Development and multicenter international validation of a diagnostic tool to differentiate between pemphigoid gestationis and polymorphic eruption of pregnancy.

BACKGROUND: Pemphigoid gestationis (PG) and polymorphic eruption of pregnancy (PEP) may be similar morphologically but confer different maternal and fetal risks. Direct immunofluorescence is the gold standard test used to differentiate between the 2 diagnoses but is not always available. OBJECTIVE: To develop and validate a clinical scoring system to differentiate PG from PEP. METHODS: After developing a scoring system based on differentiating clinical factors reported in existing literature, we tested its diagnostic accuracy in a retrospective international multicenter validation study in collaboration with the European Academy of Dermatology and Venereology's Skin Diseases in Pregnancy Taskforce. RESULTS: Nineteen pregnancies (16 patients) affected by PG and 39 pregnancies (39 patients) affected by PEP met inclusion criteria. PG had a mean score of 4.6 (SD, 2.5) and PEP had a mean score of -0.3 (SD, 2.0). The area under the curve was 0.93 (95% CI, 0.86-1.00). Univariate analysis revealed that almost all criteria used in the scoring system were significantly different between the groups (P < .05), except for skip pregnancy and multiple gestations, which were then removed from the final scoring system. LIMITATIONS: Small retrospective study. CONCLUSION: The Pregnancy Dermatoses Clinical Scoring System may be useful to differentiate PG from PEP in resource-limited settings.

COL7A1 Recessive mutations in two siblings with distinct subtypes of dystrophic epidermolysis bullosa: pruriginosa versus nails only.

Dystrophic epidermolysis bullosa (DEB) is a rare, clinically heterogeneous, blistering genodermatosis inherited as either autosomal dominant or recessive trait. All DEB forms are caused by mutations in the COL7A1 gene, which encodes for type VII collagen, the major component of the anchoring fibrils ensuring epithelial-mesenchymal adhesion. Major determinants of clinical heterogeneity in DEB are COL7A1 mutation types and their consequences at mRNA and protein levels; nevertheless, siblings with the same genetic alterations can manifest highly variable clinical signs. Here, we report novel compound heterozygous recessive COL7A1 missense mutations in 2 siblings presenting different DEB clinical subtypes. Our findings document the rare occurrence of recessive inheritance for the nails only DEB variant and emphasize the role of acquired phenotype-modifying factors in DEB pruriginosa pathogenesis.

Epidemiology and clinical aspects of Werner's syndrome in North Sardinia: description of a cluster.

Werner syndrome (WS, MIM#277700) is a very rare autosomal recessive disorder. WS clinical signs include altered distribution of subcutaneous fat, juvenile bilateral cataracts, a mask-like face and bird-like nose, trophic ulcers of the feet, diabetes mellitus, and premature atherosclerosis. The habitus is characteristic, with short stature, stocky trunk and slender extremities. WS frequency has been roughly estimated to be 1: 100,000 in Japan and 1: 1,000,000-1: 10,000,000 outside of Japan. The only exception to the latter data can be seen in the clustering of WS in Sardinia. Since 2001, 5 new cases have been observed: 4 members of the same family and 1 sporadic case. Therefore, since 1982 the total number of cases described in North Sardinia amounts to 18: 15 are familial (11 members of the same family group) and 3 sporadic. A short clinical description of the 5 new cases is reported.

CD4+ and CD8+ T-cell skewness in classic Kaposi sarcoma.

It is widely accepted that a deranged immune system plays a key role in the onset and evolution of classic Kaposi sarcoma (CKS). Nevertheless, the usage of the T-cell receptor (TCR) ß-variable (BV) chain repertoire expressed by peripheral blood lymphocytes in patients with CKS is still unknown. With the aim of providing some further insights into the complex role of the immune system in CKS pathogenesis, we performed an extensive analysis of the TCR BV repertoire in both CD4(+) and CD8(+) T cells in 30 human herpesvirus 8-positive Sardinian patients with CKS and an equal number of age-matched healthy controls. We used a panel of monoclonal antibodies covering approximately 70% of human BV subfamilies and third complementarity determining region (CDR3) spectratyping. Patients with CKS showed an increased frequency of BV expansions in both CD4(+) and CD8(+) lymphocytes, with no prevalent clones. On spectratyping analysis, most of the 720 BV CDR3 profiles obtained from both CD4(+) and CD8(+) T cells in patients with CKS were skewed. In particular, the surprising increase of BV skewing observed in CD4(+) lymphocytes mimics the pattern of progressive TCR BV narrowing described in responses to persistent viral antigen stimulations. Our findings support the hypothesis that CKS evolution is associated with inadequate activation rather than impairment of the immune system.