Angioedema Diagnosis

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 (acute allergic angioedema), as a response to certain medications (non-allergic angioedema), or be genetic (hereditary angioedema), the results of a malfunctioning immune system (acquired angioedema), or appear without a known cause (idiopathic angioedema).

The disease is similar to hives or urticaria, but while hives are swelling in the upper layers of the skin (the epidermis and dermis), angioedema is swelling in layers below the skin (the subcutaneous and submucosal layers). Angioedema and hives can occur independently or at the same time.

To diagnose the condition, the doctor will try to figure out what may have caused the disease, review the symptoms, examine the affected area, carefully analyze the patient’s medical history and perform some tests to distinguish the different types of angioedema.

Allergic Angioedema

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 may perform a skin prick test or a blood test.

Skin prick 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 whether there is a reaction. If the patient is allergic to the substance, a raised, red, itchy bump (wheal) that may look like a mosquito bite will appear within 15 minutes. The test is painless and very safe. Patients should not take antihistamines before the test because they can interfere with the results.

Blood tests

A sample of the patient’s blood is collected and analyzed for specific antibodies that the immune system produces in response to an allergen.

Non-allergic angioedema

Because non-allergic angioedema is induced by renin-angiotensin-aldosterone-system (RAE) blockers and angiotensin-converting enzyme (ACE) inhibitors, the medical history of the patient is usually sufficient to diagnose this type of angioedema.

Hereditary angioedema

Hereditary angioedema can be divided into three types depending on the gene that is affected. Hereditary angioedema types 1 and 2 are caused by mutations in the SERPING1 gene that provides the instructions for making a protein called C1-inhibitor (C1-INH), while hereditary angioedema type 3 is caused by mutations in the F12 gene, which encodes for coagulation factor 12.
Genetic testing is advised when the patient has a family history of hereditary angioedema, or chronic and recurring swelling episodes, intestinal pain, and nausea. Those tests include the search for mutations in the  SERPING1 and the F12 genes.
If mutations occur in a very specific region of the SERPING1 gene called exon 8, which causes a less-effective C1-INH protein to be produced, the patient has hereditary angioedema type 2. If mutations in SERPING1 are found to prevent the production of enough C1-INH, measured by a blood test, the patient has hereditary angioedema type 1.

If no mutations are found in the SERPING1 gene,  the F12 gene is analyzed to see if the patient has hereditary angioedema type 3.

Genetic testing also can help determine a person’s risk of passing the disease to their children.

Acquired angioedema

Acquired angioedema occurs when levels of C1-INH are too low due to antibodies mistakenly targetting it for destruction. In this case, blood tests can be used to evaluate the level of C1-INH and anti-C1-INH antibodies in the blood.

Idiopathic angioedema

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


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