History
A 1.5-year-old 0.26-kg (0.57-lb) sexually intact male pet hairless rat was presented because of its declining physical condition related to an undiagnosed swelling in the left tarsal region (hock). Approximately 1 month earlier, the rat was examined at a veterinary teaching hospital because of acute swelling of the left hock with non–weight-bearing lameness. It was noted that the rat was sneezing. An excoriation was present on the medial aspect of the left thigh just proximal to the swollen hock. At that time, radiography revealed soft tissue swelling, but no fracture. The rat was prescribed meloxicam (1.15 mg/kg [0.52 mg/lb], PO, q 8 h) as needed for pain control and tramadol (11.5 mg/kg [5.23 mg/lb], PO, q 12 h for 7 days). The owner was asked to house the rat separate from its cagemate and to restrict the rat's exercise. Subsequently, there was minor improvement in the rat's condition, but it continued to have difficulty with ambulation. The rat eventually was found in lateral recumbency and was presented to the Emergency Service of the veterinary teaching hospital for euthanasia (by an IP overdose injection of euthanasia solution); a necropsy was authorized.
Gross Findings
At necropsy, the rat was in poor body condition. The swollen left hock was 1 cm in diameter and contained yellow-green exudate; similar exudate was expressed from the prepuce (Figure 1). A 9-mm-diameter abscess was identified in the right cranial lung lobe, and 5 abscesses (2- to 15-mm diameter) were identified in the kidneys. One abscess on the cranial pole of the right kidney was firmly adhered to the right lateral liver lobe.
Photograph of the ventrum, perineum, and hind limbs (A) and the removed kidneys and liver (B) of a 1.5-year-old pet hairless rat that was presented for euthanasia because of its declining physical condition related to an undiagnosed swelling in the left tarsal area. In panel A, the left tarsal area is swollen (white arrow), and exudate is expressed from the prepuce (black arrow). In panel B, the right kidney (arrow) has multiple abscesses, one of which is adhered to the right lateral liver lobe. The left kidney (arrowhead) has a solitary, large abscess. Marker = 1 cm.
Citation: Journal of the American Veterinary Medical Association 257, 9; 10.2460/javma.257.9.921
Photograph of the ventrum, perineum, and hind limbs (A) and the removed kidneys and liver (B) of a 1.5-year-old pet hairless rat that was presented for euthanasia because of its declining physical condition related to an undiagnosed swelling in the left tarsal area. In panel A, the left tarsal area is swollen (white arrow), and exudate is expressed from the prepuce (black arrow). In panel B, the right kidney (arrow) has multiple abscesses, one of which is adhered to the right lateral liver lobe. The left kidney (arrowhead) has a solitary, large abscess. Marker = 1 cm.
Citation: Journal of the American Veterinary Medical Association 257, 9; 10.2460/javma.257.9.921
Photograph of the ventrum, perineum, and hind limbs (A) and the removed kidneys and liver (B) of a 1.5-year-old pet hairless rat that was presented for euthanasia because of its declining physical condition related to an undiagnosed swelling in the left tarsal area. In panel A, the left tarsal area is swollen (white arrow), and exudate is expressed from the prepuce (black arrow). In panel B, the right kidney (arrow) has multiple abscesses, one of which is adhered to the right lateral liver lobe. The left kidney (arrowhead) has a solitary, large abscess. Marker = 1 cm.
Citation: Journal of the American Veterinary Medical Association 257, 9; 10.2460/javma.257.9.921
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page→
Histopathologic and Microbiological Findings
Histologic examination of sections of the tarsal region revealed areas of suppurative necrosis with neutrophils and macrophages in the joint spaces and adjacent bones. Lymphocytes and macrophages had infiltrated the hyperplastic synovium and periarticular fibrosis.
All visceral abscesses contained an exudate composed of degenerated and necrotic neutrophils and macrophages, and the abscess walls were infiltrated by lymphocytes, neutrophils, and some macrophages with occasional plasma cells. In the exudate, especially adjacent to the abscess walls, intralesional, gram-positive coccobacilli were evident in macrophages and had formed free colonies (Figure 2). Silver staining revealed no cilia-associated bacilli on the tracheobronchial epithelium. Additionally, the lungs had severe alveolar emphysema, but there was minimal hyperplasia of bronchial-alveolar lymphoid tissue. Aerobic bacterial culture of a specimen of the left hock yielded many pure colonies of Corynebacterium kutscheri.
Photomicrographs illustrating features of a renal abscess in the pet hairless rat in Figure 1. A—The abscess wall is fibrous and interfaced (arrowheads) with a rim of foamy macrophages that surrounds an exudate of degenerated neutrophils with bacterial colonies at the periphery (arrows). H&E stain; bar = 50 mm. B—The bacterial colonies (arrows) in the exudate are gram positive. Modified Gram (Hucker-Twort) stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 257, 9; 10.2460/javma.257.9.921
Photomicrographs illustrating features of a renal abscess in the pet hairless rat in Figure 1. A—The abscess wall is fibrous and interfaced (arrowheads) with a rim of foamy macrophages that surrounds an exudate of degenerated neutrophils with bacterial colonies at the periphery (arrows). H&E stain; bar = 50 mm. B—The bacterial colonies (arrows) in the exudate are gram positive. Modified Gram (Hucker-Twort) stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 257, 9; 10.2460/javma.257.9.921
Photomicrographs illustrating features of a renal abscess in the pet hairless rat in Figure 1. A—The abscess wall is fibrous and interfaced (arrowheads) with a rim of foamy macrophages that surrounds an exudate of degenerated neutrophils with bacterial colonies at the periphery (arrows). H&E stain; bar = 50 mm. B—The bacterial colonies (arrows) in the exudate are gram positive. Modified Gram (Hucker-Twort) stain; bar = 50 μm.
Citation: Journal of the American Veterinary Medical Association 257, 9; 10.2460/javma.257.9.921
Morphologic Diagnosis and Case Summary
Morphologic diagnosis: disseminated renal and pulmonary abscesses and chronic suppurative tarsal arthritis with suppurative osteomyelitis, synovial hyperplasia, and mild periarticular fibrosis and numerous, intralesional gram-positive coccobacilli.
Case summary: disseminated C kutscheri infection in a pet hairless rat.
Comments
The hairless rat of the present report was obtained as a pet from an unknown supplier, but it was not an athymic, immune-suppressed nude rat. Without published literature on the pet breed's origin and from information available on rat fancier websites, it appears that pet hairless rats are not considered truly hairless by rat fanciers. These hairless rats most commonly are a result of crossbreeding between rex rats; thus, the rex gene becomes more strongly expressed in the offspring. The offspring generally retain their whiskers and have a variably thin haircoat.
In our experience, the frequency of C kutscheri infection in modern laboratory rat colonies is no longer high because of good laboratory practices, but such infections among pet rats are quite common. Corynebacterium kutscheri was described by Kutscher1 in 1894 as the cause of one of the first diseases characterized in rodents. Corynebacterium kutscheri is a gram-positive coccobacillus and is sometimes referred to as the Chinese letter bacillus because of its bacterial cell pleomorphism. Corynebacterium kutscheri infection was initially called pseudotuberculosis because the associated lesions resemble the caseous lesions of tuberculosis. Infection with this bacterium does not result in development of tubercles; rather, it causes chronic suppurative necrosis that may appear caseous.2,3 Early studies4–7 showed that this organism was commonly harbored latently in colonies of mice, rats, and hamsters, but disease develops most commonly in stressed rats and mice.3,5–11 The sites that commonly harbor the bacteria are the oral cavity, cecum, and oropharyngeal, cervical, and maxillary lymph nodes. Latent transmission of the disease between individuals is considered to be primarily through the fecal-oral route.3,8,9 In rats and mice, sites of active infection are primarily the lungs, kidneys, joints, and liver. Clinical signs of C kutscheri–associated disease may develop in mice, rats, and guinea pigs.2,3 In rats and mice, latent infections have been experimentally converted to active infections through immunosuppression by stresses such as administration of cortisone or indomethacin, whole-body irradiation, and consumption of a vitamin-deficient diet.3,6–9 During active infection, dissemination probably occurs through the hematogenous route to the thoracic and abdominal viscera and results in abscess formation. Among rats and mice, there appears to be no age predilection for C kutscheri infection. Rats are said to be largely unaffected by the disease except when a precipitating stress factor exists.5,6 Disseminated infections, such as that in the rat of the present report, are uncommonly reported.12
Clinical signs of C kutscheri infection in rats include weight loss, respiratory distress, humped posture, ruffled hair coat, and anorexia.3,11 The pathogenesis of C kutscheri–induced disease involves upregulation of galectin, a proinflammatory lectin that causes chemoattraction of macrophages and activation of neutrophils.13 Interestingly, the anti-inflammatory cytokine interleukin-10 has a key defensive role in C kutscheri infections by increasing the clearance of the bacteria, presumably by decreasing tissue damage caused by the host's defenses. Interleukin-10 knockout mice with experimentally induced C kutscheri infection have a higher survival rate than similarly infected wild-type mice.14 Perhaps, the proinflammatory stimulus of upregulated expression of galectin has an important role in morbidity in individuals with systemic C kutscheri infection through promotion of more extensive local tissue damage and bacterial spread.
Histologically, lesions associated with C kutscheri infection in rats were described initially as focal areas of interstitial parenchymal necrosis that expand and become surrounded by neutrophils and macrophages to form abscesses. Typically, the colonies of gram-positive rods were seen at the periphery of the abscesses. Airway-oriented bronchopneumonia and bronchiectasis were not described.2,3,11 Unlike the case described in the present report, pet rats with C kutscheri infection usually develop bronchopneumonia and bronchiectasis and often have coinfections with other primary respiratory pathogens, such as cilia-associated respiratory bacilli, Mycoplasma pulmonis, and murine viruses. Corynebacterium kutscheri is commonly a secondary pathogen.3 Cilia-associated respiratory bacillus and Mycoplasma infections are associated with prominent peribronchiolar and perivascular infiltration of lymphocytes and plasma cells and bronchial-alveolar lymphoid tissue hyperplasia.3,15 In the rat of the present report, cilia-associated respiratory bacilli were not demonstrable, and there was no airway disease or bronchopneumonia with marked bronchial-alveolar lymphoid tissue hyperplasia. The emphysema without hemorrhage or inflammation was presumed to be attributable to chronic sneezing related to inhalation of dust created in the closed cage while cagemates interacted or fought. That problem had resolved when the cagemates were separated after the initial evaluation of the rat.
Streptobacillus moniliformis and Spirillum minus cause classic rat-bite fever in humans in North America and Asia, respectively,16 but the potential for human infection with C kutscheri should be considered in cases of rat bites, especially in children. Corynebacterium kutscheri infection in an otherwise healthy 7-month-old infant following a rat bite has been reported.17 The infection did resolve, but only following IV and oral treatment of the infant with antimicrobials. The infant's case confirmed that biting can result in cross-species C kutscheri infection. Although C kutscheri infections among rodents in modern laboratory breeding and research facilities are not common, pet rodents may harbor the organism in their mouths and shed it in feces. In pet rats, the presence of balanitis, arthritis, and caseous abscesses may be a useful indicator of C kutscheri infection, and such lesions also may alert veterinarians to systemic disease. Tissues, feces, and exudate from affected animals may be sources of infection for veterinarians and clients. This zoonotic disease potential should be considered when dealing with rat bites in general and, in particular, with bites from systemically ill rats. Proper cleansing of rat bites and postbite monitoring are warranted.
References
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