A35-03 Interstitial Lung Disease in Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic (VEXAS) Syndrome

Abstract Introduction Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an adult onset autoinflammatory syndrome caused by somatic loss of function mutation affecting ubiquitin-like modifier activating enzyme 1 (UBA1) gene in hematopoietic stem cells. We present the case of an adult male diagnosed with VEXAS syndrome after presenting with interstitial lung disease. Case Presentation A 65-year-old male presented with cough, dyspnea, and malaise. He was previously diagnosed with myelodysplastic syndrome on bone marrow biopsy after evaluation for macrocytic anemia, and perivascular dermatitis with a recurrent maculopapular rash. CT chest demonstrated multifocal pulmonary opacities, noncalcified mediastinal and hilar lymph nodes, and pleural effusions. Blood work revealed an elevated erythrocyte sedimentation rate and C-reactive protein levels. Prior autoimmune workup was positive for ANA multiplex, mildly elevated dsDNA, and remaining serological testing, including myositis panel, was negative. He was treated with antibiotics and corticosteroids with clinical improvement, however symptoms recurred after tapering prednisone. Pulmonary function tests showed mild restriction, air trapping and moderately decreased diffusion capacity. Six months later, a repeat CT scan showed right sided predominant pulmonary fibrosis corresponding to previous consolidations. Surgical lung biopsy via VATS revealed fibrosing interstitial pneumonia with honeycomb changes, fibroblastic foci in UIP pattern, and foci of organizing pneumonia. He was followed by rheumatology and ultimately referred to a VEXAS specialist as well as a geneticist. Genetic testing confirmed a pathogenic UBA1 p.Met41Val mutation, consistent with VEXAS syndrome. He was restarted on prednisone and initiated on tocilizumab with clinical improvement, though attempts to wean prednisone lower than 20 mg were met with increased symptom burden. Discussion VEXAS syndrome results from somatic UBA1 mutations causing widespread systemic inflammation. Pulmonary involvement is the second most common manifestation, present in about 50-72% of patients. Most common findings are ground glass opacities, consolidations, and pleural effusions, but progression to fibrosis is rare. In a systematic review of 269 patients, idiopathic interstitial pneumonia was reported in 3.3% of cases with only a single case of nonspecific interstitial pneumonia specifically described. Therefore we described a case of VEXAS syndrome with interstitial lung disease as its pulmonary manifestation due to its rare presentation. Conclusion Given a spectrum of manifestations across multiple systems, VEXAS is often misdiagnosed as other autoimmune or hematologic diseases. Recognition of common presentations, including combination of anemia, recurrent rash, and steroid-dependent pulmonary symptoms, should raise concern for VEXAS syndrome. This abstract is funded by: None