The histoplasmin skin test is a valuable epidemiological tool that has permitted mapping of the endemic area. However, it is worthless in individual case diagnosis. A positive skin test means only that the person is one of many millions who have had histoplasmosis, probably remotely and without sequelae. It does not mean that a current illness under investigation is being caused by the fungus.

Primary histoplasmosis is usually not diagnosed at all. Sputum cultures are positive in less than 10 percent of cases. Most recognized cases are diagnosed by serology. Serologic tests include immunodiffusion (M and H bands) and complement fixation (yeast and mycelial antigens) tests. An M band by immunodiffusion is fairly specific. The H band is never found alone. When present with the M band (10 to 20 percent of the time), it adds further to specificity. Unfortunately, the immunodiffusion test is insensitive and appears slowly after primary infection. Less than 25 percent of symptomatic patients have a positive test 2 weeks after the onset of clinical illness (Davies 1986). The complement fixation test is more sensitive but less specific. The titer against the mycelial antigen is not important because it is almost always lower than the titer against the yeast antigen. A titer of 1 to 32 or higher against the yeast antigen is diagnostic if the clinical picture suggests histoplasmosis. Unfortunately, only 60 percent of patients have a positive test 2 weeks after the onset of clinical illness, and many have 1:8 or 1:16 titers (Davies 1986). What this means is the serologic tests are most useful for diagnosing patients who have already recovered. Patients with rapidly progressive pneumonias not responding to antibacterial antibiotics need urgent diagnosis, especially if respiratory failure is impending or actually develops. Some patients are diagnosed by serology. Others require lung biopsy for histopathological diagnosis, because a negative serology cannot exclude the diagnosis, and empirical treatment for all possible causes of progressive pulmonary infection is not possible.

Chronic cavitary histoplasmosis is easier to diagnose. The pace is slower. Tuberculosis is suspected first, but the tuberculin skin test is negative and the sputum is negative for tuberculosis by smear and culture. Sputum cultures for H. capsulatum are usually positive, as are serologic tests (immunodiffusion: 75 percent; complement fixation: 90 percent).

Disseminated histoplasmosis is difficult to diagnose because the illness is so nonspecific. Serologic tests are positive in over half of cases and may pro vide an important clue. Sérodiagnostic tests are least helpful in the immunosuppressed because they are less sensitive and because the pace of the illness may be so fast that there is no time to wait for the results. Histopathological examination of tissue biopsies is the method of diagnosis in most cases. Bone marrow biopsy is particularly valuable in febrile illnesses without localizing features. Special stains, such as one of the many modifications of the silver stain, are necessary to ensure visualization of the organisms. Cultures of blood, bone marrow, and other tissues and of body fluids may also give the diagnosis in some cases.

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