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

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.