Clinical Pearls & Morning Reports

Posted by Carla Rothaus, MD

Published February 7, 2024


What are some differences between coccidioidomycosis and histoplasmosis?

Coccidioidomycosis and histoplasmosis differ in important characteristics, even though both infections are dimorphic endemic fungal diseases. Read the NEJM Review Article here.

Clinical Pearls

Q: Do histoplasma and coccidioides have a similar geographic distribution?

A: Histoplasma has been noted in many diverse areas worldwide, but in the Western Hemisphere, it is most commonly distributed in the central and mideastern United States and in Central America, where it thrives in soil with a high nitrogen content. Coccidioidomycosis occurs exclusively in the Western Hemisphere. It is most prominent in arid regions, especially those of Arizona and California. Climate change is predicted to expand its domain across much of the western United States.

Q: Is the acute clinical illness caused by histoplasma or coccidiodes easy to distinguish from community-acquired pneumonia?

A: In cases of both histoplasmosis and coccidioidomycosis, the initial infection is acquired by inhalation of airborne conidia (spores) from the environment. For most persons, this does not result in clinical illness. Among the third of persons who become ill after exposure to coccidioides, the illness develops after a 1-to-3-week incubation period. The initial syndrome is not easily distinguishable from community-acquired pneumonia from any cause. In the small number of patients who become ill from exposure to histoplasma, symptoms develop 2 to 3 weeks later. As with coccidioidomycosis, most infections are related to inhalation of a small number of conidia during everyday activities, and symptoms suggest community-acquired pneumonia (fever, mild chest discomfort, and dry cough).

Morning Report Questions

Q: What are some differences between coccidioidomycosis and histoplasmosis?

A: Arthralgias and erythema nodosum occur with histoplasmosis but less often than noted with coccidioidomycosis. With coccidioides infection, immunity is lifelong, and reinfection does not occur, whereas histoplasma infection does not guarantee lifelong immunity, and reinfection can occur, especially with extensive exposure. After uncomplicated coccidioidal infections, chest radiographs may show residual nodules, up to several centimeters in diameter, that appear to be solitary. Computed tomographic scans often reveal smaller satellite nodules in the surrounding lung. The nodules can persist for many years, usually do not become calcified, and may be metabolically active, making it difficult to distinguish them from malignant nodules. Needle biopsy or a surgical procedure is often necessary to clarify the diagnosis. After histoplasma infection, nodules are frequently seen, which are usually small, numerous, and calcified. Skin and skeletal lesions, which are common in disseminated coccidioidal infection, are infrequent findings in disseminated histoplasmosis.

Q: How are coccidioidomycosis and histoplasmosis treated?

A: For most patients who require treatment of coccidioidomycosis, the triazole of choice is fluconazole. Itraconazole is also effective, especially with infections of osteoarticular structures, but is associated with more adverse effects and has more variable absorption. For patients with severe disease, therapy with a lipid formulation of amphotericin B should be provided initially, with a step down to a triazole once clinical improvement is apparent. Severe pulmonary or disseminated histoplasmosis should be treated initially with a lipid formulation of amphotericin B. Histoplasma is exquisitely sensitive to this agent, and clinical improvement generally occurs within 1 to 2 weeks after the initiation of therapy. For step-down therapy and for initial therapy of less severe disease, oral itraconazole is the agent of choice, with proper attention to achieving serum concentrations that are adequate for the resolution of infection and are not toxic. In contrast to the treatment of coccidioidomycosis, fluconazole is not as efficacious as itraconazole and is not recommended.

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