History and Physical Examination Findings
A 2-year-old 3.15-kg (6.93-lb) spayed female Mini Lop mixed-breed rabbit (Oryctolagus cuniculus) presented to the University of Wisconsin (UW)-Madison School of Veterinary Medicine on an emergent basis after a 24-hour history of diarrhea and lethargy preceded by a week of inappetence. Three weeks earlier, the rabbit had presented to the referring veterinarian for an abscess in the ventral cervical region. The abscess was treated with surgical removal and placement of antibiotic-impregnated beads. Postoperatively, the rabbit received enrofloxacin and meloxicam. The owner reported that the rabbit had a decreased appetite since surgery. The rabbit’s previous recorded weight was 3.3 kg (7.26 lb). On physical examination, the rabbit was lethargic, severely dehydrated on the basis of prolonged skin tent, underconditioned (2/9 body condition score), and normothermic with a temperature of 38.5 °C (normal, 38.5 to 40.0 °C)1; had gas palpable within the gastrointestinal tract; and was uncomfortable on abdominal palpation. Diarrhea with extensive perianal fecal staining was present.
Diagnostic Findings and Interpretation
The patient was sedated with dexmedetomidine (0.04 mg/kg), midazolam (1.0 mg/kg), and buprenorphine (0.03 mg/kg) IM. Atipamezole (0.4 mg/kg, IM) and flumazenil (0.1 mg/kg, SC) were given to reverse the sedation. Naloxone (0.04 mg/kg, IM) was administered because of a slow recovery, and the patient recovered over a 2-hour period. Initial diagnostics included a full-body CT scan, ultrasound-guided abdominal aspirate, CBC count, plasma biochemistry (Small Mammal Profile, VetScan VS2; Zoetis), and fecal occult (Hemoccult SENSA; Beckman Coulter). Clinically relevant CT findings included a large amount of abdominal fluid attenuation, consistent with peritoneal effusion. Marked diffuse thickening of the jejunal muscularis layer (Figure 1) was identified during ultrasound-guided sampling of the peritoneal effusion. Cytology revealed a transudative effusion. The initial CBC count showed a normal Hct of 37% (reference interval [RI], 31.3% to 43.3%) and a moderate leukocytosis (17.4 X 103/µL; RI, 4.1 X 103 to 10.8 X 103/µL]), with a mild heterophilia (heterophils, 8.2 X 103/µL; RI, 1.1 X 103 to 7.4 X 103/µL).1 On plasma biochemistry, albumin could not be detected because of a machine error and total protein was mildly decreased at 4.6 g/dL (RI, 5.3 to 8.5 g/dL). Other abnormalities included moderate elevation of BUN (72.0 mg/dL; RI, 9 to 29 mg/dL), mild hyperphosphatemia (8.3 mg/dL; RI, 3.0 to 6.2 mg/dL), and mild hypokalemia (3.3 mg/dL; RI, 3.4 to 5.1 mg/dL).1 A fecal occult blood test was negative. Differentials for the clinical findings included acute enteritis secondary dysbiosis (Clostridium spp) or, less likely, viral (rotavirus) versus chronic enteritis (inflammatory bowel disease), versus an infiltration round cell neoplasia such as lymphoma.
Abdominal ultrasound images of the jejunum of a rabbit diagnosed with inflammatory bowel disease (IBD). A—Initial presentation: marked diffuse thickening of the muscularis layer of the jejunum is evident (arrow), with an overall wall thickness of up to 0.4 cm measured. In addition, a small amount of anechoic peritoneal effusion is present (asterisk). B—Twenty days later, a repeated abdominal ultrasound showed resolution of the marked jejunal thickening (arrow; oval wall thickness measured 0.15 cm).
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.11.0730
Treatment and Outcome
Hospitalization occurred with supportive care including subcutaneous fluids (60 mL/kg), maropitant (4 mg/kg, SC, q 24 h), enrofloxacin (10 mg/kg, PO, q 12 h; compounded by UW Veterinary Care pharmacy), metronidazole (20 mg/kg, PO, q 12 h; compounded by UW Veterinary Care pharmacy), and syringe feedings (50 mL, PO, q 8 h). Plasma biochemistry was repeated 18 hours later and showed resolving elevation of BUN (48 mg/dL) and that all variables other than albumin (2.0 g/dL; RI, 2.8 to 4.0 g/dL) were within their RI.1 Meloxicam (1 mg/kg, PO, q 24 h) was given to alleviate the discomfort. The diarrhea transitioned to irregular, soft fecal production after 4 days of hospitalization. Due to a lack of clinical improvement within the first 36 hours, prednisolone (0.5 mg/kg, q 12 h; compounded by UW Veterinary Care) was started after a 1-day washout of meloxicam. Hospitalization and supportive care were continued for a total of 7 days before the rabbit was discharged home for continued syringe feeding, enrofloxacin, metronidazole, and prednisolone for 14 days. Foods other than hay and pellets were eliminated from this rabbit’s diet. The patient’s appetite had mildly improved, and the feces continued to be irregular and soft at 7 days. The prednisolone was continued at a tapering dose of 0.5 mg/kg every 12 hours for 3 days, 0.5 mg/kg every 24 hours for 3 days, then 0.5 mg/kg every 48 hours for 3 doses.
Two weeks following discharge, the rabbit was reevaluated. The owner reported a significant improvement in appetite and energy level. However, the rabbit continued to lose weight and had abnormal soft and irregular feces. The rabbit’s body weight was 3 kg, and it had lost 5% compared to its initial weight. An abdominal ultrasound demonstrated that jejunal thickening and peritoneal effusion were resolved (Figure 1). Enrofloxacin, metronidazole, and prednisolone (0.5 mg/kg, q 48 h) were continued as previously prescribed for an additional 2 weeks. Two weeks later, the rabbit’s weight had further decreased to 2.8 kg (–11%) despite a ravenous appetite, and diffuse muscle wasting was evident on physical examination. The prednisolone frequency was increased to 0.5 mg/kg every 12 hours, and the antibiotics were discontinued.
Eleven weeks after the initial visit, the rabbit had a ravenous appetite and normal feces. Body weight had increased to 3.37 kg, with an improved body condition to 3/9. A CBC was repeated, and mild leukopenia (2.8 X 103/µL; RI, 4.1 X 103 to 10.8 X 103/µL) was identified. Prednisolone was continued at 0.5 mg/kg twice daily. The rabbit developed pneumonia, diagnosed on CT 1 month later, and was started on trimethoprim-sulfamethoxazole (30 mg/kg, q 12 h). At that time, the patient’s weight was 3.52 kg, with a body condition score of 4/9. Prednisolone was decreased to 0.5 mg/kg every 24 hours for 7 days, then every 48 hours for 7 doses before discontinuing.
The rabbit had a stable weight of 3.5 kg, normal feces, a good appetite, and normal energy for 5 months after completing prednisolone. Nine months after initial presentation, the rabbit presented on an emergent basis for an acute history of hunched posture and no fecal output. A biochemistry revealed a markedly increased ALT (323 U/L; RI, 48 to 96 U/L).1 The CBC parameters were all within reference range. An ultrasound was performed, identifying a caudate liver lobe torsion and jejunal-jejunal intussusception. The owners elected humane euthanasia due to the poor prognosis. The patient was sedated SC with 0.05 mg of buprenorphine/kg, 5.0 mg of ketamine/kg, and 1 mg of midazolam/kg prior to full anesthesia with isoflurane. After a deep anesthetic plane was reached, confirmed by negative withdrawal reflexes, 0.5 mL of pentobarbital was given by intracardiac injection. Death was confirmed via auscultation. Necropsy confirmed the caudate liver lobe torsion. Histological examination of the small intestine revealed the lamina propria was diffusely infiltrated by lymphocytes and plasma cells with few macrophages and rare eosinophils (Figure 2). Hemosiderophages were often aggregated at villous tips. Gut-associated lymphoid tissue was expanded by prominent follicles with germinal centers (Figure 3). Mesenteric lymph nodes were similarly hyperplastic and reactive. Overall, histopathology showed mild to moderate chronic diffuse lymphoplasmacytic enteritis, which is consistent with a chronic inflammatory process.
Photomicrograph of the jejunum from the rabbit diagnosed with IBD. The lamina propria of the mucosa is expanded by a mixed population of lymphocytes and plasma cells (asterisk) that variably widen and distort the villi. At villous tips, there are frequent aggregates of hemosiderophages (arrow). H&E stain; bar = 50 µm. Inset—Phagocytosed iron in hemosiderophages stains positively (blue). Prussian blue iron stain; bar = 50 µm.
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.11.0730
Photomicrograph of the ileum from the rabbit diagnosed with IBD. Expanding the submucosal gut-associated lymphoid tissue are several hyperplastic lymphoid follicles with pale germinal centers (asterisks). Bar = 500 µm.
Citation: Journal of the American Veterinary Medical Association 2025; 10.2460/javma.24.11.0730
Comments
Inflammatory bowel disease (IBD) describes a group of idiopathic disorders that are typically characterized by inflammation of the gastrointestinal tract with persistent or recurrent clinical signs, including vomiting (canine and feline), diarrhea, weight loss, and hyporexia to anorexia. The exact etiology is unknown; however, it is hypothesized to be a combination of genetic and immunologic factors of the host responding to commensal microbiota, food components, and environmental factors.2 Diagnosis of IBD is challenging and typically achieved by histopathologic evaluation of intestinal biopsies for increased infiltration of lymphocytes and plasma cells in the lamina propria of the intestinal mucosa.2
Database searches of Pubmed, CAB, Scopus, and Google Scholar were utilized, covering the years 1957 to 2024, and were negative for documented cases of IBD in pet rabbits. However, rabbits have been used as models in laboratory medicine for IBD research.2
Endoscopy and intestinal biopsy were not utilized in the case of this rabbit because of financial constraints of the client. A confirmatory diagnosis of IBD was identified postmortem on histological evaluation in the absence of other potential causes for enteritis. Unlike the small intestines, there were no detectable abnormalities within the large intestine. This finding is consistent with the rabbit IBD model and histological findings of canine and feline patients.2,3
Treatment of IBD typically includes feeding an elimination diet and administering corticosteroids, immunosuppressive drugs, and/or select antibiotics.2 The reasoning for dietary therapy is to restrict the exposure to antigens like dietary proteins known to exaggerate the host responses and perpetuate intestinal inflammation.2 For this rabbit, all other food products aside from hay (timothy and alfalfa) and pellets were eliminated from the diet. Prednisolone and metronidazole combination therapy has been demonstrated to be a successful treatment in canine IBD patients with a reduction in clinical signs and weight gain. Steroid use in rabbits is controversial due to concerns of inducing immunosuppression, leading to secondary bacterial infections and other complications4; however, recent studies have demonstrated that corticosteroids can be used without detrimental effects on rabbits.5 Prednisolone (0.5 to 2.0 mg/kg) was started to reduce the inflammation within the gastrointestinal tract since there had been no clinical improvement while the rabbit was on meloxicam. This rabbit developed bacterial pneumonia during its treatment course, but it could not be definitively linked to prednisolone use. The authors recommend careful monitoring during the administration of exogenous corticosteroids in rabbits. Similarly to the canine findings, this rabbit’s clinical signs had significantly improved, with resolution of the diarrhea, increased activity level, and weight gain. Since intestinal biopsies were not obtained at the time of diagnosis, it is difficult to assess the effect of treatment histopathologically. Yet there were still significant histopathological changes at the time of necropsy. Further research is necessary to better understand the role of corticosteroid treatment in rabbits with IBD.
Acknowledgments
None reported.
Disclosures
Dr. Mans is a member of the JAVMA Scientific Review Board, but was not involved in the editorial evaluation of or decision to accept this article for publication.
No AI-assisted technologies were used to generate this manuscript.
Funding
The authors have nothing to disclose.
References
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Jergens AE, Simpson KW. Inflammatory bowel disease in veterinary medicine. Front Biosci (Elite Ed). 2012;4(4):1404-1419. doi:10.2741/e470
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Anthony D, Savage F, Sams V, Boulos P. The characterization of a rabbit model of inflammatory bowel disease. Int J Exp Pathol. 1995;76(3):215-224.
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Petritz OA, Chen S. Therapeutic contraindications in exotic pets. Vet Clin North Am Exot Anim Pract. 2018;21(2):327-340. doi:10.1016/j.cvex.2018.01.004
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Fakhir M, Adnan F, Najem E, Hashim J. Effect of prednisolone on the histology and histochemistry of rabbits liver and kidney. Inter J Drug Deliv Tech. 2019;9:217-221.
