A 3-year-7-month old female neutered domestic shorthair cat presented to the Queen's Veterinary School Hospital with a 2 day history of acute onset progressive ataxia, dullness and reduced appetite. Prior to presentation it had no medical history, had never been outside of the UK, was vaccinated against feline panleukopenia virus, feline herpes virus, feline calicivirus and feline leukaemia virus (FeLV), and received regular preventive antiparasitic medications (praziquantel and moxidectin/imidacloprid). No toxin exposure was reported; however, it was a mixed indoor/outdoor cat with a known history of hunting. No other clinical signs were reported by the owner at the time of presentation or in the preceding period.
On clinical examination the cat was depressed and poorly responsive. It weighed 2.97 kg, with a body condition score of 3/9. It was pyrexic (rectal temperature 40.0oC) with a normal heart rate (184 beats per min), with a normal respiratory rate (24 breaths per min). Oral examination, thoracic auscultation and abdominal palpation were unremarkable. No detectable peripheral lymphadenopathy was present, and no detectable changes in mucous membrane moistness or skin elasticity were noted to indicate significant dehydration. Direct ophthalmoscopic examination was unremarkable. Neurological examination was performed, which identified reduced mentation, absent menace response bilaterally, absent response to nasal planum stimulation and ataxia on all four limbs. The cat appeared visual, with normal pupillary light reflexes and response to moving objects. It had a wide-based stance with truncal sway. The remainder of the cranial nerve reflexes and the spinal reflexes and proprioceptive responses were all within normal limits.
Biochemistry revealed moderate increases in alanine aminotransferase (ALT) (194 IU/l; reference interval [RI] 17-62 IU/l), aspartate aminotransferase (AST; 150 IU/l [RI 0-51 IU/l]) and total bilirubin (20 micromol/l [RI 0-11micromol/l]). Alkaline phosphatase and gamma-glutamyl transferase were below the detectable limit on the assay. A mild hyperglycaemia (9.8 mmol/l [RI 3.9-5.8 mmol/l]) was reported; however, the remainder of the biochemistry, including urea, albumin and globulin, was unremarkable. Haematology identified a marked leukopenia (1.83 x109 /l [RI 5.5-19.5 x109 /l]) with neutropenia (1.17 x109 /l [RI 2.5-12.5]) with left shift and toxic change and lymphopenia (0.4 x109 /l [RI 1.5-7.0x109 /l]). All other white cell, red blood cell (RBC) and platelet parameters were within the RIs.
ELISA testing for feline immunodeficiency virus/FeLV was negative. Serology for toxoplasmosis (IgM and IgG) was performed on a single sample and was negative at 1:20 and 1:200, respectively. Urinalysis by cystocentesis identified an increase in urine protein:creatinine ratio (0.94 [RI 0.0-0.2]) and mild increase in RBC numbers 7/high-power field (RI 0-5). On urine dipstick, 3+ bilirubin was present. Urine specific gravity by refractometry was 1.023. Urine culture was negative. MRI of the brain was undertaken and identified no abnormalities. Cerebrospinal fluid (CSF) tap found an increased specific gravity 1.008 (RI 1.004-1.006) but was otherwise unremarkable, with no increased cellularity or protein. Toxoplasma PCR was performed on the CSF sample and was negative. MRI and CSF tap were performed under general anaesthetic, during which intravenous fluid therapy was provided and monitoring by a diploma-holding anaesthetist was undertaken.
The cat initially recovered well from anaesthesia; however, it showed a marked deterioration over the subsequent 24 h, after which time the biochemistry and haematology were repeated. This identified further moderate increases in ALT (265 IU/l), AST (205 IU/l) and total bilirubin (42.9 micromol/l). Abdominal ultrasound was performed under sedation with dexmedetomidine and methadone, and identified no abnormalities, with normal size and echotexture of the liver and no abdominal lymphadenomegaly. The pancreas and biliary tree were reported to be unremarkable. Cytology of the liver was performed by fine-needle aspiration and showed a marked, mixed, predominantly neutrophilic bacterial inflammation with intra- and extracellular rod-shaped bacteria. Smaller numbers of macrophages were also reported, potentially suggestive of a more chronic course.
Minimally invasive laparotomy using a small incision and ring retractor (Figure 1) was subsequently performed under general anaesthetic to acquire hepatic biopsies and bile aspirate. Three liver samples from different areas were taken into formalin and two samples were taken for fresh submission. The cat was placed on intravenous fluid therapy for the duration of the procedure and for the subsequent 3 days until adequate voluntary food intake was achieved and hydration status considered to be normal. During the postoperative period the cat received opioid analgesia (initially methadone 0.3 mg/kg IV q4h, reducing to buprenorphine 0.02 mg/kg q6h after 24 h). Coagulation testing prior to surgery would have been desirable; however, this was overlooked in the face of the marked deterioration in the cat's clinical status and the rapid progression to biopsy.
The gross appearance of the liver was suggestive of multifocal abscessation (Figure 1.) After sample acquisition the cat was placed on potentiated amoxicillin (20 mg/kg IV q8h) as broad-spectrum empiric treatment for a suspected bacterial hepatitis. Histology identified macroscopic focal lesions roughly 1-2 mm in diameter on the sample and cut surfaces. Microscopic examination identified severe (60% of assessed area) necrotising and pyogranulomatous hepatitis (Figure 2) with intralesional gram-negative bacterial microcolonies (rods). Toxoplasma PCR on liver tissue was negative. Samples were submitted to the reference laboratory for culture of the bile and fresh hepatic tissue. These were both positive for Yersinia pseudotuberculosis. Fluorescent in situ hybridisation for eubacteria, and including Salmonella, Campylobacter, Helicobacter and Leptospira species, was negative for all other bacteria.
The cultured Yersinia pseudotuberculosis was tested for sensitivity by disc diffusion and was found to be sensitive to amoxicillin, marbofloxacin and oxytetracycline (resistant to cephalexin, metronidazole and clindamycin). On the basis that Yersinia species are not typically sensitive to amoxicillin, and that previous reported cases had responded poorly to therapy, additional treatment with marbofloxacin was instituted (1.7 mg/kg IV q24h) alongside the potentiated amoxicillin. The cat was also started on combined s-adenosyl methionine (SAMe) and silybin (Denamarin; Protexin, 30 mg/kg PO q24h). The cat remained hospitalised for a further 6 days during which time it showed rapid improvement in all clinical signs, with return to partial voluntary calorie intake within 24 h, and subsequent return to full voluntary food intake within 3 days. Fluid therapy was continued at maintenance rates throughout this period. Pyrexia resolved within 48 h of institution of antimicrobial treatment. Intravenous medications were transitioned to orally administered enteral formulations 1 day prior to discharge.
Biochemistry was repeated at the time of discharge, at which point all clinical signs had resolved. This revealed a reduced ALT (201 IU/l), AST (50 IU/l) and total bilirubin (11.1 micromol/l). Haematology identified a moderate, left-shifted neutrophilia (22.03 x109 /l [RI 2.5-12.5 x109 /l]) that was considered likely due to postoperative inflammation. The remaining haematological parameters were unremarkable. Clinical and neurological examinations were repeated daily during hospitalisation and showed gradual improvement, and at the time of discharge the neurological abnormalities present at presentation had resolved in their entirety.
The cat remained on treatment with both potentiated amoxicillin (21 mg/kg PO q12h) and marbofloxacin (1.66 mg/kg PO q24h) for an initial 4 week course. At the time of the 4 week recheck, the ALT level was found to have increased mildly; therefore, these medication courses were extended for a further 4 weeks to a total of 8 weeks as a precaution. This decision was driven heavily by the reported poor prognosis in previous cases of hepatic yersiniosis. At the time of the recheck the cat was otherwise well and no other biochemical or haematological changes were found. After this extension, the marbofloxacin was withdrawn and the potentiated amoxicillin maintained for a further 4 weeks before this and the SAMe/silybin were withdrawn. The cat remained clinically well, with no changes in biochemical parameters and therefore it was considered that no further treatment was required.
The cat was seen for multiple rechecks over the following 14 months. At all appointments it was reported to be clinically normal, and clinical and neurological examinations identified no abnormalities. Biochemistry was monitored on each occasion (Table 1). All haematological parameters remained within normal limits from the time of discharge. The cat remains alive and free of clinical signs at 23 months post-diagnosis.