title: Misdiagnosis trends in patients with hereditary angioedema from the real-world clinical setting.
abstract: Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE) causes swelling in the skin and upper airways and pain in the abdomen because of mucosal swelling. C1-INH-HAE is frequently misdiagnosed, leading to delays in diagnosis, inadequate treatment, and unnecessary procedures.
  
  
  
  To evaluate the history of misdiagnosis in patients participating in the Icatibant Outcome Survey (IOS).
  
  
  
  The IOS is an observational study in which safety and effectiveness of icatibant have been evaluated since 2009. As part of the IOS, patients record any misdiagnoses received before being diagnosed as having C1-INH-HAE.
  
  
  
  In January 2016, a total of 418 of 633 IOS patients with C1-INH-HAE type I or II had provided misdiagnosis data. Of these, 185 of 418 (44.3%) received 1 or more prior misdiagnoses. The most common misdiagnoses were allergic angioedema (103 of 185) and appendicitis (50 of 185). A variety of other misdiagnoses were reported, including a substantial number of gastrointestinal disorders (excluding appendicitis). Misdiagnosis rates were similar between males (41.1%) and females (46.5%) and between C1-INH-HAE type I (43.7%) and type II (51.6%). Patients with family members diagnosed as having C1-INH-HAE were significantly less likely to be misdiagnosed than patients without a family history (140 of 366 [41.7%] vs 38 of 58 [65.5%], respectively; P = .001). Patients with a prior misdiagnosis had longer median delay to C1-INH-HAE diagnosis (13.3 years) than patients without (1.7 years; P < .001).
  
  
  
  From this large database, approximately 50% of patients with C1-INH-HAE type I or II have previously had their conditions misdiagnosed, most commonly as allergic angioedema or appendicitis. Misdiagnosis results in marked delays in receiving the correct diagnosis, during which time patients cannot access effective, lifesaving treatment.
  
  
  
  ClinicalTrials.gov: NCT01034969.
authors.affiliation: Department of Biomedical and Clinical Sciences Luigi Sacco, University of Milan, ASST Fatebenefratelli Sacco, Milan, Italy. Electronic address: andrea.zanichelli@unimi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanichelli
authors.affiliation: Department of Immunology, Barts Health NHS Trust, London, United Kingdom.
authors.forename: Hilary J
authors.initials: HJ
authors.lastname: Longhurst
authors.affiliation: Department of Dermatology and Allergy, Allergie-Centrum-Charité, Charité-Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Maurer
authors.affiliation: National Reference Centre for Angioedema, Internal Medicine Department, Grenoble University Hospital, Grenoble, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Bouillet
authors.affiliation: Department of Dermatology and Venereology, Medical University of Graz, Graz, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Aberer
authors.affiliation: Shire, Zug, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fabien
authors.affiliation: Shire, Zug, Switzerland.
authors.forename: Irmgard
authors.initials: I
authors.lastname: Andresen
authors.affiliation: Allergy Department, Hospital La Paz Institute for Health Research, Biomedical Research Network on Rare Diseases (CIBERER, U754), Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Caballero
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054179:Angioedemas, Hereditary / Q000175:diagnosis*; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001920:Bradykinin / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D003951:Diagnostic Errors / Q000639:trends*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; C065679:icatibant; D001920:Bradykinin