title: Pathophysiology of hereditary angioedema.
abstract: BACKGROUND
  Laryngeal angioedema may be associated with significant morbidity and even mortality. Because of the potential severity of attacks, both allergists and otolaryngologists must be knowledgeable about the recognition and treatment of laryngeal angioedema. This study  describes the clinical characteristics and pathophysiology of bradykinin-mediated angioedema.
  
  
  METHODS
  A literature review was conducted concerning the clinical characteristics and pathophysiology of types I and II hereditary angioedema (HAE), type III HAE, acquired C1  inhibitor (C1INH) deficiency, and angiotensin-converting enzyme (ACE) inhibitor-associated angioedema.
  
  
  RESULTS
  The diagnosis of type I/II HAE is relatively straightforward as long as the clinician maintains a high index of suspicion. Mutations in the SERPING1 gene  result in decreased secretion of functional C1INH and episodic activation of plasma kallikrein and Hageman factor (FXII) of the plasma contact system with cleavage of high molecular weight kininogen and generation of bradykinin. In contrast, there are no unequivocal criteria for making a diagnosis  of type III HAE, although a minority of these patients may have a mutation in the factor XII gene. Angioedema attacks and mediator of swelling in acquired C1INH deficiency are similar to those in type I or II HAE; however, it occurs on a sporadic basis because of excessive consumption of C1INH  in patients who are middle aged or older. ACE inhibitor-associated angioedema should always be considered in any patient taking an ACE inhibitor who experiences angioedema. ACE is a kininase, which when inhibited is thought to result in increased bradykinin levels. Bradykinin acts on  vascular endothelial cells to enhance vascular permeability.
  
  
  CONCLUSIONS
  Laryngeal swelling is not infrequently encountered in bradykinin-mediated angioedema. Novel therapies are becoming available that for the first time provide effective treatment for bradykinin-mediated  angioedema. Because the characteristics and treatment of these angioedemas are quite distinct from each other and from histamine-mediated angioedema, it is crucial that the physician be able to recognize and distinguish these swelling disorders.
authors.affiliation: Department of Medicine, University of California, San Diego, and San Diego Veteran's Affairs Medical Center, La Jolla, California, USA. bzuraw@ucsd.edu
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Zuraw
authors.forename: Sandra C
authors.initials: SC
authors.lastname: Christiansen
mesh_terms: D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000235:genetics; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000378:metabolism; D001920:Bradykinin / Q000009:adverse effects / Q000378:metabolism / Q000627:therapeutic use; D002199:Capillary Permeability; D003174:Complement C1 Inactivator Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D050718:Complement C1 Inhibitor Protein; D003937:Diagnosis, Differential; D006801:Humans; D007819:Laryngeal Edema / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation / Q000235:genetics
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D003174:Complement C1 Inactivator Proteins; D050718:Complement C1 Inhibitor Protein; C469952:SERPING1 protein, human; D001920:Bradykinin