Anne Pagnier

and 14 more

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.