title: Persisting mixed cryoglobulinemia in Chikungunya infection.
abstract: BACKGROUND
  Chikungunya virus (CHIKV), an arbovirus, is responsible for a two-stage disabling disease, consisting of an acute febrile polyarthritis for the first 10 days, frequently followed by chronic rheumatisms, sometimes lasting for years. Up to now, the pathophysiology of the chronic stage has been elusive. Considering the existence of occasional peripheral vascular disorders and some unexpected seronegativity during the chronic stage of the disease, we hypothesized the role of cryoglobulins.
  
  
  METHODS
  From April 2005 to May 2007, all travelers with suspected CHIKV infection were prospectively recorded in our hospital department. Demographic, clinical and laboratory findings (anti-CHIKV IgM and IgG, cryoglobulin) were registered at the first consultation or hospitalization and during follow-up.
  
  
  RESULTS
  Among the 66 travelers with clinical suspicion of CHIKV infection, 51 presented anti-CHIKV IgM. There were 45 positive with the serological assay tested at room temperature, and six more, which first tested negative when sera were kept at 4 degrees C until analysis, became positive after a 2-hour incubation of the sera at 37 degrees C. Forty-eight of the 51 CHIKV-seropositive patients were screened for cryoglobulinemia; 94% were positive at least once during their follow-up. Over 90% of the CHIKV-infected patients had concomitant arthralgias and cryoglobulinemia. Cryoglobulin prevalence and level drop with time as patients recover, spontaneously or after short-term corticotherapy. In some patients cryoglobulins remained positive after 1 year.
  
  
  CONCLUSIONS
  Prevalence of mixed cryoglobulinemia was high in CHIKV-infected travelers with long-lasting symptoms. No significant association between cryoglobulinemia and clinical manifestations could be evidenced. The exact prognostic value of cryoglobulin levels has yet to be determined. Responsibility of cryoglobulinemia was suspected in unexpected false negativity of serological assays at room temperature, leading us to recommend performing serology on pre-warmed sera.
authors.affiliation: Laboratoire de Biochimie, Hôpital d'Instruction des Armées Laveran, Marseille, France.
authors.forename: Manuela
authors.initials: M
authors.lastname: Oliver
authors.forename: Marc
authors.initials: M
authors.lastname: Grandadam
authors.forename: Catherine
authors.initials: C
authors.lastname: Marimoutou
authors.forename: Christophe
authors.initials: C
authors.lastname: Rogier
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Botelho-Nevers
authors.forename: Hugues
authors.initials: H
authors.lastname: Tolou
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Moalic
authors.forename: Philippe
authors.initials: P
authors.lastname: Kraemer
authors.forename: Marc
authors.initials: M
authors.lastname: Morillon
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Morand
authors.forename: Pierre
authors.initials: P
authors.lastname: Jeandel
authors.forename: Philippe
authors.initials: P
authors.lastname: Parola
authors.forename: Fabrice
authors.initials: F
authors.lastname: Simon
mesh_terms: D000328:Adult; D000368:Aged; D018354:Alphavirus Infections / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology / Q000821:virology; D002646:Chikungunya virus / Q000502:physiology*; D003449:Cryoglobulinemia / Q000175:diagnosis* / Q000209:etiology* / Q000821:virology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged