A bone marrow sample obtained from an immunocompromised patient revealed small intracellular cells using a Wright’s stain preparation. Growth on Sabouraud-dextrose agar plates of a mold phase at 25 degrees Celsius and a yeast phase at 37 degrees Celsius designates the organism as dimorphic. The mold phase produced thick, spherical tuberculated macroconidia. What is the most likely identification?
Initial clues point towards some sort of systemic organism of fungi origin. Growth at both 25 and 37 degrees confirms dimorphism which is important for the differential diagnosis.
Microscopy examination revealed macroconidia indicative of Histoplasma capsulatum. When all other information is taken into consideration, a diagnosis H. capsulatum seems most plausible.
Histoplasma capsulatum is mostly found in its natural setting in the soil. It is endemic in the Ohio and Mississippi river valleys, and in some parts of South America as well. Transmission of the mycosis occurs through inhalation of aerosolized microconidia with activity that disturbs the natural environment. The severity of the illness depends on the host immunity status coupled with the intensity of the exposure. Only 1% of infections are symptomatic.
In this case the patient was immunocompromised. There are three distinct courses the disease can take depending on the immune status of the host. Acute primary histoplasmosis is typically a self-limiting disease. Localized to the lung and the patient may experience fever, cough, chest pain, and malaise (general unwell). Chronic cavitary histoplasmosis is characterized by atypical pulmonary lesions that resemble tuberculosis. Progression can lead to disabling respiratory dysfunction. Progressive disseminated histoplasmosis is generalized involvement of the RES with hepatosplenomegaly, lymphadenopathy, bone marrow involvement, with sometimes GI involvement.
The yeast form is able to survive within circulating monocytes and tissue macrophages. This is the primary way that the fungi disseminates. When H. capsulatum converts to the yeast form, it expresses proteins that interact with the phagocytic receptors on the macrophage surface. These interactions allow entry into the macrophage without activating it to undergo phagocytosis.
Treatment for the patient mentioned above should include amphotericin B including combinations of both liposomal and lipid formulations as well as itraconazole. Amphotericin B binds to ergosterol which is a component of fungal cell membranes. This causes pores to form in the membrane causing leakage of the monovalent ions K+, Na+, H+ and Cl- which subsequently induces fungal cell death.