Hereditary Angioedema – Classification and Differential Diagnosis

Czech version

Authors: I. Krčmová
Authors‘ workplace: Ústav klinické imunologe a alergologie, Fakultní nemocnice Hradec Králové, přednosta prof. RNDr. Ctirad Andrýs, Ph. D.
Published in: Čes-slov Derm, 99, 2024, No. 3, p. 115-124
Category: Reviews (Continuing Medical Education)

Overview

Hereditary angioedema (HAE) is a rare, genetically determined disease with autosomal dominant transmission and a variable spectrum of clinical and life-threatening manifestations. In a broader context, it is an immunodeficiency disease, classified into HAE with a deficiency of C1 inhibitor (HAE-C1-INH, formerly HAE-I and HAE-II) and HAE with a normal level and function of C1 inhibitor (HAE nC1-INH), also referred to as HAE-III type, with mutations of another (often still unknown) type. The clinical manifestation is massive swelling of the subcutaneous tissue and/or mucous membranes due to uncontrolled activation of the complement and kinin systems. Local overproduction of bradykinin results in typical angioedema. More rarely, C1-inhibitor deficiency can arise in connection with other pathological conditions (autoimmune, lymphoproliferation, monoclonal gammopathy) – this is acquired angioedema (AAE). Angioedema induced by ACE inhibitors (AE-ACEi) is considered a separate clinical syndrome that must be distinguished from acquired angioedema. The pharmacological anamnesis is important, sartans, mTOR inhibitors, gliptins can also be risky, aliskiren, sacubitril, tissue plasminogen activator are mentioned among other drugs. The emergence of centers for the diagnosis and care of patients with HAE/AAE significantly improved the lives of these patients. Patients with atypical angioedema (predominantly of bradykinin etiology) are also sent to the centers on a consular basis.

Keywords:

hereditary angioedema – diagnosis – differential diagnosis – therapy

Sources

BANERJI, A., RIEDL, M. A., BERNSTEIN, J. A. et al. Effect of lanadelumab compared with placebo on prevention of hereditary angioedema attacks: a randomized clinical trial. JAMA, 2018, 320, p. 2108–2121.
BANERJI, A., BERNSTEIN, J. A., JOHNSTON, D. T. et al. Long-term prevention of hereditary angioedema attacks with lanadelumab: The HELP Study. Allergy, 2022, 77(3), p. 979–990.
BUSSE, P., BYGUM, A., EDELMAN, J. et al. Safety of C1-esterase inhibitor in acute and prophylactic therapy of hereditary angioedema: findings from the ongoing international Berinert patient registry. J Allergy Clin Immunol Pract., 2015, 3, p. 213–219.
BUSSE, P. J., CHRISTIANSEN, S. C. Hereditary angioedema. N Engl J Med., 2020, 382, p. 1136–1148.
BUSSE, P. J., CHRISTIANSEN, S. C., RIEDL, M. A. et al. US HAEA Medical Advisory Board 2020 Guidelines for the Management of Hereditary Angioedema. J Allergy Clin Immunol Pract., 2021, 9(1), p. 132–150.e3.
BUTTGEREIT, T., VERA, C., WELLER, K. et al. Lanadelumab Efficacy, Safety, and Injection Interval Extension in HAE: A Real-Life Study. J Allergy Clin Immunol Pract., 2021, 9(10), p. 3744–3751.
CRAIG, T., ZURAW, B., LONGHURST, H. et al. Long-Term Outcomes with Subcutaneous C1-Inhibitor Replacement Therapy for Prevention of Hereditary Angioedema Attacks. J Allergy Clin Immunol Pract., 2019, 7(6), p. 1793–802.e2.
HAKL, R. Současné možnosti léčby hereditárního angioedému. Vnitr Lek., 2016, 62(9), p. 736–739.
KRČMOVÁ, I. Hereditární angioedém – trendy v léčbě. Interní Med., 2017, 19(3), p. 131–137.
PETERSEN, R. S., BORDONE, L., RIEDL, M. A. et al. A phase 2 open-label extension study of prekallikrein inhibition with donidalorsen for hereditary angioedema. Allergy, 2024, 79(3), p. 724–734. doi: 10.1111/all.15948.
MALBRAN, A., RIEDL, M., RITCHIE, B. et al. Repeat treatment of acute hereditary angioedema attacks with open-label icatibant in the FAST-1 trial. Clin Exp Immunol., 2014, 177, p. 544–553.
MAURER, M., MAGERL, M., BETSCHEL, S. et al. The international WAO/EAACI guideline for the management of hereditary angioedema – The 2021 revision and update. Allergy, 2022, 77, p. 1961–1990. doi: 10.1111/all.15214
RIEDL, M. A., GRIVCHEVA-PANOVSKA, V., MOLDOVAN, D. et al. Recombinant human C1 esterase inhibitor for prophylaxis of hereditary angio-oedema: a phase 2, multicentre, randomised, double-blind, placebo-controlled crossover trial. Lancet, 2017, 390, p. 1595–1602.
SETTIPANE, R. A., BUKSTEIN, D., RIEDL, M. Shared decision making in HAE management. Allergy Asthma Proc., 2020, 41, p. S55–S60.
SOBOTKOVÁ, M., KRÁLÍČKOVÁ, P. et al. Hereditární angioedém. Praha: Current media s.r.o. 2021.
SOBOTKOVÁ, M. et al. Acquired angioedema with C1-inhibitor deficiency – occurrence, clinical features and management: A nationwide retrospective study in the Czech Republic patients. International Archives of Allergy and Immunology, 2021, 182(7), p. 642–649. doi: 10.1159/000512933.
SOBOTKOVÁ, M. Současná doporučení v léčbě hereditárního angioedému. Farmakoter Revue, 2023, 8(5), p. 400–404.
STOLZ, L. E., HORN, P. T. Ecallantide: a plasma kallikrein inhibitor for the treatment of acute attacks of hereditary angioedema. Drugs Today (Barc), 2010, 46(8), p. 547–555.
VALERIEVA, A., SENTER, R., WU, M. A., ZANICHELLI, A. et al. Lanadelumab for the prevention of attacks in hereditary angioedema. Expert Rev Clin Immunol., 2019, 15(12), p. 1239–1248.
VALERIEVA, A., STAEVSKA, M., JESENAK, M. et al. Recombinant human C1 esterase inhibitor as shortterm prophylaxis in patients with hereditary angioedema. J Allergy Clin Immunol Pract., 2020, 8(2),p. 799–802.
WAT, M. et al. Network meta-analysis for indirect comparison of lanadelumab and berotralstat for the treatment of hereditary angioedema. J Comp Eff Res., 2023, 12(6), p. e220188. doi: 10.57264/cer2022-0188.
ZURAW, B. L., BUSSE, P. J., WHITE, M. et al. Nanofiltered C1 inhibitor concentrate for treatment of hereditary angioedema. N Engl J Med., 2010, 363, p. 513–522.
ZURAW, B. L., DAVIS, D. K., CASTALDO, A. J. et al. Tolerability and effectiveness of 17-alpha-alkylated androgen therapy for hereditary angioedema: a re-examination. J Allergy Clin Immunol Pract., 2016, 4, p. 948–955.