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 inherited angioedema (HAE) which has a genetic component.

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

Common Causes

Angioedema can be triggered by exposure to a variety of 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 a number of important body functions.

Histaminergic

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 they're 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

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 bradykinergic angioedema.

These substances play a number of 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 legs, arms, genitals, face, lips, larynx, and gastrointestinal (GI) tract are affected.

ACE inhibitors, which are used to 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. Around 52% of people who experience idiopathic angioedema go to the ER at least once and 55% are treated with high-dose corticosteroids to bring down the swelling.

Genetics

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

There are three types of HAE. Two 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 ADGRE2 gene which allows mast cells to more easily release histamine.

Summary

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 the flow of air to the lungs and is a medical emergency.