Hereditary angioedema

  • Definition
    • Hereditary angioedema is a rare but serious problem with the immune system. The problem is passed down through families. It causes swelling, particularly of the face and airways, and abdominal cramping.

  • Alternative Names
    • Quincke disease; HAE- Hereditary angioedema; Kallikrein inhibitor-HAE: bradykinin receptor antagonist-HAE; C1-inhibitors-HAE; Hives-HAE

  • Causes
    • Angioedema is swelling that is similar to hives, but the swelling is under the skin instead of on the surface.

      Hereditary angioedema (HAE) is caused by a low level or improper function of a protein called the C1 inhibitor. With HAE, the blood vessels are affected. An HAE attack can result in rapid swelling of the hands, feet, limbs, face, intestinal tract, larynx (voicebox), or trachea (windpipe).

      Attacks of swelling can become more severe in late childhood and adolescence.

      There is usually a family history of the condition. But relatives may be unaware of previous cases, which may have been reported as an unexpected, sudden, and premature death of a parent, aunt, uncle, or grandparent.

      Dental procedures, sickness (including colds and the flu), and surgery may trigger HAE attacks.

  • Symptoms
    • Symptoms include:

      • Airway blockage -- involves throat swelling and sudden hoarseness
      • Repeat episodes of abdominal cramping without obvious cause
      • Swelling in the hands, arms, legs, lips, eyes, tongue, throat, or genitals
      • Swelling of the intestines -- can be severe and lead to abdominal cramping, vomiting, dehydration, diarrhea, pain, and occasionally shock
      • A non-itchy, red rash
  • Exams and Tests
    • Blood tests (ideally done during an episode):

  • Treatment
    • Antihistamines and other treatments used for angioedema do not work well for HAE. Epinephrine should be used in life-threatening reactions. There are a number of newer FDA-approved treatments for HAE.

      Some are given through a vein (IV) and can be used at home. Others are given as an injection under the skin by the patient.

      • Choice of which agent may be based on the age of patient and where the symptoms occur.
      • Names of new drugs for treatment of HAE include cinryze, berinert, ruconest, kalbitor, and firazyr.

      Before these newer medicines became available, androgen medications, such as danazol, were use to reduce the frequency and severity of attacks. These medicines help the body make more C1 inhibitor. However, many women have serious side effects from these medicines. They can also not be used in children.

      Once an attack occurs, treatment includes pain relief and fluids given through a vein by an intravenous (IV) line.

      Helicobacter pylori, a type of bacteria found in the stomach, can trigger abdominal attacks. Antibiotics to treat the bacteria help decrease abdominal attacks.

  • Outlook (Prognosis)
    • Hereditary angioedema can be life threatening and treatment options are limited. How well a person does depends on the specific symptoms.

  • Possible Complications
    • Swelling of the airways may be deadly.

  • When to Contact a Medical Professional
    • Call or visit your health care provider if you are considering having children and have a family history of this condition. Also call if you have symptoms of hereditary angioedema.

      Swelling of the airway is a life-threatening emergency. If you are having difficulty breathing due to swelling, seek immediate medical attention.

  • Prevention
    • Genetic counseling may be helpful for prospective parents with a family history of hereditary angioedema.

  • References
    • Dreskin SC. Urticaria and angioedema. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine. 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 260.

      Riedl MA. Creating a comprehensive treatment plan for hereditary angioedema. Immunol Allergy Clin N Am. 2013;33:471-85. PMID: 24176212

      Zuraw BL, Christiansen SC. Hereditary angioedema and bradykinin-mediated angioedema. In: Adkinson NF, Bochner BS, Burks AW, eds. Middleton's Allergy: Principles and Practice. 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 37.