Causes of Angioedema

Angioedema is swelling under the surface of the skin. It occurs when fluid leaks out of blood vessels into nearby subcutaneous tissue and mucus membranes, such as those that line the inside of the nose or genitals.

There are several types of angioedema, each with different causes. The most common is an allergic reaction to something in the environment. Certain medications, infections, and diseases also can cause angioedema.

Some people have a condition called hereditary angioedema (HAE), which has a genetic component.

This article looks at the various types of angioedema and their causes. It explains what happens in the body when swelling occurs and describes the wide variety of triggers for this reaction.

Angioedema is not the same thing as urticaria, or hives, which is swelling of the surface of the skin rather than the tissue beneath it. Angioedema can occur along with hives.

angioedema causes

Common Causes

Angioedema can be triggered by exposure to various substances, from common allergens to prescription medications. It also can be a symptom or side effect of certain diseases or medical procedures.

There are two types of angioedema—one occurs when the immune system releases histamine, the other when the body releases peptides called bradykinins that regulate many important body functions.


Most of the time, angioedema occurs when the immune system mistakes an otherwise harmless substance as a danger to the body. In defense, it releases a chemical called histamine into the bloodstream.

Histamine causes tiny blood vessels to leak fluid into nearby subcutaneous tissue. This is why this type of angioedema is known as histaminergic. Most histaminergic angioedema is itchy and is also accompanied by hives; more rarely, it can occur in isolation.

Allergens can be triggers of such reactions. Among the most common allergens associated with angioedema are:

  • Latex
  • Pet dander (microscopic flecks of skin shed by animals with fur or feathers)
  • Pollen
  • Foods—especially dairy, eggs, fish and shellfish, tree nuts, peanuts, soy, and wheat
  • Insect bites or stings
  • Certain medications

There are a handful of less obvious causes of histaminergic angioedema. Some people experience swelling when exposed to extreme heat or cold, sunlight, or vibration—for example, while using a lawnmower, riding in a bumpy vehicle, or even toweling off after a shower.


Non-histaminergic angioedema is swelling that does not involve histamine. Instead, it’s caused by the release of peptides called bradykinins. It’s often referred to as bradykinin-mediated angioedema.

These substances play many roles in the body. One is to dilate (widen) blood vessels. This is important for several body functions, such as keeping blood pressure at normal levels.

If bradykinins are released when they aren’t needed, their effect on the blood vessels can cause them to leak into surrounding tissue and cause swelling. Most often, the feet, hands, genitals, face, lips, larynx, and gastrointestinal (GI) tract are affected.

ACE inhibitors, which treat high blood pressure, heart attack, failure, and nephropathy, are common causes of drug-induced non-histaminergic angioedema.

Sometimes the cause of angioedema isn’t clear, meaning it’s “idiopathic.” In most cases, the face, mouth, and tongue are affected.


Angioedema is swelling under the skin when fluid leaks from blood vessels. It occurs when the body releases histamine or bradykinin, which causes fluid to leak from blood vessels into nearby tissue. Triggers range from common allergens to certain medications, diseases, and medical procedures.


Some people who experience bradykinin-mediated angioedema have a gene mutation that makes them susceptible to triggers. This is called hereditary angioedema and an autosomal dominant disorder, meaning you must inherit the responsible gene from only one parent.

There are three types of HAE, two of which are caused by mutations in the SERPING1 gene. The cause of the third type of HAE is less understood, but a small fraction of these patients are thought to have HAE caused by a mutation of the F12 gene.

Genetics also may factor in vibratory angioedema. Autosomal dominant vibratory urticaria has been linked to a mutation in the ADGRE2 gene, which allows mast cells to release histamine more easily.

HAE is rare, occurring in one of every 50,000 people, and is often only suspected if someone with angioedema does not respond to antihistamines or has a family history of angioedema.


Angioedema is the swelling of tissue underneath the skin. It occurs when either histamine, an immune system chemical, or peptides called bradykinins are mistakenly released into the bloodstream, where they cause fluid to leak from blood vessels.

There is a wide variety of reasons this can happen, ranging from exposure to an allergen that triggers histamine to certain medications or medical conditions or procedures that trigger bradykinins. A tendency to develop angioedema also can be inherited.

A Word From Verywell

If you or someone else experiences sudden swelling or any symptoms of angioedema, you should get medical attention. Angioedema that affects the GI tract can cause violent vomiting, intense pain, and dehydration.

When swelling affects the face, mouth, tongue, larynx, or throat, it can restrict air flow to the lungs and is a medical emergency.

Frequently Asked Questions

  • What causes angioedema?

    Angioedema is triggered by an increase of histamine and/or bradykinin which stimulate a cascade of inflammatory reactions, causing blood vessels to dilate and fluid to leak into underlying tissues. When this occurs in deeper subcutaneous and submucosal tissues, angioedema is the result.

  • What is hereditary angioedema?

    Hereditary angioedema is a genetic disorder usually characterized by a deficient quantity or function of C1 inhibitor, a substance the body uses to regulate a peptide known as bradykinin. In rare cases, hereditary angioedema can be associated with normal quantities and function of C1 inhibitors. Like histamine, bradykinin induces blood vessel dilation. Without C1 inhibitors to temper the response, the accumulation of bradykinin can trigger excessive tissue swelling.

  • Is angioedema autoimmune?

    Chronic and relapsing angioedema is often linked to autoimmune diseases, like lupus and Hashimoto’s thyroiditis. Some studies suggest that as many as 30% to 50% of idiopathic angioedema (meaning angioedema of unknown origin) may be associated with some autoimmune diseases. In such cases, itchy hives (urticaria) commonly accompany the deeper tissue swelling.

  • How does pressure cause angioedema?

    Pressure angioedema develops when steady pressure applied to an area of the skin causes immediate or delayed deep tissue swelling. It is believed to be autoimmune in nature. Examples include wearing tight clothes or sitting for long periods, during which sustained pressure causes mast cells found in vascular tissues to break open and release histamine. Extreme vibrations can do the same.

  • What drugs are most likely to cause angioedema?

    Angioedema can occur due to exposure to certain drugs:

    ACE inhibitors like Vasotec (enalapril) and Zestril (lisinopril) can cause the accumulation of bradykinins by blocking their breakdown.

Regardless of what causes it, angioedema in the GI tract can cause violent vomiting, intense pain, and dehydration. When swelling affects the face, mouth, tongue, larynx, or throat, it can restrict the flow of air to the lungs and is a medical emergency.

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Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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By Daniel More, MD
Daniel More, MD, is a board-certified allergist and clinical immunologist. He is an assistant clinical professor at the University of California, San Francisco School of Medicine and currently practices at Central Coast Allergy and Asthma in Salinas, California.