Gut check: How HAE affects gastro health

Last updated Nov. 19, 2024, by Lindsey Shapiro, PhD
Fact-checked by Inês Martins, PhD

Hereditary angioedema (HAE), a genetic form of angioedema, is commonly associated with gastrointestinal (GI) symptoms such as nausea, abdominal pain, vomiting, and diarrhea. More than 90% of patients report at least one of these symptoms.

These digestive symptoms are from sudden swelling attacks affecting your digestive tract, including the stomach, intestines, or other organs. But they can be easily missed or mistaken for other more common gut issues, leading to improper diagnoses and unnecessary medical procedures.

Understanding how angioedema can affect the gut and which symptoms may be a sign of an abdominal swelling attack is critical for helping you get the right care as soon as possible. Typically, it involves a combination of HAE medications and lifestyle changes to keep GI symptoms under control.

How HAE affects gastrointestinal health

HAE is caused by genetic mutations that result in an overproduction of bradykinin, a molecule involved in regulating blood pressure and inflammation. Bradykinin causes blood vessels to dilate, which makes them more permeable, or leaky.

When there is too much bradykinin, fluid leaks from the bloodstream into surrounding tissues, leading to the characteristic swelling of an HAE attack. The swelling can occur anywhere in the body, including in the tissue lining the digestive tract, which is why there is a connection between HAE and the gut.

The GI system is made up of all organs involved with the processing of food and liquids, including breaking them down for energy and removing the waste products from the body. It includes the mouth, throat (pharynx), esophagus, stomach, small intestine, large intestine, rectum, and anus. Other organs, including the liver, gallbladder, and pancreas, which help with digestion, are also part of your GI system.

While HAE can affect any of these tissues and organs, the swelling is not always noticeable because it occurs internally. But you may experience a range of digestive HAE symptoms, some of which can be mild and others that can eventually cause more serious complications.

These digestive symptoms often are similar to what’s experienced with more common conditions, such as irritable bowel syndrome and food allergies. This is why it’s important that you understand how gut symptoms manifest in HAE to ensure you are treated promptly and correctly.

GI symptoms

GI problems are among the most common HAE symptoms, and often the first signs of the disease. It is also not unusual that, for many years, gut issues are the sole HAE symptom.

Because any part of the digestive tract can be affected, you may experience a range of symptoms during a GI swelling attack, which can vary in severity and duration.

The most common symptoms of gut angioedema attacks are related to swelling in the stomach and small intestines. These attacks often lead to abdominal pain or discomfort, which have been reported in 43%-93% of patients.

Abdominal pain may be moderate or severe, with some people describing the feeling as cramping and colicky, or coming and going in waves. Pain can also come on suddenly and be severe, and may in some cases be the only symptom of an HAE attack.

Other symptoms you may experience if you have swelling in the stomach or small intestines include:

abdominal distension, or bloating, which is reported in around three-quarters of HAE attacks
nausea, which may occur in about two-thirds of HAE attacks
vomiting, reported in 21%-78% of attacks
diarrhea, which is estimated to occur in about 14%-65% of attacks.

When other parts of the GI system are affected, you may experience additional symptoms, including swallowing problems if swelling occurs in the esophagus or pharynx, and constipation when swelling is in the colon, a part of the large intestine.

In most cases, gut symptoms from an HAE swelling attack last 2-4 days. They may be preceded by symptoms of irritability, fatigue, and changes in appetite.

While rare, GI swelling in HAE can result in serious complications that require more urgent medical intervention, including:

intussusception, where one part of the intestine folds inside of the other, leading to bowel obstruction
pancreatitis, or inflammation of the pancreas that occurs when swelling of the pancreas causes a partial obstruction in the ducts that carry the digestive fluid bile through the digestive tract
ascites, or fluid buildup in the abdomen that’s often related to liver swelling
hypovolemic shock, or circulatory collapse, which happens when the body loses so much fluid the heart can’t pump enough to all your organs.

In HAE, hypovolemic shock can occur as a consequence of blood vessel dilation, fluid loss from vomiting and diarrhea, and fluid leakage due to swelling in the bowels, which together cause low blood volume.

If you experience symptoms such as severe and sudden abdominal pain, blood in the vomit or stools, sweating, rapid breathing, confusion, weakness, agitation, or loss of consciousness, you should seek immediate care. Your healthcare team can determine if your symptoms are associated with a serious GI complication.

Treatment and diagnosis

HAE digestive symptoms can overlap substantially with other, more common conditions, so diagnosing HAE solely based on those symptoms can be tricky and lead to significant diagnostic delays.

Moreover, up to one-third of HAE patients with GI symptoms undergo unnecessary surgeries or invasive medical procedures due to misdiagnosis.

HAE may be confused with a wide range of other GI conditions, including inflammatory bowel disease, celiac disease, or irritable bowel syndrome. But, in contrast with those disorders, gut symptoms in HAE are generally limited to periods of swelling, and you may be entirely asymptomatic in between.

To determine if gut symptoms are caused by swelling, your doctor may take a detailed medical history. They may ask you to describe all symptoms you’ve been experiencing and their duration, and if you have any family history of HAE.

Your doctor may also request tests to help reach an HAE diagnosis, which may include:

Physical examination, to look for other signs of HAE swelling and identify active abdominal swelling, is most useful during an acute swelling attack
Blood tests may be needed to look for characteristic biomarkers of HAE. Genetic tests looking for HAE disease-causing mutations can also be requested.
Abdominal imaging, particularly a CT scan, may show signs of intestinal swelling, ascites, bowel obstruction, or thickening of the bowel fold tissue that occurs during an active swelling attack. Imaging can also rule out other causes of GI symptoms.
Colonoscopy, where a doctor uses a camera to look inside the GI tract, may be needed; if you have HAE, significant swelling will likely be observed.

If HAE is identified as the underlying cause of your GI symptoms, treatment will likely involve standard HAE management strategies, including on-demand medications to relieve active swelling attacks and prophylactic therapies to prevent them from occurring.

Classes of medications that may be used to treat or prevent GI swelling attacks may include:

C1-INH replacement therapies
bradykinin receptor antagonists
kallikrein inhibitors.

It’s important to know that some medications for treating HAE may cause GI side effects. So let your doctor know if you experience any GI problems after starting on any HAE medications.

Lifestyle and dietary changes

In addition to medications, maintaining good HAE gastro health may involve lifestyle changes to avoid HAE triggers and keep gut symptoms at bay.

Some adjustments to help you manage or prevent digestive symptoms include:

Diet modifications may be needed to avoid known allergens or trigger foods. A range of foods have been linked to HAE attacks in the digestive tract, but there is no definitive rule as to what foods trigger HAE attacks, as this varies individually.
Managing stress and protecting your mental health are key as stress can be a trigger for an HAE attack and also has known negative effects on the gastrointestinal system.
Exercise can relieve stress and is good for general gastro health. But for some people, exercising too intensely can trigger an HAE attack, so it’s important to find a balance.
Practice good hygiene, try to stay away from people who are sick, and keep up to date on vaccines, as infections can trigger HAE attacks.

Every person has different triggers for their GI symptoms and what helps you avoid attacks may not be the same for someone else with HAE.

It’s a good idea to keep a journal that includes information about your GI symptoms, how severe they were, and how long they lasted, as well as what you think might have caused them. Doing this can help you identify your own triggers and, in consultation with your healthcare team, figure out lifestyle changes that help you avoid HAE flare-ups.

Intestinal angioedema

Other causes of angioedema that are not related to genetics can also lead to GI symptoms. In these cases, gut angioedema is most often associated with angiotensin-converting enzyme inhibitors (ACEIs), a class of medications commonly used to treat high blood pressure, heart, and kidney problems. Less commonly, it’s triggered by allergic reactions to certain foods.

Just like HAE, intestinal angioedema can be challenging to diagnose, as the symptoms have significant overlap with other gut disorders. The symptoms of intestinal angioedema may seem very similar to those of an HAE gut swelling attack, including recurrent bouts of abdominal pain, diarrhea, and vomiting.

Treatment of intestinal angioedema related to medications and foods often involves corticosteroids or antihistamines to suppress the immune system and relieve swelling. You should also avoid any medications and foods associated with angioedema attacks.

Angioedema News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.