Fatal interstitial lung disease induced by rituximab‐containing chemotherapy, treatment with TNF ‐α antagonist and cytokine profiling: a case‐report and review of the literature

Summary What is known and objective Rituximab, an anti‐CD20 monoclonal antibody, is widely used with good response for the treatment of B‐cell lymphoma and various refractory autoimmune diseases. Although rituximab is effective, rare but serious pulmonary adverse reactions have been reported. We report on a case of rituximab‐induced life‐threatening interstitial lung disease in a patient with diffuse large B‐cell lymphoma (DLBCL), and describe the patient's serum cytokine profile during anti‐TNF‐α treatment. Case summary : A 71‐year‐old woman diagnosed with DLBCL was treated with three cycles of rituximab‐containing chemotherapy. She developed a fatal respiratory failure, which was eventually diagnosed as rituximab‐induced interstitial lung disease (R‐ILD). The R‐ILD in this patient did not respond to intensive steroid treatment, or to enternacept, an anti‐TNF therapy. During therapy, we observed that the serum level of IL‐6 was much higher at the beginning of treatment than was usual for other DLBCL patients. Levels of IL‐6 and TNF‐α also increased during the course of the clinical exacerbation. We undertook a literature search and reviewed similar cases of R‐ILD. What is new and conclusion Although rituximab is generally effective and safe, caution is required for high‐risk patients, as in our case, and as reported in several other cases in the literature. Cytokine analysis may help in identifying patients at high risk of R‐ILD. Better intensive therapeutic approaches other than steroids are required even during the early stages of the complication.