Most cases of histoplasmosis are asymptomatic or mild and thus go unrecognized. Past infection is recognized by pulmonary and splenic calcification noted on incidental radiographs. Symptomatic infection may present with mild influenza-like illness, often lasting 1–4 days. Moderately severe infections are frequently diagnosed as atypical pneumonia. These patients have fever, cough, and mild central chest pain lasting 5–15 days.
Clinically evident infections occur in several forms: (1) Acute pulmonary histoplasmosis frequently occurs in epidemics, often when soil containing infected bird or bat droppings is disturbed. Clinical manifestations can vary from a mild influenza-like illness to severe pneumonia (eFigure 36–1). The illness may last from 1 week to 6 months but is almost never fatal. (2) Progressive disseminated histoplasmosis is commonly seen in patients with underlying HIV infection (with CD4 cell counts usually less than 100 cells/mcL) or other conditions of impaired cellular immunity. Disseminated histoplasmosis has also been reported in patients from endemic areas taking tumor necrosis factor (TNF)-alpha inhibitors. It is characterized by fever and multiple organ system involvement. Chest radiographs may show a miliary pattern. Presentation may be fulminant, simulating septic shock, with death ensuing rapidly unless treatment is provided. Symptoms usually consist of fever, dyspnea, cough, loss of weight, and prostration. Ulcers of the mucous membranes of the oropharynx may be present. The liver and spleen are nearly always enlarged, and all the organs of the body are involved, particularly the adrenal glands; this results in adrenal insufficiency in about 50% of patients. Gastrointestinal involvement may mimic inflammatory bowel disease. Central nervous system (CNS) invasion occurs in 5–10% of individuals with disseminated disease. (3) Chronic pulmonary histoplasmosis is usually seen in older patients who have underlying chronic lung disease. Chest radiographs show various lesions including complex apical cavities, infiltrates, and nodules. (4) Complications of pulmonary histoplasmosis include granulomatous mediastinitis characterized by persistently enlarged mediastinal lymph nodes and fibrosing mediastinitis in which an excessive fibrotic response to Histoplasma infection results in compromise of pulmonary vascular structures. An accumulation of CD20-positive lymphocytes has been demonstrated within the inflammatory material.
A 33-year-old man presented with a 6-month history of fatigue but no other symptoms. Chest radiograph showed a 4-cm mass overlying the right hilum and the irregular contour of the left hilum suggested lymphadenopathy. Histoplasmosis was diagnosed on bronchoscopic biopsies. (Reproduced, with permission, from Miller WT, Jr. Diagnostic Thoracic Imaging. New York, NY: McGraw-Hill; 2006:357, Figure 7-52A.)
Most patients with chronic pulmonary disease show anemia of chronic disease. Bone marrow involvement with pancytopenia may be prominent in disseminated forms. Marked lactate dehydrogenase (LD) and ferritin elevations are also common, as are mild elevations of serum aspartate aminotransferase.
With pulmonary involvement, sputum culture is rarely positive except in chronic disease; antigen testing of bronchoalveolar lavage fluid may be helpful in acute disease. The combination of a first morning urine and serum polysaccharide antigen assays has an 83% sensitivity for the diagnosis of acute pulmonary histoplasmosis. Blood or bone marrow cultures from immunocompromised patients with acute disseminated disease are positive more than 80% of the time, but may take several weeks for growth. The urine antigen assay has a sensitivity of greater than 90% for disseminated disease in immunocompromised patients and a declining titer can be used to follow response to therapy. Diagnosis of CNS disease requires antigen and antibody testing of the cerebrospinal fluid (CSF) and serum as well as urine antigen testing.