Although inflammatory bowel disease (IBD) starts in the gut, it doesn’t always stay there. According to a 2015 study in the journal Inflammatory Bowel Disease, up to 47% of people with IBD will develop what are called “extraintestinal manifestations,” or EIMs. That means the disease ranges outside of the gut and causes problems in other tissues or organs. Not only are EIMs common, but many people experience more than one of them. That same 2015 study found that up to a quarter of IBD patients who develop an EIM will have more than one.

The skin, joints, and eyes are among the most common sites of these beyond-the-bowel disease manifestations. But the pancreas is another organ that, over time, can be caught up in IBD’s sprawling web of harm. Some researchers have estimated that up to 18% of people with IBD may have some sort of pancreatic involvement at some point, although that does not always lead to symptoms or medical problems. (For example, there’s evidence that many people with IBD produce too much of certain pancreatic enzymes, which may or may not cause any health issues.) On the other hand, IBD is also associated with both acute and chronic pancreatitis, autoimmune pancreatitis, gallstones, and other pancreatic conditions that can present more significant medical risks.

“Both the IBD-ologists and the pancreas specialists are very interested in how these conditions might be linked, and I think there’s more than one answer to that,” says Dr. David Sachar, an IBD specialist and professor of medicine at the Mount Sinai School of Medicine in New York City. Sachar is coauthor of a 2016 review study on the relationship between IBD and pancreatitis. He says there are actually a handful of different ways that Crohn’s disease and ulcerative colitis—the two primary forms of IBD—may cause problems in the pancreas. But some are much more likely to be a factor than others.

Here, Sachar and other experts break down the most common pancreatic issues that turn up among people with IBD. They explain why these issues arise, how they’re treated, and what people can do to protect themselves.

IBD and pancreatitis

Pancreatitis is a catchall term for several different forms of inflammation that arise in the pancreas.

The most common form of pancreatitis among IBD patients is acute pancreatitis. This is a sudden, symptomatic, and potentially life-threatening form of inflammation that is often brought on by gallstones (which are particularly common among people with Crohn’s disease), but also by several common IBD medications—namely thiopurines such as azathioprine and 6-mercaptopurine. “If the acute pancreatitis is related to thiopurines, it will present in the first 90 days after starting on the drug,” says Dr. Faten Aberra, a gastroenterologist and associate professor of medicine at the Hospital of the University of Pennsylvania. Acute pancreatitis can also be a consequence of high blood calcium levels or alcohol consumption.

“The main symptom of acute pancreatitis is abdominal pain, and it tends to be in the upper abdomen,” Aberra says. According to the Mayo Clinic, some other symptoms include abdominal tenderness, fever, a racing heart, nausea, and vomiting. If this type of pancreatic inflammation goes untreated, it can lead to something called systemic inflammatory response syndrome—a storm of inflammation in the body that can cause organ damage or death.

Chronic pancreatitis is another type of pancreatic inflammation. It’s less common than acute pancreatitis—both in people with IBD and in the general population. It’s a condition in which ongoing (as opposed to temporary) inflammation damages the operation of the pancreas. Once again, abdominal pain is a symptom. According to Johns Hopkins Medicine, other signs of chronic pancreatitis include vomiting, weight loss, persistent diarrhea, and glucose intolerance.

Finally, compared to the general population, people with IBD may be at an increased risk for autoimmune pancreatitis, or AIP. “Autoimmune pancreatitis comes in two forms—Type 1 and Type 2—and the bulk of IBD patients who develop AIP tend to have Type 2,” Aberra says. The symptoms of Type 1 AIP usually resemble chronic pancreatitis in terms of symptoms and presentation, while Type 2 often looks more like acute pancreatitis, she explains. Ironically, she says that some of the same IBD drugs that may cause acute pancreatitis are also used to treat autoimmune pancreatitis.

The exact relationship between autoimmune pancreatitis and IBD is not well understood. “That’s one mystery we haven’t unraveled, but it probably boils down to the altered gut microbiome,” says Dr. Prabhleen Chahal, a pancreatic disease specialist at Cleveland Clinic. The microbiome is the ecosystem of microorganisms that live in the gut. These microorganisms have a huge impact on the operation of the immune system, both within and outside of the gastrointestinal tract. It may be that microbiome-related disruptions caused by IBD lead to other forms of immune dysfunction, including Type 2 AIP. But at this point, that’s still just speculation. While it’s not a common complication among anyone with IBD, she says that Type 2 AIP is more likely to turn up in people with Crohn’s disease. Roughly one-third of patients with Type 2 AIP have underlying ulcerative colitis, Chahal adds.

Read More: How to Maintain Your Social Life When You Have IBD

Other IBD-linked pancreatic issues

There are several other pancreatic conditions that seem to have a relationship with IBD.

Pancreatic cysts are fluid-filled pockets or sacs that develop on or in the pancreas. They’re mostly benign (less than 3% are cancerous), and they tend not to cause symptoms. They are also very common. Often, they’re found incidentally during MRI or CT scans for other conditions; in other words, doctors find them by accident during these types of imaging procedures. By some estimates, between 2% and 20% of people who undergo one of these imaging tests for any reason will turn out to have a pancreatic cyst. “A lot of people with IBD are going to get CT scans or MRIs, and so we often find these cysts,” Chahal says.

There’s not much evidence that people with IBD are at elevated risks for these cysts. Some research has found that people with IBD may be diagnosed with these cysts at a younger age. However, that earlier presentation doesn’t seem to be linked with higher rates of cancerous cysts or any other elevated risks. Chahal says medical providers will usually monitor the cyst for growth or worrisome changes, and at some point removal surgery may be necessary. But the same is true for non-IBD patients who have these cysts.

There are a handful of other pancreatic issues that may be somewhat more common among people with IBD compared to the general population. These include pancreatic fibrosis, which is a thickening of the organ’s connective tissue that may or may not be reversible. Pancreatic duct abnormalities and elevated enzyme levels may also occur more frequently in people with IBD, but these issues are not always a problem. Experts sometimes refer to these as “silent” abnormalities because they don’t always cause symptoms or require medical intervention.

How are IBD and pancreatic diseases connected?

There’s more than one answer to this question. In fact, Sachar says there are five explanations that he and other researchers have explored.

“Number one is that IBD leads directly to pancreatic disease,” he says. For example, if the ileum (which is the final section of the small intestine) becomes inflamed due to IBD, this could lead to changes in the digestive system’s levels of bile salts, which in turn could raise a person’s risk for gallstones. Gallstones are hardened deposits that can lodge in the pancreas and cause inflammation (acute pancreatitis).

The second possibility is that some kind of pancreatic disease causes IBD, but Sachar says this is highly unlikely. “I’ve never seen it,” he adds. The third scenario is that an underlying health issue gives rise to both diseases. “An example would be some kind of a derangement in the immune regulatory system,” he says. This derangement could lead to any number of autoimmune conditions or symptoms, which means that a person’s immune system starts attacking normal parts of their body. If a person’s immune system is disturbed, this could lead to both inflammatory bowel disease and autoimmune pancreatitis.

The fourth scenario is “just bad luck,” Sachar says. In other words, the conditions have nothing to do with each other, apart from the fact that they turned up in the same person. “The fifth and final scenario is probably much more common, and much more overlooked,” he says. “This is when the treatment for one of these conditions causes the other.” Several types of IBD medications have been strongly linked to the development of acute pancreatitis. Again, these include thiopurines, steroids, and several others. “Something like 1 in 20 patients who take thiopurines are going to get pancreatitis,” Sachar says.

Read More: These Environmental Factors Increase the Risk of IBD

How people with IBD can protect themselves

The first and most important thing people with IBD should do is to talk with their medical provider about the medications they’re taking—whether for IBD or for other conditions. Sachar says this can help reduce the risks of medication-related pancreas problems.

Apart from keeping an eye on your meds, Chahal says the most common causes of pancreatic inflammation are heavy alcohol consumption and gallstones. “I think it’s very important to use alcohol in moderation,” she says. Meanwhile, high levels of blood cholesterol and triglycerides can increase a person’s risks for pancreatitis, so it’s important to monitor your levels of both and take steps to keep them in a healthy range. Smoking is also a risk factor for pancreatitis, she adds. While smoking is unhealthy for anyone, people with IBD can consider the risk of pancreas inflammation one more reason not to light up.

Finally, Chahal says that a healthy lifestyle can help decrease all manner of IBD-related complications, including those that arise in the pancreas. “We encourage everyone to follow a Mediterranean sort of diet,” she says. That basically means lots of plant-based and whole-grain foods, using olive oil instead of butter, and limiting your consumption of red meat. Exercise, getting a good night’s sleep, avoiding sedentary time, and managing stress are also essential components of a healthy lifestyle—and the types of things most medical professionals recommend to reduce the risks of health complications.

Finally, keep in mind that most pancreatic problems that emerge among people with IBD are treatable. Few of them are chronic issues or likely to severely impact a person’s quality of life. If pancreatic problems do arise during your IBD journey, there’s a good chance you and your care team will be able to find an effective remedy.

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