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Hereditary Angioedema: Diagnosis, Pathogenesis, and Therapy

  • Urticaria and Atopic Dermatitis (M Furue and T Nakahara, Section Editors)
  • Published:
Current Treatment Options in Allergy Aims and scope Submit manuscript

Abstract

Purpose of Review

This review will focus on our current understanding of the pathogenesis of hereditary angioedema (HAE) and its therapy. HAE is classically meant to describe C1 inhibitor deficiency, a form of angioedema that leads to overproduction of bradykinin due to loss of control of enzymatic reactions. Treatment can be directed to acute attacks and/or focused on prophylaxis to prevent attacks that can vary from peripheral to gastrointestinal, to laryngeal individually or in any combination.

Recent Findings

Acute therapy employs a bradykinin B-2 receptor antagonist, inhibition of plasma kallikrein, or an intravenous bolus of C1 inhibitor. Prophylaxis can include intravenous C1 inhibitor twice weekly, subcutaneous C1 inhibitor, a monoclonal antibody to plasma kallikrein administered every 2 weeks, or an oral plasma kallikrein inhibitor taken daily. There are now 6 types of hereditary angioedema in which C1 inhibitor is normal (HAEN). Whereas many of the therapeutic modalities listed above are helpful, a particular role for tranexamic acid to bind to plasminogen and inhibit plasmin formation, or progesterone to antagonize estrogen effects, have been successfully employed for two of them in which there is a mutation of either factor XII or plasminogen.

Summary

A new finding regarding pathogenesis highlight fibrinolytic proteins including plasmin activation of factor XII which is markedly augmented when factor XII is mutated, and direct activation of both kininogens when plasminogen is mutated and converted to plasmin. A new emphasis on the therapeutic efficacy of transexamic acid and progesterone is associated with HAEN while therapy of types I and II HAE (C1 inhibitor deficiency) have new approaches including administration of subcutaneous C1 INH, or a monoclonal antibody to plasma kallikrein, and an oral once-daily kallikrein inhibitor. A recombinant C1 INH produced in rabbits is available for as-needed treatment.

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    Allen P. Kaplan M.D.

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Review cases for adjudication of allergic reactions for Novartis, Genentech, Roche, Astra Zeneca, Sanofi-Aventis, and Abb-RISA. Consultant for BioCryst, Pharvaria, Biomarin, CSL-Behring, Novartis, Celldex, Annexon, and Takeda Pharmin.

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Kaplan, A.P. Hereditary Angioedema: Diagnosis, Pathogenesis, and Therapy. Curr Treat Options Allergy 9, 118–136 (2022). https://doi.org/10.1007/s40521-022-00308-3

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