Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease

N Engl J Med. 2005 Jul 28;353(4):362-8. doi: 10.1056/NEJMoa051586. Epub 2005 Jun 9.

Abstract

The prior diagnosis of fatal astrocytoma in a 60-year-old man with Crohn's disease treated with natalizumab, a monoclonal antibody against alpha4 integrins, was reclassified as JC virus-related progressive multifocal leukoencephalopathy (PML). Analysis of frozen serum samples showed that JC virus DNA had appeared in the serum three months after the initiation of open-label natalizumab monotherapy and two months before the appearance of symptomatic PML. There was staining of the brain lesion for polyomavirus. This case report, along with two others, suggests that anti-alpha4-integrin therapy can result in JC virus-induced PML.

Publication types

  • Case Reports

MeSH terms

  • Antibodies, Monoclonal / adverse effects*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Astrocytoma / diagnosis
  • Brain / pathology
  • Brain / virology
  • Brain Neoplasms / diagnosis
  • Crohn Disease / drug therapy*
  • DNA, Viral / blood
  • Diagnostic Errors
  • Fatal Outcome
  • Genotype
  • Humans
  • Integrin alpha4 / immunology*
  • JC Virus* / genetics
  • JC Virus* / isolation & purification
  • Leukocyte Count
  • Leukoencephalopathy, Progressive Multifocal / chemically induced*
  • Leukoencephalopathy, Progressive Multifocal / pathology
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Natalizumab
  • Opportunistic Infections / chemically induced*
  • Opportunistic Infections / pathology
  • Viral Load

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • DNA, Viral
  • Natalizumab
  • Integrin alpha4