Rituximab is an anti-CD20 humanized chimeric monoclonal antibody and was initially developed to treat B cell malignancies [
4,
18]. Following initial success, Rituximab has also been approved for the management of rheumatoid arthritis and has undergone clinical trials demonstrating the successful use in a growing number of autoimmune diseases, including systemic lupus erythematosis, ITP, pemphigus, multiple sclerosis, and ANCA-associated vasculitis [
19‐
23], in which dysregulated B cells are involved in the pathogenesis. A systematic review on the utilization of rituximab in ITP was published in 2007, included 313 patients from a total of 19 (eligible) studies and reported an overall response rate of 62.5% (as defined by a platelet increase to >50 × 10
9 cells/L) when given at a dose of 375 mg/m
2 iv once weekly for 4 weeks [
24]. The median duration of the response was 10.5 months [
24]. More recent reports indicate that Rituximab may be more effective than various other immunosuppressants, particularly in the setting of refractory cases of ITP. Accordingly, Rituximab has been recognized as a useful drug in the second line of treatment for ITP either alone or in combination with corticosteroid, although it is not recommended as standard first-line therapy [
25]. However, whereas initial response rates are high, long-term follow up data on patients treated with Rituximab are sparse. It is still under investigation, how patients should be monitored and how frequently treatment should be repeated. In general, Rituximab is considered a relatively safe drug with only modest toxicity and infectious complications [
4]. Among side effects described are infusion-related reactions, serum sickness, and agranulocytosis [
19,
26]. Due to the depletion of the B cell-mediated arm of the immune system, infections are a major concern. In different studies, the rate of serious infections has been between 2.8% to 45% (mean 12%) and the use of Rituximab as a direct cause of death has been estimated to 7% [
27]. These numbers may be difficult to interpret, since most of the patients were immunocompromised even prior to Rituximab treatment due to autoimmunity and the concomitant use of additional immunosuppressive agents. A recent multicenter retrospective study on the use of Rituximab in CVID-associated immune cytopenias reported a response rate of 85%, including 74% complete responses. However, after a mean follow-up time of 30 months after Rituximab, 10 out of the initial reponders relapsed and required re-treatment, and severe infections occurred in 24% [
28].