Treatment of 193 Episodes of Laryngeal Edema With C1 Inhibitor Concentrate in Patients With Hereditary Angioedema

Abstract

HEREDITARY angioedema (HAE), first described clinically by Osler in 1888,¹ is a well-defined autosomal dominant disease (Mendelian Inheritance in Man 106100²) caused by an inherited deficiency of functional C1-esterase inhibitor (C1-INH). Donaldson and Evans³ discovered the defect in 1963. The defective C1-INH gene produces no C1-INH (type I HAE [HAE I]) or a dysfunctional C1-INH (type II HAE [HAE II]). In HAE I, which represents 85% of patients, plasma levels of C1-INH are 5% to 30% of normal values. In HAE II, levels of C1-INH are normal or elevated. Both forms are clinically indistinguishable. Until now, more than 100 different C1 INH gene mutations have been described in HAE, including missense and nonsense mutations, large deletions, and frame-shift and splice-site mutations.^4,5 The exact prevalence of HAE is unknown; current estimates suggest that the disease affects between 1 in 10 000 and 1 in 50 000 persons.⁶ The clinical features of the disease are recurrent transient episodes of skin swelling and intestinal and laryngeal edema. These transient episodes of edema last 2 to 5 days, after which they regress spontaneously. The episodes of intestinal wall edema may be accompanied by transient ascites.⁷ Asphyxiation due to obstruction of the upper airways is the most common cause of death.⁸ Upper airway obstruction is usually due to laryngeal and glottal edema. In some patients, however, laryngeal edema may extend into lower parts of the airway, and some patients may have pulmonary edema also. Since this is rare, we use the term laryngeal edema. The unexpected occurrence of laryngeal edema associated with the risk for asphyxiation is the most important feature of this disease.