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1. Diagnostic and therapeutic management of hereditary angioedema due to C1-inhibitor deficiency: The Italian experience

Author

Cancian, M, Arcoleo, F, Bafunno, V, Barca, Mp, Borrelli, P, Bova, M, Di Rocco PC, Cicardi, M, Cillari, E, De Carolis, C, De Pasquale, T, Del Corso, I, Guarino, Md, Massaro, I, Minale, P, Montinaro, V, Neri, S, Perricone, R, Pucci, S, Quattrocchi, P, Rossi, O, Senter, Riccardo, Triggiani, M, Zanichelli, A, Zanierato, G, and Zoli, A.

Subjects
Adult, C1 inhibitor deficiency, Immunology, Bradykinin, Genetically Modified, C1-inhibitor, Complement C1 Inactivator Proteins, Animals, Genetically Modified, attenuated androgens, bradykinin receptor antagonist, hereditary angioedema, prophylaxis, Animals, Complement C1 Inhibitor Protein, Humans, Italy, Peptides, Rabbits, Recombinant Proteins, Angioedemas, Hereditary, Immunology and Allergy, Medicine (all), chemistry.chemical_compound, medicine, heterocyclic compounds, Hereditary Angioedema, Italy, ITACA, biology, Angioedema, business.industry, Angioedemas, biochemical phenomena, metabolism, and nutrition, respiratory system, bacterial infections and mycoses, medicine.disease, respiratory tract diseases, Genetically modified organism, ITACA, Hereditary, chemistry, Hereditary angioedema, biology.protein, medicine.symptom, business, Rare disease
Abstract

Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency (C1-INH-HAE) is a rare disease, with a reported prevalence of about 1 : 50 000. C1-INH-HAE causes disabling symptoms, which may be life-threatening if swelling affects upper airways. Diagnostic procedures are now well established and the role of bradykinin as the main mediator of plasma outflow eliciting angioedema formation has been clearly elucidated.Increased understanding of the pathogenesis of C1-INH-HAE allowed in recent years the development of new drugs targeted to inhibit bradykinin synthesis (Ecallantide) or activity (Icatibant). At the same time, a recombinant C1-INH concentrate (Ruconest) was produced from the milk of transgenic rabbits and two plasma-derived C1-INHs (Berinert, Cinryze) underwent controlled trials to obtain marketing authorization. In 2012, an Italian network for C1-INH-HAE (ITACA) was established by physicians of 17 HAE reference centres to collect data from Italian patients and to homogenize and improve the diagnostic and therapeutic approach to the disease.Although there is a widespread agreement on therapeutic goals and treatment of C1-INH-HAE acute attacks, different approaches to prophylaxis are still present among HAE experts. The clinical experience of ITACA on a large population of C1-INH-HAE patients followed for several years may help in identifying the most effective strategies for the management of the disease.

Published
2015

2. Anisakis hypersensitivity in Italy: prevalence and clinical features: a multicenter study

Author

AAITO IFIACI Anisakis Consortium, Heffler, Enrico Marco, Nebiolo, F, Rizzini, Fl, Tosoni, C, Cinquini, M, Colombo, G, Yacoub, Mr, Mason, C, della Torre, F, Manzotti, G, Asero, R, Dugnano, P, Conte, M, Senna, G, Crivellaro, M, Villalta, D, De Carli, M, Renato, A, Bertolini, C, Minale, P, Ridolo, E, Olivieri, E, Emiliani, F, Quercia, O, Savi, E, Peveri, S, Cortellini, G, Cecchi, L, Macchia, D, Capretti, S, Antonicelli, L, Bilò, Mb, Polillo, Br, Bresciani, M, Greco, E, Murzilli, F, Colangelo, C, Di Rocco PC, Di Claudio, F, Cervone, M, Rapone, C, Cichella, S, Lo Schiavo, M, Gargano, D, Montera, Mc, Pio, A, Pezzuto, F, Munno, G, Giannoccaro, F, Longo, R, and Arena, A.

Subjects
Italy, Fishes, Prevalence, Animals, Humans, Anisakis, Food Hypersensitivity, Skin Tests
Abstract

Anisakis simplex (As), a parasite in fish, is able to sensitize humans via the alimentary tract. The prevalence of hypersensitivity and allergy to As outside the Iberian peninsula has not been investigated so far. We investigated Anisakis hypersensitivity in different areas of Italy.Consecutive subjects seen at 34 Italian allergy centers from October to December 2010 were investigated both by specific interview and by skin prick test (SPT) with As extract.A total of 10 570 subjects were screened, of which 474 (4.5%) scored positive on Anisakis SPT and 66 of these (14% of those sensitized; 0.6% of the studied population) had a history of As allergy. Marinated anchovies were the most frequent cause of allergic reactions. Thirty-four (52%) patients were mono-sensitized to Anisakis. Sensitization rate showed marked geographic differences (range: 0.4-12.7%), being highest along the Adriatic and Tyrrhenian coasts, where homemade marinated anchovies are an age-old tradition. In inland centers in northern Italy, the prevalence was directly related to the number of inhabitants. The analysis of the impact of immigration on the prevalence of Anisakis hypersensitivity showed that about 60% of sensitized subjects in Milano and Torino came from southern Italy or from non-European countries.Anisakis hypersensitivity and allergy are mainly a matter of dietary habits. Areas where marinated anchovies are popular can be considered as 'endemic' for this type of food allergy, whereas immigration and, possibly, new or imported trendy food styles, such as eating raw fish carpaccios or sushi, are a major causative factor in big cities of inland zones.

Published
2011

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

Author

Zanichelli A, Arcoleo F, Barca MP, Borrelli P, Bova M, Cancian M, Cicardi M, Cillari E, De Carolis C, De Pasquale T, Del Corso I, Di Rocco PC, Guarino MD, Massaro I, Minale P, Montinaro V, Neri S, Perricone R, Pucci S, Quattrocchi P, Rossi O, Triggiani M, Zanierato G, and Zoli A

Subjects
Adolescent, Adult, Female, Humans, Italy epidemiology, Male, Middle Aged, Young Adult, Angioedemas, Hereditary epidemiology, Angioedemas, Hereditary genetics
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.

Published
2015
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