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HAE GLOSSARY
Acquired angioedema due to C1INH deficiency
A rare, bradykinin-mediated angioedema that causes recurrent swelling of the skin, gastrointestinal tract, or airway. It typically occurs later in life (after age 40) and is often associated with hematological or autoimmune disorders.1,2
Angioedema attack
An episode of localized, non-pitting, non-pruritic swelling that can affect subcutaneous tissues, the gastrointestinal tract, or airway, often progressing over hours.3
Bradykinin
A potent vasodilatory peptide that increases vascular permeability and causes swelling. In HAE, excessive bradykinin leads to the clinical manifestations of recurrent attacks of angioedema.4,5
Bradykinin B2 receptor
The primary receptor mediating bradykinin’s effects in most types of HAE. Activation of this receptor on endothelial cells leads to vasodilation and fluid extravasation.4,6
Bradykinin-mediated angioedema
A non-histaminergic type of angioedema, generally due to increased bradykinin levels. The 2 main types are hereditary angioedema (due to C1 inhibitor deficiency or dysfunction) and acquired angioedema due to C1 inhibitor deficiency (often linked to hematological or autoimmune disorders).7,8
C1 inhibitor (C1INH)
A serine protease inhibitor that regulates the complement, contact, and fibrinolytic systems. Deficiency or dysfunction leads to uncontrolled bradykinin production and angioedema in HAE types 1 and 2.9
HAE with normal C1 Inhibitor
A more rare type where C1INH levels are normal, but the HAE may be caused by other genetic mutations.9,10
Hereditary angioedema (HAE)
A rare genetic disorder characterized by recurrent episodes of severe, localized swelling (angioedema) affecting the skin, gastrointestinal tract, and airway, generally caused by overproduction of bradykinin, leading to increased vascular permeability.4,11
High-molecular-weight kininogen (HMWK)
A plasma protein that serves as the substrate for plasma kallikrein. Its cleavage releases bradykinin during an HAE attack.4,11
Laryngeal edema
A life-threatening manifestation of HAE characterized by swelling of the upper airway, requiring prompt recognition and emergency treatment.4
Plasma kallikrein
A protease in the contact activation system that cleaves HMWK to release bradykinin. Dysregulation leads to excess bradykinin production in HAE.4,5
Prodrome
Subtle symptoms (e.g., fatigue, erythema marginatum, tingling) that precede an angioedema attack.3,12
Type 1 HAE
The most common form (~85% of cases), characterized by low levels of functional C1INH due to decreased production.9,13
Type 2 HAE
A less-common variant where C1INH levels are normal or elevated but functionally defective.4,9
References
- Otani IM, et al. Immunol Allergy Clin North Am. 2017;37(3):497-511.
- Cicardi M, et al. N Engl J Med. 2010;363:532-541.
- Azmy V, et al. Allergy Asthma Proc. 2020;41(6):S18-S21.
- Maurer M, et al. Allergy. 2022;77(7):1961-1990.
- Lima H, et al. Front Allergy. 2023;10(4):1-5.
- Smith TD, et al. Ann Allergy Asthma Immunol. 2024;133:380-390.
- Lacuesta G, et al. Allergy Asthma Clin Immunol. 2024;20(65):1-9.
- Reshef A, et al. J Allergy Clin Immunol. 2024;154(2):398-411.e1.
- Sinnathamby ES, et al. Adv Ther. 2023;40:814-827.
- Busse PJ, et al. J Allergy Clin Immunol Pract. 2021;9(1):132-150.
- Shamanaev A, et al. Front Physiol. 2023;14:1146834:1-13.
- Leibovich-Nassi I, et al. Clin Rev Allergy Immunol. 2021;61:15-28.
- Nzeako UC, et al. Arch Intern Med. 2001;161:2417-2429.
