Reviewed by Flavia Cecilia Lega Hoyte, MD

There are two main subtypes of angioedema: mast-cell mediated and bradykinin-mediated angioedema. 

Mast Cell-Mediated Angioedema

Mast cell-mediated angioedema is more likely to be associated with hives or other symptoms of an allergic reaction. When occurring as an isolated episode, it is termed “acute” (sudden) and is most commonly due to an allergic trigger, although sometimes this trigger is difficult to pinpoint.  When angioedema occurs repeatedly for 6 consecutive weeks or more, it is termed “chronic”. The most common cause of chronic angioedema is idiopathic angioedema, which means that no specific cause can be identified despite a thorough evaluation.

Bradykinin-Mediated Angioedema

Bradykinin-mediated angioedema is more likely to occur without associated symptoms, although flushing or blotchiness of the skin can occur.  It is sometimes the result of a commonly used class of heart and blood pressure medications called ACE inhibitors, which include lisinopril, captopril, and enalapril. Angioedema related to the use of these medications is rare but can happen at any time a person is taking the medicine, even years after he or she has been taking it.

The other types of angioedema that are bradykinin-mediated are hereditary angioedema (HAE) and acquired angioedema (AAE), which are due to decreased amount or function of an enzyme called C1 esterase inhibitor. A familial form of angioedema that occurs in females (estrogen-dependent) is due to mutation in another enzyme called Hageman Factor (Factor XII).  

Clinical History

The most important step in determining what is causing a person’s angioedema is the clinical history, which is a detailed description of the details surrounding the angioedema episodes. Keeping a diary can help you remember these details and sometimes allow for identification of common features from one episode to the next. 

Since angioedema can accompany systemic rheumatologic disorders, it is important to tell your healthcare provider about other symptoms you are having, even if they seem to be unrelated to the angioedema. In addition, you should provide a complete medication list, including all supplements and over-the-counter medications you are taking. These medications can sometimes make angioedema more likely to happen.

There are several laboratory tests that your healthcare provider may want to check after hearing the details of your angioedema episodes. These tests are used to help distinguish between the possible causes of angioedema described above. If an allergic cause is suspected, particularly for acute reactions, your physician might also order allergy skin testing or an allergen challenge.  

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