title: An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients.
abstract: BACKGROUND
  We describe an immune reconstitution syndrome (IRS)-like entity in the course of evolution of Cryptococcus neoformans infection in organ transplant recipients.
  
  
  METHODS
  The study population comprised a cohort of 83 consecutive organ transplant recipients with cryptococcosis who were observed for a median of 2 years in an international, multicenter study.
  
  
  RESULTS
  In 4 (4.8%) of the 83 patients, an IRS-like entity was observed a median of 5.5 weeks after the initiation of appropriate antifungal therapy. Worsening of clinical manifestations was documented, despite cultures being negative for C. neoformans. These patients were significantly more likely to have received tacrolimus, mycophenolate mofetil, and prednisone as the regimen of immunosuppressive therapy than were all other patients (P = .007). The proposed basis of this phenomenon is reversal of a predominantly Th2 response at the onset of infection to a Th1 proinflammatory response as a result of receipt of effective antifungal therapy and a reduction in or cessation of immunosuppressive therapy.
  
  
  CONCLUSIONS
  This study demonstrated that an IRS-like entity occurs in organ transplant recipients with C. neoformans infection. Furthermore, this entity may be misconstrued as a failure of therapy. Immunomodulatory agents may have a role as adjunctive therapy in such cases.
authors.affiliation: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. nis5+@pitt.edu
authors.forename: Nina
authors.initials: N
authors.lastname: Singh
authors.forename: Olivier
authors.initials: O
authors.lastname: Lortholary
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Alexander
authors.forename: Krishan L
authors.initials: KL
authors.lastname: Gupta
authors.forename: George T
authors.initials: GT
authors.lastname: John
authors.forename: Kenneth
authors.initials: K
authors.lastname: Pursell
authors.forename: Patricia
authors.initials: P
authors.lastname: Munoz
authors.forename: Goran B
authors.initials: GB
authors.lastname: Klintmalm
authors.forename: Valentina
authors.initials: V
authors.lastname: Stosor
authors.forename: Ramon
authors.initials: R
authors.lastname: del Busto
authors.forename: Ajit P
authors.initials: AP
authors.lastname: Limaye
authors.forename: Jyoti
authors.initials: J
authors.lastname: Somani
authors.forename: Marshall
authors.initials: M
authors.lastname: Lyon
authors.forename: Sally
authors.initials: S
authors.lastname: Houston
authors.forename: Andrew A
authors.initials: AA
authors.lastname: House
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Pruett
authors.forename: Susan
authors.initials: S
authors.lastname: Orloff
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
authors.forename: Lorraine
authors.initials: L
authors.lastname: Dowdy
authors.forename: Julia
authors.initials: J
authors.lastname: Garcia-Diaz
authors.forename: Andre C
authors.initials: AC
authors.lastname: Kalil
authors.forename: Robert A
authors.initials: RA
authors.lastname: Fisher
authors.forename: Shahid
authors.initials: S
authors.lastname: Husain
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use; D015331:Cohort Studies; D003453:Cryptococcosis / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D006801:Humans; D007154:Immune System Diseases / Q000209:etiology*; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives; D016377:Organ Transplantation / Q000009:adverse effects*; D011241:Prednisone / Q000009:adverse effects; D016559:Tacrolimus / Q000009:adverse effects
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus