Pulmonary manifestations in VEXAS syndrome.

BACKGROUND: Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is a recently recognized multisystem disorder caused by somatic mutations in the UBA1 gene. METHODS: A retrospective cohort study was conducted on all patients with VEXAS syndrome evaluated at our institution from June 2020 through May 2022. Medical records and chest imaging studies were reviewed. RESULTS: We identified 45 subjects with median age of 68 years (range, 57-89), all men. Prior to VEXAS diagnosis, most patients had been diagnosed with various hematologic, rheumatologic, and dermatologic disorders. Most patients (84%) demonstrated canonical UBA1 methionine-41 (p.Met41) somatic mutations in hematopoietic cells. Fever (82%), skin lesions (91%), and respiratory symptoms (93%) were common presenting features. Chest CT manifested abnormalities in 91% of patients including parenchymal opacities in 25 (74%), most commonly ground-glass opacities (47%), along with mediastinal lymphadenopathy (29%), airway abnormalities (29%), and pleural effusion (24%). Pulmonary function test results available in 18 (40%) patients demonstrated mild restrictive impairment or normal results. Bronchoalveolar lavage and lung biopsy performed in a minority of patients demonstrated neutrophilic alveolitis and parenchymal inflammation, respectively. All patients received glucocorticoid therapy with at least partial response, but relapses were common and other immunosuppressive agents were employed in most patients. Pulmonary involvement appeared to improve in patients who received tocilizumab and JAK inhibitors. CONCLUSION: The pulmonary manifestations in VEXAS are relatively nonspecific and nonsevere, occur in the context of systemic inflammation and are responsive to escalation in glucocorticoid dosing.

VEXAS Syndrome-A Review of Pathophysiology, Presentation, and Prognosis.

ABSTRACT: VEXAS ( V acuoles, E 1 enzyme, X -linked, A utoinflammatory, S omatic) syndrome is a newly identified disease caused by somatic mutations in the UBA1 gene resulting in refractory autoinflammatory features, frequently accompanied by cytopenias. Although the prevalence of this syndrome is yet unknown, understanding the clinical phenotype can assist clinicians in prompt recognition of cases among patients with glucocorticoid-responsive but immunosuppressive-resistant inflammatory symptoms. The pathophysiology, clinical presentation, diagnostic methods, treatment, and prognosis of VEXAS are herein reviewed.

Clinical Heterogeneity of the VEXAS Syndrome: A Case Series.

The objective of this study is to describe the clinical features and outcomes of patients with the newly defined vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Nine men with somatic mutations in the UBA1 gene were identified; the most frequent variant was p.Met41Thr (7 of 9, 78%). The median age at VEXAS diagnosis was 74 (67, 76.5) years, and patients had a median duration of symptoms for 4 years before diagnosis. Refractory constitutional symptoms (88%), ear and nose chondritis (55%), and inflammatory arthritis (55%) were common clinical features. Vasculitis was noted in 44%. All patients had significantly elevated inflammatory markers and macrocytic anemia. Thrombocytopenia was present in 66% at diagnosis of VEXAS. Eight patients had bone marrow biopsies performed. All bone marrows were hypercellular, and there was vacuolization of the erythroid (100%) or myeloid precursors (75%). Glucocorticoids attenuated symptoms at prednisone doses ≥20 mg per day, but no other immunosuppressive agent showed consistent long-term control of disease. One patient with coexisting plasma-cell myeloma received plasma-cell-directed therapy with improvement of the inflammatory response, which is a novel finding. In conclusion, VEXAS syndrome is a clinically heterogeneous, treatment-refractory inflammatory condition caused by somatic mutation of the UBA1 gene. Patients often present with overlapping rheumatologic manifestations and persistent hematologic abnormalities. As such, internists and subspecialists, including pathologists, should be aware of this condition to avert diagnostic delay, now that the etiology of this syndrome is known.

Diffuse large B cell lymphoma involving Meckel's cave masquerading as biopsy-negative giant cell arteritis: a case report.

BACKGROUND: Given the absence of consensus diagnostic criteria for giant cell arteritis, clinicians may encounter difficulty with identification of new-onset headache in patients older than age 50 years presenting with visual changes and elevated inflammatory markers, particularly if temporal artery biopsies are performed and negative. CASE PRESENTATION: We present a case of a 57-year-old white man with headache, diplopia, and jaw paresthesia initially diagnosed and managed as steroid-refractory biopsy-negative giant cell arteritis. Further investigation disclosed evidence of soft tissue infiltration into Meckel's (trigeminal) cave bilaterally. Positron emission tomography suggested the presence of a lymphoproliferative disorder. Histology confirmed the diagnosis of diffuse large B cell lymphoma. CONCLUSIONS: Metastatic involvement in Meckel's cave in diffuse large B cell lymphoma is extremely rare and presents a diagnostic challenge. Patients with suspicion of giant cell arteritis should undergo advanced imaging, particularly those with negative biopsy, atypical features, or lack of response to standard therapy, in order to assess for the presence of large-vessel vasculitis or other mimicking pathologies.