Signs and symptoms

• Rheumatologic symptoms such as severe arthritis, pericarditis, and erythema nodosum may be seen in 10% to 30% of patients with endemic fungi.2,6

• Dissemination outside the lung is common in patients with suppressed cellular immunity and frequently produces signs of progressing infection.

• Ulcerative oral and cutaneous lesions may also arise with any endemic fungal infections.

• Verrucose skin lesions on sun-exposed areas on the face are particularly suggestive of progressing blastomycosis and are frequently mistaken for cutaneous malig-

nancy.6

• Dissemination of the fungi to bone marrow may result in anemia or thrombocytopenia.

• Hepatomegaly, splenomegaly, and adrenal insufficiency can also occur with dissemination of the endemic fungi to these internal organs.

• Seizures, meningeal signs, and hydrocephalus are common findings with dissemination to the CNS and portend an especially poor prognosis in the setting of disseminated coccidioidomycosis.

Definitive diagnosis of an endemic fungal infection requires growth of the fungus from body fluids or tissue, or evidence of cellular or tissue invasion in clinical samples by histopathologic staining. However, cultures may only be positive in the setting

of high inoculum exposures, pneumonia, or disseminated disease. Serologic testing is helpful in the diagnosis and management of patients with histoplasmosis or coc-cidioidomycosis but lacks sufficient specificity for diagnoses of B. dermatitidis 6 In general, a fourfold rise in antibody titers of Histoplasma or Coccidioides, or any titer greater than 1:16 suggests active infection. However, many clinicians still consider titers as low as 1:8 as evidence of active disease because undetectable titers may be present in one-third of all active infections.4 Enzyme-linked immunosorbent assays (ELISAs) have been developed for detection of Histoplasma antigen in serum and urine, and a new radioimmunoassay directed against surface proteins of B. dermatitidis has shown promising sensitivity and specificity. Serial antigen testing can also provide a means for assessing response to antifungal therapy and early detection of relapse in patients with histoplasmosis or coccidioidomycosis.

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