Histoplasmosis

see also my usmle page for histoplasmosis information

concentration in the Mississippi and Ohio River Valleys

good for your path lab case presentation

The appropriate evaluation of a lung nodule is a significant clinical challenge. There are many potential causes for lung nodules, however as clinicians we are most concerned with the separation of malignant and inflammatory disease. This is an important distinction because the diagnostic and therapeutic approach differs significantly for the two disease categories. Infectious causes of lung nodules will differ among different geographic areas. In the great river valleys of the central United States, the most common cause of infectious lung nodule is Histoplasma capsulatum infection.

The organism Histoplasma capsulatum was first described in 1906 by Dr. Samuel Darling in the Panama Canal Zone. The name referred to his belief that the organism, found in reticuloendothelial cells, was an encapsulated plasmodium. The name persists despite the fact that it is now known to be a non-encapsulated yeast.

The organism is found world wide, but in the United States it is endemic to the Mississippi and Ohio River valleys. High concentrations of the organism can be found in bird roosts, caves inhabited by bats, school yards, areas with rotten or decaying wood, and chicken coops. Human activities in and around theses regions may lead to infection. In all cases, the lung is the point of entry. In the 1940's a skin test was developed by Christie and Peterson for histoplasmin, and it was soon found that vast numbers of people in endemic areas had positive tests but were asymptomatic. Shortly thereafter large numbers of people with calcified lung lesions on radiographs and a negative tuberculin skin test were found to have positive histoplasmin skin tests.

Once the organism is in the lungs, it is ingested by alveolar macrophages and taken to regional lymph nodes with subsequent dissemination throughout the body. In normal hosts, the disease is usually self-limited without symptoms or radiographic abnormalities. However, in patients with reduced T-cell immunity the disease can disseminate and quickly become fatal. The patient's T cell immunity is the key to determining the course of the infection. For patients with a normal T cell immune system, less than 1% will develop a systemic infection.

Symptoms, when present, are usually nonspecific. Common symptoms are flu-like and include fever, chills, headache, muscle pain, anorexia, cough, and retrosternal or pleuritic chest pain. Physical exam is usually normal, but rales, lymphadenopathy, and skin lesions may be found.

The radiographic appearance of Histoplasmosis in the chest is quite variable and can mimic an number of diseases including, active tuberculosis, sarcoidosis, lymphoma, primary lung cancer and metastases.

In a normal host the radiograph will usually demonstrate a single airspace opacity in the acute phase of the illness. This is most often found in the upper portions of the lower lobe and is often associated with ipsilateral hilar and mediastinal adenopathy. (example) Over time the area of airspace opacity contracts to form a 1-2 cm nodule that may calcify. (example) The hilar and mediastinal lymph nodes will also calcify over time. During the time when the lung nodule is uncalcified it is impossible to differentiate from a bronchogenic carcinoma. However if the nodule on plain film or CT (Examples) is uniformly calcified or has a central dense nidus of calcification then the lesion is benign and no further work up is required. A chest CT with phantom calibration is more sensitive to the presence of calcium. However, patients who are found to have calcium only with the phantom should be followed for 2 years to make sure that the lesion is not growing.

If the inoculum is large as may occur when spelunking or cleaning a chicken coop then the patient may present with numerous indistinct nodules during the acute phase. These nodules may be difficult to differentiate from metastases. These nodules will also calcify in the healing phase. (example)

Chronic fibrocavitary histoplasmosis has a similar radiographic appearance to active tuberculosis. The great majority of these patients are cigarette smokers with advance upper lobe emphysema. Air space opacity and apparent cavitation dominate the radiographic picture.

Mediastinal granuloma may present as a mediastinal mass on chest radiography. The mass is formed by a group of encapsulated lymph nodes that is involved with granulomatous inflammation. The mass may surround mediastinal structures including major veins, the esophagus, pulmonary artery or bronchus. (example)

Fibrosing Mediastinitis may be viewed as a progressive form of mediastinal granuloma with resulting obstruction of the superior vena cava, pulmonary arteries or bronchi. (example) This mass of tissue is difficult to differentiate radiographically from lymphoma.

The current gold standard for diagnosis is to identify the fungus in the appropriate clinical setting. Samples for smear and culture are obtained by needle aspiration or by bronchoscopy. However, it is unusual to identify the organism in normal hosts or in old lesions. The diagnosis is often made in these settings by exclusion. When the disseminated form is suspected, a sample from the reticuloendothelial system is required. This can be obtained from bone marrow or liver.