title: Presentation, diagnosis and treatment of angioedema without wheals: a retrospective analysis of a cohort of 1058 patients.
abstract: BACKGROUND
  The first classification of angioedema without wheals was recently reported and comprises different forms of the disease distinguished by aetiology, mediator of oedema and inheritance.
  
  
  METHODS
  In total, 1725 consecutive patients with angioedema without wheals were examined at our centre between 1993 and 2012. We excluded from the analysis 667 patients because of incomplete data or because angioedema was related to a specific factor.
  
  
  RESULTS
  According to the new classification of angioedema, the 1058 patients included in this analysis were diagnosed with hereditary (HAE; n = 377) or acquired angioedema (AAE; n = 681). The former group included HAE with C1-inhibitor (C1-INH) deficiency (C1-INH-HAE; n = 353) and HAE with normal C1-INH levels (n = 24), of which six had a factor XII mutation (FXII-HAE) and 18 had disease of unknown origin (U-HAE). The AAE group included disease with C1-INH deficiency (C1-INH-AAE; n = 49), AAE related to angiotensin-converting enzyme inhibitor treatment (n = 183), idiopathic histaminergic (IH-AAE; n = 379) and idiopathic nonhistaminergic angioedema (InH-AAE; n = 70). We compared hereditary and AAE with uncertain aetiopathogenesis: the FXII-HAE and U-HAE groups pooled (FXII/U-HAE) versus InH-AAE. The median age at onset of FXII/U-HAE and InH-AAE was 26 and 38 years, respectively. In addition, 56% of patients with FXII/U-HAE and 81% of those with InH-AAE reported more than five attacks per year (median duration of 48 h). The location of angioedema in patients with FXII/U-HAE versus those with InH-AAE was the following: face, 70% versus 86%; tongue, oral cavity or larynx, 55% versus 68%; limbs, 70% versus 56%; and gastrointestinal mucosa, 50% versus 20%. Prophylaxis with tranexamic acid was effective in all six patients with U-HAE and in 37 of 38 with InH-AAE who were started on this treatment.
  
  
  CONCLUSIONS
  Our findings in this cohort of patients with angioedema provide new information on the clinical characteristics, diagnosis and treatment of this disease.
authors.affiliation: Department of Biomedical and Clinical Science "Luigi Sacco", Università degli Studi di Milano, Ospedale Luigi Sacco, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Mansi
authors.forename: A
authors.initials: A
authors.lastname: Zanichelli
authors.forename: A
authors.initials: A
authors.lastname: Coerezza
authors.forename: C
authors.initials: C
authors.lastname: Suffritti
authors.forename: M A
authors.initials: MA
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Vacchini
authors.forename: C
authors.initials: C
authors.lastname: Stieber
authors.forename: S
authors.initials: S
authors.lastname: Cichon
authors.forename: M
authors.initials: M
authors.lastname: Cicardi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000799:Angioedema / Q000175:diagnosis* / Q000209:etiology / Q000628:therapy; D054179:Angioedemas, Hereditary / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects; D002648:Child; D050718:Complement C1 Inhibitor Protein / Q000235:genetics; D005174:Factor XII / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010375:Pedigree; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D050718:Complement C1 Inhibitor Protein; D005174:Factor XII
keywords: C1-inhibitor; FXII mutation; bradykinin; nonhistaminergic angioedema