Symptoms of Hereditary Angioedema

Hereditary angioedema (HAE) is characterized by acute, recurrent attacks of localized edema. Edema related to HAE does not respond to epinephrine, antihistamines, or glucocorticoids.3

Once edema begins, it usually develops rapidly over a 24-hour period, and then subsides over several (usually 1 to 5) days. Approximately 30% of patients have more than 12 HAE attacks a year.3

The attacks seem to occur spontaneously and with no apparent cause, but anxiety, stress, trauma, and dental and surgical procedures, as well as viral and bacterial infections, have been cited as potential triggers. Female patients report an increase in attacks during their menstrual cycle. Similarly, ACE inhibitors, oral contraceptives, and female hormonal treatments are known triggers of HAE attacks.3

The age of onset varies, but statistics show that 40% of patients experience HAE symptoms before age 12.3,4 Prodromal symptoms may include erythema marginatum, mood changes, irritability, aggressiveness, anxiety, extreme fatigue, or a tingling sensation of the skin where the swelling will begin.3,5,6

Although it may be uncomfortable and disfiguring, swelling that results from an attack of HAE is non-pruritic. HAE attacks can involve the subcutaneous tissue, abdomen, face, hands, feet, genitalia, and larynx.6

Laryngeal edema: laryngeal attacks of HAE are the most dangerous, since laryngeal, nasal, and sinus edema can compromise the airway. Approximately 50% of all HAE patients experience at least 1 laryngeal attack, and some patients have them repeatedly.6 Mortality rates are estimated at 15%-33%.7

Abdominal edema: HAE-related abdominal edema causes acute abdominal pain, which progresses to nausea, vomiting, and often diarrhea as the attack evolves. Some patients report the onset of nausea minutes, hours, or even a day or two before the onset of a full-blown attack. During an attack, the abdomen is usually tender to the touch. Thus, this type of attack can be difficult to distinguish from a surgical emergency. Yet, even if untreated, symptoms usually subside within several days. Unfortunately, some patients undergo unnecessary surgical procedures before HAE is diagnosed.8

8 simple questions to differentiate HAE from other angioedema

Patients who answer "yes" to all or most of the first 7 questions and "no" to question 8 may require further workup for HAE:

  • Have you had unexplained attacks of swelling in your hands, feet, arms, legs, face, throat, or genitals?
  • Have these swelling attacks occurred on just 1 side of your body, for example, just your left hand or just your right foot?
  • Have you had unexplained attacks of abdominal pain?
  • Have these attacks of swelling or abdominal pain occurred more than once?
  • Has anyone in your family had similar episodes of swelling or abdominal pain?
  • Do you sometimes feel early warning signs (such as fatigue, tingling, nausea, or flu- like symptoms) when an attack begins?
  • Have prescription medications, such as antihistamines (e.g., Benadryl®), epinephrine (e.g., EpiPens®), or steroid shots, provided little relief, if any?
  • When you've had these attacks, have your eyes been watery or itchy?

Download Ask 8 to Differentiate Print out this helpful tool to implement in your practice, provide it as a didactic aid for students, or share it with others who may see patients with undiagnosed HAE.


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Diagnosing HAE

HAE is often misdiagnosed because its symptoms mimic those of other conditions, such as allergic reaction, acute appendicitis, and gallbladder attack. Learn more about diagnosing HAE.

Emergency treatment of HAE

Swelling related to HAE does not respond to commonly used emergency medications, such as epinephrine, antihistamines, or glucocorticoids.
See how to treat an acute attack.