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Histoplasmosis

Half million cases per year in the U.S.

Endemic infection in most of the U.S.

It is endemic in Central and South America.

H.capsulatum is a dimorphic fungus highly endemic in the Ohio-Mississippi valleys.

Histoplasmosis capsulatum is separated into four species based on genetic differences. H. Capsulatum, H, mississippience,  H ohiense,  H. suramericanum.

It can also be found in the eastern US, Texas, central and south America.

Grows as a mold in the environment and a yeast at body temperature.

Conidiophores inhabit soil with high nitrogen content, often arise from bird droppings and resulting in infection through inhalation when the soil is disturbed.

Mold spores are dispersed by soil disturbance, and can be inhaled by humans.

Histoplasmosis is found in high concentrations in bird and bat droppings, so individuals with exposure to chicken coops or caves are at increased risk for infection.

In the lungs, the conidia transform from a mold state to a yeast state, after which the time they are phagocytized by the alveolar macrophages.

Up to 90% of persons with exposure to the fungus have only mild or no symptoms.

Symptomatic disease occurs in a small portion of persons infected with Histoplasma.

Patients with a high inoculation burden or those who who are immunosuppressed are at risk for severe or disseminated disease.

Following inhalation spores reaching lung temperature convert into budding yeast.

Mold colonies have septate hyphae and large round thick walled macroconidia, with cylindrical surface projections.

40 million people in the U.S. are infected with 500,000 new cases each year.

Primary infection with Histoplasma is often asymptomatic, but can have a pneumonic syndrome with extra pulmonary features.

Ordinarily causes self-limiting or slowly progressive chronic infection.

histoplasmosis can affect numerous organ systems, including the G.I. tract, although it most commonly causes pulmonary disease.

Causes a latent infection that can reactivate years after a patient has left an endemic area, especially when CD4 T lymphocyte count falls below 100 per cubic millimeter.

With disseminated disease adenopathy is almost always present.

Patients with disseminated disease present with fever, weight loss, respiratory symptoms, hepatosplenomegaly, anemia, lymphadenopathy and sepsis.

Histoplasmosis is associated with a wide range of pulmonary manifestations.

Approximately 10% present with acute pulmonary histoplasmosis, which includes fever, cough, and dyspnea.

Of these patients 5% of skin with joint manifestations, such as arthralgias, arthritis, erythema, nodosum, or erythema multiforme.’

With acute pulmonary histoplasmosis, diffuse opacities are seen on imaging of the lung, along with mediastinal and hilar lymphadenopathy.

Chest imaging typically shows small nodular opacities with a diffuse distribution.

Gastrointestinal findings include polypoid masses/ulcerations in the small bowel and colon.

A complication of long-term steroids, AIDS, leukemia and lymphoma and other immunocompromised states.

Occurs in bout 5% of patients with HIV/AIDS in areas where the process is endemic like the Central U.S., particularly the Mississippi, Ohio and Missouri river valleys, the Caribbean, Central and South America.

Hiwwstoplasmosis is a common cause of pulmonary nodules.

Associated with the use of low-dose methotrexate.

Not transmissible from person to person contact.

Infections caused by spores from sources such as soil, bird roosts, and buildings contaminated with bird or bat droppings.

Occurs by inhalation of airborne conidia.

The mycelial form is found in soil and they produce the spores which when become airborne can be inhaled into the alveoli of the lung.

Diagnosis includes fungal culture, or histologic evaluation.

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 other clinical specimens can be performed.

History should be assessed for activities that result in high exposure risk: digging in soil where there are bird of bat droppings, cleaning chicken coops, exploring caves, or remodeling/demolishing old buildings.

Immunoassay for urinary enzyme Histoplasma capsulatum antigen is highly sensitive for the diagnosis.

Amphotericin B or one of its lipid-bound formulations is recommended for immunocompromised and/or seriously ill patients.

Itraconazole is the treatment of choice for infected patients with mild to moderately severe symptoms.

Fluconazole not as effective as itraconazole and more likely to be associated with development of drug resistance.

Achieves excellent concentrations in the CNS and is used for maintenance therapy after amphotericin B or its formulations for Histoplasma meningitis.

Disseminated infection is associated with fever, weight loss and fatigue.

Disseminated disease occurs in up to 30% of patients with AIDS and is AIDS defining disease in up to 50% of those patients.

Up to 12% of AIDS patients with disseminated histoplasmosis have GI involvement, most commonly in the colon.

70% of patients with disseminated infection have chest x-ray abnormalities of interstitial or reticulonodular infiltrates.

The most sensitive rapid test is an analysis of urine for Histoplasma antigen, which is positive in 90% of patients with disseminated disease.

The urine test for Histoplasma antigen has cross-reactivity with other dimorphic fungi, which makes this antigen sensitive but not specific marker of acute and disseminated infections.

Serologic tests for H capsulatum positive in 70-80% of patients with disseminated disease.

Histoplasmosis produces 1,3 beta-D glucan, a component of the fungal cell wall and measurement of the blood level of 1,3 beta-D can can be a marker invasive fungal infection.

Fungal blood cultures should be performed in all patients suspected of having disseminated disease, and 50-70% of such cultures will be positive.

Common cause of splenic calcification.

The use of tumor necrosis factor-alpha inhibitors predispose patients to the development of disseminated disease.

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