Understanding patient perspectives on vaccine decision making in adults with autoimmune bullous diseases: a qualitative study.

Patients with autoimmune bullous diseases are at an increased risk of infection, both from the underlying skin disease and from immunosuppressive treatments. Limited information is available on vaccine beliefs and behaviors in dermatology patients and adults with autoimmune bullous diseases in particular. To understand vaccine decision making, identify perceived risks and benefits of vaccinations, and discuss individual experiences in patients with autoimmune bullous diseases in the United States. A qualitative study was performed utilizing semi-structured interviews, and analysis was conducted on NVivo. Patterns were identified in the coded data, and representative quotations were recorded for each major theme. Interviews were conducted between February 15, 2022 and September 15, 2022. Twenty patients with a diagnosis of bullous pemphigoid, mucous membrane pemphigoid, pemphigus vulgaris, or pemphigus foliaceous were interviewed. Of the 20 participants, 14 (70%) were female, with a mean (SD, range) age of 64.8 (13.2, 34-83) years. Key themes that emerged from qualitative analysis of the interviews included patient concerns regarding their increased susceptibility to infection, potential exacerbation of skin disease following vaccination, and the effect of immunosuppressive medications on humoral response to vaccines. Lack of appointment availability, difficulty accessing vaccines, and cost were commonly identified barriers to vaccination. These findings provide valuable knowledge for dermatologists in regard to providing counseling specific to patient concerns and to improve communication surrounding vaccination in the dermatology setting.

Monocyte-to-High-Density Lipoprotein Ratio Is Associated with Systemic Inflammation, Insulin Resistance, and Coronary Subclinical Atherosclerosis in Psoriasis: Results from 2 Observational Cohorts.

Systemic inflammation or insulin resistance drive atherosclerosis. However, they are difficult to capture for assessing cardiovascular risk in clinical settings. The monocyte-to-high-density lipoprotein ratio (MHR) is an accessible biomarker that integrates inflammatory and metabolic information and has been associated with poorer cardiovascular outcomes. Our aim was to evaluate the association of MHR with the presence of subclinical atherosclerosis in patients with psoriasis. The study involved a European and an American cohort including 405 patients with the disease. Subclinical atherosclerosis was assessed by coronary computed tomography angiography. First, MHR correlated with insulin resistance through homeostatic model assessment for insulin resistance, with high-sensitivity CRP and with 18F-fluorodeoxyglucose uptake in spleen, liver, and bone marrow by positron emission tomography/computed tomography. MHR was associated with both the presence of coronary plaques >50% of the artery lumen and noncalcified coronary burden, beyond traditional cardiovascular risk factors (P < .05). In a noncalcified coronary burden prediction model accounting for cardiovascular risk factors, statins, and biologic treatment, MHR added value (area under the curve base model = 0.72 vs area under the curve base model plus MHR = 0.76, P = .04) within the American cohort. These results suggests that MHR may detect patients with psoriasis who have subclinical burden of cardiovascular disease and warrant more aggressive measures to reduce lifetime adverse cardiovascular outcomes.

Patient-Reported Outcomes and Mortality in Cutaneous Chronic Graft-vs-Host Disease.

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.

Vaccination recommendations for adults receiving biologics and oral therapies for psoriasis and psoriatic arthritis: Delphi consensus from the medical board of the National Psoriasis Foundation.

BACKGROUND: For psoriatic patients who need to receive nonlive or live vaccines, evidence-based recommendations are needed regarding whether to pause or continue systemic therapies for psoriasis and/or psoriatic arthritis. OBJECTIVE: To evaluate literature regarding vaccine efficacy and safety and to generate consensus-based recommendations for adults receiving systemic therapies for psoriasis and/or psoriatic arthritis receiving nonlive or live vaccines. METHODS: Using a modified Delphi process, 22 consensus statements were developed by the National Psoriasis Foundation Medical Board and COVID-19 Task Force, and infectious disease experts. RESULTS: Key recommendations include continuing most oral and biologic therapies without modification for patients receiving nonlive vaccines; consider interruption of methotrexate for nonlive vaccines. For patients receiving live vaccines, discontinue most oral and biologic medications before and after administration of live vaccine. Specific recommendations include discontinuing most biologic therapies, except for abatacept, for 2-3 half-lives before live vaccine administration and deferring next dose 2-4 weeks after live vaccination. LIMITATIONS: Studies regarding infection rates after vaccination are lacking. CONCLUSION: Interruption of antipsoriatic oral and biologic therapies is generally not necessary for patients receiving nonlive vaccines. Temporary interruption of oral and biologic therapies before and after administration of live vaccines is recommended in most cases.

Chronic Graft-versus-Host Disease-Associated Muscle Cramps: Severity and Response to Immunomodulatory Therapies.

Muscle cramps in patients with chronic graft-versus-host disease (cGVHD) are common and associated with impaired quality of life and symptom burden. Muscle cramps are not currently captured in the 2014 National Institutes of Health (NIH) response criteria, and thus characterization and response to immunomodulatory therapies are lacking. The objective of this study was to characterize muscle cramp frequency, duration, and pain level in patients with steroid-refractory cGVHD undergoing extracorporeal photopheresis (ECP). A single-center cohort of patients who underwent ECP for the indication of steroid-refractory cGVHD with muscle cramps at treatment initiation were followed from April 2021 to April 2023. Of 22 patients receiving ECP for cGVHD during the study period, 9 (41%) had muscle cramps at ECP initiation (6 males [66%]; median age, 59 years; range, 25 to 66 years). Seven of these 9 patients (78%) had multiple organs involved, and 7 (78%) had severe disease by the NIH Global Severity scale. Over a median treatment duration of 28 weeks (range, 10 to 48 weeks), 8 patients (89%) had decreased frequency of muscle cramps from a median of 5 episodes per week (range, 3 per day to 2 per week) to a median of <1 episode per week (range, 1 per month to 3 per week). The pain and duration of muscle cramps were not changed meaningfully. The NIH Global Severity score remained unchanged in 6 patients (67%) and was improved in 3 patients (33%). Muscle cramping is a morbid feature of cGVHD that may be sensitive to change with standard immunomodulatory therapies. Muscle cramp frequency should be further validated as a response measure in cGVHD.

Incident Asthma, Asthma Exacerbations, and Asthma-Related Hospitalizations in Patients With Atopic Dermatitis.

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.

Neuropsychiatric disorders in adults with atopic dermatitis: A population-based cohort study.

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.

Cardiovascular and Venous Thromboembolic Risk With JAK Inhibitors in Immune-Mediated Inflammatory Skin Diseases: A Systematic Review and Meta-Analysis.

Importance: Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions. Objective: To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions. Data Sources: PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023. Study Selection: This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded. Data Extraction and Synthesis: This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO. Main Outcomes and Measures: Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE. Results: The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04). Conclusions and Relevance: In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.

Association of the Complement System with Subclinical Atherosclerosis in Psoriasis: Findings from an Observational Cohort Study.

Psoriasis is a chronic and inflammatory disease that affects the skin and joints and is associated with multiple comorbidities and cardiovascular risk factors. Consequently, patients with psoriasis have an increased risk of cardiovascular diseases such as atherosclerosis, a chronic pathology that shares common inflammatory and immune-response mechanisms with psoriasis, including vascular inflammation and complement activation. To better understand the relationship between atherosclerosis and psoriasis, a proteomics study followed by a bioinformatics analysis was carried out, with a subsequent validation step using ELISA and western blotting. When the plasma from patients with psoriasis alone was compared with that from patients with psoriasis and atherosclerosis, 31 proteins of interest related to the complement system and oxygen transport were identified. After the validation phase, 11 proteins appeared to define the presence of subclinical atherosclerosis in patients with psoriasis, indicating the importance of complement cascades in the development of atherosclerotic plaques in individuals with psoriasis. These results are a step forward in understanding the pathological pathways implicated in the cardiovascular risk associated with this population, which may represent an interesting starting point for developing predictive tools that improve the follow-up of these patients and design more effective therapies.

Early Detection and Progression of Subclinical Atherosclerosis in Psoriasis (EDSAP): protocol for an observational, single-centre, prospective cohort study.

INTRODUCTION: Life expectancy of patients with psoriasis is reduced by 4-5 years due to cardiovascular disease with an increased risk of myocardial infarction at an earlier age compared with the general population. This increased risk is independent of traditional cardiovascular risk factors and higher in moderate-to-severe forms of psoriasis. Inflammation may play a key role in the development of atherosclerosis in these patients. METHODS AND ANALYSIS: A prospective cohort study, Early Detection and Progression of Subclinical Atherosclerosis in Psoriasis (EDSAP), was initiated in January 2020 to investigate the presence and progression of subclinical atherosclerosis in patients with psoriasis. 120 patients aged 30-65 years and eligible for biological treatment have been recruited at Hospital Ramón y Cajal in Madrid, Spain. Patients undergo a baseline visit, and 1-year follow-up visit after starting biological therapy. Each visit includes: assessment of cardiovascular risk factors, screening for subclinical atherosclerosis by two-dimensional/three-dimensional ultrasound of carotid and femoral arteries, cardiac CT of coronary arteries and blood sampling. All baseline visits were completed by December 2022, and the remaining follow-up visits will be concluded by the end of 2023. The EDSAP study aims to identify new molecular and imaging markers associated with the presence of atherosclerosis and its progression in a chronic inflammatory state such as psoriasis. This has the potential to: (1) help improve primary cardiovascular prevention strategies in these patients; (2) understand the effect of biological drugs on the cardiovascular system; and (3) serve as a model for understanding atherosclerosis in other chronic inflammatory diseases. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Review Board of the Hospital Ramón y Cajal in Madrid. We will present our findings at national and international congresses, and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05858099.

Incidence of Cardiovascular Disease and Venous Thromboembolism in Patients With Atopic Dermatitis.

BACKGROUND: Atopic dermatitis (AD) may increase risk for atherothrombotic and cardiovascular (CV) disease. OBJECTIVE: Determine CV disease and venous thromboembolism risk among patients with AD. METHODS: Cohort study using electronic health data from U.K. general practices in 1994 to 2015. Children (<18 y) and adults (≥18 y) with AD were matched to patients without AD on age, same practice, and encounter date. Treatments and specialist referrals served as proxies of AD severity. Outcomes were incident myocardial infarction, cerebrovascular accident (CVA), diabetes, hypertension, dyslipidemia, deep vein thrombosis (DVT), and pulmonary embolism. Cox regression analysis was used to compare outcomes in AD versus non-AD patients. RESULTS: Comparing 409,341 children with AD (93.2% mild, 5.5% moderate, and 1.3% severe) to 1,809,029 unaffected children, AD was associated with higher risk of DVT (hazard ratio [HR] 1.23; 95% confidence interval [95% CI] 1.02-1.48) and severe AD was associated with higher risk of CVA (HR 2.43; 95% CI 1.13-5.22) and diabetes (HR 1.46; 95% CI 1.06-2.01). Comparing 625,083 adults with AD (65.7% mild, 31.4% moderate, and 2.9% severe) to 2,678,888 unaffected adults, AD, especially when severe, was associated with higher risk of DVT (HR 1.14; 95% CI 1.11-1.18; and HR 1.64; 95% CI 1.49-1.82, respectively) and small but increased risks of CVA, diabetes, and dyslipidemia. Adults with severe AD had higher risk of myocardial infarction (HR 1.27; 95% CI 1.15-1.39), CVA (HR 1.21; 95% CI 1.13-1.30), diabetes (HR 1.15; 95% CI 1.09-1.22), dyslipidemia (HR 1.11; 95% CI 1.06-1.17), and pulmonary embolism (HR 1.39; 95% CI 1.21-1.60) compared with adults without AD. CONCLUSIONS: Atopic dermatitis, particularly when severe, is associated with small but increased risks of CV risk factors and events and significantly increased risk of venous thromboembolism.

Risk of Inflammatory Bowel Disease in Patients With Atopic Dermatitis.

Importance: Data on the association between atopic dermatitis (AD) and inflammatory bowel disease (IBD) are inconsistent. Few studies have examined the association of AD or AD severity with risk of ulcerative colitis (UC) and Crohn disease (CD) separately. Objectives: To examine the risk of new-onset IBD, UC, and CD in children and adults with AD. Design, Setting, and Participants: This population-based cohort study assessed patients with AD matched with up to 5 controls on age, practice, and index date. Treatment exposure was used as a proxy for AD severity. Data were retrieved from The Health Improvement Network, a UK electronic medical record database, for January 1, 1994, to February 28, 2015. Data analysis was performed from January 8, 2020, to June 30, 2023. Main Outcomes and Measures: Outcomes of interest were incident IBD, UC, and CD. Logistic regression was used to examine the risk for each outcome in children and adults with AD compared with controls. Results: A total of 1 809 029 pediatric controls were matched to 409 431 children with AD (93.2% mild, 5.5% moderate, and 1.3% severe). The pediatric cohort ranged in median age from 4 to 5 years (overall range, 1-10 years), was predominantly male (936 750 [51.8%] controls, 196 996 [51.6%] with mild AD, 11 379 [50.7%] with moderate AD, and 2985 [56.1%] with severe AD), and with similar socioeconomic status. A total of 2 678 888 adult controls were matched to 625 083 adults with AD (65.7% mild, 31.4% moderate, and 2.9% severe). The adult cohort ranged in median age from 45 to 50 years (overall range, 30-68 years) and was predominantly female (1 445 589 [54.0%] controls, 256 071 [62.3%] with mild AD, 109 404 [55.8%] with moderate AD, and 10 736 [59.3%] with severe AD). In fully adjusted models, children with AD had a 44% increased risk of IBD (hazard ratio [HR], 1.44; 95% CI, 1.31-1.58) and a 74% increased risk of CD (HR, 1.74; 95% CI, 1.54-1.97), which increased with worsening AD; however, they did not have increased risk of UC (HR, 1.09; 95% CI, 0.94-1.27) except for those with severe AD (HR, 1.65; 95% CI, 1.02-2.67). Adults with AD had a 34% (HR, 1.34; 95% CI, 1.27-1.40) increased risk of IBD, a 36% (HR, 1.36; 95% CI, 1.26-1.47) increased risk of CB, and a 32% (HR, 1.32; 95% CI, 1.24-1.41) increased risk of UC, with risk increasing with worsening AD. Conclusion and Relevance: In this cohort study, children and adults with AD had an increased risk of IBD, with risk varying by age, AD severity, and IBD subtype. These findings provide new insights into the association between AD and IBD. Clinicians should be aware of these risks, particularly when selecting systemic treatments for AD in patients who may have coincident gastrointestinal symptoms.

Malignancy risk in patients with atopic dermatitis: a population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is associated with immunological dysfunction, which may influence cancer development. Previous studies of AD and cancer demonstrate inconsistent results and few of these studies examined children or AD severity and treatment. OBJECTIVES: To determine malignancy risk among children and adults with AD. METHODS: We conducted a cohort study using electronic health records data from UK general practices in The Health Improvement Network between 1994 and 2015. Children (< 18 years old) and adults (≥ 18 years old) with AD were matched on age, practice and index date to patients without AD. AD was categorized as mild, moderate or severe using treatments and dermatology referrals as proxies. The primary outcome was any incident malignancy, including in situ malignancy, identified using diagnosis codes and categorized into haematological, skin and solid organ malignancies. Secondary outcomes included specific malignancies: leukaemia, lymphoma, melanoma, nonmelanoma skin cancer (NMSC) and common solid-organ cancers. RESULTS: Among 409 431 children with AD (93.2% mild, 5.5% moderate, 1.3% severe) and 1 809 029 children without AD who had median follow-up of 5-7 years, the incidence rates of malignancy were 1.9-3.4 and 2.0 per 10 000 person-years (PY), respectively. The adjusted risk of malignancy overall did not differ with respect to AD [hazard ratio (HR) 1.02 (95% confidence interval 0.92-1.12)]. Severe AD was associated with increased lymphoma risk [HR 3.18 (1.41-7.16), excluding cutaneous T-cell lymphoma (CTCL)], and mild AD was associated with increased NMSC risk [1.55 (1.06-2.27)]. Among 625 083 adults with AD (65.7% mild, 31.4% moderate, 2.9% severe) and 2 678 888 adults without AD who had median follow-up of 5 years, incidence rates of malignancy were 97.4-125.3 per 10 000 PY and 103.7 per 10 000 PY, respectively. The adjusted risk of any malignancy did not differ with respect to AD [HR 1.00 (0.99-1.02)]. However, adults with severe AD had a twofold higher risk of non-CTCL lymphoma. AD was also associated with slightly higher skin cancer risk [HR 1.06 (1.04-1.08)] and slightly lower solid cancer risk [0.97 (0.96-0.98)] but results varied by specific cancers and AD severity. CONCLUSIONS: Epidemiological evidence does not support a strong overall malignancy risk in AD but lymphoma risk may be increased with severe AD.