May 2013

Premature senescence of KS primary keratinocytes


Piccinni et al. investigated how kindlin-1 deficiency affects the proliferative potential of primary human keratinocytes. Kindler syndrome (KS) keratinocytes exhibited a precocious senescence and strongly reduced clonogenic potential. KS cultures also showed an increased percentage of aborted colonies (paraclones) already at early passages indicating an early depletion of stem cells. Immunoblotting analysis of KS keratinocyte extracts showed reduced levels of the stemness markers p63 and Bmi-1, upregulation of p16 and scant amounts of hypophosphorylated Rb protein, which indicated cell cycle-arrested status. Treatment of normal human primary keratinocytes with siRNA targeting kindlin-1 proved that its deficiency was directly responsible for p63, Bmi-1 and pRb downregulation and p16 induction. Findings underline the crucial contribution of kindlin-1 deficiency in the premature ageing of primary human keratinocytes.

Piccinni E, Di Zenzo G, Maurelli R et al. Induction of senescence pathways in Kindler syndrome primary keratinocytes. Br J Dermatol 2013; 168: 1019–26.

DOI: 10.1111/bjd.12184

Small melanocytic lesions and in vivo confocal microscopy


Twenty-four melanomas and 72 naevi were examined using dermoscopy and reflectance confocal microscopy (RCM) along with histopathology. The seven-point dermoscopic checklist score was ≥ 3 in 22 melanomas and in 33 naevi. The pleomorphism and architectural disorder of cells were the most striking criteria for consistent diagnosis of small melanoma. The presence of more than five atypical cells per mm2, and roundish atypical cells at the dermoepidermal junction showed the highest odds ratios. From logistic regression, the presence of at least five pagetoid cells per mm2, tangled lines within the epidermis, and atypical roundish cells at the dermoepidermal junction resulted in the three independent confocal parameters that characterized small melanomas. The authors highlight the role of RCM in diagnosing small melanomas and in differentiating them from naevi.

Pupelli G, Longo C, Veneziano L et al. Small-diameter melanocytic lesions: morphological analysis by means of in vivo confocal microscopy. Br J Dermatol 2013; 168: 1027–33.

DOI: 10.1111/bjd.12212

Dermatomyositis and ischaemic stroke


Lai et al. investigated the risks of acute myocardial infarction (AMI) and ischaemic stroke in patients with dermatomyositis (DMS). A total of 907 patients with DMS were compared with a non-DMS control group consisting of 4535 age- and sex-matched, randomly sampled subjects without DMS. During the 2-year follow-up period, 14 patients with DMS (1·5%) and 18 patients in the non-DMS control group (0·4%) suffered AMIs, crude hazard ratio (HR) 3·96 (P = 0·0001), and adjusted HR 3·37 (P = 0·0007) taking into account demographic characteristics and cardiovascular comorbidities. During the same follow-up period, 46 patients (5·1%) and 133 subjects in the control group (2·9%) developed ischaemic strokes, crude HR 1·78 (P = 0·0007), and adjusted HR 1·67 (P = 0·0028). Findings suggest that DMS is associated with an increased risk of cardiovascular and cerebrovascular events.

Lai Y-T, Dai Y-S, Yen M-F et al. Dermatomyositis is associated with an increased risk of cardiovascular and cerebrovascular events: a Taiwanese population-based longitudinal follow-up study. Br J Dermatol 2013; 168: 1054–59.

DOI: 10.1111/bjd.12245

Shared susceptibility between psoriatic arthritis and psoriasis

Authors investigated the recently identified psoriasis susceptibility loci in Chinese patients with psoriatic arthritis (PsA) and psoriasis, and healthy controls. PsA showed a significant association with markers at TNIP1, IL28RA, IL12B, ERAP1, PTTG1 and GJB2 when compared with the control group. In psoriasis a significant association was found for IL28RA, TNIP1 and ERAP1. These results support the hypothesis that genetic aetiology of psoriasis is the same in both PsA and psoriasis and also supports the higher genetic component of PsA than psoriasis.

Yang Q, Liu H, Qu L et al. Investigation of 20 non-HLA (human leucocyte antigen) psoriasis susceptibility loci in Chinese patients with psoriatic arthritis and psoriasis vulgaris. Br J Dermatol 2013; 168: 1060–65.

DOI: 10.1111/bjd.12142