Exocrine pancreatic insufficiency

Loss of pancreatic enzymes leads to maldigestion and malabsorption. Other symptoms may include:{{Cite journal |last1=Othman |first1=Mohamed O. |last2=Harb |first2=Diala |last3=Barkin |first3=Jodie A. |date=February 2018 |title=Introduction and practical approach to exocrine pancreatic insufficiency for the practicing clinician |journal=International Journal of Clinical Practice |language=en |volume=72 |issue=2 |pages=e13066 |doi=10.1111/ijcp.13066 |pmc=5873407 |pmid=29405509}}

• Abdominal discomfort or pain
• Bloating
• Diarrhea
• Anemia (vitamin B12, iron, folate deficiency)
• Bleeding disorders (vitamin K malabsorption)
• Edema (hypoalbuminemia)
• Fatigue
• Flatulence and abdominal distention (bacterial fermentation of unabsorbed food)
• Hypocalcemia
• Metabolic bone disease (vitamin D deficiency)
• Neurologic manifestation
• Steatorrhea
• Weight loss

In humans, the most common causes of EPI are likely related to diabetes (10.5% global prevalence of diabetes,{{Cite journal |last1=Sun |first1=Hong |last2=Saeedi |first2=Pouya |last3=Karuranga |first3=Suvi |last4=Pinkepank |first4=Moritz |last5=Ogurtsova |first5=Katherine |last6=Duncan |first6=Bruce B. |last7=Stein |first7=Caroline |last8=Basit |first8=Abdul |last9=Chan |first9=Juliana C. N. |last10=Mbanya |first10=Jean Claude |last11=Pavkov |first11=Meda E. |last12=Ramachandaran |first12=Ambady |last13=Wild |first13=Sarah H. |last14=James |first14=Steven |last15=Herman |first15=William H. |date=2022-01-01 |title=IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045 |journal=Diabetes Research and Clinical Practice |volume=183 |pages=109119 |doi=10.1016/j.diabres.2021.109119 |pmid=34879977 |pmc=11057359 |hdl=20.500.11820/85919e8b-f73d-433d-a236-058a9561e24d |hdl-access=free }} with EPI rates of ranging from 30–50% in Type 1 and 20–30% of Type 2) and IBS-D (7.6–10.8% global prevalence of IBS-D,{{cite journal |last1=Oka |first1=Priya |last2=Parr |first2=Heather |last3=Barberio |first3=Brigida |last4=Black |first4=Christopher J |last5=Savarino |first5=Edoardo V |last6=Ford |first6=Alexander C |title=Global prevalence of irritable bowel syndrome according to Rome III or IV criteria: a systematic review and meta-analysis |journal=The Lancet Gastroenterology & Hepatology |date=October 2020 |volume=5 |issue=10 |pages=908–917 |doi=10.1016/S2468-1253(20)30217-X |pmid=32702295 |url=https://eprints.whiterose.ac.uk/165295/3/thelancetgastrohep-D-20-00505R1%20CLEAN.pdf }} with EPI rates around 5–6%). Other causes of EPI include acute or chronic pancreatitis and cystic fibrosis, Crohn's disease, ulcerative colitis, celiac, advanced renal disease, older age, IBD, HIV, alcohol-related liver disease, Sjogren's syndrome, tobacco use, and use of somatostatin analogues.

EPI can also occur in 10–20% of the general population.{{cite journal |last1=Campbell |first1=Jennifer A. |last2=Sanders |first2=David S. |last3=Francis |first3=Katherine A. |last4=Kurien |first4=Matthew |last5=Lee |first5=Sai |last6=Taha |first6=Hatim |last7=Ramadas |first7=Arvind |last8=Joy |first8=Diamond |last9=Hopper |first9=Andrew D. |title=Should we Investigate Gastroenterology Patients for Pancreatic Exocrine Insufficiency? A Dual Centre UK Study |journal=Journal of Gastrointestinal and Liver Diseases |date=September 2016 |volume=25 |issue=3 |pages=303–309 |doi=10.15403/jgld.2014.1121.253.uks |pmid=27689193 |doi-access=free }}{{Cite journal |last1=Herzig |first1=Karl-Heinz |last2=Purhonen |first2=Anna-Kaisa |last3=Räsänen |first3=Kati M |last4=Idziak |first4=Joanna |last5=Juvonen |first5=Petri |last6=Phillps |first6=Ryszard |last7=Walkowiak |first7=Jaroslaw |date=December 2011 |title=Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus |journal=BMC Geriatrics |volume=11 |issue=1 |pages=4 |doi=10.1186/1471-2318-11-4 |pmc=3039595 |pmid=21266058 |doi-access=free }}

The three main tests used in considering a diagnosis of EPI are: fecal elastase test, fecal fat test, and a direct pancreatic function test.{{cite journal |author=Domínguez-Muñoz, JE |date=2011 |title=Pancreatic insufficiency: diagnosis and treatment |journal=J Gastroenterol Hepatol |volume=26 |issue=Supplement s2 |pages=12–16 |doi=10.1111/j.1440-1746.2010.06600.x |pmid=21323992 |hdl=20.500.11940/5522 |hdl-access=free }} The latter is a less used test that assesses exocrine function in the pancreas by inserting a tube into the small intestine to collect pancreatic secretions.

The fecal elastase test is a less cumbersome test that has replaced the 72-hour fecal fat test; in the fecal elastase test, pancreatic enzyme replacement therapy (enzyme supplementation, the treatment for EPI) does not have to be stopped for or during fecal elastase testing.{{Cite journal |last1=Struyvenberg |first1=Maarten R. |last2=Martin |first2=Camilia R. |last3=Freedman |first3=Steven D. |date=December 2017 |title=Practical guide to exocrine pancreatic insufficiency – Breaking the myths |journal=BMC Medicine |volume=15 |issue=1 |pages=29, s12916–017–0783-y |doi=10.1186/s12916-017-0783-y |pmc=5301368 |pmid=28183317 |doi-access=free }}

EPI is treated with pancreatic enzyme replacement therapy (PERT) called pancrelipase, which is used to break down fats (via a lipase), proteins (via a protease), and carbohydrates (via amylase) into units that can be digested.{{cite web|url=https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm063031.htm |archive-url=https://web.archive.org/web/20090622235833/http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/Over-the-CounterOTCDrugs/StatusofOTCRulemakings/ucm063031.htm |url-status=dead |archive-date=June 22, 2009 |title=FDA rulemaking history of OTC EPI drug products |website=Fda.gov |access-date=2011-11-08}} Pancrelipase is typically porcine derived in the prescription products although over-the-counter options also exist, including those made with plants and other non-porcine materials. In the US, there are 6 FDA-approved PERT products available on the market as of 2012.

Dosing can vary based on the need of the individual.{{Cite journal |last1=Trang |first1=Tony |last2=Chan |first2=Johanna |last3=Graham |first3=David Y |date=2014-09-07 |title=Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century |journal=World Journal of Gastroenterology |volume=20 |issue=33 |pages=11467–11485 |doi=10.3748/wjg.v20.i33.11467 |pmc=4155341 |pmid=25206255 |doi-access=free }} PERT is considered to be safe, effective, and tolerable for people with EPI regardless of the cause of EPI.{{Cite journal |last1=Gan |first1=Can |last2=Chen |first2=Yan-Hua |last3=Liu |first3=Ling |last4=Gao |first4=Jin-Hang |last5=Tong |first5=Huan |last6=Tang |first6=Cheng-Wei |last7=Liu |first7=Rui |date=2017-10-07 |title=Efficacy and safety of pancreatic enzyme replacement therapy on exocrine pancreatic insufficiency: a meta-analysis |journal=Oncotarget |volume=8 |issue=55 |pages=94920–94931 |doi=10.18632/oncotarget.21659 |pmc=5706924 |pmid=29212278}}

In addition, various nutrient deficiencies that can be caused by EPI need to be evaluated, tested, and treated. The impact of nutrient deficiencies on the body's metabolic pathways, muscle tissue, bone density, organs, and overall health can cause a wide range of often misdiagnosed symptoms for those impacted by exocrine pancreatic insufficiency.{{Cite book |last=Toxopeus |first=A. |title=Primal Pancreas - Pancreas Damage Survival Guide |year=2019 |isbn=978-0-9600679-1-6 |pages=180–200|publisher=Delft Consulting LLC }}

EPI also occurs in dogs and other animals. Chronic pancreatitis is the most common cause of EPI in cats. In dogs, the most common cause is pancreatic acinar atrophy, arising as a result of genetic conditions, a blocked pancreatic duct, or prior infection.

Pancreatic acinar atrophy and chronic pancreatitis are the most common causes of exocrine pancreatic insufficiency in dogs and cats.{{cite journal |last1=Cridge |first1=Harry |last2=Williams |first2=David A. |last3=Barko |first3=Patrick C. |title=Exocrine pancreatic insufficiency in dogs and cats |journal=Journal of the American Veterinary Medical Association |date=February 2024 |volume=262 |issue=2 |pages=246–255 |doi=10.2460/javma.23.09.0505 |pmid=37944252 |doi-access=free }}

In dogs, EPI is most common in young German Shepherds, and in Finland Rough Collies,{{cite journal |author1=Westermarck, E. |author2=Wiberg, M. |title=Exocrine pancreatic insufficiency in dogs |journal=Vet Clin N Am Small Animal Pract |volume=33 |issue=5 |pages=1165–79, viii–ix |year=2003 |pmid=14552166 |doi=10.1016/S0195-5616(03)00057-3}} and is inherited.{{cite web | last = Hall | first = Edward J. | title = Exocrine Pancreatic Insufficiency | work = Proceedings of the 28th World Congress of the World Small Animal Veterinary Association | year = 2003 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2003&PID=6553&O=Generic | access-date = 2007-02-24 }} In German Shepherds, the method of inheritance is through an autosomal recessive gene.{{cite journal |last1=Clark |first1=Leigh Anne |last2=Wahl |first2=Jacquelyn M. |last3=Steiner |first3=Jörg M. |last4=Zhou |first4=Wenli |last5=Ji |first5=Wan |last6=Famula |first6=Thomas R. |last7=Williams |first7=David A. |last8=Murphy |first8=Keith E. |title=Linkage analysis and gene expression profile of pancreatic acinar atrophy in the German Shepherd Dog |journal=Mammalian Genome |date=December 2005 |volume=16 |issue=12 |pages=955–962 |doi=10.1007/s00335-005-0076-1 |pmid=16341675 }} In these two breeds, at least, the cause appears to be immune-mediated as a sequela to lymphocytic pancreatitis.{{cite journal |last1=Wiberg |first1=M. E. |last2=Saari |first2=S. A. M. |last3=Westermarck |first3=E. |title=Exocrine Pancreatic Atrophy in German Shepherd Dogs and Rough-coated Collies: An End Result of Lymphocytic Pancreatitis |journal=Veterinary Pathology |date=November 1999 |volume=36 |issue=6 |pages=530–541 |doi=10.1354/vp.36-6-530 |pmid=10568434 }} The German Shepherd makes up about two-thirds of cases seen with EPI.{{cite journal |last1=Kim |first1=Ju Won |last2=Jung |first2=Dong In |last3=Kang |first3=Byeong Teck |last4=Kim |first4=Ha Jung |last5=Park |first5=Chul |last6=Park |first6=Eun Hee |last7=Lim |first7=Chae Young |last8=Park |first8=Hee Myung |title=Canine exocrine pancreatic insufficiency treated with porcine pancreatic extract |journal=Journal of Veterinary Science |date=2005 |volume=6 |issue=3 |pages=263–266 |doi=10.4142/jvs.2005.6.3.263 |pmid=16131834 |doi-access=free }} Other breeds reported to be predisposed to EPI include terrier breeds, Cavalier King Charles Spaniels, Chow Chows, and Picardy Shepherds.

In animals, signs of EPI are not present until 85 to 90 percent of the pancreas is unable to secrete its enzymes.{{cite book|author1=Ettinger, Stephen J. |author2=Feldman, Edward C. |title=Textbook of Veterinary Internal Medicine|edition=4th|publisher=W.B. Saunders Company|year=1995|isbn=0-7216-6795-3}}{{pn|date=October 2024}} In dogs, symptoms include weight loss, poor hair coat, flatulence, increased appetite, coprophagia, and diarrhea. Feces are often yellow-gray in color with an oily texture. There are many concurrent diseases that mimic EPI, and severe pancreatitis is one that if allowed to continue unabated can lead to EPI.{{citation needed|date=July 2018}}

The most reliable test for EPI in dogs and cats is serum trypsin-like immunoreactivity (TLI);{{cite journal |author1=Steiner, J. |author2=Rutz, G. |author3=Williams, D. |title=Serum lipase activities and pancreatic lipase immunoreactivity concentrations in dogs with exocrine pancreatic insufficiency |journal=Am J Vet Res |volume=67 |issue=1 |pages=84–7 |year=2006 |pmid=16426216 |doi=10.2460/ajvr.67.1.84|doi-access=free }} a low value indicates EPI. Fecal elastase levels may also be used for diagnosis in dogs.{{cite web | last = Rallis | first = Timoleon S. |author2=Adamama-Moraitou, K. | title = Exocrine Pancreatic Insufficiency in Dogs and Cats: An Update | work = Proceedings of the 29th World Congress of the World Small Animal Veterinary Association | year = 2004 | url = http://www.vin.com/proceedings/Proceedings.plx?CID=WSAVA2004&PID=8673&O=Generic | access-date = 2007-02-24 }}

In dogs, the best treatment is to supplement the animals' food with dried pancreatic extracts. There are commercial preparations available, but chopped bovine pancreas from the butcher can also be used. (Pork pancreas should not be used because of the rare transmission of pseudorabies).{{cite web | title = Exocrine Pancreatic Insufficiency | work = The Merck Veterinary Manual | year = 2006 | url = http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/23404.htm | access-date = 2007-02-24 }} Symptoms usually improve within a few days, but lifelong treatment is required to manage the condition. A rare side-effect of use of dried pancreatic extracts is oral ulceration and bleeding.{{cite journal |author=Snead E |title=Oral ulceration and bleeding associated with pancreatic enzyme supplementation in a German shepherd with pancreatic acinar atrophy |journal=Can Vet J |volume=47 |issue=6 |pages=579–82 |year=2006 |pmid=16808232 |pmc=1461413}}

Because of malabsorption, serum levels of cyanocobalamin (vitamin B12) and tocopherol (vitamin E) may be low. These may be supplemented, although since cyanocobalamin contains the toxic chemical cyanide, dogs that have serious cobalamin issues should instead be treated with hydroxocobalamin or methylcobalamin.{{citation needed|date=November 2011}}

Cyanocobalamin deficiency is very common in cats with EPI because about 99 percent of intrinsic factor (which is required for cyanocobalamin absorption from the intestine) is secreted by the pancreas. In dogs, this figure is about 90 percent, and only about 50 percent of dogs have this deficiency.

Cats may suffer from Vitamin K deficiencies. If there is bacterial overgrowth in the intestine, antibiotics should be used, especially if treatment is not working.

In dogs failing to gain weight or continuing to show symptoms, modifying the diet to make it low-fiber and highly digestible may help. Despite previous belief that low-fat diets are beneficial in dogs with EPI, more recent studies have shown that a high-fat diet may increase absorption of nutrients and better manage the disease.{{cite journal |vauthors=Biourge V, Fontaine J |title=Exocrine pancreatic insufficiency and adverse reaction to food in dogs: a positive response to a high-fat, soy isolate hydrolysate-based diet |journal=J Nutr |volume=134 |issue=8 Suppl |pages=2166S–2168S |year=2004 |doi=10.1093/jn/134.8.2166S |pmid=15284428|doi-access=free }} However, it has been shown that different dogs respond to different dietary modifications, so the best diet must be determined on a case-by-case basis.{{cite journal |author1=Westermarck, E. |author2=Wiberg, M. |title=Effects of diet on clinical signs of exocrine pancreatic insufficiency in dogs |journal=J Am Vet Med Assoc |volume=228 |issue=2 |pages=225–9 |year=2006 |pmid=16426193 |doi=10.2460/javma.228.2.225|doi-access=free }}

One possible sequela, volvulus (mesenteric torsion), is a rare consequence of EPI in dogs.

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{{Medical resources

| DiseasesDB =

| ICD10CM = {{ICD10CM|K86.81}}

| ICD10 = {{ICD10|K86.8}}

| ICD9 = {{ICD9|577.8}}

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| MedlinePlus =

| eMedicineSubj =

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| MeshID = D010188

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{{Gastroenterology}}

Category:Dog diseases

Category:Pancreas disorders

Category:Steatorrhea-related diseases