title: Practical issues in using eculizumab for children with atypical haemolytic uraemic syndrome in the acute phase: A review of four patients.
abstract: OBJECTIVE
  Recently eculizumab, a monoclonal antibody to C5, was found to improve the disease course of atypical haemolytic uraemic syndrome (aHUS) and has been recommended as the first line treatment by an international consensus guideline. However, several practical issues in the use of eculizumab for the acute phase of aHUS have yet to be resolved.
  
  
  METHODS
  Children who received eculizumab with diagnosis of aHUS between March 2010 and December 2015 at Tokyo Metropolitan Children's Medical Center were enrolled. aHUS was diagnosed according to the haemolytic uraemic syndrome (HUS) criteria after excluding Shiga toxin-inducing Escherichia coli (STEC) -associated HUS and thrombocytopaenic purpura. We retrieved and analyzed data from the electronic medical records at our institution.
  
  
  RESULTS
  We reviewed four patients with suspected aHUS. Eculizumab was discontinued in one patient in whom STEC-HUS was later diagnosed. Treatment was continued in the remaining three patients without recurrence. Practical issues included difficulty in diagnosing aHUS, particularly in the acute phase, risk of infection by encapsulated organisms, especially Neisseria meningitis, and infusion reaction. In addition to issues relating to the acute phase, discontinuing eculizumab in stable patients in the chronic phase must be considered.
  
  
  CONCLUSIONS
  Eculizumab, the first line treatment for children with aHUS, is usually effective. However, certain problems associated with its use require caution to be exercised. As clinical information on eculizumab are still very limited, and the rationale for its long-term use has yet to be established, physicians are advised to exercise care when using eculizumab to manage aHUS.
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Japan.
authors.forename: Chikako
authors.identifier: http://orcid.org/0000-0001-5033-9270
authors.initials: C
authors.lastname: Terano
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Japan.|Division of Nephrology and Rheumatology, National Center for Child Health and Development, Japan.
authors.forename: Kenji
authors.identifier: http://orcid.org/0000-0003-2692-6437
authors.initials: K
authors.lastname: Ishikura
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Japan.
authors.forename: Riku
authors.initials: R
authors.lastname: Hamada
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Kubota
authors.affiliation: Department of Pediatrics, Shiga University of Medical Science, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuda
authors.affiliation: Department of Pediatrics, National Hospital Organization Saitama National Hospital, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Shinozuka
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Harada
authors.affiliation: Department of Bacteriology I, National Institute of Infectious Diseases, Japan.
authors.forename: Sunao
authors.initials: S
authors.lastname: Iyoda
authors.affiliation: Department of Blood Transfusion Medicine, Nara Medical University, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimura
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Japan.|Department of Pediatric Nephrology, Faculty of Medicine, Toho University, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hamasaki
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hataya
authors.affiliation: Department of Nephrology, Tokyo Metropolitan Children's Medical Center, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Honda
mesh_terms: D000367:Age Factors; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000009:adverse effects; D065766:Atypical Hemolytic Uremic Syndrome / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D002675:Child, Preschool; D051056:Complement Inactivating Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D003875:Drug Eruptions / Q000209:etiology; D057286:Electronic Health Records; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000139:chemically induced / Q000276:immunology / Q000382:microbiology; D009894:Opportunistic Infections / Q000139:chemically induced / Q000276:immunology / Q000382:microbiology; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014041:Tokyo; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; C481642:eculizumab
keywords: Atypical haemolytic uraemic syndrome; Children; Eculizumab; Infusion reaction; Meningococcal infection