Associations between school difficulties and health-related problems and risky behaviours in early adolescence: A cross-sectional study in middle-school adolescents in France.

Health-related problems and risky behaviours (substance use) are frequent in adolescents, may alter their physical and mental capabilities, and may thus generate school absenteeism, low academic performance, and school dropout ideation. This study assessed their associations and the contribution of socioeconomic factors among 1559 middle-school adolescents (mean age 13.5+1.3) from north-eastern France. They completed a questionnaire including socioeconomic characteristics, health-related problems (poor physical health, psychological health, social relationships, and living environment) assessed with the World Health Organization's quality of life measure (score<25th percentile), risky behaviours, school absences during the present school year, last-trimester academic performance, and school dropout ideation. Data were analysed using logistic regression models. School absenteeism was frequent (12.6% of subjects for 8-14 days, and 6.0% for ≥15 days); 8.2% of subjects had low academic performance (average school-mark <10/20) and 3.9% school dropout ideation. All school difficulties were strongly associated with all health-related problems (gender-age-school-level-adjusted odds ratios gasOR between 1.5 and 4.2), and with risky behaviours (gasOR between 1.4 and 14). Socioeconomic factors differently contributed to these associations (contribution reaching 77%). Policy makers, schools, physicians and parents should be more aware of the problems and help adolescents to reduce health-related problems and risky behaviours and to increase resilience.

Long-term remissions of severe pemphigus after rituximab therapy are associated with prolonged failure of desmoglein B cell response.

Pemphigus is a severe blistering condition of the skin and mucosa caused by autoantibodies directed against desmogleins, which are a type of keratinocyte adhesion protein. B cell depletion by rituximab has short-term efficacy against pemphigus. We aimed to assess the long-term course of pemphigus patients after B cell depletion and to understand the immunological mechanisms that mediate long-lasting remissions. We evaluated the clinical course of 22 pemphigus patients treated with rituximab after a 79-month median follow-up and compared the anti-desmoglein B cell response and B and T lymphocyte subpopulations and repertoire between patients who achieved complete remission (CR) and those who had incomplete remission (IR). Thirteen patients (59%) experienced CR during the study, including 10 patients off treatment and 3 patients with prednisone doses <10 mg/day; 9 patients had IR. A marked increase was observed in the ratio of CD19(+)CD27(-) naïve B cells to CD19(+)CD27(+) memory B cells. Indeed, patients in CR had a fourfold higher number of transitional B cells and interleukin-10-secreting regulatory B cells than those in IR. Furthermore, CR was associated with modification of the initial B cell repertoire and the disappearance of desmoglein-specific circulating immunoglobulin G-positive (IgG(+)) B lymphocytes, whereas a skewed B cell repertoire was observed in patients in IR. Thus, a blockage of B cell maturation, a prolonged repopulation with naïve B cells, and a delayed reappearance of memory B cells, which resulted in the disappearance of circulating desmoglein-specific IgG(+) B lymphocytes, contribute to the long-lasting effectiveness of rituximab for treating pemphigus.

A comparison of two regimens of topical corticosteroids in the treatment of patients with bullous pemphigoid: a multicenter randomized study.

Superpotent topical corticosteroids (CS) have been demonstrated to improve bullous pemphigoid (BP) patients' survival. We assessed whether a mild regimen using lower doses of topical CS and a shorter duration could improve the outcome of BP patients even more. Three-hundred and twelve BP patients were included in a multicenter randomized controlled trial and stratified depending on the extent of BP as moderate (n=134) or extensive (n=178). Patients were randomly assigned to the standard regimen (clobetasol propionate cream, 40 g per day initially, with CS tapering over 12 months) or the mild regimen (10-30 g per day), with CS tapering over 4 months. A noninferior rate of BP control was obtained with the mild regimen 156/159 (98%) as compared with the standard regimen 150/150 (100%; P=0.005). Event-free survival, that is, the combined outcome of deaths and life-threatening adverse events did not differ between the two treatment groups (P=0.77). However, upon adjusting through the Cox model for age and Karnofsky score, a strong beneficial effect of the mild regimen was observed in patients with moderate BP, with an almost twofold decrease in the risk of death or life-threatening adverse events relative to the standard regimen (hazard ratio=0.54; 95% confidence interval, 0.30-0.97; P=0.039). This mild regimen allows a 70% reduction of the cumulative doses of CS and improves BP patients' outcome.

A single cycle of rituximab for the treatment of severe pemphigus.

BACKGROUND: The combination of multiple cycles of rituximab and intravenous immune globulins has been reported to be effective in patients with severe pemphigus. The aim of this study was to assess the efficacy of a single cycle of rituximab in severe types of pemphigus. METHODS: We studied 21 patients with pemphigus whose disease had not responded to an 8-week course of 1.5 mg of prednisone per kilogram of body weight per day (corticosteroid-refractory disease), who had had at least two relapses despite doses of prednisone higher than 20 mg per day (corticosteroid-dependent disease), or who had severe contraindications to corticosteroids. The patients were treated with four weekly infusions of 375 mg of rituximab per square meter of body-surface area. The primary end point was complete remission 3 months after the end of rituximab treatment; complete remission was defined as epithelialization of all skin and mucosal lesions. RESULTS: Eighteen of 21 patients (86%; 95% confidence interval, 64 to 97%) had a complete remission at 3 months. The disease relapsed in nine patients after a mean of 18.9+/-7.9 months. After a median follow-up of 34 months, 18 patients (86%) were free of disease, including 8 who were not receiving corticosteroids; the mean prednisone dose decreased from 94.0+/-10.2 to 12.0+/-7.5 mg per day (P=0.04) in patients with corticosteroid-refractory disease and from 29.1+/-12.4 to 10.9+/-16.5 mg per day (P=0.007) in patients with corticosteroid-dependent disease. Pyelonephritis developed in one patient 12 months after rituximab treatment, and one patient died of septicemia 18 months after rituximab treatment. These patients had a profound decrease in the number of circulating B lymphocytes but normal serum levels of IgG. CONCLUSIONS: A single cycle of rituximab is an effective treatment for pemphigus. Because of its potentially severe side effects, its use should be limited to the most severe types of the disease. (ClinicalTrials.gov number, NCT00213512 [ClinicalTrials.gov].).

Allele variations in the OCA2 gene (pink-eyed-dilution locus) are associated with genetic susceptibility to melanoma.

The occuloalbinism 2 (OCA2) gene, localized at 15q11, encodes a melanosomal transmembrane protein that is involved in the most common form of human occulo-cutaneous albinism, a human genetic disorder characterized by fair pigmentation and susceptibility to skin cancer. We wondered whether allele variations at this locus could influence susceptibility to malignant melanoma (MM). In all, 10 intragenic single-nucleotide polymorphisms (SNPs) were genotyped in 113 patients with melanomas and in 105 Caucasian control subjects with no personal or family history of skin cancer. By comparing allelic distribution between cases and controls, we show that MM and OCA2 are associated (p value=0.030 after correction for multiple testing). Then, a recently developed strategy, the 'combination test' enabled us to show that a combination formed by two SNPs was most strongly associated to MM, suggesting a possible interaction between intragenic SNPs. In addition, the role of OCA2 on MM risk was also detected using a logistic model taking into account the presence of variants of the melanocortin 1 receptor gene (MC1R, a key pigmentation gene) and all pigmentation characteristics as melanoma risk factors. Our data demonstrate that a second pigmentation gene, in addition to MC1R, is involved in genetic susceptibility to melanoma.

A comparison of oral and topical corticosteroids in patients with bullous pemphigoid.

BACKGROUND: Bullous pemphigoid is the most common autoimmune blistering skin disease of the elderly. Because elderly people have low tolerance for standard regimens of oral corticosteroids, we studied whether highly potent topical corticosteroids could decrease mortality while controlling disease. METHODS: A total of 341 patients with bullous pemphigoid were enrolled in a randomized, multicenter trial and stratified according to the severity of their disease (moderate or extensive). Patients were randomly assigned to receive either topical clobetasol propionate cream (40 g per day) or oral prednisone (0.5 mg per kilogram of body weight per day for those with moderate disease and 1 mg per kilogram per day for those with extensive disease). The primary end point was overall survival. RESULTS: Among the 188 patients with extensive bullous pemphigoid, topical corticosteroids were superior to oral prednisone (P=0.02). The one-year survival rate was 76 percent in the topical-corticosteroid group and 58 percent in the oral-prednisone group. Disease was controlled at three weeks in 92 of the 93 patients in the topical-corticosteroid group (99 percent) and 86 of the 95 patients in the oral-prednisone group (91 percent, P=0.02). Severe complications occurred in 27 of the 93 patients in the topical-corticosteroid group (29 percent) and in 51 of the 95 patients in the oral-prednisone group (54 percent, P=0.006). Among the 153 patients with moderate bullous pemphigoid, there were no significant differences between the topical-corticosteroid group and the oral-prednisone group in terms of overall survival, the rate of control at three weeks, or the incidence of severe complications. CONCLUSIONS: Topical corticosteroid therapy is effective for both moderate and severe bullous pemphigoid and is superior to oral corticosteroid therapy for extensive disease.