Histoplasmosis and cryptococcosis (Proceedings)

Histoplasmosis

Histoplasmosis is a systemic fungal infection caused by Histoplasma capsulatum.

The mycelial form grows in soil enriched with bird manure or other organic materials therefore areas of old chicken coops and bird roosts present a potential hazard. The spores (microconidia) produced by the mycelium are small and can be inhaled into the lungs where at body temperatures they transform into the yeast form. The yeast are phagocytized by macrophages and distributed throughout the body.

A subclinical infection can develop and the organisms can persist for a long time without significant clinical signs. In endemic areas, Histoplasma organisms can be recovered by culture from mesenteric and tracheobronchial lymph nodes of asymptomatic dogs.

In cats, the respiratory tract is a main site of infection but bone, bone marrow, liver, spleen, skin, and lymph nodes also affected. The intestinal tract, eyes, kidneys, adrenals, and brain less frequently involved

In dogs, the intestinal tract is frequently involved with liver, lung, spleen, and lymph nodes often involved. The bones, bone marrow, kidneys, adrenals, oral cavity, tongue, eyes, and testes may affected.

Traditionally the Ohio, Missouri, Mississippi, Tennessee, and St. Lawrence River basins have areas where histoplasmosis is common but Texas, the southeastern U.S., and the Great Lakes region have also seen histoplasmosis.

All ages can be infected but infections in young cats are common. Most infected dogs are middle aged.

In cats, anorexia, weight loss and dyspnea are associated with respiratory involvement. Coughing may be seen and lameness is associated with bone involvement. The eyes and skin can be involved. Diarrhea with intestinal infection is less commonly seen.

In dogs, diarrhea and weight loss is the most common sign. Dyspnea, coughing and exercise intolerance occurs with lung involvement. Lymphadenopathy is occasional seen as is eye involvement.

Fever is common and harsh lung sounds occur especially if there is enlargement of the tracheobronchial lymph nodes with compression of the tracheal bifurcation. Hilar lymphadenopathy is common and may persist after other signs of infection have resolved.

Emaciation occurs especially in animals with intestinal histoplasmosis because of a combination of anorexia and malabsorption. The bowel loops may feel thickened. Signs of large bowel diarrhea with blood and mucous may be seen. Liver and splenic enlargement is common in animals with intestinal histoplasmosis. Some animals may be icteric. Pale mucous membranes may be seen because histoplasmosis may cause a hemolytic anemia. Lameness with bone pain is noted with boney involvement. Chorioretinitis and anterior uveitis may been seen.

A diagnosis made by identification of the organism is most reliable. The clinician should be suspicious of histoplasmosis when there is multiorgan disease that is unresponsive to antibiotic therapy. Lung radiographs may be characteristic of a fungal pneumonia but other conditions such as lymphosarcoma may resemble the lungs of histoplasmosis.

In severe chronic diarrhea and weight loss, consider histoplasmosis as well as lymphocytic plasmacytic enteritis and lymphosarcoma. Organisms are ofter found on cytology of rectal scrapings. Cytology may identify colonic lymphosarcoma. In animals with hepatomegaly and spenomegaly, needle aspirates will often identify the organisms. Bone marrow aspirates are likely to yield Histoplasma organisms when there is systemic disease.

Complete blood counts may have a leukocytosis but this is non-specific. Moderate anemia is a common finding. The anemia may be the anemia of chronic inflammation but may be a hemolytic anemia. At times the antibodies produced to the Histoplasma organisms cross react with the red blood cells thereby producing a Coombs positive anemia. Liver involvement may produce increases in ALT and Alkaline Phosphatase while severe gut involvement may produce hypoproteinemia due to protein losing enteropathy. The Agar Gel ImmunoDiffusion (AGID) for antibodies strongly supports a diagnosis of histoplasmosis but many infected dogs will be negative early in the disease. Cross reactivity between Blastomyces and Histoplasma organisms is expected.

There is a urine and serum antigen test for histoplasmosis that may be helpful in making a diagnosis but there is little information about its usefulness in the diagnosis of histoplasmosis. The urine antigen test appears to be quite sensitive in dogs with blastomycosis but no studies have been published in animals with histoplasmosis. More information can be obtained from the company website at miravistalabs.com. Identification of organisms on cytology, histopathology, or culture provides a definitive diagnosis. Enlarged lymph nodes, liver, and spleen are good sites to aspirate. Rectal scrapings may be rich in organisms as are bone marrow or lung aspirates. Tracheal washes give inconsistent results.

Itraconazole is the drug of choice if there is adequate intestinal absorption. The itraconazole pellets should be given with a fatty meal to enhance absorption. Be leery of compounded intraconazole as the absorption may not be good. Itraconazole at a dose of 5mg/kg twice a day for at least 90 days or for 1 month after all signs of disease have resolved.

With severe inflammatory bowed disease and malabsorption, amphotericin B is the drug of choice at 0.5 mg/kg given IV over 3 or 4 hours every other day in dogs. In cats a starting dose of 0.25 mg/kg every other day should be given. Animals need to be well hydrated before starting amphotericin B. BUNs need to be checked before every dose of amphotericin B. When the appetite returns and there is weight gain, the amphotericin B therapy can be changed to itraconazole. It may be necessary to initiate intravenous total parenteral nutrition in emaciated animals until gut absorption improves.

In dogs with severe inflammatory bowel disease and malabsorption—use amphotericin B until patient begins to gain weight; then start on itraconazole.

Some dogs with tracheobronchial lymph node enlargement may need modest doses of steroids after the infection has resolved to control the chronic coughing.

Cryptococcosis

Cryptococcosis is a localized or systemic fungal infection caused by the environmental yeast Cryptococcus neoformans. The organism grow in decaying vegetation and pidgeon droppings appear to be an excellent growth media. Dried fecal material that is aerosolized may facilitate infection. In cats most infections are established in the nasal passage. The organism may establish itself in the terminal airways. Hematogenous dissemination to many tissues especially the brain, eyes and lung can occur.

Cryptococcosis is much more common in cats than in dogs. There is a worldwide distribution of the disease but there it is more often seen in Southern California and Australia. There appears to be an association with eucalyptus trees.

Dogs and cats with cryptococcosis may be lethargic and anorexic. Nasal discharge, nasal obstruction and sneezing are the most common signs in cats. Cats may have a bump on their nose where the infection is breaking through the nasal bones. Skin ulceration and neurologic signs such as seizures, ataxia, paresis and blindness may be seen. There may be respiratory signs with lung involvement. In cats with nasal involvement, nasal lymphosarcoma and chronic sinusitis must be eliminated.

Laboratory findings are usually minimal because Cryptococcal organisms do not produce strong inflammatory responses. Swabs, needle aspirates or surgical biopsies of lesions will usually identify the organisms. When cryptococcosis is suspected the latex agglutination or an ELISA test for cryptococcal capsular antigen in serum is helpful. The test appears quite reliable for cats but may be negative in dogs with cryptococcosis. This antigen test is also helpful in monitoring the course of treatment. The magnitude of the antigen titer seems to correlate to the amount of infection. In neurologic cases, the organism may be found in the cerebral spinal fluid. The antigen assay should also be done on the CSF if no organisms are found. In cats with upper respiratory obstruction or severe respiratory noise, there may be agranulomatous polyp in the nasopharyn. By pulling the soft palate forward with a spay hook, the polyp can be exposed and biopsied.

Biopsies of skin lesions of the head and aspirates of the involved lymph nodes will usually identify the organisms.

Nasal examination with an otoscope speculum in cats will usually identify a gray, gelatinous material produced by the polysaccharide capsule of the organism. This material is usually rich in organisms. There may be optic neuritis, chorioretinitis and retinal detachment in some animals.

Fluconazole is the preferred treatment when there is eye or brain involvement. It can be dosed at 5 mg/kg twice a day or cats can be treated with a 50 mg tablet twice a day. Itraconazole is also a good drug at 5 mg/kg twice a day with a fatty meal. Be leery of the generic compounded itraconazole because of poor absorption. In cats, the capsular antigen titers can be used as a guide to duration of treatment. There should be a 2 to 4 fold decrease in titers after 2 months of treatment if the therapy is effective. The titers should be nearly zero before therapy is discontinued. Titers should be monitored after discontinuation of treatment to identify increasing titers that reflect persistent or recurrent infection. Cryptococcal organisms often develop drug resistance during treatment. Increasing titers during therapy can be attributed to drug resistance. Terbinafine at 5 mg/kg twice a day is a suitable alternative when resistance to the azoles occurs. Cats that are infected with feline leukemia virus or feline immunodeficiency virus are more likely to fail treatment. Monitor for hepatic toxicity with the azoles and the terbinafine. There may be an ulcerative dermatitis in some dogs receiving itraconazole.