Hereditary angioedema in children: review and practical perspective for
clinical management
Abstract
Hereditary angioedema (HAE) is a rare, life-threatening genetic disorder
characterized by acute, recurrent and unpredictable episodes of
cutaneous or submucosal angioedema, mediated by bradykinin, due to C1
inhibitor (C1INH) abnormalities in the vast majority of cases. The
epidemiology of the disease is poorly documented in children. Clinical
manifestations usually appear during childhood or early adolescence.
Classical signs, preceded by prodromal symptoms in 50 % of cases,
include transient, localized, non-pitting, non-pruritic swelling of deep
dermal/subcutaneous or mucosal/submucosal tissues, leading to oedema of
the extremities, face, lips, tongue, trunk and genitals, recurring
gastrointestinal symptoms and laryngeal edema possibly causing
asphyxiation and death. Diagnosis is often delayed due to low awareness
in the medical community, and particularly challenging in case of
isolated abdominal crises or atypical presentation and in neonates or
infants. It relies on biological tests (measurement of serum/plasma
levels of C1INH function, C1INH protein, and C4), genetic testing in
selected cases, and imaging for differential diagnosis of acute
abdominal crises. Main differential diagnosis for peripheral oedema is
mast cell-mediated oedema that accounts for 95 % of angioedema in
clinical practice. Quality of life can be significantly impaired.
Disease management includes treatment of attacks, short-term and
long-term prophylaxis, psychological support, avoidance of triggers,
patients’ and parents’ education and coordination of all stakeholders,
ideally within a specialized healthcare network. New plasma kallikrein
inhibitors, namely lanadelumab (subcutaneous route) and berotralstat
(oral route) have facilitated long-term prophylaxis thanks to improved
usability.