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Basics

Basics

Definition

A systemic, mycotic infection caused by the dimorphic soil organism Blastomyces dermatitidis.

Pathophysiology

  • A small spore (conidia) is shed from the mycelial phase (Ajellomyces dermatitidis) of the organism growing in the soil and inhaled, entering the terminal airway.
  • At body temperature, the spore transforms to its yeast form, which initiates the infection in the lungs.
  • From this focus of mycotic pneumonia, the yeast disseminates hematogenously throughout the body.
  • The immune response to the invading organism produces a pyogranulomatous infiltrate to control the organism.

Systems Affected

  • Respiratory-85% of affected dogs have lung disease.
  • Eyes, skin, subcutaneous tissues, lymphatic system, testes, CNS, and bones-commonly affected.
  • Prostate, mammary gland, nasal cavity, nasopharynx, gums, heart, and vulva-less commonly affected.
  • Subclinical infection is uncommon.

Incidence/Prevalence

Depends on environmental and soil conditions that favor growth of Blastomyces. Growth of the organism requires sandy, acid soil, and a proximity to water.

Geographic Distribution

Most common along the Mississippi, Ohio, and Tennessee river basins. Also reported in the area of the Great Lakes and St. Lawrence River, southern Canada, mid-Atlantic states, and has been found outside the endemic area in Colorado.

Signalment

Species

  • Predominantly dog
  • Occasionally cat

Breed Predilections

Large-breed dogs weighing 25kg, especially sporting breeds; may reflect increased exposure rather than susceptibility.

Mean Age and Range

  • Dogs-most common in 1–5 years of age; uncommon after 7 years of age.
  • Cats-no age predilection noted for cats.

Predominant Sex

  • Dogs-males in most studies.
  • Cats-none noted.

Signs

Historical Findings

  • Weight loss; depressed appetite.
  • Cough and dyspnea
  • Eye inflammation and discharge
  • Lameness
  • Draining skin lesions
  • Syncope if cardiac involvement

Physical Examination Findings

Dogs

  • Fever up to 104°F (40°C)-approximately 50% of patients.
  • Harsh, dry lung sounds associated with increased respiratory effort-common.
  • Generalized or regional lymphadenopathy with or without skin lesions or subcutaneous swellings.
  • Uveitis with or without secondary glaucoma and conjunctivitis, ocular exudates, and corneal edema.
  • Lameness-bone involvement in up to 30% cases.
  • Testicular enlargement and prostatomegaly-occasionally seen.
  • Murmur and AV block-with endocarditis and myocarditis.

Cats

  • Increased respiratory effort
  • Granulomatous skin lesions
  • Visual impairment

Risk Factors

  • Wet environment-banks of rivers, streams, and lakes or in swamps; most affected dogs live within 400meters of water.
  • Exposure to recently excavated areas.
  • Blastomycosis has been reported in indoor-only cats.

Diagnosis

Diagnosis

Differential Diagnosis

  • Respiratory signs-bacterial pneumonia, neoplasia, heart failure, pleural effusion, or other fungal infection.
  • Lymph node enlargement-similar to lymphoma.
  • The combination of respiratory disease with ocular, bony, or skin/subcutaneous involvement in a young dog suggests the diagnosis.

CBC/Biochemistry/Urinalysis

  • CBC changes reflect mild to moderate inflammation; may note mild anemia in chronic cases.
  • High serum globulins with borderline low albumin concentrations with chronic infection.
  • Hypercalcemia (generally mild) in some dogs secondary to the granulomatous changes.
  • Blastomyces yeasts may be found in the urine of dogs with prostatic involvement; mild proteinuria consistent with systemic inflammation/disease.

Other Laboratory Tests

  • Urine or serum antigen testing-useful for making a diagnosis if organisms cannot be found on cytology or histopathology; positive test strongly supports diagnosis with a sensitivity of >90%; greater sensitivity reported with urine antigen test.
  • Urine antigen test cross-reacts with some other fungal infections such as histoplasmosis.
  • AGID-is not sensitive early in the disease but very specific for fungal infection.

Imaging

Radiographs

  • Lungs-generalized interstitial to nodular infiltrate but can see non-uniform distribution of lesions.
  • Tracheobronchial lymphadenopathy-common.
  • Changes-inconsistent with bacterial pneumonia; may resemble metastatic tumors, especially hemangiosarcoma.
  • Chylothorax secondary to blastomycosis has been reported in dogs.
  • Focal bone lesions-lytic and proliferative; can be mistaken for osteosarcoma.

Diagnostic Procedures

  • Cytology of lymph node aspirates, lung aspirates, tracheal wash fluid, or impression smears of draining skin lesions-best method for diagnosis.
  • Histopathology of bone biopsies or enucleated blind eyes-identify the organism.
  • Organisms-usually plentiful in the tissues; may be scarce in tracheal washes if there is no productive cough.

Pathologic Findings

  • Lesions-pyogranulomatous with budding yeast 5–20 µm diameter with a thick, refractile, double-contoured cell wall; occasionally very fibrous with few organisms found.
  • Lungs with large amounts of inflammatory infiltrate do not collapse when the chest is opened.
  • Special fungal stains-facilitate finding the organisms.

Treatment

Treatment

Nursing Care

Severely dyspneic dogs-require an oxygen cage/support for a protracted period ( days to more than a week); about 25% of dogs have worsening of lung disease during the first few days of treatment, attributed to an inflammatory response after the Blastomyces organisms die and release their contents.

Activity

Patients with respiratory compromise must be restricted.

Diet

Palatable and high quality to stimulate the appetite.

Client Education

  • Inform owner that treatment is costly and requires a minimum of 60–90 days.
  • Reassure owners that an infected dog is not contagious to other animals or people (although other dogs in the house may have also been environmentally exposed).

Surgical Considerations

  • Removal of an abscessed lung lobe may be required when medical treatment cannot resolve the infection.
  • Blind eyes should be enucleated to remove potential sites of residual infection.

Medications

Medications

Drug(s) Of Choice

Itraconazole

  • Dogs-5 mg/kg PO q12h with a fat-rich meal, such as canned dog food, for the first 3 days to achieve a therapeutic blood concentration as soon as possible; then reduce to 5 mg/kg q24h.
  • Cats-5mg/kg PO q12h; open the 100 mg capsules containing pellets and mix with palatable food.
  • Avoid antacid drugs. as itraconazole absorption is best in an acidic environment.
  • Treat for a minimum of 90 days or for 1month after all signs of disease have disappeared (whichever is longer).
  • Absorption of compounded itraconazole is highly unreliable and the use of compounded itraconazole is not recommended.

Fluconazole

  • Dogs-5 mg/kg PO q12h; has been reported as efficacious.
  • Cats-50 mg PO q12–24h.
  • Cheaper alternative but may require longer treatment duration.

Intravenous Amphotericin B

  • Dogs with neurologic signs or life-threatening disease should be treated with AMB.
  • 0.5–1.0 mg/kg IV q48h in dogs that cannot take oral medication or that do not respond to azole therapy (see Histoplasmosis); use the lipid complex for dogs with renal dysfunction.

Contraindications

Corticosteroids-usually contraindicated because the anti-inflammatory effects allow uninhibited proliferation of the organisms; patients with previous steroid therapy require a longer duration of treatment; for dogs with life-threatening dyspnea, dexamethasone (0.1–0.2 mg/kg daily) for 2–3 days may be lifesaving when given in conjunction with itraconazole treatment; taper and discontinue steroids as soon as possible.

Precautions

Itraconazole and Fluconazole Toxicity

  • Anorexia-most common sign; attributed to liver toxicity; monitor serum ALT monthly for duration of treatment or when anorexia occurs; temporarily discontinue drug for patients with anorexia and moderate ALT elevation; after appetite improves, restart at half the previously used dose.
  • Ulcerative dermatitis-seen in some dogs; the result of vasculitis; dose-related condition; temporarily discontinue drug; when ulcers have resolved, restart at half the previously used dose.

Amphotericin B Toxicity

  • Only absolute contraindication to therapy is anaphylaxis but the major limiting factor is cumulative nephrotoxicity.
  • Monitor creatinine throughout therapy-elevation above normal or 20% greater than baseline is considered significant.

Follow-Up

Follow-Up

Patient Monitoring

Serum chemistry-monthly to monitor for hepatic toxicity or if anorexia develops.

Thoracic Radiographs

  • Determine duration of treatment.
  • Considerable permanent pulmonary changes (fibrosis/scarring) may occur after the infection has resolved, making determination of persistent active disease difficult.
  • At 90 days of treatment-if active lung disease is seen, continue treatment for an additional 30 days.
  • If lungs are normal, stop treatment and repeat radiographs again in 30 days.
  • At 120 days of treatment-if the lungs are the same as day 90, changes are residual (fibrosis).
  • If better than day 90, continue treatment for 30more days, if lesions are significantly worse than at 90 days, change treatment to amphotericin B and then repeat radiographs.
  • Continue treatment as long as there is improvement in the lungs; if there is no further improvement and no indication of active disease, the lesions are likely the result of scarring.

Prevention/Avoidance

  • Location of environmental growth of Blastomyces organisms unknown, thus difficult to avoid exposure; exposure to lakes and streams could be restricted but is not very practical.
  • Dogs that recover from the infection may be immune to reinfection.

Expected Course and Prognosis

  • Death-25% of dogs die during the first week of treatment; early diagnosis improves chance of survival.
  • More severe pulmonary disease and invasion into the CNS decrease prognosis.
  • Recurrence-about 20% of dogs; usually within 3–6months after completion of treatment; may occur >1 year after treatment; a second course of azole treatment cures most patients; drug resistance has not been observed.
  • With early detection of blastomycosis, the prognosis in cats appears similar to dogs.

Miscellaneous

Miscellaneous

Zoonotic Potential

  • Yeast form is not spread from animals to humans, except through bite wounds; inoculation of organisms from dog bites has occurred.
  • Avoid cuts during necropsy of infected dogs and avoid needle sticks when aspirating lesions.
  • Warn clients that blastomycosis is acquired from an environmental source and that they may have been exposed at the same time as the patient; the incidence in dogs is 10times that in humans.
  • Encourage clients with respiratory and skin lesions to inform their physicians that they may have been exposed to blastomycosis.

Pregnancy/Fertility/Breeding

Azole drugs can have teratogenic effects (embryotoxicity found at high doses) and should ideally be avoided during pregnancy (but the risk of not treating the mother needs to be balanced with the theoretical risk of azole therapy to the fetuses).

Abbreviations

  • AGID = agar gel immunodiffusion
  • ALT = alanine transaminase
  • AMB = amphotericin B
  • CBC = complete blood count
  • CNS = central nervous system

Internet Resources

Information on antigen testing: www.miravistalabs.com.

Author Daniel S. Foy

Consulting Editor Stephen C. Barr

Acknowledgment The author and editors acknowledge the prior contribution of Alfred M. Legendre.

Client Education Handout Available Online

Suggested Reading

Crews LJ, Feeney DA, Jessen CR, et al. Radiographic findings in dogs with pulmonary blastomycosis: 125cases (1989–2006). J Am Vet Med Assoc 2008, 232:215221.

Gilor C, Graves TK, Barger AM, et al. Clinical aspects of natural infection with Blastomyces dermatitidis in cats: 8cases. J Am Vet Med Assoc 2006, 229:9699.

Legendre AM. Blastomycosis. In: Greene CE, ed., Infectious Diseases of the Dog and Cat, 4th ed. St. Louis, MO: Saunders Elsevier, 2012, pp. 606614.

Legendre AM, Rohrbach BW, Toal RL, et al. Treatment of blastomycosis with itraconazole in 112dogs. J Vet Intern Med 1996, 10:365371.

Mazepa AS, Trepanir LA, Foy DS. Retrospective comparison of the efficocy of fluconazole or itraconazole for the treatment of systemic blastomycosis in dogs. J Vet Intern Med 2011, 25:440445.

Spector D, Legendre AM, Wheat J, et al. Antigen and antibody testing for the diagnosis of blastomycosis in dogs. J Vet Intern Med 2008, 22:839843.