Why a speckled naevus is speckled, and what the blood says at week two

The edition in brief

A short edition, and an honest one - today's dermatology literature is mechanism rather than trial, and is presented as such. Molecular analysis of three cases of nevus spilus-type congenital melanocytic naevus, with epidermis and dermis separated before sequencing, found postzygotic NRAS variants in 10 of 11 dermal samples from the background brown macule and 16 of 16 from the superimposed dark macules, with copy-neutral loss of heterozygosity across the NRAS locus in 14 of 16 superimposed samples and none of the background ones - supporting a two-step model in which an early mosaic variant produces the background and later independent events produce the speckles. Single-cell RNA sequencing of untreated localised scleroderma skin found T follicular helper-like cells more prevalent than in healthy skin, with expanded TREM2+ and FCN1+ macrophages and LAMP3+ dendritic cells carrying an interferon signature, and increased ligand-receptor signalling between T/NK and myeloid compartments through CXCL, CCL, TNF and type II interferon pathways. In mice, contact hypersensitivity drove skin macrophages towards a CD14+SPP1+ population whose secreted osteopontin engaged CD44 on hair follicle stem cells to activate PI3K-AKT and trigger proliferation, with TNF-α and IL-1 signalling dispensable. And blood transcriptomes from 86 patients with plaque psoriasis on a TNF-α inhibitor identified 3,351 time-course drug-response genes, a co-expression module negatively correlated with outcome whose hub gene TNFSF10 predicted poor response, and a module-level change by week two that occurred in responders and not in non-responders.