Pulmonary Histoplasmosis: A Clinical Update

Abstract

Histoplasma capsulatum, the etiological agent for histoplasmosis, is a dimorphic fungus that grows as a mold in the environment and as a yeast in human tissues. The areas of highest endemicity lie within the Mississippi and Ohio River Valleys of North America and parts of Central and South America. The most common clinical presentations include pulmonary histoplasmosis, which can resemble community-acquired pneumonia, tuberculosis, sarcoidosis, or malignancy; however, certain patients can develop mediastinal involvement or progression to disseminated disease. Understanding the epidemiology, pathology, clinical presentation, and diagnostic testing performance is pivotal for a successful diagnosis. While most immunocompetent patients with mild acute or subacute pulmonary histoplasmosis should receive therapy, all immunocompromised patients and those with chronic pulmonary disease or progressive disseminated disease should also receive therapy. Liposomal amphotericin B is the agent of choice for severe or disseminated disease, and itraconazole is recommended in milder cases or as "step-down" therapy after initial improvement with amphotericin B. In this review, we discuss the current epidemiology, pathology, diagnosis, clinical presentations, and management of pulmonary histoplasmosis.

Keywords: histoplasmosis; pulmonary histoplasmosis.

Figure 1

World map epidemiology of Histoplasmosis. Dark green represents areas likely to be hyperendemic, green represents areas where infection occurs regularly. Light green represents areas where local infections have been reported.

Figure 2

Pathogenesis of histoplasmosis. Aerosolized microconidia are inhaled by the host. Host temperature (37 °C) triggers morphological transformation to yeast. Surfactant A and D (collectins) display a direct fungicidal role through a calcium-dependent mechanism of yeast permeabilization. Heat shock protein 60 (HSP60) is recognized by complement receptor 3 (CR3) and promotes phagocytosis. If Dectin-1 is activated by interaction with 1-3 β D glucan, the macrophage is able to produce a profound inflammatory cascade. To avoid it, the yeast covers the 1-3 β D glucan with 1-3 α glucan. Once in the phagolysosome, antigen M inhibits the reactive oxygen species (ROS). The infected macrophage can migrate to any other organ in the body, including liver, spleen, and bone marrow. Dendritic cells are able to kill the yeast and present antigens to T helper cells (Th0) and promote their polarization into Th1, which in turn increases pro-inflammatory cytokines leading to further macrophage activation.

Figure 3

(A) Giemsa stain showing intracellular small ovoid yeast. (B) Grocott-Gomori’s methenamine silver showing small ovoid, narrow-based budding yeasts. (C) Hematoxylin-eosin stain of a caseating pulmonary granuloma. (D) Grocott-Gomori’s methenamine silver showing small yeast in a pulmonary granuloma.

Figure 4

Chest CT of acute pulmonary histoplasmosis showing a large consolidation with air bronchogram.

Figure 5

Incidental pulmonary nodule in a patient from a highly endemic area. Biopsies often reveal granulomatous changes and calcifications.

Figure 6

Chronic cavitary pulmonary histoplasmois. Multiple thick wall cavitations in a patient with emphysematous disease.

Figure 7

Fibrosing mediastinitis. (Left image) Arrows points at heavy calcification in the mediastinum. (Right image) both arrows point at severe stenosis of bronchial lumen.

Figure 8

Progressive disseminated histoplasmosis. CT chest showing diffuse reticulonodular infiltrates with large mediastinal lymphadenopathies.