Guillaume Bayer1, Marie-Sara Agier2, Bertrand Lioger3, Marion Lepelley4, Marie Zenut5, Mary-Christine Lanoue6, François Maillot7, Annie-Pierre Jonville-Bera8. 1. CHRU de Tours, Service de médecine interne, Tours, France; Université François Rabelais, Tours, France. Electronic address: guillaume.bayer@hotmail.fr. 2. CHRU de Tours, Centre Régional de pharmacovigilance Centre Val de Loire, Tours, France. 3. CHRU de Tours, Service de médecine interne, Tours, France. 4. CHRU de Grenoble, Centre Régional de pharmacovigilance, Grenoble, France. 5. CHRU de Clermont-Ferrand, Centre Régional de pharmacovigilance, Clermont-Ferrand, France. 6. CHRU de Tours, OMEDIT Centre Val de Loire, Tours, France. 7. CHRU de Tours, Service de médecine interne, Tours, France; Université François Rabelais, Tours, France. 8. CHRU de Tours, Centre Régional de pharmacovigilance Centre Val de Loire, Tours, France; Université de Tours, Université de Nantes, INSERM, SPHERE U1246, Tours, France.
Abstract
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.
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.