Angioedema is swelling in the skin. It has several causes, including allergic reactions and hereditary causes. While their symptoms are similar, knowing the underlying cause helps identify the most effective treatment.

The majority of angioedema cases are allergic in nature. This means the swelling responds to allergy medications, such as corticosteroids or antihistamines, and is most often not life threatening. Very rarely, this allergic type of swelling may involve the airways and can be life threatening.

Another type of angioedema is nonallergic in nature and does not respond to allergy medications. It is very rare. Most often, this type of angioedema is inherited and carries a risk of potentially life threatening airway swelling.

The inherited kind of angioedema is known as hereditary angioedema (HAE). Experts estimate 1 in 50,000–150,000 people have HAE across the globe.

This article reviews the similarities between the hereditary and allergic types of angioedema as well as the differences in their causes, diagnosis, treatment, and more.

Angioedema is swelling that occurs in the deep layers of the skin and surrounding tissues. It occurs when fluid leaks out of surrounding blood vessels.

The swelling can occur anywhere in the body. It can be associated with additional symptoms depending on the cause.

Common symptoms

Hereditary and allergic angioedema share some similar features. Both involve swelling that typically starts in the deep layers of the skin and other tissues.

Angioedema often develops in the following areas:

  • lips
  • eyes
  • mouth
  • genitalia
  • tongue
  • extremities, such as the arms, legs, feet, or hands

However, it can also cause swelling in the airways and gastrointestinal (GI) tract. Though any form can cause symptoms in the airways or GI tract, HAE is more likely to cause symptoms here.

Symptoms that may occur when these areas are involved can include:

  • abdominal pain
  • shortness of breath
  • dizziness
  • fainting
  • nausea
  • diarrhea
  • vomiting

In severe cases, angioedema can cause restrictions to the airways that require immediate medical attention. Signs of a restricted airway include:

  • voice changes
  • sudden, severe difficulty breathing
  • harsh vibrating noise when breathing (stridor)
  • swollen tongue or throat

While both types of angioedema cause swelling, there are several distinctions between them. The following is a comparison of the two based on:

  • the person affected
  • symptoms
  • causes
  • diagnosis

Who it affects

Allergic angioedema is the most common form of angioedema. It can show up as a symptom of chronic spontaneous urticaria, a chronic condition affecting 1 in 100 people.

By contrast, HAE affects fewer than 50,000 people in the United States. Some estimates state it may affect 1 in 150,000 people worldwide.

Both can start at any age, though HAE often starts in childhood.

Symptoms

While the two types of angioedema share similar symptoms based on what areas the condition affects, there are key differences.

When allergic angioedema occurs, a person often develops hives and itching. Hives are areas of raised skin that may appear reddish or the same color as the surrounding skin. Itching is very common in allergic angioedema. Itching is typically absent in HAE.

Another key difference is when symptoms start. Allergic angioedema tends to start quickly after exposure. HAE symptoms can start spontaneously and resolve on their own within 2–4 days.

People with HAE may also show signs of an attack coming. People may experience:

  • sudden mood changes
  • extreme fatigue
  • changes to voice, such as hoarseness
  • tingling of the skin

An important way doctors differentiate allergic angioedema from HAE is through a person’s responses to treatment.

Allergic angioedema typically improves within minutes to hours of taking antihistamines, corticosteroids, and, when necessary, epinephrine.

HAE, however, does not improve with these medications. It typically runs its course in 2–5 days regardless of whether a person took these medications.

Causes

Allergic angioedema occurs due to an allergic reaction. This means a person comes into contact with a substance that triggers the immune system, resulting in swelling and often hives.

Common triggers of allergic angioedema include:

  • food, such as shellfish or tree nuts
  • medications, such as antibiotics
  • stings and bites from insects
  • latex
  • pet dander

Allergic angioedema triggers are not limited to external ones. It also commonly occurs as part of chronic spontaneous urticaria, which is due to an internal trigger.

On the other hand, HAE occurs due to a genetic defect that either causes low levels of C1-INH protein in the blood or from the C1-INH protein not functioning properly.

The defect is due to an autosomal dominant form. This means a person only needs to inherit one copy of the defective gene for the condition to occur. The risk of a child inheriting the condition from a single parent with the condition is 50%.

HAE triggers can also vary from person to person. Some common triggers that can cause an attack include:

  • illnesses, such as colds and flu
  • surgery
  • anxiety
  • dental procedures
  • medications

A person can keep a journal to help them identify and learn about their potential triggers and early warning signs of an attack. This can then help them avoid triggers or prepare for an impending attack.

A genetic defect, as mentioned above, is one cause of nonallergic angioedema. The other two causes of nonallergic angioedema are side effects from ACE inhibitors, a class of blood pressure medications, and autoimmune problems or conditions.

Diagnosis

Diagnosis for either type of angioedema can be challenging for doctors to make. They have to determine the underlying cause of the swelling.

To start the diagnostic process, a doctor will review a person’s symptoms and exposures over the past few days. They may ask about known allergies, medication use, and family history.

If a person’s angioedema is not responding to treatment for allergic angioedema or symptoms suggest a nonallergic type of angioedema, then doctors can run a blood test to screen for nonallergic causes.

It can often take longer to diagnose HAE. This is because the condition is so rare as well as the need to rule out other possible causes.

The blood test to diagnose HAE will check the level and function of C1-INH in the blood.

Treatment

Episodes of allergic or nonallergic angioedema often improve temporarily without treatment.

Allergic angioedema typically responds well to antihistamines, corticosteroids, and epinephrine. Epinephrine is an injection often given when the airways constrict, cutting off breathing. A person can inject the medication using a special injector that they can carry with them.

HAE does not respond well to these therapies.

A person who has HAE runs the risk of repeated attacks that may lead to serious obstructions to the airways. Because of this, it is important for people to clarify with their doctor to determine whether the condition is indeed HAE, especially if family members are affected or allergy medications are not helpful.

To treat HAE, a doctor may use intubation or surgical airway intervention to restore breathing in emergency situations.

Treatment for HAE may also include medications such as:

  • C1 inhibitor concentrate
  • ecallantide (kallikrein inhibitor)
  • icatibant (bradykinin receptor antagonist)

These medications can help treat attacks and help prevent them from occurring.

A person should use an emergency epinephrine injection or seek emergency medical attention immediately if they have trouble breathing.

HAE occurs due to a defective gene passed down from a parent. It is not a very common form of angioedema, so it may take some time for doctors to diagnose. Treatment can help reduce the severity of an attack and help prevent new ones from occurring.

Allergic angioedema occurs with or without exposure to an external allergen. Treatments can help reduce swelling quickly and help a person breathe normally again.

Both conditions can cause similar symptoms and cut off the airways, requiring emergency treatment. Proper diagnosis is important because HAE typically does not respond to the same medications as allergic angioedema in an emergency.

A person can typically manage either type of angioedema by taking steps to avoid triggers and having medications on hand to treat an attack when it occurs.