Severe Reactions to Rituximab in Children: A Cohort Study of Rituximab-Induced Serum Sickness and Anaphylaxis

Severe infusion-related reactions to rituximab are rare; we aim to extend our knowledge about them in children, focusing on rituximab-induced serum sickness (RISS) and anaphylaxis.

We conducted a monocentric retrospective study on children and adolescents who received rituximab. Patients were defined as having RISS if they had fever and at least rash and/or arthralgia, 1 to 30 days following infusion, and without another diagnosis to explain symptoms. Anaphylaxis was defined according to the diagnostic criteria proposed by the World Allergy Organization.

1534 rituximab infusions in 391 patients were analyzed. Seven patients developed RISS; all received rituximab for an autoimmune disease, including four for immune thrombocytopenia (ITP). Six patients had fever, rash, and arthralgia. C-reactive protein or sedimentation rate was increased in all patients, and complement was decreased in 83%. Evolution was favorable within a few days with corticosteroids and/or intravenous immunoglobulins. Rituximab was reinfused in one patient, which resulted in an immediate anaphylactoid reaction. Lower doses of rituximab were less likely to induce RISS. RISS was associated with a greater chance of achieving ITP remission. Seven patients developed anaphylaxis; five successfully received further infusions using desensitization protocols.

RISS in children is a severe complication of rituximab infusion. Our study suggests that it may be more frequent in individuals treated for autoimmune conditions, especially ITP. The classical triad of fever, rash, and arthralgia appeared to be frequently present, and biological inflammation and/or low complement can further support the diagnosis. In contrast to anaphylaxis, where rituximab may be safely rechallenged upon desensitization protocol, treatment alternatives should be pursued in patients experiencing RISS, given the higher risk of severe RISS recurrence.