Case study by Dr Gemma Birnie
Ruby is a six-year-old cavoodle who presented to Brisbane Veterinary Specialist Centre for management of exocrine pancreatic insufficiency.
Approximately six months prior to presentation Ruby had developed loose faeces and her owners had observed weight loss. A diet, anti-parasitic and antibiotic trial had been ineffective.
A CBC, biochemistry and TLI was performed which identified hypoproteinaemia characterised by hypoalbuminaemia 16mg/L (reference rage 23-40g/L), hypercholesterolaemia 3.2mmol/L (reference range 3.5- 9.0mmol/L) and a TLI less than 1ug/L (reference range 5.4-32.0ng/L). She was diagnosed with exocrine pancreatic insufficiency and commenced on Enzymplex pancreatic enzymes half a scoop each meal. There was an initial improvement although she continued to lose weight, had persistent loose stools and became progressively more lethargic.
When Ruby was first assessed at BVSC she weighed 4.6kg. Her body condition score was 2/9 and muscle condition score was 1/3. The rest of her physical examination was unremarkable. Her fur coat was pale yellow and dull.
Serum cobalamin (vitamin B12) was assessed which was less than 111pmol/L (ref range 150-1020pmol/L). Cobalamin supplementation was commenced with weekly 50micgrogram/kg SC injections.
Her pancreatic enzyme dosing was increased to 1 scoop BID with food and she was commenced on a hydrolysed diet, metronidazole 10mg/kg PO BID and omeprazole 1mg/kg PO BID.
Initially, there was a partial response to therapy and her faeces became formed. Unfortunately, her appetite markedly reduced and there was progressive lethargy and weakness. Her serum albumin remained reduced at 19g/L (reference rage 23-40g/L).
Upper GIT endoscopy and biopsies were performed. Histopathology was consistent with lymphoplasmacytic gastritis supporting a diagnosis of inflammatory bowel disease.
She was commenced on prednisolone 1mg/kg SID with further increases in her pancreatic enzymes to 2 scoops BID.
After an initial partial response to therapy, she deteriorated with the return of greasy faeces and lethargy. Her serum albumin was improved at 22g/L and serum cobalamin was within normal limits. She was suffering from prednisolone side effects with marked polydipsia and polyuria.
It was elected to change her pancreatic enzyme supplementation to Creon™ 25,000IU capsules, one capsule with each meal. There was a significant improvement with resolution of her diarrhoea and progressive weight gain.
Her metronidazole and omeprazole doses were weaned and discontinued. Over the next two months, her prednisolone dose was weaned and discontinued.
Four months after commencing Creon™ supplementation, Ruby was clinically normal and had gained 2.7kg. Her body condition score was normal. She had a gorgeous red shiny coat! Serum cobalamin and albumin were within normal limits.
Exocrine pancreatic insufficiency is most commonly caused by pancreatic acinar atrophy as a result of immune mediated destruction. It is typically recognised in young dogs with clinical signs most often observed between 1-5 years of age. Chronic pancreatitis can also lead to the development of EPI as a result of the progressive destruction of the pancreatic tissue.
Clinical signs of disease occur when more than 90% of the exocrine pancreas is atrophied. The lack of pancreatic enzymes leads to maldigestion and malassimilation. Diarrhoea, weight loss, coprophagy, borborygmus and polyphagia are the most frequently reported clinical signs.
The gold standard diagnostic test for EPI is the assessment of trypsin-like immunoreactivity (TLI). This assay assesses trypsin and trypsinogen enzyme concentrations. These enzymes originate from the pancreas and hence abnormally low concentrations plus the observation of concurrent clinical signs allows a clinician to reach the diagnosis of EPI.
Exogenous replacement of the pancreatic digestive enzymes is required to treat this disorder. Various sources of pancreatic enzymes are available including powdered supplements, enteric-coated granules and raw pancreas from pigs or cows. A number of different powdered supplements have been reported in the veterinary literature. Oral bleeding may result from the use of powdered supplements which necessitates dose reduction. Overseas, powdered pancreatic enzymes are considered more effective than enteric-coated forms. In Australia however, we have limited powdered pancreatic supplements available and actually enteric coated Creon™ is anecdotally the treatment of choice.
Several complications of EPI have been identified including malabsorption of cobalamin, small intestinal dysbiosis and concurrent small intestinal disease.
Cobalamin deficiency is very common in dogs with EPI. In one study 82% of dogs with EPI had a decreased serum cobalamin concentration. Hypocobalaminaemia can further contribute to diarrhoea and weight loss and may also lead to lethargy, reduction in appetite and haematological abnormalities.
The postulated mechanisms for cobalamin deficiency development in EPI are: reduced/absent pancreatic secretion of intrinsic factor which is vital in cobalamin absorption, impaired releasez of cobalamin from haptocorrin limiting its ability to bind to intrinsic factor, secondary small intestinal dysbiosis compromising endogenous production of cobalamin, and compromise of the small intestine from toxic metabolites from this dysbiosis. Hypocobalaminaemia has been identified as a negative prognostic factor in dogs with EPI in two studies and hence supplementation is very important.
Small intestinal dysbiosis may necessitate the use of antimicrobial use in some patients. Dysbiosis results from increased substrates for bacteria, a lack of bacteriostatic factors, altered gastrointestinal motility and immunity. Tylosin and metronidazole are the most common antimicrobial choices.
Diet alteration may be beneficial for some patients. The diet should be individualised to the patient, with some dogs having concurrent small intestinal disease. Typically, a highly digestible diet with low fibre and moderate fat should be selected. There are mixed opinions in the veterinary literature regarding the benefit of dietary change and treatment success.
The use of gastroprotectants has been advocated in some patients who are failing to respond to pancreatic supplementation. Altering the gastric pH may prevent the destruction of the ingested pancreatic enzymes.
The prognosis for dogs diagnosed with EPI is considered good with approximately 50% of dogs responding to pancreatic supplementation. Partial response is reported in 20% and unfortunately, a poor response is described in 20%.
Batchelor DJ, Noble PJ, Taylor RH, Cripps PJ, German AJ. Prognostic factors in canine exocrine pancreatic insufficiency: prolonged survival is likely if clinical remission is achieved. J Vet Intern Med. 2007;21(1):54‐60.
Soetart N, Rochel D, Drut A, Jaillardon L. Serum cobalamin and folate as prognostic factors in canine exocrine pancreatic insufficiency: an observational cohort study of 299 dogs. Vet J. 2019;243:15‐20.
Kather S, Grützner N, Kook PH, Dengler F, Heilmann RM. Review of cobalamin status and disorders of cobalamin metabolism in dogs. J Vet Intern Med. 2020; 34(1): 13‐ 28.
Westermarck E, Wiberg M, Steiner JM. Exocrine pancreatic insufficiency in dogs and cats. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. St. Louis, Missouri: Elsevier Saunders; 2005:1492‐1495.
Dr Gemma Birnie BVSc FANZCVS Internal Medicine Specialist
Dr Birnie graduated from Massey University in New Zealand in 2009 and then spent two years in private practice in Victoria. In 2012, she did a rotating internship at Sydney University where she focused on Internal Medicine and Emergency Critical Care.
Dr Birnie passed her memberships in Small Animal Medicine in 2013 and worked as an ICU vet at a specialist referral clinic in Melbourne.
She joined Brisbane Veterinary Specialist Centre (BVSC) in 2014 and undertook an internal medicine residency.
Dr Birnie passed her fellowship exams and is Board Certified in Internal Medicine. She is a mentor-supervisor for BVSC medicine residents. Her special interests include immune mediated disease, neurology, endocrinology and oncology.