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 Stoser, Marilyn M. Wagener, Nina Singh

Research output: Contribution to journalArticle

35 Citations (Scopus)

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 (X2 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.

Original languageEnglish (US)
Pages (from-to)36-44
Number of pages9
JournalClinical Infectious Diseases
Volume60
Issue number1
DOIs
StatePublished - Jan 1 2015

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Immune Reconstitution Inflammatory Syndrome
Cryptococcosis
Immunosuppression
Transplants
Central Nervous System Diseases
Odds Ratio
Transplant Recipients
Fungemia
Graft Rejection
Neuroimaging

Keywords

  • Cryptococcus
  • Fungal infections
  • Immunosuppression
  • Transplant

ASJC Scopus subject areas

  • Medicine(all)
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis : Implications for the management of immunosuppression. / Sun, Hsin Yun; Alexander, Barbara D.; Huprikar, Shirish; Forrest, Graeme N.; Bruno, Didier; Lyon, G. Marshall; Wray, Dannah; Johnson, Leonard B.; Sifri, Costi D.; Razonable, Raymund R; Morris, Michele I.; Stoser, Valentina; Wagener, Marilyn M.; Singh, Nina.

In: Clinical Infectious Diseases, Vol. 60, No. 1, 01.01.2015, p. 36-44.

Research output: Contribution to journalArticle

Sun, HY, Alexander, BD, Huprikar, S, Forrest, GN, Bruno, D, Lyon, GM, Wray, D, Johnson, LB, Sifri, CD, Razonable, RR, Morris, MI, Stoser, V, Wagener, MM & Singh, N 2015, 'Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis: Implications for the management of immunosuppression', Clinical Infectious Diseases, vol. 60, no. 1, pp. 36-44. https://doi.org/10.1093/cid/ciu711
Sun, Hsin Yun ; Alexander, Barbara D. ; Huprikar, Shirish ; Forrest, Graeme N. ; Bruno, Didier ; Lyon, G. Marshall ; Wray, Dannah ; Johnson, Leonard B. ; Sifri, Costi D. ; Razonable, Raymund R ; Morris, Michele I. ; Stoser, Valentina ; Wagener, Marilyn M. ; Singh, Nina. / Predictors of immune reconstitution syndrome in organ transplant recipients with cryptococcosis : Implications for the management of immunosuppression. In: Clinical Infectious Diseases. 2015 ; Vol. 60, No. 1. pp. 36-44.
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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 (X2 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.",
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T2 - Implications for the management of immunosuppression

AU - Sun, Hsin Yun

AU - Alexander, Barbara D.

AU - Huprikar, Shirish

AU - Forrest, Graeme N.

AU - Bruno, Didier

AU - Lyon, G. Marshall

AU - Wray, Dannah

AU - Johnson, Leonard B.

AU - Sifri, Costi D.

AU - Razonable, Raymund R

AU - Morris, Michele I.

AU - Stoser, Valentina

AU - Wagener, Marilyn M.

AU - Singh, Nina

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 (X2 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.

AB - 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 (X2 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.

KW - Cryptococcus

KW - Fungal infections

KW - Immunosuppression

KW - Transplant

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