Blastomycosis
Blastomycosis, caused by the dimorphic fungus Blastomyces dermatitidis, is characterized by pyogranulomatous lesions in various tissues. It is most common in people, dogs, and cats but has also been described in such widely divergent species as horses, ferrets, deer, wolves, African lions, bottlenosed dolphins, and sea lions. It appears not to be a disease of cattle, sheep, or pigs. Blastomycosis is generally limited to North America, and most cases have occurred in the Mississippi, Missouri, Tennessee, and Ohio River basins and along the Great Lakes and the St. Lawrence Seaway. There is an endemic area in the Pacific northwest. Even within these river basins, the organism is found in geographically restricted areas. Beaver dams and other habitats where soil is moist, acidic, and rich in decaying vegetation may serve as the ecologic niche for the organism, but it is often difficult to find in the environment. The organism has also been recovered from pigeon and bat feces. Rain, dew, or fog may play a critical role in liberating the infective conidia, which then are aerosolized and inhaled. When respiratory defenses are overwhelmed or immunosuppressed, disseminated disease occurs via hematogenous spread from the lungs. Cutaneous lesions may result from a primary entry through the skin or, more commonly, by dissemination from a pulmonary focus. Needle-stick injuries to veterinary personnel after aspiration of cutaneous lesions from infected animals have resulted in primary cutaneous infection. Ocular lesions tend to develop first in the posterior segment, resulting in granulomatous chorioretinitis and retinal detachment. Anterior segment involvement often follows, resulting in anterior uveitis and panophthalmitis.
Clinical Findings:
The signs vary with organ involvement and are not specific. Weight loss may be accompanied by coughing, anorexia, lymphadenopathy, dyspnea, ocular disease, lameness, skin lesions, and fever. Dry, harsh lung sounds from lung lesions are common in dogs with blastomycosis. Signs of pulmonary involvement are seen in as many as 85% of affected dogs. Severe pulmonary involvement results in hypoxemia, which indicates a poor prognosis. Lymph node involvement is seen in approximately half of affected dogs, which is about the same proportion of dogs that have cutaneous involvement. Skin lesions may include proliferative granulomas and subcutaneous abscesses that ulcerate and drain a serosanguineous discharge. The skin lesions are often very small and multifocal in dogs, but large abscesses are occasionally seen, especially in cats. The planum nasale, face, and nail beds are most often involved. Signs of ocular blastomycosis are seen in 30%–50% of affected dogs and include blindness, uveitis, glaucoma, and retinal detachment. Lameness associated with fungal osteomyelitis or severe paronychia occurs in approximately one quarter of affected dogs. CNS signs are uncommon, occurring in <5% of dogs, but they may be more common in cats. The pattern of systemic involvement is similar in cats, but cats are affected far less commonly than dogs. Hematuria and dysuria may be seen with urogenital blastomycosis.
Lesions:
Gross lesions consist of few to numerous, variable-sized, irregular, firm, gray to yellow areas of pulmonary consolidation and nodules in the lungs and thoracic lymph nodes. Dissemination may result in nodular lesions in various organs but especially the skin, eyes, and bone. Cutaneous lesions are single or multiple papules, or chronic, draining, nodular pyogranulomas.
Diagnosis:
Blastomycosis should be considered in dogs with draining cutaneous nodules and signs of respiratory disease. In cats, respiratory tract involvement is seen most frequently, followed by involvement of the CNS, regional lymph nodes, skin, eyes, and GI and urinary tracts. Radiographic findings in the lungs include noncalcified nodules or consolidation, with enlargement of the bronchial and mediastinal lymph nodes. The predominant patterns on thoracic radiographs are those of diffuse nodular interstitial and peribronchial densities. Commonly, the bronchial lymph nodes are greatly enlarged and appear in radiographs as dense masses. Diagnosis can be made from biopsy of tissue or aspirated specimens taken from cutaneous lesions or other involved organs by the presence of thick-walled yeast that often have daughter cells budding from a broad base. These round to ovoid, pale pink (H&E;) blastospores measure 8–25 μm and have a refractile, double-contoured wall. They may be empty or contain basophilic nuclear material and have single, broad-based buds. An antibody response, detected by agar gel immunodiffusion, usually occurs, but this response is neither sensitive nor specific when attempting to make a definitive diagnosis. An enzyme immunoassay for antibodies to rBAD-1 repeat has shown improved sensitivity. A recently developed antigen enzyme immunoassay has been used in both serum and urine to detect cell-wall galactomannan that is immunologically indistinguishable in histoplasmosis and blastomycosis. Although the titer is not useful in differentiating between the two infections, it helps diagnose the presence of one of these two systemic mycoses.
Treatment:
Itraconazole (5 mg/kg/day) is the treatment of choice for dogs and cats with blastomycosis. A minimum of 2 mo of treatment is necessary, and the drug should be continued until active disease is not apparent. Clinical cure can be expected in ~70% of dogs, with recurrence months or years after treatment noted in ~20% of treated dogs. Most dogs will respond to retreatment with itraconazole. Other azoles such as fluconazole and ketoconazole are not as effective as itraconazole, but a study evaluating cost-effectiveness of fluconazole showed it to be a less expensive alternative, despite longer treatment times. In fulminating cases of blastomycosis, especially those with evidence of hypoxemia, combination therapy with amphotericin B and itraconazole is recommended. Short courses of anti-inflammatory dosages of glucocorticoids have been advocated during the first few days of treatment by some, but steroid use is controversial and may actually worsen the prognosis. The prognosis is best for dogs with only mild lung disease, is more guarded for dogs with moderate to severe lung disease, and is poorest for dogs with CNS involvement.
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