Genetic Welfare Problems of Companion Animals

An information resource for prospective pet owners

German Shepherd Dog (Alsatian)

German Shepherd Dog (Alsatian)

Exocrine Pancreatic Insufficiency

Related terms: Pancreatic acinar atrophy (PAA), maldigestion, pancreatic insufficiency.

Outline: In exocrine pancreatic insufficiency, the secretion of digestive enzymes by the pancreas into the intestine is reduced so digestion and absorption of food are greatly impaired. Affected dogs progressively lose body condition whilst remaining very hungry and eating profusely. The effects on the digestive system can cause discomfort and pain. In the late stages there is weakness, collapse and death. It is a common disease of German Shepherd dogs and it is thought to have a polygenic basis.


Summary of Information

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1. Brief description

Exocrine pancreatic insufficiency (EPI) is caused by a degenerative disease of the pancreas. The pancreas has two distinct functions: (i) the regulation of the blood glucose level through secretion of the hormones insulin and glucagon (the endocrine function) into the blood and (ii) the secretion of substances into the intestine that are vital for the digestion of food. The latter is the exocrine function that fails in this disease.

The usual cause of exocrine pancreatic insufficiency in German Shepherd dogs is pancreatic acinar atrophy (PAA), in which progressive destruction of the acinar cells of the pancreas occurs. These cells are involved with the production of enzymes, chemicals and fluid that flow, via the main pancreatic ducts into the small intestine as “pancreatic juice”. Their destruction results in insufficient production of pancreatic juice for the digestion process (Simpson and Rishniw 2005) and bicarbonate.

In time, EPI can lead to severe malnutrition because affected dogs, although eating normally, may not be able to digest and absorb sufficient nutrients. Deficiencies of specific vitamins including B12 (cobalamin), E and K may occur (Williams 1996). Dogs with EPI show mild to marked weight loss, despite being ravenously hungry. Other signs include: large volumes of diarrhoea of variable consistency, which may be foul-smelling; flatulence and intestinal borborgymi (gurgling). Sometimes there is vomiting and increased drinking and coats may become poor and greasy (Williams 1996, Hall et al 2003, Simpson and Rishniw 2005). Unless successfully treated, there can be severe emaciation with muscle wasting and weakness and, eventually, death (Williams 1996, Simpson and Rishniw 2005).

Treatment has to be life-long. The outlook for treated dogs is generally good but treatment is expensive.

2. Intensity of welfare impact   

The welfare implications of EPI can be severe as affected dogs suffer near constant, ravenous hunger with occasional abdominal discomfort and nausea. Ultimately they become too weak to maintain normal activities, and are likely to experience profound malaise as body systems fail, leading eventually to death by starvation.

3. Duration of welfare impact

EPI can occur in dogs of any age but signs are usually first seen between 6 months and 6 years of age (Hall et al 2003). Unless treated, the disease progresses over weeks and months leading to starvation. Treatment has to be life-long.

4. Number of animals affected

The proportion of GSDs affected has not been documented as far as we are aware. The disease is more common in GSDs than in other breeds and GSDs comprise two thirds of cases of EPI due to pancreatic acinar atrophy in dogs (Hall et al 2003). From data on estimates of total dog population in the UK and on the percentage of all micro-chip registered dogs that are GSDs (Lucy Asher, 2011, personal communication), we estimate that the UK population size of this breed may be around 400,000. 

5. Diagnosis

If signs typically associated with this condition, of hunger, weight loss and diarrhoea, are shown by a GSD of less than 5 years of age, EPI is likely to be suspected. EPI can be confirmed by measurement of blood trypsinogen levels. This is the serum trypsin-like immunoreactivity (TLI) test. Other tests may be needed to rule out other possible causes and complications (Williams 1996, Simpson and Rishniw 2005).

6. Genetics

EPI is believed to be a polygenic disorder involving multiple genes and maybe also environmental influences (Clark 2009, Westermarck et al 2010). This has yet to be confirmed. .

7. How do you know if an animal is a carrier or likely to become affected?

Currently it is not known if animals that are unaffected themselves can pass the disease on to their offspring (Clark 2009). When choosing a puppy, it is important to check that its parents are free of EPI. The older the parents are the less likely they are to go on to develop EPI at a later date. There are currently no tests that can show whether or not a puppy is likely to develop EPI when older.

8. Methods and prospects for elimination of the problem

As far as we are aware, there are no breeding schemes aimed at tackling EPI in GSDs. Current recommendations include:

  • avoid breeding from any animals that have the condition (not all show signs prior to breeding age)
  • avoid repeat matings between dogs that have produced affected offspring
  • avoid line-breeding (the pairing of dogs which share common ancestors but which are not closely related) (Clark 2009, Steiner 2010).

Bell (2010) has suggested the use of breeding values in deciding which animals should be mated in order to tackle polygenetic disorders. Breeding values take account of all available genetic and phenotypic information for the individual and its close relatives (including siblings) (Bell 2010). Establishing breeding values for all GSDs to be used for breeding will require the cooperation of the majority of GSD breeders.


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1. Clinical and pathological effects

Exocrine pancreatic insufficiency (EPI) is caused by a degenerative disease of the pancreas. The pancreas has two distinct functions: (i) the regulation of the blood glucose level through secretion of the hormones insulin and glucagon (the endocrine function) into the blood and (ii) the secretion of substances into the intestine that are vital for the digestion of food. The latter is the exocrine function that fails in this disease.

The usual cause of exocrine pancreatic insufficiency in German Shepherd dogs is pancreatic acinar atrophy (PAA), in which progressive destruction of the acinar cells of the pancreas occurs. These cells are involved with the production of enzymes, chemicals and fluid that flow, via the main pancreatic ducts into the small intestine as “pancreatic juice”.

The main chemical constituent of pancreatic juice is bicarbonate, this acts to neutralise acid from the stomach. It also contains enzymes which are proteins that act as catalysts in the chemical reactions that break down foodstuffs into molecules small enough to pass through the intestinal wall and be absorbed. These enzymes include proteases that break down protein into amino acids; lipase and phospholipase that break down fats; nucleases that breakdown nucleic acids (DNA and RNA); and amylase that breaks down starch and glycogen.

EPI occurs when the acinar cells fail to produce sufficient pancreatic juice for the digestion process (Simpson and Rishniw 2005). The commonest reason for this in young GSDs is pancreatic acinar atrophy (PAA) in which acinar cells are progressive destroyed.

The exocrine pancreas has considerable functional reserve so that signs of EPI only appear when about 90% of the pancreas has been destroyed (Williams 1996, Brooks 2008). The cause of pancreatic acinar atrophy in GSDs is unknown. However, it has been suggested that it may be an auto-immune disease because lymphocytic pancreatitis has been reported to precede the atrophy (Wiberg et al 1999a, Hall et al 2003, Wiberg 2004). The endocrine function of the pancreas is usually spared so diabetes mellitus is not usually seen concurrently (Neiger et al 1996).

Secondary bacterial overgrowth in the gut is common in dogs with EPI probably due to loss of antibacterial properties of pancreatic juice or a disturbance in the gut’s motility or immune defences (Williams 1996).

In time, EPI can lead to severe malnutrition because affected dogs, although eating normally, may not be able to digest and absorb sufficient nutrients. Deficiencies of specific vitamins including B12 (cobalamin), E and K may occur (Williams 1996). Dogs with EPI show mild to marked weight loss, despite being ravenously hungry. Other signs include: large volumes of diarrhoea of variable consistency, which may be foul-smelling; flatulence and intestinal borborgymi (gurgling). Sometimes there is vomiting and increased drinking and coats may become poor and greasy (Williams 1996, Hall et al 2003, Simpson and Rishniw 2005). Unless successfully treated, there can be severe emaciation with muscle wasting and weakness and, eventually, widespread failure of metabolic homeostasis and death (Williams 1996, Simpson and Rishniw 2005).

Treatment involves oral supplementation of pancreatic enzymes and regular injections of Vitamin B12 and, in some cases, other vitamins (Williams 1996, Hall et al 2003, Simpson and Rishniw 2005). Various dietary modifications have been recommended, in particular, a low fat diet but this is controversial (Simpson and Rishniw 2005). Dogs with secondary bacterial overgrowth may require antibiotics. The prognosis with treatment is generally good although Batchelor et al (2007a) found 23% of dogs had a poor response to initial treatment and 17% had only a partial response. In one study, 19% of dogs were euthanased within the first year of treatment (Batchelor et al’s 2007a). Some of these may have been euthanased because of the cost of treatment, which is significant and necessarily life-long (Williams 1996).

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2. Intensity of welfare impact

The welfare implications of EPI can be severe. Affected dogs appear ravenously hungry most of the time. They may, from time to time, also feel ill, nauseous (suffering from vomiting) and suffer from abdominal discomfort. Unless successfully treated, the disease progresses to cause weakness due to muscle wastage. If the disease causes vitamin K deficiency, dogs may show spontaneous bleeds (Williams 1996). As the disease progresses, dogs become too weak to maintain normal activities, display increasing malaise, and become sicker and sicker as their body systems close down and they die of starvation.

The intense hunger can lead to ingestion of inappropriate materials, which may cause painful secondary gastrointestinal upsets or gastrointestinal obstructions.

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3. Duration of welfare impact

EPI can occur in dogs of any age but in GSDs signs usually become apparent between 6 months and 6 years of age (Hall et al 2003). Batchelor et al (2007b) found the median age of diagnosis in GSDs was 36 months. If left untreated dogs starve to death over weeks and months. Treatment has to be life-long.

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4. Number of animals affected

Williams (1996, p184) suggested that EPI is “very prevalent in young GSDs” and GSDs form about two thirds of all cases of EPI due to PAA (Hall et al 2003, Brooks 2008). Freudiger (1976) estimated that about 1% of the GSD population was affected. We are not aware of any more recent estimates. From data on estimates of total dog population in the UK and on the percentage of all micro-chip registered dogs that are GSDs (Lucy Asher, 2011, personal communication), we estimate that the UK population size of this breed may be around 400,000. If Freudiger’s estimate of the prevalence is correct, then the disease may be affecting around 4000 GSDs in the UK, and very many more around the world.

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5. Diagnosis

If signs typically associated with this condition, of hunger, weight loss and diarrhoea, are shown by a GSD of less than 5 years of age, EPI is likely to be suspected.EPI can be confirmed by measurement of blood trypsinogen levels. This is the serum trypsin-like immunoreactivity (TLI) test. Other tests may be needed to rule out other possible causes and complications (Williams 1996, Simpson and Rishniw 2005).

Low TLI concentrations (0.1-2.5 µg/l; normal is 5 - 35µg/l) are considered diagnostic for EPI in young dogs (Hall et al 2003, Simpson and Rishniw 2005). Recently a test to measure faecal elastase levels has been developed for EPI diagnosis but the TLI test remains the most trusted (Simpson and Rishniw 2005).

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6. Genetics

It was thought that EPI in GSDs had an autosomal recessive pattern of inheritance (Weber and Freudiger 1977, Westermarck 1980, Moeller et al 2002, Clark et al 2005), however, this is now not believed to be the case (Westermarck et al 2010). Instead, it is thought that EPI is a polygenic disorder involving multiple genes and possibly environmental factors also (Clark 2009, Westermarck et al 2010). This has yet to be confirmed.

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7. How do you know if an animal is a carrier or likely to become affected?

The genetics of the condition remain unclear and it is not known if carriers (animals that can pass the disease to their offspring without being affected themselves) exist (Clark 2009). When choosing a puppy, it is important to check that its parents are free of EPI. The older the parents are, the less likely they are to go on to develop EPI at a later date. There are currently no tests that can show whether or not a puppy is likely to develop EPI when older.

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8. Methods and prospects for elimination of the problem

As far as we are aware, there are no breeding schemes aimed at tackling EPI in GSDs. It has been recommended that animals that have EPI should not be used for breeding (but EPI does not always become apparent prior to breeding age), nor should pairs that have produced affected offspring be paired again. Likewise, line-breeding is not recommended (breeding from dogs which share common ancestors but are not closely related) (Clark 2009, Steiner 2010). These restrictions might result in significant decrease in the size of the gene pool significantly.

EPI is not the only genetic disease of GSDs that has significant welfare effects; others include megaoesophagus, hip dysplasia, degenerative myelopathy, haemophilia A, von Willebrand disease, and hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis (Wahl et al 2008). Therefore, when developing breeding strategies to tackle EPI, it is desirable to also take these into account. The ideal is for breeding programmes to be informed by the results of disease monitoring programmes and for the estimation of breeding values (EBV) – the relative genetic values of animals in the breeding population – in relation to breeding to eliminate these diseases (Lewis et al 2010).  EBVs are calculated using all available information on the dog including its pedigree, health status and physical characteristics. Planning matings based on EBVs has proven successful in reducing the prevalence of other diseases, eg in reducing the prevalence of epilepsy in the Belgian Tervuren (Oberbauer 2005). This may be a good approach to simultaneously tackling several genetic welfare problems in GSDs, although it may take many generations.  For this approach to be successful, the cooperation of the majority of GSD breeders is required so that the breeding values of individuals can be established.

Opinions differ as to whether it is ethically acceptable to breed animals whose welfare is likely to be compromised. Another approach to reducing the prevalence of EPI (and which avoids risks of further inbreeding) would be to outbreed with unaffected dogs of other breeds.

It seems feasible that repeated TLI values could be used to help identify animals with sub-clinical (inapparent) EPI. Research is underway at Clemson University in South Carolina, USA, to try to determine the genes responsible for EPI (http://www.epi4dogs.com/research.htm). The development of a genetic test would be likely to be very helpful in tackling the disease.

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9. Acknowledgements

UFAW is grateful to Rosie Godfrey BVetMed MRCVS and David Godfrey BVetMed FRCVS for their work in compiling this section.

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10. References

Batchelor DJ, Noble P-JM, Taylor RH, Cripps P and German A (2007a) Prognostic Factors in Canine Exocrine Pancreatic Insufficiency: Prolonged Survival is Likely if Clinical Remission is Achieved. Journal of Veterinary Internal Medicine 21: 54-60

Batchelor DJ, Noble P-JM, Cripps P, Taylor RH, McLean L, LeibL MA and German A (2007b) Breed associations for canine exocrine pancreatic insufficiency. Journal of Veterinary Internal Medicine 21: 207-214

Bell JS (2010) Genetic Testing and Genetic Counseling in Pet and Breeding Dogs. World Small Animal Veterinary Association World Congress Proceedings

Brooks W (2008) Exocrine Pancreatic Insufficiency – Client handout. On-line  http://www.VeterinaryPartner.com/Content.plx?P=AandA=1627. Accessed 30.3.11

Clark LA, Wahl JM, Steiner JM, Zhou W, Wan J, Famula TR, Williams DA and Murphy KE (2005) Linkage analysis and gene expression profile of pancreatic acinar atrophy in the German Shepherd Dog Mammalian Genome 16: 955-62

Clark LA (2009) Researcher’s comments. On-line http://www.epi4dogs.com/research.htm. Accessed 31.3.11

Freudiger U (1976) Epidemiologie, Ätiologie, Klinik und Diagnose der chronischen exokrinen Pankreasinsuffizienz. Prakt Tierarzt 5: 300-314

Hall EJ, Murphy KF and Darke PGG (2003) on Exocrine Pancreatic Insufficiency. In: Notes on Canine Internal Medicine pp 197-198. Blackwell Publishing: Oxford, UK

Lewis T, Woolliams J and Blott S (2010) Optimisation of breeding strategies to reduce the prevalence of inherited disease in pedigree dogs. Animal Welfare 19(S): 93-98

Moeller EM, Steiner JM, Clark LA, Murphy KE, Famula TR, Williams DA, Stankovics ME and Vose AS (2002) Inheritance of pancreatic acinar atrophy in German Shepherd Dogs. American Journal of Veterinary Research 63: 1429-1434

Neiger R, Bornaud Jaunin V and Boujon CE (1996) Exocrine pancreatic insufficiency combined with insulin- dependent diabetes mellitus in a juvenile German Shepherd dog. Journal of Small Animal Practice 37: 344-349

Oberbauer A (2005) Strategies for Identifying and Managing Complex Genetic Disorders. Tufts’ Canine and Feline Breeding and Genetics Conference 30th Sept – 1st Oct 2005, Sturbridge, MA, USA. Available from VIN Associate

Simpson K and Rishniw M (2005) Exocrine Pancreatic Insufficiency. On-line VIN associate http://www.vin.com/Members/Associate/Associate.plx?DiseaseId=1217. Accessed 31.3.11

Steiner JM (2010) quoted comments in Purina Proclub Update: Exocrine Pancreatic Insufficiency May Have Complex Inheritance Pattern. 9: 1-2

Wahl J, Herbst S, Clar L, Tsai K and Murphy K (2008) A review of hereditary diseases of the German Shepherd dog. Journal of Veterinary Behaviour 3: 255-265

Weber W and Freudiger U (1977) Erbanalytische Untersuchungen uber die chronisce exocrine Pankreasinsuf?zienz beim Deutshen Scha ¨ ferhund. Schweiz Arch Tierheilkd 119: 257–263

Westermarck E (1980) Hereditary nature of canine pancreatic degenerative atrophy in the German Shepherd Dog. Acta Vet Scand 21: 389–394

Westermarck E, Saari SAM and Wiberg ME (2010) Heritability of exocrine pancreatic insufficiency in German Shepherd dogs. Journal of Veterinary Internal Medicine 24: 450-2

Wiberg ME (2004) Pancreatic acinar atrophy in German Shepherd dogs and rough-coated collies. Etiopathogenesis, diagnosis and treatment. A review. The Veterinary Quarterly 26: 61-75

Wiberg ME, Saari SAM and Westermarck E (1999a) Exocrine Pancreatic Atrophy in German Shepherd Dogs and Rough-coated Collies: An End Result of Lymphocytic Pancreatitis Veterinary Pathology 36: 530-541

Wiberg ME and Westermarck E (2002) Subclinical exocrine pancreatic insufficiency in dogs. Journal of American Veterinary Medicine Association 220: 1183-7

Williams DA (1996) Exocrine Pancreatic Disease. In Thomas DA, Simpson JW and Hall EJ (Eds) Manual of Canine and Feline Gastroenterology. p171-189. BSAVA: Cheltenham, UK

http://www.epi4dogs.com/research.htm

© UFAW 2011