The Journal of dermatology最新文献

Nagashima-type palmoplantar keratoderma (NPPK) is a hereditary non-epidermolytic keratoderma predominantly reported in East Asian populations. It is mainly caused by biallelic loss-of-function variants in SERPINB7, but the functional impact of certain variants remains unclear. In this study, we performed Sanger sequencing on three unrelated Chinese patients with clinically diagnosed NPPK and identified biallelic pathogenic SERPINB7 variants in all cases. Among these, a novel in-frame indel variant (c.806_814delinsT, p.Ser269_Glu273delinsLeu) and three known founder variants (c.796C>T, c.522dupT, and c.455G>T) were detected. Transcript analysis revealed that the c.455G>T variant, despite being located at the exon-intron 6 junction, functions as a missense variant (p.Gly152Val) without affecting mRNA splicing. Functional studies, including protein structural modeling and legumain protease activity assays, revealed that both variants impaired the inhibitory function of SERPINB7, leading to increased legumain activity. These findings expand the mutational spectrum of SERPINB7 and provide new insights into the pathogenicity of the c.806_814delinsT and c.455G>T variants in the Chinese population.

Prurigo nodularis (PN) is a chronic, intensely pruritic dermatosis driven by neuroimmune dysregulation for which targeted therapies are emerging. The objective of our study is to evaluate the efficacy and safety of Janus kinase inhibitors (JAK-Is) for the treatment of PN. We conducted a systematic search in sources including PubMed/Medline, Scopus, Web of Science, and Embase; the search was completed on September 9, 2025. Inclusion criteria were the use of any JAK-I in a patient with confirmed PN, and exclusion criteria were reviews, duplicate reports, and studies with incomplete outcome data. Risk of bias was assessed using the NHLBI quality assessment tools for observational studies and the Murad et al. checklist for case reports and case series. Ten clinical studies (n = 180 patients) and 21 case reports/series (n = 31 patients) were included (total n = 211). Agents evaluated included upadacitinib, tofacitinib, abrocitinib, and baricitinib. Applying standardized response criteria, 139/180 patients (77.2%) in clinical studies achieved meaningful clinical improvement. Rapid itch relief was frequently observed (days to weeks). Quality of life improved substantially (mean reduction from 20.4 to 3.9). Reported adverse events were generally mild (infections, laboratory abnormalities, dyslipidemia, acneiform eruption); serious events were rare. Limitations include small sample sizes, predominance of uncontrolled and observational designs, heterogeneity of outcomes, and limited long-term safety data. Current evidence suggests JAK-Is are highly effective and generally well tolerated for PN, warranting larger randomized controlled trials with extended follow-up.

Ritlecitinib is an oral JAK3/TEC family kinase inhibitor approved for individuals aged ≥ 12 years with severe alopecia areata. Here we report interim efficacy and safety results with ritlecitinib up to Month 24 in the Asian subpopulation from the ALLEGRO phase 2b/3 and ALLEGRO-LT studies. Data are reported for participants with Severity of Alopecia Tool score ≥ 50 who received ritlecitinib 50 mg with (200/50-mg group) or without (50-mg group) an initial 4-week 200-mg daily loading dose in ALLEGRO-2b/3, and continued ritlecitinib 50 mg in ALLEGRO-LT. In long-term studies, it is common for summaries at later time points to reflect participants who remained in the study, tolerated the drug, and had a positive treatment response. To account for this, efficacy summaries were presented both as observed and by using the last observation carried forward method. At Month 12, 51.7% and 44.7% (last observation carried forward) of Asian participants in the 50-mg (n = 58) and 200/50-mg groups (n = 47), respectively, achieved Severity of Alopecia Tool score ≤ 20 (≤ 20% scalp hair loss); the respective proportions were 50.0% and 47.8% at Month 24. Of participants who achieved Severity of Alopecia Tool score ≤ 20 at Month 12 in the 50-mg and 200/50-mg groups, 68.2% and 86.7% sustained this response through Month 24, respectively. At Month 12, 74.0% and 57.9% of participants in the 50-mg and 200/50-mg groups, respectively, had an eyebrow hair regrowth response; at Month 24, the proportions were 72.0% and 48.7%. At Month 12, 65.1% and 54.1% of participants in the 50-mg and 200/50-mg groups, respectively, had an eyelash hair regrowth response; the proportions were 65.1% and 52.8% at Month 24. The proportion of participants with a Patients' Global Impression of Change response of "moderately" or "greatly" improved since baseline increased through Month 24 in both groups. Ritlecitinib had an acceptable safety profile, consistent with that in the overall population. Overall, ritlecitinib 50 mg (±200-mg loading dose) demonstrated clinically meaningful and sustained efficacy through Month 24 in the Asian subpopulation, consistent with results in the overall population. Trial Registration: ClinicalTrials.gov: NCT04006457.