Introduction

Blastomycosis is a systemic fungal infection caused by the dimorphic fungus Blastomyces dermatitidis. Dogs are commonly infected in the endemic regions of the Mississippi, Missouri, and Ohio river valleys.¹ The organism is typically inhaled in the infective mycelial form and transforms into the yeast form when exposed to body temperature. Once established in the lungs, the organism disseminates systemically with commonly affected sites of infection including the eyes, brain, skin, lymph nodes, and bones.²

The primary site of infection is the respiratory system, and the majority of cases present with some form of respiratory involvement. The clinical respiratory manifestations of blastomycosis typically involve cough, dyspnea, and hypoxemia due to pulmonary parenchymal involvement.^2,3 This report describes an unusual clinical manifestation of this disease presenting as an upper airway obstruction due to primary laryngeal blastomycosis.

Case Report

A 30 kg 9 yr old female spayed Labrador retriever presented for a 48 hr history of respiratory distress. The dog had a 3 wk history of stridor and weight loss. Previous diagnostics included thoracic radiographs, a complete blood count, and a biochemistry profile, all showing no abnormalities. A total thyroxine was measured at 0.7 μg/dL (0.8–3.5). Treatment had been attempted with doxycycline, prednisone, trimeprazine, amoxicillin, and trazodone, all without significant improvement.

On presentation the dog had a temperature of 102.8°F. There was evidence of a fixed upper airway obstruction with inspiratory stridor and severe inspiratory and expiratory dyspnea. There were no dermal lesions, and all peripheral lymph nodes were normal. Abdominal palpation was unremarkable. Neurologic, orthopedic, and ophthalmic examinations were not performed until later in the hospital stay because of the dog’s unstable presentation, but no abnormalities were identified. Pulse oximetry was 92%. The dog was sedated with 0.2 mg/kg butorphanol and 0.01 mg/kg acepromazine IV and placed in an oxygen cage. A 500 mL IV fluid bolus was administered and 0.2 mg/kg dexamethasone sodium phosphate was given IV. The temperature normalized after initial stabilization and remained normal. The dyspnea worsened several hours after presentation, and the dog was emergently anesthetized and intubated. The dog was subsequently extubated for laryngoscopy. The arytenoid cartilages were severely thickened and there were masses associated with the corniculate processes bilaterally (Figure 1A). A temporary tracheostomy tube was placed, and the masses were biopsied and debulked with cup biopsy forceps. The dog recovered from anesthesia and remained stable with no respiratory difficulty following temporary tracheostomy tube placement.

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Additional diagnostics were performed following stabilization. Thoracic radiographs were normal. Hematological abnormalities included a normocytic, normochromic anemia (hematocrit 36%, 37–55) and thrombocytopenia (187 × 10³/μL, 200–500). Biochemical profile revealed hypernatremia (154 mEq/L, 141–151), hypocalcemia (9.4 mg/dL, 9.7–11.3), increased alanine aminotransferase (85 IU/mL, 19–80), increased alkaline phosphatase (493 IU/mL, 20–150), hypocholesterolemia (99 mg/dL, 132–300), and an increased anion gap (21, 8–17). Urinalysis was unremarkable.

While histopathology was pending, the dog was hospitalized for monitoring and management of the tracheostomy tube. Treatment was initiated with prednisone 1 mg/kg per os (PO) q 24 hr^a, amoxicillin clavulanic acid 16.7 mg/kg PO q 12 hr^b, gabapentin 10 mg/kg PO q 8 hr^c, and trazodone 5 mg/kg PO q 8 hr^d. On day 5 of hospitalization, histopathology results confirmed pyogranulomatous laryngitis secondary to blastomycosis (Figure 2). A Blastomyces urine antigen test was submitted to obtain a baseline for purposes of treatment monitoring with a positive result (3.34 ng/mL)^e.

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Upon receiving the diagnosis of blastomycosis, prednisone and amoxicillin clavulanic acid were discontinued. Treatment for blastomycosis was initiated with terbinafine at 29 mg/kg PO q 12 hr^f and amphotericin B (AMB)^g. Amphotericin B was given on a Monday, Wednesday, Friday schedule at an initial dose of 0.25 mg/kg IV over 4 hr and 0.5 mg/kg for all subsequent doses. Intravenous fluids were administered during hospitalization to protect from renal damage associated with AMB. A total of four doses were given for a cumulative dose of 1.75 mg/kg. Urinalyses and serum biochemical profiles were monitored prior to each dose of AMB with no significant change in creatinine or urinary casts observed.

On day 11, the tracheostomy tube was removed and the dog was able to breathe comfortably without evidence of ongoing airway obstruction. On day 12, itraconazole was started at 6.7 mg/kg PO q 24 hr^h. On day 13, the dog was discharged, and treatment with itraconazole and terbinafine was continued at home.

Shortly after discharge from the hospital, the dog had resumed all normal activities and had had no further clinical signs. Seven months after discharge, the Blastomyces urine antigen test was negative. Itraconazole and terbinafine were discontinued after an additional month of treatment. Nine months after discharge, laryngoscopy was performed at the time of anesthesia for a dental procedure and the larynx appeared grossly normal (Figure 1B).

Discussion

This case illustrates an example of laryngeal infiltration from blastomycosis resulting in a fixed upper airway obstruction. Blastomycosis infections in the dog have a wide variety of clinical manifestations but most commonly present as disseminated disease with multiple organ sites infected, particularly the lungs, skin, and eyes.^2,3 Upper airway manifestations of blastomycosis in the dog are uncommon but have been reported, including two dogs with laryngeal blastomycosis.^4–6 The first case presented with upper airway obstruction and had lesions identified concurrently in the pharynx and the lungs.⁵ In the second case, there was concurrent pulmonary involvement.⁴ Blastomycosis presumed to be limited to the larynx, or primary laryngeal blastomycosis, has been reported rarely in humans.^7,8 To the authors’ knowledge, this is the first reported case of primary laryngeal blastomycosis in the dog.

The major route of blastomycosis infection is believed to be inhalation of spores from the environment that subsequently transform into the yeast phase when exposed to body temperatures. The organism can then travel to other sites in the body via hematogenous or lymphatic routes.⁹ In humans with primary laryngeal blastomycosis, it has been speculated that infection involves either direct inoculation of the larynx with infected respiratory secretions or infection of the larynx via the hematogenous route.^7,10 In these cases, the presumptive initial pulmonary infection results in no appreciable clinical signs or lesions. While pulmonary involvement is seen in the majority of dogs, 6% of cases of canine blastomycosis have been reported to have normal thoracic radiographs.²

In humans with blastomycosis, isolated laryngeal involvement is reported uncommonly and the diagnosis can be delayed or missed, with the primary differential diagnosis being laryngeal neoplasia.^8,11–13 In canine patients, for which management of obstructive laryngeal disease is expensive and invasive, euthanasia may be elected if the underlying diagnosis is not likely to have a good long-term outcome, as with neoplasia.¹⁴ This case illustrates the importance of considering blastomycosis for dogs in endemic areas, as the prognosis is more favorable.

Amphotericin B was chosen for treatment of this dog because it is the treatment of choice for life-threatening fungal infections. Given the airway obstruction and consequential dependence on a tracheostomy tube, AMB was initially selected over itraconazole. The dog was transitioned to itraconazole for long-term use at home once no longer dependent on a tracheostomy tube. Terbinafine was added to the antifungal protocol because of in vitro efficacy against B dermatitidis and possible synergism with azoles in some systemic mycoses in humans.^15,16 It is unclear whether the addition of terbinafine helped speed the recovery of this dog. Itraconazole was not administered concurrently with AMB because of concerns for antagonistic effects.^17,18

While the need for temporary tracheostomy tube placement and hospitalization for tube care and monitoring can be financially daunting for many owners, after less than a week of antifungal therapy and a cumulative dose of 1.75 mg/kg AMB, the tracheostomy tube was successfully removed in this patient. In a previously reported case of upper airway obstruction due to laryngeal blastomycosis in a dog, itraconazole alone resulted in resolution of disease; however, this case was managed with a permanent tracheostomy.⁵ Whether the case reported here could have been successfully managed with itraconazole alone, while still avoiding dependence on permanent tracheostomy, is unknown.

It is notable that this dog did have a positive Blastomyces urine antigen test. While this test is not specific for blastomycosis infection and can have false negatives, this case illustrates that this noninvasive diagnostic test could be performed in cases of nonemergent (nonobstructive) laryngeal disease for which owners are unwilling or unable to pursue a histopathologic diagnosis.^19,20

Conclusion

To the authors’ knowledge, this is the first report of laryngeal obstruction secondary to primary laryngeal blastomycosis in the dog. The dog was successfully managed with a temporary tracheostomy tube and made a complete recovery with antifungal therapy. Blastomycosis should be considered as a differential diagnosis for dogs in endemic areas presenting with laryngeal disease.