Case study: a monument to histoplasmosis.

BACKGROUND

Histoplasmosis occurs throughout the world. (1) An estimated 40 million people in the United States have been infected with H. capsulatum. Experts feel that 500,000 new cases occur each year. (2) The vast majority of these are sub-clinical. (3) In the United States, the disease is endemic in the Ohio-Mississippi river valleys extending into parts of northern Maryland, southern Pennsylvania, central New York, and Texas. (4) Smaller pockets of the disease (microfoci) have been reported in other states, such as Florida. (5)

H. capsulatum grows as a mold in nature or when cultured at room temperature but converts to a small (1 to 5 [micro]m in diameter) yeast cell when heated to 37[degrees] C (98.6[degrees] F) and when invading host cells. Infection follows inhalation of mold conidia (spores) in soil or dust that has been contaminated with bird or bat droppings. Severe disease is more common after heavy, prolonged exposure and occurs often in men, infants, or those with compromised T cell-mediated immunity. (6)

The disease has three main forms of initial presentation. Acute primary histoplasmosis is usually asymptomatic. If symptoms develop, they are usually nonspecific, and include fever, cough and malaise of varying severity. Acute pneumonia is sometimes evident on physical examination or chest x-ray.

Disseminated histoplasmosis begins in the lungs and is spread by blood. It is not contained by normal cell-mediated host defense mechanisms. This form is characterized by generalized involvement of the reticuloendothelial system. Hepatosplenomegaly, lymphadenopathy and bone marrow involvement are typical. Oral or gastrointestinal ulcerations can occur, particularly in chronic cases. (7) Disseminated histoplasmosis is a rare disease that occurs primarily among persons who are immunocompromised. It is especially common among persons who are HIV positive, especially those with CD4 lymphocyte counts below 150 to 200 per [mm.sup.3]. (8) Individuals with lymphoreticular neoplasms and people who are receiving corticosteroids, cytotoxic therapy and post-transplantation or innnunosuppressive agents are also predisposed to disseminated histoplasmosis. (9)

The third main form is chronic, cavitary histoplasmosis. This features pulmonary lesions that are often apical. This form of histoplasmosis resembles cavitary tuberculosis. It is characterized by worsening cough and dyspnea that eventually progresses to disabling respiratory dysfunction. Dissemination does not occur. (10)

Another chronic but rare form of histoplasmosis is fibrosing mediastinitis that ultimately causes circulatory compromise. Histoplasmosis may be a cause of blindness in presumed ocular histoplasmosis syndrome. Organisms are not present in lesions, antifungal and chemotherapy are not helpful and the link to H. capsulatum infection has not been established with certainty. (11)

In general, the course of histoplasmosis is usually subacute or chronic, and is characterized by nonspecific, often subtle symptoms such as fatigue, weakness or malaise. Individuals who are HIV-positive may experience an unexplained worsening of their condition. (12)

Severe manifestations of histoplasmosis occur most often in infants and immunocompromised persons. Addison's disease is an uncommon but potentially serious condition that must be ruled out and distinguished from other causes of adrenal insufficiency such as tuberculosis, sarcoidosis, lymphoma, or leukemia.

Culture of H. capsulatum from sputum, lymph nodes, bone marrow, liver biopsy, blood, urine or oral ulcerations confirms the diagnosis. Lysis-centrifugation or culture of buffy coat improves the yield from blood …