JAMA dermatology最新文献

Importance: Janus kinase 2 (JAK2) gene fusions characterize cytotoxic cutaneous T-cell lymphoma (CTCL) including primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma (pcAETCL). The identification of these fusions is rarely reported in indolent CTCL.

Objective: To characterize patients with CTCL to better understand the diagnostic, prognostic, and therapeutic significance of this molecular alteration in CTCL.

Design, setting, and participants: A retrospective case series of patients with CTCL with JAK2 fusions identified between the years 2000 and 2025. Fusions were identified by a custom RNA sequencing panel and by a targeted hybrid-capture-based next-generation DNA sequencing-based panel. The study included a single referral cancer center in the US.

Results: Overall, 43 patients (12 female [27.9%] and 31 male individuals [72.1%]; median [range] age, 45 [16-65] years) with CTCL who were found to have JAK2 gene fusions during evaluation and follow-up were included. Thirty-eight of the 43 identified patients (88.4%) with fusions of JAK2 and 10 different gene partners (most frequently ATXN2L, CAPRIN1, and PCM1) had mycosis fungoides (MF), CD30-positive lymphoproliferative disorders (LPD), or overlap presentations, whereas 4 pcAETCL and 1 peripheral T-cell lymphoma not otherwise specified were identified. Secondary genetic events included mutations of epigenetic and transcriptional regulators. Neither mutational burden, type, or fusion partner distinguished cases with early-stage or aggressive CTCL.

Conclusions and relevance: This case series found that JAK2 fusions were seen in aggressive cytotoxic CTCL as well as in T-cell lymphomas with more indolent behavior, possibly representing a precursor lesion to aggressive evolution with age and comorbidities. The prominence of these fusions supports a potentially larger role for JAK2 targeting in patients with early-stage MF, CD30-positive LPD, or overlap presentations.

Importance: Compounded with barriers to care, stigmatization, lack of trust, and high rates of psychiatric comorbidities, transmasculine patients face a high psychosocial burden from acne. Acne is a common sequela of masculinizing hormone therapy, and understanding its epidemiology may improve care for transmasculine patients.

Objective: To summarize current literature regarding prevalence and factors associated with acne in transmasculine patients.

Evidence review: A search was performed using Ovid MEDLINE, Web of Science, Scopus, CINAHL, ProQuest Dissertations & Theses, Scientific Electronic Library Online, Cochrane Library, and Global Index Medicus. Studies were included if they reported acne prevalence, severity, or treatment among 1 or more transmasculine patients.

Findings: Of 429 references identified by search terms, 38 met inclusion criteria. There were 12 010 patients across all studies, with 32 of the 38 articles focusing on transmasculine adults rather than adolescents. Methods of acne quantification varied among included studies. Studies using systematic grading scales reported an acne rate of 61.9% (223 of 360 patients) compared to 29.6% (1233 of 4163 patients) among retrospective reviews and 31.3% (892 of 2847 patients) among studies using self-reported data. Most studies showed the largest increase in acne prevalence at 6 to 12 months after masculinizing hormone therapy initiation. There was an association between younger age and increased acne but no meaningful associations between testosterone dosage nor route of administration.

Conclusions and relevance: In this scoping review, acne prevalence among transmasculine patients ranged from 29.6% to 61.9%, depending on methodology. Acne commonly developed within 6 to 24 months after testosterone initiation but occurred as early as the first month. Younger age at hormone initiation was associated with acne development, whereas dose and route of administration were not, suggesting that other factors in addition to exogenous testosterone play a role in the pathogenesis of acne for transmasculine patients.

Importance: Acute digital ischemia, digital ulcers, and gangrene are debilitating complications of systemic sclerosis and other vasculopathies and are often refractory to standard vasodilator and immunosuppressive therapies. Botulinum toxin (BTX) has emerged as a potential rescue therapy, but its clinical effectiveness and safety remain unclear.

Objective: To evaluate the effectiveness and safety of BTX injections for ischemic digital complications and identify predictors of treatment response using individual participant data (IPD).

Data sources: MEDLINE (PubMed), Embase (Ovid), and Scopus were searched from inception through April 20, 2024.

Study selection: Eligible studies included patients who presented with acute digital ischemia, ischemic digital ulcers, or gangrene. Studies were limited to Raynaud disease without digital ulcers or gangrene were excluded. Two reviewers independently screened articles using Covidence, with discrepancies resolved by consensus with the senior author. Of 116 studies screened, 31 (27%) met inclusion criteria.

Data extraction and synthesis: Data were extracted in duplicate and study quality was assessed using the Joanna Briggs Institute checklist. Descriptive statistics were used to summarize baseline characteristics, treatment regimens, and outcomes.

Main outcomes and measures: The primary outcome was complete response (CR), which was defined as resolution of ischemia or ulcer healing. Secondary outcomes included adverse events and time to response. Cox regression was used to identify factors associated with CR.

Results: This systematic review and IPD meta-analysis included 119 patients (72 female individuals [75.0%]; mean [SD] age, 49.0 [15.1] years). BTX was associated with high CR rates for ischemia (93.1%), ulcers (90.1%), and gangrene (87.5%). Adverse events were infrequent, with transient muscle weakness (7.6%) and injection site pain (5.9%) being most common. No associated factors reached statistical significance in multivariable models, but autoimmune etiology and younger age were associated with faster response in Kaplan-Meier analyses.

Conclusions and relevance: The results of this systematic review and IPD meta-analysis suggest that BTX injections appear to be a safe and effective adjunct for refractory digital ischemia in systemic sclerosis. Prospective trials are needed to confirm long-term effectiveness and standardize administration protocols.

Importance: Hidradenitis suppurativa (HS) is a chronic inflammatory dermatological disease with prevalence estimates ranging from 0.1% to 0.5% in clinical settings to 1% to 2% in general populations. While tertiary care data show that 22% of patients progress to severe disease within 2 years, estimates of disease development outside the hospital setting remain unknown.

Objective: To investigate HS development in a non-hospital-based setting and to identify baseline factors associated with remission and progression to severe disease in the community.

Design, setting, and participants: This prospective cohort study used 10-year follow-up data on HS disease severity among a municipality-based cohort identified via a questionnaire in the Danish General Suburban Population Study conducted from 2010 to 2013. Disease severity (mild, moderate, severe) was determined using a modified Hurley score. Progression (severe disease at follow-up) and remission (no active HS symptoms for 6 months or longer at follow-up) rates were calculated by severity level. Separate Cox proportional hazard regression analyses explored whether baseline demographic variables associated with disease severity at follow-up in 2023 could be used to estimate changes in disease severity. Data analysis was performed from March 2024 to September 2025.

Main outcomes and measures: HS remission and progression rates across baseline severity groups as determined at follow-up in January to February 2023. Measures included baseline HS disease severity, body mass index, smoking history, employment status, and number of anatomical areas with active lesions.

Results: The analysis included 107 patients with HS (mean [SD] age, 47.1 [8.8] years; 88 female [82.2%] and 19 male [17.8%] individuals). At baseline, 57 patients (53.3%) had mild, 20 (18.7%) had moderate, and 30 (28.0%) had severe disease. During the follow-up period, 16.9% of patients with nonsevere disease progressed (13.0% to severe disease), while 71.0% of all patients experienced regression (63.6% to full remission). Stratified by baseline severity, 73.7%, 60.0%, and 46.7% of patients with mild, moderate, and severe disease, respectively, experienced full remission. Cox regression analyses did not reveal any baseline demographic factors capable of predicting disease development at follow-up.

Conclusions and relevance: This cohort study found that estimates from hospital-based cohorts likely overstate HS disease progression and underestimate its remission. In this community-based cohort, HS progression to severe disease was 10.4 times lower and rates of HS remission were 3.8 times higher than reported within hospitals, suggesting a more favorable disease course than previously reported.

Importance: Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) survivors experience substantial long-term sequelae. Research on physical symptoms experienced during acute hospitalization is well documented, but limited studies have been completed on the long-term biopsychosocial effects of SJS/TEN, particularly from the patient's perspective.

Objective: To increase the understanding of the long-term complications of SJS/TEN.

Design, setting, and participants: This qualitative investigation was completed from within a community-based study, the SJS Survivors Study, using a semistructured, in-depth interview guide to query participants about their SJS/TEN experience postdischarge from the hospital. Interviews took place by phone from July 2021 through August 2023. This study included adults who experienced SJS/TEN within the United States.

Main outcome and measures: A biopsychosocial theory-based framework and hierarchical coding system were utilized to understand the long-term life impacts of survivors of SJS/TEN.

Results: The 29 participants, aged 26 to 76 years, were 66% female and 69% White and had experienced SJS/TEN from a wide range of drugs. Patients experienced support while in the hospital, but once discharged, felt isolated and without support to understand the potential sustained impacts of SJS/TEN in their lives and the lives of their family members. Patients experienced ongoing biological symptoms, such as skin issues, debilitating visual impairment, blindness, and lack of functional autonomy. Psychological impacts included symptoms of anxiety, obsessive thinking, flashbacks, and depression. Socially, some survivors expressed a sense of abandonment and described negative impacts on their careers. Survivors also expressed frustration and isolation with having to navigate posthospital care alone. There was a lack of preemptive discharge education and SJS/TEN-specific planning. Lack of physician knowledge about SJS/TEN was particularly noted and survivors turned to the internet for guidance instead of receiving direction from their physicians. Medical distrust among survivors was frequently noted.

Conclusions and relevance: The findings highlight the need for postdischarge care coordination among patients and their primary physicians, including mental health support. This care coordination should be arranged prior to discharge to ensure the availability of adequate support and optimal health outcomes. It is essential that clinicians and researchers prioritize the understanding of long-term sequelae of SJS/TEN and improve current discharge education and protocols for patients and their families.

Importance: Accurate classification and reliability in assessment for lesions of hidradenitis suppurativa (HS) by investigators is critical to the determination of responder status and to overall data quality in clinical trials.

Objective: To establish consensus-based morphological definitions of HS lesions and guidance statements that standardize investigator lesion assessments for implementation in clinical trials.

Evidence review: Health professionals (primarily dermatologists) with expertise in the measurement of HS disease activity as well as novice raters completed a preliminary questionnaire in which participants were asked to assess images of HS lesions and provide qualitative feedback on their decision making. Based on this feedback, detailed morphologic definitions for lesions and guidance statements that standardize lesion assessments were formulated and presented for consensus voting in 2 electronic Delphi surveys. A virtual group discussion after round 1 supported participants in round 2 voting.

Findings: Response rates were 84.7% (50 of 59), 86.0% (43 of 50), and 90.9% (40 of 44) in the preliminary, electronic Delphi round 1, and electronic Delphi round 2 surveys, respectively. Morphological definitions for 11 lesion types achieved the prespecified 70% consensus threshold, with 9 definitions reaching at least 90% agreement. After 2 electronic Delphi rounds, 16 of 18 guidance statements achieved the prespecified consensus threshold, with 13 statements receiving endorsement from more than 80% of participants. Two guidance statements related to assessment of tunneled plaques with multiple openings and assessment of scalp lesions failed to reach consensus.

Conclusions and relevance: Common morphologic definitions and guidance that standardize assessment of HS lesions can be implemented in clinical trial protocols and investigator trainings with the goals of improving accuracy and reliability of investigator ratings.