Review Article

Hereditary Angioedema: Implications of Management

Authors: Mohini Pathria, MD, Guha Krishnaswamy, MD, Juan C. Guarderas, MD

Abstract

Hereditary angioedema (HAE) is a genetic condition that is characterized by frequent episodes of localized angioedema. It is a rare disorder that a primary care provider, otolaryngologist, dermatologist, or rheumatologist may encounter only occasionally. This disease is being reviewed because of the significant advances in further understanding the genetics, biology, and therapeutic management surrounding the condition. Histamine-mediated angioedema responds to steroids, antihistamines, and epinephrine, whereas bradykinin-mediated angioedema is resistant to those interventions and requires specialized therapy. Previously used medications have significant adverse effects. Approved medications for HAE have been effective in decreasing morbidity and mortality in patients with this condition. We review the presentation, diagnosis, and available pharmaceutical options for HAE and explore the limitations of implementing recommended therapy.

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References

1. Osler W. Landmark publication from The American Journal of the Medical Sciences: hereditary angio-neurotic oedema. 1888. Am J Med Sci 2010;339:175-178.
 
2. Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med 1976;84:580-593.
 
3. Canonica GW, Rossi O. Diagnosis and treatment of hereditary angioedema. Panminerva Med 2012;54:241-253.
 
4. Donaldson VH, Evans RR. A biochemical abnormality in hereditary angioneurotic edema: absence of serum inhibitor of C'1-esterase. Am J Med 1963;35:37-44.
 
5. Cicardi M, Agostoni A. Hereditary angioedema. N Engl J Med 1996;334:1666-1667.
 
6. 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;106:1147-1154.
 
7. Kaplan AP, Joseph K. The bradykinin-forming cascade and its role in hereditary angioedema. Ann Allergy Asthma Immunol 2010;104:193-204.
 
8. Rosen FS, Pensky J, Donaldson V, et al. Hereditary angioneurotic edema: two genetic variants. Science 1965;148:957-958.
 
9. Bork K. Hereditary angioedema with normal C1 esterase inhibitor activity including hereditary angioedema with coagulation factor XII gene mutations. Immunol Allergy Clin North Am 2006;26:709-724.
 
10. Longhurst H, Cicardi M. Hereditary angio-oedema. Lancet 2012;379:474-481.
 
11. Agostoni A, Cicardi M. Hereditary and acquired C1-inhibitor deficiency: biological and clinical characteristics in 235 patients. Medicine (Baltimore) 1992;71:206-215.
 
12. Bork K, Siedlecki K, Bosch S, et al. Asphyxiation by laryngeal edema in patients with hereditary angioedema. Mayo Clin Proc 2000;75:349-354.
 
13. Binkley KE, Davis A, 3rd. Clinical, biochemical, and genetic characterization of a novel estrogen-dependent inherited form of angioedema. J Allergy Clin Immunol 2000;106:546-550.
 
14. Bork K, Meng G, Staubach P, et al. Hereditary angioedema: new findings concerning symptoms, affected organs, and course. Am J Med 2006;119:267-274.
 
15. Bork K, Meng G, Staubach P, et al. Treatment with C1 esterase inhibitor concentrate in abdominal pain attacks of patients with hereditary angioedema. Transfusion 2005;45:1774-1784.
 
16. Farkas H, Harmat G, Kaposi PN, et al. Ultrasonography in the diagnosis and monitoring of ascites in acute abdominal attacks of hereditary angioneurotic oedema. Eur J Gastroenterol Hepatol 2001;13:122-1230.
 
17. Farkas H. Pediatric hereditary angioedema due to C1-inhibitor deficiency. Allergy Asthma Clin Immunol 2010;6:18.
 
18. Prematta MJ, Kemp JG, Gibbs JG, et al. Frequency, timing, and type of prodromal symptoms associated with hereditary angioedema attacks. Allergy Asthma Proc 2009;30:506-511.
 
19. Farkas H, Harmat G, Fay A, et al. Erythema marginatum preceding an acute oedematous attack of hereditary angioneurotic oedema. Acta Derm Venereol 2001;81:376-377.
 
20. Banerji A, Busse P, Christiansen SC, et al. Current state of hereditary angioedema management: a patient survey. Allergy Asthma Proc 2015;36:213-217.
 
21. Fouche AS, Saunders EF, Craig T. Depression and anxiety in patients with hereditary angioedema. Ann Allergy Asthma Immunol 2014;112:371-375.
 
22. Bygum A. Hereditary angio-edema in Denmark: a nationwide survey. Br J Dermatol 2009;161:1153-1158.
 
23. Grigoriadou S, Longhurst HJ. Clinical immunology review series: an approach to the patient with angio-oedema. Clin Exp Immunol 2009;155:367-377.
 
24. Cicardi M, Zanichelli A. Acquired angioedema. Allergy Asthma Clin Immunol 2010;6:14.
 
25. Vasekar M, Craig TJ. ACE-inhibitor-induced angioedema. Curr Allergy Asthma Rep 2012;12:72-78.
 
26. Sanchez-Borges M, Capriles-Hulett A, Caballero-Fonseca F. NSAID-induced urticaria and angioedema: a reappraisal of its clinical management. Am J Clin Dermatol 2002;3:599-607.
 
27. Lin TY, Chiang CH, Cheng PS. Melkersson-Rosenthal syndrome. J Formos Med Assoc 2016;115:583-584.
 
28. Feldman MF, Khan DA, Brown ES, et al. Factitious angioedema: a mimic of refractory "angioedema". J Allergy Clin Immunol Pract 2014;2:795-797.
 
29. Wagenaar-Bos IG, Drouet C, Aygoren-Pursun E, et al. Functional C1-inhibitor diagnostics in hereditary angioedema: assay evaluation and recommendations. J Immunol Methods 2008;338:14-20.
 
30. Brecy H, Hartmann L. Distinction between hereditary and acquired angioneurotic oedema according to the complement system. Biomedicine 1975;23:328-334.
 
31. Gompels MM, Lock RJ, Morgan JE, et al. A multicentre evaluation of the diagnostic efficiency of serological investigations for C1 inhibitor deficiency. J Clin Pathol 2002;55:145-147.
 
32. 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.
 
33. Cicardi M, Johnston DT. Hereditary and acquired complement component 1 esterase inhibitor deficiency: a review for the hematologist. Acta Haematol 2012;127:208-220.
 
34. Prematta MJ, Bewtra AK, Levy RJ, et al. Per-attack reporting of prodromal symptoms concurrent with C1-inhibitor treatment of hereditary angioedema attacks. Adv Ther 2012;29:913-922.
 
35. 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;104:314-320.
 
36. 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;124:801-808.
 
37. Zuraw B, Cicardi M, Levy RJ, et al. Recombinant human C1-inhibitor for the treatment of acute angioedema attacks in patients with hereditary angioedema. J Allergy Clin Immunol 2010;126:821-827. e14.
 
38. Cohen G, Peterson A. Treatment of hereditary angioedema with fresh frozen plasma. Ann Allergy 1972;30:690-692.
 
39. Prematta M, Gibbs JG, Pratt EL, et al. Fresh frozen plasma for the treatment of hereditary angioedema. Ann Allergy Asthma Immunol 2007;98:383-388.
 
40. Cicardi M, Banerji A, Bracho F, et al. Icatibant, a new bradykinin-receptor antagonist, in hereditary angioedema. N Engl J Med 2010;363:532-541.
 
41. Cicardi M, Levy RJ, McNeil DL, et al. Ecallantide for the treatment of acute attacks in hereditary angioedema. N Engl J Med 2010;363:523-531.
 
42. 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;286:808-812.
 
43. Blohme G. Treatment of hereditary angioneurotic oedema with tranexamic acid. A random double-blind cross-over study. Acta Med Scand 1972;192:293-298.
 
44. 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;295:1444-1448.
 
45. Falus A, Feher K, Walcz E, et al. Hormonal regulation of complement biosynthesis in human cell lines-I. Androgens and gamma-interferon stimulate the biosynthesis and gene expression of C1 inhibitor in human cell lines U937 and HepG2. Mol Immunol 1990;27:191-195.
 
46. Craig TJ. Appraisal of danazol prophylaxis for hereditary angioedema. Allergy Asthma Proc 2008;29:225-231.
 
47. Giardino F, Cicardi M, Neri S. Use of subcutaneous-C1 INH for acute therapy and prophylaxis of a child with HAE. Pediatr Allergy Immunol 2015;26:296-297.
 
48. Craig T, Aygö-Püü E, Bork K, et al. WAO guideline for the management of hereditary angioedema. World Allergy Org J 2012;5:182-199.
 
49. Craig TJ. Recent advances in hereditary angioedema self-administration treatment: summary of an International Hereditary Angioedema Expert Meeting. Int Arch Allergy Immunol 2013;161(1 suppl):26-27.
 
50. Wang A, Fouche A, Craig TJ. Patients perception of self-administrated medication in the treatment of hereditary angioedema. Ann Allergy Asthma Immunol 2015;115:120-125.
 
51. Petraroli A, Squeglia V, Di Paola N, et al. Home therapy with plasma-derived C1 inhibitor: a strategy to improve clinical outcomes and costs in hereditary angioedema. Int Arch Allergy Immunol 2015;166:259-266.
 
52. Boysen HB, Bouillet L, Aygoren-Pursun E. Challenges of C1-inhibitor concentrate self-administration. Int Arch Allergy Immunol 2013;161(1 suppl):21-25.