An immune reconstitution syndrome-like illness associated with Cryptococcus neoformans infection in organ transplant recipients.
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.
Singh
Nina
N
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. nis5+@pitt.edu
Lortholary
Olivier
O
Alexander
Barbara D
BD
Gupta
Krishan L
KL
John
George T
GT
Pursell
Kenneth
K
Munoz
Patricia
P
Klintmalm
Goran B
GB
Stosor
Valentina
V
del Busto
Ramon
R
Limaye
Ajit P
AP
Somani
Jyoti
J
Lyon
Marshall
M
Houston
Sally
S
House
Andrew A
AA
Pruett
Timothy L
TL
Orloff
Susan
S
Humar
Atul
A
Dowdy
Lorraine
L
Garcia-Diaz
Julia
J
Kalil
Andre C
AC
Fisher
Robert A
RA
Husain
Shahid
S
D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000627:therapeutic use; D015331:Cohort Studies; D003453:Cryptococcosis / Q000188:drug therapy / Q000209:etiology*; D005260:Female; D006801:Humans; D007154:Immune System Diseases / Q000209:etiology*; D007166:Immunosuppressive Agents / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives; D016377:Organ Transplantation / Q000009:adverse effects*; D011241:Prednisone / Q000009:adverse effects; D016559:Tacrolimus / Q000009:adverse effects
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid; D011241:Prednisone; D016559:Tacrolimus