Rituximab in Patients With Acute Rheumatic Fever

Acute Rheumatic Fever is an autoimmune inflammatory post-infectious syndrome, mainly caused by type A streptococcus. It is characterized as an inadequate immune response. It may provoke carditis, combined with articular, skin and neurologic signs. Only carditis, prevalent in 60% of acute rheumatic diseases, may provoke valvular sequels, which define rheumatic cardiopathy. Antibiotherapy based on penicillin is the standard treatment of both acute rheumatic fever and its prevention. Although no anti-inflammatory treatment has proved its efficacy, with or without steroids anti-inflammatory treatments are administered in acute episode of ARF. Up to date, only prevention strategies have shown efficacy.

Inclusion Criteria:Children aged between >= 5 and < 17 years old;Diagnosed acute rheumatic fever with at least one progressive rheumatic valvular lesion confirmed through a cardiac echography.Informed consent, signed and dated by both parents or legal guardians of the patientExclusion Criteria:Simultaneous active infection, such as HIV, hepatitis B, C, tuberculosis, Epstein-Barr virus (EBV), or history of frequent, unusual or serious infections ;Pathologies likely to affect immunity (cancer, multiple sclerosis, diabetes, other auto-immune diseases)Recent history of drug administration that may affect the immune system, for the past 4 weeks (immunosuppressive drugs, corticosteroids, anticancer drugs);Hypersensitivity reaction to rituximab or one of its components. Hypersensitivity to penicillinHistory of monoclonal antibodies administrationRecent vaccination (less than a month) or planned within the 12 months after randomization;History of heart failureRenal failure with a creatinine clearance <45 ml/min/1,73m²Pregnancy (a negative urinary test is necessary for women who had their first menstruations or aged 14 years old and more)Patients diagnosed with Guillain-Barré syndromePatient with at least one of the following biological features : Hemoglobin < 8,5 g/dL, Platelets < 100 G/L, Neutrophils < 1,5 G/L, Leucocytes < 3 G/L, AST or ALT increased > 2,5 the normal superior limit)Any acute or chronic infection clinically significant which would limitate the patient's capacity to follow up the study protocol, which remains under appreciation of the investigator.Any participation in another clinical trial in the 6 months before the pre-randomization visit