Pulmonary Cryptococcosis in Solid Organ Transplant Recipients: Clinical Relevance of Serum Cryptococcal Antigen
Nina Singh
14
Barbara D. Alexander
13
Olivier Lortholary
12
Franc oise Dromer
Krishan L. Gupta
0
George T. John
2
Ramon del Busto
11
Goran B. Klintmalm
19
Jyoti Somani
18
G. Marshall Lyon
18
Kenneth Pursell
17
Valentina Stosor
16
Patricia Mu noz
10
Ajit P. Limaye
21
Andre C. Kalil
20
Timothy L. Pruett
15
Julia Garcia-Diaz
9
Atul Humar
1
Sally Houston
6
Andrew A. House
3
Dannah Wray
4
Susan Orloff
5
Lorraine A. Dowdy
7
Robert A. Fisher
8
Joseph Heitman
13
Marilyn M. Wagener
14
Shahid Husain
14
0
Postgraduate Institute of Medical Education and Research
, Chandigarh
1
University Health Network, Toronto General Hospital
,
Toronto
2
Christian Medical College Hospital
, Vellore,
India
3
University of Western Ontario
,
London
, Ontario,
Canada
4
Medical University of South Carolina
,
Charleston
5
Oregon Health Sciences University
, Portland
6
University of South Florida
, Tampa
7
University of Miami
, Miami,
Florida
8
Virginia Commonwealth University
,
Richmond
9
Ochsner Clinic
, New Orleans,
Louisiana
10
Hospital General Universitario Gregorio Maranon
,
Madrid, Spain
11
Henry Ford Hospital
, Detroit,
Michigan
12
Faculte de Medecine Paris Descartes, Hopital Necker-Enfants Malades,
Paris, France
13
Duke University Medical Center
,
Durham, North Carolina
14
University of Pittsburgh
,
Pennsylvania
15
University of Virginia
,
Charlottesville
16
Northwestern University
,
Chicago, Illinois
17
University of Chicago
18
Emory University
,
Atlanta, Georgia
19
Baylor University Medical Center
,
Dallas, Texas
20
University of Nebraska
, Omaha
21
University of Washington
,
Seattle
Background. The role of serum cryptococcal antigen in the diagnosis and determinants of antigen positivity in solid organ transplant (SOT) recipients with pulmonary cryptococcosis has not been fully defined. Methods. We conducted a prospective, multicenter study of SOT recipients with pulmonary cryptococcosis during 1999-2006. Results. Forty (83%) of 48 patients with pulmonary cryptococcosis tested positive for cryptococcal antigen. Patients with concomitant extrapulmonary disease were more likely to have a positive antigen test result (P p .018), and antigen titers were higher in patients with extrapulmonary disease (P p .003 ) or fungemia (P p .045). Patients with single nodules were less likely to have a positive antigen test result than were those with all other radiographic presentations (P p .053). Among patients with isolated pulmonary cryptococcosis, lung transplant recipients were less likely to have positive cryptococcal antigen test results than were recipients of other types of SOT (P p .003). In all, 38% of the patients were asymptomatic or had pulmonary cryptococcosis detected as an incidental finding. Nodular densities or mass lesions were more likely to present as asymptomatic or incidentally detected pulmonary cryptococcosis than as pleural effusions and infiltrates (P p .008). Conclusions. A positive serum cryptococcal antigen test result in SOT recipients with pulmonary cryptococcosis appears to reflect extrapulmonary or more advanced radiographic disease. Cryptococcosis occurs in 0.3%-5.3% and in a mean of 2.8% of solid organ transplant (SOT) recipients [1-3] Twenty-five percent to 54% of transplant recipients with cryptococcosis have pulmonary disease, and in
-
6%33%, disease is limited to the lungs [4, 5].
Disseminated infection, including CNS disease and fungemia,
occur in 52%61% and 20%25% of SOT recipients,
respectively [2, 6, 7].
Cryptococcal antigen assays that measure
polysaccharide released from Cryptococcus neoformans have
proven to be valuable diagnostic tests for cryptococcosis
[810]. The sensitivity and specificity of serum antigen
for the diagnosis of cryptococcal meningoencephalitis
largely approaches that of the CSF [11, 12]. The test,
however, is considered to be of limited value for the
diagnosis of pulmonary cryptococcosis [1317]. Case
series have documented a wide variability in the
frequency of positive serum antigen test results, ranging
from 33% to 100% among SOT recipients with pulmonary
cryptococcosis [2, 5, 1821]. The diagnostic utility and
determinants of serum cryptococcal antigen positivity in SOT
recipients with pulmonary cryptococcosis have not been fully
defined. A prospective database comprising data for a large
cohort of organ transplant recipients with cryptococcosis
offered a unique opportunity to address these issues [6].
Therefore, the goals of this study were to determine the role of serum
cryptococcal antigen in the diagnosis of pulmonary
cryptococcosis, to determine which variables influence antigen
positivity, and to assess prognostic implications in SOT recipients
with pulmonary cryptococcosis.
The study population was derived from a cohort of organ
transplant recipients with cryptococcosis in a prospectively
conducted multicenter study during 19992006. A detailed
description of this cohort has been published elsewhere [6]. None
of the patients were HIV infected. Cryptococcal disease (...truncated)