title: Safety of intravenous immunoglobulin in the treatment of juvenile dermatomyositis: adverse reactions are associated with immunoglobulin A content.
abstract: OBJECTIVE
  Anecdotal reports have suggested differences in children's tolerance to different intravenous immunoglobulin products; however, there has been little research on this issue. We sought to determine whether different intravenous immunoglobulin products used in the treatment of juvenile dermatomyositis are equally well tolerated by patients and, if not, whether differences in tolerance are linked to immunoglobulin A content.
  
  
  METHODS
  The intravenous immunoglobulin infusion history (product given and history of adverse events) of patients who were attending the juvenile dermatomyositis clinic at the Hospital for Sick Children from 1986 to 2005 was reviewed. Products with an immunoglobulin A content of >15 microg/mL were classified as "high immunoglobulin A." Data were analyzed by using logistic regression models adjusted for repeated measures.
  
  
  RESULTS
  Thirty-eight patients with juvenile dermatomyositis received 1056 infusions at the Hospital for Sick Children. Adverse events were reported on 92 occasions (9%), affecting 25 patients (66%), a frequency that is higher than that usually reported in adult patients (<1%-5%). Adverse events were reported more often with products that contained high immunoglobulin A (15.0% vs 8.0%). These were accounted for specifically by fever (8.0% vs 1.0%), lethargy or malaise (2.0% vs 0.1%), and nausea or vomiting (5.0% vs 1.0%). Of the possible pharmacologic predictors, including dose, immunoglobulin G concentration, immunoglobulin A level, pH, glycine content, sugar content, sodium content, and osmolality, only immunoglobulin A level was significantly associated with adverse events.
  
  
  CONCLUSIONS
  Intravenous immunoglobulin was found to be safe and well tolerated by most children with juvenile dermatomyositis. However, in contrast to adult studies, we found that significant differences existed in tolerance to different intravenous immunoglobulin products, most likely because of immunoglobulin A concentration. This study confirms anecdotal reports that a high level of immunoglobulin A in intravenous immunoglobulin is less well tolerated by children and provides evidence that product choice is important in pediatrics.
authors.affiliation: Division of Rheumatology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Cedric
authors.initials: C
authors.lastname: Manlhiot
authors.forename: Pascal N
authors.initials: PN
authors.lastname: Tyrrell
authors.forename: Lisa
authors.initials: L
authors.lastname: Liang
authors.forename: Adelle R
authors.initials: AR
authors.lastname: Atkinson
authors.forename: Wendy
authors.initials: W
authors.lastname: Lau
authors.forename: Brian M
authors.initials: BM
authors.lastname: Feldman
mesh_terms: D000293:Adolescent; D000553:Ambulatory Care; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003882:Dermatomyositis / Q000175:diagnosis* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006776:Hospitals, Pediatric; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D020714:Maximum Tolerated Dose; D015999:Multivariate Analysis; D009864:Ontario; D011336:Probability; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D007070:Immunoglobulin A; D016756:Immunoglobulins, Intravenous