Disseminated Nocardiosis in a Dog

Nocardia bacteria are facultative intracellular pathogens that uncommonly cause disease in dogs. Clinical manifestations include cutaneous–subcutaneous, pulmonary, and disseminated nocardiosis. This case report describes a case of disseminated nocardiosis with dermatologic, respiratory, and neurologic signs in a dog.

Signalment and History

A 6-month-old, 24-kg, female intact Rottweiler presented to the University of Pennsylvania Emergency Service as a referral for a 2-week history of respiratory distress, tracheobronchial lymphadenopathy, fever, and diarrhea that were not responsive to medical management, including multiple antibiotics (doxycycline, ampicillin and sulbactam, and metronidazole), fluconazole, and steroids. Diagnostics prior to presentation included multiple sets of thoracic radiographs showing progressive tracheobronchial lymphadenopathy; fungal testing for blastomycosis, histoplasmosis, and cryptococcus, with negative results; and an abdominal ultrasound that was unremarkable. The dog was hospitalized multiple times, but her signs continued to progress. A generalized seizure prompted referral.

About a month prior to the onset of respiratory signs, the patient developed ulcerative skin lesions on her vaginal mucosa and ventral abdomen that resolved with prednisone (dose unknown). The owners reported that 2 littermates of the patient died at 4 months of age after developing similar dermatologic, respiratory, and neurologic signs; both were reportedly negative for rabies and canine distemper virus (CDV).

Presentation and Diagnosis

On presentation, the patient was tachypneic with increased expiratory effort and a frequent cough. Harsh lung sounds were auscultated bilaterally. Her rectal temperature was 103.3 °F. The remainder of the physical examination was unremarkable.

Arterial blood gas testing performed on room air showed hypoxemia (PaO₂ = 63 mm Hg; reference range, 80 to 105 mm Hg) and a mild hyperlactatemia (2.5 mmol/L; normal, <2 mmol/L).^1,2 Thoracic radiography revealed marked middle tracheobronchial lymphadenopathy and a mixed pulmonary pattern (FIGURE 1). 

Figure 1. Thoracic radiographs obtained at admission. Marked middle tracheobronchial lymphadenopathy and a mixed pulmonary pattern are present. (A) Right lateral view.

Figure 1. Thoracic radiographs obtained at admission. Marked middle tracheobronchial lymphadenopathy and a mixed pulmonary pattern are present. (A) Right lateral view. (B) Left lateral view.

Figure 1. Thoracic radiographs obtained at admission. Marked middle tracheobronchial lymphadenopathy and a mixed pulmonary pattern are present. (C) Ventral-dorsal view.

The patient was admitted and treated as described in BOX 1. Clindamycin and ceftazidime were selected to provide broad-spectrum coverage without using classes of antimicrobials that the patient had previously received.

The next morning, the patient was transferred to the intensive care unit. Her physical examination was largely unchanged from presentation, although her respiratory status appeared worsened, as she was less tolerant of coming out of the oxygen cage. All treatments were continued except the fluconazole, and levetiracetam (30 mg/kg IV q8h) was added due to the seizure history. She was anesthetized for computed tomography (CT) of the head and thorax, cerebrospinal fluid (CSF) collection, and bronchoscopy. For anesthesia, she was premedicated with butorphanol (0.3 mg/kg IV) and induced with propofol (1.5 mg/kg IV). She was maintained on isoflurane for the CT and CSF tap. For bronchoscopy, she was maintained on a propofol continuous rate infusion (50 to 300 µg/kg/min IV). The bronchoscopy showed severe extraluminal compression of the right mainstem bronchus (FIGURE 2). A bronchoalveolar lavage (BAL) sample was submitted for cytology and culture. A bronchoscopy-guided transbronchial needle aspirate of the tracheobronchial lymph node was submitted for cytology.

Figure 2. Endoscopic image of the right mainstem bronchus showing severe extraluminal compression, evidenced by the bulging, smooth, mass-like structure protruding into the lumen.

The thoracic CT report described marked to severe tracheobronchial lymphadenopathy causing a severe mass effect with concurrent right caudal/right middle lung consolidation, a suspect atelectatic accessory lung lobe, and scant pleural effusion, most consistent with an abscessed tracheobronchial lymph node with concurrent bronchopneumonia and possible early lung abscessation/necrosis and pyothorax (FIGURE 3). Cranial CT showed subjectively widened cerebral sulci likely associated with the young age and incomplete brain development of the patient; however, underlying brain atrophy could not be definitively ruled out. No other intracranial lesions to explain seizures were identified.

Figure 3. Thoracic computed tomography scan showing marked to severe tracheobronchial lymphadenopathy (a) causing compression of the right mainstem bronchus (b) as well as right caudal and right middle consolidated lung lesions (c).

CSF analysis showed minimally increased total protein but was otherwise within normal limits. BAL cytology showed suppurative inflammation with a mixed bacterial infection with fine filamentous bacilli, short bacilli, and cocci. The lymph node aspirate showed chronic suppurative inflammation and fine filamentous bacteria (FIGURE 4). A modified Ziehl-Neelsen stain showed partially acid-fast bacteria most compatible with Nocardia species. Aerobic culture of the BAL sample yielded no growth; anaerobic culture was not submitted.

Figure 4. Tracheobronchial lymph node cytology showing fine filamentous bacilli (a) enmeshed within inflammatory cells, including many macrophages (b). 100× magnification, Wright-Giemsa stain.

The patient’s respiratory status continued to worsen throughout the day, and she became severely dyspneic whenever the oxygen cage door was opened. Repeat arterial blood gas performed on room air that evening revealed worsening hypoxemia (PaO₂ = 50.4 mm Hg).

Treatment Plan and Outcome

Given the concern for tracheobronchial and pulmonary abscessation as well as pyothorax, an exploratory thoracotomy was recommended. The potential need for mechanical ventilation was discussed based on her severe hypoxemia. However, due to poor prognosis, the owners elected humane euthanasia. A necropsy was performed and confirmed severe pyogranulomatous tracheobronchial lymphadenitis with Nocardia bacteria. While premortem culture samples were negative, aerobic culture of the tracheobronchial lymph node postmortem isolated Nocardia species. Anaerobic cultures resulted in no growth.

There was also evidence of severe multifocal acute pulmonary hemorrhage with alveolar necrosis, interstitial pneumonia, and hyaline membranes consistent with acute respiratory distress syndrome. No evidence of CDV infection (i.e., intraepithelial nuclear and/or cytoplasmic viral inclusion bodies or central nervous system perivascular cuffing) was identified on thorough histologic tissue survey. The cerebrum, cerebellum, and brainstem were all found to be normal on both gross and histologic examination.

Discussion

Nocardia bacteria are filamentous, branching, gram-positive bacteria that are ubiquitous in soil and may also be present in water and dust and on decaying plants and fecal matter. Infections are generally acquired via inhalation or puncture wounds and can be localized or disseminated. Disseminated nocardiosis is uncommon in dogs and is most often associated with immunosuppression.^3-8

Most other case reports of nocardiosis in dogs involve immunosuppressive drug administration,^3,6-8 but the patient in this report had no history of receiving immunosuppressive medications, although the dose of prednisone to treat her initial skin lesions was unknown. However, her skin lesions may have been the earliest sign of Nocardia infection. There are 2 case reports of nocardiosis with concurrent CDV infection,^4,5 and it is hypothesized that immunosuppression caused by CDV allowed for the opportunistic infection in these cases. While the patient in this case was not tested specifically for CDV, no histologic evidence of CDV infection was identified on necropsy. Additionally, the owner verbally reported that the other 2 affected puppies in the litter were tested for CDV and were negative, although records could not be obtained to confirm these results.

Given that other littermates reportedly had similar signs, a genetic immunodeficiency was suspected in this puppy. A possible immunodeficiency in related Rottweilers has been described and is characterized by a markedly low serum immunoglobulin A (IgA) concentration (<0.1 mg/mL). These dogs also showed decreased CD3⁺ T lymphocytes in secondary lymphoid tissues, irregularities of plasma cell development, and lack of plasma cells within mucosal and cutaneous sites.⁹ However, immunoglobulin testing of this puppy revealed a normal IgA level (2.6 mg/mL). Other types of inherited immunodeficiency cannot be ruled out.

There is one case report of systemic nocardiosis in a 12-week-old intact female husky caused by Nocardia cyriacigeorgica with no obvious predisposing cause. This patient did not have a history of immunosuppressive drug administration or concurrent infection with CDV, and canine parvovirus was excluded via polymerase chain reaction testing.¹⁰ A 1983 review of Nocardia infection in animals included 52 cases of nocardiosis in dogs and found that no predisposing factor was identified in 67.3% of cases. Additionally, 65.4% of affected dogs were less than 1 year of age and 82.7% of dogs were less than 2 years of age.¹¹ These results suggest that Nocardia bacteria may be primary pathogens in young dogs, not requiring immunosuppression or a predisposing condition for infection. This review, however, did not differentiate between cutaneous, pulmonary, and disseminated forms of the disease. In humans, nocardiosis is generally associated with immunosuppressive conditions, but up to 33% of patients are immunocompetent, particularly with cutaneous infections. Disseminated nocardiosis is more common in immunocompromised hosts.¹²

Treatment of disseminated nocardiosis consists of appropriate antimicrobial therapy combined with surgical drainage or debridement of any abscesses or lesions. Sulfonamides are the first-line antimicrobial drugs for treatment of nocardiosis, although drug choices should be made based on site of infection, host immune status, Nocardia species, and susceptibility testing. Further treatment was not pursued in this patient due to poor prognosis but would have included an exploratory thoracotomy to debride the suspect abscessed tracheobronchial lymph node as well as addition of appropriate antibiotics, such as trimethoprim–sulfamethoxazole.

Prognosis for nocardiosis is generally poor. The 1983 review of 52 cases in dogs found that 50% of the dogs died from the infection and 38.5% were euthanized based on lack of response to therapy.¹¹ This review did not discuss how the cases were treated. In humans, prognosis varies based on the site of the disease, with cure rates of approximately 100% for skin and soft tissue infections, 80% for pleuropulmonary infections, 50% to 85% for cases with central nervous system involvement, and 3% for disseminated nocardiosis.¹² The high mortality rate in veterinary patients may be due to underlying disease, delayed diagnosis, inadequate treatment, and/or financial constraints. However, it is possible that with more aggressive and advanced treatment prognosis could improve.

Conclusion

This report describes a case of disseminated nocardiosis in a 6-month-old female Rottweiler with dermatologic, pulmonary, and neurologic signs with no identifiable underlying cause. While disseminated disease is commonly associated with immunosuppression, it is possible that Nocardia species could be primary pathogens in dogs, particularly young dogs.