The Diagnostic Maze: Why Was I Misdiagnosed?

Finding the cause of your rare disease can feel like a long journey. Many people with hereditary angioedema (HAE) spend years looking for answers. This condition is rare and often looks like other health problems. You may feel alone or confused by your symptoms.^1-3

The history of unnecessary surgery

Many people with HAE have a history of surgeries they did not need. HAE often causes severe pain in the belly. This pain can be so bad that it feels like a medical emergency. Doctors who do not know about HAE may think you have appendicitis. They might also think your gallbladder is failing.^2,3

Compared to the general population, people with HAE are much more likely to undergo unnecessary surgery before they get a correct diagnosis. In one study, more than 30 percent of people with HAE had been misdiagnosed during an abdominal attack and underwent an appendectomy, exploratory laparotomy, or both.^2,3

The "masquerade" of HAE is very common in emergency rooms. Doctors may see signs of a "surgical abdomen" and act fast to help you. However, surgery does not stop an HAE attack. You may wake up from a procedure only to have the swelling return later on. This happens because the root cause of the pain is not an infection.^2,3

Be sure to share your full history of belly pain with your healthcare team. This can help them see a pattern of recurring attacks.^2,3

HAE abdomen versus a typical infection

It is important to know how an HAE attack differs from an infection. A typical "acute abdomen" like appendicitis often comes with a fever. It also usually shows a high white blood cell count in blood tests. HAE abdominal attacks are different because they do not involve a fever. While white blood cells may rise during a crisis, typical markers of infection (like fever or certain proteins) are usually absent.^2,3

An HAE attack causes swelling in the walls of the intestines. This swelling often results in a buildup of fluid in the abdomen. This fluid is called transient ascites. A doctor can often see this fluid using an ultrasound or a CT scan. If you have severe belly pain but no fever, ask your doctor about HAE. Mentioning the absence of infection markers can help them think beyond common diagnoses.^2,3

Why allergy treatments fail for HAE

You may have tried to treat your swelling with standard allergy medicines like antihistamines, steroids, and epinephrine. For most people with HAE, these drugs do not work. This is because HAE is not an allergy. Normal allergies are driven by a chemical called histamine. Histamine comes from cells in your body called mast cells.^4-6

HAE involves a different process called the bradykinin cascade. Bradykinin is a protein that tells your blood vessels to leak fluid. This leakage causes the deep tissue swelling you feel.^1,4-6

Your body normally uses a protein called C1-inhibitor to keep bradykinin in check. If you have HAE, you do not have enough of this protein. Or, the protein you have does not work well. Since allergy drugs only target histamine, they cannot stop the bradykinin from causing swelling.^1,4-6

The triple test for a clear diagnosis

If you suspect you have HAE, you need specific blood tests. General blood work will not show this condition. There are 3 main tests that doctors use to find HAE. These provide the clinical evidence needed for a diagnosis.^1,3-5

• C4 levels – This is the best first step for screening. Levels of C4 are almost always low in people with HAE. This is true even when you are not having an attack.
• C1-INH antigenic – This test measures the total amount of the C1-Inhibitor protein in your blood. A low number suggests you have Type 1 HAE.
• C1-INH functional – This test measures how well your C1-Inhibitor protein works. This is very important for finding Type 2 HAE. In Type 2, you may have enough protein, but it does not function correctly.

If these three tests come back normal but symptoms persist, ask about genetic testing for HAE with normal C1-inhibitor.^1,3-5

Diagnosis can be a challenge

The road to an HAE diagnosis can be hard and long. Understanding the "masquerade" of this condition is the first step toward better health. You now know why surgery or allergy drugs may not have helped in the past.⁶

Use this information to advocate for yourself. Ask your doctor for the triple test of C4 and C1-inhibitor levels. A correct diagnosis can stop the cycle of unnecessary procedures and lead to the right treatment. Modern treatments now include oral options and long-acting preventatives that have drastically changed patients' quality of life.^1-3