Background: No published data presently exist concerning hereditary angioedema (HAE) in Greece. The aim of this study was to present the results from patients recorded by the Greek Hereditary Angioedema Registry over the last 3 years (July 2010 to June 2013). Methods: A systematic recording of HAE cases was undertaken following a physician awareness campaign and confirmation of diagnosis. A questionnaire was also used for the assessment of key parameters of the patients' disease-specific quality of life. Results: One hundred and sixteen patients from 41 non-related families were recorded. There were 33 (80.5%) families with type I HAE, 7 (17%) with type II HAE and 1 (2.5%) with non-C1 inhibitor (C1-INH), non-FXII HAE. Two further non-C1-INH, non-FXII HAE sporadic cases were recorded. An investigation of non-symptomatic family members revealed another 6 asymptomatic individuals with C1-INH deficiency. The average delay in diagnosis was 16.5 years and the incidence of death in the families of patients was 1 for every 2 families. The use of newer therapeutic agents seems to fall significantly short of the existing needs. HAE was found to affect the quality of life slightly in 14%, greatly in 63% and significantly in 23% of the patients. Conclusion: Until recently, there has been a significant degree of underdiagnosis of HAE in Greece. Very low compliance with the provisions of the applicable international guidelines and consensus positions, with adverse consequences on the patients' quality of life, was also observed. The centralized model we used to uncover the patients could be effective in other countries presenting with comparable disease characteristics. © 2014 S. Karger AG, Basel

Keywords:
C1 inhibitor, Disease-specific quality of life, Greek Hereditary Angioedema Registry, Hereditary angioedema
1.
Zuraw BL: Hereditary angioedema. N Engl J Med 2008;359:1027-1036.
2.
Hsu D, Shaker M: An update on hereditary angioedema. Curr Opin Pediatr 2012;24:638-646.
3.
Bork K, Davis-Lorton M: Overview of hereditary angioedema caused by C1-inhibitor deficiency: assessment and clinical management. Eur Ann Allergy Clin Immunol 2013;45:7-16.
4.
Gösswein T, Kocot A, Emmert G, Kreuz W, Martinez-Saguer I, Aygören-Pürsün E, Rusicke E, Bork K, Oldenburg J, Müller CR: Mutational spectrum of the C1INH (SERPING1) gene in patients with hereditary angioedema. Cytogenet Genome Res 2008;121:181-188.
5.
Pappalardo E, Caccia S, Suffritti C, Tordai A, Zingale LC, Cicardi M: Mutation screening of C1 inhibitor gene in 108 unrelated families with hereditary angioedema: functional and structural correlates. Mol Immunol 2008;45:3536-3544.
6.
Kaplan A: Type III hereditary angioedema: defined, but not understood. Ann Allergy Asthma Immunol 2012;109:153-154.
7.
Fernando SL: The nebulous diagnosis of type III hereditary angioedema. Ann Allergy Asthma Immunol 2013;111:65-66.
8.
Lunn ML, Santos CB, Craig TJ: Is there a need for clinical guidelines in the United States for the diagnosis of hereditary angioedema and the screening of family members of affected patients? Ann Allergy Asthma Immunol 2010;104:211-214.
9.
Lumry WR: Overview or epidemiology, pathophysiology, and disease progression in hereditary angioedema. Am J Manag Care 2013;19:S103-S110.
10.
Roche O, Blanch A, Caballero T, Sastre N, Callejo D, López-Trascasa M: Hereditary angioedema due to C1 inhibitor deficiency: patient registry and approach to the prevalence in Spain. Ann Allergy Asthma Immunol 2005;94:498-503.
11.
Cicardi M, Craig TJ, Martinez-Saguer I, Hébert J, Longhurst HJ: Review of recent guidelines and consensus statements on hereditary angioedema therapy with focus on self-administration. Int Arch Allergy Immunol 2013;161(suppl 1):3-9.
12.
Lumry WR: Management and prevention of hereditary angioedema attacks. Am J Manag Care 2013;19:S111-S118.
13.
Morgan BP: Hereditary angioedema - therapies old and new. N Engl J Med 2010;363:581-583.
14.
Lumry WR, Castaldo AJ, Vernon MK, Blaustein MB, Wilson DA, Horn PT: The humanistic burden of hereditary angioedema: impact on health-related quality of life, productivity, and depression. Allergy Asthma Proc 2010;31:407-414.
15.
Cardarelli W: Managed care implications of hereditary angioedema. Am J Manag Care 2013;19:S119-S124.
16.
Lane CJ, Grant JA, Dougherty D 3rd: Life with hereditary angioedema: then and now. Postgrad Med 2012;24:144-151.
17.
Papadopoulou-Alataki E, Foerster T, Antari V, Pavlitou-Tsiontsi A, Varlamis G: Molecular diagnosis and management of hereditary angioedema in a Greek family. Int Arch Allergy Immunol 2008;147:166-170.
18.
Speletas M, Boukas K, Papadopoulou-Alataki E, Tsitsami E, Germenis AE: Hereditary angioedema in Greek families caused by novel and recurrent mutations. Hum Immunol 2009;70:925-929.
19.
Bowen T, Cicardi M, Farkas H, et al: 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol 2010;6:24.
20.
Frank MM, Gelfand JA, Atkinson JP: Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med 1976;84:580-593.
21.
Lunn ML, Santos CB, Craig TJ: Is there a need for clinical guidelines in the United States for the diagnosis of hereditary angioedema and the screening of family members of affected patients? Ann Allergy Asthma Immunol 2010;104:211-214.
22.
Riedl M, Gower RG, Chrvala CA: Current medical management of hereditary angioedema: results from a large survey of US physicians. Ann Allergy Asthma Immunol 2011;106:316-322.
23.
Roche O, Blanch A, Caballero T, Sastre N, Callejo D, López-Trascasa M: Hereditary angioedema due to C1 inhibitor deficiency: patient registry and approach to the prevalence in Spain. Ann Allergy Asthma Immunol 2005;94:498-503.
24.
Bygum A: Hereditary angio-oedema in Denmark: a nationwide survey. Br J Dermatol 2009;161:1153-1158.
25.
Bork K, Meng G, Staubach P, Hardt J: Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med 2006;119:267-274.
26.
Kesim B, Uyguner ZO, Gelincik A, Mete Gökmen N, Sin AZ, Karakaya G, Erdenen F, Ardeniz O, Ozşeker F, Gülbahar O, Colakoğlu B, Dal M, Büyüköztürk S: The Turkish Hereditary Angioedema Pilot Study (TURHAPS): the first Turkish series of hereditary angioedema. Int Arch Allergy Immunol 2011;156:443-450.
27.
Agostoni A, Cicardi M: Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. Medicine 1992;71:206-215.
28.
Gompels MM, Lock RJ, Abinun M, Bethune CA, Davies G, Grattan C, Fay AC, Longhurst HJ, Morrison L, Price A, Price M, Watters D: C1 inhibitor deficiency: consensus document. Clin Exp Immunol 2005;139:379-394.
29.
Bouillet L, Gompel A: Hereditary angioedema in women: specific challenges. Immunol Allergy Clin North Am 2013;33:505-511.
30.
Craig TJ: Recent advances in hereditary angioedema self-administration treatment: summary of an International Hereditary Angioedema Expert Meeting. Int Arch Allergy Immunol 2013;161(suppl 1):26-27.
31.
Lumry W, Castaldo AJ, Vernon M, Blaustein MB, Wilson DA, Horn PT: The humanistic burden of hereditary angioedema: Impact on health-related quality of life, productivity and depression. Allergy Asthma Proc 2010;31:407-414.
32.
Craig T, Aygören-Pürsün E, Bork K, Bowen T, Boysen H, Farkas H, Grumach A, Katelaris CH, Lockey R, Longhurst H, Lumry W, Magerl M, Martinez-Saguer I, Ritchie B, Nast A, Pawankar R, Zuraw B, Maurer M: WAO guideline for the management of hereditary angioedema. World Allergy Organ J 2012;5:182-199.
33.
Cicardi M, Craig TJ, Martinez-Saguer I, Hébert J, Longhurst HJ: Review of recent guidelines and consensus statements on hereditary angioedema therapy with focus on self-administration. Int Arch Allergy Immunol 2013;161(suppl 1):3-9.
34.
Wilson DA, Bork K, Shea EP, Rentz AM, Blaustein MB, Pullman WE: Economic costs associated with acute attacks and long-term management of hereditary angioedema. Ann Allergy Asthma Immunol 2010;104:314-320.
35.
Landmesser LM, Mariano D: Impact of a self-administration training and support program on site of care in patients with hereditary angioedema receiving nanofiltered C1 esterase inhibitor for routine prophylaxis. J Manag Care Pharm 2012;18:549.
36.
Longhurst HJ, Farkas H, Craig T, Aygören-Pürsün E, Bethune C, Bjorkander J, Bork K, Bouillet L, Boysen H, Bygum A, Caballero T, Cicardi M, Dempster J, Gompels M, Gooi J, Grigoriadou S, Huffer U, Kreuz W, Levi MM, Long J, Martinez-Saguer I, Raguet M, Reshef A, Bowen T, Zuraw B: HAE international home therapy consensus document. Allergy Asthma Clin Immunol 2010;6:22.
37.
Cardarelli W: Managed care implications of hereditary angioedema. Am J Manag Care 2013;19:S119-S124.
38.
Poon E, Seed PT, Greaves MW, Kobza-Black A: The extent and nature of disability in different urticarial conditions. Br J Dermatol 1999;140:667-671.
39.
Huang SW: Results of an on-line survey of patients with hereditary angioedema. Allergy Asthma Proc 2004;25:127-131.
40.
Bygum A, Andersen KE, Mikkelsen CS: Self-administration of intravenous C1-inhibitor therapy for hereditary angioedema and associated quality of life benefits. Eur J Dermatol 2009;19:147-151.
41.
Prior N, Remor E, Gómez-Traseira C, López-Serrano C, Cabañas R, Contreras J, Campos Á, Cardona V, Cimbollek S, González-Quevedo T, Guilarte M, de Rojas DH, Marcos C, Rubio M, Tejedor-Alonso MÁ, Caballero T: Development of a disease-specific quality of life questionnaire for adult patients with hereditary angioedema due to C1 inhibitor deficiency (HAE-QoL): Spanish multi-centre research project. Health Qual Life Outcomes 2012;10:82.
42.
Bouillet L, Launay D, Fain O, Boccon-Gibod I, Laurent J, Martin L, Montauban V, Finck K, Bouée S, Gompel A, Kanny G; French National Reference Center for Hereditary Angioedema (CREAK): Hereditary angioedema with C1 inhibitor deficiency: clinical presentation and quality of life of 193 French patients. Ann Allergy Asthma Immunol 2013;111:290-294.
43.
Speletas M, Szilagyi A, Psarros F, Moldovan D, Magerl M, Kompoti M, Gramoustianou E, Bors A, Mihaly E, Tordai A, Avramouli A, Varga L, Maurer M, Farkas H, Germenis AE: Hereditary angioedema: molecular and clinical differences among european populations. J Allergy Clin Immunol, 2014 (in press).
© 2014 S. Karger AG, Basel
2014
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