Rituximab is increasingly used off label for difficult-to-treat auto-immune 
diseases. We reviewed the main case series or clinical studies to identify the 
best indications of rituximab and the situations at substantial risks for 
adverse events. Refractory immune thrombocytopenic purpura was the main 
indication. However, the long term benefit-to-risk ratio of rituximab treatment 
before or after splenectomy is unknown. A single 375 mg/m2 infusion may be as 
efficacious as the classical four infusions cycle. Rituximab is the best 
treatment for cold agglutinin disease. In warm agglutinin auto-immune anaemia, 
its efficacy has essentially been reported in chronic lymphocytic leukemia (CLL) 
patients and in children. In CLL patients, lethal adverse events occurred in 
patients also receiving cyclophosphamide. Rituximab seems to have an interesting 
benefit-to-risk ratio in Wegener granulomatosis (excepted in granulomatous 
lesions), HCV-associated symptomatic cryoglobulinemia in patients unresponsive 
to anti-viral therapy, pemphigus and thrombotic thrombocytopenic purpura. 
Efficacy and safety data in lupus are difficult to interpret. Serum sickness 
disease is not exceptional in immune thrombocytopenic purpura (ITP), lupus and 
sicca syndrome patients. A substantial infectious risk has been reported in 
pemphigus patients and in post-renal transplant cryoglobulinemia. Double-blind 
randomised controlled trials and phase IV studies are mandatory in most clinical 
settings to confirm the overall favourable perception of rituximab benefit to 
risk ratio.