Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (491 page)

   
CNS
: A significant proportion of AIDS patients with clinically significant pulmonary cryptococcosis progress to cryptococcal meningoencephalitis or infection in other organs. Frequent symptoms include altered mental status, fever, headache, seizures, and visual disturbances.

   
Bone and joint
: Osteomyelitis usually occurs in vertebrae or bony prominences due to hematogenous spread from a primary pulmonary infection. Cryptococcal arthritis may occur by spread from a contiguous osteomyelitis.

   
Lymphadenopathy
: usually cervical or supraclavicular.

   
Prostate
: Asymptomatic, persistent infection of the prostate may occur, most commonly in AIDS patients, and serves as a reservoir for recurrent infection.

   
Skin
: May represent primary infection but usually represents hematogenous dissemination from a primary pulmonary infection. A wide variety of cutaneous lesions have been described.

   Laboratory Findings

Radiology
: In immunocompetent patients, solitary or few noncalcified nodules are most commonly seen. Cavitation is uncommon. In AIDS patients, bilateral interstitial infiltrates, which may mimic
Pneumocystis jirovecii
or other opportunistic infection, are common.

Gram stain
: Gram stain may demonstrate yeast consistent with
C. neoformans
.

Culture
:
Cryptococcus neoformans
may be isolated from 90 to 100% of infected specimens submitted from patients with cryptococcosis. Coinfection with other opportunistic pathogens has been reported in pulmonary cryptococcosis in AIDS patients.

Histopathology
:
Cryptococcus neoformans
cells may be seen in biopsy material using a variety of stains, including H&E, silver, Fontana-Masson, and mucicarmine.

Serology
: Serology is not useful for diagnosis of acute cryptococcal infection.

Cryptococcal antigen (CA)
: Detection of specific polysaccharide antigen is sensitive and specific for diagnosis of cryptococcosis. LA assays are most commonly used and provide rapid results. CA can be detected in CSF >90% of patients with cryptococcal meningitis. Serum CA may also be used as a less sensitive screen for meningitis or cryptococcal infection at other sites but should be confirmed by culture of the infected site.

CSF CA titers
are useful for predicting outcome and monitoring therapy in AIDS patients with cryptococcal meningoencephalitis. Patients with an initial titer of ≤1:2,048 predict a favorable outcome. Relapse is likely in patients with persistently elevated CA titers in spite of effective antifungal therapy. False-positive CA tests may be caused by RF, cross-reaction with
Trichosporon beigelii
, or
Capnocytophaga canimorsus
or syneresis fluid from culture media. The EIA does not show a prozone effect and is not affected by RF. The turnaround time for EIA results is longer than for LA testing.

Laboratory findings (cryptococcal meningitis)
: Meningitis should be considered, regardless of symptoms, in immunocompromised patients with pulmonary cryptococcosis, and relevant diagnostic testing performed. Relapse is less frequent when increase in protein and cells is marked rather than moderate. Poor prognosis is suggested if initial CSF examination shows positive India ink preparation, low glucose (<20 mg/dL), and low WBC count (<20/μL). CBC and ESR usually remain normal.

CSF findings
: Positive culture is related to CSF volume submitted and is improved when ≥10 mL is available. Protein is increased in 90% of patients (<500 mg/dL). Glucose is moderately decreased in approximately 55% of patients. CSF cell count is almost always increased, but ≤800 cells (more lymphocytes than leukocytes).

FUSARIOSIS

   Definition

Fusariosis is caused by infection with species of the genus
Fusarium
. These fungi form septate, nonpigmented hyphae. These fungi are saprophytic with a wide distribution in the environment. Disease is transmitted primarily by inhalation or direct inoculation, usually at a site of trauma. Proliferation at the site of inoculation may result in localized infection or disseminated disease.

   Who Should Be Suspected?

Major risk factors for invasive infection include hematologic malignancy, especially in patients with hematopoietic stem cell transplantation, glucocorticoid treatment, prolonged neutropenia, and disruption of skin integrity (e.g., burns, long-term central venous catheter placement, trauma). Significant disease is uncommon in immunocompetent patients. As with other opportunistic molds, broad range of disease may be caused by
Fusarium
, from superficial and allergic, to locally invasive, to disseminated, multiorgan disease. Affected patients and clinical manifestations include the following:

   
Immunocompetent patients
: Localized infection is most commonly seen; onychomycosis and keratitis are the most common types of infection. Infections at other sites, including sinusitis, pulmonary infection, and foreign body– associated infection, are described but occur infrequently. Keratitis occurs almost exclusively in contact lens users and may be associated with use of specific lens solutions.