Sullivan, Megan M

Objective Vacuoles, E1 enzyme, X‐linked, autoinflammatory, somatic syndrome (VEXAS) syndrome is characterized by a complex spectrum of inflammatory and hematologic manifestations. Clinical research to identify effective therapies is urgently needed but is hindered by the lack of validated outcome measures. A VEXAS‐specific disease activity index (DAI) is an essential tool for reliably capturing changes in disease activity over time, thereby supporting clinical research and informing patient care in this emerging disease. This study aimed to develop a comprehensive DAI to assess disease‐related inflammation across affected organ systems in patients with VEXAS syndrome. Methods Inflammatory manifestations of VEXAS were previously identified through a systematic literature review and expert input. A multinational expert advisory committee developed the VEXAS‐DAI using modified Delphi methodology until consensus (defined as ≥75% concurrence) was reached. Item grading was adapted from the Common Terminology Criteria for Adverse Events. Scoring criteria were developed based on 158 test cases using the Physician Global Assessment of Inflammation. Results Consensus on the VEXAS‐DAI was achieved after four Delphi rounds. The index assesses inflammatory activity at the time of evaluation across 12 domains: inflammatory rash, chondritis, periorbital, ophthalmologic, joint, pulmonary, cardiovascular, genitourinary, neurologic, oral and gastrointestinal, renal, and constitutional symptoms. The total score ranges from 0 to 40. Conclusion The VEXAS‐DAI is a novel instrument designed to quantify active inflammation over time in patients with VEXAS. Prospective validation within a clinical trial setting is ongoing. image

Abstract Objectives We aimed to evaluate the effects of GLP-1 receptor agonists (GLP-1RA) on symptom burden and opioid use in patients with fibromyalgia using real-world data. Methods We conducted a retrospective cohort study using the TriNetX Research Network. Patients with fibromyalgia (≥2 diagnostic encounters) were divided into two groups: those with and without ≥2 prescriptions for GLP-1RA. Propensity score matching at a 1:1 ratio for age, sex and key comorbidities, including diabetes mellitus, obesity, osteoarthritis, inflammatory arthritis, ischemic heart disease, sleep disorders, migraine and medication use, was performed. Outcomes were assessed over a five-year follow-up period. This included opioid use, diagnostic codes for pain, fatigue and disability, body mass index and haemoglobin A1C. Statistical analysis included odds ratios, risk differences and t tests. Results After propensity score matching, there were 48 025 patients in each cohort. Baseline characteristics were well matched, though BMI and Haemoglobin A1c were higher in the GLP-1RA cohort than in non-GLP-1RA users. GLP-1RA use was associated with significantly reduced odds of opioid prescription (OR 0.65), pain diagnostic codes (OR 0.79) and fatigue diagnostic codes (OR 0.68) (all P < 0.001). There was no significant difference in disability-related diagnostic codes. BMI and HbA1C remained higher in patients on GLP-1RA. Conclusion GLP-1RA use was associated with reduced opioid prescription and a reduction in the use of ICD-10 codes related to fibromyalgia, potentially reflecting lower symptom burden. Further studies using validated outcome measures are needed to confirm these findings.

Background: Rheumatoid arthritis is a relatively common rheumatic disease that can present with inflammatory arthritis and subcutaneous nodules. Multicentric reticulohistiocytosis and fibroblastic rheumatism are rarer entities that also present with these features. Methods: Two cases, one of each of fibroblastic rheumatism and multicentric reticulohistiocytosis, are described highlighting characteristic clinical, radiographic, and histologic findings. A narrative review of the literature on these rarer conditions, compared with rheumatoid arthritis, is provided with a focus on articular and cutaneous findings, available information on disease presentations, and key contrasting features that can aid in diagnosis. Results: Radiographic erosion distribution and joint space narrowing, clinical nodule distribution and characteristics, and nodule histology can differ between these diseases. Conclusions: Multicentric reticulohistiocytosis and fibroblastic rheumatism should be considered in the evaluation of seronegative rheumatoid arthritis, especially in cases that do not respond predictably to standard therapies, and cutaneous nodule biopsy can aid in differentiating these three conditions.

Objective: Pulmonary involvement is commonly observed in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), presenting with manifestations such as diffuse alveolar hemorrhage, inflammatory infiltrates, pulmonary nodules, and tracheobronchial disease. We aimed to identify distinct subgroups of tracheobronchial disease patterns in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) using latent class analysis (LCA), and to evaluate their clinical characteristics and outcomes. Methods: We conducted a retrospective cohort study using electronic medical records of patients aged >18 years diagnosed with AAV and tracheobronchial disease between 1 January 2002 and 6 September 2022. Patients with follow-up <6 months were excluded. LCA was employed to identify disease subtypes based on 10 pre-defined indicators. Maximum likelihood estimation with 10 repetitions per model ensured robustness in model selection, guided by the Akaike information criterion (AIC). Patient and disease characteristics were summarized and compared across predicted classes. Statistical analyses included Kruskal–Wallis and Fisher’s exact tests for continuous and categorical variables, respectively. The primary outcome was time to relapse of the tracheobronchial inflammation after starting immunosuppressive medication, analyzed using the Kaplan–Meier method and log-rank tests. Secondary outcomes included severity of pulmonary disease on pulmonary function tests, endoscopic interventions, tracheostomy, or mortality during follow-up. Results: Among 136 identified AAV patients assessed for tracheobronchial involvement, 111 (81.6%) were included after excluding 25 without tracheal or bronchial disease. Predominant findings included subglottic stenosis (91.0%), lower tracheal stenosis (16.2%), and bronchial stenosis (17.1%). LCA identified a three-class model as optimal: tracheal predominant (n = 94), tracheobronchial (n = 12), and bronchial predominant (n = 5). Tracheal predominant patients showed reduced risk of ear, eye, and lower respiratory manifestations, with milder obstruction on pulmonary function testing (PFT). Tracheobronchial-class patients were prone to saddle nose deformity (50%), extensive lower respiratory involvement (91.7%), and renal disease (66.7%). Bronchial predominant patients exhibited severe obstructive disease (median forced expiratory volume in 1 s (FEV1)% predicted: 58, IQR 34–66; FEV1/forced vital capacity (FVC) ratio: 56.9, interquartile range (IQR) 43–63.3) but lacked systemic AAV manifestations. LCA classes did not predict outcomes such as endoscopic intervention, tracheostomy, recurrent tracheobronchial narrowing, or mortality. Conclusion: LCA shows promise in subtype stratification of AAV patients, yet its utility in predicting outcomes and guiding treatment remains limited based on our analysis. Future studies with enhanced phenotypic data and larger cohorts are warranted to improve predictive accuracy.

Abstract Objectives To define the prevalence, distribution and characteristics of patients with VEXAS (vacuoles, E1-enzyme, X-linked, autoinflammation, somatic) syndrome who have confirmed vasculitis. Methods Patients with VEXAS syndrome, verified by positive UBA1 mutation, were included. Chart review was performed to identify patient characteristics and outcomes. Vasculitis diagnosis was based on either histopathology showing vascular inflammation or non-invasive angiography findings. Summary statistics were calculated. Results Eighty-nine patients met inclusion criteria. All were male with a median age of onset of 66.9 years (interquartile range 60.1, 72.7). Median (interquartile range) follow-up was 3.8 (2.2–5.5) years, during which 21 patients (23.6%) had evidence of vasculitis. Vasculitis subtypes included small vessel vasculitis (19.1%), cutaneous medium vessel vasculitis (2.2%) and large vessel vasculitis (2.2%). No patient had more than one vessel size involved. Histopathology in small vessel vasculitis patients was consistent with cutaneous leukocytoclastic vasculitis in the majority, though one patient had leukocytoclastic peritubular capillaritis on renal biopsy. Cranial symptoms (headache, vision changes or jaw pain) were noted in 18.0%. Two additional patients not experiencing cranial symptoms exhibited large vessel involvement with confirmed carotid thickening on non-invasive angiography; one of these had a positive temporal artery biopsy. Conclusion VEXAS syndrome manifests as a variable vessel vasculitis in a quarter of patients, with cutaneous small and medium vessel involvement being particularly common. Some patients may have positive ANCA serologies or even renal vasculitis leading to misdiagnosis. Cranial symptoms are common and may mimic GCA, though documented large vessel inflammation is rare.

Abstract Objectives Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) syndrome is an autoinflammatory disease caused by somatic mutation of UBA1 and affects multiple organ systems. Involvement of the kidneys is not well characterized. We aimed to investigate the incidence, risk factors and histopathologic features of acute kidney injury (AKI) in VEXAS syndrome. Methods Patients with genetically confirmed UBA1 mutation consistent with VEXAS were included. Charts were manually reviewed. Cox regression analysis was used to identify variables associated with time-to-first AKI event. For patients with a kidney biopsy, histopathologic findings were reviewed. Results Eighty-one patients were included, all white men, with a mean age of 66.3 ± 8.6 years. Median (IQR) follow up was 3.5 (2.1–5.2) years during which 20 (25%) developed AKI and 22% died. AKI relapsed in 90% of cases for a median of 6 times during the follow up period. Cumulative incidence estimates (95% CI) for AKI at 1, 3 and 5 years were 6.2% (0.80–11.3%), 16.7% (7.5–25.0%) and 27.9% (14.9–38.9%), respectively. Age and baseline C-reactive protein (CRP) were significantly associated with time-to-first AKI event. Six patients underwent a kidney biopsy. Findings included, plasma cell-rich interstitial nephritis (n = 3), neutrophilic-rich interstitial inflammation (n = 1), leukocytoclastic peritubular capillaritis (n = 1) and acute tubular injury (n = 1). AKI responded well to treatment with glucocorticoids but had relapse upon tapering. Conclusion AKI is an underrecognized feature of VEXAS occurring in 25% of patients in this cohort. Age at diagnosis and CRP were associated with time to first AKI event during follow up. Plasma cell-rich interstitial nephritis was the most common histopathologic finding.

ObjectiveNew‐onset and relapsed dermatomyositis (DM) has been reported following SARS‐CoV‐2 infection or COVID‐19 vaccination. This study aims to show the characteristics of a DM cohort after COVID‐19 infection and vaccination.MethodsA retrospective review was performed on patients treated for DM between March 1, 2020, and October 31, 2022. Charts were evaluated for the presence of new‐onset DM or relapse of preexisting DM following either SARS‐CoV‐2 infection or COVID‐19 vaccination. Data on symptom onset, timing of vaccination, type of vaccination, and disease characteristics were collected.ResultsNinety‐eight patients treated for DM at our institution in the Division of Rheumatology were included. In total, 12 of 98 patients (12.2%) experienced DM symptoms (either incident or relapse) following either infection or vaccination. Of the 12 patients who developed incident disease or relapse, 7 (58.3%) developed postinfection symptoms, and 8 (66.7%) developed symptoms after vaccination (3 patients had symptoms following both infection and vaccination). The mean onset of symptoms following COVID‐19 infection was 3.2 days (median 0.5 days), and mean onset following COVID‐19 vaccination was 5.75 days (median 3.5 days). Nine of 12 patients (75%) had a positive myositis‐specific antibody, and the remaining 3 (25%) had myositis‐associated antibodies. There was no predominant vaccine associated with the development of postvaccination DM symptoms.ConclusionThis retrospective review revealed a strong temporal relationship between DM symptoms and COVID‐19 infection or vaccination in 12.2% of all patients with DM evaluated in our clinic during the pandemic. Additional studies are required to understand the possible pathophysiology behind this association.

Introduction: Granulomatosis with polyangiitis (GPA) is a vasculitic process that can cause neurological dysfunction in addition to characteristic sinus and pulmonary manifestations. This case report highlights the spectrum of nervous system manifestations and includes rarely reported autonomic and pituitary involvement. Case Report: A 62-year-old woman presented with orthostatic intolerance, tachycardia, dry mouth, and temperature sensitivity; subsequent autonomic reflex study demonstrated widespread postganglionic sympathetic sudomotor, cardiovagal, and cardiovascular adrenergic impairment reflective of autonomic neuropathy and overall autonomic failure. Additional progressive symptoms included dysarthria, dysphagia, bilateral hearing loss, voice hoarseness, and right-sided facial numbness with multiple cranial neuropathies identified on neurological examination. The diagnosis of central diabetes insipidus was also confirmed. Pachymeningitis was present on brain magnetic resonance imaging. Pathologic review of the dural biopsy specimen revealed necrotizing granulomatous vasculitis consistent with GPA. She was treated with intravenous methylprednisolone and rituximab. Over the next 2 months, she had near-complete resolution of her symptoms with normalization on repeat autonomic testing. Conclusions: This is a unique GPA case presenting with autonomic failure and pituitary dysfunction with conclusive objective findings of autonomic dysfunction. Autonomic dysfunction and other disease manifestations were responsive to immunosuppressive therapy.