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. 2015 Feb 6:10:11.
doi: 10.1186/s13023-015-0233-x.

A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in Italy

Andrea Zanichelli  1 , Francesco Arcoleo  2 , Maria Pina Barca  3 , Paolo Borrelli  4 , Maria Bova  5 , Mauro Cancian  6 , Marco Cicardi  7 , Enrico Cillari  8 , Caterina De Carolis  9 , Tiziana De Pasquale  10 , Isabella Del Corso  11 , Paola Cesinaro Di Rocco  12 , Maria Domenica Guarino  13 , Ilaria Massaro  14 , Paola Minale  15 , Vincenzo Montinaro  16 , Sergio Neri  17 , Roberto Perricone  18 , Stefano Pucci  19 , Paolina Quattrocchi  20 , Oliviero Rossi  21 , Massimo Triggiani  22 , Giuseppina Zanierato  23 , Alessandra Zoli  24
Affiliations

A nationwide survey of hereditary angioedema due to C1 inhibitor deficiency in Italy

Andrea Zanichelli et al. Orphanet J Rare Dis. .

Abstract

Introduction: 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.

Conclusion: 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.

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Figures

Figure 1
Figure 1
Distribution per decades of life of C1-INH-HAE patients compared to Italian population (*p < 0.05 versus general population).
Figure 2
Figure 2
Median age at diagnosis of probands from 1973 to 2013. Numbers reported on top of histogram indicate new families diagnosed in each 5-year-period.
See this image and copyright information in PMC

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