Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (490 page)

   
CF antibodies
: CF assays primarily reflect the presence of IgG antibody. These antibodies typically develop later but are more persistent than precipitin antibodies. High CF titers are more commonly seen in patients with extensive infection. Changes in CF titer may be used to predict progression or regression of disease.

   
EIA
: EIA techniques have been developed and are sensitive and specific for detection of IgG and IgM antibodies in serum and CSF. EIA methods represent the most efficient serologic method, but results may not correlate exactly with other methods.

   
LA
: These methods are convenient in resource-limited settings, but the increased occurrence of false-positive reactions limits their use.

   
Precipitin antibodies
: Carbohydrate cell wall antigen reagents are used to detect specific antibody by precipitin formation. Precipitin antibodies are primarily of the IgM class. Approximately 90% of patients develop precipitin antibodies in the first weeks of symptomatic infection, but levels fall with resolution of infection. Cross-reactions with
Histoplasma capsulatum
and
B. dermatitis
are reported.

   
Skin test reactivity
: Patients with coccidioidomycosis develop a hypersensitivity to specific antigens, manifested by erythema and induration at the site of intradermal injection. Skin testing may be useful for seroepidemiologic studies. The utility of testing is limited for acute disease because skin test reactivity cannot differentiate between acute and past infection; many patients with coccidioidomycosis may be anergic on the basis of their underlying disease or therapy.

Routine laboratory
: Most routine laboratory tests are unremarkable. Decreased peripheral blood lymphocyte count, increased ESR, or slight elevation of WBC is often seen; eosinophilia may be seen.

Radiology
: Abnormal radiologic studies are common in pulmonary and extrapulmonary disease and help delineate the extent of disease. Bone scans can be used to screen for osteomyelitis.

   
Septic arthritis
: Arthroscopy with synovial biopsy may be used to establish infection.

   
Meningitis
: Culture is usually negative. Mononuclear pleocytosis (100–200 WBCs/μL), decreased glucose, increased protein. Detection of IgG-specific antibody is diagnostic of meningitis in undiluted CSF and is detected in approximately 75% of patients with
Coccidioides
meningitis. Serology may be used to document response to antifungal therapy. Detection of specific IgG may be used to document relapse for 1–2 years after end of therapy. Serum titers are often negative or only borderline positive.

CRYPTOCOCCOSIS (
CRYPTOCOCCUS NEOFORMANS
)

   Definition

Several species of the genus
Cryptococcus
, including
Cryptococcus neoformans
and
Cryptococcus gattii
, are capable of causing disease in humans. The typical geographic distribution of
C. gattii
is restricted to tropical and subtropical regions with eucalyptus trees.
Cryptococcus neoformans
, on the other hand, has a worldwide distribution and is responsible for most cases of cryptococcosis worldwide. Organisms are able to survive in the gut of pigeons and in dried pigeon droppings; this is likely responsible for wide distribution through the environment. Infection is acquired by inhalation of organisms present in the environment, and personto-person transmission does not occur.

   Who Should Be Suspected?

In immunocompetent individuals, exposure usually results in self-limited asymptomatic or mild disease; progressive and chronic disease is uncommon. Immunocompromised patients, however, are at risk for more severe disease with progression to extrapulmonary tissues. Conditions associated with increased risk of disseminated cryptococcosis include AIDS, glucocorticoid therapy, organ transplantation, malignancy, and/or sarcoidosis. Types of infection include the following:

   
Pulmonary
: Symptoms of pulmonary cryptococcosis include chest pain, cough, dyspnea, fever, sputum production, and weight loss. Hematogenous dissemination may occur.