HISTOPLASMOSIS

By Lisa Cellio, DVM, Diplomate AVCIM (Small Animal Internal Medicine)

Histoplasmosis is a soil-borne dimorphic fungus that lives in warm moist and humid conditions. The causative agent is Histoplasma capsulatum and grows best in soil rich in nitrogen organic matter (such as areas with bird or bat excrement.) Histoplasmosis is endemic in temperate and subtropical regions and, in the United States. is most commonly found around the Ohio, Missouri, and Mississippi river valleys.

Infections occur after inhalation of the microconidia. In the body, the microconidia convert to the yeast phase in the lungs and reproduce by budding. The yeast are phagocytized by mononuclear cells. The incubation period is 12-16 days. Infections usually start in the lungs and spread to the lymph nodes and then other organs, including the gastrointestinal system, liver, spleen, bone marrow, adrenal glands, eyes, and, occasionally, the skin or CNS. Occasionally there is an occurrence of the gastrointestinal histoplasmosis without respiratory involvement suggesting the gastrointestinal tract may also be a primary source of infection.

Clinical signs vary with species. Cats have nonspecific signs because of disseminated disease. Dyspnea, tachypnea and abnormal respiratory sounds are common findings. Dogs more commonly have signs of inappetance, fever and weight loss. Signs may be limited to the respiratory tract but most have gastrointestinal involvement. Pointers, Weimaraners, and Brittany spaniels seem to be overrepresented.

Diagnosis is best made by the identification of small (2-4 um) organisms with halos seen on aspirates or impression smears. Occasionally these can also be found in circulating white blood cells or even in CSF. Organisms are most commonly found in the lung, lymph node or bone marrow aspirates in cats. In dogs, rectal scrapes, imprints of colonic biopsies or aspirates of the liver, lung, spleen or bone marrow are best. Histoplasmosis can be difficult to detect in biopsy specimens with hematoxylin and eosin stain. Special fungal stains should be used on biopsy specimens. Fungal isolation is not recommended because the organism is pathogenic. Serology is unreliable. The Histoplasmosis antigen test (Mira Vista) is gaining popularity. It can be used to support disease and is useful in monitoring for resolution with treatment.

Other abnormalities noted include a normocytic, normochromic, nonregenative anemia. Hypoalbuminemia occurs more commonly in cats. Occasionally, clotting times can be abnormal suggestive of microangiopathic hemolysis. Chest radiographs may reveal a linear or diffuse pulmonary interstitial pattern. Hilar lymphadenopathy is more common in dogs than in cats.

Itraconazole is the treatment of choice in both dogs and cats. Side effects include anorexia, vomiting and diarrhea, increased liver enzymes and a dose-dependent cutaneous vasculitis or dermatitis. Itraconazole should be continued 30 days past resolution of clinical signs and usually is a 4-6 month course. Histoplasma antigen can also be monitored. Pulmonary histoplasmosis in dogs can be self-limiting and may resolve without treatment. Itraconazole has poor penetration to the eyes and CNS but has led to resolution. Fluconazole has better penetration to the eye and CNS but is not as effective overall as itraconazole in the treatment of Histoplasmosis. It may also antagonize amphotercin B. Lipid complexed amphotercin B can be used alone or in combination with itraconazole for severe disease. It is helpful in animals that are anorexic or having gastrointestinal signs which may worsen on oral antifungal medications.

Corticosteriods often need to be used early in the course of treatment, although their use is controversial. They may help to decrease the inflammation associated with destruction of the fungus. They can also help to increase the appetite of cats or dogs with histoplasmosis. Initial response to therapy with itraconazole may take 7-14 days. Some animals may experience worsening in their respiratory signs in the first week of therapy. Bloodwork should be monitored approximately every month for changes in the liver enzymes while animals are on itraconazole. Increasing liver enzymes or persistent anorexia in animals undergoing treatment may lead to dosage adjustment or changing of the medication to a different antifungal agent. The prognosis for animals with Histoplasmosis is guarded to fair.

References:
1. Greene, CE. Histoplasmosis, In: Greene, CE.ed. Infectious Disease of the Dog and Cat, 2nd ed. Philadelphia: WB Saunders; 1998, pp.577-583.
2. Sellon, RK, Legendre, AM. Systemic Fungal Infections, In: Bonagura, JD ed. Current Veterinary Therapy XIV. St. Louis: Saunders; 2009, pp.1265-1267

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