April 2013

Glutathione S-transferase and claudin-1 gene polymorphisms in contact sensitization

A population of 3471 adult Danes was studied to determine the role of −polymorphisms of glutathione −S-transferase (GST) genes and the claudin-1 (CLDN1) gene on the risk of contact sensitization, taking common mutations of the filaggrin (FLG) gene into account. In individuals without ear piercings, a higher prevalence of nickel sensitization was found in those with the minor allele of CLDN1 single nucleotide polymorphism (SNP) rs9290927 (Ptrend = 0·013). For CLDN1 rs17501010, −contact −sensitization to organic −compounds was −associated with the major allele (Ptrend = 0·031). The risk pattern was also identified for self-reported nickel −dermatitis (Ptrend = 0·011). The prevalence of fragrance sensitization −differed in a pairwise comparison of the CLDN1 rs893051 SNP genotypes (= 0·022), with the minor allele being associated with a higher prevalence. An association between GST gene −polymorphisms and contact sensitization was not found. FLG mutations did not −affect the observed associations.

Ross-Hansen K, Linneberg A, Johansen JD et al. The role of glutathione S-transferase and claudin-1 gene polymorphisms in contact sensitization: a cross-sectional study. Br J Dermatol 2013; 168: 762–70

DOI: 10.1111/bjd.12126

Long-term ustekinumab safety in psoriasis


This report evaluated the largest psoriasis clinical trial cohort to date with the longest duration of follow-up. Analyses included 3117 patients (8998 patient years) who received one or more doses of ustekinumab, with 1482 patients treated for ≥ 4 years (including 838 patients treated for ≥ 5 years). At year 5, the event rates for 45 mg and 90 mg ustekinumab, respectively, for overall adverse events (AEs) (242·6, 225·3), serious AEs (7·0, 7·2), serious infections (0·98, 1·19), nonmelanoma skin cancers (0·64, 0·44), other malignancies (0·59, 0·61) and major adverse cardiovascular events (0·56, 0·36) were comparable between dose groups. Rates of overall mortality and other malignancies were comparable with those expected in the general U.S. population. Safety outcomes after 5 years of ustekinumab treatment are consistent with shorter-term reports and are generally comparable with observations from studies of other biologics in patients with psoriasis.

Papp KA, Griffiths CEM, Gordon K et al. Long-term safety of ustekinumab in patients with moderate-to-severe psoriasis: final results from 5 years of follow-up. Br J Dermatol 2013; 168: 844–54

DOI: 10.1111/bjd.12214

Epidermolysis bullosa simplex with PLEC mutations


Charlesworth et al. report seven new patients with epidermolysis bullosa simplex (EBS), four of whom have novel clinical phenotypes. Eleven novel mutations of the plectin (PLEC) gene are reported. Results confirm that EBS associated with pyloric atresia is linked to mutations in the distal exons 1–30 and 32 of PLEC. Long-term survival is possible, with skin improvement, but a delayed onset of muscular dystrophy (MD) is probable. While EBS associated with MD is linked to PLEC mutations in all exons, in most cases one of the mutations affects exon 31. The precocity of MD seems to be linked to the type and localization of the PLEC mutation(s), but no correlation with mucosal involvement has been found.

Charlesworth A, Chiaverini C, Chevrant-Breton J et al. Epidermolysis bullosa simplex with PLEC mutations: new phenotypes and new mutations. Br J Dermatol 2013; 168: 808–14

DOI: 10.1111/bjd.12202

Propranolol in haemangioma treatment


Hermans et al. prospectively analysed data from 174 patients with infantile haemangioma (IH) treated with propranolol between September 2008 and January 2012. All children had a potentially threatening and/or complicated IH; the girl/boy ratio was 123/51, and the mean age at the start of treatment was 4·8 months. In 173 cases treatment was successful, as assessed nonquantitatively by clinical observation. The mean duration of treatment was 10·7 months. The most important −adverse effects were hypotension (3·4%), wheezing (9·2%), nocturnal restlessness (22·4%) and cold extremities (36·2%). The use of propranolol in this patient group with severe functional or life-threatening situations is clear: to take a more active approach in prevention of disfigurement requires careful consideration by an experienced physician.

Hermans DJJ, Bauland CG, Zweegers J et al. Propranolol in a case series of 174 patients with complicated infantile haemangioma: indications, safety and future directions. Br J Dermatol 2013; 168: 837–43

DOI: 10.1111/bjd.12189