Idiopathic angioedema is characterized by local edema involving the deeper dermis and subcutaneous tissue and triggered by the release of mediators that cause vasodilatation and increased capillary permeability. [1] Cicardi M. Bergamaschini L. Zingale L.C. Gioffré D. Agostini A. Idiopathic nonhistaminergic angioedema. Am J Med. 1999; 106: 611-615 Abstract Full Text Full Text PDF Scopus (87) Google Scholar Acute attacks most commonly occur in the periphery, but patients also may experience laryngeal or bowel angioedema. Idiopathic angioedema shares some clinical features with hereditary angioedema (HAE) types I and II and is physiologically distinct in that patients with idiopathic angioedema exhibit normal C4 and C1 esterase inhibitor levels and function. [2] Kaplan A.P. Enzymatic pathways in the pathogenesis of hereditary angioedema: The role of C1 inhibitor therapy. J Allergy Clin Immunol. 2010; 126: 918-925 Abstract Full Text Full Text PDF PubMed Scopus (89) Google Scholar Patients with type III HAE also exhibit normal C4 levels with normal quality and quantity of C1 esterase inhibitor; however, guidelines published by an international expert panel in 2012 on hereditary angioedema with normal C1 inhibitor function require that these patients have a family history significant for angioedema to establish a diagnosis of type III HAE. [3] Zuraw B. Hereditary angioedema with normal C1 inhibitor function: consensus of an international expert panel. Allergy Asthma Proc. 2012; (Dec 13. [Epub ahead of print]) Google Scholar A subpopulation of patients have a missense mutation in the factor XII gene, [4] Bork K. Hereditary angioedema with normal C1 inhibitor activity including hereditary angioedema with coagulation factor XII gene mutations. Immunol Allergy Clin North Am. 2006; 26: 709-724 Abstract Full Text Full Text PDF PubMed Scopus (69) Google Scholar which the 2012 consensus requires if family history is not present for the diagnosis of type III HAE. If no other causative factors are elucidated, patients with angioedema who do not qualify as HAE according to the 2012 Consensus guidelines are classified as having idiopathic angioedema.