JAMA dermatology最新文献

Importance: The long-term effectiveness of biologic therapies in psoriasis may decline over time. Gut microbiota alterations induced by antibiotics have been proposed as a potential mechanism impairing biologic persistence.

Objective: To evaluate the association between antibiotic exposure and the persistence of biologic therapies in patients with psoriasis.

Design, setting, and participants: This retrospective cohort study used data from the French National Health Insurance database between June 2011 and December 2022. Adults initiating a biologic therapy for psoriasis were included, excluding those with preexisting inflammatory bowel disease at baseline. Data were analyzed from January to September 2024.

Exposures: At baseline, antibiotics exposure was classified as none, 1, or 2 or more dispensations in the 6 months preceding the index date. During follow-up, time-dependent antibiotics exposure was defined as none, 1, or 2 or more antibiotics dispensations in the 6 months prior to each time of follow-up.

Main outcomes and measures: The primary outcome was discontinuation or switch of the initial biologic therapy. Exposure to antibiotics was assessed within 6 months prior to biologic initiation and during follow-up. A weighted Cox marginal structural model was used to estimate adjusted hazard ratios.

Results: Of 36 129 included patients, 11 228 (42.0%) were female, 20 192 (55.9%) were male, and the mean (SD) age was 48.4 (15.1) years. A total of 9366 (25.9%) were exposed to antibiotics at baseline and 21 900 (60.6%) during follow-up. The most commonly prescribed antibiotic classes were β-lactams, macrolides, and fluoroquinolones. Antibiotic exposure was associated with a higher risk of biologic discontinuation (weighted hazard ratio, 1.12; 95% CI, 1.08-1.16), with a stronger effect observed for multiple dispensations (weighted hazard ratio, 1.29; 95% CI, 1.24-1.35), suggesting a dose-response relationship.

Conclusions and relevance: In this cohort study, antibiotic exposure was significantly associated with an increased risk of discontinuation of biologic therapies in psoriasis. These findings support the hypothesis that antibiotics, potentially through gut dysbiosis, may reduce biologic persistence. However, unmeasured confounders limit causal interpretation. Further studies are necessary to validate these findings.

Clinical question: Which topical anti-inflammatory treatments are most effective and safe for managing atopic dermatitis?

Bottom line: In a network meta-analyses, very potent/potent topical corticosteroids; tacrolimus, 0.1%; and topical Janus kinase inhibitors were among the most effective treatments for short-term control of atopic dermatitis symptoms, while phosphodiesterase-4 inhibitors were among the least effective. Topical calcineurin inhibitors and crisaborole were associated with application-site irritation, and short-term topical steroid use was not associated with skin thinning. However, these findings were of low to moderate certainty, and longer-term data remain limited for many agents.

Importance: T-cell receptor (TCR) clonotype patterns across disease stages and histologic subtypes in mycosis fungoides (MF) and Sézary syndrome (SS) remain poorly characterized, limiting their use in risk stratification.

Objectives: To assess the association of TCR β (TCRB) and γ (TCRG) clonotypes with disease stage, folliculotropism, large-cell transformation, and overall survival (OS) as well as clonal abundance (percentage of total reads) with immune checkpoint expression.

Design, setting, and participants: This retrospective cohort study conducted at City of Hope (Duarte, California) included patients with stage IA to IVB MF/SS who underwent TCR next-generation sequencing on lesional skin biopsy specimens collected between June 2020 to October 2024; duplicate samples were excluded. Analyses were performed from November 2024 to April 2025.

Main outcomes and measures: Associations between clinical and genetic categorical variables were evaluated using the Fisher exact test. OS was analyzed using Kaplan-Meier estimates, with univariate and multivariable models applied to assess prognostic factors.

Results: Of the 125 patients (42 female [33.6%] and 74 male individuals [66.4%]; mean [SD] age, 62.4 [15.9] years) who underwent TCR sequencing, at least 1 clonal TCRB and/or TCRG gene segment was identified in 98 patients (78%). Clonal TCRB and TCRG segments were detected in 72 (57.6%) and 92 patients (73.6%), respectively. The clonal Vb20 segment was significantly associated with folliculotropism and concurrent large-cell transformation compared with classic MF/SS (7 of 17 [41%] vs 0 of 30 [0%]; P < .001), marginally significantly associated with advanced-stage MF/SS compared with early-stage MF (8 of 38 [21%] vs 0 of 34 [0%]; P = .01). Clonal Vg8 was significantly associated with advanced-stage MF/SS compared with early-stage MF (25 of 53 [47%] vs 8 of 39 [21%]; P = .01) and correlated with poorer OS. Additionally, the higher percentage of total reads for TCRG was positively correlated with increased expression of immune checkpoints programmed cell death 1 and inducible T-cell costimulator but not with programmed cell death ligand 1.

Conclusions and relevance: This cohort study's analysis of TCRB and TCRG repertoires identified specific clonotypes that were associated with more aggressive subtypes and poorer survival in patients with MF/SS. Incorporating TCR sequencing into clinical practice may enhance risk stratification, enabling earlier identification of high-risk patients who could benefit from closer monitoring and timely implementation of more intensive treatment strategies in the disease course to improve clinical outcomes.

Importance: The epithelial barrier theory (EBT) proposes that epithelial barrier disruption is implicated in the development of skin, respiratory, gastrointestinal, and ocular diseases (epithelial barrier diseases, or EBDs). There is a need to better understand the relationship between seborrheic dermatitis and EBDs, and we hypothesize that seborrheic dermatitis, characterized by epithelial barrier dysfunction, is associated with increased frequency of other EBDs.

Objective: To explore the association between seborrheic dermatitis and EBDs.

Design, setting, and participants: This retrospective cohort study used a large US administrative claims database, which included data collected from multiple health care centers and patient care settings across the US from January 1, 2016, through June 30, 2022. This study consisted of patients aged 18 years and older at enrollment, with at least 1 year of continuous enrollment, and with a minimum of 2 visits on unique days to a medical professional. The mean (SD) patient follow-up time was 3.46 (1.80) years with a total follow-up of more than 70 million person-years. Individuals with missing data for demographic covariates, including age, sex, and division (ie, billing region), were excluded. Data were analyzed from January to September 2025.

Exposures: Diagnosis of seborrheic dermatitis at any point during the observation period.

Main outcomes and measures: Diagnosis of an EBD at any point during the observation period.

Results: Of 20 274 189 patients, 733 776 (3.62%) had seborrheic dermatitis (median [IQR] age, 62.63 [41.53-70.55] years; 54.7% female). Using adjusted models, seborrheic dermatitis was positively associated with atopic dermatitis (odds ratio [OR], 3.21; 95% CI, 3.18-3.24), alopecia areata (OR, 4.02; 95% CI, 3.93-4.11), contact dermatitis (OR, 2.25; 95% CI, 2.23-2.26), psoriasis (OR, 3.26; 95% CI, 3.23-3.29), rosacea (OR, 4.52; 95% CI, 4.49-4.56), hidradenitis suppurativa (OR, 1.63; 95% CI, 1.58-1.68), chronic spontaneous urticaria (OR, 1.35; 95% CI, 1.33-1.37), pemphigus vulgaris (OR, 1.48; 95% CI, 1.31-1.69), bullous pemphigoid (OR, 1.60; 95% CI, 1.51-1.70), rhinosinusitis (OR, 1.24; 95% CI, 1.24-1.25), celiac disease (OR, 1.36; 95% CI, 1.32-1.39), irritable bowel syndrome (OR, 1.32; 95% CI, 1.31-1.33), ocular allergy (OR, 1.39; 95% CI, 1.37-1.41), and dry eye (OR, 1.48; 95% CI, 1.48-1.49) and was negatively associated with chronic obstructive pulmonary disease (OR, 0.72; 95% CI, 0.71-0.72) and pulmonary hypertension (OR, 0.70; 95% CI, 0.69-0.71).

Conclusions and relevance: These findings support the EBT as a shared driver in the pathogenesis of seborrheic dermatitis and other diverse EBDs and encourage further investigation into the underlying mechanisms of disease pathogenesis.