title: Diagnosis, Course, and Management of Angioedema in Patients With Acquired C1-Inhibitor Deficiency.
abstract: BACKGROUND
  Acquired angioedema due to C1-inhibitor deficiency (C1-INH-AAE) is a rare disease with no prevalence data or approved therapies.
  
  
  OBJECTIVE
  To report data on patients with C1-INH-AAE followed at Angioedema Center, Milan (from 1976 to 2015).
  
  
  METHODS
  Diagnostic criteria included history of recurrent angioedema without wheals; decreased C1-INH antigen levels and/or functional activity of C1-INH and C4 antigen less than 50% of normal; late symptom onset (>40 years); no family history of angioedema and C1-INH deficiency.
  
  
  RESULTS
  In total, 77 patients (58% females; median age, 70 years) were diagnosed with C1-INH-AAE and 675 patients with hereditary angioedema due to C1-INH deficiency (C1-INH-HAE) (1 patient with C1-INH-AAE/8.8 patients with C1-INH-HAE). Median age at diagnosis was 64 years. Median time between symptom onset and diagnosis was 2 years. Sixteen patients (21%) died since diagnosis, including 1 because of laryngeal edema. Angioedema of the face was most common (N = 63 [82%]), followed by abdomen (N = 51 [66%]), peripheries (N = 50 [65%]), and oral mucosa and/or glottis (N = 42 [55%]). Forty-eight of 71 patients (68%) had autoantibodies to C1-INH. In total, 56 patients (70%) used on-demand treatment for angioedema including intravenous pdC1-INH 2000 U (Berinert, CSL Behring, Marburg, Germany) (N = 49) and/or subcutaneous icatibant 30 mg (Firazyr, Shire; Milano, Italy) (N = 27). Eventually, 8 of 49 patients receiving pdC1-INH became nonresponsive; all had autoantibodies. Thirty-four patients received long-term prophylaxis with tranexamic acid (effective in 29) and 20 with androgens (effective in 8).
  
  
  CONCLUSIONS
  The incidence of C1-INH-AAE was 1 for every 8.8 patients with C1-INH-HAE. Thirty percent of the deaths were related to the disease. Treatments approved for C1-INH-HAE are effective in C1-INH-AAE, although with minimal differences.
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy. Electronic address: andrea.zanichelli@unimi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanichelli
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy.
authors.forename: Giulia Maria
authors.initials: GM
authors.lastname: Azin
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy.
authors.forename: Maddalena Alessandra
authors.initials: MA
authors.lastname: Wu
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Suffritti
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Maggioni
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Caccia
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Perego
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy.
authors.forename: Romualdo
authors.initials: R
authors.lastname: Vacchini
authors.affiliation: Department of Biomedical and Clinical Sciences, Luigi Sacco Hospital, University of Milan, Milan, Italy; ASST Fatebenefratelli Sacco, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cicardi
mesh_terms: D017668:Age of Onset; D000368:Aged; D000728:Androgens / Q000627:therapeutic use; D000799:Angioedema / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D054179:Angioedemas, Hereditary / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D001323:Autoantibodies / Q000097:blood; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D050718:Complement C1 Inhibitor Protein / Q000235:genetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D014148:Tranexamic Acid / Q000627:therapeutic use
chemical_list: D000728:Androgens; D001323:Autoantibodies; D050718:Complement C1 Inhibitor Protein; D014148:Tranexamic Acid; C065679:icatibant; D001920:Bradykinin
keywords: Acquired angioedema; C1-INH deficiency; Diagnosis; Icatibant; Plasma-derived C1-inhibitor; Prevalence; Treatment