Symptoms of Hereditary Angioedema

Hereditary angioedema (HAE) is characterized by acute, recurrent attacks of localized edema. Edema related to HAE (ie, angioedema) does not respond to epinephrine, antihistimines, or glucocorticoids.11

The age of onset varies, but statistics show that almost 40% of patients experience HAE symptoms before age 5. Once an HAE attack begins, angioedema usually develops over a 12- to 36-hour period, then subsides over several (usually 2 to 5) days.11

HAE 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. ACE inhibitors, oral contraceptives, and female hormonal treatments are medications thought to possibly trigger HAE attacks.11

Patients may notice prodromal symptoms preceding or at the onset of an attack. These may include erythema marginatum (non-itching pink “rings” on the trunk or limbs—generally not facial), mood changes, irritability, aggressiveness, anxiety, extreme fatigue, or a tingling sensation of the skin where the swelling will begin.1, 5, 11

Although it may be uncomfortable and disfiguring, swelling that results from an attack of HAE is non-pruritic (ie, does not itch). HAE attacks can involve the subcutaneous tissue, abdomen, face, hands, feet, genitalia, and larynx.1

Laryngeal edema: Because laryngeal, nasal, and sinus edema can compromise the airway, laryngeal HAE attacks are the most dangerous. One survey indicates that laryngeal attacks represent about 1% of HAE attacks, and that about 50% of patients with HAE experience at least one episode involving the larynx.3

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. 5, 12

Seven Simple Questions to Differentiate HAE from Edema and Other Angioedema

Patients who answer "yes" to all or most of the 7 questions 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 at one site 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 anti-allergy medications, such as antihistamines, epineprhine or steroid shots, provided little relief (if any)?

Download and 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