Epidemiology

Immune reconstitution syndrome may occur in organ transplant recipients

Last Updated: 2005-06-01 15:39:14 -0400 (Reuters Health)

NEW YORK (Reuters Health) - Apparently successful treatment of Cryptococcus neoformans infection in organ transplant recipients may be followed by an immune reconstitution syndrome (IRS)-like illness that is potentially fatal, investigators report in the June 15th issue of Clinical infectious Diseases.

IRS "is believed to result from enhanced -- but partially reconstituted -- pathogen-specific, cell-mediated immunity and induction of proinflammatory cytokines, leading to an exaggerated inflammatory reaction," explain Dr. Nina Singh, at the University of Pittsburgh Medical Center, and other members of the Cryptococcal Collaborative Transplant Study Group. IRS has been particularly associated with immune restoration in HIV infection.

Dr. Singh's group reports on a series of 83 organ transplant recipients with cryptococcosis, four of whom developed an IRS-like entity. The patients ranged in age from 34 to 65 years when they underwent transplantation (liver, kidney, or kidney and pancreas) with the initial diagnosis of C. neoformans occurring 3 to 29 months later.

All four were being treated with tacrolimus, mycophenolate mofetil (MMF) and prednisone as the immunosuppressive regimen when the IRS-like entity was detected, compared with 21 of the remaining 79 patients (26.6%, p = 0.007), the authors note, but this was the only significant difference that they identified.

In all four cases, MMF was discontinued and tacrolimus and prednisone decreased or discontinued. Two days to 3 months after instituting antifungal therapy, symptoms of the infection reappeared, C. neoformans titers increased, but the organism could not be grown in culture.

The IRS-syndrome led to forearm amputation in one patient, while one patient died 5 months after his initial infection. One patient died of MI 2 years after the initial infection. The other two patients remain alive 2 to 3 years later.

"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," the study group indicates.

They also speculate that careful use of immunomodulatory agents such as interferon-gamma may be of use in such cases, with monitoring of serum levels to avoid a heightened inflammatory response or allograft rejection.

J Infect Dis 2005;40:1756-1761.