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
  1. Hsin-Yun Sun: Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei.
  2. Barbara D Alexander: Duke University Medical Center, Durham, North Carolina.
  3. Shirish Huprikar: Icahn School of Medicine at Mount Sinai, New York, New York.
  4. Graeme N Forrest: University of Maryland School of Medicine, Baltimore.
  5. Didier Bruno: Department of Internal Medicine, Hospital Universitario Fundación Favaloro, Buenos Aires, Argentina.
  6. G Marshall Lyon: Department of Medicine, Emory University, Atlanta, Georgia.
  7. Dannah Wray: Medical University of South Carolina, Charleston.
  8. Leonard B Johnson: St John Medical Center, Detroit, Michigan.
  9. Costi D Sifri: Department of Medicine, University of Virginia, Charlottesville.
  10. Raymund R Razonable: Department of Medicine, Mayo Clinic, Rochester, Minnesota.
  11. Michele I Morris: Miller School of Medicine, University of Miami, Florida.
  12. Valentina Stosor: Department of Medicine, Northwestern University, Chicago, Illinois.
  13. Marilyn M Wagener: Department of Medicine, University of Pittsburgh, Pennsylvania.
  14. Nina Singh: Department of Medicine, University of Pittsburgh, Pennsylvania.

Abstract

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.

Keywords

References

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MeSH Term

Aged
Calcineurin Inhibitors
Cryptococcosis
Female
Humans
Immune Reconstitution Inflammatory Syndrome
Immunosuppression Therapy
Male
Middle Aged
Organ Transplantation
Prevalence
Risk Factors
Transplant Recipients

Chemicals

Calcineurin Inhibitors

Word Cloud

Created with Highcharts 10.0.0IRSrecipientsP=risktransplantcryptococcosisfactorsimmunosuppressionSOT2patientsimmunereconstitutionsyndromeorgandefineddevelopedCNSdisease03discontinuationcalcineurinindependentlyassociated6%withoutcomparedBACKGROUND:RiskincludingchangesinfluenceoccurrencesolidfullyMETHODS:identifiedfollowed12monthsbasedpreviouslyproposedcriteriaRESULTS:891314%Centralnervoussystemadjustedoddsratio[AOR]623inhibitorAOR511021/13188%6/321factor50%6/12χtrend0001AmongneuroimagingabnormalitieslikelydevelopirrespectiveserumCSFcryptococcalantigentitersfungemiaGraftrejectionobserved154%2/132/7607CONCLUSIONS:determinedvariablesposeshowninhibitors5-foldincreasedPredictorscryptococcosis:implicationsmanagementCryptococcusfungalinfections

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