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FINAL DIAGNOSIS: Disseminated Blastomycosis in a Dog

History: A 3-year-old, male German Shepherd dog was submitted to the Animal Disease Diagnostic Laboratory for necropsy.  Reportedly, the dog had a history of anorexia and lethargy for three weeks.  The dog had been treated with a course of antibiotics for 10 days with some improvement.  Six days prior to death, the dog reportedly had an Addison’s crisis and was treated with steroids.  The dog was referred to Purdue University Teaching Hospital.  On presentation, the dog was tachypneic, pale and painful in the abdomen.  Ophthalmology exam revealed retinal granulomas in both eyes.  An aspirate of the popliteal lymph node showed pyogranulomatous inflammation and Blastomyces dermatitidis organisms.  The dog was humanely euthanized.

Gross Findings: Fibrous tags adhered the right caudal lung lobe, right middle lung lobe, and pericardial sac to the parietal pleura of the thoracic cavity.  The lungs were diffusely tan and dark red, mottled and firm on palpation.  Multifocal to confluent, circumscribed, firm, gray, variably-sized granulomas ranging from 1-10 mm in diameter were disseminated throughout the lungs.  The bronchial lymph nodes were enlarged and firm and measured approximately 2 x 1.5 cm.  The gastric contents were dark brown to black, liquid, and opaque.  The pyloric antrum of the stomach contained numerous multifocal mucosal ulcers which ranged from 4-7 mm in diameter.  Some of the ulcers had blood clots adhered to them.  Similar mucosal ulcers were found in the small and large intestine.

Histopathologic Findings:  The primary lesion in the lungs was a multifocal to confluent pyogranulomatous pneumonia.  Numerous intralesional, 10-20μm in diameter, spherical yeasts with a thick, double refractile cell wall, basophilic granular central zone, and occasional broad-based budding consistent with Blastomyces dermatitidis were present.   Bronchial lymph node lesions included pyogranulomatous lymphadenitis with intralesional Blastomyces dermatitidis. All sections of brain examined had multifocal pyogranulomatous encephalitis with intralesional Blastomyces dermatitidis organisms.  The primary morphologic alterations in the right and left eyes were multifocal sub-retinal accumulations of Blastomyces dermatitidis organisms with very little inflammatory reaction, retinal detachment, and small multifocal granulomas in the choroid.  Sections of stomach, duodenum, ileum, and jejunum contained acute multifocal mucosal ulcers.

Discussion: Blastomycosis is a systemic mycotic disease caused by the dimorphic fungus Blastomyces dermatitidis.  The disease primarily affects dogs and humans, but has been reported in cats, horses, sea lions, lions, wolves, ferrets and polar bears.  Young, male, large breed dogs (especially sporting breeds and hounds) living near water are at an increased risk.  It is generally restricted to the Mississippi River and OhioRiver basins and the central Atlantic states.

Most cases of blastomycosis are acquired by inhalation of aerosolized conidia into the lungs.  After inhalation, the conidia are phagocytized by alveolar macrophages and transform the mycelial phase to the yeast phase.  The yeast stimulates local cell-mediated immunity which results in a marked suppurative or pyogranulomatous inflammation.  The incubation period varies from 5-12 weeks.

The acute pulmonary phase of the illness may be asymptomatic or self-limiting or may result in acute fulminate infection.  The preferred sites of dissemination in the dog are the skin, eyes, bones, lymph nodes, subcutaneous tissues, external nares, brain, and testes.  Less commonly affected sites are mouth, nasal passages, prostate, liver, mammary gland, vulva, and heart.  The size of the yeast when it grows at body temperature prevents it from entering the terminal airway in an aerosol.  Therefore, aerosol transmission of the yeast phase from infected animals is not possible.  However, penetrating wounds can transmit the disease.  Primary cutaneous blastomycosis has been reported in veterinarians after accidental laceration while performing a necropsy on a dog with blastomycosis, following a dog bite from a dog with blastomycosis, and accidental inoculation with a needle used on a dog with blastomycosis.  Cutaneous blastomycosis is rare in the dog and should be considered a manifestation of disseminated disease.

The dog appears to be more susceptible to infection than humans, and serves as a sentinel for the disease.  Dogs have a shorter prepatent period and develop the disease before people do when exposed at the same time.  Most dogs with disseminated disease are probably immunosuppressed, since the majority of dogs experimentally infected by exposure of contaminated soil recover from blastomycosis without treatment.

Clinical signs in dogs with blastomycosis include anorexia, weight loss, cough, dyspnea, ocular disease, lameness, lymphadenopathy, and proliferative or draining skin lesions.  Signs of disease usually have been present for a few days to a week but may have been apparent for several months.  In many cases there has been a history of antibiotic therapy with minimal or temporary improvement.  A majority (85%) of dogs with blastomycosis have lung lesions, and up to 40% have ocular lesions, the most common of which is uveitis.  Skin lesions are found in 20-40% of dogs with blastomycosis.  Bone involvement occurs in up to 30% of infected dogs.  Diffuse lymphadenopathy is seen in 40% of dogs with blastomycosis.

The yeast organisms range from 5-20 μm in diameter and are characterized by broad based budding with a thick, refractile, double-contoured cell wall.  Diagnosis is usually based on finding the characteristic yeasts in cytologic or histologic preparations.  Hematology is usually not helpful in the diagnosis since complete blood count (CBC) results are often normal.  Radiographic assessment can be helpful in the diagnosis.  Thoracic radiographs often reveal a nodular interstitial pattern or diffuse interstitial pattern.  Serology should be used diagnostically only when a high degree of suspicion for Blastomyces exists and repeated attempts have failed to demonstrate the organisms.

Spontaneous recovery from symptomatic blastomycosis rarely occurs in dogs but has been reported in people.  Therefore, it is suggested that all cases of symptomatic blastomycosis in dogs should be treated.  Itraconazole is considered the treatment of choice, except in cases of moderate to severe hypoxemia when amphotericin B should be considered.  Approximately 70-75% of treated cases recover from blastomycosis.  Treatment failure most likely occurs in dogs that are hypoxemic or have three or more systems involved.

-by Dr. Phaedra Stiles, ADDL Graduate Student

References:

1.  Baumgardner EJ and Burdick JS: 1991. An Outbreak of Human and Canine Blastomycosis.  Review of Infectious Diseases 13: 898-905.
2.  Krohne SG:2000.  Canine Systemic Fungal Infections.  Vet Clinics of North America: Small Animal Practice 30 (5): 1063-1089.
3.  Legendre AM, et al: 1981.  Canine Blastomycosis: A Review of 47  Clinical Cases.  JAVMA 178:  1163- 1168.
4.  Lengendre AM: 1998. Blastomycosis.  In Green CE (ed) Infectious Diseases of Dog and Cat, W.B. Saunders Co., Philadelphia, pp 371-377.
5.  Ramsey DT:1994.  Blastomycosis in a Veterinarian.  JAVMA. 205: 968.
6.  Rudman DG: 1992.  Evaluation of Risk Factors for lastomycosis in Dogs: 857 cases (1980-1990). JAVMA 201: 1754-1759
7. Taboada J: 2000.  Systemic Mycoses. In Ettinger SJ (ed). Textbook of Veterinary Internal medicine, W.B. Saunders Co., Philadelphia. pp 458-462.

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