The treatment of acute rheumatic fever. Treatment of rheumatic fever and rheumatic carditis. Observations providing a basis for the selection of aspirin or adrenocortical steroids. A double-blind placebo-controlled trial of prednisone in active rheumatic carditis. Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial. Therapeutic agents in rheumatic carditis; comparative effects of acetylsalicylic acid, corticotropin, and cortisone.
nan nan In view of the controversy surrounding the use of corticosteroids in the management of active rheumatic carditis, a prospective double-blind controlled clinical trial comparing prednisone (2 mg/kg/24 h in three divided doses) versus placebo was carried out in 35 children with this disease, using strict clinical criteria to define carditis and excluding cases where the diagnosis was doubtful. The duration of the study, which included long-term follow-up, was 7 years. The results failed to show that prednisone at this dosage and frequency was of any benefit either in the short-term clinical response or in the long-term follow-up with regard to later requirement of valvular surgery (using the 5% level of significance). Other findings were that one-third of cases improved with time, irrespective of treatment, most of them having mild to moderate carditis initially. Acute rheumatic fever (ARF) remains the leading cause of acquired heart disease in children worldwide. No therapeutic agent has been shown to alter the clinical outcome of the acute illness. Immunological mechanisms appear to be involved in the pathogenesis of ARF. Intravenous immunoglobulin (IVIG), a proven immunomodulator, may benefit cardiac conditions of an autoimmune nature. We investigated whether IVIG modified the natural history of ARF by reducing the extent and severity of carditis.
                This prospective, double-blind, randomized, placebo-controlled trial evaluated IVIG in patients with a first episode of rheumatic fever, stratifying patients by the presence and severity of carditis before randomization. Patients were randomly allocated to receive 1 g/kg IVIG on days 1 and 2 and 0.4 g/kg on days 14 and 28, or they received a placebo infusion. Clinical, laboratory, and echocardiographic evaluation was performed at 0, 2, 4, 6, 26, and 52 weeks. Fifty-nine patients were treated, of whom 39 had carditis (including 4 subclinical) and/or migratory polyarthritis (n=39). There was no difference between groups in the rate of normalization of the erythrocyte sedimentation rate or acute-phase proteins at the 6-week follow-up. On echocardiography, 59% in the IVIG group and 69% in the placebo group had carditis at baseline. There was no significant difference in the cardiac outcome, including the proportion of valves involved, or in the severity of valvar regurgitation at 1 year. At 1 year, 41% of the IVIG and 50% of the placebo group had carditis.
                IVIG did not alter the natural history of ARF, with no detectable difference in the clinical, laboratory, or echocardiographic parameters of the disease process during the subsequent 12 months. nan
There is little evidence of benefit from using corticosteroids or intravenous immunoglobulins to reduce the risk of heart valve lesions in patients with acute rheumatic fever. The antiquity of most of the trials restricted adequate statistical analysis of the data and acceptable assessment of clinical outcomes by current standards. Additionally there was substantial risk of bias, so results should be viewed with caution. New randomised controlled trials in patients with acute rheumatic fever to assess the effects of corticosteroids such as oral prednisone and intravenous methylprednisolone, and other new anti-inflammatory agents are warranted. Advances in echocardiography will allow for more objective and precise assessments of cardiac outcomes.