title: Rituximab-associated progressive multifocal leukoencephalopathy in rheumatoid arthritis.
abstract: OBJECTIVE
  To describe the development of progressive multifocal leukoencephalopathy (PML) in patients with rheumatoid arthritis (RA) treated with rituximab.
  
  
  METHODS
  Case study.
  
  
  METHODS
  Clinical care for patients with rheumatologic diseases. Most were referred to academic centers for care after diagnosis (Washington University, St Louis, Missouri; Karolinska Insitute, Stockholm, Sweden; and Royal Melbourne Hospital, Melbourne, Australia) while one was cared for in a neurology practice in Dallas, Texas, with consultation by an academic neurovirologist from the University of Colorado in Denver.
  
  
  METHODS
  Four patients developing PML in the setting of rituximab therapy for RA.
  
  
  METHODS
  Rituximab therapy.
  
  
  METHODS
  Clinical and pathological observations.
  
  
  RESULTS
  Four patients from an estimated population of 129 000 exposed to rituximab therapy for RA are reported in whom PML developed after administration of this drug. All were women older than 50 years, commonly with Sjögren syndrome and a history of treatment for joint disease ranging from 3 to 14 years. One case had no prior biologic and minimal immunosuppressive therapy. Progressive multifocal leukoencephalopathy presented as a progressive neurological disorder, with diagnosis confirmed by detection of JC virus DNA in the cerebrospinal fluid or brain biopsy specimen. Two patients died in less than 1 year from PML diagnosis, while 2 remain alive after treatment withdrawal. Magnetic resonance scans and tissue evaluation confirmed the frequent development of inflammatory PML during the course of the disease.
  
  
  CONCLUSIONS
  These cases suggest an increased risk, about 1 case per 25 000 individuals, of PML in patients with RA being treated with rituximab. Inflammatory PML may occur in this setting even while CD20 counts remain low.
authors.affiliation: Department of Neurology, Washington University, St Louis, MO 63110, USA. cliffordd@neuro.wustl.edu
authors.forename: David B
authors.initials: DB
authors.lastname: Clifford
authors.forename: Beau
authors.initials: B
authors.lastname: Ances
authors.forename: Craig
authors.initials: C
authors.lastname: Costello
authors.forename: Shari
authors.initials: S
authors.lastname: Rosen-Schmidt
authors.forename: Magnus
authors.initials: M
authors.lastname: Andersson
authors.forename: Deborah
authors.initials: D
authors.lastname: Parks
authors.forename: Arie
authors.initials: A
authors.lastname: Perry
authors.forename: Raju
authors.initials: R
authors.lastname: Yerra
authors.forename: Robert
authors.initials: R
authors.lastname: Schmidt
authors.forename: Enrique
authors.initials: E
authors.lastname: Alvarez
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Tyler
mesh_terms: D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D006801:Humans; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced* / Q000473:pathology*; D008875:Middle Aged; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000069283:Rituximab