Hereditary angioedema - an otolaryngologist’s perspective

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Hereditary angioedema (HAE) is a rare autosomal dominant disease consisting of recurrent angioedema attacks, varying in severity, possibly life-threatening and with frequent involvement of the head and neck areas. The patophysiology of HAE differs from histamine-mediated allergic angioedema. Three types of reduced quality or quantity in various complement or coagulation factors, leading to massive release of bradykinin, increase vascular permeability and produce capilary leakage. Clinical manifestations of HAE include swelling located predominantly in the head and neck area, hands, feet and urogenital area and abdominal pain caused by edema of the gastrointestinal tract mucosa. Diagnosis requires laboratory tests for complement components and genetic tests. A timely and correct diagnosis in the emergency room is of utmost importance, the medical treatment of HAE being substantially different from that of allergic angioedema. Although new therapies are available and in development, airway intervention and surgery are still life-saving procedures and the ENT surgeon is an important part of the multidisciplinary team managing an HAE attack.

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  • 1. Moldovan D. Bara N. Gábos G. Mihály E. - Deaths caused by Hereditary Angioedema Attacks. Data from the Romanian HAE Registry. Revista Societatii Romane de Alergologie si Imunologie Clinica 2015;XII(2):24-26.

  • 2. Bygum A. Aygören-Pürsün E. Caballero T. Beusterien K. Gholizadeh S. Musingarimi P. Wait S. Boysen H. - The hereditary angioedema burden of illness study in Europe (HAE-BOIS-Europe): background and methodology. BMC Dermatol. 2012;12:4. doi: 10.1186/1471-5945-12-4.

  • 3. Ghazi A. Grant J.A. - Hereditary angioedema: epidemiology management and role of icatibant. Biologics. 2013;7:103-13. doi: 10.2147/BTT. S27566. Epub 2013 May 3.

  • 4. Nzeako U.C. Frigas E. Tremaine W.J. - Hereditary angioedema: a broad review for clinicians. Arch Intern Med. 2001;161(20):2417-2429.

  • 5. Bork K. - Diagnosis and treatment of hereditary angioedema with normal C1 inhibitor. Allergy Asthma Clin Immunol. 2010;6(1):15. doi: 10.1186/1710-1492-6-15.

  • 6. 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(4):498-503.

  • 7. Zuraw B.L. - Clinical practice. Hereditary angioedema. N Engl J Med. 2008;359(10):1027-1036. doi: 10.1056/NEJMcp0803977.

  • 8. Bork K. Meg G. Staubach P. Hardt J. - Hereditary angioedema: new findings concerning symptoms affected organs and course. Am J Med. 2006;119(3):267-274.

  • 9. Zilberberg M. Nathanson B.H. Jacobsen T. Tillotson G. - Descriptive epidemiology of hereditary angioedema hospitalizations in the United States 2004-2007. Allergy Asthma Proc. 2011;32(3):248-254.

  • 10. Kim S.J. Brooks J.C. Sheikh J. Kaplan M.S. Goldberg B.J. - Angioedema deaths in the United States 1979-2010. Ann Allergy Asthma Immunol. 2014;113(6):630-634. doi: 10.1016/j.anai.2014.09.003. Epub 2014 Oct 3.

  • 11. Davis A.E. 3rd. - The pathophysiology of hereditary angioedema. Clin Immunol. 2005;114(1):3-9.

  • 12. Zuraw B.L. - The Pathophysiology of Hereditary Angioedema. World Allergy Organ J. 2010;3(Suppl 3):S25-S28.

  • 13. Caccia S. Suffritti C. Cicardi M. - Pathophysiology of Hereditary Angioedema. Pediatr Allergy immunol Pulmonol. 2014;27(4):159-163. doi: 10.1089/ped.2014.0425.

  • 14. Bas M. Adams V. Suvorava T. Niehues T. Hoffmann T.K. Kojda G. - Nonallergic angioedema: role of bradykinin. Allergy 2007;62(8):842-856.

  • 15. Cugno M. Zanichelli A. Foieni F. Caccia S. Cicardi M. - C1-inhibitor deficiency and angioedema: molecular mechanisms and clinical progress. Trends Mol Med. 2009;15(2):69-78. doi: 10.1016/j.molmed. 2008.12.001. Epub 2009 Jan 21.

  • 16. Craig T. Aygoren-Pursun E. Bork K. Bowen T. Boysen H Farkas H. Grumach A. Katelaris C.H. Lockey R. Longhurst H. et al. - WAO Guideline for the Management of Hereditary Angioedema. World Allergy Organ J. 2012;5(12):182-199. doi: 10.1097/ WOX.0b013e318279affa.

  • 17. Starr J.C. Brasher G.W. Rao A. Posey D. - Erythema marginatum and hereditary angioedema. South Med J. 2004;97(10):948-950.

  • 18. Khan D.A. - Hereditary angioedema: Historical aspects classification pathophysiology clinical presentation and laboratory diagnosis. Allergy Asthma Proc. 2011;32(1):1-10. doi: 10.2500/aap.2011.32.3411.

  • 19. Yucelten D. Kus S. - Chicken-wire erythema but not urticaria as the presenting sign of hereditary angioedema. Eur J Dermatol. 2006;16(2):197-198.

  • 20. Frank M.M. - Hereditary Angioedema. Available at Accessed May 10 2016.

  • 21. Ali M.A. Borum M.L. - Hereditary angioedema: what the gastroenterologist needs to know. Clin Exp Gastroenterol. 2014;7:435-445.

  • 22. Agostoni A. Aygoren-Pursun E. Binkley K.E. Blanch A. Bork K. Bouillet L. Bucher C. Cstaldo A.J. Cicardi M. Davis A.E. De Carolis C. et al. - Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. J Allergy Clin Immunol. 2004;114(Suppl 3):S51-S131.

  • 23. Bork K. Hardt J. Schicketanz K.H. Ressel N. - Clinical Studies of Sudden Upper Airway Obstruction in Patients With Hereditary Angioedema Due to C1 Esterase Inhibitor Deficiency. Arch Intern Med. 2003;163(10):1229-1235.

  • 24. 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. doi: 10.1016/j.jaci.2012.05.055. Epub 2012 Jul 28.

  • 25. Bowen T. Cicardi M. Farkas H. Bork K. Longhurst H.J. Zuraw B. et al. - 2010 International consensus algorithm for the diagnosis therapy and management of hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6(1):24. doi: 10.1186/1710-1492-6-24

  • 26. Aygören-Pürsün E. Martinez Saguer I. Kreuz W. Klingebiel T. Schwabe D. - Risk of angioedema following invasive or surgical procedures in HAE type I and II - the natural history. Allergy 2013;6 (8):1034-1039. doi: 10.1111/all.12186.

  • 27. Rice S. Cochrane T.J. Millwaters M. Ali N.T. - Emergency management of upper airway angio-oedema after routine dental extraction in a patient with C1 esterase deficiency. Br J Oral Maxillofac Surg. 2008;46(5):394-396.

  • 28. Bork K. Barnstedt S.E. - Laryngeal edema and death from asphyxiation after tooth extraction in four patients with hereditary angioedema. J Am Dent Assoc. 2003;134(8):1088-1094.

  • 29. Bork K. Wulff K. Hardt J. Witzke G. Staubach P. - Hereditary angioedema caused by missense mutations in the factor XII gene: clinical features trigger factors and therapy. J Allergy Clin Immunol. 2009;124(1):129-134. doi: 10.1016/j.jaci.2009.03.038. Epub 2009 May 27.

  • 30. Bouillet L. - Hereditary angioedema in women. Allergy Asthma Clin Immunol. 2010;6(1):17. doi: 10.1186/1710-1492-6-17.

  • 31. Bouillet L. Longhurst H. Boccon-Gibod I. Bork K. Bucher C. Bygum A. Caballero T. Drouet C. Farkas H. Massot C. Nielsen E.W. Ponard D. Cicardi M. - Disease expression in women with hereditary angioedema. Am J Obst Gynecol. 2008;199(5):484e1-e4. doi: 10.1016/j. ajog.2008.04.034. Epub 2008 Jun 13.

  • 32. Kuoppala A. Lindstedt K.A. Saarinen J. Kovanen P.T. Kokkonen J.O. - Inactivation of bradykinin by angiotensin-converting enzyme and by carboxypeptidase N in human plasma. Am J Physiol Heart Circ Physiol. 2000;278(4):H1069-H1074.

  • 33. Nielsen E.W. Gramstad S. - Angioedema from angiotensin-converting enzyme (ACE) inhibitor treated with complement 1 (C1) inhibitor concentrate. Acta Anaesthesiol Scand. 2006;50(1):120-122.

  • 34. Wilkerson R.G. - Angioedema in the emergency department: an evidence- based review. Emerg Med Pract. 2012;14(11):1-21. Epub 2012 Oct 20.

  • 35. Vitrat-Hincky V. Gompel A. Dumestre-Perard C. Boccon-Gibod I. Drouet C. Cesbron J.Y. Lunardi J. Massot C. Bouillet L. - Type III hereditary angio-oedema: clinical and biological features in a French cohort. Allergy 2010;65(10):1331-1336.

  • 36. Gras J. - Icatibant for hereditary angioedema. Drugs Today (Barc). 2009;45(12):855-864. doi: 1396674/dot.2009.45.12.1424267.

  • 37. Boccon-Gibod I. Bouillet L. - Safety and efficacy of icatibant self-administration for acute hereditary angioedema. Clin Exp Immunol. 2012;168(3):303-307.

  • 38. MacGinnitie A.J. Campion M. Stolz L.E. Pullman W.E. - Ecallantide for treatment of acute hereditary angioedema attacks: analysis of efficacy by patient characteristics. Allergy Asthma Proc. 2012;33(2):178-185.

  • 39. Cicardi M. Levy R.J. McNeil D.L. Li H.H. Sheffer A.L. Campion M. Horn P.T. Pullman W.E. - Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med. 2010;363(6):523-531.

  • 40. Farkas H. Gyeney L. Gidofalvy E. Fust G. Varga L. - The efficacy of short-term danazol prophylaxis in hereditary angioedema patients undergoing maxillofacial and dental procedures. J Oral Maxillofac Surg. 1999;57(4):404-408.

  • 41. Farkas H. Zotter Z. Csuka D. Szabo E. Nebenfuhrer Z. Temesszentandrasi G. Jakab L. Varga L. Harmat G. Karadi I. - Shortterm prophylaxis in hereditary angioedema due to deficiency of the C1- inhibitor--a long-term survey. Allergy 2012;67(12):1586-1593. doi: 10.1111/all.12032. Epub 2012 Oct 1.

  • 42. Farkas H. Varga L. - Human Plasma-Derived Nanofiltered C1-Inhibitor Concentrate (Cinryze®) a Novel Therapeutic Alternative for the Management of Hereditary Angioedema Resulting from C1-Inhibitor Deficiency. Biol Ther. 2012;2(1):2. doi: 10.1007/s13554-012-0002-5.

  • 43. Jaffe C.J. Atkinson J.P. Gelfand J.A. Frank M.M. - Hereditary angioedema: the use of fresh frozen plasma for prophylaxis in patients undergoing oral surgery. J Allergy Clin Immunol. 1975;55(6):386-393.

  • 44. Caballero T. Farkas H. Bouillet L. Bowen T. Gompel A. Fagerberg C. Bjokander J. Bork K. Bygum A. Cicardi M. de Carolis C. Frank M. Gooi J.H. - International consensus and practical guidelines on the gynecologic and obstetric management of female patients with hereditary angioedema caused by C1 inhibitor deficiency. J Allergy Clin Immunol. 2012;129(2):308-320. doi: 10.1016/j.jaci.2011.11.025. Epub 2011 Dec 24.

  • 45. Craig T.J. Kalra N. - Contemporary Issues in Prophylactic Therapy of Hereditary Angioedema. Medscape Education Allergy & Clinical Immunology. Released: 10/04/2010; Reviewed and Renewed: 07/30/2012; Valid for credit through 07/30/2013.

  • 46. Maurer M. Magerl M. - Long-term prophylaxis of hereditary angioedema with androgen derivates: a critical appraisal and potential alternatives. J Dtsch Dermatol Ges. 2011;9(2): 99-107. doi: 10.1111/j.1610-0387.2010.07546.x. Epub 2010 Oct 15.

  • 47. Cocchio C. Marzella N. - Cinryze a Human Plasma-Derived C1 Esterase Inhibitor for Prophylaxis Of Hereditary Angioedema. P T. 2009;34(6):293-328.

  • 48. Wood A. Choromanski D. Orlewicz M. - Intubation of patients with angioedema: A retrospective study of different methods over three year period. Int J Crit Illn Inj Sci. 2013;3(2):108-112. doi: 10.4103/2229-5151.114267.

  • 49. Cicardi M. Zuraw B. - Hereditary angioedema: Treatment of acute attacks. Available at Accessed May 10 2016.

  • 50. Nickson C. - Angioedema. Available at Accessed May 10 2016.

  • 51. Paix B.R. Griggs W.M. - Emergency surgical cricothyroidotomy: 24 successful cases leading to a simple 'scalpel-finger-tube' method. Emerg Med Australas. 2012;24(1):23-30. doi: 10.1111/j.1742-6723.2011.01510.x. Epub 2011 Dec 7.

  • 52. Farkas H. - Management of upper airway edema caused by hereditary angioedema. Allergy Asthma Clin Immunol. 2010;6:19. doi: 10.1186/1710-1492-6-19.

  • 53. Maestre M.L. Litvan H. Galan F. Puzo C. Villar Landeira J.M. - Impossibility of intubation due to angioedema secondary to an angiotensin- converting enzyme inhibitor. Rev Esp Anestesiol Reanim. 1999;46(2):88-91.

  • 54. Jonas N. Mulwafu W. Joubert J. - Emergency percutaneous tracheostomy. S Afr J Surg. 2007;45(3):105-106.

  • 55. Engels P.T. Bagshaw S.M. Meier M. Brindley P.G. - Tracheostomy: from insertion to decannulation. Can J Surg. 2009;52(5):427-433.

  • 56. Agostoni A. Cicardi M. - Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. Medicine (Baltimore). 1992;71(4):206-215.

  • 57. Kieu M.C. Bangiyev J.N. Thottam P.J. Levy P.D. - Predictors of Airway Intervention in Angiotensin-Converting Enzyme Inhibitor-Induced Angioedema. Otolaryngol Head Neck Surg. 2015;153(4):544-550. doi:10.1177/0194599815588909. Epub 2015 Jun 17.

  • 58. Ishoo E. Shah U.K. Grillone G.A. Stram J.R. FuleihanN.S. - Predicting airway risk in angioedema: staging system based on presentation. Otolaryngol Head Neck Surg. 1999;121(3):263-268.

  • 59. Bentsianov B.L. Parhiscar A. Azer M. Har-El G. - The role of fiberoptic nasopharyngoscopy in the management of the acute airway in angioneurotic edema. Laryngoscope 2000;110(12):2016-2019.

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