C42-37 A Decade Later: A Unique Case of Delayed-Onset Rituximab-Induced Lung Injury

Abstract Introduction Rituximab is a B-cell-depleting anti-CD20 monoclonal antibody used for autoimmune, rheumatologic, and neurological diseases, including neuromyelitis optica spectrum disorder (NMOSD). Major adverse events include infusion reactions, serious infections, cytopenias, but rarely pulmonary toxicity. Interstitial lung disease (ILD) occurs in 1% of patients and can have varied pulmonary manifestations. We present a unique case of delayed onset Rituximab-induced ILD. Case description A 59-year-old woman with a history of left breast ductal carcinoma in situ five years ago (treated with lumpectomy, radiation, and anastrozole), pulmonary embolism on anticoagulation, and stable NMOSD on biannual 1000mg rituximab infusions for eleven years; presented with a gradually worsening productive cough, dyspnea, new onset hypoxia, and low-grade fever for one week. She was managed with antibiotics for presumed community-acquired pneumonia given bilateral patchy airspace disease on chest x-ray; however, continued to remain hypoxic for which corticosteroids and bronchodilators were trialed outpatient with minimal benefit. A chest CT at six weeks showed diffuse bilateral ground-glass opacities with chronic traction bronchiectasis and scarring, significantly worse from prior scans. Pulmonary function tests (PFTs) revealed severe restriction (FVC 37%, FEV 39%) and reduced DLCO (28%). Wedge lung biopsy showed a predominantly cellular non-specific interstitial pattern (NSIP) with uniform interstitial thickening, lymphocytic infiltration, temporal heterogeneity, and absence of granulomas or fibroblastic foci. Extensive workup excluded infection, connective tissue/ autoimmune disease, NMOSD-related pathology, and alternate drug toxicity. Long-term Rituximab exposure was attributed as the likely culprit and she was subsequently switched to Mycophenolate. She underwent pulmonary rehabilitation and was eventually weaned off oxygen, with serial PFTs showing near-complete recovery. Discussion Rituximab-induced ILD (R-ILD) is mainly associated with hematologic malignancies, where higher cytotoxic dosing contrasts with the relatively lower immunomodulatory dosing used in autoimmune conditions. It typically develops within the first few cycles or months of therapy. Our patient’s NMOSD was stable on biannual rituximab infusions for several years before disease onset, an exceptionally delayed presentation. Diagnosis was challenging due to overlapping infectious and inflammatory features with a confounding past history. Although delayed-onset R-ILD has been reported, latency spanning several years is exceedingly rare, and its incidence and prevalence remain undefined in literature. No studies have specifically compared steroid responsiveness between early and delayed R-ILD, or evaluated if delayed-onset disease exhibits poorer response. This case highlights the limitted understanding of this rare pulmonary complication of rituximab and the need for continued surveillance in patients on pneumotoxic therapies prone to cumulative or acute-on-chronic lung injury. This abstract is funded by: None