Case Presentation: 76 year old male with non-Hodgkin lymphoma presented with shortness of breath and cough and was admitted with acute hypoxic respiratory failure (AHRF). Last chemotherapy treatment was one month before presentation with rituximab, in addition to other agents. He had completed 2 out of 6 planned chemotherapy cycles. On physical exam, there were mild rhonchi at lung bases bilaterally, and bilateral trace pitting lower extremity edema. CT imaging revealed bilateral upper and lower lobe ground glass opacities. The patient required intubation and underwent bronchoscopy. Infectious work up including viral and tuberculosis PCR, blood and bronchoalveolar lavage bacterial and fungal cultures, Pneumocystis DFA cytology, serum Aspergillus antigen, and beta D glucan were negative. Additionally, rheumatologic workup was negative including ANA, ANCA, SSB, SSA antibody, and RF. White Blood Cell count was not elevated. Patient was empirically treated with Ceftriaxone and Azithromycin for 5 days. Finally, the patient was treated with prednisone taper, successfully extubated, and discharged after 19 days. Post treatment CT scan showed minimal pulmonary scarring. Based on the timeline of presentation and otherwise negative workup rituximab induced ILD was diagnosed.
Discussion: It is known that certain drugs may trigger an immune response involving antibodies and T-cells, resulting in immune-mediated drug induced interstitial lung disease (DI-ILD) (1). Although not commonly associated with DI-ILD, there have been cases of rituximab-associated ILD (1,2). Rituximab is a monoclonal antibody directed against the CD20 antigen of B-lymphocytes. The proposed type 4 hypersensitivity reaction is to the anti-CD20 antibody. Rituximab-induced pneumonitis may be diagnosed based on a temporal relationship between the medication and symptoms, the patient’s history, and radiographic findings. Although not necessary for diagnosis, bronchoscopy may be useful in ruling out other causes of lung injury such as malignancy or infection (3). The diagnosis is more likely if symptoms improve once rituximab is stopped. DI-ILD due to rituximab is managed with steroids. Even after recovery from DI-ILD, re-challenging is not usually recommended given an increased risk of mortality, though may be considered at a reduced dose if alternative treatment options are not available (3). Overall estimate of mortality is 37.5% (4).
Conclusions: Given the potential severity of rituximab-induced lung disease, hospitalists should have a strong suspicion for this reaction in patients on known rituximab therapy presenting with AHRF. As the first line provider before subspecialists are involved in the patient’s care, awareness of this rare side effect is necessary for a comprehensive differential. Special considerations include that the risk is greatest approximately 15 days after the last infusion and around the fourth cycle of treatment overall. Secondly, respiratory symptoms, however mild, should prompt chest radiography as this is the most reliable way to assess for this diagnosis. Chest x-ray findings are typically patchy diffuse opacities. Finally, when findings support a diagnosis of rituximab-induced lung disease, steroid therapy should be started immediately, as this improves the outcome. Typical regimen suggested is prednisone, 0.5 mg/kg per day (up to 30 mg per day), given as a single daily dose, although dose and duration have not been formally studied. This dose is maintained for 1-2 weeks and then tapered over 2-4 weeks.