Clinical Pearls & Morning Reports
Published October 4, 2023
It is hypothesized that tumor necrosis factor (TNF)-α plays a central role in protection against histoplasma, potentially through the expansion of T cells, and that, correspondingly, treatment with a TNF-α inhibitor confers a predisposition to the development of disseminated histoplasmosis. Read the NEJM Clinical Problem-Solving Article here.
Q: Are patients with histoplasmosis usually symptomatic?
A: Histoplasma conidia inhabit soil with a high nitrogen content; they often arise from bird or bat droppings and result in infection through inhalation when the soil is disturbed. In the lungs, the conidia transform from a mold state to a yeast state (dimorphic fungus), after which time they are phagocytized by the alveolar macrophages. Most patients with histoplasmosis are asymptomatic or have mild symptoms with a self-limited disease course. However, patients with a high inoculation burden or those who are immunosuppressed are at risk for severe or disseminated disease.
Q: Describe elements of the diagnostic evaluation for suspected histoplasmosis.
A: The reference-standard tests for the diagnosis of histoplasmosis are fungal culture or histologic evaluation. However, a positive enzyme immunoassay targeting the galactomannan antigen contained within the histoplasma polysaccharide cell wall is strongly suggestive of histoplasmosis. Antigen testing of urine and most other clinical specimens can be performed; the sensitivity for the detection of galactomannan antigen is increased when antigen testing is combined with histoplasma serum antibody testing. In areas where histoplasmosis is endemic, history taking should assess for activities that result in a high exposure risk, such as digging in soil where there are bird or bat droppings, cleaning chicken coops, exploring caves, or remodeling or demolishing old buildings.
A: Histoplasmosis can affect numerous organ systems, including the gastrointestinal tract, although it most commonly causes pulmonary disease. Chest imaging characteristically shows small nodular opacities with a diffuse distribution. Gastrointestinal findings can include polypoid masses or ulcerations (or both) in the small bowel and colon, findings that can mimic inflammatory bowel disease. In a large case series involving patients presenting with disseminated disease, approximately 70% of the patients were found to have gastrointestinal involvement at autopsy, but only 3 to 12% were known to have clinical gastrointestinal manifestations. Perforation is a rare complication of disseminated histoplasmosis. When it occurs, the most common sites are the terminal ileum or proximal colon, perhaps because of the high density of lymph nodes that may harbor histoplasma in these regions.
A: Treatment of patients with moderate-to-severe disseminated histoplasmosis includes liposomal amphotericin B and oral itraconazole. Induction therapy with liposomal amphotericin B for 1 to 2 weeks is recommended, followed by oral itraconazole therapy for at least 12 months with treatment continued until clinical and laboratory findings have returned to normal. In a randomized trial in which induction therapy with liposomal amphotericin B was compared with the deoxycholate formulation of amphotericin B for 2 weeks (in both cases followed by oral itraconazole) in patients with moderate-to-severe histoplasmosis and acquired immunodeficiency syndrome, the regimen containing liposomal amphotericin B was associated with a higher incidence of clinical success and a lower incidence of nephrotoxicity. Alternative azole therapies may be used in patients with itraconazole adverse effects or drug interactions, although data are limited to inform the relative benefits and risks of these agents.