Hereditary angioedema (HAE) is an episodic swelling disease associated with the deficiency of C1-esterase inhibitor.

Epidemiology

• Incidence - defect is rare
• Age - onset usually in childhood
• Gender - equal gender distribution

Risk Factors

• Genetics
  • Autosomal dominant inheritance
• Pressure applied to an extremity
• Stress

Pathophysiology

• C1-esterase inhibitor (C1-INH) is a multispecific, protease inhibitor
• It regulates the enzymes of the complement, coagulation, fibrinolytic and kinin-forming systems, including:
  • C1r and C1s subunits of activated first component of complement
  • Activated Hageman factor (factor XIIa) and Hageman factor fragments
  • Activated plasma thromboplastin antecedent (PTA or factor XIa)
  • Kallikrein (Fletcher factor)
  • Plasmin
• HAE is a quantitative deficiency in C1-INH
  • Types include null (type 1) and dysfunctional (type 2)
  • Deficiency of functionally active component may lead to life-threatening angioedema
  • Rare type 3 defect associated with similar clinical presentation but normal C1-INH levels
• Acquired C1-INH deficiency is a qualitative (functional) deficiency of inhibitor

Clinical Presentation

• Acquired deficiency is associated with a variety of diseases, including lymphoid malignancies
• Transient, but recurrent attacks of non-pruritic, deep-seated swelling of various tissues occur throughout the body
• Gastrointestinal tract often involved, with recurrent episodes of cramping abdominal pain
• Most frequent cause of death is airway obstruction secondary to laryngeal edema

Treatment

• Therapy for congenital defect is androgen treatment which partially corrects the biochemical defect
• Aminocaproic acid may be used for preoperative prophylaxis
• Aminocaproic acid contraindicated in patients with thrombotic tendencies

Diagnosis

• Laboratory testing
  • HAE - C-1-Esterase Inhibitor levels
  • Acquired deficiency - functional assays