Systemic fungal diseases (Proceedings)
The fungal organisms most commonly associated with systemic disease are Blastomyces dermatitidis, Histoplasma capsulatum, Coccidioides immitis and cryptococcosis.
Blastomycosis refers to the systemic disease caused by Blastomyces dermatitidis. Blastomycosis is most common in North America along the larger river valleys (Mississippi, Ohio, Missouri) and east coast (mid-Atlantic states) into Canada. This is a dimorphic fungus that exists in the environment in a saprophytic mycelial form. Acidic, sandy soil near water is believed to be the most common source of exposure. The mycelial form reproduces sexually in the environment producing infective spores.Disease is much more common in the dog than the cat. There is no sex, age or breed predilection in the cat. In the dog being male, younger, large breed, or a sporting breed may be risk factors. The disease does have a seasonal occurrence in some, but not all, regions. These spores are inhaled and become yeasts within the body. These yeasts are then disseminated via vascular or lymphatic routes. More common sites of infection include the lungs, skin, eyes, lymph nodes, bone, brain, and testes. Common clinical signs include fever, anorexia, weight loss, dyspnea, cutaneous nodules, draining tracts, lameness, and ocular lesions.
Bloodwork may reveal a mild normocytic normochromic anemia, moderate luekocytosis, hyperglobulinemia, and hypoalbuminemia due to chronic inflammation and infection. Hypercalcemia is also sometimes seen due to a PTH-independent increase in 1,25 - dihydroxyvitamin D.
Radiographic findings within the thorax include tracheobronchial lymphadenopathy and diffuse nodular interstitial or bronchointerstitial changes. Mass like lesions and effusion are less common. Radiographic changes in bone include osteolysis, periosteal proliferation and soft tissue swelling.
Diagnosis is typically made by identification of the yeast in tissues cytologically (most commonly) or histologically. Cytology is typically done on lymph node or cutaneous aspirates but vitreal taps, bronchial washes, lung aspirates, urinalysis, and csf can be evaluated for organisms. The yeast is ovoid, 5 to 20 µm, single or budding, with a thick refractile wall. Histopatholgy, on tissues suspicious of infection, is performed when cytology is not possible or diagnostic and reveals organisms as well as granulomatous or pyogranulomatous inflammation. Antibody detection via serology is not typically performed. With acute infections dogs may not have detectable titers and, although it appears uncommon, dogs without clinical disease may have antibody titers. There is a blastomyces antigen enzyme immunoassay available for dogs that detects cell wall galactomannan in serum, urine and csf. Unfortunately there is cross reactivity in dogs with blastomycosis and histoplasmosis. In humans there is cross reactivity between histoplasmosis, coccidiomycosis, paracoccidiomycosis, and penicillosis. Utilizing this immunoassay, antigen levels can also be followed during treatment. PCR has been performed on histologic samples but is not as readily available. Culture can be performed but is not typically necessary or recommended.
Itraconazole is used most commonly to treat this disease in dogs and cats. Amphotericin B was utilized historically but itraconazole appears as effective with fewer side effects and less expense. Amphotericin B is recommended when there is severe clinical disease and evidence of CNS involvement. Voriconazole and fluconazole can be used with CNS and ocular involvement. Fluconazole is also recommended when there is urinary tract involvement because of its excretion into urine. Treatment is for a minimum of 90 days and 30 days past resolution of signs. Glucocorticoids have been used short term in severe respiratory infections and when airway obstruction secondary to tracheobronchial lymphadenopathy occurs.
Most dogs treated effectively recover from infection. Recurrence (not reinfection) can occur in some animals. CNS involvement or severe pulmonary infection carries a higher mortality rate. If there is ocular involvement, vision may be lost and, in fact, the eye may remain infected. For this reason, enucleation of non-visual eyes is recommended.