It is a disorder of complement regulation in which C1 esterase inhibitor (C1INH), an inhibitor of spontaneous activation of C1, is lacking. This produces circumscribed, nonpitting subepithelial edema involving the lips, eyelids, tongue, larynx, pharynx, respiratory tract, gastrointestinal tract, renal system, and occasionally the central nervous system.
Angioedema; Hereditary Angioneurotic Edema; HANE Syndrome; C1 Esterase Inhibitor Deficiency; Quincke’s Syndrome.
It is recognized that the original observation of this disorder was provided in 1586 by Marcello Donati. The first description of this medical condition was published by J. L. Milton in 1876. Dr Heinrich Quincke presented the first clinical report in 1882. The term “Hereditary Angio-Neurotic Edema” was suggested by William Osler in 1888, who noticed that some cases had a hereditary basis. The link with C1 esterase inhibitor deficiency was proved in 1963.
There are two types of angioedema that consists of:
Acquired: It is triggered by external conditions either immunologic, nonimmunologic, or idiopathic. It is associated with allergies leading to urticaria that can be provoked by certain medications, particularly ACE inhibitors. It is characterized by repetitive episodes of swelling usually located in the face, lips, tongue, limbs, and genitals. Clinically, individuals consult for severe abdominal pain that results from severe edema of the gastrointestinal mucosa. The presence of edema in the upper respiratory tract may be life-threatening and must be treated immediately with adrenaline.
Hereditary Angioedema (HAE): It is believed inherited as an autosomal dominant pattern and is divided in three forms. Types I and II are caused by mutations in the SERPING1 gene, that causes a decrease in the level of the C1-inhibitor protein (type I HAE) or results in a dysfunction of the same protein (type II HAE). Type III HAE has been linked to mutations in the F12 gene that also affects the coagulation protein factor XII. All forms of HAE lead to abnormal activation of the complement system. Type III is believed inherited as X-linked recessive pattern and affects mainly women. If HAE involves the upper airway and the larynx, it can be life-threatening.
Estimated incidence of the hereditary form is 1:50,000 to 150,000 live births in the United States. Angioedema accounts for 80,000 to 115,000 admissions to emergency departments annually. It represents the number one allergic reaction leading to hospitalization in the United States.
In the hereditary form, transmission is via an autosomal dominant pattern, with males affected twice as often as females. Human C1 inhibitor gene is localized to chromosome 11q11-q13.1. In more than 20% of patients with hereditary angioedema, the mutations are de novo; thus there is no family history of the disease.