Optimizing hereditary angioedema management through tailored treatment approaches

References

• Papers of special note have been highlighted as:
   Google Scholar
• • of interest
   Google Scholar
• •• of considerable interest
   Google Scholar

• Longhurst H, Cicardi M. Hereditary angio-oedema. Lancet. 2012;379(9814):474–481.
   PubMed Web of Science ®Google Scholar
• Roche O, Blanch A, Caballero T, et al. Hereditary angioedema due to C1 inhibitor deficiency: patient registry and approach to the prevalence in Spain. Ann Allergy Asthma Immunol. 2005;94(4):498–503.
   PubMed Web of Science ®Google Scholar
• Bowen T, Cicardi M, Farkas H, et al. 2010 International consensus algorithm for the diagnosis, therapy and management of hereditary angioedema [Internet]. Allergy Asthma Clin Immunol. 2010;6(1):24. Available from: http://www.aacijournal.com/content/6/1/24.
   PubMedGoogle Scholar
• Bygum A. Hereditary angio-oedema in Denmark: a nationwide survey. Br J Dermatol. 2009;161(5):1153–1158.
   PubMed Web of Science ®Google Scholar
• Bork K, Hardt J, Witzke G. Fatal laryngeal attacks and mortality in hereditary angioedema due to C1-INH deficiency. J Allergy Clin Immunol. 2012;130(3):692–697.
   PubMed Web of Science ®Google Scholar

•• Retrospective review of frequency, risk factors for and time course of fatal laryngeal attacks in a cohort of patients with access to best standard of care prior to 2012. Highlights the importance of diagnosis of HAE, and rapid recognition and early definitive treatment of symptoms of upper airway swelling. Describes the clinical course of mild symptoms, followed by a rapidly progressive airway obstruction if untreated

• Siedlecki K, Bosch S, Schopf RE, et al. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc. 2000;75(4):349–354.
   PubMed Web of Science ®Google Scholar
• Caballero T, Aygören-Pürsün E, Bygum A, et al. The humanistic burden of HAE: results from the Burden Illness study in Europe. Allergy Asthma Proc. 2014;35(1):47–53.
   PubMed Web of Science ®Google Scholar
• Agostoni A, Cicardi M. Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. Medicine (Baltimore). 1992;71(4):206–215.
   PubMed Web of Science ®Google Scholar
• Bork K, Meng G, Staubach P, et al. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med. 2006;119(3):267–274.
   PubMed Web of Science ®Google Scholar
• Bouillet L. Hereditary angioedema in women [Internet]. Allergy Asthma Clin Immunol. 2010;6(1):17. Available from: http://www.aacijournal.com/content/6/1/17.
   PubMedGoogle Scholar
• Zuraw BL. Hereditary angioedema. N Engl J Med. 2008;359(10):1027–1036.
   PubMed Web of Science ®Google Scholar
• Bork K, Staubach P, Eckardt AJ, et al. Symptoms, course, and complications of abdominal attacks in hereditary angioedema due to C1 inhibitor deficiency. Am J Gastroenterol. 2006;101(3):619–627.
   PubMed Web of Science ®Google Scholar

• These two papers described for the first time the natural history of untreated abdominal angioedema attacks and those treated with C1 inhibitor. Retrospective review of symptom and treatment diaries of a large cohort of patients demonstrated a reduction in severity and length of symptoms with treatment and a greater benefit when treatment was given early (see also reference 47)

• Lumry WR, Castaldo AJ, Vernon MK, et al. The humanistic burden of HAE: impact on health-related quality of life, productivity, and depression. Allergy Asthma Proc. 2010;31(5):407–414.
   PubMed Web of Science ®Google Scholar
• Aygören-Pürsün E, Bygum A, Beusterien K, et al. Socioeconomic burden of hereditary angioedema: results from the hereditary angioedema burden of illness study in Europe [Internet]. Orphanet J Rare Dis. 2014;9:99. Available from: http://www.ojrd.com/content/9/1/99.
   PubMed Web of Science ®Google Scholar
• Wilson DA, Bork K, Shea EP, et al. Economic costs associated with acute attacks and long-term management of hereditary angioedema. Ann Allergy Asthma Immunol. 2010;104(4):314–320.
   PubMed Web of Science ®Google Scholar
• Bork K. Hereditary angioedema with normal C1 inhibitor. Immunol Allergy Clin North Am. 2013;33(4):457–470.
   PubMed Web of Science ®Google Scholar
• Wagenaar-Bos IG, Hack CE. Structure and function of C1-inhibitor. Immunol Allergy Clin North Am. 2006;26(4):615–632.
   PubMed Web of Science ®Google Scholar

• Elegant review of structure and multiplicity of functions of C1 inhibitor

• Kaplan AP, Joseph K. The bradykinin-forming cascade and its role in hereditary angio-oedema. Ann Allergy Asthma Immunol. 2010;104(3):193–204.
   PubMed Web of Science ®Google Scholar
• Cicardi M, Bork K, Caballero T, et al, Evidence-based recommendations for the therapeutic management of angioedema owing to hereditary C1 inhibitor deficiency: consensus report of an International Working Group. Allergy. 2012;67(2):147–157.
   PubMed Web of Science ®Google Scholar

•• Clear and concise consensus review of diagnostic and management controversies and options

• Zanichelli A, Magerl M, Longhurst H, et al. Hereditary angioedema with C1 inhibitor deficiency: delay in diagnosis in Europe [Internet]. Allergy Asthma Clin Immunol. 2013;9(1):29. Available from: http://www.aacijournal.com/content/9/1/29.
   PubMed Web of Science ®Google Scholar
• Bork K, Siedlecki K, Bosch S, et al. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc. 2000;75(4):349–354.
   PubMed Web of Science ®Google Scholar
• Tarzi MD, Hickey A, Förster T, et al. An evaluation of tests used for the diagnosis and monitoring of C1 inhibitor deficiency: normal serum C4 does not exclude hereditary angio-oedema. Clin Exp Immunol. 2007;149(3):513–516.
   PubMed Web of Science ®Google Scholar
• Gompels MM, Lock RJ. C1 inhibitor deficiency: diagnosis. Clin Exp Dermatol. 2005;30(4):460–462.
   PubMed Web of Science ®Google Scholar
• C1 inhibitor gene mutation database [Internet]. Hungary: National Medical Center, Laboratory of Molecular Biology. [cited 2015 Jun 1]. Available from: http://hae.enzim.hu.
   Google Scholar
• Pappalardo E, Cicardi M, Duponchel C, et al. Frequent de novo mutations and exon deletions in the C1 inhibitor gene of patients with angioedema. J Allergy Clin Immunol. 2000;106(6):1147–1154.
   PubMed Web of Science ®Google Scholar
• Bork K. Hereditary angioedema with normal C1 inhibitor. Curr Allergy Asthma Rep. 2009;9(4):280–285.
   PubMed Web of Science ®Google Scholar
• Manson AL, Price A, Dempster J, et al. In pursuit of excellence: an integrated care pathway for C1 inhibitor deficiency. Clin Exp Immunol. 2013;173(1):1–7.
   PubMed Web of Science ®Google Scholar
• Zuraw BL, Busse PJ, White M, et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med. 2010;363(6):513–522.
   PubMed Web of Science ®Google Scholar
• Waytes AT, Rosen FS, Frank MM. Treatment of hereditary angioedema with a vapor-heated C1 inhibitor concentrate. N Engl J Med. 1996;334(25):1630–1634.
   PubMed Web of Science ®Google Scholar
• Kunschak M, Engl W, Maritsch F, et al. A randomized, controlled trial to study the efficacy and safety of C1 inhibitor concentrate in treating hereditary angioedema. Transfusion. 1998;38(6):540–549.
   PubMed Web of Science ®Google Scholar
• Zuraw B, Cicardi M, Levy RJ, et al. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema [Internet]. J Allergy Clin Immunol. 2010;126(4):821-7.e14. Available from: http://www.jacionline.org/article/S0091-6749(10)02347-X/abstract.
   PubMed Web of Science ®Google Scholar
• Cicardi M, Banerji A, Bracho F, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med. 2010;363(6):532–541.
   PubMed Web of Science ®Google Scholar
• Cicardi M, Levy RJ, McNeil DL, et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010;363(6):523–531.
   PubMed Web of Science ®Google Scholar
• Craig TJ, Levy RJ, Wasserman RL, et al. Efficacy of human C1 esterase inhibitor concentrate compared with placebo in acute hereditary angioedema attacks. J Allergy Clin Immunol. 2009;124(4):801–808.
   PubMed Web of Science ®Google Scholar
• Levi M, Choi G, Picavet C, et al. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angio-oedema caused by C1-inhibitor deficiency. J Allergy Clin Immunol. 2006;117(4):904–908.
   PubMed Web of Science ®Google Scholar
• Gelfand JA, Sherins RJ, Alling DW, et al. Treatment of hereditary angioedema with danazol. Reversal of clinical and biochemical abnormalities. N Engl J Med. 1976;295(26):1444–1448.
   PubMed Web of Science ®Google Scholar
• Sheffer AL, Fearon DT, Austen KF. Methyltestosterone therapy in hereditary angioedema. Ann Intern Med. 1977;86(3):306–308.
   PubMed Web of Science ®Google Scholar
• Sheffer AL, Austen KF, Rosen FS. Tranexamic acid therapy in hereditary angioneurotic edema. N Engl J Med. 1972;287(9):452–454.
   PubMed Web of Science ®Google Scholar
• Frank MM, Sergent JS, Kane MA, et al. Epsilon aminocaproic acid therapy of hereditary angioneurotic edema. A double-blind study. N Engl J Med. 1972;286(15):808–812.
   PubMed Web of Science ®Google Scholar
• Constantino G, Casazza G, Bossi I, et al, Long-term prophylaxis in hereditary angio-oedema: a systematic review [Internet]. BMJ Open. 2012;2(4). Available from: http://bmjopen.bmj.com/content/2/4/e000524.full.
   Google Scholar

• Systematic review of evidence for current prophylactic options (androgens, antifibrinolytics and C1 inhibitor)

• Saule C, Boccon-Gibod I, Fain O, et al. Benefits of progestin contraception in non-allergic angioedema. Clin Exp Allergy. 2013;43(4):475–482.
   PubMed Web of Science ®Google Scholar
• Banerji A, Busse P, Christiansen SC, et al. Current state of hereditary angioedema management: a patient survey. Allergy Asthma Proc. 2015;36(3):213–217.
   PubMed Web of Science ®Google Scholar
• Lumry WR, Miller DP, Newcomer S, et al, Quality of life in patients with hereditary angioedema receiving therapy for routine prevention of attacks. Allergy Asthma Proc. 2014;35(5):371–376.
   PubMed Web of Science ®Google Scholar

• Double-blind post hoc analysis showing improvement in quality of life parameters while using intravenous C1 inhibitor prophylaxis, compared with placebo

• Zuraw BL, Kalfus I. Safety and efficacy of prophylactic nanofiltered C1-inhibitor in hereditary angioedema. Am J Med. 2012;125(9):938.e1-e7.
   Web of Science ®Google Scholar
• Bork K. Pasteurized C1 inhibitor concentrate in hereditary angioedema: pharmacology, safety, efficacy and future directions. Expert Rev Clin Immunol. 2008;4(1):13–20.
   PubMed Web of Science ®Google Scholar
• Bork K, Barnstedt SE. Treatment of 193 episodes of laryngeal edema with C1 inhibitor concentrate in patients with hereditary angioedema. Arch Intern Med. 2001;161(5):714–718.
   PubMed Web of Science ®Google Scholar
• Bork K, Meng G, Staubach P, et al. Treatment with C1 inhibitor concentrate in abdominal pain attacks of patients with hereditary angioedema. Transfusion. 2005;45(11):1774–1784.
   PubMed Web of Science ®Google Scholar

• Lumry WR, Li HH, Levy RJ, et al. Randomized placebo-controlled trial of the bradykinin B₂ receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011;107(6):529–537.
   PubMed Web of Science ®Google Scholar
• Levy RJ, Lumry WR, McNeil DL, et al. EDEMA4: a phase 3, double-blind study of subcutaneous ecallantide treatment for acute attacks of hereditary angio-oedema. Ann Allergy Asthma Immunol. 2010;104(6):523–529.
   PubMed Web of Science ®Google Scholar
• Moldovan D, Reshef A, Fabiani J, et al. Efficacy and safety of recombinant human C1-inhibitor for the treatment of attacks of hereditary angioedema: European open-label extension study. Clin Exp Allergy. 2012;42(6):929–935.
   PubMed Web of Science ®Google Scholar
• Longhurst H. Rhucin, a recombinant C1 inhibitor for the treatment of hereditary angioedema and cerebral ischemia. Curr Opin Investig Drugs. 2008;9(3):310–323.
   PubMed Web of Science ®Google Scholar
• Reshef A, Moldovan D, Obtulowicz K, et al. Recombinant human C1 inhibitor for the prophylaxis of hereditary angioedema attacks: a pilot study. Allergy. 2013;68(1):118–124.
   PubMed Web of Science ®Google Scholar
• Hack CE, Relan A, Van Amersfoort ES, et al. Target levels of functional C1-inhibitor in hereditary angioedema. Allergy. 2012;67(1):123–130.
   PubMed Web of Science ®Google Scholar
• Aberer W, Maurer M, Reshef A, et al. Open label, multicenter study of self-administered icatibant for attacks of hereditary angioedema. Allergy. 2014;69(3):305–314.
   PubMed Web of Science ®Google Scholar
• Prematta M, Gibbs JG, Pratt EL, et al. Fresh frozen plasma for the treatment of hereditary angioedema. Ann Allergy Asthma Immunol. 2007;98(4):383–388.
   PubMed Web of Science ®Google Scholar
• SPC Octaplas. Octaplas: Summary of Product Characteristics (SPC) by Octapharma Limited [Internet]. [cited 2015 June 30]. Available from: http://www.medicines.org.uk/emc/medicine/26651.
   Google Scholar
• SPC Berinert [Internet]. Berinert: Summary of Product Characteristics (SPC) by CSL Behring Limited. [cited 2015 June 30]. Available from: http://www.medicines.org.uk/emc/medicine/21650.
   Google Scholar
• Longhurst HJ, Carr S, Khair K. C1-inhibitor concentrate home therapy for hereditary angioedema: a viable, effective treatment option. Clin Exp Immunol. 2007;147(1):11–17.
   PubMed Web of Science ®Google Scholar
• Longhurst HJ, Tarzi MD, Ashworth F, et al. C1 inhibitor deficiency: 2014 United Kingdom consensus document. Clin Exp Immunol. 2015;180(3):475–483.
   PubMed Web of Science ®Google Scholar
• Craig T, Aygören-Pürsün E, Bork K, et al. WAO guideline for the management of hereditary angioedema. World Allergy Organ J. 2012;5(12):182–199.
   PubMedGoogle Scholar
• Betschel S, Badiou J, Binkley K, et al. Canadian hereditary angioedema guideline [Internet]. Allergy Asthma Clin Immunol. 2014;10(1):50. Available from: http://www.aacijournal.com/content/10/1/50.
   PubMedGoogle Scholar
• Longhurst HJ, Farkas H, Craig T, et al. HAE international home therapy consensus document [Internet]. Allergy Asthma Clin Immunol. 2010;6(1):22. Available from: http://www.aacijournal.com/content/6/1/22.
   PubMedGoogle Scholar
• Zuraw BL, Banerji A, Bernstein JA, et al. US Hereditary Angioedema Association Medical Advisory Board. US Hereditary Angioedema Association Medical Advisory Board 2013 recommendations for the management of hereditary angioedema due to C1 inhibitor deficiency. J Allergy Clin Immunol Pract. 2013;1(5):458–467.
   PubMed Web of Science ®Google Scholar
• Maurer M, Aberer W, Bouillet L, et al. Hereditary angioedema attacks resolve faster and are shorter after early icatibant treatment [Internet]. PLoS One. 2013;8(2):e53773. Available from: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0053773.
   PubMed Web of Science ®Google Scholar
• Craig TJ, Rojavin MA, Machnig T, et al. Effect of time to treatment on response to C1 esterase inhibitor concentrate for hereditary angioedema attacks. Ann Allergy Asthma Immunol. 2013;111(3):211–215.
   PubMed Web of Science ®Google Scholar
• Strawczynski H, Stachewitsch A, Morgenstern G, et al. Delivery of care to hemophilic children: home care versus hospitalization. Pediatrics. 1973;51(6):986–991.
   PubMed Web of Science ®Google Scholar
• 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(2):147–151.
   PubMed Web of Science ®Google Scholar
• Aygören-Pürsün E, Martinez-Saguer I, Rusicke E, et al. On demand treatment and home therapy of hereditary angioedema in Germany - the Frankfurt experience [Internet]. Allergy Asthma Clin Immunol. 2010;6(1):21. Available from: http://www.aacijournal.com/content/6/1/21.
   PubMedGoogle Scholar
• Craig TJ, Li HH, Riedl M, et al. Characterization of anaphylaxis after ecallantide treatment of hereditary angioedema attacks. J Allergy Clin Immunology: In Pract. 2015;3(2):206-212.e4.
   Google Scholar
• Drouet C, Désormeaux A, Robillard J, et al. Metallopeptidase activities in hereditary angioedema: effect of androgen prophylaxis on plasma aminopeptidase P. J Allergy Clin Immunol. 2008;121(2):429–433.
   PubMed Web of Science ®Google Scholar
• Bork K, Bygum A, Hardt J. Benefits and risks of danazol in hereditary angio-oedema: a long-term survey of 118 patients. Ann Allergy Asthma Immunol. 2008;100(20):153–161.
   PubMed Web of Science ®Google Scholar
• Cicardi M, Castelli R, Zingale LC, et al. Side effects of long-term prophylaxis with attenuated androgens in hereditary angioedema: comparison of treated and untreated patients. J Allergy Clin Immunol. 1997;99(2):194–196.
   PubMed Web of Science ®Google Scholar
• Binkley KE. Factor XII mutations, estrogen-dependent inherited angioedema, and related conditions. Allergy Asthma Clin Immunol [Internet]. 2010;6(1):16. Available from: http://www.aacijournal.com/content/6/1/16.
   PubMedGoogle Scholar
• Kalaria S, Craig T. Assessment of hereditary angioedema treatment risks. Allergy Asthma Proc. 2013;34(6):519–522.
   PubMed Web of Science ®Google Scholar
• Gandhi PK, Gentry WM, Bottorff MB. Thrombotic events associated with C1 esterase inhibitor products in patients with hereditary angioedema: investigation from the United States Food and Drug Administration adverse event reporting system database. Pharmacotherapy. 2012;32(10):902–909.
   PubMed Web of Science ®Google Scholar
• Bork K, Hardt J, Staubach-Renz P, et al. Risk of laryngeal edema and facial swellings after tooth extraction in patients with hereditary angioedema with and without prophylaxis with C1 inhibitor concentrate: a retrospective study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(1):58–64.
   PubMed Web of Science ®Google Scholar
• Manson AL, Dempster J, Grigoriadou S, et al. Use of recombinant C1 inhibitor in patients with resistant or frequent attacks of hereditary or acquired angioedema. Eur J Dermatol. 2014;24(1):28–34.
   PubMed Web of Science ®Google Scholar
• Magerl M, Aygören-Pürsün E, Graff J, et al, BCX4161, an oral Kallikrein inhibitor, showed significant benefits on reducing disease burden and improving quality of life in subjects with hereditary angioedema in the Opus-1 study. J Allergy Clin Immunol. 2015;135(2): AB278.
   Web of Science ®Google Scholar

• Aygören-Pürsün E, Magerl M, Graff J, et al. Efficacy correlates with plasma levels in Opus-1, a proof-of-concept study of oral kallikrein inhibitor BCX4161 as a prophylaxis against attacks of hereditary angioedema (HAE). J Allergy Clin Immunol. 2015;135(2): AB192.
   Web of Science ®Google Scholar
• BioCryst Pharmaceuticals. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). [cited 2015 Sept 10]. Available from: https://www.clinicaltrials.gov/ct2/show/NCT01984788?term=4161&rank=4 NLM Identifier: NCT02125162
   Google Scholar
• Martinez-Saguer I, Cicardi M, Suffritti C, et al. Pharmacokinetics of plasma-derived C1-esterase inhibitor after subcutaneous versus intravenous administration in subjects with mild or moderate hereditary angioedema: the PASSION study. Transfusion. 2014;54(6):1552–1561.
   PubMed Web of Science ®Google Scholar
• Zuraw BL, Cicardi M, Longhurst HJ, et al. Phase II study results of a replacement therapy for hereditary angioedema (HAE) with subcutaneous C1-inhibitor concentrate. Allergy. [Epub ahead of print] 2015; doi:10.1111/all.12658
   PubMed Web of Science ®Google Scholar
• CSL Behring Limited. A study to evaluate the clinical efficacy and safety of subcutaneously administered C1-esterase inhibitor in the prevention of hereditary angioedema. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). [cited 2015 Sept 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT01912456?term=subcutaneously+administered+C1-esterase&rank=1 Identifier NCT01912456
   Google Scholar
• Riedl MA, Lumry WR, Li HH, et al. Subcutaneous human C1-inhibitor with recombinant human hyaluronidase for the prevention of angioedema attacks in patients with hereditary angioedema: results of a randomized, double-blind, dose-ranging, crossover study. J Allergy Clin Immunol. 2015;135(2): AB278.
   Web of Science ®Google Scholar
• Schranz J, Levy R, Lumry W, et al. Safety, pharmacokinetics (PK), and pharmacodynamics (PD) of subcutaneous (SC) Cinryze® (C1 inhibitor (C1 INH) with recombinant human hyaluronidase (rHuPH20) in subjects with hereditary angioedema (HAE). J Allergy Clin Immunol. 2012;129(2Supp): AB369.
   Google Scholar
• Chyung Y, Vince B, Iarrobino R, et al. A phase 1 study investigating DX-2930 in healthy subjects [Internet]. Ann Allergy Asthma Immunol. 2014;113(4):460-6.e2. Available from: http://www.annallergy.org/article/S1081-1206(14)00377-9/fulltext.
   PubMed Web of Science ®Google Scholar
• Dyax Corp. Double-blind, multiple ascending dose study to assess safety, tolerability and pharmacokinetics of DX-2930 in hereditary angioedema subjects. In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). [cited 2015 Sept 10]. Available from: https://clinicaltrials.gov/ct2/show/NCT02093923?term=DX-2930&rank=1 Identifier NCT02093923
   Google Scholar
• Cao H, Biondo M, Rayzman V, et al. Development and characterization of an Anti-FXIIA monoclonal antibody for the treatment of hereditary angiodema. 9th C1-inhibitor Deficiency Workshop AB O-07. Budapest (Hungary); 2015.
   Google Scholar
• Kaplan AP, Joseph K. Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway. Adv Immunol. 2014;121:41–89.
   PubMed Web of Science ®Google Scholar
• Ferrone JD, Derosier F, Schneider E, et al. Antisense inhibitors of plasma prekallikrein (PKK) reduce plasma PKK and vascular permeability in pre-clinical rodent models, and reduce plasma PKK in a dose-dependent manner in healthy human volunteers. 9th C1-inhibitor Deficiency Workshop: AB P-37. Budapest (Hungary); 2015.
   Google Scholar
• Nathwani AC, Reiss UM, Tuddenham EG, et al. Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med. 2014;371(21):1994–2004.
   PubMed Web of Science ®Google Scholar
• Mikkelsen JG Genetic engineering for cellular modeling of HAE disease mechanisms in cell lines, patient derived fibroblasts and mice. 9th C1-inhibitor Deficiency Workshop: AB I-02. Budapest (Hungary); 2015.
   Google Scholar
• Klausegger A, Wiednig M, Urban C, et al. Successful allogeneic cord blood transplantation in a patient with Evans syndrome leads to correction of hereditary angioedema type I as secondary effect. Bone Marrow Transplant. 2012;47(9):1259–1261.
   PubMed Web of Science ®Google Scholar
• Touzot F, Hacein-Bey-Abina S, Fischer A, et al. Gene therapy for inherited immunodeficiency. Expert Opin Biol Ther. 2014;14(6):789–798.
   PubMed Web of Science ®Google Scholar
• Ott De Bruin LM, Volpi S, Musunuru K. Novel genome-editing tools to model and correct primary immunodeficiencies [Internet]. Fron Immunol. 2015;(6)250. Available from: http://journal.frontiersin.org/article/10.3389/fimmu.2015.00250/full.
   Google Scholar
• Björkqvist J, De Maat S, Lewandrowski U, et al. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III. J Clin Invest. 2015;12583132–3146. 10.1172/JCI77139 Epub 2015 Jul 20
   PubMed Web of Science ®Google Scholar
• Zuraw BL, Bork K, Binkley KE, et al. Hereditary angioedema with normal C1 inhibitor function: consensus of an international expert panel. Allergy Asthma Proc. 2012;33(suppl 1):S145–S156.
   PubMed Web of Science ®Google Scholar
• Ruconest Summary of Product Characteristics [Internet]. Sobi BioVitrum Limited. [cited 2015 Sept 21]. Available from: https://www.medicines.org.uk/emc/medicine/24632.
   Google Scholar
• Schneider L, Lumry W, Vegh A, et al. Critical role of kallikrein in hereditary angioedema pathogenesis: a clinical trial of ecallantide, a novel kallikrein inhibitor. J Allergy Clin Immunol. 2007;120(2):416–422.
   PubMed Web of Science ®Google Scholar
• Longhurst HJ. Emergency treatment of acute attacks in HAE due to C1 INH deficiency: what is the evidence? Int J Clinical Pract. 2005;59:594–599.
   PubMed Web of Science ®Google Scholar