Histoplasmosis is a chronic, noncontagious, disseminated, granulomatous disease of people and other animals caused by the dimorphic fungus Histoplasma capsulatum. The organism is commonly found in soil that contains bird and bat manure. It produces mycelial growth in the soil and in culture at room temperature and grows in a yeast form in tissues and in cultures at 37°C.
Histoplasmosis is found worldwide. Endemic areas in the USA include the Mississippi and Ohio River valleys. Infection has been described in many animal species, but disease is uncommon to rare in all but dogs and cats. Infection is commonly via aerosol contamination of the respiratory tract, and the lungs and thoracic lymph nodes are the sites of primary infection, although the GI tract may be a primary site of infection, especially in dogs. The organisms enter the bloodstream from a primary focus and become disseminated throughout the body; they may localize in bone marrow or the eyes, where they produce chorioretinitis or endophthalmitis.
The signs vary and are nonspecific, reflecting the various organs involved. Chronic GI signs, especially large intestinal diarrhea, are usually most obvious in dogs, but cats tend to have respiratory and nonspecific clinical signs. Many dogs have a protracted course of weight loss to emaciation, chronic cough, persistent diarrhea, fever, anemia, hepatomegaly, splenomegaly, lymphadenopathy, and nasopharyngeal and GI ulceration. Obstructive respiratory difficulty due to tracheobronchial lymphadenopathy also has been seen in dogs. Dissemination may involve the skin, in which weeping, ulcerated, nodular lesions develop. Polyarthropathy, chorioretinitis, and retinal detachment have also been reported in a dog with disseminated histoplasmosis. Acute histoplasmosis may be fatal after 2–5 wk. In cats, disseminated infection is common. Clinical signs may be nonspecific but often include respiratory difficulty, fever, depression, anorexia, and weight loss. Lymphadenopathy, hepatomegaly, ocular disease (conjunctivitis, granulomatous chorioretinitis, retinal detachment, optic neuritis), lameness, and cutaneous nodules or ulcers may also be seen.
Gross lesions include enlargement of the liver, spleen, and mesenteric lymph nodes; ascites; yellow-white, variable-sized nodules in the lungs; and enlargement of bronchial lymph nodes. The enlarged liver may have multiple, scattered, irregular-shaped, pale yellow foci of granulomatous inflammation. Pale foci may be present in the myocardium, and the small intestine may have thickened, gray walls and ulceration of the mucosa.
Histoplasmosis should be considered when the clinical signs include weight loss, chronic diarrhea, respiratory distress, enlarged bronchial lymph nodes, and pulmonary nodules. Histoplasma organisms are usually numerous in affected tissues, and a definitive diagnosis can often be made by fine-needle aspiration and exfoliative cytology. Cytology of bone marrow may be diagnostic in cats. Tissue biopsy may be required if cytology is not diagnostic. Histoplasma organisms are difficult to detect with routine H&E stain but stain well with PAS, Gomori methenamine silver, and Gridley fungal stains. Yeast forms in macrophages and giant cells are round to ovoid (1–4 μm) structures with a thin cell wall and a thin, clear zone between the cell wall and cellular cytoplasm. H capsulatum can also be cultured from tissue specimens, fine-needle aspirates, and body fluids. Antigen testing using a quantitative antigen ELISA can be performed on urine, serum, and CSF. Cross-reactivity occurs with blastomycosis.
Itraconazole (10 mg/kg/day) is the treatment of choice for disseminated histoplasmosis in dogs and cats, although fluconazole is probably also effective. Ketoconazole, 10–15 mg/kg, bid for 4–6 mo, may be effective in early or mild cases of histoplasmosis in dogs. For severe cases, concurrent treatment with amphotericin B or amphotericin B lipid complex is suggested.