Diagnosing Hereditary Angioedema (HAE)

Hereditary angioedema (HAE) is a very rare genetic condition. It causes severe and sudden swelling in different parts of the body. This swelling can affect your skin, your stomach, and your throat. Throat swelling can block your airway and become life-threatening if left untreated.^1,2

The swelling happens because of a problem with a blood protein. This protein helps control swelling in your body. Without enough working protein, fluid leaks into your body tissues. This leak causes the severe swelling attacks.^1,2

HAE attacks can happen without a clear reason. However, certain things can trigger an attack. Common triggers include physical stress, dental work, illnesses, hormonal changes, and emotional stress. Knowing your triggers can help you or your loved one manage the condition.^1,2

Common misdiagnoses for people with HAE

Many people with HAE face a long delay before they get a correct diagnosis. It often takes several years to find the true cause of the swelling. Doctors frequently mistake the symptoms for other common medical problems.¹

People with HAE are often misdiagnosed with typical allergic reactions. They may be told they have standard food or environmental allergies. However, HAE swelling is very different from an allergy.¹

Here are the key differences between HAE and an allergic reaction:^1,2

• HAE attacks do not cause itching.
• HAE attacks do not cause hives.
• HAE swelling does not respond to allergy medicines like antihistamines.
• HAE swelling can cause severe stomach pain and vomiting.
• HAE attacks last for days.

Doctors may also mistake stomach swelling for appendicitis or irritable bowel syndrome (IBS). This mistake can lead to unnecessary surgeries. It can also lead to hospital stays and wrong treatments.¹

How doctors test and diagnose hereditary angioedema

Medical experts use specific guidelines to identify this condition. The process requires reviewing your symptoms and medical history. Doctors must also use specific laboratory tests to confirm the diagnosis.^1-3

Physical exam and family history

Your doctor will start with a detailed physical exam. They will look closely at your swelling patterns. They will ask if you have hives or itching. They will also ask about your family medical history and whether anyone in your family has HAE.^2,3

HAE is an autosomal dominant genetic condition. This means a parent can pass the condition to a child. Around 75 percent of people with HAE have a family history of swelling.^2,3

The other 25 percent of cases come from a new gene mutation. Your doctor will map out your family medical history. This history provides a major clue for your diagnosis. ³

Blood work and genetic testing

Blood tests are the most important tools for a clear diagnosis. Doctors measure specific proteins in your blood sample. These tests check your immune defense system (complement system).^1-3

Doctors look for 3 specific markers in your blood work:^1-3

• Low levels of a protein called complement 4 (C4).
• Low levels of the C1 inhibitor protein.
• Low functional activity of the C1 inhibitor protein.

Low C4 levels are present in almost all people with HAE. If your C4 level is normal, you likely do not have the condition. Doctors use the C1 inhibitor tests to determine the exact type of HAE.³

Genetic testing is another option for families. It looks for mutations in the C1 inhibitor gene (SERPING1). This gene tells your body how to make the C1 inhibitor protein.^1-3

Genetic testing is very helpful for testing newborn babies. It is also useful if your protein blood tests show normal results.^1-3

What you should do if you suspect HAE

You should take action if you experience unexplained swelling without hives.^1-3

Start by keeping a detailed journal of your symptoms.

Track when the swelling starts, where it happens, and how long it lasts. Note if your swelling improves with allergy medications (antihistamines).

Schedule an appointment with an Allergy and Immunology specialist.

Share your symptoms and your family history with them. Ask the specialist to order the specific C1 inhibitor blood tests. You can also connect with a patient advocacy group for expert doctor recommendations.^1-3

Be prepared for your doctor visit.

Bring your symptom journal and photographs of your swelling. Photographs are very useful if you do not have swelling during your visit. Write down your questions before you go to the clinic.

Work closely with your healthcare team

Getting a correct diagnosis is the first step toward managing HAE effectively. Understanding the proper diagnostic criteria can prevent dangerous misdiagnoses. Work closely with your healthcare team to get the right blood tests.³

A proper diagnosis will help you find the right treatment plan. It will also give you peace of mind.