B35-34 Intersecting Immunodeficiency and Autoimmunity: Rituximab Response in Cvid-Associated Granulomatous-Lymphocytic Interstitial Lung Disease

Abstract Introduction Common Variable Immunodeficiency (CVID) is a heterogeneous primary immunodeficiency characterized by hypogammaglobulinemia, recurrent infections, autoimmune disorders, and granulomatous inflammation. Granulomatous-lymphocytic interstitial lung disease (GL-ILD) affects approximately 10-20% of CVID patients and poses diagnostic challenges due to overlapping clinical and radiographic features with sarcoidosis and other interstitial lung diseases. This case report aims to illustrate the clinical course, diagnostic complexity, and therapeutic response to Rituximab in a patient with CVID-associated GL-ILD complicated by multisystem autoimmune manifestations. Case summary The patient was diagnosed with CVID in 2015 at age 56, presenting with recurrent sino-pulmonary infections, significantly reduced immunoglobulin levels (IgG, IgA, IgM), splenomegaly, elevated alkaline phosphatase, and hepatomegaly. Initial chest imaging revealed bilateral pulmonary nodules, retrocaval lymphadenopathy, and hepatomegaly, prompting differential diagnoses of GL-ILD versus sarcoidosis. She received chronic low-dose prednisone and intravenous immunoglobulin (IVIG), with partial symptomatic improvement.In 2021, the patient developed febrile neutropenia and hypoxemia necessitating hospitalization and initiation of regular IVIG therapy. Following this, immunoglobulin levels normalized, and there was improvement in pulmonary function and physical mobility. However, she experienced recurrent pulmonary exacerbations, including COVID-19 infections in 2022 and 2023, complicating disease management.Due to ongoing granulomatous inflammation, organizing pneumonia, bronchiolitis, anemia, and thrombocytopenia, Rituximab infusions were started in 2023 and administered over one year. Post-treatment, pulmonary function stabilized with minimal cough, and exercise tolerance improved substantially. Prednisone was maintained at 5 mg daily to prevent relapse, as attempts to taper below this dose triggered symptom flares. Serial imaging showed no progression of pulmonary nodules or lymphadenopathy. Liver enzyme abnormalities persisted, consistent with nodular regenerative hyperplasia or nonalcoholic steatohepatitis but remained clinically stable. Despite contracting COVID-19 in September 2023, the patient recovered uneventfully and undertook international travel without complications. Conclusions This case underscores the challenges in diagnosing GL-ILD in CVID, particularly given its clinical and radiographic resemblance to sarcoidosis and its atypical late presentation. Standard therapies such as corticosteroids and immunoglobulin replacement may be insufficient in controlling multisystem immune dysregulation. Rituximab demonstrated significant clinical efficacy, stabilizing pulmonary disease and systemic autoimmune manifestations, and improving patient quality of life without major adverse effects. These findings advocate for early consideration of B-cell-targeted therapy in refractory CVID-associated GL-ILD and highlight the importance of multidisciplinary management in complex immunodeficiency syndromes. This abstract is funded by: None