TY - JOUR
T1 - Hereditary Angioedema with Normal C1 Inhibitor
T2 - an Updated International Consensus Paper on Diagnosis, Pathophysiology, and Treatment
AU - Zuraw, Bruce L.
AU - Bork, Konrad
AU - Bouillet, Laurence
AU - Christiansen, Sandra C.
AU - Farkas, Henriette
AU - Germenis, Anastasios E.
AU - Grumach, Anete S.
AU - Kaplan, Allen
AU - López-Lera, Alberto
AU - Magerl, Markus
AU - Riedl, Marc A.
AU - Adatia, Adil
AU - Banerji, Aleena
AU - Betschel, Stephen
AU - Boccon-Gibod, Isabelle
AU - Bova, Maria
AU - Boysen, Henrik Balle
AU - Caballero, Teresa
AU - Cancian, Mauro
AU - Castaldo, Anthony J.
AU - Cohn, Danny M.
AU - Corcoran, Deborah
AU - Drouet, Christian
AU - Fukunaga, Atsushi
AU - Hide, Michihiro
AU - Katelaris, Constance H.
AU - Li, Philip H.
AU - Longhurst, Hilary
AU - Peter, Jonny
AU - Psarros, Fotis
AU - Reshef, Avner
AU - Ritchie, Bruce
AU - Selva, Christine N.
AU - Zanichelli, Andrea
AU - Maurer, Marcus
N1 - Publisher Copyright:
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2025.
PY - 2025/12
Y1 - 2025/12
N2 - Hereditary angioedema (HAE) has been recognized for almost 150 years. The newest form of HAE, where C1 inhibitor levels are normal (HAE-nC1INH), was first described in 2000. Over the last two decades, new types of apparent non-mast cell–mediated angioedema with normal quantity and activity of C1INH have been described, in some cases with proven genetic pathogenic variants that co-segregate with angioedema expression within families. Like HAE due to C1INH deficiency, HAE-nC1INH patients are at risk of serious morbidity and mortality. Therefore, proactive management and treatment of HAE-nC1INH patients after an expert physician diagnosis is critically important. The underlying pathophysiology responsible for the angioedema has also been clarified in some of the HAE-nC1INH types. While several clinical guidelines and practice parameters including HAE-nC1INH have been published, we have made substantial progress in our understanding encompassing diagnostic criteria, pathophysiology, and treatment outcomes. HAE International (HAEi) and the US HAE Association (HAEA) convened a symposium of global HAE-nC1INH experts to synthesize our current knowledge in the area. Given the paucity of high-level evidence in HAE-nC1INH, all recommendations are based on expert opinion. This review and expert opinion on the best practice approach to diagnosing and treating HAE-nC1INH will support physicians to better manage patients with HAE-nC1INH.
AB - Hereditary angioedema (HAE) has been recognized for almost 150 years. The newest form of HAE, where C1 inhibitor levels are normal (HAE-nC1INH), was first described in 2000. Over the last two decades, new types of apparent non-mast cell–mediated angioedema with normal quantity and activity of C1INH have been described, in some cases with proven genetic pathogenic variants that co-segregate with angioedema expression within families. Like HAE due to C1INH deficiency, HAE-nC1INH patients are at risk of serious morbidity and mortality. Therefore, proactive management and treatment of HAE-nC1INH patients after an expert physician diagnosis is critically important. The underlying pathophysiology responsible for the angioedema has also been clarified in some of the HAE-nC1INH types. While several clinical guidelines and practice parameters including HAE-nC1INH have been published, we have made substantial progress in our understanding encompassing diagnostic criteria, pathophysiology, and treatment outcomes. HAE International (HAEi) and the US HAE Association (HAEA) convened a symposium of global HAE-nC1INH experts to synthesize our current knowledge in the area. Given the paucity of high-level evidence in HAE-nC1INH, all recommendations are based on expert opinion. This review and expert opinion on the best practice approach to diagnosing and treating HAE-nC1INH will support physicians to better manage patients with HAE-nC1INH.
KW - Bradykinin
KW - Diagnosis
KW - HAE
KW - HAE-C1INH
KW - HAE-nC1INH
KW - Pathophysiology
KW - Treatment
UR - http://www.scopus.com/inward/record.url?scp=86000282701&partnerID=8YFLogxK
U2 - 10.1007/s12016-025-09027-4
DO - 10.1007/s12016-025-09027-4
M3 - Article
C2 - 40053270
AN - SCOPUS:86000282701
SN - 1080-0549
VL - 68
JO - Clinical Reviews in Allergy and Immunology
JF - Clinical Reviews in Allergy and Immunology
IS - 1
M1 - 24
ER -