Hereditary angioedema

Disease Overview

Hereditary angioedema (HAE) is a disease characterized by recurrent episodes (also called attacks) of severe swelling of the skin and mucous membranes.[14820] The age at which attacks begin varies, but most people have their first one in childhood or adolescence.[14821] The frequency of attacks usually increases after puberty. Attacks most often affect 3 parts of the body:[14821][14822]

• Skin – the most common sites are the face (such as the lips and eyes), hands, arms, legs, genitals, and buttocks. Skin swelling can cause pain, dysfunction, and disfigurement, although it is generally not dangerous and is temporary.
• Gastrointestinal tract – the stomach, intestines, bladder, and/or urethra may be involved. This may cause symptoms such as nausea, vomiting, diarrhea, and abdominal pain.
• Upper airway (such as the larynx and tongue) – this can cause upper airway obstruction and may be life-threatening. The majority of attacks affecting the airway resolve before complete airway obstruction.

Attacks may involve one area of the body at a time, or they may involve a combination of areas. They always go away on their own but last from 2 to 4 days. While people with HAE have reported various triggers of attacks, emotional stress, physical stress, and dental procedures are the most commonly reported triggers.[14821]

There are several types of HAE.[14820] Types I and II are caused by mutations in the C1NH gene (also called the SERPING1 gene), which provides instructions for making the C1 inhibitor protein.[14820][14822] Type I is due to deficiency of C1 inhibitor, and type II is due to dysfunction of C1 inhibitor.[14820] These types are also characterized by abnormal complement protein levels. Inheritance of types I and II is autosomal dominant, but not all people with a SERPING1 gene mutation will develop symptoms of HAE. A third type is called HAE with normal C1 inhibitor. This type is characterized by normal C1 inhibitor and normal complement protein levels, and usually begins in adulthood.[14823] While some cases of type III are due to mutations in the F12 gene, in other cases the cause is not yet known.[14820][2938] The inheritance of this form is also thought to be autosomal dominant.[14823]

Management of HAE involves treatment of sudden (acute) attacks and preventing attacks (prophylaxis).[14822] Treatment for acute attacks in types I and II includes replacement with C1 inhibitor concentrates, a kallikrein inhibitor, or fresh-frozen plasma (by infusion).[14822] Sudden attacks involving the upper airway may involve intubation if stridor or signs of respiratory distress are present.[14823] HAE with normal C1 inhibitor levels is treated similarly, however C1 inhibitor infusion is not effective. Prophylaxis may involve regular injections of C1 inhibitor concentrates, long-term androgen (male hormone) therapy, or antifibrinolytics.[14822][14824]

The long-term outlook varies depending on the frequency and location of attacks, and the severity of attacks in each person. Attacks generally continue throughout life, but the frequency of attacks can be significantly reduced with therapy.[14821]

Synonyms

• HAE
• Hereditary angioneurotic edema
• HANE
• Deficiency of C1 esterase inhibitor
• Hereditary angioedema type 1
• Angioedema, hereditary