Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis: implications for the management of immunosuppression.
Hsin-Yun Sun, Barbara D Alexander, Shirish Huprikar, Graeme N Forrest, Didier Bruno, G Marshall Lyon, Dannah Wray, Leonard B Johnson, Costi D Sifri, Raymund R Razonable, Michele I Morris, Valentina Stosor, Marilyn M Wagener, Nina Singh
Author Information
Hsin-Yun Sun: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei.
Barbara D Alexander: Duke University Medical Center, Durham, North Carolina.
Shirish Huprikar: Icahn School of Medicine at Mount Sinai, New York, New York.
Graeme N Forrest: University of Maryland School of Medicine, Baltimore.
Didier Bruno: Department of Internal Medicine, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
G Marshall Lyon: Department of Medicine, Emory University, Atlanta, Georgia.
Dannah Wray: Medical University of South Carolina, Charleston.
Leonard B Johnson: St John Medical Center, Detroit, Michigan.
Costi D Sifri: Department of Medicine, University of Virginia, Charlottesville.
Raymund R Razonable: Department of Medicine, Mayo Clinic, Rochester, Minnesota.
Michele I Morris: Miller School of Medicine, University of Miami, Florida.
Valentina Stosor: Department of Medicine, Northwestern University, Chicago, Illinois.
Marilyn M Wagener: Department of Medicine, University of Pittsburgh, Pennsylvania.
Nina Singh: Department of Medicine, University of Pittsburgh, Pennsylvania.
BACKGROUND: Risk factors including how changes in immunosuppression influence the occurrence of immune reconstitution syndrome (IRS) in solid organ transplant (SOT) recipients with cryptococcosis have not been fully defined. METHODS: SOT recipients with cryptococcosis were identified and followed for 12 months. IRS was defined based on previously proposed criteria. RESULTS: Of 89 SOT recipients, 13 (14%) developed IRS. Central nervous system (CNS) disease (adjusted odds ratio [AOR], 6.23; P = .03) and discontinuation of calcineurin inhibitor (AOR, 5.11; P = .02) were independently associated with IRS. Only 2.6% (1/13) of the patients without these risk factors developed IRS compared with 18.8% (6/32) with 1 risk factor, and 50% (6/12) with both risk factors (χ(2) for trend, P = .0001). Among patients with CNS disease, those with neuroimaging abnormalities (P = .03) were more likely to develop IRS, irrespective of serum or CSF cryptococcal antigen titers and fungemia. Graft rejection after cryptococcosis was observed in 15.4% (2/13) of the patients with IRS compared with 2.6% (2/76) of those without IRS (P = .07). CONCLUSIONS: We determined variables that pose a risk for IRS and have shown that discontinuation of calcineurin inhibitors was independently associated with 5-fold increased risk of IRS in transplant recipients with cryptococcosis.