Towards a better understanding of adult idiopathic epidermal necrolysis: a retrospective study of 19 cases.

BACKGROUND: Most cases of Stevens-Johnson syndrome and toxic epidermal necrolysis are drug-induced. A small subset of cases remain with unknown aetiology (idiopathic epidermal necrolysis [IEN]). OBJECTIVE: We sought to better describe adult IEN and understand the aetiology. METHODS: This retrospective study was conducted in 4 centres of the French national reference centre for epidermal necrolysis. Clinical data were collected for the 19 adults hospitalized for IEN between January 2015 and December 2019. Wide toxicology analysis of blood samples was performed. Histology of IEN cases was compared with blinding to skin biopsies of drug-induced EN (DIEN, 'controls'). Available baseline skin biopsies were analysed by shotgun metagenomics and transcriptomics and compared to controls. RESULTS: IEN cases represented 15.6% of all EN cases in these centres. The median age of patients was 38 (range 16-51) years; 68.4% were women. Overall, 63.2% (n = 12) of cases required intensive care unit admission and 15.8% (n = 3) died at the acute phase. Histology showed the same patterns of early- to late-stage EN with no difference between DIEN and IEN cases. One toxicology analysis showed unexpected traces of carbamazepine; results for other cases were negative. Metagenomics analysis revealed no unexpected pathological microorganism. Transcriptomic analysis highlighted a different pro-apoptotic pathway in IEN compared to DIEN, with an overexpression of apoptosis effectors TWEAK/TRAIL. CONCLUSIONS: IEN affects young people and is a severe form of EN. A large toxicologic investigation is warranted. Different pathways seem involved in IEN and DIEN, leading to the same apoptotic effect, but the primary trigger remains unknown.

miR455 is linked to hypoxia signaling and is deregulated in preeclampsia.

Preeclampsia is a severe pregnancy-related disorder and a leading cause of maternal and fetal mortality worldwide. Early identification of patients with an increased risk for preeclampsia is thus one of the most important goals in obstetrics. Here we identify two related human microRNAs as potential biomarkers to detect at-risk pregnancies. We demonstrate that miR455-3P and miR455-5P are significantly downregulated in placentas from preeclampsia patients, whereas other placenta-specific microRNAs remain unaffected. microRNA target prediction and validation revealed a potential link of miR455-3P to hypoxia signaling. Together with our observation that expression levels of miR455-3P and miR455-5P are upregulated during trophoblast differentiation, our results suggest a model in which miR455-3P represses a hypoxia response that might otherwise prevent cytotrophoblasts from syncytiotrophoblast differentiation. In summary, our work reveals aberrant hypoxia signaling in preeclampsia that can be explained by deregulated expression of miR455. As miR455 has been found in circulating blood, the development of noninvasive prenatal tests enabling early diagnosis of preeclampsia may be possible.