Basics of blastomycosis (Proceedings)

Blastomycosis is a systemic fungal infection caused by the dimorphic fungi Blastomyces dermatitidis. Blastomycosis affects dogs, cats, horses, sea lions, lions, rhesus monkeys and polar bears. Dogs are the species most often infected. In endemic areas, dogs are infected at a rate of 10 times that of people. It is suspected that being close to the ground and sniffing the soil accounts for the increased incidence of blastomycosis in dogs. The geographic distribution of disease in animals parallels that in people with most cases in the Mississippi, Ohio and Missouri River basins. In the south, there is no distinct seasonal occurrence but in areas such as Wisconsin disease often follows the fall hunting season. Proximity to water is a major risk factor in dogs with most infected dogs living within 500 yards of water. Larger dogs are more likely to become infected probably because they are more likely to roam. Sporting dogs such as Labrador Retrievers are at increased risk. Some non-sporting breeds such as Doberman Pinschers are at increased risk because of suspected increased breed susceptibility to infection with Blastomyces. Outbreaks in neighborhoods suggest a common source of infection or "ecologic niche" where many animals come in contact with the organism and become infected.

Most cases of blastomycosis are acquired by inhalation of the spores from mycelial growth in the environment. The spores enter the terminal airway and establish a primary infection in the lungs. The size of the yeast when it grows at body temperature precludes its entering the terminal airway in an aerosol. Most dogs with blastomycosis first develop a fungal pneumonia. The organism then disseminates throughout the body with skin, lymph nodes, eye and bone often infected. Subclinical infections are uncommon and apparent localized skin lesions are usually part of a systemic disease. Less common sites of infection are testes, mammary glands, prostate, heart and brain. Eye involvement produces a uveitis, chorioretinitis, retinal detachment and secondary glaucoma.

Dogs with blastomycosis usually have signs of anorexia, weight loss, cough, dyspnea, ocular disease, lameness, or skin lesions. Signs of disease usually have been present for a few days to a week but may have been apparent for up to a year. In some dogs, the disease process seems to stabilize; animals may show minimal signs for weeks to months, and then the disease suddenly progresses with worsening of signs.

Eighty-five percent of dogs with blastomycosis have lung lesions with characteristic dry, harsh lung sounds. Dogs with mild lung disease show exercise intolerance, and severely affected dogs have dyspnea at rest. Coughing is a variable finding. Thoracic radiographs are indicated for dogs suspected of having blastomycosis because some dogs have lung changes without respiratory signs. Diffuse, nodular interstitial and bronchointerstitial lung changes are most commonly seen. Other less common manifestations include well-marginated solitary to multiple cystic or solid nodules to masses. Tracheobronchial lymphadenomegaly occurs in some dogs. Pleural effusion, pneumomediastinum, and cavitary lung lesions are also observed. Chylothorax and solid fibrous masses are uncommon manifestations of thoracic blastomycosis. Solid fibrous masses may partially occlude the great vessels.

Up to 40% of dogs with blastomycosis have ocular lesions, the most common of which is uveitis. Early signs of uveitis are aqueous flare, miosis, blepharospasm, and photophobia . Retinal separation with detachment, retinal granulomas, and vitreal hemorrhage are also seen. Severe corneal edema may prevent good visualization of the internal ocular structures. Glaucoma secondary to angle closure occurs in blastomycosis. Periorbital cellulitis and involvement of the nictitating membrane also occur. Uveitis in conjunction with signs of respiratory or skin disease should alert the clinician to consider blastomycosis. Early diagnosis and appropriate treatment are essential to preservation of vision in blastomycosis. Anterior segment disease has a worse prognosis for maintaining vision because glaucoma is a common sequela to ocular blastomycosis.

Skin lesions, found in 20% to 40% of dogs with blastomycosis, may be ulcerated with drainage of a serosanguineous or purulent fluid. Other lesions may be granulomatous, proliferative, and meaty. There may be welldefined subcutaneous abscesses. Although the skin lesions may be found anywhere, the planum nasale, the face, and the nail beds appear to be preferred sites.

Bone involvement occurs in up to 30% of infected dogs. Lameness is the primary sign in affected animals and may be the only sign of disease. Special procedures, such as bone scans, may identify a greater percentage of dogs with bone involvement. Lesions usually involve the appendicular skeleton; they are usually osteolytic with periosteal proliferation and soft tissue swelling . A majority of the bone lesions are solitary and occur distal to the stifle and elbow. Fungal osteomyelitis must be differentiated from primary and metastatic bone tumors and bacterial osteomyelitis.

Organisms can be readily identified by cytology and histology in over half the cases. The Agar Gel Immunodiffusion test (AGID) has a sensitivity of 40 to 90% but a specificity of 90 to 100%. A positive AGID in the face of compatible clinical signs is strongly supportive of a diagnosis of blastomycosis. A new and exciting diagnostic approach using antigen testing to identify infected dogs has been evaluated. Most urine and serum samples from dogs infected with blastomycosis had antigen titers well above the range for negative specimens. Only 1 of 44 control urine samples and none of the 44 control serum samples had values considered to be positive. The sensitivity and specificity for the assay on urine was 93% and 98% respectively while the serum assays had a sensitivity of 87% and a specificity of 100%. There was a dramatic decline in serum antigen concentrations 30 days after the initiation of treatment with itraconazole. Urine antigen concentrations were maintained at 30 days but declined after 60 days of treatment. Urine antigen concentrations declined at a slower rate than the serum antigen concentrations.

Preliminary findings support the use of the antigen assay in the diagnosis of blastomycosis in dogs. There were fewer false negative results from the urine antigen assay than from the serum antigen assay. False positive results appear to be rare making the assay valuable to rule in the diagnosis of blastomycosis. Further studies are needed to determine if there are cross reactions in the assay between Blastomyces sp. and other fungal organisms. Further studies are needed to determine if antigen concentrations can be used to determine duration of antifungal treatment needed for cure of blastomycosis.

Further information on the antigen test can be obtained from the Mira Vista website at www.miravistalabs.com.

The current treatment of choice in animals is itraconazole for 60 to 90 days. Itraconazole is as effective as amphotericin B and has fewer adverse effects. Central nervous system disease has a guarded prognosis and should be treated with amphotericin B. About 20% of dogs with severe lung involvement will die during the initial week of treatment. In dogs that recover from blastomycosis, about 20% of the dogs treated will have a recurrence of disease. The Blastomyces organisms do not develop resistance and another course of treatment with itraconazole is usually curative.

A Blastomyces organism with a deletion of the BAD-1 gene coding for an adhesion molecule has been produced in Dr. Bruce Klein's laboratory. The BAD-1 gene product is a virulence factor necessary for production of disease. The gene-deleted organism can protect mice from a lethal challenge of Blastomyces organisms. The modified organism does not produce disease in dogs. Subcutaneous injections with up to 107 organisms did not produce systemic disease and rarely could a few organisms be cultured from a regional lymph node. Field trials are planned to assess the effectiveness of the vaccine in dogs living in endemic areas.

Care must be taken when doing aspirates of suspected lesions of blastomycosis to avoid needle sticks. Pathologists have become infected by cutting themselves while doing necropsies on dogs with blastomycosis. Aerosol transmission is not considered to occur. Culture of blastomycosis lesions should be done in a laboratory with adequate facilities to avoid infection.