Blastomycosis In Dogs and Cats

Adam L. Mordecai, DVM; Perry J. Bain, DVM, PhD; and Kenneth S. Latimer, DVM, PhD 

Class of 2003 (Mordecai), Department of Pathology (Bain, Latimer), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7388 

Epidemiology

Blastomycosis, caused by the agent Blastomyces dermatitidis, is a systemic fungal disease that primarily affects dogs and humans, but has also been known to infect cats, sea lions and horses. Blastomyces dermatitidis is a dimorphic soil fungus that is found in the Mississippi, Missouri, and Ohio River valleys, as well as the mid-Atlantic states and the Canadian provinces of Quebec, Manitoba and Ontario.¹ Its exact ecologic niche has yet to be characterized, but most agree it requires wet, sandy, acidic soils rich in organic matter and in close proximity to water. At room temperature (25°C), the organism is found in the mycelial (hyphal) form and produces conidia, while at body temperature, the organism usually occurs in the yeast form.¹

Infection occurs primarily through inhalation. In the lung, alveolar macrophages phagocytize spores and the organism transforms to the yeast phase. Pulmonary macrophages transport the organism to the pulmonary interstitium. Other routes of infection include skin lesions or penetrating injuries that introduce the organism into the body. Dissemination can occur in patients that are immunosuppressed.¹

Risk Factors

Dogs are approximately 10 times more likely to be infected with B. dermatitidis than humans and can be considered sentinel animals.² Male dogs and large breed dogs have a higher incidence of blastomycosis, and most cases occur in dogs between 1 and 5 years of age.¹ In one study, Bluetick Coonhounds, Treeing Walker Coonhounds, Pointers, and Weimaraners were found to have an increased incidence of blastomycosis when compared with mixed-breed dogs.³ Another study found Labrador Retrievers, Golden Retrievers, Doberman Pinschers, and Cocker Spaniels to have an increased incidence of disease.⁴ The increased incidence in large breed dogs and in intact male dogs may be due to a tendency for these animals to spend a larger amount of time outdoors, or a greater tendency to roam, which may increase exposure to the organism.

Blastomycosis is less common in cats than in dogs, and risk factors have not been studied.

Clinical Signs and Physical Findings

In one retrospective study, clinical signs included respiratory tract problems (49%), depression (48%), anorexia (48%), ocular problems (43%), weight loss (37%), dermatologic abnormalities (29%), lethargy (26%, fever of unknown origin (26%), lameness (23%), exercise intolerance (19%), gastrointestinal tract problems (16%), polyuria or polydipsia (9%), mammary gland mass (3%) and urogenital tract problems (2%).⁴ Cats show similar clinical signs as dogs, with respiratory difficulty characterized by dyspnea or chronic cough being the most common sign. Depression, dehydration, ocular disease, and CNS signs are also seen.⁵ 

Physical findings reflect clinical history and vary greatly. These include lymphadenopathy (56%), fever (62%), harsh lung sounds (50%), draining skin lesions (49%), chorioretinitis (43%), anterior uveitis (42%), cough (32%), emaciation (25%), retinal detachment (23%), soft–tissue mass (16%), secondary glaucoma (16%), tachypnea (16%), dehydration (15%), bony mass or swelling (14%), nasal discharge (8%), CNS signs (6%), prostatomegaly (5%), mammary gland mass (3%), orchitis (2%), joint effusion (1.7%), and vulvar mass (1.2%).⁴  Ocular lesions were the only physical sign of infection in 3% of dogs in another study.⁶

Diagnosis

Diagnosis should be made based on history, presentation, and clinical findings. Unfortunately, identification of the organism is the only definitive means of diagnosis. Hematologic and biochemical findings are nonspecific. The most common hematologic abnormality in affected dogs is a neutrophilic leukocytosis with a mild left shift.⁴ Hypoalbuminemia (77%), hyperglobulinemia (58%), and corrected hypercalcemia (13.7%) may also be observed.⁴

Thoracic radiographs should be taken if respiratory difficulty is observed. Typical radiological findings (Fig.1) include nodular interstitial pattern (39%), tracheobronchial lymphadenopathy (29%), interstitial pattern (22%), mixed pattern (15%), bronchointerstitial pattern (9%), alveolar pattern (9%), pleural disease (8%), mediastinal mass (2%), and pneumothorax (1%). Up to 6% of animals have normal thoracic radiographic studies.⁴

Figure 1. Thoracic radiograph from a dog with blastomycosis, showing diffuse miliary to nodular interstitial infiltrate (Photo courtesy of Dr. Royce Roberts, Univ. of Georgia Dept. of Anatomy and Radiology).

Blastomycosis may be diagnosed by identification of the organisms in cytologic samples (Fig. 2). Blastomyces dermatitidis usually is seen in the form of round yeast ranging from approximately 5-20 µm in diameter. The organisms stain blue with Wright’s or Diff-Quik stains, have a thick cell wall, and broad-based budding is typically observed. The presence of B. dermatitidis in cytologic specimens is usually associated with granulomatous to pyogranulomatous inflammation.

Figure 2. Pyogranulomatous inflammation with budding B. dermatitidis yeast in a tissue aspirate from a dog (Wright's stain).

Pulmonary blastomycosis may be diagnosed by transtracheal wash (TTW), bronchoalveolar lavage (BAL), or fine-needle aspirate of the lung parenchyma. In one study, BAL was diagnostic for blastomycosis in 5 of 7 infected animals, while TTW was diagnostic in 3 of 7 animals with blastomycosis.⁷ Multiple lung lobes (2 to 4 in each animal) were sampled while performing the BAL, but not all sampled lobes were affected.⁷ Therefore, multiple samples should be taken to evaluate the smaller pathways.

BAL fluid is representative of the deep portions of the lung and can accurately reflect the inflammatory response at the level of the alveoli. A thorough examination of the fluid should be performed because of the potential for low numbers of organisms in the sample. Furthermore, the saline used as lavage fluid may alter the appearance of the organism, resulting in a "crenated" appearance that may complicate identification of the organism.

Fine-needle aspiration (FNA) of focal lung parenchymal lesions has also yielded good results. Indications for ultrasound-guided FNA of pulmonary lesions include the presence of a suppurative inflammatory process in which BAL or TTW failed to yield a diagnosis, when the severity of illness precludes general anesthesia, a suspected neoplasm where exploratory thoracotomy is not warranted, undiagnosed thoracic lesions, or pulmonary disease unresponsive to conventional treatment.⁸ FNA of the lung is limited to masses located peripherally in the lung. Contraindications for lung FNA include coagulopathy, pulmonary bullae, severely compromised pulmonary function, pulmonary hypertension, or an unstable clinical condition. Pre-medicating with atropine to prevent severe vagal bradycardia is recommended. 

Skin and lymph nodes samples offered the highest number of positive samples submitted in one retrospective study.⁹ The type of inflammatory reaction was related to the type of tissue sampled. In solid tissues, like skin or subcutaneous tissues, the reaction tended to be pyogranulomatous; whereas in fluid tissues like joint, prostatic, or ocular fluid, the reaction tended to be mildest. In this study, the finding of pyogranulomatous inflammation, or any purulent inflammation with a marked tendency to form clusters of neutrophils was the most accurate indicator that a careful search for yeast cells should be undertaken.⁹ 

If the disease has an ocular component, and less invasive diagnostic procedures have failed, vitreous aspirates or histologic examination of enucleated eyes may identify the organism. In a study surveying the ocular characteristics of B. dermatitidis infections, 25% were affected in the right eye, 27% in the left eye and 48% were affected in both eyes. Furthermore, in this study, 48% of dogs had ocular manifestations of the disease. This may be attributed to the sample population having more advanced disease or to increased recognition of the ocular manifestations of systemic blastomycosis. Thus, a more complete ocular examination is recommended in dogs suspected or confirmed to have the disease.⁹

In dogs with urinary tract or prostatic blastomycosis, the organism may be found in the urine sediment. With CNS signs, organisms are rarely found on CSF examination. Culture of cytologic specimens when blastomycosis is suspected is not recommended because of potential danger to laboratory personnel. 

Serologic testing can be used if identification of the organism is not possible or not definitive. The agar-gel immunodiffusion test (AGID) is the most common serologic test used. It has as sensitivity and specificity of greater than 90% in the dog. Despite this, test results may be negative early in the development of infections.¹ Results are relatively unrewarding in cats with one of three cats testing positive in one retrospective study.¹⁰ 

Treatment and Prognosis

Amphotericin B (AMB) is considered the standard treatment for systemic fungal infections like blastomycosis. It is a rapid-acting, effective treatment; however, it must be given intravenously and it is nephrotoxic. Attempts to reduce nephrotoxicity by prior administration of IV saline have not prevented nephrotoxicity, and most dogs treated with AMB still develop some degree of acute renal failure.¹¹ The recommended dosage of AMB is 0.5 mg/kg of body weight IV every other day. Drug therapy should be stopped when a cumulative dose of 8-10 mg/kg of body weight is reached, or if the blood urea nitrogen (BUN) concentration approaches 50 mg/dl.¹ BUN should be monitored closely during AMB therapy.

Itraconazole (ITZ) therapy has replaced AMB as the drug of choice for treatment of blastomycosis because it as effective as AMB, but safer.¹ While more expensive per dose, it is administered orally, allowing patients to be treated at home. Considering the expense of hospitalization, frequent renal function testing and IV maintenance associated with amphotericin B treatment, the two treatments have a similar overall cost. Furthermore, itraconazole penetrates the eye in dogs with active disease.³ ITZ, however, is not excreted in the urine and cannot be used for the treatment of urinary tract disease. ITZ is also hepatotoxic and animals should be monitored for elevations in liver enzymes.¹² ITZ should be started at a dose of 5mg/kg of body weight every 12 hours for 5 days to maximize blood levels rapidly, and thereafter reduced to once a day treatment. Treatment should be administered for at least 60 days or 1 month after clinical signs of disease have resolved.¹ Dogs with severe lung involvement should be treated for at least 90 days.

Combination therapy of AMB with ITZ or ketoconazole has also been evaluated. This has similar efficacy to single agent therapy while using lower dosages of each drug to reduce toxicity.⁴

An AMB lipid complex has been formulated which has reduced nephrotoxicity.¹³ The therapeutic dosage of the AMB lipid complex was found to be similar to or slightly greater than the dose of AMB, but higher doses can be used safely due to the reduced toxicity.

Cats may be treated with 5 mg/kg of body weight every 12 hours with ITZ. This is considered an effective and safe treatment for most cats.¹

Prognosis for any animal diagnosed with blastomycosis is guarded to good. In one retrospective study, the fatality rate for dogs with blastomycosis was 41.4% (18% died and 23.4% were euthanized).³ The two most important prognostic indicators are brain involvement and severity of lung disease. Prognosis is poor for dogs with brain involvement, but some can be successfully treated. Approximately 50% of the dogs with severe lung disease die from pulmonary failure within the first week of treatment.¹

Recurrences occur in approximately 20% of animals that survive treatment.¹ Relapse after apparently successful treatment typically occurs in the first 6 months but can occur up to 15 months post-treatment. Recurrence of disease is treated with another 60 to 90 day regimen of ITZ. Recurrence usually occurs due to reactivation of a residual site of infection. Retreatment has an 80% or greater chance of producing a cure.

Summary

Blastomycosis is rare fungal disease with a prevalence of 205/100,000 cases presenting to tertiary facilities.³ While it is a rare disease, it should be considered as a differential diagnosis in any case exhibiting the clinical signs discussed above. If other more common conditions have been excluded, blastomycosis should be investigated. It is an insidious disease that often is recognized only through extensive search for the organism or through a combination of clinical signs, history and signalment. This web page presents only a brief overview of blastomycosis as well as its presenting signs of disease and treatment. Please refer to the references below for a more detailed discussion, including the benefits and consequences of each therapeutic regimen.

References

1. Legendre AM. Chapter 59, Blastomycosis. In: CE Greene (ed): Infectious Diseases of the Dog and Cat. W.B. Saunders Co., St. Louis, 1990, pp. 371-377.

2. Furcolow ML, Busey JF, Menges RW, Chick EW. Prevalence and incidence studies of human canine blastomycosis II. Yearly incidence studies in three selected states, 1960-1967. Am J Epidemiol 92:121-131, 1970.

3. Rudmann DG, Coolman BR, Perez CM, Glickman LT. Evaluation of risk factors for blastomycosis in dogs: 857 cases (1980-1990). J Am Vet Med Assoc 201:1755-1759, 1992.

4. Arceneaux KA, Taboada J, Hosgood G. Blastomycosis in dogs: 115 cases (1980-1995). J Am Vet Med Assoc 213:658-663, 1998.

5. Breider MA, Walker TL, Legendre AM, VanEe RT. Blastomycosis in cats: Five cases (1979-1986). J Am Vet Med Assoc 193:570-572, 1988.

6. Bloom JD, Hamor RE, Gerding PA Jr. Ocular blastomycosis in dogs: 73 cases, 108 eyes (1985-1983). J Am Vet Med Assoc 209:1271-1274, 1996.

7. Hawkins EC, DeNicola DB. Cytologic analysis of tracheal wash specimens and bronchoalveolar lavage fluid in the diagnosis of mycotic infections in dogs. J Am Vet Med Assoc 197:79-83, 1990.

8. Wood EF, O'Brien RT, Young KM. Ultrasound-Guided Fine-Needle Aspiration of Focal Parenchymal Lesions of the Lung in Dogs and Cats. J Vet Intern Med 12:338-342, 1998.

9. Garma-Avina, A. Cytologic findings in 43 cases of blastomycosis diagnosed ante-mortem in naturally-infected dogs. Mycopathologia 131:87-91, 1995.

10. Miller, Paul E. DVM. et. al. Feline Blastomycosis: A report of three cases and literature review (1961-1988). J Am Anim Hosp Assoc 26:417-424, 1990.

11. Rubin SI, Krawiec DR, Gelberg H, Shanks RD. Nephrotoxicity of amphotericin B in dogs: a comparison of two methods of administration. Can J Vet Res 53:23-28, 1989.

12. Legendre, AM, et. al. Treatment of Blastomycosis with Itraconazole in 112 Dogs. J Vet Int Med 1996 10(6):365-371.

13. Krawiec DR, McKiernan BC, Twardock AR, Swenson CE, Itkin RJ, Johnson LR, Kurowsky LK, Marks CA. Use of an amphotericin B lipid complex for treatment of blastomycosis in dogs. J Am Vet Med Assoc 209:2073-2075, 1996.

Acknowledgement

The watercolor "Bluetick Coonhound" by Carlos Durazo is from the absolutearts.com web site.

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