We used Mendelian randomization to investigate whether genetic proxies of glucagon-like peptide-1 receptor (GLP1R) expression are associated with risk of psoriasis and psoriatic arthritis (PsA). Higher GLP1R expression was associated with reduced susceptibility to psoriasis and PsA, independent of metabolic traits, while no risk-reducing effects were observed for other immune-mediated inflammatory diseases. These results highlight a disease-specific association between GLP1 pathway activity and psoriatic disease.

Importance:Clinician-reported and patient-reported outcomes are critical measures of therapeutic efficacy in cutaneous chronic graft-vs-host disease (cGVHD) but are not always correlated. Discordance in treatment response between clinicians and patients hinders interpretation of outcomes in clinical trials and complicates therapeutic decision-making in clinical practice. Objective:To identify factors associated with discordance in clinician-reported and patient-reported treatment response assessments and to evaluate the association of clinician-reported and patient-reported responses with survival. Design, Setting, and Participants:This multicenter longitudinal cohort study included adults 18 years and older with cutaneous cGVHD at study enrollment, assembled from 2 observational studies and 1 randomized clinical trial. Data were collected from August 2007 to March 2024, and data were analyzed from July 2024 to May 2025. Main Outcomes and Measures:A global 8-point cutaneous cGVHD treatment response assessment (with 1 indicating resolved and 8 indicating very much worse) was reported by clinicians and patients 3 to 6 months after study enrollment. Clinician-reported and patient-reported treatment responses were categorized into improved, stable, and worse from the 8-point scale, and discordance was defined as a difference in response between clinicians and patients. Positive clinician discordance indicates the clinician reported a better response than the patient, and negative clinician discordance indicates the clinician reported a worse response than the patient. The association of clinician-reported and patient-reported responses with survival was measured by nonrelapse mortality. Results:Of 489 adults with cutaneous cGVHD, 192 (39.3%) were female, 297 (60.7%) were male, and the median (IQR) age was 55 (43-62) years. A total of 321 adults (65.6%) had concordant responses and 168 (34.4%) had discordant responses between clinician-reported and patient-reported treatment responses. Patients with sclerotic cGVHD had greater odds of discordance compared with those without sclerosis, with clinicians reporting both better and worse treatment response than patients (positive clinician discordance: adjusted odds ratio, 3.14; 95% CI, 1.41-6.95; P = .005; negative clinician discordance: adjusted odds ratio, 2.33; 95% CI, 1.19-4.56; P = .01). Worsening compared with improved overall cutaneous cGVHD was associated with nonrelapse mortality when reported by clinicians (adjusted hazard ratio, 2.28; 95% CI, 1.46-3.54; P < .001) and patients (adjusted hazard ratio, 1.86; 95% CI, 1.12-3.08; P = .02), while only patient-reported worsening was significantly associated with nonrelapse mortality in patients with sclerotic disease (adjusted hazard ratio, 2.00; 95% CI, 1.02-3.90; P = .04). Conclusions and Relevance:In this cohort study, discordance in treatment response assessments between clinicians and patients was common in cutaneous cGVHD, yet clinician-reported and patient-reported treatment responses were both associated with survival. In patients with sclerosis who were more likely to experience discordance, patient-reported response was a critical treatment end point, and approaches should be developed to bridge discordance.

Background:Psoriasis is associated with increased epicardial adipose tissue (EAT), a metabolically active fat depot in direct contact with the myocardium, and a mediator of coronary artery disease and atrial fibrillation. The effects of psoriasis treatments on EAT are largely unknown. We conducted a post hoc analysis of the Vascular Inflammation in Psoriasis (VIP) trial (NCT01553058, NCT01866592). Methods:VIP compared, in a 1:1:1 randomized manner, placebo (n=27), adalimumab (n=31), and phototherapy (n=28) from baseline to week 12, with all subjects then receiving adalimumab for 52 weeks. EAT volume was quantified from CT imaging at baseline, week 12, and week 52, with concurrent assessment of clinical variables and metabolic and inflammatory biomarkers. Results:At baseline (N=86), EAT volume was positively correlated with age (r = 0.51, p= 2.44 × 10-), body mass index (r = 0.48, p= 2.01×10-6), and weight (r = 0.52, p= 3.17 × 10-), and with inflammatory biomarkers GlycA (r = 0.27, p= 9.48×10-3), C-reactive protein (r = 0.25, p= 9.94×10-3), and IL-6 (r = 0.23, p= 0.02). Over 12 weeks, adalimumab treatment reduced EAT volume (mean change -11.9 cm3, p=0.04; baseline mean EAT 183.1 cm3), with no improvement observed in the placebo or phototherapy groups. When compared with the placebo and phototherapy arms combined, adalimumab was associated with a greater reduction in EAT at week 12 (between-group difference -13.9 cm3, p=0.03). The reduction in EAT was not significantly associated with changes in weight or PASI. No additional reduction in EAT was observed after 52 weeks of adalimumab treatment. Conclusion:Adalimumab was associated with an early reduction in EAT that was not significantly correlated with changes in weight or psoriasis activity. These findings indicate treatment-specific effects on a high-risk cardiac fat depot and suggest that TNF inhibition may influence cardiac adiposity relevant to cardiovascular disease.

Background: Atopic dermatitis (AD) is thought to induce asthma via the "atopic march," but the effects of AD on incident asthma and asthma severity have not been fully characterized. Objective: To determine risk of asthma, asthma exacerbations, and asthma-related hospitalizations among patients fwith AD. Methods: A cohort study was conducted using electronic health records data from UK general practices from 1994 to 2015. Children (<18 years old) and adults (>= 18 years) with AD were matched on age, practice, and index date to patients without AD. AD severity was categorized using treatments and dermatologist referrals. Outcomes were incident asthma among all patients and asthma exacerbation or hospitalization among patients with asthma. Results: On comparing 409,341 children with AD (93.2% mild, 5.5% moderate, 1.3% severe) with 1,809,029 unaffected children, those with AD were found to be associated with a 2-fold greater risk of asthma compared with those without AD (hazard ratio, 1.96; 95% CI, 1.93-1.98). On comparing 625,083 adults with AD (65.7% mild, 31.4% moderate, and 2.9% severe) with 2,678,888 unaffected adults, AD was found to be associated with a 38% higher risk of asthma (hazard ratio, 1.38; 95% CI, 1.36-1.40). Asthmatic patients with AD also had a 21% to 63% greater risk of asthma exacerbations and a 20% to 64% greater risk of asthma-related hospitalizations compared with asthmatic patients without AD. Risk of asthma, asthma exacerbation, or asthma-related hospitalization increased with AD severity in a dose-dependent manner in both the pediatric and adult cohorts. Conclusions: AD, especially in children and when more severe, is associated with greater risk of asthma as well as greater risk of asthma exacerbations and hospitalizations among asthmatic patients.

The effect of objective clinical measures of psoriasis severity on the risk of cardiovascular disease (CVD) is not well-characterized. We conducted a population-based, prospective cohort study of 8,930 psoriasis patients matched to 89,096 non-psoriasis patients aged 25-65 within a United Kingdom medical records database.[1] Psoriasis severity was assessed via questionnaires sent to general practitioners, estimating body surface area (BSA) affected and severity category (<3% BSA – mild; 3-10% BSA – moderate; >10% BSA – severe).[2] The outcome was a validated composite of 12 CVD subtypes (atrial fibrillation/flutter, aortic aneurysm, conduction system disease, stroke/transient ischemic attack, endocarditis, heart failure, ischemic heart disease, myocarditis/pericarditis, peripheral arterial disease, supraventricular arrhythmias, valve disorders, and pulmonary embolism), and subtypes separately.[3] Multivariate Cox regression models were adjusted for known cardiovascular risk factors including age, sex, BMI, smoking, drinking, socioeconomic status, comorbidities, and CVD history. After adjustment, psoriasis was independently associated with higher risk of CVD [HR 1.09 (1.01, 1.18)] driven by the >10% BSA cohort [1.23 (1.01, 1.50)]. For every 5% increase in BSA affected, CVD disease risk increased 4% (p=0.01). Regarding individual outcomes: the <3% BSA cohort had increased risk of supraventricular arrhythmia [1.89 (1.12, 3.17)], while the 3-10% BSA cohort had increased risk of heart failure [1.48 (1.06, 2.08)] and atrial fibrillation/flutter [1.53 (1.19, 1.97)], and the >10% BSA cohort had increased risk of valve disorders [1.91 (1.15, 3.16)]. In conclusion, CVD risk increases with BSA affected by psoriasis.

Importance:Office-based phototherapy is cost-effective for psoriasis but difficult to access. Home-based phototherapy is patient preferred but has limited clinical data, particularly in patients with darker skin. Objective:To compare the effectiveness of home- vs office-based narrowband UV-B phototherapy for psoriasis. Design, Setting, and Participants:The Light Treatment Effectiveness study was an investigator-initiated, pragmatic, open-label, parallel-group, multicenter, noninferiority randomized clinical trial embedded in routine care at 42 academic and private clinical dermatology practices in the US. Enrollment occurred from March 1, 2019, to December 4, 2023, with follow-up through June 2024. Participants were 12 years and older with plaque or guttate psoriasis who were candidates for home- and office-based phototherapy. Interventions:Participants were randomized to receive a home narrowband UV-B machine with guided mode dosimetry or routine care with office-based narrowband UV-B for 12 weeks, followed by an additional 12-week observation period. Main Outcomes and Measures:The coprimary effectiveness outcomes were Physician Global Assessment (PGA) dichotomized as clear/almost clear skin (score of ≤1) at the end of the intervention period and Dermatology Life Quality Index (DLQI) score of 5 or lower (no to small effect on quality of life) at week 12. Results:Of 783 patients enrolled (mean [SD] age, 48.0 [15.5] years; 376 [48.0%] female), 393 received home-based phototherapy and 390 received office-based phototherapy, with 350 (44.7%) having skin phototype (SPT) I/II, 350 (44.7%) having SPT III/IV, and 83 (10.6%) having SPT V/VI. A total of 93 patients (11.9%) were receiving systemic treatment. At baseline, mean (SD) PGA was 2.7 (0.8) and DLQI was 12.2 (7.2). At week 12, 129 patients (32.8%) receiving home-based phototherapy and 100 patients (25.6%) receiving office-based phototherapy achieved clear/almost clear skin, and 206 (52.4%) and 131 (33.6%) achieved DLQI of 5 or lower, respectively. Home-based phototherapy was noninferior to office-based phototherapy for PGA and DLQI in the overall population and across all SPTs. Home-based phototherapy, compared to office-based phototherapy, was associated with better treatment adherence (202 patients [51.4%] vs 62 patients [15.9%]; P < .001), lower burden of indirect costs to patients, and more episodes of persistent erythema (466 of 7957 treatments [5.9%] vs 46 of 3934 treatments [1.2%]; P < .001). Both treatments were well tolerated with no discontinuations due to adverse events. Conclusions and Relevance:In this randomized clinical trial, home-based phototherapy was as effective as office-based phototherapy for plaque or guttate psoriasis in everyday clinical practice and had less burden to patients. Trial Registration:ClinicalTrials.gov Identifier: NCT03726489.

Psoriasis is a cardiovascular disease (CVD) risk enhancer warranting earlier use of statins for primary prevention of CVD and reduction in all-cause mortality. Despite the breadth of evidence, CV risk factors such as hyperlipidemia remains under-treated in patients with psoriasis. We aimed to quantify the epidemiology of hyperlipidemia and statin utilization in psoriasis, stratified by severity, using a large UK population-based electronic health records database [THIN (The Health Improvement Network)] from 1994-2021. A total of 356,907 psoriasis patient were matched on age, practice and index date to 1,402,046 controls. Severity was defined using treatments as a proxy. We observed an association between psoriasis and hyperlipidemia compared to controls [Odds ratio (OR): 1.08 (1.07-1.10)] and in a "dose response" manner with disease severity [mild (OR: 1.06: (1.05-1.07); moderate/severe (OR: 1.39 (1.34-1.44)]. Statin Adherence was measured using proportion of days covered (PDC), calculated as total days of supply divided by total follow up time, with a PDC ≥0.8 deemed as adherent. We found that psoriasis patients with a known diagnosis of hyperlipidemia were less likely to be adherent when compared to controls [OR: 0.95 (0.92-0.98]. Similar trends were observed in mild [OR: 0.95 (0.93-0.98)]; and moderate/severe disease [OR: 0.91 (0.84-0.99)]. Our findings highlight the need of providing a standard approach to hyperlipidemic screening in psoriasis, and insights into the value of early diagnosis and treatment adherence in affected patients, to potentially improve overall survival in patients with psoriasis.

The Press Ganey (PG) Outpatient Medical Practice Survey measures patients’ experiences of healthcare access in the U.S. We aimed to identify differences in experiences of access to care by patient race, ethnicity, and other sociodemographic characteristics, an important first step in informing health policy and ensuring equitable healthcare delivery. We performed a cross-sectional analysis of PG surveys for adult outpatient visits within the University of Pennsylvania Health System from 2014–2017, including 119,373 unique patients. Compared with White patients, Black (odds ratio [OR] 0.84; 95% confidence interval [CI] 0.80–0.87), Asian (OR 0.62; 95% CI 0.58–0.66), and other/unknown race patients (OR 0.83; 95% CI 0.72–0.94) were each less likely to report the maximum score for timely access to care. Patients of all minoritized groups, as well as those whose primary language was not English, reported lower scores in secondary access measures related to communication and respect, compared to White and primarily English-speaking patients, respectively. Efforts to improve the experience of access to care among racial and ethnic minoritized patients are imperative to achieve equity in healthcare delivery.

To the Editor: The geographic maldistribution of dermatologists in the United States is suggested to cause racial and ethnic disparities in access to care based on limited evidence.1-3 To better understand how dermatologist distribution may impact access to dermatologic care, we performed a cross-sectional study to evaluate associations between geographic and county-level sociodemographic factors and dermatologist supply in the United States.

BACKGROUND:Atopic dermatitis (AD) is a common inflammatory disease of the skin that begins early in life and can be lifelong. The purpose of our study was to evaluate whether fetal exposure and/or early-life exposure of a child to antibiotics increases the risk of early-onset AD. OBJECTIVES:We hypothesize that antibiotic exposure in utero or early in life (e.g. first 90 days) increases the likelihood that children develop AD. METHODS:Utilizing a large, prospectively collected electronic medical records database, we studied the association of antibiotic exposure received in utero or very early in life and the relative risk of onset of AD in a population-based cohort study. Associations were estimated using proportional hazards models as hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS:The risk of AD in childhood was increased after in utero or early-life antibiotic exposure. For any in utero antibiotic exposure the HR (CI) was 1.38 (1.36-1.39). However, penicillin demonstrated the strongest association with AD for both in utero exposure [1.43 (1.41-1.44)] and for childhood exposure [1.81 (1.79-1.82)]. HRs were higher in children born to mothers without AD than in those with AD pointing to effect modification by maternal AD status. CONCLUSIONS:Children born to mothers exposed to antibiotics while in utero had, depending on the mother's history of AD, approximately a 20-40% increased risk of developing AD. Depending on the antibiotic, children who received antibiotics early in life had a 40-80% increased risk of developing AD. Our study supports and refines the association between incident AD and antibiotic administration. It also adds population-based support to therapeutic attempts to treat AD by modifying the skin microbiome.

Background: Atopic dermatitis (AD) may be associated with an increased burden of neuropsychiatric outcomes such as anxiety and depression, but longitudinal data on the impact of AD severity is lacking, and a comprehensive assessment of neuropsychiatric disease in adults with AD is needed. Objectives: Determine risk of incident neuropsychiatric disease among adults with AD by severity. Methods: A cohort study using electronic health records data from UK general practices from 1994 to 2015. Adults (>= 18 years) with AD were matched on age, practice and index date to patients without AD. AD severity was categorized using treatments and dermatology referrals. Outcomes were incident anxiety, depression, bipolar disorder, schizophrenia, attention-deficit/ hyperactivity disorder (ADHD), autism, obsessive-compulsive disorder (OCD), suicidality and completed suicide. Results: Comparing 625,083 adults with AD to 2,678,888 adults without AD, AD was associated with higher risk of anxiety [HR 1.14 (1.13-1.15)], depression [1.14 (1.13-1.15)] and OCD [1.48 (1.38-1.58)] across all severities. Mild or moderate AD was also associated with higher risk of autism, ADHD, bipolar disorder and suicidality. Conclusions: Atopic dermatitis is associated with a higher risk of multiple neuropsychiatric conditions, but these risks differ by specific condition and AD severity. Clinicians should inquire about mental health in patients with AD.

This cross-sectional study evaluates the frequency of skin biopsies, as an indicator of diagnostic uncertainty, by race and ethnicity among patients with psoriasis seen in an academic dermatology practice.

Importance:Chronic graft-vs-host disease (GVHD) is associated with impaired quality of life and symptom burden. The independent association of skin involvement with patient-reported outcomes (PROs) and their utility as a clinical prognostic marker remain unknown. Identification of patients with cutaneous chronic GVHD and impaired PROs could assist in initial risk stratification and treatment selection. Objective:To compare the association of sclerotic and epidermal-type chronic GVHD with longitudinal PROs and to evaluate whether PROs can identify patients with cutaneous chronic GVHD at high risk for death. Design, Setting, and Participants:This multicenter prospective cohort study involved patients from the Chronic GVHD Consortium of 9 US medical centers, enrolled between August 2007 and April 2012, and followed up until December 2020. Participants included adults 18 years and older with a diagnosis of chronic GVHD requiring systemic immunosuppression and with skin involvement during the study period. Main Outcomes and Measures:Patient-reported symptom burden was assessed using the Lee Symptom Scale (LSS) skin subscale with higher scores indicating worse outcomes. Quality of life was measured using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) instrument with lower scores indicating worse outcomes. Nonrelapse mortality, overall survival, and their association with PROs at diagnosis were also assessed. Results:Among 436 patients with cutaneous chronic GVHD (median [IQR] age at transplant, 51 [41.5-56.6] years; 261 [59.9%] male), 229 patients had epidermal-type chronic GVHD (52.5%), followed by 131 with sclerotic chronic GVHD (30.0%), and 76 with combination disease (17.4%). After adjusting for confounders, patients with sclerotic chronic GVHD had mean FACT-BMT scores 6.1 points worse than those with epidermal disease (95% CI, 11.7-0.4; P = .04). Patients with combination disease had mean LSS skin subscale scores 9.0 points worse than those with epidermal disease (95% CI, 4.2-13.8; P < .001). Clinically meaningful differences were defined as at least 7 points lower for FACT-BMT and 11 points higher for LSS skin subscale. At diagnosis, clinically meaningful worsening in FACT-BMT score was associated with an adjusted odds of nonrelapse mortality increased by 9.1% (95% CI, 2.0%-16.7%; P = .01). Similarly, for clinically meaningful worsening in LSS skin subscale score, adjusted odds of nonrelapse mortality increased by 16.4% (95% CI, 5.4%-28.5%; P = .003). These associations held true after adjusting for clinical severity by the National Institutes of Health Skin Score. Conclusions and Relevance:The results of this cohort study demonstrated that skin chronic GVHD was independently associated with long-term PRO impairment, with sclerotic and combination disease carrying the highest morbidity. The degree of impairment at skin chronic GVHD diagnosis was a prognostic marker for mortality. Therefore, PROs could be useful for risk stratification and treatment selection in clinical practice and clinical trials.

Psoriasis is an inflammatory disease associated with premature mortality, largely explained by an excess risk of cardiovascular (CV) events (Elmets et al, 2019; Gelfand et al, 2006). Dermatology and cardiology guidelines define psoriasis as a CV risk enhancer warranting more intensive management of traditional CV risk factors (Elmets et al, 2019; Grundy et al, 2019). However, identification and management of these risk factors in patients with psoriasis are insufficient, resulting in preventable morbidity and mortality (Eder et al, 2018).