History

A 3-year-old 9-kg spayed female Wirehaired Dachshund was referred to the Cummings School of Veterinary Medicine emergency clinic at Tufts University for acute respiratory distress. Clinical signs began 3 weeks prior and included mild respiratory symptoms (coughing, sneezing, and serous nasal discharge), pyrexia (39.4 °C; reference range, 37.5 °C to 39.2 °C), lethargy, and hyporexia. At that time, the patient was treated with a 5-day course of doxycycline by the referring veterinarian. When clinical signs persisted after treatment, a CBC was performed by the referring veterinarian and revealed mild leukocytosis (17.2 X 10³ WBCs/μL; reference range, 4.0 to 15.5 X 10³ WBCs/μL) and mild neutrophilia (absolute 11.86 X 10³ neutrophils/μL; reference range, 2.0 to 10.6 X 10³ neutrophils/μL) with no band neutrophils. A baseline serum chemistry panel was performed and was unremarkable. The doxycycline was stopped, a steroid injection was given, and the patient was started on cefpodoxime. The patient remained lethargic and gastrointestinal signs (vomiting and loose stools) developed soon after. Abdominal radiographs were unremarkable, and the patient was started on carprofen and probiotics. Days later, the patient returned for progressive lethargy and was treated with subcutaneous fluids and a cefovecin injection. The patient’s basal cortisol was measured and was normal (1.7 μg/dL; reference range, 1.0 to 5.0 μg/dL). The patient then began displaying signs of shallow, audible breathing and tachypnea. The patient was up to date on core vaccinations as well as fluralaner for flea and tick prevention. The patient lived in western Massachusetts and had a recent history of traveling to the New Hampshire/Vermont border. The patient’s clinical signs then progressed to acute respiratory distress described as non-stop panting, tachypnea, dyspnea, and restlessness. Upon presentation to Tufts, the dog was alert, responsive, and distressed. The dog’s rectal temperature (37.7 °C; reference range, 37.5 °C to 39.2 °C) and pulse rate (110 beats per minute; reference range, 70 to 120 beats per minute) were both within normal limits. The respiratory rate (140 breaths per minute; reference range, 18 to 34 breaths per minute) was markedly elevated with short, shallow breaths and neck stretching noted. The patient was subjectively < 5% dehydrated but was otherwise unremarkable on physical exam. A Thoracic Focused Assessment with Sonography for Trauma (TFAST) was performed and revealed diffuse coalescing B-lines bilaterally with no evidence of pleural or pericardial effusion and a normal left atrial to aortic ratio of 1:1 (reference range < 1.7 is normal). The patient was hospitalized for further stabilization procedures and diagnostics, including 3-view thoracic radiographs (Figure 1).

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Right lateral (A) and ventrodorsal thoracic (B) radiographic projections of a 3-year-old spayed female Wirehaired Dachshund presenting for acute respiratory distress.

Citation: Journal of the American Veterinary Medical Association 262, 12; 10.2460/javma.24.07.0472

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Radiographic Findings and Interpretation

Thoracic radiographs revealed innumerable small, rounded, soft tissue opaque pulmonary foci dispersed throughout all lung lobes (Figure 2). These findings were consistent with a severe diffuse micronodular/miliary interstitial to alveolar pattern. The remainder of the thoracic structures and musculoskeletal structures were normal. The differential diagnoses for the diffuse micronodular pulmonary pattern included infectious processes such as fungal pneumonia (blastomycosis, pneumocystis) or hematogenous bacterial pneumonia, and noninfectious inflammatory processes such as pneumoconiosis (interstitial lung disease due to inhaled particulate material such as asbestos or silica). Given the young age of the patient, diffuse pulmonary lymphoma or metastatic neoplasia such as hemangiosarcoma were considered less likely.

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Zoomed-in image of the caudodorsal lung fields on the right lateral view. Note the innumerable small, rounded pulmonary foci evenly dispersed throughout each lung lobe (arrows).

Citation: Journal of the American Veterinary Medical Association 262, 12; 10.2460/javma.24.07.0472

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Treatment and Outcome

Bronchoalveolar lavage was performed, and cytology revealed evidence of neutrophilic/macrophagic inflammation and numerous variable (small to large) numbers of small, spherical structures aggregated into larger spherical groups. This was initially believed to be consistent with Pneumocystis sp. A fine needle aspirate of the lung was then performed, which contained similarly appearing spherical aggregates. Special staining with Grocott methenamine silver stain demonstrated the presence of many large, round pairs of yeast with broad-based budding diagnostic for blastomycosis. After diagnosis, the patient was placed on high-flow nasal oxygen (28 L per minute, 100% fraction of inspired oxygen; 33 °C) and started on itraconazole (10 mg/kg, PO, q 24 h), dexamethasone sodium phosphate (1 mg/kg, IV, q 24 h), sulfamethoxazole/trimethoprim (15 mg/kg, IV, q 8 h), and fluid therapy. The patient responded transiently but then relapsed. Due to progressive dyspnea, the owner elected for humane euthanasia after 1 day of hospitalization.

Comments

Blastomycosis is a systemic fungal disease resulting from an infection with Blastomyces sp which are endemic to the midwestern and southeastern areas of the United States, especially the Ohio and Mississippi river valleys.^1,2 However, recently there has been an increase in disease incidence outside of the previously considered endemic areas. Vermont and the surrounding New England areas have seen a rise in documented human cases.¹ Blastomycosis predominantly occurs in young large breed dogs (Labrador Retriever and Golden Retrievers).³

The spore form of Blastomyces is found in the soil and causes disease when inhaled by a host. Once within the lung, Blastomyces can colonize and result in local respiratory disease with varying severity. It can disseminate through lymphohematogenous systems to lymph nodes, eyes, bones, brain, meninges, kidneys, liver, spleen, heart, or skin.² Clinical signs of disseminated blastomycosis can be nonspecific and variable as they depend on the organ system involved.

Based on previous cases, 85% of dogs with blastomycosis have pulmonary involvement⁴ and present with clinical signs such as cough, increased respiratory rate, and increased lung sounds.² This makes it beneficial to include orthogonal thoracic radiographs as an initial diagnostic step. On radiographs, pulmonary blastomycosis is classically described as having a diffuse micronodular or miliary lung pattern, as in our patient.^2–4 Other conditions that can mimic this appearance are other fungal infections, diffuse neoplasia such as lymphoma or metastatic hemangiosarcoma, or pneumoconiosis (interstitial lung disease caused by inhaling particulate matter such as asbestos).⁵ Though the “classic” radiographic appearance of pulmonary blastomycosis is a micronodular/miliary interstitial pattern, a more recent study³ described significant variability in pulmonary patterns with only 51/125 (40.8%) of patients displaying diffuse nodular interstitial pulmonary pattern. Half of the patients (66/125 [50.3%]) had alveolar patterns or pulmonary masses that could be mistaken for other etiologies such as lobar pneumonia or primary pulmonary neoplasia.

To avoid making an inaccurate diagnosis, diagnostic tests such as cytology or histology are useful. Cytology can be collected from skin lesions, lymph nodes, transtracheal aspirates, bronchoalveolar lavage, or transthoracic lung aspirates.⁴ Due to the Blastomyces organism frequently causing interstitial lung disease in dogs, transtracheal aspirates can have a low sensitivity (50% to 69%).⁴ Lung fine needle aspirate, as done in this case, has a higher reported sensitivity of 80%.⁴ Serology can also be utilized as an adjunctive confirmatory test when the disease is longstanding. Antibody titers can often be negative during early blastomycosis infection leading to a false negative agar-gel immunodiffusion test result.²

In this specific case, the patient had recently traveled to the New Hampshire/Vermont border, an area with a high prevalence of blastomycosis. Given this travel history, presenting respiratory clinical signs that were unresponsive to multiple antibiotics, classic radiographic findings, and positive cytologic results, blastomycosis was definitively diagnosed. When an early diagnosis of blastomycosis is made and treatment is immediately started, the prognosis for a patient to fully recover is good.² Prognosis significantly worsens with severe pulmonary disease (as seen in this case) or when the disease disseminates to the brain.² There is a decrease in the survival rates of dogs with > 4 lung lobes involved.³ The treatment of choice for blastomycosis is itraconazole at 5 mg/kg, PO once daily, for at least 4 to 6 months due to ease of oral administration and reduced adverse effects.²

Establishing a definitive diagnosis for blastomycosis can be a challenge due to its varied radiographic presentation, low sensitivity of diagnostic tests such as a transtracheal wash and bronchoalveolar lavage, and its ability to disseminate and cause nonspecific clinical signs. The present case highlights the importance of utilizing a complete history (including response to prior medications and travel history), a thorough physical exam, classic radiographic findings, and cytology from bronchoalveolar lavage and/or fine needle aspirates to increase the likelihood of an accurate and timely diagnosis of blastomycosis. In most cases, travel history and clinical signs are sufficient to consider blastomycosis as a likely differential. However, this patient did not have a travel history to a historically endemic area. Visualizing a miliary interstitial pulmonary pattern on this patient’s thoracic radiographs led to a fungal inflammatory process being highly suspected. It is clear that radiographs are a crucial initial diagnostic tool that can improve both case management and the outcome of these complex cases.

Disclosures

The authors have nothing to disclose. No AI-assisted technologies were used in the generation of this manuscript.

Funding

The authors have nothing to disclose.