Hereditary AngioedemaNext Topic

Hereditary angioedema (HAE) is a rare, autosomal dominant disease characterized by recurrent episodes of subcutaneous and/or submucosal edema of the upper respiratory tract, gastrointestinal tract, arms, legs, hands, feet, genitalia, trunk, and face (Zuraw, 2008). There are several different types of HAE, the majority of which are caused by a quantitative or qualitative deficiency of C1 inhibitor, a member of the serpin family of serine protease inhibitors, and a necessary protein involved in the complement, coagulation and contact cascades (Bernstein 2008).

Normal C1-INH function is required to inhibit critical proteases in each of these cascades (Zuraw, 2008). Several enzymes at various points in the cascade complexes require proteolytic activation and are negatively regulated by the irreversible binding of C1-INH to its substrate. Insufficient amounts of functional C1-INH results in the unregulated proteolytic cleavage and continuous activation of the cascades thereby generating several vasoactive substances, including bradykinin, kallikrein, and plasmin (Figure 1) (Zuraw 2008; Cicardi 1996; Morgan 2010; Davis 2008).

Bradykinin is a physiologically and pharmacologically active nanopeptide that binds to the bradykinin B2 receptor on the surface of endothelial cells. In HAE patients, deficient or non-functional C1-INH results in the intermittent and excessive build-up of bradykinin followed by the increased vascular permeability and associated symptoms of HAE described in Table 1 (Kaplan 2005; Zuraw 2008; Cugno 2009).

Figure 1: Pathogenesis of Hereditary Angioedema

Table 1: Clinical Features of Hereditary Angioedema

Affected Organ System/Domain Features
Respiratory:
  • Nasopharynx
  • Larynx
  • Pharyngeal edema
  • Laryngeal edema
  • Airway constriction
Gastrointestinal system
  • Abdominal pain
  • Nausea
  • Vomiting
  • Diminished bowel sounds
  • Diarrhea
  • Abdominal distension
Skin
  • Erythema marginatum
Muscle, soft tissue
  • Episodic, nonpruritic, nonurticarial, nonpitting edema
  • Edema of the extremities, genitals, and face
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