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BackgroundStaphylococcal and herpes simplex virus (HSV) infections are commonly recognized in atopic dermatitis (AD), but less is known about other types of infections.ObjectivesTo determine the risk of herpesvirus infections, serious infections and opportunistic infections in patients with AD.MethodsWe conducted a population-based cohort study using UK-based electronic medical records data. Patients with AD were each matched to up to five unaffected patients on age, practice and index date. AD severity was defined using treatments as a proxy. Outcomes were incident herpesvirus infections [cytomegalovirus (CMV), Epstein-Barr virus (EBV), HSV or varicella zoster virus (VZV)], serious infections and opportunistic infections.ResultsAmong 409 431 children and 625 083 adults with AD matched to 1 809 029 children and 2 678 888 adults without AD, respectively, adjusted Cox regression models showed children and adults with AD had a 50-52% greater risk of HSV and 18-33% greater risk of VZV, with risk increasing in parallel with AD severity. CMV risk was elevated among children with AD [hazard ratio (HR) 2·50, 95% confidence interval (95% CI) 1·38-4·54] and adults with severe AD (HR 4·45, 95% CI 1·76-11·25). Patients with AD had a 26-40% increase in risk of serious infections, with severe AD carrying the greatest risk. Although rare, opportunistic infections were associated with all severities of AD in adults (overall HR 1·31, 95% CI 1·20-1·42), but were not associated with AD in children. All estimates remained consistent after excluding patients receiving immunosuppressive treatments for AD.ConclusionsAD is significantly associated with herpesvirus infections, serious infections and opportunistic infections in a 'dose-dependent' manner with increasing severity. AD may increase susceptibility to infections exclusive of immunosuppressive medications.

Background and purposeMR imaging is essential for MS diagnosis and management, yet it has limitations in assessing axonal damage and remyelination. Gadolinium-based contrast agents add value by pinpointing acute inflammation and blood-brain barrier leakage, but with drawbacks in safety and cost. Neurite orientation dispersion and density imaging (NODDI) assesses microstructural features of neurites contributing to diffusion imaging signals. This approach may resolve the components of MS pathology, overcoming conventional MR imaging limitations.Materials and methodsTwenty-one subjects with MS underwent serial enhanced MRIs (12.6 ± 9 months apart) including NODDI, whose key metrics are the neurite density and orientation dispersion index. Twenty-one age- and sex-matched healthy controls underwent unenhanced MR imaging with the same protocol. Fifty-eight gadolinium-enhancing and non-gadolinium-enhancing lesions were semiautomatically segmented at baseline and follow-up. Normal-appearing WM masks were generated by subtracting lesions and dirty-appearing WM from the whole WM.ResultsThe orientation dispersion index was higher in gadolinium-enhancing compared with non-gadolinium-enhancing lesions; logistic regression indicated discrimination, with an area under the curve of 0.73. At follow-up, in the 58 previously enhancing lesions, we identified 2 subgroups based on the neurite density index change across time: Type 1 lesions showed increased neurite density values, whereas type 2 lesions showed decreased values. Type 1 lesions showed greater reduction in size with time compared with type 2 lesions.ConclusionsNODDI is a promising tool with the potential to detect acute MS inflammation. The observed heterogeneity among lesions may correspond to gradients in severity and clinical recovery after the acute phase.

Disability measures in multiple sclerosis (MS) rely heavily on ambulatory function, and current metrics fail to capture potentially important variability in walking behavior. We sought to determine whether remote step count monitoring using a consumer-friendly accelerometer (Fitbit Flex) can enhance MS disability assessment. 99 adults with relapsing or progressive MS able to walk ≥2-min were prospectively recruited. At 4 weeks, study retention was 97% and median Fitbit use was 97% of days. Substudy validation resulted in high interclass correlations between Fitbit, ActiGraph and manual step count tally during a 2-minute walk test, and between Fitbit and ActiGraph (ICC = 0.76) during 7-day home monitoring. Over 4 weeks of continuous monitoring, daily steps were lower in progressive versus relapsing MS (mean difference 2546 steps, p

Objective Identification of a particular cause of meningoencephalitis can be challenging owing to the myriad bacteria, viruses, fungi, and parasites that can produce overlapping clinical phenotypes, frequently delaying diagnosis and therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease diagnostics are known for their ability to identify unusual or novel viruses and thus are well suited for investigating possible etiologies of meningoencephalitis. Methods We present the case of a 74-year-old woman with endophthalmitis followed by meningoencephalitis. MDS of her cerebrospinal fluid (CSF) was performed to identify an infectious agent. Results Sequences aligning to Balamuthia mandrillaris ribosomal RNA genes were identified in the CSF by MDS. Polymerase chain reaction subsequently confirmed the presence of B. mandrillaris in CSF, brain tissue, and vitreous fluid from the patient's infected eye. B. mandrillaris serology and immunohistochemistry for free-living amoebas on the brain biopsy tissue were positive. Interpretation The diagnosis was made using MDS after the patient had been hospitalized for several weeks and subjected to costly and invasive testing. MDS is a powerful diagnostic tool with the potential for rapid and unbiased pathogen identification leading to early therapeutic targeting.

We present a precision medicine application developed for multiple sclerosis (MS): the MS BioScreen. This new tool addresses the challenges of dynamic management of a complex chronic disease; the interaction of clinicians and patients with such a tool illustrates the extent to which translational digital medicine - that is, the application of information technology to medicine - has the potential to radically transform medical practice. We introduce 3 key evolutionary phases in displaying data to health care providers, patients, and researchers: visualization (accessing data), contextualization (understanding the data), and actionable interpretation (real-time use of the data to assist decision making). Together, these form the stepping stones that are expected to accelerate standardization of data across platforms, promote evidence-based medicine, support shared decision making, and ultimately lead to improved outcomes.

Background and purposeAutoimmune encephalopathies (AEs) are a heterogeneous group of neurological disorders that affect cognition. Although memory difficulties are commonly endorsed, few reports of AEs inclusively assess all cognitive domains in detail. Our aim was to perform an unbiased cognitive evaluation of AE patients with voltage-gated potassium channel complex antibodies (VGKCC -Abs) in order to delineate cognitive strengths and weaknesses.MethodsSerial VGKCC -Ab AE subjects (n = 12) were assessed with a comprehensive evaluation of memory, executive functions, visuospatial skills and language. Clinical magnetic resonance imaging (MRI) (n = 10/12) was evaluated. Five subjects had serial cognitive testing available, permitting descriptive analysis of change.ResultsSubjects demonstrated mild to moderate impairment in memory (mean Z = -1.9) and executive functions (mean Z = -1.5), with variable impairments in language and sparing of visuospatial skills. MRI findings showed T2 hyperintensities in medial temporal lobe (10/10) and basal ganglia (2/10). Serial cognitive examination revealed heterogeneity in cognitive function; whereas most patients improved in one or more domains, residual impairments were observed in some patients.ConclusionsThis study augments previous neuropsychological analyses in VGKCC -Ab AE by identifying not only memory and executive function deficits but also language impairments, with preservation of visuospatial functioning. The study further highlights the importance of domain-specific testing to parse out the complex cognitive phenotypes of VGKCC -Ab AE.

Objective: In multiple sclerosis (MS), cerebral gray matter (GM) atrophy correlates more strongly than white matter (WM) atrophy with disability. The corresponding relationships in the spinal cord (SC) are unknown due to technical limitations in assessing SC GM atrophy. Using phase-sensitive inversion recovery (PSIR) magnetic resonance imaging, we determined the association of the SC GM and SC WM areas with MS disability and disease type. Methods: A total of 113 MS patients and 20 healthy controls were examined at 3T with a PSIR sequence acquired at the C2/C3 disk level. Two independent, clinically masked readers measured the cord WM and GM areas. Correlations between cord areas and Expanded Disability Status Score (EDSS) were determined. Differences in areas between groups were assessed with age and sex as covariates. Results: Relapsing MS (RMS) patients showed smaller SC GM areas than age- and sex-matched controls (p = 0.008) without significant differences in SC WM areas. Progressive MS patients showed smaller SC GM and SC WM areas compared to RMS patients (all p ≤ 0.004). SC GM, SC WM, and whole cord areas inversely correlated with EDSS (rho: -0.60, -0.32, -0.42, respectively; all p ≤ 0.001). The SC GM area was the strongest correlate of disability in multivariate models including brain GM and WM volumes, fluid-attenuated inversion recovery lesion load, T1 lesion load, SC WM area, number of SC T2 lesions, age, sex, and disease duration. Brain and spinal GM independently contributed to EDSS. Interpretation: SC GM atrophy is detectable in vivo in the absence of WM atrophy in RMS. It is more pronounced in progressive MS than RMS and contributes more to patient disability than SC WM or brain GM atrophy.

Background: Despite widespread dissatisfaction and low treatment persistence in moderate to severe psoriasis, patients' reasons behind treatment discontinuation remain poorly understood.Objectives: We sought to characterize patient-reported reasons for discontinuing commonly used treatments for moderate to severe psoriasis in real-world clinical practice.Methods: A total of 1095 patients with moderate to severe plaque psoriasis from 10 dermatology practices who received systemic treatments completed a structured interview. Eleven reasons for treatment discontinuation were assessed for all past treatments.Results: A total of 2231 past treatments were reported. Median treatment duration varied by treatment, ranging from 6.0 to 20.5 months (P < .001). The frequency of each cited discontinuation reasons differed by treatment (all P < .01). Patients who received etanercept (odds ratio [OR] 5.19; 95% confidence interval [CI] 3.23-8.33) and adalimumab (OR 2.10; 95% CI 1.20-3.67) were more likely to cite a loss of efficacy than those who received methotrexate. Patients who received etanercept (OR 0.34; 95% CI 0.23-0.49), adalimumab (OR 0.48; 95% CI 0.30-0.75), and ultraviolet B phototherapy (OR 0.21; 95% CI 0.14-0.31) were less likely to cite side effects than those who received methotrexate, whereas those who received acitretin (OR 1.56; 95% CI 1.08-2.25) were more likely to do so. Patients who underwent ultraviolet B phototherapy were more likely to cite an inability to afford treatment (OR 7.03; 95% CI 3.14-15.72).Limitations: The study is limited by its reliance on patient recall.Conclusions: Different patterns of treatment discontinuation reasons are important to consider when developing public policy and evidence-based treatment approaches to improve successful long-term psoriasis control. [ABSTRACT FROM AUTHOR]

Chinese translation BACKGROUND: Hidradenitis suppurativa (HS) is a chronic, painful skin disease characterized by abscesses, nodules, and draining fistulas in the axilla and groin of young adults. OBJECTIVE: To evaluate the efficacy and safety of adalimumab, an anti-tumor necrosis factor-[alpha] antibody, in patients with moderate to severe HS. DESIGN: Phase 2, parallel, randomized, placebo-controlled trial consisting of a blinded 16-week period (period 1) and an open-label 36-week period (period 2). All study personnel, investigators, and patients remained blinded to treatment group throughout the study. (ClinicalTrials.gov: NCT00918255) SETTING: 26 academic and private practice medical centers in the United States and Europe. PATIENTS: 154 adult patients with moderate to severe HS who were unresponsive or intolerant to oral antibiotics. INTERVENTION: Patients were assigned in a 1:1:1 ratio to adalimumab, 40 mg/wk; adalimumab, 40 mg every other week (EOW); or placebo. All patients received adalimumab, 40 mg EOW, at the beginning of period 2 but switched to weekly dosing if the response was suboptimal (HS Physician's Global Assessment [PGA] score of moderate or worse) at weeks 28 or 31. MEASUREMENTS: The primary outcome measure (clinical response) was the proportion of patients achieving an HS-PGA score of clear, minimal, or mild with at least a 2-grade improvement relative to baseline at week 16. RESULTS: At week 16, 3.9% of placebo patients (2 of 51), 9.6% of EOW patients (5 of 52), and 17.6% of weekly patients (9 of 51) achieved clinical response (EOW vs. placebo strata-adjusted difference, 5.6% [95% CI, -4.0% to 15.3%]; P = 0.25; weekly vs. placebo strata-adjusted difference, 13.7% [CI, 1.7% to 25.7%]; P = 0.025). Serious adverse event rates were 3.9%, 5.8%, and 7.8% for placebo, EOW, and weekly patients, respectively (EOW vs. placebo difference, 1.8% [CI, -6.4% to 10.1%]; weekly vs. placebo difference, 3.9% [CI, -5.2% to 13.0%]). Significantly greater improvements in patient-reported outcomes and pain were seen in the weekly dosing group than in the placebo group. A decrease in response was seen after the switch from weekly to EOW dosing in period 2. LIMITATIONS: Weeks 16 to 52 of the study were open-label. The study was not powered to assess the risk for known serious adverse effects of adalimumab, such as tuberculosis, other serious infections, and demyelinating disorders. CONCLUSION: Adalimumab dosed once per week alleviates moderate to severe HS. PRIMARY FUNDING SOURCE: Abbott Laboratories. [ABSTRACT FROM AUTHOR]

The Canadian Guidelines for the Management of Plaque Psoriasis were reviewed by the entire National Psoriasis Foundation Medical Board and updated to include newly approved agents such as ustekinumab and to reflect practice patterns in the United States, where the excimer laser is approved for psoriasis treatment. Management of psoriasis in special populations is discussed. In the updated guidelines, we include sections on children, pregnant patients or pregnant partners of patients, nursing mothers, the elderly, patients with hepatitis B or C virus infections, human immunodeficiency virus-infected patients, and patients with malignant neoplasms, as well as sections on tumor necrosis factor blockers, elective surgery, and vaccinations. [ABSTRACT FROM AUTHOR]

Background: There is a need to better understand the safety of tumor necrosis factor (TNF) inhibitors in patients with psoriatic disease in whom TNF inhibitors are frequently used as monotherapy.Objective: We sought to examine the risks of infection and malignancy with the use of TNF antagonists in adult patients with psoriatic disease.Methods: We conducted a systematic search for trials of TNF antagonists for adults with plaque psoriasis and psoriatic arthritis. We included randomized, placebo-controlled trials of etanercept, infliximab, adalimumab, golimumab, and certolizumab for the treatment of plaque psoriasis and psoriatic arthritis. Twenty of 820 identified studies with a total of 6810 patients were included. Results were calculated using fixed effects models and reported as pooled odds ratios.Results: Odds ratios for overall infection and serious infection over a mean of 17.8 weeks were 1.18 (95% confidence interval [CI] 1.05-1.33) and 0.70 (95% CI 0.40-1.21), respectively. When adjusting for patient-years, the incidence rate ratio for overall infection was 1.01 (95% CI 0.92-1.11). The odds ratio for malignancy was 1.48 (95% CI 0.71-3.09) and 1.26 (95% CI 0.39-4.15) when nonmelanoma skin cancer was excluded.Limitations: Short duration of follow-up and rarity of malignancies and serious infections are limitations.Conclusions: There is a small increased risk of overall infection with the short-term use of TNF antagonists for psoriasis that may be attributable to differences in follow-up time between treatment and placebo groups. There was no evidence of an increased risk of serious infection and a statistically significant increased risk in cancer was not observed with short-term use of TNF inhibitors. [ABSTRACT FROM AUTHOR]

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fifth of 6 sections of the guidelines of care for psoriasis, we discuss the use of ultraviolet (UV) light therapy for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety as well as offer recommendations for the use of phototherapy, including narrowband and broadband UVB and photochemotherapy using psoralen plus UVA, alone and in combination with topical and systemic agents. We will also discuss the available data for the use of the excimer laser in the targeted treatment of psoriasis. Finally, where available, we will summarize the available data that compare the safety and efficacy of the different forms of UV light therapy. [ABSTRACT FROM AUTHOR]

The skin and cardiovascular systems are connected in unique and meaningful ways, and many diseases conventionally considered as being limited to one organ system are more closely related than previously believed. Major cardiovascular diseases and phenomena such as infective endocarditis, congestive heart failure, Kawasaki disease and thromboembolism are associated with specific skin findings, and advances in genetics, immunology and clinical epidemiology show that inflammatory dermatological diseases, such as psoriasis, have serious cardiovascular and cardiometabolic consequences. Additionally, commonly used cardiovascular therapies, such as antihypertensive medications, are associated with important cutaneous adverse effects, including photosensitivity, photocarcinogenesis and eczematous skin reactions. Moreover, systemic dermatological therapies, including retinoids, Janus kinase inhibitors and biologics, can alter the risk of cardiovascular and cardiometabolic diseases. In this Review on cardiodermatology, we provide interdisciplinary insights from dermatology and cardiology that will be of practical use to both cardiologists and generalists who manage cardiovascular and cardiometabolic diseases in patients with dermatological findings or histories. We discuss specific skin findings associated with cardiovascular diseases to aid in diagnosis; important cutaneous adverse effects of common cardiovascular therapies, for the purpose of treatment monitoring; and the effect of dermatological diseases and dermatological treatment on cardiovascular risk., Competing Interests: Competing interests J.M.G. has served as a consultant for and has received honoraria from Abbvie, Artax (Data Safety and Monitoring Board (DSMB)), BMS, Boehringer Ingelheim, Celldex (DSMB), FIDE (which is sponsored by multiple pharmaceutical companies), GSK, Inmagene (DSMB), Lilly, Leo, Moonlake (DSMB), Janssen Biologics, Neuroderm (DSMB), Novartis, UCB (DSMB) and Veolia North America; receives research grants (to the trustees of the University of Pennsylvania) from Amgen, BMS and Pfizer; received payment for continuing medical education work related to psoriasis that was supported indirectly by pharmaceutical sponsors; is a co-patent holder of resiquimod for the treatment of cutaneous T cell lymphoma; is a Deputy Editor for the Journal of Investigative Dermatology, receiving honoraria from the Society for Investigative Dermatology; is Chief Medical Editor for Healio Dermatology (receiving honoraria); and is a member of the Board of Directors for the International Psoriasis Council and the Medical Dermatology Society (receiving no honoraria). M.S.G. has received consultant fees from Agepha, BMS, Horizon Therapeutics and Kiniksa, has received research grant support from Pfizer, and is supported by an NIH NHLBI grant (K23HL152013). The other authors declare no competing interests., (© 2024. Springer Nature Limited.)

Abstract: Chronic graft-versus-host disease (cGVHD) is the leading cause of morbidity and nonrelapse mortality after allogeneic hematopoietic cell transplantation. Skin biopsy of cGVHD is recommended when clinical features are not diagnostic, yet the histopathologic features of skin cGVHD are not well described. The objective of this study is to describe the histopathologic features of skin cGVHD in epidermal, sclerotic, and combination cGVHD. Of 49 patients with skin cGVHD, 30 of 49 (61.2%) were male, and mean age was 55 years (SD 11.1). Clinically, 33 of 49 (67.3%) had epidermal cGVHD (E-cGVHD), 1 of 49 (2.1%) had sclerotic cGVHD (S-cGVHD), and 15 of 49 (30.6%) had combination disease. The 49 patients corresponded to 83 unique pathologic specimens with 67 of 83 (80.7%) taken from E-cGVHD, and 16 of 83 (19.3%) from S-cGVHD lesions. Nearly all biopsy specimens from E-cGVHD showed minimal features of active GVHD, including apoptosis in the epidermal basal layer (n = 63, 94.0%), vacuolar change (n = 62, 92.5%), and lymphocyte satellitosis (n = 57, 85.1%). The predominant histologic pattern of E-cGVHD was lichen planus/interface dermatitis (n = 31, 47.0%). S-cGVHD specimens also showed minimal features of active GVHD with apoptosis of the epidermal basal layer (n = 11, 68.8%) and vacuolar change (n = 8, 50.0%). In addition, S-cGVHD showed sclerosis of the papillary and reticular dermis and subcutaneous septae (n = 8, 50.0%; n = 11, 68.8%; n = 5, 31.2%, respectively). The predominant histologic pattern of S-cGVHD was lichen sclerosus/morphea-like pattern (n = 10, 62.5%). Although minimal pathologic features of active GVHD are common, the majority of cGVHD biopsies share features with the inflammatory skin diseases that they clinically resemble. Complete histologic reporting is recommended with implications for disease endotyping and personalized therapy., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Health-related stigma and its internalization among individuals with chronic health conditions contribute to impaired mental and physical health and quality of life. Research on health-related stigma has been siloed, with disease-specific measures that may not capture the experiences of individuals with multiple health conditions and that prevent comparisons across health conditions. The current study aimed to develop and test a transdiagnostic measure of internalized health-related stigma for use among adults with different physical health conditions., Methods: An existing measure of internalized mental health stigma was adapted to assess stigma due to chronic physical health conditions following COSMIN procedures, with input from advisory boards of community members living with a range of stigmatized health conditions (obesity, type 1 and type 2 diabetes, skin diseases, HIV, chronic pain, and cancers) and of health professionals who specialized in these conditions. The new Internalized Health-Related Stigma (I-HEARTS) Scale was tested in an online sample of 300 adults with these health conditions, recruited from ResearchMatch. Additional psychosocial measures of mental health and quality of life were administered, and participants provided information about their health conditions and demographic characteristics. Exploratory factor analysis and tests of reliability and validity were conducted to determine the psychometric properties of the I-HEARTS Scale, and k-means clustering and receiver of characteristic curve analysis were used to determine a clinically meaningful cutoff score indicating high levels of internalized stigma., Results: Factor analysis results yielded a 25-item scale with a 3-factor solution, with subscales of Perceived and Anticipated Stigma, Stereotype Application and Self-Devaluation, and Stigma Resistance. Psychometric properties for internal consistency, inter-item and item-total correlations, and test-retest reliability were strong. Certain demographics (e.g., younger age) and characteristics related to health conditions (e.g., greater symptom severity) were associated with higher levels of internalized stigma. I-HEARTS Scale scores correlated moderately to strongly with related but distinct psychosocial measures, and a cutoff score of 3.40 or higher on the 1-7 rating scale was determined to indicate clinically meaningful levels of internalized stigma., Conclusions: The I-HEARTS Scale is a reliable and valid measure for the assessment of internalized health-related stigma among adults with varied stigmatized chronic health conditions. STUDY PRE-REGISTRATION: https://osf.io/84c5d/?view&#95;only=87238512f6d6475c87f8f64280a8a15f ., (© 2024. The Author(s).)

Ataxia with anti-regulator of G-protein signaling 8 autoantibodies (RGS8-Abs) is an autoimmune disease recently described in four patients. The present study aimed to identify other patients with RGS8-Abs, describe their clinical features, including the link between RGS8-related autoimmune cerebellar ataxia (ACA) and cancer. Patients with RGS8-Abs were identified retrospectively in the biological collections of the French Reference Center for Paraneoplastic Neurological Syndrome and the University of California San Francisco Center for Encephalitis and Meningitis. Clinical data were collected, and cerebrospinal fluid, serum, and tumor pathological samples were retrieved to characterize the autoantibodies and the associated malignancies. Only three patients with RGS8-Abs were identified. All of them presented with a pure cerebellar ataxia of mild to severe course, unresponsive to current immunotherapy regimens for ACA. Two patients presented with a Hodgkin lymphoma of the rare specific subtype called nodular lymphocyte-predominant Hodgkin lymphoma, with very mild extension. Autoantibodies detected in all patients enriched the same epitope on the RGS8 protein, which is an intracellular protein physiologically expressed in Purkinje cells but also ectopically expressed specifically in lymphoma cells of patients with RGS8-related ACA. The present results and those of the four cases previously described suggest that RGS8-Abs define a new paraneoplastic neurological syndrome of extreme rarity found mostly in middle-aged males that associates pure cerebellar ataxia and a particular lymphoma specifically expressing the RGS8 antigen. As in other paraneoplastic ACA with intracellular antigen, the disease course is severe, and patients tend to exhibit a poor response to immune therapy., (© 2024. The Author(s).)

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.

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 18 F-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., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Autoimmune encephalitis (AIE) encompasses a spectrum of rare autoimmune-mediated neurological disorders, which are characterized by brain inflammation and dysfunction. Autoantibodies targeting the N -methyl-d-aspartic acid receptor (NMDAR) and leucine-rich glioma-inactivated 1 (LGI1) are the most common subtypes of antibody-positive AIE. Currently, there are no approved therapies for AIE. Interleukin-6 (IL-6) signaling plays a role in the pathophysiology of AIE. Satralizumab, a humanized, monoclonal recycling antibody that specifically targets the IL-6 receptor and inhibits IL-6 signaling, has demonstrated efficacy and safety in another autoantibody-mediated neuroinflammatory disease, aquaporin-4 immunoglobulin G antibody-positive neuromyelitis optica spectrum disorder, and has the potential to be an evidence-based disease modifying treatment in AIE., Objectives: CIELO will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics of satralizumab compared with placebo in patients with NMDAR-immunoglobulin G antibody-positive (IgG+) or LGI1-IgG+ AIE., Study Design: CIELO (NCT05503264) is a prospective, Phase 3, randomized, double-blind, multicenter, basket study that will enroll approximately 152 participants with NMDAR-IgG+ or LGI1-IgG+ AIE. Prior to enrollment, participants will have received acute first-line therapy. Part 1 of the study will consist of a 52-week primary treatment period, where participants will receive subcutaneous placebo or satralizumab at Weeks 0, 2, 4, and every 4 weeks thereafter. Participants may continue to receive background immunosuppressive therapy, symptomatic treatment, and rescue therapy throughout the study. Following Part 1, participants can enter an optional extension period (Part 2) to continue the randomized, double-blind study drug, start open-label satralizumab, or stop study treatment and continue with follow-up assessments., Endpoints: The primary efficacy endpoint is the proportion of participants with a ≥1-point improvement in the modified Rankin Scale (mRS) score from study baseline and no use of rescue therapy at Week 24. Secondary efficacy assessments include mRS, Clinical Assessment Scale of Autoimmune Encephalitis (CASE), time to rescue therapy, sustained seizure cessation and no rescue therapy, Montreal Cognitive Assessment, and Rey Auditory Verbal Learning Test (RAVLT) measures. Safety, pharmacokinetics, pharmacodynamics, exploratory efficacy, and biomarker endpoints will be captured., Conclusion: The innovative basket study design of CIELO offers the opportunity to yield prospective, robust evidence, which may contribute to the development of evidence-based treatment recommendations for satralizumab in AIE., Competing Interests: S-TL reports advisory roles for Roche/Genentech, Biofire Diagnostics, GC Pharma, Celltrion, and Advanced Neural Technologies. HA is a consultant and speaker for Biogen, Genentech, BMS, Horizon, and Alexion. HA has served as a consultant and/or advisory board member for Cycle Pharma, Alpine Pharma, and Axonics. HA received honoraria from Neurology Live. HA receives research support from Genentech, BMS, Novartis, Sanofi, UCB, and the Guthy-Jackson Charitable Foundation. HA receives royalties from UpToDate. HA serves as an Assistant Editor for Neurology Journal. SI has received honoraria/research support from UCB, Immunovant, Roche, Janssen, Cerebral Therapeutics, ADC Therapeutics, Brain, CSL Behring, and ONO Pharma. SI receives licensed royalties on patent application WO/2010/046716 entitled ‘Neurological Autoimmune Disorders,’ and has filed two other patents entitled “Diagnostic method and therapy” (WO2019211633 and US-2021-0071249-A1; PCT application WO202189788A1) and “Biomarkers” (PCT/GB2022/050614 and WO202189788A1). HN reports being a consultant/advisor for F. Hoffmann-La Roche Ltd. and has received speaker honoraria from Alexion, Biogen, Daiichi Sankyo, Eisai, Mitsubishi Tanabe, Kirin, and Takeda. AP reports research grants from the University of Colorado, Rocky Mountain MS Center, and the Foundation for Sarcoidosis; consulting fees from Genentech/Roche, UCB, EMD Serono, and Alexion; and honoraria from MedLink and publication royalties from Springer as co-editor of a medical textbook. AP serves as an unpaid member of the Medical Advisory Board for the Autoimmune Encephalitis Alliance. SP reports grants, personal fees, and nonfinancial support from Alexion Pharmaceuticals; grants, personal fees, and nonfinancial support from MedImmune, Viela Bio, and Horizon; grants from Adimune; grants, personal fees, and nonfinancial support from Genentech and Roche, and personal fees for consulting from UCB, Astellas, and Arialys. SP has two patents issued (8889102; application 12-678350; Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia; and 9891219B2; application 12-573942; Methods for Treating Neuromyelitis Optica [NMO] by Administration of Eculizumab to an Individual That is Aquaporin-4 [AQP4]-IgG Autoantibody-Positive), for which he has received royalties. SP also has patents pending for IgGs to the following proteins as biomarkers of autoimmune neurological disorders: septin-5, kelch-like protein 11, GFAP, PDE10A, and MAP1B. SP is an employee of Mayo Clinic, which offers commercial NMDAR and LGI1-IgG testing. SP receives no royalties from the sale of tests done at the neuroimmunology laboratory at Mayo Clinic. EY has received research funding from NMSS, CMSC, CIHR, NIH, OIRM, SCN, CBMH Chase an Idea, SickKids Foundation, Rare Diseases Foundation, MS Scientific Foundation, McLaughlin Centre, Leong Center, and Peterson Foundation, and investigator-initiated research funding from Biogen. EY has served on a scientific advisory board for F. Hoffmann-La Roche and a data safety monitoring board for TG Therapeutics and has received speaker honoraria from Biogen, JHU, Saudi Epilepsy Society, NYU, MS-ATL, ACRS, PRIME, and CNPS. JW serves as a trial steering committee member for the CIELO study. JO and MG are employees and shareholders of F. Hoffmann-La Roche Ltd. JS, JSL, and ME-K are employees of Roche Products Ltd. and shareholders of F. Hoffmann-La Roche Ltd. SR is an employee and shareholder of Genentech, Inc. JG receives research support to his institution from F. Hoffmann-La Roche Ltd. for clinical trials and serves as chair of the Trial Steering Committee for the CIELO study. JG has also received research support to his institution for clinical trials from Vigil Neurosciences; and received personal fees for consulting for Arialys and Ventyx Bio. The authors declare that this study received funding from F. Hoffmann-La Roche. The sponsor had the following involvement in the study: study design, collection, analysis and the decision to submit it for publication. Medical writing assistance was provided by Reece Bracewell, MBiolSci and Nicole Ellman, PhD, of Apothecom, London, UK, and was funded by F. Hoffmann-La Roche Ltd. All authors contributed to the conceptualisation, drafting, revising, and critical reviewing of the manuscript for intellectual content, and approved the final version of this manuscript to be published., (Copyright © 2024 Lee, Abboud, Irani, Nakajima, Piquet, Pittock, Yeh, Wang, Rajan, Overell, Smith, St Lambert, El-Khairi, Gafarova and Gelfand.)

National guidelines define psoriasis as a risk enhancer for cardiovascular disease and recommend increased monitoring and more intense management of cardiovascular risk factors in these patients, who face an increased burden of cardiovascular disease morbidity and mortality. Screening for modifiable cardiovascular risk factors, including blood pressure, weight, cholesterol, glucose, and smoking, can be efficiently incorporated into routine dermatology clinical practice. Partnerships with primary care providers and preventive cardiologists are essential to improving management of cardiovascular risk in patients with psoriasis., Competing Interests: Disclosure J.M. Gelfand served as a consultant for Abbvie, Artax (DSMB), BMS, Boehringer Ingelheim, Celldex (DSMB), FIDE (which is sponsored by multiple pharmaceutical companies) GSK, Inmagene (DSMB), Twill, Lilly (DMC), Leo, Moonlake (DSMB), Janssen Biologics, Novartis Corp, UCB (DSMB), Neuroderm (DSMB), and Veolia North America receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from Amgen, United States, BMS, United States, and Pfizer Inc., United States; received payment for continuing medical education work related to psoriasis that was supported indirectly by pharmaceutical sponsors; is a co-patent holder of resiquimod for the treatment of cutaneous T-cell lymphoma; is a Deputy Editor for the Journal of Investigative Dermatology receiving honoraria from the Society for Investigative Dermatology; is the Chief Medical Editor for Healio Dermatology (receiving honoraria); and is a member of the Board of Directors for the International Psoriasis Council and the Medical Dermatology Society, receiving no honoraria. D.E. Soffer has served as consultant for Akcea, Amgen, Amryt, Ionis, Novartis, and Partnership for Health Analytics Research; was an investigator for Akcea, Amgen, Amryt, Ionis, Novartis, Regeneron, and Verve Therapeutics; and did data monitoring for Amgen., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Vitamin B12 is critical for hematopoiesis and myelination. Deficiency can cause neurologic deficits including loss of coordination and cognitive decline. However, diagnosis relies on measurement of vitamin B12 in the blood, which may not accurately reflect the concentration in the brain. Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Anti-CD320 impaired cellular uptake of cobalamin (B12) in vitro by depleting its target from the cell surface. Despite a normal serum concentration, B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic B12 supplementation were associated with increased B12 in the CSF and clinical improvement. Optofluidic screening enabled isolation of a patient-derived monoclonal antibody that impaired B12 transport across an in vitro model of the blood-brain barrier (BBB). Autoantibodies targeting the same epitope of CD320 were identified in seven other patients with neurologic deficits of unknown etiology, 6% of healthy controls, and 21.4% of a cohort of patients with neuropsychiatric lupus. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. However, these individuals did not display any hematologic signs of B12 deficiency despite systemic CD320 impairment. Using a genome-wide CRISPR screen, we found that the low-density lipoprotein receptor serves as an alternative B12 uptake pathway in hematopoietic cells. These findings dissect the tissue specificity of B12 transport and elucidate an autoimmune neurologic condition that may be amenable to immunomodulatory treatment and nutritional supplementation.

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., Competing Interests: Conflicts of interest Dr Chat, Dr Ellebrecht, Ms. Kingston, and Dr Cordoro have no conflicts of interest to declare. Dr Bell is an employee of the National Psoriasis Foundation. Author Gondo is an employee of the National Psoriasis Foundation. Dr Desai has served as a research investigator, consultant, speaker, and/or advisor for AbbVie, Galderma, Foundation for Research & Education of Dermatology, Almirall, Dermavant, Ferndale Laboratories, Inc, Incyte Corporation, Gore Range Capital, AOBiome, LLC, Bristol Myers Squibb, Verrica Pharmaceuticals, UCB, Ortho Dermatologics, Scientis, EPI Health, Avita, Pfizer, Lilly, LEO, Incyte Corporation, L'Oreal USA, Inc, Beiersdorf, Inc, and Johnson and Johnson; is a board member of the National Psoriasis Foundation and Women's Derm Society; and is a stockholder for Gore Range Capital. Dr Duffin has been a consultant, advisor, or served as an investigator for AbbVie, AnaptysBio, Amgen, Bristol-Myers Squib, Celgene, CorEvitas/Corrona, Boehringer-Ingelheim, Janssen, Lilly, Novartis, Ortho Dermatologica, Pfizer, Regeneron, Sienna, Stiefel, and UCB. Dr Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen Inc, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, SunPharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Valeant, Menlo, Merck & Co, Qurient Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Advance Medical, Suncare Research, Informa, UpToDate and the National Psoriasis Foundation; is the founder and majority owner of www.DrScore.com; is a founder and part owner of Causa Research; and has stock in Sensal Health. Dr Garg is an advisor for AbbVie, Aclaris Therapeutics, Anaptys Bio, Aristea Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Incyte, InflaRx, Insmed, Janssen, Novartis, Pfizer, UCB, and Viela Biosciences; receives honoraria; and receives research grants from AbbVie, UCB and National Psoriasis Foundation. Dr Gelfand served as a consultant for Abbvie, BMS, Boehringer Ingelheim, Celldex (DSMB), FIDE (which is sponsored by multiple pharmaceutical companies) GSK, Happify, Lilly (DMC), Leo, Janssen Biologics, Neumentum, Novartis Corp, Pfizer, UCB (DSMB), Neuroderm (DSMB), Regeneron, Trevi, and Mindera Dx., receiving honoraria; receives research grants (to the Trustees of the University of Pennsylvania) from Boehringer Ingelheim, and Pfizer Inc; and received payment for continuing medical education work related to psoriasis that was supported indirectly pharmaceutical sponsors. Dr Gelfand is a co-patent holder of resiquimod for treatment of cutaneous T cell lymphoma. Dr Gelfand is a Deputy Editor for the Journal of Investigative Dermatology receiving honoraria from the Society for Investigative Dermatology, is Chief Medical Editor for Healio Psoriatic Disease (receiving honoraria) and is a member of the Board of Directors for the International Psoriasis Council, receiving no honoraria. Dr Gladman has served as a consultant for AbbVie, Amgen, BMS, Eli Lily, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB; and has received grants from AbbVie, Amgen, Eli Lily, Janssen, Novartis, Pfizer, and UCB. Dr Green is a research investigator, speaker, and/or consultant for AbbVie, Amgen, Arcutis, BMS, Dermavant, Lilly, MC2, SunPharma, and UCB. Dr Gudjonsson has served as an advisor for Novartis, Janssen, Almirall, Eli Lilly, Sanofi, and Boehringer Ingelheim; and has received research support from Almirall, Eli Lilly, Prometheus, BMS, and Janssen. Dr Han has served as a research investigator, consultant, and/or speaker for AbbVie, Amgen, Boehringer Ingelheim, BMS, Dermavant, Janssen, Lilly, UCB, Novartis, Leo Pharma, Regeneron, Sanofi Genzyme, Ortho Dermatologics, Bond Avillion, Pellepharm, MC2, Athenex, Celgene, Sun Pharma, and Pfizer. Dr Hawkes is an advisor and/or consultant for AbbVie, Arcutis, Boehringer Ingelheim, Janssen, LearnSkin, LEO, Lilly, Novartis, Pfizer, Regeneron-Sanofi Genzyme, and UCB; is a board member of the National Psoriasis Foundation; and has stock ownership/equity of Regeneron Pharmaceuticals. Dr Kircik is a research investigator, speaker, advisor, and/or consultant for Abbott Laboratories, Allergan, Almirall, Amgen, Arcutis, Biogen-Idec, BMS, Boehringer-Ingleheim, Breckinridge Pharma, Celgene, Centocor, Inc, Cellceutix, Cipher, Combinatrix, Connetics Corporation, Coria, Dermavant, Dermira, Dow Pharmaceutical Sciences, Inc, Dr Reddy's Lab, Eli Lilly, Galderma, Genentech, Inc, GlaxoSmithKline, PLC, Idera, Leo, Maruho, Merck, Medicis Pharmaceutical Corp., Novartis AG, Promius, PharmaDerm, Pfizer, Serono, Stiefel Laboratories, Inc, Sun Pharma, Taro, UCB, Valeant Pharmaceuticals Intl, and XenoPort. Dr Koo is a speaker and/or advisor for AbbVie, Amgen, Lilly, UCB, Ortho Dermatologics, LEO, Sun Pharma, Janssen, and Epi Pharm. Dr Langley has been an investigator, served on the scientific advisory board, and/or has provided a lecture for AbbVie, Amgen, Boehringer Ingelheim, Celgene, Leo, Lilly, Merck, Novartis, Pfizer, and UCB. Dr Lebwohl is an employee of Mount Sinai; receives research funds from AbbVie, Amgen, Arcutis, Avotres, Boehringer Ingelheim, Cara Therapeutics, Dermavant Sciences, Eli Lilly, Incyte, Janssen Research & Development, LLC, Ortho Dermatologics, Regeneron, and UCB, Inc; and is a consultant for Aditum Bio, Almirall, AltruBio Inc, AnaptysBio, Arcutis, Inc, Arena Pharmaceuticals, Aristea Therapeutics, Arrive Technologies, Avotres Therapeutics, BiomX, Brickell Biotech, Boehringer-Ingelheim, Bristol Myers Squibb, Cara Therapeutics, Castle Biosciences, Corevitas, Dermavant Sciences, Dr Reddy's Laboratories, Evelo Biosciences, Evommune, Inc, Facilitatation of International Dermatology Education, Forte Biosciences, Foundation for Research and Education in Dermatology, Helsinn Therapeutics, Hexima Ltd., LEO Pharma, Meiji Seika Pharma, Mindera, Pfizer, Seanergy, and Verrica. Dr Lewitt has received speaking and/or consulting support from AbbVie, Lilly, Janssen, Ortho Dermatologics, UCB, Galderma, Pfizer; received honoraria; and served as an advisor for AbbVie, Janssen, and Dermavant. Dr Liao has received research/grant support from AbbVie, Amgen, Janssen, Leo, Novartis, Trex Bio, Pfizer, and Regeneron. Dr Martin has served as an advisor for Bristol Meyers Squibb, DUSA/SUN, AbbVie, Ortho/Bausch Health, Galderma, Pfizer, LEO, Janssen, Horizon, UCB, Trevi, Almirall, Dermavent, Incyte, and Lilly; has served as a consultant for Bristol Meyers Squibb, DUSA/SUN, AbbVie, Ortho/Bausch Health, Galderma, Pfizer, LEO, UCB, Trevi, Almirall, Lilly, Arcutis, and Dermavant; and has received speaking support from UCB, Almirall, LEO, Incyte, Dermavant, and Bristol Meyers Squibb. Dr Orbai is a consultant and/or advisor for Janssen, Novartis, and UCB; and receives research support from AbbVie, Amgen, and Celgene. Dr Reddy has served as a consultant for Novartis, AbbVie, Janssen, and UCB; and has received grant support from Pfizer. Ms Richardson has served as an advisor for and received honoraria from Boehringer Engelheim and Lilly. Dr Ritchlin is a consultant and/or speaker for Novartis, Lilly, AbbVie, Janssen, UCB, and Pfizer. Dr Schwartzman has received speaking support from AbbVie, Janssen, Lilly, Pfizer, Novartis, and UCB; served as a consultant for Abbvie, Janssen, Lilly, Myriad, Novartis, Regeneron, Sanofi, UCB, Stelexis, Jubilant, and Teijin; is a board member of the National Psoriasis Foundation; and served as an advisor for Myriad. Dr Siegel has served as an advisor, speaker, and/or consultant for Abbvie, UCB, Lilly, Horizon, and BMS. Dr Van Voorhees has served as a research investigator and/or scientific advisor for Lilly, AbbVie, UCB, Bristol Meyers Squibb, Amgen, Boehringer Ingelheim, Novartis, and Merck. Dr Wallace serves as an investigator for Pfizer and Target RWE. Dr Weinberg is a research investigator, consultant, and/or speaker for Novartis, Lilly, Amgen, AbbVie, Sun, Janssen, and BMS. Dr Winthrop is a consultant for Pfizer, AbbVie, Union Chimique Belge (UCB), Eli Lilly & Company, Galapagos, GlaxoSmithKline (GSK), Roche, Gilead, Bristol Myers Squibb (BMS), Regeneron, Sanofi, AstraZeneca, and Novartis; and receives research funding from BMS and Pfizer. Dr Yamauchi serves as a research investigator, consultant, and speaker for Abbvie, Amgen, BMS, Janssen, Lilly, Novartis, Pfizer, Sun Pharma, UCB. Dr Armstrong has served as a research investigator, scientific advisor, and/or speaker to AbbVie, Almirall, Arcutis, ASLAN, Beiersdorf, BI, BMS, EPI, Incyte, Leo, UCB, Janssen, Lilly, Mindera, Nimbus, Novartis, Ortho Dermatologics, Sun, Dermavant, Dermira, Sanofi, Regeneron, and Pfizer., (Copyright © 2024. Published by Elsevier Inc.)

Although B cells are implicated in multiple sclerosis (MS) pathophysiology, a predictive or diagnostic autoantibody remains elusive. In this study, the Department of Defense Serum Repository (DoDSR), a cohort of over 10 million individuals, was used to generate whole-proteome autoantibody profiles of hundreds of patients with MS (PwMS) years before and subsequently after MS onset. This analysis defines a unique cluster in approximately 10% of PwMS who share an autoantibody signature against a common motif that has similarity with many human pathogens. These patients exhibit antibody reactivity years before developing MS symptoms and have higher levels of serum neurofilament light (sNfL) compared to other PwMS. Furthermore, this profile is preserved over time, providing molecular evidence for an immunologically active preclinical period years before clinical onset. This autoantibody reactivity was validated in samples from a separate incident MS cohort in both cerebrospinal fluid and serum, where it is highly specific for patients eventually diagnosed with MS. This signature is a starting point for further immunological characterization of this MS patient subset and may be clinically useful as an antigen-specific biomarker for high-risk patients with clinically or radiologically isolated neuroinflammatory syndromes., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Competing Interests: Dr Gelfand served as a consultant for AbbVie, Artax (DSMB), BMS, Boehringer Ingelheim, Celldex (DSMB), FIDE (which is sponsored by multiple pharmaceutical companies) GSK, Inmagene (DSMB), Twill, Lilly (DMC), Leo, Moonlake (DSMB), Janssen Biologics, Novartis Corp, UCB (DSMB), Neuroderm (DSMB), and Veolia North America receiving honoraria; and receives research grants (to the Trustees of the University of Pennsylvania) from Amgen and Pfizer Inc. Dr Lo Sicco is a current investigator for Pfizer Inc; former investigator for Regen; and consultant for Pfizer Inc and Acquis. Dr Garshick is a consultant for AbbVie and Horizon Therapeutics. Authors Kearney, Saha, Mata Vivas, and Garelik have no conflicts of interest to declare.