An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients.

Nina Singh, Olivier Lortholary, Barbara D Alexander, Krishan L Gupta, George T John, Kenneth Pursell, Patricia Munoz, Goran B Klintmalm, Valentina Stosor, Ramon del Busto, Ajit P Limaye, Jyoti Somani, Marshall Lyon, Sally Houston, Andrew A House, Timothy L Pruett, Susan Orloff, Atul Humar, Lorraine Dowdy, Julia Garcia-Diaz, Andre C Kalil, Robert A Fisher, Shahid Husain, Cryptococcal Collaborative Transplant Study Group
Author Information
  1. Nina Singh: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. nis5+@pitt.edu

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.

Grants

  1. R01 AI054719-01/NIAID NIH HHS

MeSH Term

Adult
Aged
Antifungal Agents
Cohort Studies
Cryptococcosis
Female
Humans
Immune System Diseases
Immunosuppressive Agents
Male
Middle Aged
Mycophenolic Acid
Organ Transplantation
Prednisone
Tacrolimus

Chemicals

Antifungal Agents
Immunosuppressive Agents
Mycophenolic Acid
Prednisone
Tacrolimus

Word Cloud

Created with Highcharts 10.0.0therapyentityneoformansinfectionorgantransplantrecipientsstudypatientsimmunereconstitutionCryptococcus83observedmedian4IRS-like5antifungalCimmunosuppressiveresponsemayBACKGROUND:describesyndromeIRS-likecourseevolutionMETHODS:populationcomprisedcohortconsecutivecryptococcosis2yearsinternationalmulticenterRESULTS:8%weeksinitiationappropriateWorseningclinicalmanifestationsdocumenteddespiteculturesnegativesignificantlylikelyreceivedtacrolimusmycophenolatemofetilprednisoneregimenP=007proposedbasisphenomenonreversalpredominantlyTh2onsetTh1proinflammatoryresultreceipteffectivereductioncessationCONCLUSIONS:demonstratedoccursFurthermoremisconstruedfailureImmunomodulatoryagentsroleadjunctivecasessyndrome-likeillnessassociated

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