“Exocrine pancreatic insufficiency is not a common condition,” says David Bernstein, MD, chief of hepatology at Northwell Health in Manhasset, New York. For this disorder to set in, 90 percent of the pancreas must be damaged or diseased, which rarely happens. But some people may be more at risk for EPI than others, in part because underlying health conditions can damage the pancreas over time. These conditions include:

  1. Pancreatitis An inflammation of the pancreas, pancreatitis can be acute (sudden) or chronic (over a long period of time). Acute pancreatitis is frequently traced to excessive alcohol consumption, high triglyceride levels, an abdominal injury, or certain medications, including steroids, antibiotics, and blood pressure medications. Chronic pancreatitis may be caused by a hereditary condition or many years of excessive alcohol consumption. “Both chronic pancreatitis and severe acute pancreatitis can cause significant damage to the pancreas and lead to exocrine pancreatic insufficiency,” says Deepak Agrawal, MD, chief of gastroenterology and hepatology at Dell Medical School at The University of Texas at Austin.
  2. Gastrointestinal surgery EPI can be a side effect of surgery that removes portions of your stomach or pancreas, Dr. Agrawal says. “In some cases, the pancreas may be working, but the digestive juices that come from the pancreas may not be reaching the duodenum — the area of the digestive system where these juices mix with food — which can lead to pancreatic insufficiency symptoms,” he explains.
  3. Pancreatic cancer Pancreatic cancer can also be linked to EPI when the cancer develops after pancreatitis. “Another way pancreatic cancer can cause exocrine pancreatic insufficiency is if the tumor completely blocks the pancreatic duct,” Agrawal says. If this happens, digestive juices can’t make it from the pancreas to the duodenum, where nutrients are absorbed, and pancreatic insufficiency symptoms can be severe, he adds.
  4. Cystic fibrosis Cystic fibrosis, a rare genetic disease that causes thick, sticky mucus to build up in the digestive tract, lungs, and other areas of the body, can also lead to EPI. “Cystic fibrosis causes exocrine pancreatic insufficiency by affecting the pancreatic duct’s ability to secrete digestive enzymes,” Dr. Gress says.
  5. Celiac disease Celiac disease is a genetic condition that causes difficulty digesting gluten, a type of protein found in wheat, barley, and rye. When people with celiac disease eat gluten, Gress explains, the villi (tiny, fingerlike projections that line the small intestine) shorten and are unable to absorb nutrients like they should. “As a result, fat fills the small intestine, and the pancreas makes more enzymes to try to digest it,” he says. “This creates a vicious cycle that eventually causes the pancreas to burn out, sometimes leading to pancreatic insufficiency symptoms.”
  6. High triglycerides Triglycerides are a type of fat in your blood that helps provide energy for your body. Normal triglyceride levels are below 150 mg/dL, according to the Centers for Disease Control and Prevention. “When a person’s triglycerides reach a very high level of 500 mg/dL or more, the pancreas can’t function,” Gress says. “The excess fat cannot be absorbed by the pancreas; the pancreas gets fatty, and over time that fat is replaced by scarring and inflammation or chronic pancreatitis,” he explains. This can lead to EPI.
  7. Inflammatory bowel disease Chronic inflammation of the digestive tract, which is called inflammatory bowel disease and includes Crohn’s disease and ulcerative colitis (UC), can lead to EPI. About 14 percent of people with Crohn’s and 22 percent with UC have EPI, according to a review published in October 2018 in the Journal of Clinical Medicine Research.
  8. Lupus The autoimmune disease lupus can cause a rare condition called autoimmune pancreatitis, where the body’s T cells (blood cells that fight infection) attack the pancreas. “Autoimmune pancreatitis can lead to chronic pancreatitis and, in some cases, to exocrine pancreatic insufficiency,” Gress says.
  9. Shwachman-Diamond syndrome Shwachman-Diamond syndrome, a rare genetic condition in which the body has trouble absorbing fats and other nutrients, can lead to EPI, according to the Genetic and Rare Diseases Information Center. It’s difficult for children with this syndrome who also have pancreatic insufficiency to get the nutrients they need to grow. Although EPI is a serious condition, the good news is that it’s often treatable with medication, called pancreatic enzyme replacement therapy, Gress says.