Exocrine Pancreatic Insufficiency (EPI): 5 Things to Know

Exocrine pancreatic insufficiency (EPI) arises when the pancreas is unable to produce or deliver an adequate supply of digestive enzymes, primarily affecting the digestion of fats, proteins, and carbohydrates. Fat digestion is particularly impaired owing to the role of pancreatic lipase in breaking down lipids into the simpler form needed to absorb them effectively. Consequently, patients with EPI commonly experience symptoms such as steatorrhea (pale, greasy, foul-smelling stools), weight loss, bloating, diarrhea, and abdominal discomfort. If untreated, EPI can lead to severe nutritional deficiencies, including fat-soluble vitamin malabsorption (A, D, E, and K), which may result in such complications as osteoporosis, night blindness, and increased susceptibility to infection.
EPI is most often associated with chronic pancreatitis, a condition in which longstanding inflammation progressively destroys the pancreatic tissue; however, it can also occur from other conditions that can cause pancreatic exocrine deficiency, including cystic fibrosis, diabetes, and pancreatic cancer, and after surgeries such as bariatric procedures or pancreatic resection. These conditions either damage the acinar cells responsible for enzyme production or obstruct the pancreatic ducts, thereby reducing the delivery of enzymes to the intestines.
Diagnosis of EPI typically involves noninvasive tests such as fecal elastase 1, which measures the concentration of pancreatic elastases in stool samples. Treatment primarily relies on pancreatic enzyme replacement therapy (PERT), during which patients take oral enzyme supplements with meals to replicate the normal digestive function of the pancreas.
Here are five things to know about EPI.
1. EPI is frequently underdiagnosed, leading to inappropriate treatment and excessive testing.
EPI is often underdiagnosed, partly because of its nonspecific symptoms such as bloating, steatorrhea, and malabsorption. These symptoms frequently overlap with those of other gastrointestinal (GI) conditions such as irritable bowel syndrome, leading to extensive and often unnecessary testing for other conditions. As a result, misdiagnosis delays appropriate treatment, which can exacerbate malnutrition and worsen quality of life.
EPI should be suspected in patients with a history of chronic pancreatitis, cystic fibrosis, or pancreatic ductal adenocarcinoma and those who have undergone pancreatic surgery. These high-risk patients are particularly vulnerable to EPI, with up to 85% of individuals with cystic fibrosis and 60%-90% of those with chronic pancreatitis developing the condition within 10-12 years of disease onset. Even in moderate-risk groups — such as individuals with longstanding diabetes, inflammatory bowel diseases (eg, Crohn disease), or hypersecretory conditions (eg, Zollinger-Ellison syndrome) — EPI may be present but remain undiagnosed owing to the focus on managing their primary conditions.
2. Signs and symptoms of EPI are diverse and may include GI disturbances and nutrient deficiencies.
EPI is characterized by maldigestion of nutrients, primarily fats, due to insufficient pancreatic enzyme secretion. This leads to fat malabsorption, often manifesting as steatorrhea — pale, greasy stools that are difficult to flush and may have a foul odor. Bloating, flatulence, and abdominal discomfort are frequently reported, contributing to significant GI distress.
Weight loss can be a prominent feature of EPI, especially in severe cases in which nutrient absorption is markedly impaired. The inability to absorb sufficient fats and fat-soluble vitamins (A, D, E, K) can lead to deficiencies of these essential nutrients, causing additional complications, including osteoporosis, visual disturbances, and increased risk for fracture.
Early detection and treatment are essential to prevent these complications.
3. Diagnosis of EPI relies on imaging, stool tests, and pancreatic function tests.
The diagnostic approach to EPI typically involves a combination of stool tests, imaging, and pancreatic function tests. Fecal elastase 1 testing is considered the most appropriate initial test, especially in patients with loose or semisolid stools. Additionally, it can be performed even while the patient is on PERT, making it a convenient option for ongoing management.
Imaging modalities such as CT, MRI, and endoscopic ultrasonography are often performed to rule out other causes of malabsorption, such as celiac disease or inflammatory bowel disease, that might contribute to the patient’s symptoms. Although these imaging techniques do not directly diagnose EPI, they play an important role in identifying underlying structural abnormalities in the pancreas. Cross-sectional imaging also may help assess the extent of pancreatic damage in conditions such as pancreatic cancer, where obstruction of the pancreatic ducts can cause EPI.
Direct pancreatic function tests, such as the secretin or cholecystokinin (CCK) stimulation test, can assess the ability of the pancreas to secrete digestive enzymes. Additionally, indirect tests, such as breath tests that measure fat digestion by pancreatic lipase, hold promise but are not yet widely available in the United States.
4. Medical treatment for EPI focuses on PERT to manage fat malabsorption and nutritional deficits.
PERT is the cornerstone of EPI management. PERT aims to provide the necessary digestive enzymes, particularly lipase, that the pancreas fails to secrete adequately. The goal of PERT is not only to reduce GI symptoms but also to prevent or reverse the malnutrition associated with EPI by improving absorption of macronutrients and fat-soluble vitamins.
Initial PERT dosing in adults typically involves administering at least 40,000 USP units of lipase during each meal, with adjustments made according to the size and fat content of the meal. All commercially available PERT formulations are derived from porcine sources and are equally effective at equivalent doses.
PERT must be taken with food to ensure the enzymes are adequately mixed with ingested nutrients, facilitating digestion and absorption. Adjunctive therapy with H2-blockers or proton pump inhibitors has been shown to help prevent enzyme degradation in the stomach and improve the effectiveness of PERT.
5. Nutritional support is critical in managing EPI. Small, balanced meals and supplementation are important.
Dietary management is essential to EPI treatment, complementing PERT to maximize nutrient absorption. Patients with EPI often require a well-balanced diet with moderate fat intake and frequent, small meals to aid digestion and absorption. While the aim is to prevent fat malabsorption, very low-fat diets are discouraged because they can worsen a patient’s already compromised nutritional status. Instead, healthy fats, such as those found in nuts, seeds, avocados, and fatty fish, are recommended as part of a balanced diet.
Supplementation with fat-soluble vitamins (A, D, E, K) is important because EPI impairs absorption of these nutrients, leading to deficiencies. Monitoring vitamin levels periodically and adjusting supplement dosages as needed are important aspects of long-term management.
In addition to vitamin supplementation, lifestyle modifications such as avoiding alcohol and smoking are recommended because both have been shown to worsen pancreatic function and exacerbate EPI symptoms.
Lastly, patients are advised to avoid processed foods containing unhealthy fats and excessive dietary fiber, which may interfere with fat digestion by binding to pancreatic enzymes.