EIN members recently discussed cryptococcal testing and related diagnostic issues. A member in Texas described two patients with an “unusual circumstance.” The first was a patient with alcoholic cirrhosis, with fevers but no headaches or neurological symptoms. “Blood cultures grew Cryptococcus neoformans, but serum antigen was negative (repeated twice). There was no dissemination to the central nervous system (CNS)—no growth from cerebrospinal fluid (CSF); cryptococcal antigen was also negative.”
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The second case was a patient with lymphoma who had undergone chemotherapy (with resultant neutropenia) and developed pneumonitis. According to the pathology report, no granulomas were present. Findings from a chest CT involved both lungs. Bronchoalveolar lavage specimens grew Cryptococcus neoformans. “Again, there was no involvement of the CNS proven by culture, and cryptococcal antigen was negative as well,” the member noted.
The patients were seen in different hospitals, and assays were performed by different labs. “According to the literature and guidelines, the Cryptococcus antigen assay is supposed to be very sensitive and specific,” the member wrote, asking for comments.
“Was the prozone phenomenon ruled out?” a respondent in Michigan asked. “The titers may have been very high. Though rare, the other possibility is a non-capsular Cryptococcus isolate causing this patient’s disease.”
Another member suggested the “postzone phenomenon—an antigen version of the prozone phenomenon has been described with latex agglutination CrAg.” The member cited a letter to the editor in the Aug. 13, 1982, issue of the Journal of the American Medical Association. “Try diluting the serum and then repeat the test.”
An EIN member in Florida, referencing a December 2003 Chest article, noted that “primary cryptococcoma of the lung usually has a negative serum cryptococcal antigen (CA). In a study of cryptococcal meningitis, the sensitivity of serum CA was 91.4 percent, and the specificity 83.3 percent (J Med Assoc Thai. 1999;82:65-71). So it is possible to have negative serum CA with fungemia and disseminated infections. Also, a capsule deficient strain of Cryptococcus will be serum CA negative,” the member wrote, citing a letter to the editor in the April 1985 issue of Lancet.
A respondent in Oregon offered another possibility: “Are you sure it’s neoformans and not gattii? In Oregon we’ve found serum crypto Ag to be relatively insensitive for C. gattii lung infection.”
“Small colony variants have been described as a potential cause of this uncommon occurrence,” an EIN member in California wrote, citing a 2006 article from the Scandinavian Journal of Infectious Diseases. “We have had few such cases: One occurring in a 74-year-old non-immunocompromised patient with positive CSF and blood cultures for Cryptococcus neoformans (not gattii) with negative enzyme-linked immuno assay (EIA) and latex agglutination antigen, and another in a 64-year-old female with adrenocortical carcinoma, positive serum cryptococcal antigen (1:375 EIA), negative CSF cryptococcal antigen (EIA), and positive CSF culture for Cryptococcus neoformans (not gattii).”
A recent letter published in Emerging Infectious Diseases summarizes the results of a related EIN survey of ID physicians. The survey focused on the clinical approach to diagnosing cryptococcal infections, the relative regional frequency of C. gattii, and the capacity of clinical laboratories to differentiate cryptococcal species.
Additional resources related to cryptococcal disease and diagnosis include:
E-mail the Emerging Infections Network.
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A joint project of IDSA and the Pediatric Infectious Diseases Society (PIDS) with funding from the Centers for Disease Control and Prevention (CDC), EIN tracks emerging infectious diseases and keeps the public health community up to date with new disease trends, difficult cases, and other issues affecting members’ clinical practices. The Network provides a great opportunity for members to share knowledge quickly across large geographical distances. Both IDSA and PIDS members are eligible to join. Click here for more information or to join EIN.
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