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Hereditary angioedema in childhood: an approach to management.
Paediatr Drugs 2010; 12(4):257-68PD

Abstract

Hereditary angioedema (HAE) is an inherited disorder characterized by recurrent, circumscribed, non-pitting, non-pruritic, and rather painful subepithelial swelling of sudden onset, which fades during the course of 48-72 hours, but can persist for up to 1 week. Lesions can be solitary or multiple, and primarily involve the extremities, larynx, face, esophagus, and bowel wall. Patients with HAE experience angioedema because of a defective control of the plasma kinin-forming cascade that is activated through contact with negatively charged endothelial macromolecules leading to binding and auto-activation of coagulation factor XII, activation of prekallikrein to kallikrein by factor XIIa, and cleavage of high-molecular-weight kininogen by kallikrein to release the highly potent vasodilator bradykinin. Three forms of HAE have currently been described. Type I and type II HAE are rare autosomal dominant diseases due to mutations in the C1-inhibitor gene (SERPING1). C1-inhibitor mutations that cause type I HAE occur throughout the gene and result in truncated or misfolded proteins with a deficiency in the levels of antigenic and functional C1-inhibitor. Mutations that cause type II HAE generally involve exon 8 at or adjacent to the active site, resulting in an antigenically intact but dysfunctional mutant protein. In contrast, type III HAE (also called estrogen-dependent HAE) is characterized by normal C1-inhibitor activity. The diagnosis of HAE is suggested by a positive family history, the absence of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colic, and episodes of laryngeal edema. Estrogens may exacerbate attacks, and in some patients attacks are precipitated by trauma, inflammation, or psychological stress. For type I and type II HAE, diminished C4 concentrations are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-inhibitor antigen (type I) in most kindreds, but some kindreds have an antigenically intact but dysfunctional protein (type II) and require a functional assay to establish the diagnosis. There are no particular laboratory findings in type III HAE. Prophylactic administration of either 17alpha-alkylated androgens or synthetic antifibrinolytic agents has proven useful in reducing the frequency or severity of attacks. Plasma-derived C1-inhibitor concentrate, recombinant C1-inhibitor, ecallantide (DX88; a plasma kallikrein inhibitor) and icatibant (a bradykinin B(2) receptor antagonist) have demonstrated significant efficacy in the treatment of acute attacks, whereas the C1-inhibitor concentrate has also provided a significant benefit as long-term prophylaxis. However, these drugs are not licensed in all countries and are not always readily available.

Authors+Show Affiliations

Department of Immunology, Allergology and Rheumatology, University Hospital Antwerp, Antwerp University, Universiteitsplein 1, Antwerp, Belgium.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

20593909

Citation

Ebo, Didier G., et al. "Hereditary Angioedema in Childhood: an Approach to Management." Paediatric Drugs, vol. 12, no. 4, 2010, pp. 257-68.
Ebo DG, Verweij MM, De Knop KJ, et al. Hereditary angioedema in childhood: an approach to management. Paediatr Drugs. 2010;12(4):257-68.
Ebo, D. G., Verweij, M. M., De Knop, K. J., Hagendorens, M. M., Bridts, C. H., De Clerck, L. S., & Stevens, W. J. (2010). Hereditary angioedema in childhood: an approach to management. Paediatric Drugs, 12(4), pp. 257-68. doi:10.2165/11532590-000000000-00000.
Ebo DG, et al. Hereditary Angioedema in Childhood: an Approach to Management. Paediatr Drugs. 2010 Aug 1;12(4):257-68. PubMed PMID: 20593909.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Hereditary angioedema in childhood: an approach to management. AU - Ebo,Didier G, AU - Verweij,Marjoke M, AU - De Knop,Kathleen J, AU - Hagendorens,Margo M, AU - Bridts,Chris H, AU - De Clerck,Luc S, AU - Stevens,Wim J, PY - 2010/7/3/entrez PY - 2010/7/3/pubmed PY - 2011/1/13/medline SP - 257 EP - 68 JF - Paediatric drugs JO - Paediatr Drugs VL - 12 IS - 4 N2 - Hereditary angioedema (HAE) is an inherited disorder characterized by recurrent, circumscribed, non-pitting, non-pruritic, and rather painful subepithelial swelling of sudden onset, which fades during the course of 48-72 hours, but can persist for up to 1 week. Lesions can be solitary or multiple, and primarily involve the extremities, larynx, face, esophagus, and bowel wall. Patients with HAE experience angioedema because of a defective control of the plasma kinin-forming cascade that is activated through contact with negatively charged endothelial macromolecules leading to binding and auto-activation of coagulation factor XII, activation of prekallikrein to kallikrein by factor XIIa, and cleavage of high-molecular-weight kininogen by kallikrein to release the highly potent vasodilator bradykinin. Three forms of HAE have currently been described. Type I and type II HAE are rare autosomal dominant diseases due to mutations in the C1-inhibitor gene (SERPING1). C1-inhibitor mutations that cause type I HAE occur throughout the gene and result in truncated or misfolded proteins with a deficiency in the levels of antigenic and functional C1-inhibitor. Mutations that cause type II HAE generally involve exon 8 at or adjacent to the active site, resulting in an antigenically intact but dysfunctional mutant protein. In contrast, type III HAE (also called estrogen-dependent HAE) is characterized by normal C1-inhibitor activity. The diagnosis of HAE is suggested by a positive family history, the absence of accompanying pruritus or urticaria, the presence of recurrent gastrointestinal attacks of colic, and episodes of laryngeal edema. Estrogens may exacerbate attacks, and in some patients attacks are precipitated by trauma, inflammation, or psychological stress. For type I and type II HAE, diminished C4 concentrations are highly suggestive for the diagnosis. Further laboratory diagnosis depends on demonstrating a deficiency of C1-inhibitor antigen (type I) in most kindreds, but some kindreds have an antigenically intact but dysfunctional protein (type II) and require a functional assay to establish the diagnosis. There are no particular laboratory findings in type III HAE. Prophylactic administration of either 17alpha-alkylated androgens or synthetic antifibrinolytic agents has proven useful in reducing the frequency or severity of attacks. Plasma-derived C1-inhibitor concentrate, recombinant C1-inhibitor, ecallantide (DX88; a plasma kallikrein inhibitor) and icatibant (a bradykinin B(2) receptor antagonist) have demonstrated significant efficacy in the treatment of acute attacks, whereas the C1-inhibitor concentrate has also provided a significant benefit as long-term prophylaxis. However, these drugs are not licensed in all countries and are not always readily available. SN - 1179-2019 UR - https://www.unboundmedicine.com/medline/citation/20593909/Hereditary_angioedema_in_childhood:_an_approach_to_management_ L2 - https://dx.doi.org/10.2165/11532590-000000000-00000 DB - PRIME DP - Unbound Medicine ER -