title: Intravenous immunoglobulin in acute rheumatic fever: a randomized controlled trial.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Starship Children's Hospital, Auckland, New Zealand. ssinfect@ahsl.co.nz
authors.forename: L M
authors.initials: LM
authors.lastname: Voss
authors.forename: N J
authors.initials: NJ
authors.lastname: Wilson
authors.forename: J M
authors.initials: JM
authors.lastname: Neutze
authors.forename: R M
authors.initials: RM
authors.lastname: Whitlock
authors.forename: R V
authors.initials: RV
authors.lastname: Ameratunga
authors.forename: L M
authors.initials: LM
authors.lastname: Cairns
authors.forename: D R
authors.initials: DR
authors.lastname: Lennon
mesh_terms: D000208:Acute Disease; D000209:Acute-Phase Proteins / Q000032:analysis; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D004311:Double-Blind Method; D004452:Echocardiography; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D009205:Myocarditis / Q000473:pathology; D011446:Prospective Studies; D012213:Rheumatic Fever / Q000097:blood / Q000473:pathology / Q000628:therapy*; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D016756:Immunoglobulins, Intravenous; D002097:C-Reactive Protein