Exocrine Pancreatic Insufficiency (EPI)
and the Cavalier King Charles Spaniel


Exocrine pancreatic insufficiency (EPI) is a disorder of the pancreas gland caused by inadequate production of digestive enzymes from pancreas' acinar cells, due either to severe damage to or lack of pancreatic acinar cells.

 Cavalier King Charles spaniels are among a very few breeds with increased prevalence of EPI. The German shepherd dog is the most common sufferer of EPI, primarily due to pancreatic acinar atrophy (PAA). In the CKCS, there is a strong association between EPI and chronic pancreatitis(CP). Some studies have suggested a heriditary relationship between EPI and CP in the cavalier. Other breeds similarly affected include Cocker spaniels and West Highland white terriers. EPI associated with PAA is considered a different disease than EPI associated with CP.

What It Is

The pancreas is a gland which consists of about 98% exocrine acinar cells and 2% endocrine islets. The Pancreas, from Veterinary Partnersexocrine cells secrete enzymes* which aid the digestion of protein in the smaller intestine. The endocrine cells secrete insulin, which helps control carbohydrate metabolism, and glucagon, which offsets the action of the insulin.

* Enzymes secreted include lipase, alpha-amylase, phospholipase and the proteolytic enzymes elastase, chymotrypsin, and trypsin.

Exocrine pancreatic function is due to a lack of functional pancreatic acinar cells, leading to inadequate production of digestive enzymes in the small intestinal lumen, resulting in impaired nutrient absorption, loose stools, and weight loss.

 Exocrine pancreatic diseases in dogs that may result in clinical signs of EPI include pancreatic acinar atrophy (PAA), chronic pancreatitis, and pancreatic neoplasia. EPI primarily affects the gastrointestinal (GI) system. 

Chronic pancreatitis appears to be a relatively common cause of EPI in dogs. It often occurs concurrently with diabetes mellitus, which may precede the onset of EPI. In the cavalier, chronic pancreatits is the most common disease which can lead to EPI. See our webpage on Pancreatitis for more information on that disorder. An under-diagnosis of chronic pancreatitis as a cause of EPI in dogs is suspected.

Thus far, PAA has been observed primarily in German shepherd dogs, along with rough-coat collies, English setters, and Chows.

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Symptoms

Clinical signs of EPI include: polyphagia (excessive hunger or increased appetite), weight loss, signs of maldigestion, including increased fecal volume, frequent defecation, poorly digested, loose feces, yellow feces, flatulence, coprophagia (consumption of feces), abdominal discomfort, nervousness, aggressiveness (rarely),  vomiting (rarely), possibly skin disorders.

 The exocrine pancreas has a large reserve secretory capacity, and maldigestion signs are usually not seen until 90% of the secretory capacity is lost.

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EPI-UnderweightDiagnosis

EPI is diagnosed on the basis of clinical signs together with enzyme assays – catalytic, immuno-, and enzymatic – involve measuring levels of the circulatving pancreatic enzyme, canine trypsin-like immunoreactivity (cTLI). This test is used to quantify trypsinogen and trypsin in the blood serum. Measurement of elevated circulating cTLI enzymes currently is the best test available for diagnosis. cTLI typically is low EPI. However, the presence of chronic pancreatitis may elevate cTLI into or above the normal range, confusing the diagnosis.

Serum cTLI assays are species- and pancreas-specific. Current reference ranges for cTLI in healthy dogs are 5.7 to 45.2 mcg/L. A serum cTLI concentration between 2.5 and 5.7 mcg/L may be associated with EPI. Fecal examinations of trypsin activity measurement also has been used for the diagnosis of EPI.

Because cobalamin (vitamin B12) deficiency is common in dogs with EPI, cobalamin in the dog's blood serum also likely will be measured.

Small intestinal dysbiosis (SID), also known as "leaky gut" may also be diagnosed or at least suspected. SID is a decrease of the small intestinal microbiota, which consists of a variety of microorganisms, including bacteria, viruses, and fungal organisms. Its customary symptoms are similar to those of EPI, described above.

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Treatment

Treatment usually consists of replacement of pancreatic digestive enzymes, including supplementing meals with digestive enzymes – powdered pancreatic enzyme supplements, such as pancreatin powder.

Cobalamin (vitamin B12) deficiency is common in dogs with EPI, probably as a result of increased uptake of cobalamin by the intestinal bacteria. If subnormal serum concentrations of cobalamin are found, cobalamin will be administered by injection.

TylanSpecial diets also may be recommended to maintain nutritional levels, including low fibre content, as high fibre may interfere with enzyme activity, and adding raw chopped pancreas.

Antibiotics, prebiotics, and antimicrobials also may be prescribed. Typical antibiotics to treat EPI (and SID) are, especially tylosin (Tylan), and also oxytetracycline (Terramycin) and metronidazole (Flagyl); and less likely amoxicillin-clavulanate, fluoroquinolones (a category which includes ciprofloxacin, norfloxacin, ofloxacin, gemifloxacin, levofloxacin, and moxifloxacin), and  trimethoprim/ sulfonamide (Bactrim, Septra DS, Tribrissen, Di-Bioti, Albon, Uniprim Powder, Tucoprim Powder, Borgal).

This will be a life-long condition in most every affected dog. Most dogs respond well to this therapy as long as their owners continue the treatment regimens.

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What You Can Do

Consider adding plant enzymes and probiotics to your dog's diet.

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Veterinary Resources

A survey of the diagnosis and treatment of canine exocrine pancreatic insufficiency. E. J. Hall, P. M. Bond, C. McLean, R. M. Batt, L. McLean. J. Sm. Anim. Pract. December 1991;32(12):613-619. Quote: A questionnaire was sent to veterinary surgeons who had diagnosed exocrine pancreatic insufficiency (EPI) by assay of low serum concentration of trypsin-like immunoreactivity in 302 dogs. Two-thirds of cases were German shepherd dogs, in which EPI was found equally in males and females. The disease was also diagnosed in 33 other breeds [including 18 cavalier King Charles spaniels], most commonly in crossbreeds, spaniels ... (especially Cavalier King Charles), small terriers and collies, and was more common in females. Detailed replies on 160 cases were returned; 79 dogs were alive and 41 dead, with the remainder lost to long term follow-up. The major reasons for death were euthanasia because of the cost, the prognosis, and failure to respond to treatment. An adequate response to treatment was obtained in 92 per cent of dogs. Uncoated preparations of pancreatic enzyme replacement were found to be more successful, and the use of dietary manipulation and antibiotics were frequently reported to be useful adjunctive therapies.

Serum Trypsinlike Immunoreactivity Measurement for the Diagnosis of Subclinical Exocrine Pancreatic Insufficiency. Maria E. Wiberg, Anna-Kaisa Nurmi, and Elias Westermarck. J. Vet. Intern. Med. September 1999;13(5):426–432. Quote: Dogs (n 5 158) with serum trypsinlike immunoreactivity (TLI) concentrations # 5.0 mg/L were studied. The diagnosis of clinical exocrine pancreatic insufficiency (EPI) was made in 114 [including 3 cavalier King Charles spaniels] of 158 dogs based on TLI concentration , 2.5 mg/L and clinical signs typical of EPI (eg, polyphagia, voluminous feces, weight loss). In 44 of 158 dogs, a single TLI measurement and clinical signs were not diagnostic. In 9 of 44 dogs, TLI was ,2.5 mg/L, indicating EPI, but the gastrointestinal signs were atypical or the dogs were asymptomatic. In 35 of 44 dogs, TLI was 2.5–5.0 mg/L. All 44 dogs were retested for TLI within 1–27 months (mean, 11.9 months). In 20 of 44 dogs, the retested TLI was normal (.5.0 mg/L). In 4 of 44 dogs with clinically diagnosed EPI, the retested TLI was ,2.5 mg/L. In the remaining 20 of 44 dogs, TLI was persistently ,5.0 mg/L (range, 1.0–4.9 mg/L; mean, 3.1 mg/L). Of these dogs, 15 had no clinical signs of gastrointestinal disease, and 5 had occasional clinical signs atypical for EPI. Gross examination of the pancreas (12 dogs) showed that the amount of normal pancreatic tissue was remarkably diminished. These dogs were diagnosed with subclinical EPI. The TLI-stimulation test, in which TLI is measured before and after stimulation with secretin and cholecystokinin, showed a significant response (P , .05) both in dogs with subclinical EPI and in control dogs, but showed no response in dogs with clinical EPI. In this study, EPI was diagnosed in its subclinical phase by TLI concentrations persistently , 5.0 mg/L, and a single TLI concentration , 5.0 mg/L was not diagnostic. Retesting after TLI concentrations , 5.0 mg/L is recommended even in clinically normal dogs, because of the possibility of subclinical EPI.

Exocrine pancreatic insufficiency as an end stage of pancreatitis in four dogs. P. J. Watson. J. Sm. Anim. Pract. July 2003; 44(7):306-312. Quote: Chronic pancreatitis is a common cause of exocrine pancreatic insufficiency (EPI) in humans and cats but is rarely recognised in dogs in which pancreatic acinar atrophy (PAA) is reportedly more common. This paper describes four dogs which developed EPI secondary to pancreatitis. Two of the dogs also had diabetes mellitus which developed before EPI. One diabetic dog had concurrent hyperadrenocorticism and was euthanased five months after presentation; the other diabetic dog died 48 months after diagnosis. The remaining dogs were alive 78 and 57 months after diagnosis. The number of affected dogs was comparable to the number of cases of presumed PAA seen over the same time period in the same institution. Chronic pancreatitis may be a more common cause of EPI in dogs than previously assumed and may be under-recognised because of difficulties in diagnosis. The relative importance of chronic pancreatitis as a cause of canine diabetes mellitus remains to be ascertained. ... Case 3 was a two-year-old, entire male Cavalier King Charles spaniel. ... They presented with a three-week and 10-day, respectively, history of anorexia and vomiting which was unresponsive to treatment with intravenous fluids, antiemetics, gastric acid secretory inhib-itors and antibiotics. Case 3 also had haematemesis and diarrhoea. ... Clinical examination in [Case 3]  showed depression, weakness, abdominal pain and poor body condition (bodyweight 5·4 kg and 3 kg, respectively). Case 3 also had pale mucous membranes and a grade 4/6 systolic cardiac murmur. Abdominal ultrasound examination was performed in [Case 3]. In case 3, there was free abdominal fluid and the pancreas had a mixed echogenicity suggestive of inflammation. These changes were found on both the first and second visits. ...  Blood samples showed marked elevations in amylase and lipase at various times in [Case 3]. Pancreatitis was diagnosed in [Case 3] on the basis of the blood tests and ultrasonography results. [Case 3 was] treated with intravenous fluids, cimetidine and antibiotics. Case 3 also received sucralfate. Urine output was good in [Case 3]. [Case 3 was] initially starved, followed by little and often feeding of a low fat diet (Pedigree Canine Low Fat Diet; Waltham). ... The bodyweight of case 3 fell to 4·6 kg in 14 days. Serum TLI was repeatedly low. A laparotomy was performed for intestinal and pancreatic biopsies, after a plasma transfusion to restore blood albumin levels. The pancreatic biopsy showed marked interstitial fibrosis with a slight mononuclear inflammatory cell infiltrate. There was loss of acinar secretory cells and replacement of secretory lobules by fibrous tissue. The duodenal biopsy was normal but the jejunum and ileum showed marked villous atrophy with fusion and distortion of some villi. There was a light mononuclear infiltrate in the lamina propria. A diagnosis of EPI secondary to pancreatitis and concurrent inflammatory bowel disease was made in case 3 on the basis of TLI measurements and histopathology of the gut and pancreas. Treatment was commenced with pancreatic enzyme supplementation and a hypoallergenic diet (Whiskas Feline Selected Protein Diet chicken and rice; Waltham) together with antibiotics, anti-inflammatory doses of prednisolone and coconut oil supplementation. The prednisolone and coconut oil were phased out after three weeks but the diet and enzyme supplementation were continued long term. The faeces became normal and appetite good with a weight gain from from 4·1 kg at discharge to 6·8 kg seven months later. At the time of writing, the dog remained alive and well 78 months after diagnosis. DM had not developed. Serum vitamin B12 and folate levels were measured in cases 2 and 3 on one or more occasions and were normal. ... The diagnoses of both EPI and pancreatitis in[Case 3 was] made clinicopathologically, with additional confirmation from pancreatic ultrasound ..., and histopathology in case 3. EPI was diagnosed in these cases on persistently low TLI measurements combined with compatible clinical signs which responded to enzyme supplementation. TLI dropped to low levels diagnostic of EPI on more than one occasion in cases 3 and 4. ... Cases 2, 3 and 4 all had elevated amylase and/or lipase on one or more occasions. ... At the time when these animals presented, measurement of these enzymes represented the best non-invasive method of diagnosing pancreatitis in dogs, particularly when supported by ultrasonographic evidence of pancreatic disease as in cases 3 and 4. ... Interestingly, cases 3 and 4 in this series, which showed the most clinically severe pancreatitis also had the most marked elevations in plasma lipase and amylase.aaa Ultrasonographic findings supported the diagnosis of pancreatitis in case 3. ... The findings on pancreatic histopathology in case 3 were typical of end-stage chronic pancreatitis with extensive destruction of both endocrine and exocrine tissue, inflammation and marked fibrosis. ... [Case] 3 had a histopathological diagnosis of chronic pancreatitis, although case 3 showed clinical signs of a single bout of classical ‘acute’ pancreatitis. ... The management of case 3 was complicated by concurrent inflammatory bowel disease, necessitating prednisolone therapy and a hypoallergenic diet. However, this dog was maintained long term on only diet and enzyme supplementation, suggesting that EPI was a significant part of its clinical problem. The use of coconut oil as a calorie source in this dog was unwise as it is fatdense and so could stimulate further bouts of pancreatitis.

Prevalence of Chronic Pancreatitis at Post Mortem Examination in an Unselected Population of First Opinion Dogs. PJ Watson, A Roulois, P Johnston, H Thompson, ME Herrtage. ECVIM 2005 Symposium Absract # 69. J.Vet.Intern. Med.;19(6).Quote: "The prevalence of chronic pancreatitis (CP) dogs is unknown. Previous studies have focused on acute pancreatitis and/or have used a highly biased and selected population of second opinion and critical care cases. This study aimed to assess the prevalence of chronic pancreatitis in an unselected population of first opinion dogs. Sections were obtained from 100 consecutive canine post mortems presented to Glasgow Veterinary School from surrounding first opinion practices. Most dogs were assessed as middle-aged to old. In each case, 3 sections of pancreas were taken: one from each limb and one from the body. Sections were preserved in formalin and stained with H&E and Sirius red. They were examined histologically, blind to signalment. Clinical details were not available. The dogs were grouped according to histological findings: (a) sections too autolysed to interpret; (b) no abnormalities visible; (c) non specific/non significant changes; (d) chronic or acute-on-chronic pancreatitis; (e) acute pancreatitis with no chronic changes and (f) other disease. Prevalence of each group was calculated and relative risk of CP and autolysis were calculated for different breeds. Prevalence of autolysis was 27%, a shortcoming of this type of study. Autolysis was common in large breed dogs due to slow cooling of core temperature (e.g German shepherd dogs relative risk of autolysis 3.8) so relative risk of CP could not be calculated in large breeds. The pancreas had no histological abnormalities in only 13% of dogs. Non specific changes were observed in 24% of dogs. Acute pancreatitis had a low prevalence of 2%. The prevalence of CP was 29% and breeds with a high relative risk included Cavalier King Charles spaniels (CKCS): relative risk 4.1 and Jack Russell terriers: relative risk 2.4. 6/6 CKCS had CP, with 1/6 having end stage disease and 1/6 having concurrent pancreatic neoplasia. The lesions observed are likely to correlate with clinical disease: one out of four published cases of end stage CP with exocrine pancreatic insufficiency (EPI) was a CKCS and a further 2/7 biopsy-confirmed cases of chronic pancreatitis seen at the Queen’s Veterinary School Hospital since 2002 were CKCS, both of which had EPI and one of which had diabetes mellitus. We conclude that CP is common in the first opinion dog population and that, like in the liver, end stage disease can be considered as a distinct clinically significant entity. There are strong breed-associations in CKCS and JRT, suggesting a possible genetic basis to the disease in these breeds."

Breed Associations for Canine Exocrine Pancreatic Insufficiency. Daniel J. Batchelor, Peter-John M. Noble, Peter J. Cripps, Rebecca H. Taylor, Lynn McLean, Marion A. Leibl, Alexander J. German. J. Vet. Intern. Med. March 2007;21(2):207–214. Quote: Background: Knowledge of breed associations is valuable to clinicians and researchers investigating diseases with a genetic basis. Hypothesis: Among symptomatic dogs tested for exocrine pancreatic insufficiency (EPI) by canine trypsin-like immunoreactivity (cTLI) assay, EPI is common in certain breeds and rare in others. Some breeds may be overrepresented or underrepresented in the population of dogs with EPI. Pathogenesis of EPI may be different among breeds. Animals: Client-owned dogs with clinical signs, tested for EPI by radioimmunoassay of serum cTLI, were used. Methods: In this retrospective study, results of 13,069 cTLI assays were reviewed. Results: An association with EPI was found in Chows, Cavalier King Charles Spaniels (CKCS), Rough-Coated Collies (RCC), and German Shepherd Dogs (GSD) (all P , .001). Chows (median, 16 months) were younger at diagnosis than CKCS (median, 72 months, P , .001), but not significantly different from GSD (median, 36 months, P 5 .10) or RCC (median, 36 months, P 5 .16). GSD (P , .001) and RCC (P 5 .015) were younger at diagnosis than CKCS. Boxers (P , .001), Golden Retrievers (P , .001), Labrador Retrievers (P , .001), Rottweilers (P 5 .022), and Weimaraners (P 5 .002) were underrepresented in the population with EPI. Conclusions and Clinical Implications: An association with EPI in Chows has not previously been reported. In breeds with early-onset EPI, immune-mediated mechanisms are possible or the disease may be congenital. When EPI manifests later, as in CKCS, pathogenesis is likely different (eg, secondary to chronic pancreatitis). Underrepresentation of certain breeds among dogs with EPI has not previously been recognized and may imply the existence of breed-specific mechanisms that protect pancreatic tissue from injury. ... There are strong breed associations with CP in the Cavalier King Charles Spaniel (CKCS) and Jack Russell Terrier. ... Breeds with increased prevalence: ... Cavalier King Charles Spaniel:: Number Affected [with EPI]: 64; Number Tested: 243.

Prevalence and breed distribution of chronic pancreatitis at post-mortem examination in first-opinion dogs. P. J. Watson, A. J. A. Roulois, T. Scase, P. E. J. Johnston, H. Thompson, and M. E. Herrtage. J Small Animal Prac (2007) 48:609–618. Quote: Canine EPI is believed to most commonly result from pancreatic acinar atrophy (PAA) but PAA is a histologically, clinically and pathophysiologically distinctively different disease from EPI as a result of CP [chronic pancreatitis].CP may be under-recognised in dogs because of the low-grade, nonspecific nature of the clinical signs and the difficulty of ante-mortem diagnosis by non-invasive techniques. ... A recent study of breed associations for canine exocrine pancreatic insufficiency in the UK also recognised older CKCS as having an increased risk of EPI and the authors suggested this may be because of CP, although pancreatic pathology was not available in those dogs. ... Objectives: To assess the prevalence of canine chronic pancreatitis in first-opinion practice and identify breed associations or other risk factors. Methods: Three sections of pancreas were taken from 200 unselected canine post-mortem examinations from first-opinion practices. Sections were graded for inflammation, fibrosis and other lesions. Prevalence and relative risks of chronic pancreatitis and other pancreatic diseases were calculated. Results: The prevalence of chronic pancreatitis was 34 per cent omitting the autolysed cases. Cavalier King Charles spaniels, collies and boxers had increased relative risks of chronic pancreatitis; cocker spaniels had an increased relative risks of acute and chronic pancreatitis combined. Fifty-seven per cent of cases of chronic pancreatitis were classified histologically as moderate or marked. Forty-one per cent of cases involved all three sections. Dogs with chronic pancreatitis were more commonly female and overweight, but neither factor increased the relative risk of chronic pancreatitis. There were breed differences in histological appearances and 24·5 per cent of cases were too autolysed to interpret with an increased relative risk of autolysis in a number of large breeds. Clinical Significance: Chronic pancreatitis is a common, under-estimated disease in the first-opinion dog population with distinctive breed risks and histological appearances.

Prognostic Factors in Canine Exocrine Pancreatic Insufficiency: Prolonged Survival is Likely if Clinical Remission is Achieved. Daniel J. Batchelor, Peter-John M. Noble, Rebecca H. Taylor, Peter J. Cripps, and Alexander J. German. J Vet Intern Med 2007;21:54–60. Quote: "Background: Response to therapy in canine exocrine pancreatic insufficiency (EPI) varies considerably, making it difficult to determine prognosis for individual patients. Hypothesis: Response to initial treatment (RIT) and survival are affected by signalment, clinical variables, and herapeutic regimen employed. Animals: Client-owned dogs diagnosed with EPI between 1990 and 2002 were included in this study. Methods: The study comprised a retrospective, questionnaire-based review. Results: One hundred seventy-eight completed questionnaires were returned [16 cavalier King Charles spaniels]]. RIT was good in 60% of treated dogs, partial in 17%, and poor in 23%. On univariate analysis, dogs that received antibiotics (P 5 .037) or had high serum folate concentration (P 5 .037) had a poorer RIT. On multivariate analysis, there were no strong predictors of good RIT. Nineteen percent of treated dogs were euthanized within 1 year, but overall median survival time for treated dogs was 1919 days. No clear benefit of changing to a fat-restricted diet could be demonstrated, but marked hypo-cobalaminemia (,100 ng/L) was associated with shorter survival (P 5 .012). Use of uncoated pancreatic enzyme supplements, antibacterials, or H2 antagonists was not associated with longer survival. Breed, sex, age at diagnosis (#4 years or .4 years), and clinical signs at diagnosis also made no difference. Conclusions and Clinical Importance: Long-term prognosis in canine EPI is favorable for dogs that survive the initial treatment period. Although there are few predictors of good RIT or long-term survival, severe cobalamin deficiency is associated with shorter survival. Therefore, parenteral cobalamin supplementation should be considered when hypocobalaminemia is documented."

Exocrine Pancreatic Insufficiency in the Dog: Historical Background, Diagnosis, and Treatment. Elias Westermarck, Maria Wiberg. Topics in Companion Anim. Med. August 2012;27(3):96-103. Quote: This overview summarizes research performed during the last decades that has had an impact on the diagnosis and management of exocrine pancreatic insufficiency (EPI) in dogs. ... EPI is most commonly found in German Shepherds, followed by Rough-coated Collies, Chow Chows, and Cavalier King Charles Spaniels. Female dogs are reported to be overly represented with EPI. The prevalence of the various pancreatic diseases causing clinical signs of EPI is difficult to assess, because pancreatic morphologic examination is needed for the specific diagnosis. However, PAA is reported to be by far the most common cause of severe EPI in dogs. ... Pancreatic acinar atrophy is by far the most common cause for the maldigestion signs of canine EPI. The ability to diagnose pancreatic acinar atrophy in the subclinical phase before the development of total acinar atrophy and manifestation of clinical signs has offered new possibilities to study the pathogenesis of the disease. Diagnosis of exocrine pancreatic dysfunction is based on typical findings in clinical histories and clinical signs and is confirmed with pancreatic function tests. In recent years, the measurement of serum canine trypsin-like immuno-reactivity has become the most commonly used pancreatic function test to diagnose canine EPI. Serum trypsin-like immunoreactivity measurement is species- and pancreas-specific. When clinical maldigestion signs of EPI appear, enzyme replacement therapy is indicated. Despite accurate enzyme supplementation, only a small portion of orally administered enzymes are delivered functionally intact into the small intestine. In dogs, the highest enzyme activity in the duodenum has been obtained with nonenteric-coated supplements: raw chopped pancreas or powdered enzymes. Aside from dietary enzyme supplements, dietary changes are often made to improve clinical response, but sometimes weight gain and stool quality remain suboptimal. Other medications for treatment of gastrointestinal tract signs are often used in such dogs with EPI. Antibiotics are the most common adjunctive medication. Of the antibiotics administered, tylosin is used in Finland almost exclusively.

Exocrine Pancreatic Insufficiency in the Dog: Breed Associations, Nutritional Considerations, and Long-term Outcome. Alexander J. German. Topics in Compan. Anim. Med. August 2012;27(3):104-108. Quote: Canine exocrine pancreatic insufficiency (EPI) is an alimentary tract disorder causing malabsorption and debilitations in affected individuals. ... A number of breeds have been identified as being at risk for the development of EPI, including Cavalier King Charles Spaniels (CKCS), Chows, Cocker Spaniels, German Shepherd Dogs (GSD), Rough-coated Collies (RCC), and West Highland White Terriers. ... This article covers predisposing factors to EPI and response to therapy. Although relatively easy to diagnose, knowledge of breed predispositions (and also of those breeds where the disease is less common) can guide the clinician. Numerous studies have examined therapy for EPI, and a key finding is the variability in response among affected dogs. This implies that close monitoring and individual tailoring of therapy is needed to maximize the chance of success. Important factors affecting outcome are the choice of enzyme preparation, presence of hypocobalaminemia, and the response to the first 2 to 3 months of therapy.

Chronic Pancreatitis in Dogs. Penny Watson. Topics in Compan An Med August 2012;27(3):133-139. Quote: "Chronic pancreatitis used to be considered uncommon in dogs, but recent pathological and clinical studies have confirmed that it is in fact a common and clinically significant disease. Clinical signs can vary from low-grade recurrent gastrointestinal signs to acute exacerbations that are indistinguishable from classical acute pancreatitis. Chronic pancreatitis is a significant cause of chronic pain in dogs, which must not be underestimated. It also results in progressive impairment of endocrine and exocrine function and the eventual development of diabetes mellitus or exocrine pancreatic insufficiency or both in some affected dogs at end stage. The etiology is unknown in most cases. Chronic pancreatitis shows an increased prevalence in certain breeds, and recent work in English Cocker Spaniels suggests it is part of a polysystemic immune-mediated disease in this breed. Breeds showing increased risk of chronic pancreatitis in the United Kingdom: Cavalier King Charles Spaniels, English Cocker Spaniels, Boxers, Collies. ... Cavalier King Charles Spaniels (CKCS) appear to show less obvious clinical signs and diagnostic imaging findings than other breeds, suggesting their disease is less inflammatory. ... CKCSs show a predominance of periductular and perivascular fibrosis and ductular hyperplasia. ... The histological and clinical appearance is different in different breeds, suggesting that etiologies may also be different. Diagnosis is challenging because the sensitivities of the available noninvasive tests are relatively low. However, with an increased index of suspicion, clinicians will recognize more cases that will allow them to institute supportive treatment to improve the quality of life of the patient. ... The author would have a high index of suspicion that DM [diabetes mellitus] in any older dog of a breed predisposed to CP [chronic pancreatitis] such as Cocker Spaniel or CKCS may in fact be caused by CP. ... The occurrence of DM or EPI [exocrine pancreatic insufficiency] in an older ECS [English Cocker spaniels] or CKCS greatly increases the index of suspicion for underlying CP.

Current Status of Genetic Studies of Exocrine Pancreatic Insufficiency in Dogs. Leigh Anne Clark. Topics in Comp. Anim.Med. May 2012. Quote: "Exocrine pancreatic insufficiency (EPI) is a disorder wherein the pancreas fails to secrete adequate amounts of digestive enzymes. In dogs, EPI is usually the consequence of an autoimmune disease known as pancreatic acinar atrophy. Originally believed to be a simple autosomal recessive disorder, a test-breeding recently revealed that EPI has a more complex mode of inheritance. The contributions of multiple genes, combined with environmental factors, may explain observed variability in clinical presentation and progression of this disease. Research efforts aim to identify genetic variations underlying EPI to assist breeders in their efforts to eliminate this disease from their breed and provide clinicians with new targets for therapeutic intervention and/or disease prevention. Genome-wide linkage, global gene expression, and candidate gene analyses have failed to identify a major locus or genetic variations in German Shepherd Dogs with EPI. Recently, genome-wide association studies revealed numerous genomic regions associated with EPI. Current studies are focused on alleles of the canine major histocompatibility complex. In this article we review findings from scientific investigations into the inheritance and genetic cause(s) of EPI in the purebred dog."

Pancreatitis in dogs and cats: definitions and pathophysiology. P. Watson. J. Sm. Anim. Pract. January 2015;56(1):3-12. Quote: Pancreatitis, or inflammation of the pancreas, is commonly seen in dogs and cats and presents a spectrum of disease severities from acute to chronic and mild to severe. It is usually sterile, but the causes and pathophysiology remain poorly understood. The acute end of the disease spectrum is associated with a high mortality but the potential for complete recovery of organ structure and function if the animal survives. At the other end of the spectrum, chronic pancreatitis in either species can cause refractory pain and reduce quality of life. It may also result in progressive exocrine and endocrine functional impairment. There is confusion in the veterinary literature about definitions of acute and chronic pancreatitis and there are very few studies on the pathophysiology of naturally occurring pancreatitis in dogs and cats. This article reviews histological and clinical definitions and current understanding of the pathophysiology and causes in small animals by comparison with the much more extensive literature in humans, and suggests many areas that need further study in dogs and cats. ... Dogs with EPI as a result of end-stage CP tend to be middle-aged to older medium- or small-breed dogs, particularly Cavalier King Charles spaniels (CKCS), English cocker spaniels, and Border collies. One study reported an increased prevalence of EPI in older CKCS and, although the aetiology was unknown, end stage CP was suggested because of the older age at presentation of these dogs.

Prevalence of disorders recorded in Cavalier King Charles Spaniels attending primary-care veterinary practices in England. Jennifer F Summers, Dan G O’Neill, David B Church, Peter C Thomson, Paul D McGreevy, David C Brodbelt. Canine Genetics & Epidemiology. April 2015;2:4. Quote: "Background: Concerns have been raised over breed-related health issues in purebred dogs, but reliable prevalence estimates for disorders within specific breeds are sparse. Electronically stored patient health records from primary-care practice are emerging as a useful source of epidemiological data in companion animals. This study used large volumes of health data from UK primary-care practices participating in the VetCompass animal health surveillance project to evaluate in detail the disorders diagnosed in a random selection of over 50% of dogs recorded as Cavalier King Charles Spaniels (CKCSs). Confirmation of breed using available microchip and Kennel Club (KC) registration data was attempted. Results: In total, 3624 dogs were recorded as CKCSs within the VetCompass database of which 143 (3.9%) were confirmed as KC-registered via microchip identification linkage of VetCompass to the KC database. 1875 dogs (75 KC registered and 1800 of unknown KC status, 52% of both groups) were randomly sampled for detailed clinical review. Clinical data associated with veterinary care were recorded in 1749 (93.3%) of these dogs. The most common specific disorders recorded during the study period were heart murmur (541 dogs, representing 30.9% of study group), diarrhoea of unspecified cause (193 dogs, 11.0%), dental disease (166 dogs, 9.5%), otitis externa (161, 9.2%), conjunctivitis (131, 7.4%) and anal sac infection (129, 7.4%). The five most common disorder categories were cardiac (affecting 31.7% of dogs), dermatological (22.2%), ocular (20.6%), gastrointestinal (19.3%) and dental/periodontal disorders (15.2%). Discussion and conclusions: Study findings suggest that many of the disorders commonly affecting CKCSs are largely similar to those affecting the general dog population presented for primary veterinary care in the UK. However, cardiac disease (and MVD in particular) continues to be of particular concern in this breed. ... Gastrointestinal disorders also affected a notable number of study dogs, with diarrhoea of unspecified cause and other non-specific digestive disorders (e.g., gastroenteritis) frequently recorded. It is likely that a large proportion of the events recorded as non-specific gastroenteropathies were related to non-genetic causes such as dietary indiscretion, infection, parasitic disease or foreign body ingestion. However, existing studies report a high prevalence of chronic pancreatitis and exocrine pancreatic insufficiency (EPI) in CKCSs suggesting a heritable component of these conditions in the breed. Batchelor notes that (in contrast to German Shepherd dogs) EPI is frequently not considered or tested for in CKCSs with digestive problems and may be under-recognised. A proportion of the general diarrhoea and gastroenteropathies reported in the current study could thus be attributable to undiagnosed, breed-related chronic pancreatitis and/or EPI. investigation, perhaps using prospective study designs, is required to elucidate the relevance of inherited gastrointestinal conditions in this breed. ... Further work: This work highlights the value of veterinary practice based breed-specific epidemiological studies to provide targeted and evidence-based health policies. Further studies using electronic patient records in other breeds could highlight their potential disease predispositions."

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