Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (489 page)

   Laboratory Findings

Culture
: Positive cultures from normally sterile sites support the diagnosis, but cultures must be interpreted with caution to rule out contamination with endogenous flora. The detection of candiduria in patients with bladder catheters in place most likely represents colonization. In patients without foreign bodies in the urinary tract, however, significant candiduria may be a marker of obstruction, DM, or other serious condition. There is not a clear relationship between the quantity of
Candida
in urine (CFU/mL) and clinical significance, as is seen with bacteria. Isolation of
Candida albicans
from sputum and other respiratory specimens is common but rarely associated with pulmonary infection. In CNS infection, isolation of
Candida
from CSF is diagnostic, but the concentration of organisms may be very low, so repeat testing and submission of a large volume of CSF per sample may be needed to establish the diagnosis.

Direct detection of organisms in tissue or clinical specimens
: When associated with signs of inflammation or tissue damage, this may provide reliable detection of infection. Diagnosis of oropharyngeal, esophageal, or vulvovaginal candidiasis may be made on the basis of clinical appearance and risk factors. Confirmation may be established by wet mount or Gram stain examination of scrapings from the affected sites. Negative direct examination does not rule out mucosal candidiasis.

Histopathology
: Shows yeast cells and mycelial forms, epithelial disruption with organisms invading through mucosal cells, and submucosal inflammation in mucosal candidiasis. Deep tissue candidiasis shows organisms invading and disrupting infected tissue.

Serology
: Antibody detection has played a limited role in diagnosis of candidiasis.

Core laboratory
: ALP levels are increased in patients with hepatosplenic candidiasis.

COCCIDIOIDOMYCOSIS

   Definition

Coccidioidomycosis is caused by dimorphic fungi in the genus
Coccidioides
(
Coccidioides immitis
and
Coccidioides posadasii
).
Coccidioides
species are endemic in the desert regions of the Western hemisphere, including the Southwestern United States and California. Infection is acquired by inhalation of arthroconidia produced by the mycelial form in the environment.

   Who Should Be Suspected?

   There is a wide spectrum of disease. Asymptomatic or mild disease is common as judged by seroepidemiologic studies. The risk of clinical infection is increased with increasing exposure to dust (i.e., in the dry periods following periods of rain) in endemic regions and in immunocompromised patients. Disease usually develops 1 to 4 weeks after exposure.

   Disease resolves spontaneously in most patients, resulting in lifelong immunity. However, it is likely that recovery is not associated with a complete microbiologic cure: recrudescent infection is well documented in patients as a result of acquired immunocompromise, as seen in malignancies, HIV infection, and immunosuppressive therapy.

   “Valley fever” is the most common presentation of disease. This syndrome is usually associated with low-grade fever and pneumonia, with cough, and pleuritic chest pain. Systemic symptoms, including fatigue and arthralgias, are common. Cutaneous findings may be seen, including erythema nodosum or erythema multiforme. Hoarseness is uncommon. Severe and chronic disease may be seen in a minority of normal hosts but is more common in immunocompromised patients and in those with specific conditions (e.g., chemotherapy, glucocorticoid therapy, hematologic malignancy, HIV infection, immunosuppressive therapy for autoimmune disease, preexisting chronic lung disease, and/or solid organ transplant).

   Signs and symptoms of severe and chronic disease are related to the organ system affected and degree of tissue damage. Common manifestations of progressive disease include cutaneous dissemination, extensive pulmonary disease, meningitis, osteomyelitis, and/or septic arthritis.

   Laboratory Findings

Culture
:
Coccidioides
species grow on most routine microbiologic media, including those used for bacterial culture, often within several days. It is important to alert the laboratory when a specimen is submitted from a patient in whom coccidioidomycosis is suspected;
Coccidioides
is a significant risk factor for laboratoryacquired infection. Blood cultures are rarely positive for
Coccidioides
, even with evidence of hematogenous spread.

   
Direct detection
: Detection of spherules, the tissue form of
Coccidioides
, is a strong, specific predictor of infection.

   
Serology
: Most, but not all, patients develop specific anticoccidioidal antibodies in response to infection. The appearance of antibodies may be delayed for months after the onset of acute infection. Failure or delay in seroconversion is increased in immunocompromised patients; the diagnosis of coccidioidomycosis is not ruled out by negative results. Titers may fall to undetectable levels during the course of illness in patients who resolve their acute infections. Repeat testing is recommended in patients with negative results if a high index of suspicion remains. Several serologic methods are available: