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Jennifer K. Marin Carrboro Plaza Veterinary Clinic, 104 M Hwy 54 W, Carrboro, NC 27510.

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Mason Y. Savage Blue Pearl Veterinary Partners, 455 Abernathy Rd NE, Atlanta, GA 30328.

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Brandon D. Adley Upstate Veterinary Specialists, 393 Woods Lake Rd, Greenville, SC 29607.

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Eli B. Cohen Department of Molecular and Biomedical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606.

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History

A 3-year-old 29.2-kg (64.2-lb) spayed female Labrador Retriever was evaluated at a veterinary referral hospital for a 4-week history of progressive stertor. The owners reported that the dog had free access to > 1,000 acres of land, was known to eat small animals, sounded congested, had a decreased appetite, and was lethargic. In addition, the dog had developed aphonia over the last few weeks before referral. No coughing was reported.

Five months before referral, the dog had been treated with methylprednisolone acetate (60 mg, SC, once) and cephalexin (750 mg, PO, q 12 h for 14 days) for a lick granuloma. Two weeks before referral, the primary veterinarian performed a CBC that revealed mild leukocytosis (17.1 × 103 WBCs/μL; reference range, 5 × 103 WBCs/μL to 16 × 103 WBCs/μL) and performed thoracic radiography that revealed a mild bronchial pattern. The primary veterinarian initiated empiric treatment with sulfamethoxazole-trimethoprim (480 mg, PO, q 12 h) and guaifenesin-dextromethorphan hydrobromidea (110 mg, PO, q 6 to 8 h). Three days later, treatment with clindamycin (300 mg, PO, q 12 h) and enrofloxacin (136 mg, PO, q 24 h) was added but did not result in any clinical improvement.

On initial examination at the veterinary referral hospital, the dog was bright, alert, and responsive. The dog had mild stridor, most apparent when inhaling through the nose, and a prolonged inspiratory phase of respiration. On palpation of the larynx, the right side felt thicker than the left; however, palpation did not elicit signs of pain. The dog was sedated with IV administration of butorphanol (0.20 mg/kg [0.09 mg/lb]) followed by propofol (6.2 mg/kg [2.8 mg/lb]), and a direct laryngeal examination was performed. Bilateral laryngeal paresis, but no laryngeal mass or notable swelling, was identified. Endoscopy and CT (Figure 1) were performed.

Figure 1—
Figure 1—

Transverse plane CT images at the level of the C1–2 intervertebral disk space (A) and the cranial aspect of C2 (B) of a 3-year-old 29.2-kg (64.2-lb) spayed female Labrador Retriever with a 4-week history of progressive stertor and a shorter duration of aphonia. The images were obtained after IV administration of contrast medium and reconstructed in a soft tissue algorithm.

Citation: Journal of the American Veterinary Medical Association 254, 1; 10.2460/javma.254.1.61

Determine whether additional imaging studies are required, or make your diagnosis from Figure 1—then turn the page

Diagnostic Imaging Findings and Interpretation

On the CT images, laryngeal soft tissues from the base of the epiglottis to the level of the cricoid cartilage were severely, diffusely, and circumferentially thickened up to 1.2 cm (Figures 2 and 3). The laryngeal soft tissues appeared homogeneous (49 HU) on images captured before administration of contrast medium, but were heterogeneously contrast enhancing, with regions of uniform enhancement (122 HU) and regions of nonenhancement. A moderate volume of punctate gas attenuation (−1,000 HU) was present in the right cranial aspect of the larynx and tracked somewhat linearly toward the ventral aspect of the thyroid cartilages. The laryngeal ventricles contained a small volume of gas attenuation. Soft tissues at the junction between the tongue base and the larynx were heterogeneously contrast enhancing, but no discrete foreign body was identified. No disruption or inflammation of the overlying subcutis or skin was identified. The laryngeal cartilages were nearly completely mineralized, and there was no evidence of lysis. The medial retropharyngeal lymph nodes were bilaterally enlarged (left, 0.9-cm-thick; right, 1.2-cm-thick) and mildly heterogeneously contrast enhancing; however, the mandibular lymph nodes and tonsils were within normal limits. Results of endoscopy were unremarkable beyond those changes also evident on direct examination.

Figure 2—
Figure 2—

The same CT images as in Figure 1. The medial retropharyngeal lymph nodes (arrowheads; A) are bilaterally enlarged and are mildly and heterogeneously contrast enhancing. The laryngeal soft tissues (asterisks; A and B) are severely thickened and heterogeneously contrast enhancing bilaterally. A focal region of contrast enhancement is visible in the right ventral aspect of the vertebral canal, which is a normal position for the right internal vertebral venous plexus.

Citation: Journal of the American Veterinary Medical Association 254, 1; 10.2460/javma.254.1.61

Figure 3—
Figure 3—

Sagittal (A) and dorsal (B) plane maximal intensity projection reconstruction CT images of the laryngeal region of the dog in Figure 1 after administration of contrast medium in a soft tissue algorithm. Bilateral severe thickening of the laryngeal soft tissues (white asterisks) is visible and is contacting the endotracheal tube. The cricoid (black arrowheads) and thyroid (black arrows) cartilages are marked for reference.

Citation: Journal of the American Veterinary Medical Association 254, 1; 10.2460/javma.254.1.61

A diagnosis of severe laryngeal swelling with right-sided laryngeal emphysema and bilateral (right aspect worse) medial retropharyngeal lymphadenopathy was made on the basis of CT findings. Given the track-like emphysema and history of free access to a large property, a penetrating foreign body with secondary laryngitis was suspected; however, because no foreign body was identified, other differential diagnoses, including laryngitis secondary to laryngeal paresis or infectious laryngitis, were also considered. Because of the dog's young age, laryngeal neoplasia was considered less likely.

Treatment and Outcome

After CT and endoscopy, fine-needle aspiration of the thickened laryngeal soft tissues was performed. Cytologic evaluation revealed inflammatory cells in a proteinaceous background mixed with mesenchymal cells and rare yeast forms consistent with Blastomyces dermatitidis. A cytologic diagnosis of laryngeal blastomycosis with reactive laryngeal fibroplasia was made. Results of an enzyme immunoassay testb on the dog's urine for Blastomyces antigen was positive (antigen concentration, 5.82 ng/mL), and treatment with itraconazole (5 mg/kg [2.3 mg/lb], PO, q 24 h) was initiated.

Three months later, the dog's respiratory signs had resolved and urine concentration of Blastomyces antigen had decreased to 0.68 ng/mL; however, skin lesions with crusting, inflammation, and discharge had developed on the dog's dorsum and pinnae. A skin scrape was performed, and results of cytologic evaluation of the sample were negative for Blastomyces. Therefore, a reaction to itraconazole was suspected, and the drug was discontinued. A month later, the dog's skin had improved, and treatment with itraconazole (2.5 mg/kg [1.1 mg/lb], PO q 24 h for 30 days, followed by 5 mg/kg, PO, q 24 h) was restarted. Skin lesions did not recur.

Seven months after diagnosis of laryngeal blastomycosis, the dog was returned for vomiting, anorexia, and lethargy. Results of serum biochemical analyses indicated azotemia (BUN concentration, 45 mg/dL [reference range, 7 to 25 mg/dL]; creatinine concentration, 2.5 mg/dL [reference range, 0.3 to 1.4 mg/dL]) and hyperphosphatemia (phosphate concentration, 9 mg/dL; [reference range, 2.9 to 6.6 mg/dL]). Urinalysis performed the following day revealed pyuria and bacteriuria (too numerous to count), proteinuria (2+), and urine specific gravity of 1.025. Results of a Blastomyces antigen test on a urine sample were negative. A urinary tract infection was diagnosed, and treatment with enrofloxacin (2.2 mg/kg [1 mg/lb], PO, q 24 h for 10 days) was initiated. On recheck examination 4 days later, the dog's pyuria had resolved and azotemia (BUN concentration, 30 mg/dL; creatinine concentration 1.6 mg/dL) had improved; however, the dog remained lethargic and anorexic. Mirtazapine (0.5 mg/kg [0.02 mg/lb], PO, q 24 h) and prednisone (1 mg/kg [0.45 mg/lb], PO, q 24 h for 3 days, then 1 mg/kg, PO, q 48 h for 6 days) were prescribed as appetite stimulants. Transient improvement in clinical signs occurred; however, the dog was returned 9 days later, again for lethargy and vomiting. On physical examination, the dog was laterally recumbent, bradycardic (56 beats/minute), and approximately 6% to 8% dehydrated. The dog had no evidence of stertor or other respiratory signs related to the prior diagnosis of laryngeal blastomycosis. Results of serum biochemical analyses indicated azotemia (BUN concentration, 48 mg/dL; creatinine concentration, 4.1 mg/dL), hyperphosphatemia (phosphate concentration, 16.4 mg/dL), hyperkalemia (potassium concentration, 8.5 mmol/L; reference range, 3.7 to 5.8 mmol/L]), and hyponatremia (sodium concentration, 137 mmol/L; reference range, 138 to 160 mmol/L). Hypoadrenocorticism was suspected on the basis of electrolyte abnormalities detected at that time combined with prior transient improvement with oral prednisone administration. The owners elected euthanasia for the dog.

Comments

Although blastomycosis in the upper airway of dogs has been reported,1,2 the present report is to the authors' knowledge the first with CT description of laryngeal blastomycosis in a dog. Blastomycosis should be considered in dogs with dysphonia, aphonia, or laryngeal dysfunction in Blastomyces-endemic regions (eg, mid-Atlantic states; the Ohio, Mississippi, and Missouri River Valleys; and Canadian provinces of Manitoba, Quebec, and Ontario). Blastomyces infection has also been identified in Africa, India, Europe and Central America.3 Blastomycosis in dogs can vary from self-limiting to severe pyogranulomatous disease,4 and the corticosteroid injection given 5 months previously to the dog in the present report could have facilitated infection secondary to immunosuppression.

Blastomyces dermatitidis is a thermally dimorphic fungus that exists in both mycelial and yeast forms.2,4,5 The mycelial form is found in contaminated soil, and transmission occurs when infectious conidia are inhaled. Once in a mammalian host, conidia are phagocytized by macrophages, then change from mycelial form to a broad-based budding yeast form.4,5 Following pulmonary infection, hematogenous spread can occur, resulting in pyogranulomatous inflammation in numerous organs (eg, eyes, lymph nodes, bone, brain, meninges, liver, kidneys, spleen, skin, and subcutis).2,4,5 Clinical signs in small animal patients include anorexia, weight loss, lethargy, signs of depression, cachexia, fever, tachypnea and cough.2,4,5 Diagnosis is ideally made on the basis of cytologic or histologic identification of the broad-based budding yeast form of the organisms in samples of affected tissue or results of a PCR assay performed on paraffin-embedded or unfixed samples from affected tissue. In addition, testing of urine for Blastomyces antigen has high sensitivity for dogs with active disease.6

Thoracic radiography was not diagnostic for blastomycosis in the dog of the present report because the mild bronchial pattern identified is a nonspecific finding. Typical findings from thoracic radiography in dogs with blastomycosis include a structured interstitial pattern (nodules), a diffuse unstructured interstitial pattern, a mixed bronchial and unstructured interstitial pattern, or focal alveolar pattern, alone or in combination. Pulmonary lesions are present in 65% to 85% of dogs with blastomycosis,7,8 and thoracic radiographic images appear normal in only 6% of cases.9 Computed tomography was instrumental in reaching the diagnosis in the dog of the present report because results confirmed laryngeal swelling as the source for the progressive stridor and aphonia. In addition, the swelling was not evident on direct examination, which may have been because of concurrent laryngeal paresis that could have obscured tissue thickening caudal to the rima glottis. On the basis of CT results, appropriate tissue was sampled, and the underlying cause was identified. This case highlighted the importance of considering blastomycosis as a differential diagnosis for diffuse laryngeal swelling, particularly in patients in Blastomyces-endemic regions.

Footnotes

a.

Cough tablets, Creative Science LLC, Ballwin, Mo.

b.

MVista Blastomyces quantitative EIA, MiraVista Diagnostics, Indianapolis, Ind.

References

  • 1. Salinardi BJ, Maretta SM, McCullough SM, et al. Pharyngeallaryngeal blastomycosis in a dog. J Vet Dent 2003;20:146147.

  • 2. Wehner A, Crochik S, Howerth E, et al. Diagnosis and treatment of blastomycosis affecting the nose and nasopharynx of a dog. J Am Vet Med Assoc 2008;233:11121116.

    • Crossref
    • PubMed
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    • Export Citation
  • 3. Legendre AM. Blastomycosis: In: Greene CE, ed. Infectious diseases of the dog and cat. 3rd ed. St Louis: Saunders Elsevier; 2006:569576.

    • Search Google Scholar
    • Export Citation
  • 4. Brömel C, Sykes JE. Epidemiology, diagnosis and treatment of blastomycosis in dogs and cats. Clin Tech Small Anim Pract 2005;20:233239.

  • 5. McMillan CJ, Taylor S. Transtracheal aspiration in the diagnosis of blastomycosis (17 cases: 2000–2005). Can Vet J 2008;49:5355.

  • 6. Foy DS, Trepanier LA, Kirsch EJ, et al. Serum and urine Blastomyces antigen concentrations as markers of clinical remission in dogs treated for systemic blastomycosis. J Vet Intern Med 2014;28:305310.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7. Kerl ME. Update on canine and feline fungal diseases. Vet Clin North Am Small Anim Pract 2003;33:721747.

  • 8. Legendre AM, Walker M, Buyukmihci N, et al. Canine blastomycosis: a review of 47 clinical cases. J Am Vet Med Assoc 1981;178:11631168.

  • 9. Arceneaux KA, Taboada J, Hosgood G. Blastomycosis in dogs: 115 cases (1980–1995). J Am Vet Med Assoc 1998;213:658664.

Contributor Notes

Address correspondence to Dr. Cohen (ebcohen@ncsu.edu).
  • Figure 1—

    Transverse plane CT images at the level of the C1–2 intervertebral disk space (A) and the cranial aspect of C2 (B) of a 3-year-old 29.2-kg (64.2-lb) spayed female Labrador Retriever with a 4-week history of progressive stertor and a shorter duration of aphonia. The images were obtained after IV administration of contrast medium and reconstructed in a soft tissue algorithm.

  • Figure 2—

    The same CT images as in Figure 1. The medial retropharyngeal lymph nodes (arrowheads; A) are bilaterally enlarged and are mildly and heterogeneously contrast enhancing. The laryngeal soft tissues (asterisks; A and B) are severely thickened and heterogeneously contrast enhancing bilaterally. A focal region of contrast enhancement is visible in the right ventral aspect of the vertebral canal, which is a normal position for the right internal vertebral venous plexus.

  • Figure 3—

    Sagittal (A) and dorsal (B) plane maximal intensity projection reconstruction CT images of the laryngeal region of the dog in Figure 1 after administration of contrast medium in a soft tissue algorithm. Bilateral severe thickening of the laryngeal soft tissues (white asterisks) is visible and is contacting the endotracheal tube. The cricoid (black arrowheads) and thyroid (black arrows) cartilages are marked for reference.

  • 1. Salinardi BJ, Maretta SM, McCullough SM, et al. Pharyngeallaryngeal blastomycosis in a dog. J Vet Dent 2003;20:146147.

  • 2. Wehner A, Crochik S, Howerth E, et al. Diagnosis and treatment of blastomycosis affecting the nose and nasopharynx of a dog. J Am Vet Med Assoc 2008;233:11121116.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3. Legendre AM. Blastomycosis: In: Greene CE, ed. Infectious diseases of the dog and cat. 3rd ed. St Louis: Saunders Elsevier; 2006:569576.

    • Search Google Scholar
    • Export Citation
  • 4. Brömel C, Sykes JE. Epidemiology, diagnosis and treatment of blastomycosis in dogs and cats. Clin Tech Small Anim Pract 2005;20:233239.

  • 5. McMillan CJ, Taylor S. Transtracheal aspiration in the diagnosis of blastomycosis (17 cases: 2000–2005). Can Vet J 2008;49:5355.

  • 6. Foy DS, Trepanier LA, Kirsch EJ, et al. Serum and urine Blastomyces antigen concentrations as markers of clinical remission in dogs treated for systemic blastomycosis. J Vet Intern Med 2014;28:305310.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7. Kerl ME. Update on canine and feline fungal diseases. Vet Clin North Am Small Anim Pract 2003;33:721747.

  • 8. Legendre AM, Walker M, Buyukmihci N, et al. Canine blastomycosis: a review of 47 clinical cases. J Am Vet Med Assoc 1981;178:11631168.

  • 9. Arceneaux KA, Taboada J, Hosgood G. Blastomycosis in dogs: 115 cases (1980–1995). J Am Vet Med Assoc 1998;213:658664.

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