JAMA dermatology最新文献

Importance: VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is a newly defined genetic disease with an estimated prevalence of 1 in 4269 men older than 50 years and is marked by systemic inflammation, progressive bone marrow failure, and inflammatory cutaneous manifestations.

Objective: To define the spectrum of cutaneous manifestations in VEXAS syndrome and the association of these findings with clinical, genetic, and histological features.

Design, setting, and participants: This observational cohort study included data from 112 patients who were diagnosed with VEXAS-defining genetic variants in UBA1 between 2019 and 2023. Data were collected from medical record review or from patients with VEXAS directly evaluated at the National Institutes of Health in Bethesda, Maryland.

Main outcomes and measures: To define the spectrum of cutaneous manifestations in VEXAS in association with genetic, histological, and other clinical findings. A secondary outcome was cutaneous response to treatment in VEXAS.

Results: Among the 112 patients (median [range] age, 69 [39-79] years; 111 [99%] male), skin involvement was common (93 [83%]), and the most frequent presenting feature of disease (68 [61%]). Of 64 histopathologic reports available from 60 patients, predominant skin histopathologic findings were leukocytoclastic vasculitis (23 [36%]), neutrophilic dermatosis (22 [34%]), and perivascular dermatitis (19 [30%]). Distinct pathogenic genetic variants were associated with specific cutaneous manifestations. The p.Met41Leu variant was most frequently associated with neutrophilic dermal infiltrates (14 of 17 patients [82%]), often resembling histiocytoid Sweet syndrome. In contrast, the p.Met41Val variant was associated with vasculitic lesions (11 of 20 patients [55%]) with a mixed leukocytic infiltrate (17 of 20 patients [85%]). Oral prednisone improved skin manifestations in 67 of 73 patients (92%). Patients with VEXAS treated with anakinra frequently developed severe injection-site reactions (12 of 16 [75%]), including ulceration (2 of 12 [17%]) and abscess formation (1 of 12 [8%]).

Conclusions and relevance: Results of this cohort study show that skin manifestations are a common and early manifestation of VEXAS syndrome. Genetic evaluation for VEXAS should be considered in older male patients with cutaneous vasculitis, neutrophilic dermatoses, or chondritis. Awareness of VEXAS among dermatologists is critical to facilitate early diagnosis.

Importance: Somatic variants in the RAS/MAPK pathway genes are commonly associated with melanocytic nevi and melanoma, whereas germline variants in these genes are associated with RASopathies, syndromes involving multiple organs, including the skin. Nevi counts may be higher in some RASopathies, but studies on features observed through dermoscopy are limited.

Objective: To determine the distinguishing dermoscopic features of melanocytic nevi and how the RAS pathway influences them by comparing nevi in patients with cardiofaciocutaneous syndrome (CFC) and Costello syndrome (CS).

Design, setting, and participants: In this prospective cohort study, patients with CFC and CS, 2 RASopathies caused by variants in the downstream and upstream components of the RAS/MAPK pathway, were recruited from the international CFC and CS family conferences. Some patients with CFC also elected to participate in a longitudinal follow-up study.

Main outcomes and measures: The main outcomes were dermoscopic features and, in the longitudinal follow-up study, nevi counts, which were recorded over time.

Results: A total of 39 patients, 16 with CFC and 23 with CS, were enrolled (overall cohort: 26 [66.7%] female; median [IQR] age, 13.0 [7.6-22.0] years). The 112 nevi overall frequently displayed an organized dermoscopic pattern (CFC, 61 [84.7%]; CS, 34 [85.0%]) rather than a disorganized pattern (CFC, 6 [8.3%]; CS, 1 [2.5%]). Of the organized nevi, homogenous brown was the most common pattern (CFC, 41 [67.2%]; CS, 22 [64.7%]), followed by reticular (CFC, 11 [18.0%]; CS, 7 [20.6%]) and globular (CFC, 9 [14.8%]; CS, 5 [14.7%]). Pigmented networks occurred in 12 nevi in CFC (16.7%) and 6 nevi in CS (15%; P > .99). Of these, 6 CFC-associated nevi (50%) and no CS-associated nevi had atypical networks (P = .05). Six patients with CFC in the follow-up study developed significantly more nevi within 5 years (median [IQR] increase, 24.5 [10-120] nevi; P = .04).

Conclusions and relevance: In this cohort study, the findings suggest that nevi in patients with CFC and CS commonly display organized homogenous brown dermoscopic patterns, and the number of nevi may significantly increase over time in those with CFC. A disorganized pattern and atypical networks may be more frequent in patients with CFC. Future studies are needed to determine the risk of melanoma in individuals with CFC or CS.

Importance: The incidence of melanoma in situ (MIS) has increased significantly over the past decades, and traditional guidelines for treatment of MIS have been excision with a 5-mm clinical margin; however, current Australian and other guidelines now recommend 5- to 10-mm margins. This changed recommendation was largely driven by the outcomes of studies using Mohs micrographic surgery, and recent studies using Mohs micrographic surgery are advocating for even wider excisions up to 18 mm for clearance.

Objective: To assess the rate of recurrence of MIS excised with a 5-mm margin.

Design, setting, and participants: This case series studied all MIS lesions from a single private dermatology clinic between January 1, 2011, and November 30, 2018. The criteria for inclusion were a documented 5-mm excisional margin on operation report and more than 5 years of site-specific follow-up after wide local excision. Lesions were excluded if the excisional margin was more than 5 mm or undocumented, there was less than 5 years of follow-up, or they required more than 1 wide local excision. Data analysis was performed January 30 to February 25, 2024.

Intervention: Wide local excision with 5-mm margin.

Results: A total of 351 MISs were identified from 292 patients (mean [SD] age, 60.3 [11.8] years; 162 females [55.5%]). Superficial spreading melanoma was the most common subtype diagnosed (177 lesions [50.4%]), followed by lentigo maligna (107 lesions [30.5%]) and lentiginous MIS (67 lesions [19.1%]). The trunk was the most common location of lesions (168 lesions [47.9%]), followed by upper limb (96 lesions [27.4%]) and lower limb (59 lesions [16.8%]). Scalp was the least common location (2 lesions [0.6%]). Most of the lesions were small, with 274 lesions (78.1%) having a length less than 10 mm and 312 lesions (88.9%) having a width less than 10 mm. A total of 348 lesions (99.1%) did not have clinical recurrence after excision with a 5-mm clinical margin following then current guidelines. A total of 3 lesions (0.9%) experienced local recurrence with no metastatic spread.

Conclusions and relevance: This case series found that excision with a 5-mm margin for MIS of smaller size (<10 mm) on low-risk body sites had a low rate of recurrence. Conservative 5-mm excisional margin is likely to be suitable for small MIS on lower-risk body sites.

Importance: Moderate to severe atopic dermatitis (AD) is a chronic inflammatory skin disease that often requires continuous long-term systemic management. Long-term safety and efficacy data for treatment options are critically important.

Objective: To assess the safety and efficacy of dupilumab treatment for up to 5 years in adults with moderate to severe AD.

Design, setting, and participants: The 5-year LIBERTY AD open-label extension study was conducted from September 2013 to June 2022 at 550 sites in 28 countries. The study enrolled adult patients with moderate to severe AD who had participated in previous dupilumab clinical trials. Data were analyzed from August 2022 to February 2023.

Exposures: At enrollment, patients initiated a regimen of subcutaneous dupilumab, 200 mg, weekly (400-mg loading dose). The regimen was amended in June 2014 to dupilumab, 300 mg, weekly (600-mg loading dose) based on a dose-ranging study and again in November 2019 to dupilumab, 300 mg, every 2 weeks to align with the regulatory regimen approvals.

Main outcomes and measures: The primary end points were the incidence and rate of treatment-emergent adverse events (TEAEs). Key secondary end points included incidence and rate of serious TEAEs and adverse events of special interest, proportion of patients achieving an Investigator's Global Assessment (IGA) score of 0 or 1 (clear or almost clear), and proportion of patients with 75% or more improvement in the Eczema Area and Severity Index (EASI) from the parent study baseline.

Results: A total of 2677 patients were enrolled and treated in the open-label extension study; 1611 (60.2%) were male, and the mean (SD) age was 39.2 (13.4) years. A total of 334 patients (12.5%) completed treatment up to week 260. The most common reasons for withdrawal were due to regulatory approval of dupilumab in compliance with the study protocol (810 of 1380 [58.7%]), patient withdrawal (248 of 1380 [18.0%]), and adverse events (116 of 1380 [8.4%]). Exposure-adjusted rates of TEAEs were generally stable or declined throughout the study. Common TEAEs (incidence of 5% or greater) included nasopharyngitis, worsening AD, upper respiratory tract infection, conjunctivitis, conjunctivitis allergic, headache, oral herpes, and injection-site reaction. At week 260, 220 of 326 patients (67.5%) achieved an IGA score of 0 or 1 and 288 of 324 (88.9%) achieved 75% or greater improvement in the EASI. The mean (SD) EASI score was 16.39 (14.60) at baseline and 2.75 (5.62) at end of study.

Conclusions and relevance: In this study, there was sustained safety and efficacy of continuous long-term dupilumab treatment for adults with moderate to severe AD.

Importance: Clinical characteristics associated with treatment response to biologics in patients with psoriasis have never been systematically investigated.

Objective: To evaluate the association between patient clinical characteristics and the effectiveness of biologics in treating psoriasis.

Data sources: PubMed, Embase, and Web of Science were searched from their inception through April 2022. Studies in English language that reported response to biologic treatment at approved doses in patients with psoriasis in relation to their clinical characteristics were included. In addition, eligible studies were identified through a search of the reference lists of the included studies.

Study selection: We only included studies that reported treatment outcomes as Psoriasis Area and Severity Index (PASI) 75 or PASI 90 after 12, 26, and/or 52 weeks of treatment. Both observational studies and randomized clinical trials (RCTs) were considered. Two independent authors conducted the screening process, and 107 studies were assessed for eligibility.

Data extraction and synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were followed. Relevant data were extracted independently by 2 authors. Data were pooled using random-effects models. RCTs and observational studies were pooled in separate analyses. Data were analyzed from June 1, 2023, to August 1, 2023.

Main outcomes and measures: The primary outcome was PASI 90 at 26 weeks (6 months). Before data collection began, an investigation of the association between the main (and secondary) outcomes and several clinical characteristics was planned.

Results: Overall, 40 studies with a total of 21 438 patients were included. Older age (odds ratio [OR], 0.99; 95% CI, 0.98-1.00), previous exposure to biologics (OR, 0.44; 95% CI, 0.29-0.67), higher body mass index (BMI) (OR, 0.96; 95% CI, 0.94-0.99), previous smoking (OR, 0.81; 95% CI, 0.67-0.98), and current smoking (OR, 0.78; 95% CI, 0.66-0.91) were negatively associated with achieving PASI 90 at 6 months in observational studies. In RCTs, only BMI of 30 or higher was negatively associated with treatment response (PASI 90 at 3 months: OR, 0.57; 95% CI, 0.48-0.66).

Conclusions and relevance: This meta-analysis found that patients with psoriasis who smoke or have a history of smoking, as well as those with previous exposure to biologics, older age, or higher BMI, exhibited poorer response to biologics in observational studies. However, it remains unclear whether these clinical characteristics influence treatment response differently for the different biologics available for psoriasis.