than 0.03% adapalene gel. Adapalene gel 0.1% was significantly more effective than 0.025% or tretinoin gel in one study and of the same effectiveness in the other study. Adapalene gel was always better tolerated than tretinoin gel. CONCLUSION: Adapalene 0.1% gel is a safe and effective treatment of acne vulgaris.

Roaccutane treatment guidelines: results of an international survey.

BACKGROUND: Oral isotretinoin (Roaccutane) revolutionized the treatment of acne when it was introduced in 1982. METHODS: Twelve dermatologists from several countries with a special interest in acne treatment met to formally review the survey of their last 100 acne patients treated with oral isotretinoin. The primary purpose of the survey was to identify the types of acne patients who were prescribed oral isotretinoin and how the patients were managed. RESULTS: Of the 1,000 patients reviewed, 55% of those who received oral isotretinoin had those indications treated historically, i.e. severe nodular cystic acne or severe inflammatory acne, not responding to conventional treatment. Forty-five percent of patients who were prescribed oral isotretinoin however had either moderate or mild acne. Most patients in this group had moderate acne (85%). However, 7.3% had mild acne on physical examination. The criteria for prescribing oral isotretinoin in this less severe group of patients included acne that improves < 50% after 6 months of conventional oral antibiotic and topical combination therapy, acne that scars, acne that induces psychological distress and acne that significantly relapses during or quickly after conventional therapy. Treatment is usually initiated at daily doses of 0.5 mg/kg (but may be higher) and is increased to 1.0 mg/kg. Most of the physicians aimed to achieve a cumulative dose of > 100-120 mg/kg. Mucocutaneous side-effects occur frequently but are manageable while severe systemic side-effects are rarely problematic (2%). The teratogenicity of oral isotretinoin demands responsible consideration by both female patients and their physicians. Significant cost savings when treating acne patients with oral isotretinoin as compared to other treatment modalities were further proven in this study. CONCLUSIONS: Our recommendation is that oral isotretinoin should be prescribed not only to patients with severe disease but also to patients with less severe acne, especially if there is scarring and significant psychological stress associated with their disease. Acne patients should, where appropriate, be prescribed isotretinoin sooner rather than later.

A comparison of the efficacy and safety of adapalene gel 0.1% and tretinoin gel 0.025% in the treatment of acne vulgaris: a multicenter trial.

BACKGROUND: Adapalene is a new synthetic retinoid analogue developed for the topical treatment of acne vulgaris. OBJECTIVE: The study was designed to compare the efficacy and safety and adapalene gel 0.1% with tretinoin gel 0.025% in the treatment of grade II to II facial acne vulgaris. METHODS: Three hundred twenty-three patients were enrolled in this investigator-masked, randomized, parallel group, multicenter trial. Patients applied the test materials to the entire facial area daily, for a period of 12 weeks. Efficacy and cutaneous tolerance were assessed at baseline and weeks 2,4,8, and 12. Efficacy was determined by investigator counts of noninflammatory open and closed comedones, and inflammatory papules and pustules, as well as global improvement. Cutaneous tolerance was evaluated by erythema, scaling, and dryness, along with burning and pruritus. RESULTS: Staring at weeks 2 and 4, adapalene gel produced numerically greater lesion reductions than did tretinoin gel for all lesion types. At week 12, the mean percent reduction in the different lesion counts was as follow: 49% versus 37% for total lesions (p<0.01); 46% versus 33% for noninflammatory lesions (p=0.02); 48% versus 38% for inflammatory lesions (p=0.06) in adapalene and tretinoin gel treatment groups, respectively. Cutaneous side effects were limited to a mild "retinoid dermatitis" occurring in both treatment groups; however, patients treated with adapalene gel tolerated this therapy significantly better than those treated with tretinoin gel. Laboratory test evaluations (hematology, blood chemistries, urinalysis) were performed in 54 patients before and after 3 months of treatment. No clinically significant changes were observed. CONCLUSION: Adapalene gel 0.1% applied once daily was significantly more effective in reducing acne lesions and was better tolerated than tretinoin gel 0.025% in the treatment of acne vulgaris.

Effect of naftifine on neutrophil adhesion.

Effective methods of fungal treatment involve reduction in fungal infections and host inflammatory responses. Naftifine (NF), a topical antifungal agent, is highly active in vitro and in vivo against a wide range of pathogenic fungi. Additionally NF has been shown to inhibit polymorphonuclear leukocyte (PMN) chemotaxis and respiratory burst activity in an irreversible dose-dependent and time-dependent manner. Since leukocyte adherence to endothelia is believed to be one of the initial crucial events in the recruitment of circulating leukocytes to the site of inflammation, we have investigated the in vitro effect of NF on PMN adherence to nylon fiber, BSA-coated glass chamber or polystyrene, and endothelial monolayers via three adherence assays. All three assays demonstrated a statistically significant reduction (p < 0.01-0.001) in PMN adherence to the respective media. In particular, NF (at 30-60 micrograms/ml) significantly inhibited PMN adherence to endothelial monolayers (p < 0.01) as measured spectrophotometrically by the uptake of rose bengal stain. Therefore, NF inhibits PMN adherence to endothelia in our in vitro model system. This inhibition may constitute part of the anti-inflammatory effect of NF.

Topical nicotinamide compared with clindamycin gel in the treatment of inflammatory acne vulgaris.

BACKGROUND: Systemic and topical antimicrobials are effective in the treatment of inflammatory acne vulgaris; however, widespread use of these agents is becoming increasingly associated with the emergence of resistant pathogens raising concerns about microorganism resistance and highlighting the need for alternative nonantimicrobial agents for the treatment of acne. Nicotinamide gel provides potent antiinflammatory activity without the risk of inducing bacterial resistance. METHODS: In our double-blind investigation, the safety and efficacy of topically applied 4% nicotinamide gel was compared to 1% clindamycin gel for the treatment of moderate inflammatory acne vulgaris. Seventy-six patients were randomly assigned to apply either 4% nicotinamide gel (n = 38) or 1% clindamycin gel (n = 38) twice daily for 8 weeks. Efficacy was evaluated at 4 and 8 weeks using a Physician's Global Evaluation, Acne Lesion Counts, and an Acne Severity Rating. RESULTS: After 8 weeks, both treatments produced comparable (P = 0.19) beneficial results in the Physician's Global Evaluation of Inflammatory Acne; 82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved. Both treatments produced statistically similar reductions in acne lesions (papules/pustules; -60%, nicotinamide vs. -43%, clindamycin, P = 0.168), and acne severity (-52% nicotinamide group vs. -38% clindamycin group, P = 0.161). CONCLUSIONS: These data demonstrate that 4% nicotinamide gel is of comparable efficacy to 1% clindamycin gel in the treatment of acne vulgaris. Because topical clindamycin, like other antimicrobials, is associated with emergence of resistant microorganisms, nicotinamide gel is a desirable alternative treatment for acne vulgaris.

Neonatal lupus erythematosus: discordant disease expression of U1RNP-positive antibodies in fraternal twins--is this a subset of neonatal lupus erythematosus or a new distinct syndrome?

Neonatal lupus erythematosus (NLE) is an uncommon disease that is manifested by cutaneous lesions, cardiac conduction defects, or both, that appear in utero or shortly after birth. In approximately 95% of patients, anti-Ro antibody (Ro[SS-A]) has been identified and has become the serologic marker for NLE. Since 1987 there have been four reported cases of Ro- and anti-La antibody (La[SS-B])-negative, U1RNP antibody-positive, NLE. Our affected twin, as well as all other infants with U1RNP-positive NLE, had cutaneous lesions similar to those in Ro-positive NLE, although they lacked systemic abnormalities, including cardiac conduction defects. HLA typing of mothers with infants with U1RNP-positive NLE revealed the presence of HLA-DR4, DQw1, or DQw3 phenotypes. Our typing confirms these findings. As with Ro-positive NLE, no distinct HLA associations were demonstrated in the infants. Unlike Ro-positive mothers, all mothers with a U1RNP-positive infant with NLE had connective tissue disease at the time of the diagnosis and had a different spectrum of disease. We describe the clinical, serologic, and immunogenetic findings in the first reported case of U1RNP-positive NLE in dizygotic twins in whom the NLE disease expression was discordant.