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Hereditary angioedema in Adult
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Hereditary angioedema in Adult

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Contributors: Christine Hunt MD, Sylvia Hsu MD, Lowell A. Goldsmith MD, MPH
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Angioedema is characterized by swelling involving the deep dermis and subcutaneous or submucosa tissue. It is less well-defined than the superficial dermal swelling seen with the wheals of urticaria. The affected areas are nonpruritic. Prodromal symptoms, including a tingling sensation, fatigue, or myalgia, may occur. Angioedema is often idiopathic but may also be a drug reaction, caused by foods, or hereditary. This summary discusses hereditary angioedema.

Hereditary angioedema is characterized by sudden attacks of edema associated with discomfort and pain. It has autosomal dominant inheritance and occurs in approximately 1 in 50 000 to 150 000 individuals. The condition has been reported in all ethnicities / races; it occurs equally in both sexes. Symptoms of the condition typically manifest in the second decade of life, although they may manifest in the first decade.

Swelling can affect any part of the body and multiple sites at once. Areas of angioedema can last for up to 48-72 hours. Commonly affected areas include the face, extremities, genitalia, and trunk as well as the upper respiratory tract and gastrointestinal tract. Most attacks are brought on by trauma or stress. Acute attacks involving upper airway swelling can be life-threatening. Gastrointestinal symptoms of hereditary angioedema are often attributed to more common causes or, when severe, mistaken for acute abdomen. As such, abdominal hereditary angioedema can go undiagnosed or be misdiagnosed for years.

Hereditary angioedema is caused by a deficiency in C1 esterase inhibitor. This deficiency allows for the unregulated activation of proteolytic pathways and the unchecked production of bradykinin. The resulting excess bradykinin production increases vascular permeability, leading to localized edema, and is thought to be the primary cause of swelling in the disorder. The deficiency also causes activation of the C1 complement system, resulting in low serum C4, which is a diagnostic feature.

Inherited or spontaneous (~25%) mutation in one copy of the SERPING gene for C1 esterase inhibitor results in decreased quantity of C1 esterase inhibitor (type I) in about 85% of cases, or reduced function of C1 esterase inhibitor (type II) in about 15% of cases. A more recently described type of hereditary angioedema has been recognized as type III, which is associated with normal quantity and function of C1 esterase inhibitor. It is seen primarily in women with a personal and family history of angioedema but no demonstrable deficiency of C1 esterase inhibitor or other complement abnormality. It is believed that attacks may be caused by defects in other pathways that result in bradykinin overproduction. It appears to be estrogen dependent, since affected women reported onset or worsening of symptoms with the use of estrogen-containing oral contraceptives.

For more information, see OMIM.


D84.1 – Defects in the complement system

82966003 – Hereditary angioedema

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Differential Diagnosis & Pitfalls

Acquired angioedema is typically the result of a lymphoproliferative disorder or autoimmune, neoplastic, or infectious disease. Acquired C1 esterase inhibitor deficiency may result from the formation of autoantibodies against C1 esterase inhibitor or persistent low-level activation of C1q by anti-idiotypic antibodies in patients with B-cell lymphoproliferative disorders. Symptoms of acquired angioedema closely resemble those of hereditary angioedema, but can be differentiated from it by 3 factors:
  1. Acquired angioedema first appears in middle age, whereas hereditary angioedema first manifests in childhood or adolescence.
  2. A family history of angioedema will be absent in acquired angioedema.
  3. Acquired angioedema has low C1q, as opposed to hereditary angioedema, which has normal levels of C1q.
Drug-induced angioedema without wheals is most commonly attributable to angiotensin-converting enzyme (ACE) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs). The most common sites of ACE inhibitor-induced angioedema are the lips, tongue, and face. Rarely, the bowel is also involved. It typically presents in the first 3 months of ACE inhibitor use. Normal serum C4 levels are present.

Allergic angioedema typically accompanies urticaria. It may be pruritic and may represent anaphylaxis. Normal serum C4 levels are present.

Gleich syndrome consists of episodic angioedema with eosinophilia, weight gain, and fever. Normal serum C4 levels are present.

Idiopathic angioedema refers to 3 or more episodes of recurrent angioedema with no apparent cause after comprehensive medical evaluation. Normal serum C4 levels are present.

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Last Updated: 09/08/2017
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Hereditary angioedema in Adult
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Hereditary angioedema : Abdominal pain, Diarrhea, Edema, Eyelid edema, Recurring episodes or relapses, Scrotal edema, Tongue edema, Lip edema
Clinical image of Hereditary angioedema
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