Complement C1 Esterase Inhibitor

The more common form (85% of patients) of hereditary angioneurotic edema is due to an absolute decrease in the amount of C₁ esterase inhibitor. A less common form (15% of patients) is due to a functional defect where quantitative levels may be normal. Both abnormalities must be tested for due to the potential life-threatening nature of the illness.

In addition to decreased C₁ esterase inhibitor in the serum of patients with hereditary angioneurotic edema, a unique polypeptide kinin is increased in plasma from C₁ esterase inhibitor deficient patient during attacks of swelling. Danazol, a synthetic androgenic inhibitor of gonadotropin release, with little virilizing potential, decreases the number of clinical attacks in cases of hereditary angioneurotic edema. Patients with attacks of hereditary angioneurotic edema also have low total complement, C₄ and C₂. Consequently, measurement of serum C₄ is an often used test. Hereditary angioneurotic edema is transmitted as an autosomal dominant trait. Heterozygotes also show decreased levels of C₁ esterase inhibitor. During acute attacks of the disease, complement factors C₄ and C₂ can be markedly reduced, but C₁ and C₃ are normal. The initiating stimulus of clinical attacks is often unknown.

Angioedema may also be an acquired illness. The acquired form includes nonhereditary C₁ esterase deficiency; drug induced, allergic, and idiopathic forms, angioedema associated with autoimmune disease, especially with systemic lupus erythematosus and hypereosinophilia; angioedema occasionally associated with malignancy; and angioedema caused by physical stimuli. Angioedema has occasionally been known to precede development of lymphoproliferative disorders.