Chronic Pancreatitis and
the Cavalier King Charles Spaniel


The cavalier King Charles spaniel has a high prevalence of chronic pancreatitis and is believed to be predisposed to this disease, according to several recent reports. In a 2005 report by UK researchers, they found:

"There are strong breed-associations in CKCS and JRT, suggesting a possible genetic basis to the disease in these breeds."

This breed association has been confirmed in a 2007 UK report.*

* See also this 2007 UK report and this 2007 US report and this  2011 US report and this 2013 UK report.

What It Is

The pancreas is a gland which consists of about 98% exocrine acinar cells and 2% endocrine islets. The exocrine 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.

Pancreas, from Veterinary PartnersA normally functioning pancreas is protected from premature activation of these caustic digestive enzymes, which could result in digesting the pancreas itself.  Pancreatitis occurs when the enzymes are activated while still in the pancreas, thereby causing death to its tissue by auto-digestion.

Pancreatitis is a common inflammatory disorder of the dog's pancreas, which can be either "acute" or "chronic". Acute pancreatitis is an inflammation which does not cause permanent damage to the pancreas and therefore is potentially reversible. Chronic pancreatitis, for which the cavalier appears predisposed and is at an increased risk, is a continuous inflammation which can cause permanent damage to the pancreas’ exocrine and endocrine tissues and result in insufficient creation and secretion of its enzymes, particularly an exocrine pancreatic insufficiency (EPI).

The end stage of chronic pancreatitis may result in diabetes mellitus, due to extensive destruction of pancreatic tissues.

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Symptoms

Classic signs of chronic pancreatitis include abdominal pain, vomiting, and loss of appetite. The pain can be severe and may cause the dog to take a “praying” position. The affected dog may also pass diarrhea or voluminous feces, with small amounts of fresh blood and/or mucous.

The clinical signs of pancreatitis will vary with the severity of the disease. Low-grade cases may not show all of the classic symptoms and may be confused with inflammatory bowel disease. In severe cases, the dog may become dehydrated, may collapse, be in shock, and may even suffer renal shutdown and distressed breathing.

If a dog which has diabetes mellitus suddenly begins to lose weight unexpectedly, despite having a good appetite and being under diabetic control, the dog may have developed an exocrine pancreatic insufficiency due to pancreatitis.

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Diagnosis

Blenheim Pool DiverLow grade chronic pancreatitis can be difficult to diagnose because their symptoms can be confused easily with other conditions. Recent studies have found a high rate of under-diagnosis of chronic pancreatitis in dogs.

The “gold standard” for diagnosing pancreatitis is a biopsy by making an incision through the abdominal wall. Alternatives to biopsies include blood tests, enzyme assays, x-rays, and ultrasounds. Usually blood counts, pancreatic enzyme assays and x-rays are conducted in combination, as any one alone would be insufficient to accurately diagnose chronic pancreatitis.

Enzyme assays -- catalytic, immuno, and enzymatic -- involve measuring levels of circulating pancreatic enzymes, including lipase, amylase, trypsin (cTLI), and canine pancreas specific lipase (cPLI).  Measurement of elevated circulating enzymes, including amylase, lipase, cTLI, and cPLI currently are the best tests available for diagnoses.

Ultrasounds can be very specific for pancreatitis, depending upon the extent of inflammation, when performed by skilled operators. Therefore, pancreatic ultrasounds should be performed by ultrasound specialists. Low grade chronic pancreatitis is the most difficult to detect using ultrasound.

SNAP cPLResearchers are constantly seeking to improve the accuracy of diagnosing pancreatitis. IDEXX Laboratories claims that its SPEC cPL test is the most accurate, even more so than ultrasounds.  See the IDEXX website for details. IDEXX Labs also offers a SNAP cPL test (right) for diagnosing pancreatitis. See the IDEXX website for details. In a July 2012 report of a comparison of various cPLI tests on 84 dogs, the researchers found that:

"SNAP and SPEC have higher sensitivity for diagnosing clinical AP [acute pancreatitis] than does measurement of serum amylase or lipase activity. A positive SPEC or SNAP has a good positive predictive value (PPV) in populations likely to have AP and a good negative predictive value (NPV) when there is low prevalence of disease."

The study was sponsored by IDEXX, the producer of SNAP and SPEC tests.

Other diagnostic tests are being studied, including peptides in the blood and urine, and levels of inflammatory mediators and cytokines in the blood.

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Treatment

Unless a specific cause has been determined, most cases of pancreatitis are treated to relieve the symptoms.  If the cause is known (more likely in acute cases than chronic ones), the treatment includes removing that cause.

Mild cases with vomiting and dehydration may require oral or intravenous fluids and pancreatic rest, meaning no solid food, followed by a change to a more appropriate diet. Hospitalization may be required to assure proper treatment and rest.

Antiemetics may be prescribed to reduce excessive vomiting, but they may have side effects which could increase pancreatic pain. A phenothiazine antiemetic such as chlorpromazine may avoid the additional pain, but it is not licensed for use by small animals.

Since pancreatitis is very painful, affected dogs may be given analgesia such as a morphine agonist or partial agonist, particularly buprenorphine (Buprenex), or butophanol tartrate (Torbutrol, Stadol, Torbugesic-SA, Torbugesic). Non-steroidal anti-inflammatory drugs (NSAIDs) usually are not given because of an increased risk of gastroduodenal ulceration and a potential renal failure reaction.

A long-term low fat diet, along with supplementary enzymes, likely will be recommended.

Severe cases, in which the tissue has begun to die (necrotize) and the liver has been affected, are unlikely to recover. However, in a 2009 review of the use of probiotics in veterinary practice, Dr. Susan G. Wynn reports that probiotics may benefit dogs with acute (but not chronic) necrotizing pancreatitis. :

"Probiotic organisms appear to improve the intestinal barrier, which prevents bacterial translocation, and lactic acid–producing bacteria can suppress the inflammation that makes systemic inflammation response syndrome such a deadly condition in patients with acute pancreatitis. Investigators have conducted studies in dogs with experimentally induced severe pancreatitis. Affected dogs have been provided nutrients parenterally as well as elemental enteral nutrition or dietary supplementation with probiotics."
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Research News

January 2014: Dr. Penny Watson looks for ties between fibrosis in MVD, SM, and chronic Dr. Penny Watsonpancreatitis in CKCSs. Dr. Penny Watson (right) of UK's Cambridge University's veterinary school is spearheading a new study into whether several of the CKCS breed's hereditary health problems are the result of the same genetic defect. Specifically, she intends to explore the possibility that disparate cavalier diseases, including mitral valve disease (MVD), syringomyelia (SM), and chronic pancreatitis are connected at the cellular level by unusual patterns of fibrotic changes. "Pronounced perivescular fibrosis", a feature in dogs with chronic pancreatitis, also has been tied to a condition of the central nervous system in cavaliers with SM. Dr. Watson has suggested that deterioration of cavaliers' mitral valves also may be a result of a process connected to the causes of fibrosis.

The CKCS breed's documented overabundance of serotonin, a neurotransmitter protein, has been identified as a plausible mechanism which may trigger the development of fibrotic changes in the heart's valves. Her study entails establishing primary stellate cell (SC) cultures from CKCS and define 5HT receptor subtype expression. Stellate cell (SC) activation is a key event in the development of hepatic and pancreatic fibrosis. Serotonin has been shown to activate SCs via 5HT receptors. The study is measuring the response of these cells to serotonin and other stimulators of fibrosis. She then intends to attempt to block SC activation in vitro using 5HTreceptor antagonists. Increased understanding of the factors driving fibrosis will be of benefit to the CKCS and may allow a drug trial in the breed.

March 2013: UK researcher seeks breakthroughs in understanding chronic pancreatitis in CKCSs. Dr. Penny Watson of the University of Cambridge is working closely with UK breeders of cavaliers to better understand the cause of chronic pancreatitis (CP) in the breed.* Over the past decade, she has published four research papers about CP, noting in the latter three its high prevalence in the CKCS. She also has found that the pathology of CP in the cavalier has a distinctive appearance. She said recently that "I hope we will soon be able to make some breakthroughs in understanding this disease better."

* See her 2004 report, her 2005 report, her 2007 report, and her 2012 report.

July 2012: Surprise! ISurprise!DEXX finds that its SNAP and SPEC tests are the best for diagnosing acute pancreatitis. In a July 2012 report of a comparison of various cPLI tests on 84 dogs, the researchers found that:

"SNAP and SPEC have higher sensitivity for diagnosing clinical AP [acute pancreatitis] than does measurement of serum amylase or lipase activity. A positive SPEC or SNAP has a good positive predictive value (PPV) in populations likely to have AP and a good negative predictive value (NPV) when there is low prevalence of disease."

Of course, the study was sponsored by IDEXX, the producer of SNAP and SPEC tests. However, that fact is not intended to take anything away from the value of these two tests.

May 2011:  Cavaliers and Jack Russells may be predisposed. US researchers report in a May 2011 study that cavalier King Charles spaniels are one of only two breeds which may be predisposed to chronic pancreatitis which can result in destruction of acinar cells. The other breed is the Jack Russell terrier (Parson Russell terrier in AKC).

March 2009: Probiotics may benefit dogs with acute necrotizing pancreatitis. In a March 2009 Dr. Susan G. Wynnreview of probiotics in veterinary practice, Dr. Susan G. Wynn (right) reports that probiotics may benefit dogs with acute necrotizing pancreatitis. She writes:

"Probiotic organisms appear to improve the intestinal barrier, which prevents bacterial translocation, and lactic acid–producing bacteria can suppress the inflammation that makes systemic inflammation response syndrome such a deadly condition in patients with acute pancreatitis. Investigators have conducted studies in dogs with experimentally induced severe pancreatitis. Affected dogs have been provided nutrients parenterally as well as elemental enteral nutrition or dietary supplementation with probiotics."
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Related Links

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Veterinary Resources

Control of Canine Genetic Diseases.  Padgett, G.A., Howell Book House 1998, pp. 198-199, 232.

Pancreatitis in the dog: dealing with a spectrum of disease. Penny Watson. In Practice, Feb 2004; 26:64-77.  Quote: "PANCREATITIS - whether it be acute or chronic - is a relatively common, but often misdiagnosed, problem in dogs. It is associated with a systemic inflammatory response which, in severe cases, can result in the development of multiorgan failure, diffuse intravascular coagulation and death. Classical acute pancreatitis is often straightforward to diagnose, but this only represents one end of a wide spectrum of disease. Milder and/or more chronic forms of the condition are not so easily recognised, but can cause significant pain and reduce the quality of life of an animal. There is no single diagnostic test with 100 per cent sensitivity and specificity for the disease, apart from biopsy which is relatively invasive and, hence, not often indicated. Treatment recommendations depend on the severity of the disease and range from conservative management at home to referral for intensive care. The causes of pancreatitis in dogs are usually unknown. Therefore, therapy tends to be symptomatic and non-specific. The potential long-term sequelae of chronic pancreatitis in dogs are largely uninvestigated, but can include the development of diabetes mellitus and/or exocrine pancreatic insufficiency. This article discusses the potential causes, diagnosis and treatment of acute and chronic pancreatitis in dogs."

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."

Diagnosing and Treating Pancreatitis: A roundtable discussion. David A. Williams, Jörg M. Steiner, H. Mark Saunders, David Twedt, Benita von Dehn. IDEXX Learning Center. 2006.

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: Quote: "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 hypocobalaminemia (,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."

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, and Alexander J. German. J Vet Intern Med 2007;21:207–214. 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). 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). GSD and RCC were younger at diagnosis than CKCS. Boxers, Golden Retrievers, Labrador Retrievers, Rottweilers, and Weimaraners 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."

Canine Pancreatitis--From Clinical Suspicion to Diagnosis. Thomas Spillmann. 2008 WSAVA Congress. Quote: "Breeds with reported increased risk for chronic pancreatitis are cavalier King Charles and cocker spaniels, collies, and boxers."

Pancreatitis associated with clomipramine administration in a dog. P. H. Kook, A. Kranjc, M. Dennler, T. M. Glaus. J.Sm.Ani.Prac. 2009;50(1):95-98. Quote: "A three-year-old, male, entire, Yorkshire terrier was presented with
peracute onset of abdominal pain and vomitus. Clinicopathological abnormalities included severely increased serum lipase activity, immeasurably high serum trypsin-like immunoreactivity and mild hypocalcaemia. Canine pancreatic lipase immunoreactivity (cPLI) was intended to be measured, however, the sample got lost. Ultrasonography revealed a hypoechoic pancreas with small amounts of peripancreatic fluid and hyperechogenic mesentery. Acute pancreatitis (AP) was diagnosed and the dog recovered with appropriate therapy within 48 hours. Clomipramine, a selective serotonin reuptake inhibitor (SSRI) for alleviating signs of separation anxiety had been given for seven weeks. Two similar, albeit less severe, episodes associated with previous courses of clomipramine had occurred eight months earlier that responded to discontinuing clomipramine and supportive care. As SSRIs are associated with AP in human beings and no other trigger could be identified, we conclude that clomipramine should be considered as a potential cause when investigating causes for AP in susceptible breeds or other dogs presenting with compatible clinical signs."

Probiotics in veterinary practice. Susan G. Wynn. JAVMA March 2009;234(5):606-613. Quote: "Pancreatitis: Translocation of gastrointestinal bacteria during pancreatitis can lead to septicemia and substantially worsen a patient’s prognosis. Results of studies conducted in humans and other animals by use of Lactobacillus plantarum 299, Saccharomyces boulardii, and combinations of probiotics and prebiotics suggest that probiotic administration may be of benefit in patients with acute necrotizing pancreatitis. Probiotic organisms appear to improve the intestinal barrier, which prevents bacterial translocation, and lactic acid–producing bacteria can suppress the inflammation that makes systemic inflammation response syndrome such a deadly condition in patients with acute pancreatitis. Investigators have conducted studies in dogs with experimentally induced severe pancreatitis. Affected dogs have been provided nutrients parenterally as well as elemental enteral nutrition or dietary supplementation with probiotics. In 1 study, increases in serum activity of amylase, alanine aminotransferase, and aspartate aminotransferase and plasma concentrations of endotoxin, as well as pancreatic and ileal histopathologic changes, were significantly (P < 0.05) suppressed with probiotic administration. The degree of bacterial translocation was significantly (P < 0.05) decreased with probiotic administration, which suggested that this probiotic combination (described as 40 mg of Lactobacillus spp and 40 mg of Bifidobacterium spp) enhanced gastrointestinal barrier function. Investigators in another study obtained similar results."

Breed Predispositions to Disease in Dogs & Cats (2d Ed.). Alex Gough, Alison Thomas. 2010; Wiley-Blackwell Publ. 52.

Prevalence of hepatic lesions at post-mortem examination in dogs and association with pancreatitis. P. J. Watson, A. J. A. Roulois, T.J. Scase1, R. Irvine, M. E. Herrtage. J. Sm. An. Prac. Nov 2010;51(11):566–572.  Quote: "To assess the prevalence of canine chronic hepatitis (CH) and other liver diseases in first opinion practice and identify associations with concurrent chronic pancreatitis (CP). ... The prevalence of CH was 12%. Some breeds had an increased RR of CH, although sample sizes were small. Dogs with CP had an increased RR of reactive hepatitis but no significant association with the other liver diseases. ... CH is common in the first opinion dog population but less common than CP. CP was significantly associated with reactive hepatitis but not CH. Possible breed associations mirrored another recent UK study. Some dogs with CP may be erroneously diagnosed clinically as having CH on the basis of increased serum liver enzymes because of concurrent reactive hepatitis if the diagnosis is not confirmed histologically."

Observational study of 14 cases of chronic pancreatitis in dogs. P. J. Watson, J. Archer, A. J. Roulois, T. J. Scase, M. E. Herrtage. Vet. Rec. Dec. 2010;167(25):968-976. Quote: "This study reports the clinical, clinicopathological and ultrasonographic findings from dogs with chronic pancreatitis (CP). Fourteen dogs with clinical signs consistent with CP and histological confirmation of the disease were evaluated. ... (...two Cavalier King Charles spaniels). ... Spaniels were the most common breed with CP, representing seven of the 14 dogs in this study. ... ...with Cavalier King Charles and cocker spaniels having a perilobular pattern, while other breeds had an intralobular distribution... There were a large number of spaniels in the current study, mirroring a pathology study (Watson and others 2007) that found an increased relative risk of pancreatitis in Cavalier King Charles and cocker spaniels, providing further evidence for breed-related disease in spaniels. ...CP was histologically severe in nine cases. Most dogs showed chronic low-grade gastrointestinal signs and abdominal pain. Five dogs had exocrine pancreatic insufficiency and five dogs had diabetes mellitus. The sensitivity of elevated trypsin-like immunoreactivity for CP was 17 per cent. The sensitivities of canine pancreatic lipase immunoreactivity, lipase and amylase for CP were 44 to 67 per cent or 14 to 28 per cent depending on the cut-off value used. Cholesterol was elevated in 58 per cent of samples. Liver enzymes were often elevated. The pancreas appeared abnormal on 56 per cent of ultrasound examinations. Ten dogs had died by the end of the study period; only one case was due to CP. CHRONIC pancreatitis (CP) in dogs is poorly documented clinically. However, a recent study reported the prevalence of CP to be 34 per cent in postmortem examinations of dogs from first opinion practice ... ."

Exocrine Pancreatic Insufficiency in Dogs. Joseph Cyrus Parambeth and Jӧrg M. Steiner. Consultant on Call: Gastroenterology, NAVC Clinician’s Brief ; May 2011. Quote: "Chronic pancreatitis can result in destruction of acinar cells (all breeds are affected, but cavalier King Charles spaniels and Jack Russell terriers may be predisposed)."

Genetic Connection: A Guide to Health Problems in Purebred Dogs, Second Edition. Lowell Ackerman. July 2011; AAHA Press; pg 76. Quote: "... breed predispositions have been reported for chow chows and Cavalier King Charles spaniels."

Sensitivity and Specificity of Canine Pancreas-Specific Lipase (cPL) and Other Markers for Pancreatitis in 70 Dogs with and without Histopathologic Evidence of Pancreatitis. S. Trivedi, S.L. Marks, P.H. Kass, J.A. Luff, S.M. Keller, E.G. Johnson, B. Murphy. J Vety Int Med Nov/Dec 2011;25(6):1241-1247. Quote: "Pancreatitis is a common disorder in dogs for which the antemortem diagnosis remains challenging. Objectives: To compare the sensitivity and specificity of serum markers for pancreatitis in dogs with histopathologic evidence of pancreatitis or lack thereof. Animals: Seventy dogs necropsied for a variety of reasons in which the pancreas was removed within 4 hours of euthanasia and serological markers were evaluated within 24 hours of death. Methods: Prospective study: Serum was analyzed for amylase and lipase activities, and concentrations of canine trypsin-like immunoreactivity (cTLI) and canine pancreas-specific lipase (cPL). Serial transverse sections of the pancreas were made every 2 cm throughout the entire pancreas and reviewed using a semiquantitative histopathologic grading scheme. Results: The sensitivity for the Spec cPL (cutoff value 400 μg/L) was 21 and 71% in dogs with mild (n = 56) or moderate-severe pancreatitis (n = 7), and 43 and 71% (cutoff value 200 μg/L), respectively. The sensitivity for the cTLI, serum amylase, and lipase in dogs with mild or moderate-severe pancreatitis was 30 and 29%; 7 and 14%; and 54 and 71%, respectively. The specificity for the Spec cPL based on 7 normal pancreata was 100 and 86% (cutoff value 400 and 200 μg/L, respectively), whereas the specificity for the cTLI, serum amylase, and lipase activity was 100, 100, and 43%, respectively. Conclusion and Clinical Importance: The Spec cPL demonstrated the best overall performance characteristics (sensitivity and specificity) compared to other serum markers for diagnosing histopathologic lesions of pancreatitis in dogs."

Chronic Pancreatitis in Dogs. Penny Watson. Topics in Compan An Med 27 (2012) 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."

Exocrine Pancreatic Insufficiency in the Dog: Breed Associations, Nutritional Considerations, and Long-term Outcome. Alexander J. German. Topics in Comp. Anim.Med. May 2012. Quote: "Canine exocrine pancreatic insufficiency (EPI) is an alimentary tract disorder causing malabsorption and debilitations in affected individuals. This article covers predisposing factors to EPI and response to therapy. ... EPI is most commonly found in German Shepherds, followed by Rough-coated Collies, Chow Chows, and Cavalier King Charles Spaniels. ... 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."

Pathophysiology of Acute Pancreatitis: Potential Application from Experimental Models and Human Medicine to Dogs. Caroline Mansfield. J.Vet.Intern.Med. July 2012; 26(4):875-887. Quote: "The cellular events leading to pancreatitis have been studied extensively in experimental models. Understanding the cellular events and inciting causes of the multisystem inflammatory cascades that are activated with this disease is of vital importance to advance diagnosis and treatment of this condition. Unfortunately, the pathophysiology of pancreatitis in dogs is not well understood, and extrapolation from experimental and human medicine is necessary. The interplay of the inflammatory cascades (kinin, complement, cytokine) is extremely complex in both initiating leukocyte migration and perpetuating disease. Recently, nitric oxide (NO) and altered microcirculation of the pancreas have been proposed as major initiators of inflammation. In addition, the role of the gut is becoming increasingly explored as a cause of oxidative stress and potentiation of systemic inflammation in pancreatitis."

A Multi-Institutional Study Evaluating the Diagnostic Utility of the Spec cPL™ and SNAP® cPL™ in Clinical Acute Pancreatitis in 84 Dogs. K. McCord, P.S. Morley, J. Armstrong, K. Simpson, M. Rishniw, M.A. Forman, D. Biller N. Parnell, K. Arnell, S. Hill, S. Avgeris, H. Gittelman, M. Moore, M. Hitt, G. Oswald, S. Marks, D. Burney, D. Twedt. J.Vet.Intern.Med. July 2012; 26(4):888-896. Quote: "Background: Pancreas-specific lipase is reported to aid in diagnosing acute pancreatitis (AP) in dogs but has not been rigorously evaluated clinically. Hypothesis/Objectives: To describe variability of disease in dogs with suspected clinical AP, and to evaluate accuracy of 2 pancreatic-specific lipase immunoassays, Spec cPL (SPEC) and SNAP cPL (SNAP), in diagnosing clinical AP. We hypothesized that SPEC and SNAP provide better diagnostic accuracy than serum amylase or total lipase. Animals: A total of 84 dogs; 27 without AP and 57 with clinical signs associated with AP.  Methods: Multicenter study. Dogs were prospectively enrolled based upon initial history and physical examination, then retrospectively classified into groups according to the likelihood of having clinical AP by a consensus of experts blinded to SPEC and SNAP results. Bayesian latent class analyses were used to estimate the diagnostic accuracy of SPEC and SNAP. Results: The estimates for test sensitivities and specificities, respectively, ranged between 91.5–94.1% and 71.1–77.5% for SNAP, 86.5–93.6% and 66.3–77.0% for SPEC (cutoff value of 200 μg/L), 71.7–77.8% and 80.5–88.0% for SPEC (cutoff value of 400 μg/L), and were 52.4–56.0% and 76.7–80.6% for amylase, and 43.4–53.6% and 89.3–92.5% for lipase. Conclusions and Clinical Importance: SNAP and SPEC have higher sensitivity for diagnosing clinical AP than does measurement of serum amylase or lipase activity. A positive SPEC or SNAP has a good positive predictive value (PPV) in populations likely to have AP and a good negative predictive value (NPV) when there is low prevalence of disease." Note: SPEC and SNAP are IDEXX products. IDEXX sponsored the study.

A blinded randomised controlled trial to determine the effect of enteric coating on enzyme treatment for canine exocrine pancreatic insufficiency. Aran Mas, Peter-John M Noble, Peter J Cripps, Daniel J Batchelor, Peter Graham, Alexander J German. BMC Vet. Res. July 2012;8:127. Quote: "Background: Enzyme treatment is the mainstay for management of exocrine pancreatic insufficiency (EPI) in dogs. ‘Enteric-coated’ preparations have been developed to protect the enzyme from degradation in the stomach, but their efficacy has not been critically evaluated. The hypothesis of the current study was that enteric coating would have no effect on the efficacy of pancreatic enzyme treatment for dogs with EPI. Thirty-eight client-owned dogs with naturally occurring EPI (including 1 cavalier King Charles spaniel) were included in this multicentre, blinded, randomised controlled trial. Dogs received either an enteric-coated enzyme preparation (test treatment) or an identical preparation without the enteric coating (control treatment) over a period of 56 days. Results: There were no significant differences in either signalment or cobalamin status (where cobalamin deficient or not) between the dogs on the test and control treatments. Body weight and body condition score increased in both groups during the trial (P<0.001) but the magnitude of increase was greater for the test treatment compared with the control treatment (P<0.001). By day 56, mean body weight increase was 17% (95% confidence interval 11-23%) in the test treatment group and 9% (95% confidence interval 4-15%) in the control treatment group. The dose of enzyme required increased over time (P<0.001) but there was no significant difference between treatments at any time point (P=0.225). Clinical disease severity score decreased over time for both groups (P=0.011) and no difference was noted between groups (P=0.869). No significant adverse effects were reported, for either treatment, for the duration of the trial. Conclusions: Enteric coating a pancreatic enzyme treatment improves response in canine EPI. ... VetPlus Ltd., who markets the product on which both treatments were based, funded the trial."

Chronic pancreatitis in dogs: A retrospective study of clinical, clinicopathological, and histopathological findings in 61 cases. Brier M. Bostrom, Panagiotis G. Xenoulis, Shelley J. Newman, Roy R. Pool, Geoffrey T. Fosgate, Jörg M. Steiner. Vet.J. Jan 2013; 195(1):73-79. Quote: "The objective of this study was to characterize the clinical, clinicopathological, and histopathological findings of dogs with chronic pancreatitis. The necropsy database at Texas A&M University was searched for reports of dogs with histological evidence of chronic pancreatitis defined as irreversible histologic changes of the pancreas (i.e. fibrosis or atrophy). A reference necropsy population of 100 randomly selected dogs was used for signalment and concurrent disease comparisons. Cases were categorized as clinical or incidental chronic pancreatitis based on the presence of vomiting, decreased appetite, or both vs. neither of these signs. All archived pancreas samples were scored histologically using a published scoring system. Sixty-one dogs with chronic pancreatitis were included ... mainly English Cocker Spaniels and Cavalier King Charles Spaniels. ... The most frequent clinical signs were lethargy, decreased appetite, vomiting, and diarrhea. Compared to the reference necropsy population, chronic pancreatitis cases were more likely to be older, neutered, of the non-sporting/toy breed group, and to have concurrent endocrine, hepatobiliary, or neurological disease. Clinical cases had significantly higher histological scores for pancreatic necrosis and peripancreatic fat necrosis, and were significantly more likely to have hepatobiliary or endocrine disease as well as increased liver enzyme activities, or elevated cholesterol and bilirubin concentrations. In conclusion, clinical disease resulting from chronic pancreatitis might be related to the presence of pancreatic necrosis and pancreatic fat necrosis. The signalment, presentation, and concurrent diseases of dogs with chronic pancreatitis are similar to those previously reported for dogs with acute pancreatitis."

Haemolytic anaemia and acute pancreatitis associated with zinc toxicosis in a dog. R. Blundell, F. Adam. Vety. Rec. 2013;172(1):17. Quote: "We describe a case of zinc toxicity in a 14-month-old, female, neutered, Cavalier King Charles spaniel with a 48-hour history of haematochezia, icterus and collapse. Regenerative anaemia with a packed-cell volume of 7 per cent was seen. Prior to referral, radiography had revealed a gastric, metallic foreign body which was removed at exploratory laparotomy. On presentation, the dog was comatose, hypothermic and bradycardic – resuscitation was performed successfully, but the dog then displayed marked abdominal pain. The dog died 12 hours after presentation. At postmortem examination, the animal showed severe icterus. Both kidneys were diffusely dark red; the pancreas was diffusely pale and nodular. Histopathological examination revealed evidence of intravascular haemolysis with blood vessel lumens containing haemoglobin. The renal tubules also contained large amounts of intraluminal haemoglobin with haemoglobin crystals scattered throughout the cortex and medulla. The pancreas exhibited multifocal coagulative necrosis, surrounded by a neutrophil-dominated inflammatory infiltrate. Zinc levels were markedly increased above the normal reference range in both liver and kidney. This report describes the clinical and pathological findings of a case of acute zinc toxicity in a dog following ingestion of a metallic object which resulted in marked haemolytic anaemia and acute pancreatitis."

Clinical Forum: canine pancreatitis and biliary duct obstruction. Irene Schaafsma, Kate Bradley, Andrew Denning, Esther Barett. Companion Anim. June 2013;18(4):147-150. Quote: "Part 2: The radiologist's perspective: This clinical forum will review pancreatic disease in dogs, primarily focusing on those patients that go on to develop obstruction of the biliary tree. A series of commonly asked questions relating to pancreatitis and concurrent biliary tract obstruction will be asked of a panel of specialists with varying views expressed! ... Some breeds are predisposed, including Cavalier King Charles Spaniels, English Cocker Spaniels, Miniature Schnauzers and Boxers. ... In the August 2013 issue of Companion Animal, a further article on this topic will be published giving both a surgeon's perspective on canine pancreatitis and biliary duct obstruction."

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