Loss-of-function mutations in the filaggrin gene and alopecia areata: strong risk factor for a severe course of disease in patients comorbid for atopic disease.

Alopecia areata (AA) is a common dermatological disease, which affects nearly 2% of the general population. Association of AA with atopic disease has been repeatedly reported. Loss-of-function mutations in the filaggrin gene (FLG) may be considered as promising candidates in AA, as they have been observed to be a strong risk factor in atopic dermatitis. The FLG mutations R501X and 2282del4 were genotyped in a large sample of AA patients (n=449) and controls (n=473). Although no significant association was observed in the patient sample overall, FLG mutations were significantly associated with the presence of atopic dermatitis among AA patients. Furthermore, the presence of FLG mutations had a strong impact on the clinical course of AA in comorbid patients. For example, 19 of the 22 mutation carriers among AA patients with atopic dermatitis showed a severe form of the disease (P=0.003; odds ratio (OR)=5.47 (95% confidence interval (CI): 1.59-18.76)). In conclusion, our data suggest that when AA occurs in conjunction with FLG-associated atopic disorder, the clinical presentation of AA may be more severe.

Familial aggregation of alopecia areata.

BACKGROUND: Familial aggregation of alopecia areata (AA) has been previously described, but systematic studies with information obtained directly from family members have yet to be undertaken. OBJECTIVE: We sought to study the pattern of familial aggregation of AA by assessing the affection status of patients' relatives. The study included 206 index patients with a total of 1029 first-degree and 2625 second-degree relatives. METHODS: First-degree relatives were directly interviewed, whereas information on second-degree relatives was obtained by interviewing the index patients and their first-degree relatives. RESULTS: Estimated lifetime risks were 7.1% in siblings, 7.8% in parents, and 5.7% in offspring. The risk in second-degree relatives was slightly higher than the reported population risk. Age at onset in index patients and first-degree relatives was significantly correlated. LIMITATIONS: Using patients drawn from specialized hair clinics may have produced results showing a higher proportion of early onset and severe cases. CONCLUSION: The familial aggregation of AA supports the role of genetic factors in the development of the disease. In addition, our data indicate genetic factors might contribute to the age at onset of AA.

Knowledge and management of scabies in general practitioners and dermatologists.

Scabies is an infectious skin disease with an increasing incidence during the past decade. A survey was conducted among general practitioners (GPs) and dermatologists in the region of Ghent, Belgium, to explore their knowledge on scabies. Information on the treatment advice given and the frequency of reporting scabies to the Health Inspection was also collected. The scores on the knowledge test were of an acceptable level in both GPs and dermatologists (median score 59% and 79% respectively). We found that profession (dermatologist versus GP), the number of years of experience and the estimated number of scabies patients per year had a significant effect on this score. Permethrin cream, currently regarded as the standard treatment, is prescribed as the only treatment for scabies by half of the GPs and dermatologists. Almost 50% of the GPs and dermatologists indicated they rarely or never report scabies to the Health Inspection. As a result the correct incidence of scabies in Belgium, as in many other countries, is not known.

A phase II multicenter clinical trial of systemic bexarotene in psoriasis.

BACKGROUND: Bexarotene, a novel and unique synthetic P, RXR-selective retinoid, is available as a treatment for cutaneous T-cell lymphoma. In psoriasis, a common retinoid-sensitive disease, no data are available on bexarotene treatment. OBJECTIVE: In this phase II study we investigated the safety, tolerability, and effectiveness of bexarotene in psoriasis at doses of 0.5 to 3.0 mg/kg/day. METHODS: Fifty patients with moderate to severe plaque-type psoriasis were treated with bexarotene in 4 sequential dose-defined panels of 12-13 patients at doses of 1.0, 2.0, 0.5, and 3.0 mg/kg/day for 12-24 weeks. Patients were monitored for safety and clinical efficacy. RESULTS: No serious adverse events related to the drug occurred. Bexarotene was well tolerated in most patients. Most frequently observed adverse events related to bexarotene were hypertriglyceridaemia (56%) and a decrease in free T4 serum levels (54%). Significant improvement of psoriasis after bexarotene at all doses was confirmed by a modified psoriasis area and severity index (mPASI), plaque elevation (PEL), and physician's global assessment (PGA). Overall response rates (> or =50% improvement) for mPASI, PEL, and PGA were 22%, 52%, and 36%, respectively. No significant dose-response effect was established for these parameters. CONCLUSION: The present study indicates an anti-psoriatic effect of bexarotene. Further studies are necessary to assess the optimal dose and the potential for bexarotene as a new therapy for psoriasis.