Exocrine pancreatic insufficiency (EPI) occurs when the pancreas produces a deficient amount of the enzymes amylase, protease, and lipase. Normally, the pancreatic enzymes break down undigested triglycerides into fatty acids and monoglycerides, which are then solubilized by bile salts. People with EPI, however, have impaired fat digestion and the inability to properly digest food.1 This leads to steatorrhea, weight loss, malabsorption, and maldigestion and can increase the risk of mortality in patients. The prevalence of EPI varies depending on the causal disease.2
The reduced amount of digestive enzymes produced can result from pancreatic and nonpancreatic causes. The most common pancreatic disorders that cause EPI include chronic pancreatitis, pancreatic neoplasms after surgery, cystic fibrosis, and Shwachman-Diamond syndrome.2 Clinically significant EPI is reported in 60% to 90% of patients with chronic pancreatitis where acinar cell loss and fibrosis reduce lipase secretion and 90% of pancreatic enzymes are reduced. Pancreatic resection for malignant and benign tumors often requires the removal of the pancreatic parenchyma, stomach, and/or small bowel during surgery, reducing pancreas functional capacity and EPI. Cystic fibrosis is a genetic disorder that leads to pancreatic ductal lumen fluid volume and pH decrease. A result of the disorder is also precipitation of proteinaceous secretions, which obstructs and destroys acinar cells and leads to EPI.3
Extrapancreatic disorders cause EPI less commonly than pancreatic disorders. However, patients at risk include those with diabetes, celiac disease, and a previous gastrointestinal surgery. EPI in patients with diabetes can be caused from exocrine tissue involvement in autoimmune destruction, lack of trophic action of insulin or acinar cells, microvascular damage to exocrine tissue, and effect of the enteropancreatic reflex impairment from diabetic neuropathy.3 Patients with celiac disease often has a reduction of fecal elastase levels, intestinal inflammation, and atrophy, which impairs pancreatic signaling. Gastrointestinal surgery impairs gastric relaxation and hormonal signaling, which leads to EPI in 40% to 80% of gastric surgical patients.
Screening and Diagnosis
EPI symptoms are similar to many digestive problems and include abdominal pain, gas, bloating, constipation, diarrhea, fatty stools, and unexplained weight loss. If a patient has a condition that affects the pancreas, a pancreas function test may be given to diagnose EPI.4 Unfortunately, accurate diagnoses are challenging because of the lack of an accurate diagnostic test.3
Two categories of tests are used to diagnose EPI and include direct and indirect tests for measuring pancreatic enzyme output. Indirect tests evaluate the quantitative changes of pancreatic secretions and are less expensive and easier to perform compared with direct tests. Direct tests, however, evaluate secretive production with good sensitivity. These tests are invasive, time-consuming, expensive, not standardized, and cannot monitor treatment progress.2
The gold standard test for diagnosing maldigestion or malabsorption is the 72-hour fecal fat testing, but it is difficult to use in clinical practice. This test requires a patient to ingest a high-fat diet for 5 days and then a stool collection occurs over the last 3 days. In a healthy patient, 93% of dietary fat is absorbed on a 100 g fat/day diet. Another limitation is that it does not isolate the pancreas as the cause for malabsorption.3 It is the only test accepted by the American Food and Drug Administration and the European Medicines Agency for monitoring treatment in clinical trials.2
The fecal elastase test measures the elastase levels in stools and is the only widely available test for EPI. The test measures chymotrypsin-like elastases (CELA) 3A and 3B. It can be used to measure treatment progress and has reasonable sensitivity. Limitations include high false positive rates, watery stools may give low readings, and advanced age and other medical conditions cause low fecal elastase levels. Thus, the diagnosis of EPI is reliant on patients who are at an increased risk and have clinical symptoms.
Following a positive fecal elastase test and to exclude an obstructive tumor or lesion as the cause, clinicians should perform cross-sectional imaging. A fecal elastase test should be repeated if a morphological cause of EPI is not found. In patients where fecal elastase is normal, but the patient is symptomatic with or without lower-risk associated condition and suspected maldigestion, a full malnutrition assessment with clinical history and serum markers including magnesium, vitamin E, and retinol binding protein should be performed. This should also be performed when fecal elastase is low, if micronutrient deficiency is demonstrated, and in patients who have significant weight loss.5
Treatment and Management
Treatment for EPI involves dietary management and lifestyle changes and providing activated digestive enzymes to the duodenum during the prandial and post-prandial period through pancreatic enzyme replacement therapy (PERT). In patients with chronic pancreatitis, a low-fat diet is recommended in conjunction with PERT. In patients with cystic fibrosis, however, a high-fat diet in conjunction with PERT is recommended.3
PERT should be given at a starting dose of 50,000 units lipase spread out throughout a meal and 25,000 units lipase with snacks. The dose should be adjusted if it is ineffective, and the choice of PERT preparation should consider the lipase units and number and size of capsules tolerable by the patient. If a patient cannot swallow a capsule, it must be opened and placed on an acidic puree and swallowed at intervals throughout a meal. Any remaining granules must be rinsed with a cool or room-temperature drink. Comorbidities should be considered with PERT doses exceeding 100,000 units lipase. Enteral feeds should be peptide and medium-chain triglyceride-based. PERT efficacy is vulnerable to both acid and temperature, so storage of the enzymes is important to prevent degradation. Patients with EPI receiving enteral feeds tolerate peptide preparations and require less PERT to achieve complete lipolysis. After PERT administration, nutritional status and bowel symptoms should improve. Anthropometric, biochemical, clinical, and dietary symptoms should be monitored to support ongoing treatment or dose escalation.5
Untreated EPI causes maldigestion of fats and leads to weight loss and nutrient deficiencies. Working with a doctor or nutritionist to ensure that a patient with EPI is consuming a nutrient-rich diet combined with pancreatic enzyme replacement therapy will allow dietary needs to be met.6
- Medscape. Exocrine Pancreatic Insufficiency: Practice Essentials, Anatomy, Pathophysiology. Accessed May 18, 2022. https://emedicine.medscape.com/article/2121028-overview
- Capurso G, Traini M, Piciucchi M, Signoretti M, Arcidiacono PG. Exocrine pancreatic insufficiency: prevalence, diagnosis, and management. Clin Exp Gastroenterol. 2019;12:129-139. doi:10.2147/CEG.S168266
- Perbtani Y, Forsmark CE. Update on the diagnosis and management of exocrine pancreatic insufficiency. F1000Res. 2019;8:F1000 Faculty Rev-1991. doi:10.12688/f1000research.20779.
- Cleveland Clinic. Exocrine Pancreatic Insufficiency (EPI): Pancreatitis. Accessed May 18, 2022. https://my.clevelandclinic.org/health/diseases/21577-exocrine-pancreatic-insufficiency-epi
- Phillips ME, Hopper AD, Leeds JS, et al. Consensus for the management of pancreatic exocrine insufficiency: UK practical guidelines. BMJ Open Gastroenterol. 2021;8(1):e000643. doi:10.1136/bmjgast-2021-000643
- National Pancreas Foundation. Exocrine Pancreatic Insufficiency (EPI). Accessed May 20, 2022. https://pancreasfoundation.org/patient-information/ailments-pancreas/exocrine-pancreatic-insufficiency-epi/