title: A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in Italy.
abstract: BACKGROUND
  Hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE type I) or dysfunction (C1-INH-HAE type II) is a rare disease characterized by recurrent episodes of edema with an estimated frequency of 1:50,000 in the global population without racial or gender differences. In this study we present the results of a nationwide survey of C1-INH-HAE patients referring to 17 Italian centers, the Italian network for C1-INH-HAE, ITACA.
  
  
  METHODS
  Italian patients diagnosed with C1-INH-HAE from 1973 to 2013 were included in the study. Diagnosis of C1-INH-HAE was based on family and/or personal history of recurrent angioedema without urticaria and on antigenic and/or functional C1-INH deficiency.
  
  
  RESULTS
  983 patients (53% female) from 376 unrelated families were included in this survey. Since 1973, 63 (6%) patients diagnosed with C1-INH-HAE died and data from 3 patients were missing when analysis was performed. Accordingly, the minimum prevalence of HAE in Italy in 2013 is 920:59,394,000 inhabitants, equivalent to 1:64,935. Compared to the general population, patients are less represented in the early and late decades of life: men start reducing after the 5(th) decade and women after the 6(th). Median age of patients is 45 (IQ 28-57), median age at diagnosis is 26 years (IQ 13-41). C1-INH-HAE type 1 are 87%, with median age at diagnosis of 25 (13-40); type 2 are 13% with median age at diagnosis of 31 (IQ 16-49). Functional C1INH is ≤50% in 99% of patients. Antigen C1INH is ≤50% in 99% of type 1. C4 is ≤50% in 96% of patients. The chance of having C1-INH-HAE with C4 plasma levels >50% is < 0.05.
  
  
  CONCLUSIONS
  This nationwide survey of C1-INH-HAE provides for Italy a prevalence of 1:64,935. C1-INH-HAE patients listed in our database have a shorter life expectancy than the general population. An increased awareness of the disease is needed to reduce this discrepancy. Measurement of C4 antigen can exclude diagnosis of C1-INH-HAE with an accuracy > 95%. This parameter should be therefore considered for initial screening in differential diagnosis of angioedema.
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università degli Studi di Milano, Ospedale Luigi Sacco, Milano, Italy. andrea.zanichelli@unimi.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: Zanichelli
authors.affiliation: U.O.C. Patologia Clinica, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy. francescoarcoleo@alice.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Arcoleo
authors.affiliation: Struttura complessa di Medicina Interna e Allergologia e Immunologia Clinica, AUO Cagliari, Cagliari, Italy. mpbarca@tiscali.it.
authors.forename: Maria Pina
authors.initials: MP
authors.lastname: Barca
authors.affiliation: Struttura Complessa Medicina Interna, Ambulatorio di Allergologia, Ospedale U. Parini, Aosta, Italy. PBORRELLI@ausl.vda.it.
authors.forename: Paolo
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authors.lastname: Borrelli
authors.affiliation: Centro Interdipartimentale di Ricerca in Scienze Immunologiche di Base e Cliniche, A.O.U. Federico II, Naples, Italy. bovamaria@virgilio.it.
authors.forename: Maria
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authors.affiliation: Dipartimento di Medicina, Università degli Studi di Padova, Padova, Italy. mcancian@unipd.it.
authors.forename: Mauro
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authors.lastname: Cancian
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche "Luigi Sacco", Università degli Studi di Milano, Ospedale Luigi Sacco, Milano, Italy. marco.cicardi@unimi.it.
authors.forename: Marco
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authors.affiliation: U.O.C. Patologia Clinica, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy. enrico.cillari@tiscali.it.
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authors.lastname: Cillari
authors.affiliation: UOC Ginecologia ed Ostetricia II Azienda Ospedaliera San Giovanni-Addolorata Roma, Rome, Italy. caterina.decarolis@fastwebnet.it.
authors.forename: Caterina
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authors.lastname: De Carolis
authors.affiliation: Unità Operativa di Allergologia, Presidio ospedaliero di Civitanova Marche, Civitanova Marche, Italy. fotone_it@yahoo.it.
authors.forename: Tiziana
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authors.lastname: De Pasquale
authors.affiliation: UO Immuno-Allergologia, Dipartimento di Medicina Interna, Azienda Ospedaliera Universitaria Pisana (AOUP), Pisa, Italy. i.delcorso@med.unipi.it.
authors.forename: Isabella
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authors.affiliation: U.O.D.S. di Allergologia Clinica AUSL, Pescara, Italy. allergologia.aslpe@tin.it.
authors.forename: Paola Cesinaro
authors.initials: PC
authors.lastname: Di Rocco
authors.affiliation: UOC Reumatologia, Policlinico Tor Vergata, Roma, Italy. grnmdm76@gmail.com.
authors.forename: Maria Domenica
authors.initials: MD
authors.lastname: Guarino
authors.affiliation: Centro di Ricerca, Trasferimento ed Alta Formazione Denothe, Università degli Studi di Firenze, Firenze, Italy. massaroilaria81@gmail.com.
authors.forename: Ilaria
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authors.lastname: Minale
authors.affiliation: Unità Operativa Nefrologia Universitaria Azienda Ospedaliero-Universitaria "Consorziale Policlinico" Bari, Bari, Italy. v.montinaro@nephro.uniba.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Montinaro
authors.affiliation: Dipartimento di Scienze mediche e pediatriche, Medicina Interna "A Francaviglia", Policlinico universitario di Catania, Catania, Italy. sergio.neri4@tin.it.
authors.forename: Sergio
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authors.lastname: Neri
authors.affiliation: UOC Reumatologia, Policlinico Tor Vergata, Roma, Italy. roberto.perricone@uniroma2.it.
authors.forename: Roberto
authors.initials: R
authors.lastname: Perricone
authors.affiliation: Unità Operativa di Allergologia, Presidio ospedaliero di Civitanova Marche, Civitanova Marche, Italy. allergologia.asurzona8@sanita.marche.it.
authors.forename: Stefano
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authors.lastname: Pucci
authors.affiliation: U.O.C. di Allergologia e Immunologia Clinica, Dipartimento di Medicine Specialistiche, Policlinico Universitario, Messina, Italy. paolina.quattrocchi@alice.it.
authors.forename: Paolina
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authors.lastname: Quattrocchi
authors.affiliation: SOD Immunoallergologia AOU Careggi, Florence, Italy. o.rossi@dmi.unifi.it.
authors.forename: Oliviero
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authors.lastname: Rossi
authors.affiliation: Dipartimento di Medicina e Chirurgia, Università degli Studi di Salerno, Salerno, Italy. mtriggiani@unisa.it.
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authors.lastname: Triggiani
authors.affiliation: Struttura Semplice Allergologia, Azienda Sanitaria Locale di Biella, Biella, Italy. zaniway@tiscali.it.
authors.forename: Giuseppina
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authors.lastname: Zanierato
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mesh_terms: D000293:Adolescent; D000328:Adult; D054179:Angioedemas, Hereditary / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D055815:Young Adult