Rituximab-induced serum sickness is more frequent in autoimmune diseases as compared to hematological malignancies: A French nationwide study.

Introduction: Rituximab induced serum sickness (RISS) is a rare delayed hypersensitivity reaction. The aim of this study was to describe the epidemiological and clinical characteristics of the RISS cases reported in France.

Method: Serum sickness cases involving rituximab were identified from the French PharmacoVigilance Database from 1998 to 2016.

Results: We analyzed 37 cases of RISS. Rituximab was prescribed for an autoimmune disease in 78% of cases. Serum sickness occurred mainly after the first injection (54%) with a median time to onset of 12 days. The most frequent manifestations were rheumatologic symptoms (92%), fever (87%), and skin lesions (78%). The incidence was significantly higher when rituximab was used for autoimmune diseases than for a hematological malignancies. Taking into account the existence of a Systemic Lupus Erythematosus (SLE) as the indication of rituximab or as a comorbidity, the incidence of RISS in patients with SLE was even higher.

Discussion: We report on the largest series of RISS studied to date and confirm that this reaction preferentially occurs in patients with autoimmune disease, especially SLE. This may be due to B-cell lysis, leading to the release of intracellular antigens into the serum and subsequent antigen-antibody complex formation, especially in patients with elevated autoantibody production. This could also explain why RISS often occurred after a single injection.

Conclusion: Patients generally recovered from RISS rapidly without obvious benefit from corticosteroid therapy. The risk of recurrence should prompt clinicians to question the use of rituximab after an episode of RISS.