Diagnosis of Angioedema

Angioedema is a condition characterized by swelling underneath the skin that usually appears around the lips and eyes. It can occur as part of an allergic reaction (allergic angioedema), as a response to certain medications (non-allergic angioedema), due to a genetic mutation (hereditary angioedema), because of a malfunctioning immune system (acquired angioedema), or without a clear cause (idiopathic angioedema).

The disease is similar to hives or urticaria, but while hives causes swelling in the upper layers of the skin, angioedema causes swelling in the deeper layers of the skin. Angioedema and hives can occur independently or at the same time.

To diagnose the condition, doctors will try to determine what may have caused the disease, review the symptoms, examine the affected area(s), carefully analyze the patient’s past medical history, and perform tests to distinguish between the different types of angioedema.

Symptoms and medical history

In some cases, by examining a patient’s symptoms and past medical history, physicians may be able to identify the disease and pinpoint the type of angioedema. For instance, a family history of angioedema coupled with chronic and recurring swelling episodes, may lead physicians to suspect hereditary angioedema (HAE), an inherited form of the condition.

Patients whose symptoms manifested following exposure to certain substances that can cause allergic reactions, clinicians may suspect allergic angioedema.

Patients taking certain medications, such as blood pressure-lowering angiotensin-converting enzyme (ACE) inhibitors, physicians may suspect non-allergic angioedema.

Skin prick test

If symptoms are suspected to be caused by an allergy to external substances, such as food or medications, the patient may be directed to a specialist who will perform a skin prick test or a blood test.

A skin prick test is one of the most common diagnostic tests for allergies. It attempts to provoke a small, controlled, allergic response in the skin. A drop of liquid that contains a substance the patient may be allergic to is put on the forearm. Then, the skin under the drop is gently pricked with a needle to see if there is a reaction. If the patient is allergic to the substance, a raised, red, itchy bump (a weal) that may resemble a mosquito bite will appear within about 15 minutes. The test usually is painless and very safe. Certain medications, including antihistamines, should not be taken before the test because they may interfere with the results.

Blood tests

Blood tests also may be helpful to identify allergic angioedema, as they may be used to detect the presence of specific antibodies the immune system produces in response to allergens (substances seen as a potential threat). Physicians may order blood tests to check the levels of a protein called C1-inhibitor (C1-INH), which plays a key role in regulating inflammation and blood vessel permeability (leakiness) and is directly implicated in certain forms of angioedema. Low levels of C1-INH in the blood may signal the presence of acquired angioedema or HAE.

Genetic testing

In HAE, genetic mutations are the root cause of uncontrolled swelling. There are three types of HAE, depending on the specific gene that is affected. Types 1 and 2 are caused by mutations in the SERPING1 gene that provides instructions to make C1-INH, while type 3 is caused by mutations in the F12 gene, which encodes a protein called coagulation factor 12.

Genetic tests that search for mutations in the SERPING1 and F12 genes  usually are recommended for patients who have a family history of the disease, or for those experiencing chronic and recurrent bouts of swelling. Genetic tests may help to determine a person’s risk of passing the disease to their biological children.

If mutations are found in a very specific region of the SERPING1 gene called exon 8 and lead to the production of a less-effective C1-INH protein, the patient has type 2 HAE. If mutations in SERPING1 are found to prevent the production of C1-INH, as measured by a blood test, the patient has type 1 HAE. (Exons are portions of a gene sequence that contain instructions to make a protein.)

If no mutations are found in the SERPING1 gene, then the sequence of the F12 gene may be analyzed to see if the patient has type 3 HAE.

If all the above tests fail to produce conclusive results, the patient may be diagnosed with idiopathic angioedema, which means simply that the specific cause of the disease is unknown.

 

Last updated: June 22, 2021

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