Why HAE Is Often Misdiagnosed

Medically reviewed by Puttatida Chetwong, M.D.

Written by Sherri Gordon, CLC

Posted on July 29, 2026

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Key Takeaways

Hereditary angioedema, or HAE, is a rare condition that is commonly misdiagnosed, often leaving people without the care they need for what can be a serious and life-threatening condition.

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Whether you’ve recently been diagnosed with hereditary angioedema (HAE) or your healthcare provider suspects you have the condition, it has probably been a long road getting to this point. In fact, HAE is so rare that it’s commonly misdiagnosed.

Being unaware you have HAE could mean that you don’t get the treatment you need during an HAE attack, which can be life-threatening. So it’s important to determine if you have HAE or not. Here’s why HAE is often misdiagnosed and what it’s mistaken for.

🗳️ Were you initially misdiagnosed?

Yes, with allergies or a drug sensitivity

Yes, with appendicitis or another GI issue

Yes, with a different condition or a combination of the above

Why Diagnosis Takes So Long

There are a number of reasons why it takes so long to get diagnosed with HAE.

At the top of the list is the fact that the condition is so rare that healthcare providers may be unfamiliar with the disease and don’t consider testing for it. HAE affects about 1 in 50,000 people, which means only about 6,000 people in the United States may have the condition.

The condition is so rare that healthcare providers may be unfamiliar with the disease and don’t consider testing for it.

Another common issue is that the symptoms of HAE often overlap with more common conditions like allergies or appendicitis. Plus, HAE usually doesn’t have many distinguishing characteristics that could alert a doctor to it.

Further complicating matters is the fact that even though HAE is a genetic condition, there can also be a lack of family history in about 25 percent of cases. The gene mutations (changes) that cause HAE can arise spontaneously, known as de novo mutations. More awareness on this could help reduce the number of misdiagnoses — and resulting complications.

Common Misdiagnoses and Why They Happen

If you have HAE, it’s possible you’ve spent years trying to figure out why you experience spontaneous swelling. In fact, some people have waited 13 to 20 years to be diagnosed with HAE.

About 50 percent of people who have HAE have been previously misdiagnosed, according to one observational study. Here are some of the conditions that are frequently confused with HAE and why.

Allergies

Often people with HAE are misdiagnosed with allergies. This could be because their frequent swelling causes people to seek out an allergist first for care. Or it could be because HAE and allergies share common symptoms like swelling of the lips, face, and throat.

Many people with HAE also report having allergies even after they’re diagnosed. One survey found that 54 percent of people with HAE reported also having allergies.

Drug Allergies and Sensitivities

Another possible misdiagnosis includes being labeled with a drug allergy. In fact, the rate of reported drug allergies among people with HAE is significantly higher than other groups of people. And because of this, getting an accurate diagnosis can be delayed.

Most people assume that swelling is related to allergies or a drug interaction. But when you don’t respond to treatments for these conditions, like antihistamines and steroids, it’s a clue that something else may be going on.

What’s more, healthcare providers tend not to challenge or question drug allergies once they’re in your chart. So in addition to exposing you to more health risks, being wrongly diagnosed with a drug allergy could mean you won’t be given important drugs you may need in the future.

Appendicitis and Gastrointestinal Issues

HAE abdominal attacks can involve severe abdominal pain and swelling, nausea, vomiting, and diarrhea or constipation. These symptoms also occur in appendicitis and can look like a surgical emergency to a doctor.

These overlapping symptoms may put you at risk for misdiagnosis and may also mean you’re more likely to have invasive medical tests or surgeries. One study found that people with HAE were two and a half times more likely to have abdominal surgeries than those without the condition. The study also found twice as many people with HAE had their appendixes removed than those without HAE.

Clues That Point to HAE Instead of Allergies

You Had Early Onset of Symptoms

HAE often begins in childhood, with symptoms showing up as early as age 2. About half of people with type 1 or type 2 HAE have symptoms by age 10, and nearly everyone with either type has symptoms by the time they’re 20 years old.

Other Family Members Have Swelling

Because HAE is an autosomal dominant genetic disorder, it’s most often inherited from a parent. This means that the affected gene is on a chromosome and only one parent needs to have the condition to pass it on.

Allergy Medications Are Ineffective

When treating swelling, physicians may try antihistamines, steroids, and even epinephrine, only to find that they don’t work. This is because HAE is not an allergic reaction or histamine response. Instead, your body has excess bradykinin, a substance that plays a role in inflammation.

Swelling Occurs Without Hives or Itchy Skin

HAE swelling isn’t usually accompanied by itching or urticaria (hives). If you repeatedly have swelling without hives and pruritus (itchy skin), it’s possible you could have HAE.

Talk to your healthcare provider about the possibility of HAE if you notice these clues in your specific situation. Testing for HAE is relatively simple. Just know that most cases of swelling aren’t HAE.

How HAE Is Diagnosed Once Suspected

If your healthcare provider suspects you have HAE, they’ll likely start with a physical exam and questions about your symptoms. They’ll also want to know if anyone in your family has HAE or experiences spontaneous swelling.

If your doctor suspects you have HAE or if they want to rule it out, they may order three different blood tests. These tests check your blood to determine if you have low levels of certain proteins and if they’re functioning properly. Here are the primary blood tests for HAE:

C4 blood test — This test checks your C4 protein level. People with type 1 or type 2 HAE often have low C4 levels, even between attacks.
C1 inhibitor (C1INH) blood test — This test measures the amount of C1INH protein in your blood. If you have low levels or a C1 inhibitor deficiency, then type 1 HAE is suspected. If your level is normal, type 2 HAE may be suspected.
C1INH function blood test — This test measures how well C1INH functions in your body. Type 2 HAE occurs when your C1INH protein doesn’t function properly.

Once your healthcare provider reviews the results from these blood tests, they should be able to tell you if you have HAE and which type it is. About 85 percent of all HAE cases are type 1, which means your body doesn’t make enough of the C1INH protein.

Your doctor may also recommend undergoing genetic testing in order to confirm a type 1 or type 2 diagnosis. Genetic tests will look for mutations in the SERPING1 gene, which tells the body how to make the C1INH protein.

Currently, there isn’t a reliable diagnostic test for HAE with normal C1INH, in which C1-inhibitor protein levels are normal and the proteins appear to be functional. This is when doctors may consider genetic testing to check for mutations in other genes, such as the F12 gene.

What To Do After a Diagnosis

After being diagnosed with HAE, you may want to suggest other family members get tested, since this condition tends to run in families. It’s also important to find a doctor who’s familiar with treating this genetic disease.

You and your doctor can work together on an individualized treatment plan that includes the right medications for your specific needs. It’s also important to establish an ongoing relationship with your doctor and communicate your concerns so they can monitor the frequency and severity of your attacks and adjust your treatment as needed.

If you’re having trouble finding someone who can reliably treat you, reach out to the US Hereditary Angioedema Association. This nonprofit organization can connect you with a physician who treats HAE.