History

A 3-year-old 65-kg Nubian doe had a 2-week history of lethargy and weakness that progressed to recumbency. The doe did not improve with treatment of penicillin (20,000 to 40,000 U/kg/d, IM) and meloxicam (0.5 mg/kg, SC, q 36 h) at the onset of the clinical signs. Two weeks before the clinical presentation, the doe had dystocia associated with stillbirth of twins and received fenbendazole (10 mg/kg, PO) just prior to the delivery.

Clinical and Gross Findings

On physical examination, the doe had white oral and ocular mucous membranes and continuous cough and wheezes on thoracic auscultation. The abdomen was moderately distended and abdominal ultrasonography revealed free fluid with a possible mass effect in the caudal aspect of the abdomen. Thoracic radiography revealed multifocal masses of variable sizes within the lungs. Results of McMaster fecal flotation testing were negative for ova or other evidence of parasites.

Serum biochemical analyses abnormalities included hyperglycemia (200 mg/dL; reference interval [RI], 50 to 75 mg/dL); mild hypocalcemia (8.3 mg/dL; RI, 8.9 to 11.7 mg/dL); hypomagnesemia (1.9 mg/dL; RI, 2.8 to 3.6 mg/dL); hypoalbuminemia (1.5 g/dL; RI, 2.7 to 3.9 g/dL); mild hyperbilirubinemia (0.2 mg/dL; reference limit ≤ 0.1 mg/dL); and high activity of γ-glutamyltransferase (182 U/L; RI, 34 to 65 U/L). A CBC revealed marked leukocytosis (42,120 WBCs/μL; RI, 7,200 to 17,700 WBCs/μL) with mature neutrophilia (segmented neutrophils, 38,750 cells/μL; bands, 842 cells/μL) and nonregenerative (hemoglobin concentration, 2.4 g/dL; RI, 8.2 to 12.4 g/dL), normocytic (mean corpuscular volume, 19.7 fL; RI, 15 to 23 fL), and normochromic (mean corpuscular hemoglobin concentration, 28.4 g/dL; RI, 32.5 to 38 g/dL) anemia (Hct, 8.4%; RI, 22% to 38%). A blood smear evaluation showed mild polychromasia. Abdominal fluid analysis revealed a protein concentration of < 2.5 g/dL and a total WBC count of 670 WBCs/μL. Due to the poor prognosis, the animal was euthanized using pentobarbital (150 mg/kg, IV) after sedation with xylazine (0.2 mg/kg, IM).

Gross postmortem examination revealed a tricavitary effusion with 400 mL, 20 mL, and 1.25 L of turbid, red-tinged fluid in the thoracic cavity, pericardial sac, and abdominal cavity, respectively. The lungs (Figure 1) and liver had randomly distributed, multifocal to coalescing, well-demarcated, firm, pale tan-white raised masses (0.5 to 3 cm in diameter). On cut surface, the masses had an onionskin appearance with a central area of multiple concentric laminae of friable pale tan to yellow-green material surrounded by a fibrous capsule. The tracheobronchial lymph nodes were markedly enlarged and coalesced to form a 15 X 6 X 5-cm mass. The uterus appeared to be undergoing normal postpartum involution, and there was no evidence of any traumatic event secondary to the dystocia.

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Postmortem photograph of the lungs of a 3-year-old 65-kg Nubian doe with a 2-week history of lethargy and weakness that progressed to recumbency. Multifocal, randomly distributed masses (0.5 to 3 cm in diameter) affect all lung lobes.

Citation: Journal of the American Veterinary Medical Association 260, 12; 10.2460/javma.22.03.0119

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Histopathologic, Histochemical, and Microbiological Findings

Microscopically, approximately 50% of the lungs were replaced by multifocal to coalescing pyogranulomas composed of a central area of variably mineralized necrotic cellular debris that was surrounded by a rim of degenerating neutrophils and merged into a band of macrophages intermixed with fibrous stroma (Figure 2). Numerous intrahistiocytic gram-positive coccobacilli were seen. There was marked interstitial edema. The alveolar spaces were filled with hemorrhage, fibrin, debris, neutrophils, and macrophages. Approximately 95% of the tracheobronchial lymph nodes and 50% of the hepatic parenchyma were effaced by similar pyogranulomas described in the lungs. Aerobic bacterial culture from the lung yielded heavy growth of Rhodococcus equi (4+).

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Photomicrographs of sections of lung tissue from the doe described in Figure 1. A—Lungs exhibit confluent pyogranulomas. H&E stain; bar = 500 μm. B—Higher magnification of the dashed square of panel A. The pyogranuloma has a central area of mineralized lytic necrosis surrounded by degenerating neutrophils and an outer rim of a band of macrophages containing numerous intracellular gram-positive coccobacilli. H&E stain; bar = 50 μm. Inset—Gram stain; bar = 20 μm.

Citation: Journal of the American Veterinary Medical Association 260, 12; 10.2460/javma.22.03.0119

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Morphologic Diagnosis and Case Summary

Morphologic diagnosis: marked multifocal to coalescing pyogranulomatous pneumonia, hepatitis, and lymphadenitis with myriad intrahistiocytic gram-positive coccobacilli.

Case summary: severe multiorgan pyogranulomatous inflammation secondary to disseminated Rhodococcus equi infection in a goat.

Comments

Rhodococcus equi is a gram-positive, facultative intracellular coccobacillus most commonly associated with the development of severe chronic pyogranulomatous pneumonia in young foals, usually between 3 weeks to 5 months of age.¹ Rhodococcus equi is also known to cause a number of extrapulmonary diseases in foals, including ulcerative enterocolitis and typhlitis, abdominal lymphadenitis, polysynovitis, vertebral osteomyelitis, diskospondylitis, and inflammation of the ocular structures (eg, uveitis, keratouveitis, and panophthalmitis).¹ Although the most common route of infection is via inhalation of aerosolized bacteria from the environment, ingestion should also be considered.² Adult horses are substantially less susceptible to Rhodococcus equi infection, with the disease only occurring sporadically and predominantly involving the lung, colon, and associated lymph nodes.^1,2

In goats, R equi infection is typically associated with hepatic pyogranulomas, frequently with concurrent pulmonary involvement, as seen in this case.^1,3 Reported cases of vertebral, humoral, and tibial osteomyelitis also had concomitant extensive involvement of the lung and liver.^4–6 The predominance of liver involvement suggests that transmission primarily occurs via ingestion, with an ascending infection from the intestinal tract resulting in disease of the liver and subsequent dissemination of the bacteria either hematogenously or within macrophages to other locations in the body.^4,6 Inhalation and percutaneous wound inoculations are also speculated to occur.^5,6

Clinical signs in goats are typically nonspecific, with the most common findings being anorexia, weight loss, malaise, and pyrexia.⁶ In some cases, clinical signs reflect the organs involved, such as paresis with vertebral osteomyelitis and abscess formation involving the spinal canal, lameness with osteomyelitis of the limbs, or coughing with bronchopneumonia, as seen in this case.^4,6,7 Although combination treatment with a macrolide antimicrobial (erythromycin, azithromycin, or clarithromycin) and rifampin is considered the treatment of choice in foals with rhodococcosis,¹ effective treatment in goats is still unknown.⁵ In the presented case, we hypothesized that immunosuppression caused by pregnancy may have predisposed this goat to develop R equi infection. Interestingly, this goat had marked nonregenerative, normocytic, normochromic anemia, for which there was no overt cause. However, despite the lack of evidence of gastrointestinal parasitism, the anemia in combination with hypoalbuminemia is suggestive of parasitism, and Haemonchus contortus infestation should be considered. Parasitism could have resulted in further immune impairment and susceptibility to a disseminated rhodococossis. Finally, anemia and the relevant clinical pathology findings could also be likely secondary to chronic systemic granulomatous inflammation. Overall, other speculated predisposing factors in goats include coccidial enteritis and caprine arthritis encephalitis infection, although the last one is not considered an immunosuppressive virus.^4,6,8 The goat of the present report was not tested for caprine arthritis encephalitis virus.

Differential diagnoses should include infection by Corynebacterium pseudotuberculosis (causative agent of caseous lymphadenitis) and Mycobacterium spp, both of which can cause similar macroscopic and microscopic findings and can have important herd health implications.⁵ External caseous lymphadenitis is generally associated with abscesses around the head and neck, but the internal form of the disease (more commonly seen in sheep) results in chronic wasting and abscesses that can be present anywhere in the body.⁵ Tuberculosis is usually associated with granulomas within the thoracic cavity, but disseminated disease can result in granulomas elsewhere.⁵ Grossly, these different disease processes cannot be definitively distinguished from one another, and aerobic bacterial culture is highly recommended for a definitive diagnosis as R equi grows easily on routinely used nonselective media incubated at 37 °C.² Although uncommon, R equi infection should be considered as a differential diagnosis of pyogranulomatous lesions in goats, particularly if the liver and lungs are involved.

Rhodococcus equi is also frequently cultured from the submaxillary lymph nodes of pigs and may play a role in the development of granulomatous lymphadenitis; however, a direct causal relationship between the agent and the disease has yet to be established.^1,2 Rhodococcus equi infection in wild animals has been reported only in American bison and some populations of wild boar.⁹ It is believed that immunosuppression is the underlying driving force leading to susceptibility to infection and disease rather than an inherent susceptibility, as seen in foals.^2,9 In cattle, R equi infection is a rare cause of bronchopneumonia, mastitis, metritis, ulcerative lymphangitis, and septic arthritis.¹ In dogs and cats, cases of R equi infection causing pneumonia, subcutaneous abscesses, vaginitis, hepatitis, osteomyelitis, myositis, joint infections, endophthalmitis, and endocarditis have been reported.^1,10 In humans, R equi is now being recognized as an emerging zoonotic pathogen in immunosuppressed individuals (eg, affected with HIV, undergoing chemotherapy, or organ transplant recipients), primarily causing pneumonia but also manifesting as osteomyelitis and abscesses elsewhere in the body.^2,11

The pathogenicity of R equi relies on the presence of virulence-associated proteins that allow it to survive within macrophages.^2,3 These proteins are encoded on genes present on virulence plasmids and are called virulence-associated proteins A (VapA), B (VapB), and N (VapN).³ Rhodococcus equi strains lacking VapA, VapB, or VapN genes are considered avirulent.³ The particular virulence plasmid present is also important in host tropism, with VapA predominating in horses, VapB in pigs, and vapN in cattle.³ Vap A and VapN are described in dogs.¹⁰ The virulence plasmid genotype from R equi isolates taken from 6 different goats identified that all were positive for VapN and lacked VapA and VapB, with 1 goat having both a virulent isolate (VapN) and an avirulent isolate.³ No PCR assay was performed to determine the presence or absence of virulence plasmids in this case.