Hereditary angioedema deficiency

Mechanism of Action A testosterone derivative that suppresses the pituitary-ovarian axis by inhibiting the output of pituitary gonadotropins. Causes atrophy of both normal and ectopic endometrial tissue in endometriosis. Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are depressed in fibrocystic breast disease. Inhibits steroid synthesis and binding of steroids to their receptors in breast tissues. Increases serum levels of esterase inhibitor. Therapeutic Effect Produces anovulation and amenorrhea, reduces the production of est rogen, corrects biochemical deficiency as seen in hereditary angioedema. 

Hereditary angioedema, with deficiency of Cj-esterase inhibitor (a complement inhibitor), may not respond to antihistamines or corticosteroid but only to fresh frozen plasma or preferably Cj-inhibitor concentrate. Delay in initiating the treatment may lead to death from laryngeal oedema (try adrenaline (epinephrine) i.m. in severe cases). For long-term prophylaxis an androgen (stanozolol, danazol) can be effective. 

Hereditary angioedema, which is characterized by episodic bouts of swelling of submucosal and subcutaneous tissue, is due to a hereditary abnormality of Cl esterase inhibitor, either a deficiency of the normal enzyme or more rarely the presence of an abnormal enzyme. If Cl esterase inhibitor deficiency can be demonstrated, infusion of concentrated Cl esterase inhibitor is effective in treating the attack. In three studies, no adverse effects were recorded (1-3). 

Acquired Depciency. Levels of C4 are more commonly depressed because of consumption > 60% of individuals with SLE and low C4 levels do not have genetic deficiency. Other disorders associated with consumption and low levels include hereditary angioedema (Cl inhibitor deficiency), autoimmune hemolytic anemia, and autoimmune nephritides. 

Complement deficiencies are associated with several diseases. Alternative pathway deficiencies are rare, but when they exist more than one-half of factor D or properdin-deficient individuals suffer from Neisseria infections of which 75% are fatal. Individuals with deficiencies in the MAC components, e.g., C5, C6, Cl, and C8, are also susceptible to infection with Neisseria. Deficiencies in C1, C4, and C2 are associated with systemic lupus erythematosus and glomerulonephritis. Hereditary angioedema, a disease characterized by recurrent submucosal and subcutaneous edema, is caused by a deficiency in Cl inhibitor. Complexes and interactions similar to those of the complement system are also characteristic of the clotting system (Chapter 36). 

Milk-derived recombinant human C1 inhibitor Pharming is conducting human cHni-cal trials for recombinant human Cl inhibitor (rhCll) in patients suffering hereditary angioedema (HAE), a condition caused by human Cl inhibitor deficiency [58]. Human Cl inhibitor is a 105 kDa protein which has a critical role in the inhibition of proteases involved in fibrinolytic and complement pathways. Deficiency of this inhibitor is manifested in acute swelling of soft tissues in the hands, feet, limbs, face, intestinal tract, mouth, or airway (larynx or trachea). If swelling closes the air-... 

It increases the concentration of Cl esterase inhibitor in patients with hereditary angioedema. This leads to an increased level of the C4 component of complement, which may be deficient in these patients, thus decreasing the number and severity of attacks of this disorder. 

Lumry W, Manning ME, Hurewitz DS, Davis-Lorton M, Fitts D, Kalfus IN, et al. Nanofiltered Cl-esterase inhibitor for the acute management and prevention of hereditary angioedema attacks due to Cl-inhibitor deficiency in children. J Pediatr May 2013 162(5) 1017-22. el-2. 

Anti-thrombin III deficiency (40), ai-antitrypsin deficiency (40), hereditary angioedema (41) Fructose-1,6-diphosphatase deficiency (10) Sucrase-isomaltase deficiency (42) Pyridoxine-responsive anemia (43)... 

Bork K, Witzke G. Long-term prophylaxis with Cl-inhibitor (Cl INH) concentrate in patients with recurrent angioedema caused by hereditary and acquired Cl-inhibitor deficiency. J Allergy Clin Immunol 1989 83(3) 677-82. 

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