HISTOPLASMOSIS
Histoplasmosis is caused by inhalation of spores of the fungus Histoplasma capsulatum. The organism exists widely in nature and is found throughout the United States but is most common in the St. Lawrence and Missouri–Ohio–Mississippi River valleys. It also exists in most of the river valleys throughout the world between the 45th parallel north and the 45th parallel south. Droppings of bats and birds seem to provide in their excreta the essential elements favoring sporulation of the fungus in soil. Therefore, sites commonly associated with exposure to H. capsulatum include chicken coops, caves, abandoned buildings, bird roost sites, and wood lots. Activities associated with exposure include excavation, construction, demolition, wood cutting and gathering, and exploring caves. However, in most cases, patients recall no such exposure or only do so when specifically questioned.
Infections with
H. capsulatum are extremely common; it has been estimated that up to 50
million people in the United States have been infected, and up to 500,000 new
infections occur each year. The outcome of acute infection depends on the inoculum
size, presence of underlying lung disease, general immune status, and specific
immunity to H. capsulatum. In more than 95% of cases, the infection is
subclinical. In some, the disease may manifest in the form of a flulike syndrome
or a mild or severe pneumonia, which is usually self-limited and often
undiagnosed. This illness usually presents as a subacute pulmonary infection
weeks to months after exposure. Symptoms are usually mild, and radiographs
typically show focal infiltrates and mediastinal or hilar lymphadenopathy.
Symptoms typically resolve within several weeks, but fatigue and asthenia may
persist for months.
With an acute
heavy exposure, diffuse reticulonodular or miliary infiltrates are seen, and the
infection can progress to respiratory failure or progressive extrapulmonary
dissemination. In patients with underlying lung disease, the pulmonary disease can become chronic and
progressive and closely simulates cavitary tuberculosis. Chronic disease can
also present as broncholithiasis, mediastinal granuloma, and fibrosing
mediastinitis. On even rarer occasions, primarily in immunosuppressed patients
(e.g., HIV, transplantation, tumor necrosis factor-inhibitor treatment) or
those at extremes of age, H. capsulatum may disseminate acutely
throughout the body to the
bone marrow, skin, liver, spleen, meninges, and alimentary tract. In addition,
chronic progressive disseminated histoplasmosis occurs rarely in older
immunocompetent adults.
Other pulmonary
manifestations of histoplasmosis may include a single small pulmonary density
with unilateral hilar lymphadenopathy identical to the Ghon complex; a single
nodule or coin lesion, which may simulate a bronchogenic carcinoma; multiple pulmonary
nodules simulating metastatic tumor; pleural effusions; mediastinal
lymphadenopathy simulating lymphoma; and bilateral hilar adenopathy simulating
sarcoidosis.
When the spores
from the free-living mycelial phase of H. capsulatum gain entry into the
body, they convert to the tissue or yeast phase. These appear in tissues and
respiratory secretions as intracellular, encapsulated organisms that are ovoid
and 3 to 5 m in diameter that demonstrate narrow-based budding. Accompanying
histopathologic findings include granulomas, lympho- histiocytic aggregates, and
diffuse mononuclear cell infiltrates.
Diagnosis
relies on a combination of histopathology, cultures, antigen detection (in
respiratory specimens and urine), and serologic tests (including complement
fixation and immunodiffusion). In acute diffuse pulmonary disease, antigen tests
and cultures are useful, although serology results are often negative. In acute
localized pulmonary disease, serology is often positive, but fungal detection
is more difficult. In chronic pulmonary disease, serology and culture results
are often positive. Bronchoscopy to obtain adequate respiratory specimens is
often required, and on occasion, lymph node or lung biopsy is necessary for
diagnosis.
Treatment is
indicated for cases of acute pneumonia that are unusually severe, for chronic
progressive pulmonary disease, and for disseminated histoplasmosis. Other forms
of histoplasmosis require specific treatment only if progression is
demonstrated.
TREATMENT
Patients with
mild to moderate histoplasmosis are treated with itraconazole, although
amphotericin B is indicated for moderately severe and severe infections,
especially for initial treatment. Concomitant use of systemic corticosteroids
for 1 to 2 weeks is helpful in acute severe disease manifesting as acute
respiratory distress syndrome. The duration of antifungal treatment is usually
6 to 12 weeks.
Itraconazole
for 18 to 24 months has been successful in the treatment of patients with
chronic pulmonary histoplasmosis. After completion of successful treatment,
relapse occurs in 10% to 20% of patients over 5 years. Therefore, these
patients should be carefully followed during this period. In disseminated
disease, severely ill patients should be initially treated with amphotericin B
followed by itraconazole for at least 1 year. Less severely ill patients may be
treated from the beginning with itraconazole.
