Diagnosis and management of angioedema with abdominal involvement: A gastroenterology perspective

Table 1 Molecular mechanisms of angioedema[2,4,5]

Type of AE	Mediator	Mechanism
Allergic AE	Histamine (mast cells)	Allergens react with IgE antibodies on the surface of mast cells, causing degranulation and release of histamine
ACE-I-induced	Bradykinin	ACE-Is prevent the conversion of bradykinin to inactive metabolites, leading to bradykinin accumulation
NSAID-induced AE	Leukotrienes (mast cells)	Inhibition of COX-1 leads to overproduction of vasoactive substances by shunting arachidonic acid metabolism through the lipoxygenase pathway, creating leukotrienes. Vasoactive leukotrienes act on cell-surface receptors to increase vascular permeability and promote inflammation
HAE type 1	Bradykinin	Genetic mutations in the C1 INH gene result in low levels of C1 INH. Major roles of C1 INH include inactivating coagulation factors XIIa, XIIf and XIa; blocking C1 complement autoactivation; and inhibiting activated kallikrein. Removal of these inhibitory actions results in complement activation and elevated bradykinin levels
HAE type 2	Bradykinin	Genetic mutations in the C1 INH gene result in normal levels of C1 INH, but the C1 INH is dysfunctional. Plasma cascades are unregulated in the presence of dysfunctional C1 INH, leading to bradykinin accumulation as in HAE type 1
Inherited AE with normal C1 INH	Bradykinin	Missense mutation in factor XII gene confers a significant increase in the protease activity of each activated factor XII molecule, which increases bradykinin generation. Decreased activity of enzymes such as ACE and aminopeptidase P have also been noted
Acquired AE	Bradykinin	Type 1: Immune complex formation associated with rheumatologic, lymphoproliferative, and neoplastic disorders continuously activate C1, causing C1 INH depletion and bradykinin accumulation
		Type 2: Autoantibodies inactivate C1 INH, leading to bradykinin accumulation
Idiopathic recurrent AE	Unknown	Unknown

AE: Adverse events; ACE-I: Angiotensin converting enzyme inhibitor; HAE: Hereditary angioedema; COX-1: Cyclooxygenase-1; NSAID: Non-steroidal anti-inflammatory drug; C1 INH: C1 esterase inhibitor.