ObjectiveImmunocompromised individuals with rheumatic conditions have heightened risk of tuberculosis (TB) infection, reactivation, and severe disease. Patients with social risks are especially vulnerable. After an alert of increased TB rates among individuals experiencing homelessness in Massachusetts, we leveraged the existing social risk screening infrastructure to identify those at highest risk.MethodsWe identified patients with rheumatic conditions receiving immunosuppressive or immunomodulatory medications and recent housing instability from the electronic health records (EHRs) of a multihospital medical system. We notified these patients’ rheumatologists and provided latent TB and TB symptom screening information. We tracked EHR documentation, orders, and laboratory results following this alert.ResultsThirty‐three patients with rheumatic conditions experienced housing instability. Of these, 23 (70%) patients cared for by 17 rheumatologists were prescribed ≥1 immunosuppressive or immunomodulatory medications. Following the alert, three (13%) patients had EHR documentation of symptom screening, one provider responded that their patient was not homeless, and one ordered an interferon‐gamma release assay (“T‐SPOT”). After the reminder, seven (30%) T‐SPOT tests were ordered, five (22%) patients had EHR documentation of symptom review at their subsequent rheumatology appointment, and four (18%) patients were messaged by their rheumatologists about their TB risk.ConclusionThe existing rheumatology‐based social risk factor screening infrastructure facilitated a rapid response to a relevant public health concern. Rheumatologists’ responses varied, possibly due to increased clinical stressors with limited support. Despite challenges to reaching patients with housing instability, many actions were taken. Efforts to prompt regular TB screening of patients with these vulnerabilities are underway.

Proadrenomedullin (pro-ADM) is a peptide implicated in immunomodulation, with higher levels observed in inflammatory conditions, cardiovascular impairment, and sepsis. Although extensively studied in acute disorders, its potential as a biomarker in inflammatory arthritis remains underexplored. This study aims to examine serum pro-ADM levels across different types of inflammatory arthritis and to investigate correlations with disease characteristics. We included 163 patients with inflammatory arthritis who were prospectively enrolled in our institutional Biobank. Among them, 99 patients had rheumatoid arthritis (RA), 36 patients had psoriatic arthritis (PsA), 22 patients had axial spondyloarthritis (axSpA), and 6 patients had undifferentiated spondyloarthritis (uSpA). Serum pro-ADM levels were measured using enzyme-linked immunosorbent assay, with cross-sectional assessment at baseline in all patients and longitudinal follow-up in a subset of 31 patients with RA. At baseline, patients with RA exhibited significantly higher serum pro-ADM levels (median 51.7 pg/mL) in comparison to PsA, axSpA, and uSpA (median values between 33.9 and 35.6 pg/mL; all P < 0.001). Pro-ADM showed good discriminative ability in distinguishing RA from SpA but had no correlation with markers of inflammation, disease duration, or disease activity indices. In patients with RA with follow-up data, pro-ADM levels exhibited a significant decrease from 52.5 to 30.1 pg/mL after six months (P=0.023). However, changes in pro-ADM did not correlate with changes in the Disease Activity Score in 28 joints using the C-reactive protein level. Serum pro-ADM levels are markedly elevated in RA relative to SpA, although they do not correlate with inflammatory burden or disease activity. In RA, pro-ADM levels decrease following treatment initiation or modification; nonetheless, they lack predictive value for treatment response. These findings suggest that pro-ADM reflects disease-specific pathophysiologic differences rather than representing a dynamic biomarker.

To evaluate changes in muscle edema using short-tau inversion recovery (STIR) imaging and quantitative diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) mapping in patients with refractory dermatomyositis (DM) treated with tofacitinib. This post hoc imaging analysis included patients from a 12-week, open-label trial of tofacitinib 11 mg daily in refractory DM. Bilateral thigh magnetic resonance imaging was obtained at baseline and week 12 using standardized STIR, T1-weighted, and DWI sequences. Muscle edema (ME) and fascial edema were assessed qualitatively on STIR imaging. ADC values were measured in muscles demonstrating baseline STIR hyperintensity using three nonoverlapping regions of interest per muscle. Clinical outcomes included Manual Muscle Testing of eight muscle groups (MMT-8). Ten patients completed the study. Baseline ME was present in 32 of 320 thigh muscles (10%) across four patients. Quantitative ADC analysis, performed in the 32 edematous muscles, demonstrated significant decreases in tissue diffusivity in 11 muscles (34.5%), including the rectus femoris, vastus lateralis, vastus medialis, sartorius, gracilis, and adductors. Absolute ADC reductions ranged from -0.18 to -0.37 × 10-3 mm2/s. Two patients with baseline proximal weakness showed parallel improvement in MMT-8 scores and ADC values, whereas two patients with normal strength showed subclinical ADC improvement. Tofacitinib resulted in marked clinical and radiologic improvement in refractory DM. Quantitative ADC mapping detected resolution of muscle inflammation, including subclinical improvement not evident on strength or enzyme testing. ADC metrics may serve as objective imaging biomarkers of treatment response in DM.

To assess two-year impact of bimekizumab on patient-reported outcomes (PROs), and their association with objective measures of inflammation, in patients with psoriatic arthritis (PsA) who were biologic disease-modifying antirheumatic drug (bDMARD)-naïve or had tumor necrosis factor inhibitor inadequate response or intolerance (TNFi-IR). BE OPTIMAL (NCT03895203; bDMARD-naïve) and BE COMPLETE (NCT03896581; TNFi-IR) were phase 3 studies that assessed subcutaneous bimekizumab 160 mg every four weeks. Both were double-blind, placebo-controlled to week16, then placebo patients switched to bimekizumab. BE OPTIMAL week52 or BE COMPLETE week16 completers could enter BE VITAL (NCT04009499; open-label extension), where all patients received bimekizumab. PROs, disease impact (Psoriatic Arthritis Impact of Disease-12 questionnaire [PsAID-12]), and their association with inflammation (assessed using swollen joint count [SJC]) are reported to year 2. Among 712 bDMARD-naïve and 400 TNFi-IR patients, bimekizumab resulted in long-term sustained improvements in PROs for pain, fatigue, and function (Health Assessment Questionnaire-Disability Index) to year 2. Mean change from baseline (year 2) in bimekizumab-randomized patients for pain and disease impact (PsAID-12) was -33.9 to -29.2 and -2.5 to -2.2, respectively. An achievement of SJC=0 was associated with the greatest reduction in pain. Decreased SJC was associated with improved pain, fatigue, function, and reduced disease impact to year 2. By year 2, 44.4% to 54.3% of patients originally randomized to placebo or bimekizumab reported no or low disease impact (PsAID-12 ≤1.95), and 88.0% to 92.0% of bimekizumab-randomized patients achieved a patient acceptable symptom state for disease impact (PsAID-12 ≤4), associated with concurrent improvement in SJC and skin involvement. Bimekizumab treatment resulted in sustained clinically meaningful improvements in PROs and reduced disease impact to two years in bDMARD-naïve and TNFi-IR patients with PsA. Stringent inflammation control was associated with symptom relief and reduced disease impact.

ObjectiveGain‐of‐function variants in IDH1 and IDH2 are enriched among individuals with coexisting myeloid neoplasms and autoimmune diseases. However, the association between IDH1/IDH2 variants and rheumatic diseases independent of hematologic neoplasms remains unclear. We investigated the association between rare gain‐of‐function and loss‐of‐function genetic variants in IDH1 and IDH2 and immune‐mediated rheumatic diseases.MethodsIndividuals with gain‐of‐function and loss‐of‐function variants in IDH1/IDH2 were identified by whole genome sequencing in the UK Biobank and the All of Us Research Program. These individuals were matched 1:10 to controls without IDH1 or IDH2 variants by age, sex, and ancestry. The frequency of immune‐mediated rheumatic diseases in the presence and absence of IDH1/IDH2 variants was compared using chi‐square or Fisher exact tests.ResultsFifty‐five individuals with IDH1 or IDH2 gain‐of‐function variants without pre‐existing hematologic neoplasms were identified in the UK Biobank. These individuals had a significantly higher frequency of incident immune‐mediated rheumatic diseases compared to matched controls (11 of 55 [20%] vs 20 of 550 [4%], odds ratio [OR] = 6.6, P = 2.7 × 10−5), mainly polymyalgia rheumatica (6 of 11) and rheumatoid arthritis (5 of 11). Replication in the All of Us cohort identified 65 individuals with gain‐of‐function variants and confirmed an increased odds of incident immune‐mediated rheumatic diseases compared to controls (OR = 7.7, P < 5 × 10−4), predominantly rheumatoid arthritis. There was no association between loss‐of‐function variants in IDH1/IDH2 and immune‐mediated rheumatic diseases in either cohort.ConclusionRare gain‐of‐function variants in IDH1/IDH2 are associated with increased risk of immune‐mediated rheumatic diseases, particularly rheumatoid arthritis and polymyalgia rheumatica.

The aim of this study was to describe recurrent erythema nodosum (EN) temporally associated with romosozumab in a patient with mixed connective tissue disease and to examine the biologic plausibility of this association in the context of Wnt/β-catenin-mediated immune regulation. We evaluated a patient with mixed connective tissue disease and osteoporosis who developed EN following romosozumab exposure. Clinical assessment included detailed medication reconciliation, infectious evaluation, markers of inflammation, response to glucocorticoids, and recurrence upon re-exposure. A focused literature review was conducted to assess prior reports and mechanistic relevance. A 71-year-old woman developed EN approximately one month after her first dose of romosozumab, with complete remission following prednisone therapy. Within days of the second dose, she experienced a more extensive recurrence involving the hands, thighs, and right calf, which resolved after a glucocorticoid taper. Infectious evaluation was negative, markers of inflammation were normal, and medication reconciliation did not identify alternative pharmacologic triggers. Romosozumab was discontinued, and no recurrence occurred during follow-up before transition to denosumab. This case supports a probable association between romosozumab and recurrent EN. Rechallenge, exclusion of alternative etiologies, and emerging evidence on Wnt-mediated immune regulation suggest a mechanistic link between sclerostin inhibition and panniculitic hypersensitivity reactions.

Medium-vessel vasculitis involving the visceral vasculature in adults is rare. Pancreatic ductal adenocarcinoma (PDAC) has been implicated in medium artery vascular thickening secondary to extravascular migratory metastasis with involvement of the celiac and superior mesenteric vessels. Patients presenting to the rheumatology vasculitis subspecialty clinic were retrospectively identified using an electronic health record data exploration tool evaluating for diagnosis of pancreatic cancer, periaortitis, and vasculitis between January 2015 and December 2024. We retrospectively identified four patients with PDAC initially presenting with periarterial thickening of the celiac and superior celiac and superior mesenteric vessels (100% White, 50% male, median age 70.5 years). All four patients had abdominal pain with significant unintentional weight loss, with a median weight loss of 25 pounds (range 25-50 pounds). The median time to correct diagnosis was 221 days (range 162-340 days). All four patients had an elevated carbohydrate antigen 19-9 level (range from 114 to 10,702, with a median of 341.5 U/mL). All four patients were diagnosed with endoscopic ultrasound-guided fine-needle aspirations. The median number of biopsies required to make the diagnosis was three. Isolated celiac and superior mesenteric periarterial thickening or "cuffing" is a vasculitis mimic that should prompt a comprehensive malignancy workup. Expedited referral to a tertiary center is essential given difficulty in tissue sampling with conventional methods and to avoid further delays in diagnosis.