Angioedema swelling can last for hours or days, and it may or may not happen in response to a trigger, such as an allergen or a medication. But angioedema is a broad term, and there are multiple types with key differences.

Angiotensin-converting enzyme (ACE) inhibitor angioedema and hereditary angioedema (HAE) are two types of angioedema with major differences in how they appear and how they’re treated. Below, we cover how each type is recognized, diagnosed, and treated.

How ACE Inhibitor Angioedema and HAE Are Similar

ACE inhibitor angioedema and HAE are both types of angioedema that involve swelling in the tissues just under the skin and sometimes in other areas. Although some types of angioedema cause hives along with swelling, neither ACE inhibitor angioedema nor HAE typically causes hives or itchy skin.

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Both ACE inhibitor angioedema and HAE are considered rare conditions. ACE inhibitor angioedema affects 0.1 percent to 0.7 percent of people who take ACE inhibitors, and about 1 in 50,000 people are diagnosed with HAE.

Both conditions can also cause life-threatening complications that require emergency care, including upper airway swelling that can make breathing difficult or impossible.

Underlying Causes of ACE Inhibitor Angioedema vs. HAE

Swelling in ACE inhibitor angioedema and HAE can look similar, but it doesn’t occur for the same reason. Each type of angioedema has unique underlying causes.

ACE Inhibitor Angioedema Causes

ACE inhibitor angioedema occurs as a side effect of taking ACE inhibitors, which are medications commonly prescribed for cardiovascular conditions such as hypertension and heart failure. They’re also sometimes prescribed for chronic kidney disease.

A small number of people who take ACE inhibitors experience swelling because ACE inhibitors prevent bradykinin — a molecule involved in swelling and inflammation — from breaking down. Bradykinin then builds up in the bloodstream and may cause swelling.

Most people who take ACE inhibitors don’t develop angioedema because their bodies regulate bradykinin through other pathways. This suggests that some people may be genetically susceptible to ACE inhibitor angioedema.

HAE Causes

There are several types of hereditary angioedema, all with different causes. In the most common types of HAE, swelling occurs because of problems with C1 inhibitor (C1INH), a protein in the immune system that regulates inflammation. HAE type 1 involves low C1INH levels, while HAE type 2 involves C1INH that doesn’t function normally even when levels are normal.

A rarer type, called HAE with normal C1 inhibitor, has normal C1INH test results. Health experts are still learning what causes swelling in this type and believe it is related to bradykinin.

HAE is a genetic condition, which is why most cases are passed down from a parent. In rare cases, HAE can develop in someone with no family history through a spontaneous (de novo) gene mutation.

How Each Type Shows Up

Both ACE inhibitor angioedema and HAE cause swelling, but the swelling can occur in different areas and at different times. HAE tends to cause less predictable swelling than ACE inhibitor angioedema.

When Swelling Occurs

Swelling in ACE inhibitor angioedema often begins within weeks or months of starting the medication. However, some people don’t develop swelling until they’ve been taking ACE inhibitors for years.

Swelling episodes can continue for weeks or months, even after stopping the medication. Over time, though, episodes usually stop as long as the medication is avoided.

People with HAE experience unpredictable swelling episodes throughout their lives. Triggers, which are identified in about 40 percent of HAE attacks, can include:

• Stress
• Physical trauma, including from surgery or medical procedures
• Pressure on the skin
• Infections
• Hormones, especially estrogen
• Medications, including ACE inhibitors and some forms of birth control

Where Swelling Occurs

ACE inhibitor angioedema and HAE can involve swelling in several of the same areas. For example, they can both cause swelling of the gastrointestinal (GI) tract, which can result in vomiting, diarrhea, and abdominal pain. They’re also both associated with tongue and upper airway swelling, though this is rare in HAE.

Unlike ACE inhibitor angioedema, HAE often causes swelling of the hands and feet. Swelling in the extremities or face is often visible. If a person has been prescribed on-demand medications for HAE, they should take them as soon as they notice swelling to reduce the severity of an attack.

Differences in Diagnosis

Doctors use different processes to diagnose each type of angioedema. They usually start with a physical exam and may use allergy testing to rule out an allergic reaction as the cause.

ACE Inhibitor Angioedema Diagnosis

To be diagnosed with ACE inhibitor angioedema, a person must be taking an ACE inhibitor. ACE inhibitor angioedema might not be a healthcare provider’s first guess, so they may have already tried treating the swelling with antihistamines or corticosteroids. The symptoms of ACE inhibitor angioedema won’t respond to these treatments.

Stopping the ACE inhibitor should cause swelling to resolve, which can confirm ACE inhibitor angioedema as the underlying cause. Some swelling episodes may still occur in the first few months after stopping.

HAE Diagnosis

Doctors use blood tests to check for C1INH in people who may have HAE. Using C1 blood tests, they can determine whether a person’s C1INH levels are low or whether C1INH isn’t working properly. They may also order additional blood tests to check other parts of the immune system, including complement levels.

Genetic tests aren’t always needed to diagnose HAE, but they can confirm relevant genetic mutations. They’re also helpful for identifying HAE with normal C1 inhibitor.

Differences in Treatment

ACE inhibitor angioedema and HAE require different approaches to treatment. Fortunately, both types of angioedema are treatable.

ACE Inhibitor Angioedema Treatment

The most important step in treating ACE inhibitor angioedema is stopping ACE inhibitors right away. Talk with your healthcare provider before stopping any prescribed medication. They can help you find an alternative treatment for the condition that originally required ACE inhibitors.

It’s also important to address any throat or airway swelling in ACE inhibitor angioedema. For severe throat swelling, doctors may use intubation or a tracheostomy.

HAE Treatment

HAE treatment can involve a few different strategies, including treatments that help prevent HAE attacks (prophylactic or preventive treatments) and treatments to reduce swelling during active attacks (on-demand or rescue medications). It can also help to avoid any known triggers.

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