Hereditary angioedema in children: Review and practical perspective for clinical management

Abstract

Background: Hereditary angioedema (HAE) in children has specific features and requires multidisciplinary management.

Methods: We performed a literature search and underwent in-depth discussions to provide practical tools for physicians.

Results: HAE is a rare, life-threatening genetic disorder. Its epidemiology is poorly documented in children. Clinical manifestations usually appear during childhood or early adolescence. Classical signs, often preceded by prodromal symptoms, 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.

Conclusion: Diagnostic and treatment of HAE are particularly challenging in children and require specific management by multiple stakeholders.

Keywords: daily diary; iatrogenic; suicide ideation.

FIGURE 1

Pathophysiology of C1‐INH HAE. C1‐INH, C1 inhibitor; ACE, Angiotensin converting enzyme; APP, Aminopeptidase P; DPP4, Dipeptidylpeptidase‐4; NEP, Neprilysin; B2R, Bradykinin type 2 constitutive receptor.

FIGURE 2

Etiologies of localized edema and distribution of patients.

FIGURE 3

Facial edema.

FIGURE 4

Most frequent triggers provoking HAE attacks.

FIGURE 5

Example of erythema marginatum.

FIGURE 6

Abdominal ultrasonography. (A) Uniform prominent hypoechoic folds better appreciated on longitudinal view. (B) Non‐stratified thickening of small bowel with luminal narrowing on axial view.