Acne and rosacea in skin of colour.

Acne and rosacea are common inflammatory skin conditions present in numerous racial and ethnic groups. There are distinct differences in clinical presentation, exacerbating factors, potential triggers and consequences of both conditions in individuals with skin of colour (SOC), classified as Fitzpatrick skin types III-VI. For example, acne can be complicated by the development of postinflammatory hyperpigmentation and keloid scarring in SOC, and this can influence treatment choice. Although rosacea is reported less frequently in SOC, this may be the result of delayed diagnosis or late presentation due to the difficulty in discerning the classic features of erythema in darker skin tones. In such cases, additional clues in the medical history and clinical examination may assist in making the diagnosis. This review aims to summarize nuances in both the diagnosis and management of these two common skin conditions in patients with SOC to support clinicians in providing an individualized treatment approach.

The status and outcomes of registered clinical trials for Janus kinase inhibitors in alopecia areata: are unpublished trials being overlooked?

Recent meta-analyses of Janus kinase (JAK) inhibitors in alopecia areata (AA) have excluded trial registries and may thus be subject to publication bias. This study assessed the potential for evidence selection bias and provides an overview of JAK inhibitor trials in AA. A broad search strategy of ClinicalTrials.gov was performed for AA. We also recorded whether results were published on PubMed. There were 26 trials identified, of which 9 were ongoing (mostly oral JAK inhibitors: 8 studies; 89%). Of completed/terminated trials, 4/17 (24%) had terminated prematurely, citing 'inefficacy/futility' or 'sponsor decision'. These were all topical JAK inhibitor trials (4/8, 50% termination rate), with a 0% termination rate (0/9) for oral JAK inhibitor trials. We conclude that topical JAK inhibitors may be less efficacious than has been apparent in the literature to date, with 50% of trials having terminated due to inefficacy/futility or sponsor decision and only one topical JAK inhibitor trial ongoing.

Loss-of-function desmoplakin I and II mutations underlie dominant arrhythmogenic cardiomyopathy with a hair and skin phenotype.

BACKGROUND: Arrhythmogenic cardiomyopathy (AC) is an inherited, frequently underdiagnosed disorder, which can predispose individuals to sudden cardiac death. Rare, recessive forms of AC can be associated with woolly hair and palmoplantar keratoderma, but most autosomal dominant AC forms have been reported to be cardiac specific. Causative mutations frequently occur in desmosomal genes including desmoplakin (DSP). OBJECTIVES: In this study, we systematically investigated the presence of a skin and hair phenotype in heterozygous DSP mutation carriers with AC. METHODS: Six AC pedigrees with 38 carriers of a dominant loss-of-function (nonsense or frameshift) mutation in DSP were evaluated by detailed clinical examination (cardiac, hair and skin) and molecular phenotyping. RESULTS: All carriers with mutations affecting both major DSP isoforms (DSPI and II) were observed to have curly or wavy hair in the pedigrees examined, except for members of Family 6, where the position of the mutation only affected the cardiac-specific isoform DSPI. A mild palmoplantar keratoderma was also present in many carriers. Sanger sequencing of cDNA from nonlesional carrier skin suggested degradation of the mutant allele. Immunohistochemistry of patient skin demonstrated mislocalization of DSP and other junctional proteins (plakoglobin, connexin 43) in the basal epidermis. However, in Family 6, DSP localization was comparable with control skin. CONCLUSIONS: This study identifies a highly recognizable cutaneous phenotype associated with dominant loss-of-function DSPI/II mutations underlying AC. Increased awareness of this phenotype among healthcare workers could facilitate a timely diagnosis of AC in the absence of overt cardiac features.