C32-14 Severe Flare of Immunoglobulin G4-Related Lung Disease Following Transition From Prednisone to Inebilizumab

Abstract Introduction Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder characterized by dense lymphoplasmacytic infiltration and tissue fibrosis. Pulmonary involvement can manifest with interstitial infiltrates, lymphadenopathy, and acute respiratory failure. B-cell-depleting agents such as inebilizumab, a CD19-directed monoclonal antibody, have emerged as steroid-sparing options for maintenance therapy. However, data on their real-world use in immunoglobulin G4-related lung disease (IgG4-RLD) remain limited. Case Description A 78-year-old man with known IgG4-related pulmonary disease was transitioned from long-term prednisone to inebilizumab. Prednisone was discontinued one month before presentation; he had received two inebilizumab infusions, the most recent four weeks before admission. He presented with dyspnea and fatigue. CTA revealed extensive bilateral ground-glass and consolidative opacities with smooth interlobular septal thickening and hilar lymphadenopathy. Segmental and subsegmental pulmonary emboli were also present without right heart strain. Labs showed a WBC of 4.2 × 10³/µL, CRP 17.2 mg/dL, and ESR 69 mm/hr, with normal procalcitonin and lactate. Comprehensive infectious studies, including respiratory PCR, blood cultures, sputum cultures, and fungal serologies, were negative. He was admitted to the ICU for acute hypoxemic respiratory failure requiring HHFNC. Treatment included intravenous methylprednisolone 40 mg every 6 hours, vancomycin, cefepime, and therapeutic heparin infusion. Over five days, his oxygen requirement decreased, and he was transitioned to oral prednisone 60 mg daily, Augmentin, and Bactrim for Pneumocystis prophylaxis. Heparin was switched to apixaban. The patient was discharged on hospital day 12 with a steroid taper. Discussion This case highlights a severe pulmonary flare of IgG4-RLD occurring shortly after steroid withdrawal despite concurrent inebilizumab therapy. Although an infectious etiology was initially considered, particularly given the patient’s immunosuppressed state, the absence of clinical, microbiologic, and serologic evidence of infection made this diagnosis less likely. The overall presentation was therefore most consistent with an IgG4-RLD flare. The temporal pattern suggests that incomplete or delayed B-cell and plasmablast depletion may permit disease reactivation during the early transition phase. Breakthrough flares of this severity appear uncommon, particularly those requiring ICU-level respiratory support. This case underscores the importance of cautious steroid tapering and close monitoring when transitioning from corticosteroids to biologic therapy in IgG4-RD. It also raises the question of whether an overlap period or slower taper is warranted in patients with significant pulmonary involvement. A review of the current literature does not reveal prior reports of ICU-level IgG4-RLD flare following inebilizumab initiation, making this case a meaningful addition to emerging real-world experience with CD19-targeted therapy. This abstract is funded by: None