Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (493 page)

   Increasing antigen titer, or reconversion to antigen positivity, may be a sign of relapse. Antigen becomes undetectable after antifungal therapy. Crossreactions may rarely be seen in patients with blastomycosis, coccidioidomycosis, paracoccioidomycosis, or other invasive fungal disease.

Serology

   CF and immunodiffusion (ID) tests are most useful for diagnosis of histoplasmosis. EIA screening methods are less sensitive and less specific. Positive CF and ID reactions are markers of active histoplasmosis; background seropositivity in endemic areas is low. Positive reactions, however, may be due to asymptomatic, self-limited disease. Results of serologic tests must be interpreted with consideration of clinical and other laboratory information.

   Detection in specific
H. capsulatum
antibody is seen in approximately 90% of patients with acute pulmonary infection, but because seroconversion may not occur for several months after onset of infection, negative tests should be repeated after 4–6 weeks. Virtually, all patients with chronic pulmonary or disseminated disease are seropositive.

   CF titers are slightly more sensitive but less specific than the immunodiffusion test for diagnosis of histoplasmosis. A single serum CF titer ≥1:32 or a fourfold increase in CF titer is highly suggestive of active histoplasmosis; a CF titer <1:8 is considered negative. Rising CF titers occur in >95% of patients with symptomatic primary infections. A CSF CF titer ≥1:8 is evidence for meningeal histoplasmosis. CSF antibodies, however, may not be detected until the 3rd to 6th week of infection. Positive CF titers persist for months or years. Prognosis is not indicated by level or changes in titers. IgG and IgM detection is not clinically useful because of high false-positive and false-negative results.

Core laboratory
: Increased serum aminotransferases and bilirubin suggest hepatic involvement. Anemia, leukopenia, and thrombocytopenia are more common (60–80% of cases) in acute than in subacute or chronic disseminated types. Increased serum LDH may be clue to disseminated form in AIDS patients.

CSF findings
: Lymphocytic pleocytosis, increased protein, and decreased glucose

MUCORMYCOSIS

   Definition

Mucormycosis describes diseases caused by opportunistic aseptate molds of the
Mucorales
order. Species of the genus
Rhizopus
are responsible for most clinical infection, followed by
Mucor.
Most species grow very rapidly in culture. Clinical infection is often associated with high mortality, loss of function, and disfigurement. Most infections are acquired through the respiratory tract, causing local infection and subsequent dissemination. Organisms from the upper respiratory tract may be swallowed, resulting in GI infection. Organisms are able to proliferate in the presence of high concentrations of glucose, and they have the ability to invade blood vessels, resulting in tissue infarction. Nosocomial transmission, infection due to ingestion of contaminated food, and traumatic inoculation are less common but well-described modes of transmission. Person-to-person transmission does not occur.

   Who Should Be Suspected?

Although any organ may be involved in mucormycosis, the respiratory tract is the most common site of primary infection. Disseminated infection may follow primary infections. A high index of suspicion is required for efficient diagnosis of mucormycosis; early diagnosis is critical for appropriate intervention and antifungal therapy. Factors predisposing to infection include AIDS, deferoxamine therapy, DM, glucocorticoid therapy, hematologic malignancies, immunosuppressive therapy, neutropenia, renal failure, and solid organ transplantation. Common sites of infection include the following:

   
Rhinocerebral
: Rhinocerebral disease is the most common manifestation of mucormycosis, occurring in about 50% of patients. Primary infection is initiated in the nasal mucosa and then may spread through the palate, sinuses, orbit, other facial structures, or brain. Patients usually present with symptoms similar to bacterial sinusitis with fever, purulent discharge, and headache. Infection is commonly unilateral. Eschar forms on affected mucosa, and nasal discharge may be bloody. Ipsilateral extension may result in ulceration and necrosis of sinuses or palate. Ocular involvement manifests with orbital pain, proptosis, ophthalmoplegia, visual abnormalities, conjunctivitis, and inflammation and edema of the eyelid. The brain may be involved by spread of infection across the dura, causing cavernous sinus thrombosis and cerebral disease. Cerebral mucormycosis is manifested by cranial nerve palsies, change in level of consciousness, or severe disruption of cerebral function. Blood vessel involvement may result in symptoms of stroke.

   
Pulmonary
: Pulmonary disease represents about 10% of mucormycosis cases, occurring primarily in immunocompromised patients. Patients may present with FUO and respiratory symptoms unresponsive to antibiotic therapy. Rapidly progressive pulmonary disease may present with a variety of patterns and may mimic pulmonary aspergillosis. Pulmonary necrosis may result in massive hemoptysis. Infection may progress into contiguous spaces and tissues, including the diaphragm, mediastinum, and heart.

   
GI
: GI disease occurs in <10% of patients. Symptoms and signs depend on the GI tissue involved and the type of pathology. Symptoms are nonspecific, including abdominal pain and diarrhea. Ulcerative lesions are common and may lead to perforation or massive bleeding with hematemesis or lower GI bleed.