C1 esterase inhibitor deficiency
Hereditary angioneurotic oedema is an autosomal dominantly inherited condition caused by a deficiency of C1 esterase inhibitor (1).
C1 esterase inhibitor is a protein which is produced mainly in the liver and to some extent by activated Monocytes and other cell types. C1 esterase inhibitor is the main regulator in the activation of
- complement system
- contact system (kallikrein-kinin system)
- coagulation cascade, fibrinolytic pathway (to a lesser extent) (2), (3)
In the presence of decreased C1 esterase inhibitor,
- inappropriate activation of compliment pathway
- increase in kallikrein production (leading to bradykinin formation which is a vascular permeability factor) occurs (2), (3).
Dysregulation of both the complement and contact systems is considered to be the main pathogenic mechanism of hereditary angioedema (3).
Clinically the patient suffers oedema of the skin and mucosal surfaces. Fatalities may occur if the airway is compromised.
Hereditary angioneurotic oedema affects about one in 50,000 individuals in any race (4):
- inherited in an autosomal dominant manner
- the frequency and severity of symptoms varies; affected individuals may have few, or no symptoms
- acquired forms of C1 inhibitor deficiency
- may result from autoantibody binding of C1 inhibitor, or depletion of C1 inhibitor due to C1 activation by paraprotein
- investigations typically show reduced levels of complement C4 and may reveal low levels of C1 inhibitor and the presence of a paraprotein
- 1. Tarzi M.D et al. An evaluation of tests used for the diagnosis and monitoring of C1 inhibitor deficiency: normal serum C4 does not exclude hereditary angio-oedema. Clin Exp Immunol. 2007; 149(3): 513-516
- 2. Davis A.E. New treatments addressing the pathophysiology of hereditary angioedema. Clin Mol Allergy. 2008; 6:2
- 3. Gompels M.M et al. C1 inhibitor deficiency: consensus document. Clin Exp Immunol. 2005; 139(3): 379-394
- 4. Zuraw B.L. Hereditary angioedema. NEJM 2008: 359:1027-1036
- 5. Powell RJ et al; British Society for Allergy and Clinical Immunology (BSACI). BSACI guidelines for the management of chronic urticaria and angio-oedema.Clin Exp Allergy. 2007 May;37(5):631-50.
Last reviewed 12/2019