D3.52 - Clinical spectrum and diagnostic challenges of paediatric angioedema without wheals

Angioedema without wheals in children poses a diagnostic challenge, particularly in distinguishing mast cell–mediated disease from hereditary angioedema (HAE). While HAE frequently begins in childhood, paediatric data from Japan remain scarce. We aimed to clarify the real-world diagnostic spectrum and clinical characteristics of paediatric patients referred for suspected HAE at a tertiary allergy centre in Japan.

We retrospectively reviewed paediatric patients referred between July 2023 and January 2024 for evaluation of possible HAE. Clinical presentations, family history, laboratory findings including complement testing, treatment response, and final diagnoses were analysed. Genetic testing was performed when clinically indicated. Diagnoses were determined based on clinical course, laboratory results, and response to treatment.

Fourteen paediatric patients (median age 8.5 years, range 5–16; 36% male) were evaluated. Angioedema without wheals was the most common presenting feature, and 57% had a family history of angioedema. C4 and C1 inhibitor levels were within normal limits in all patients, and no cases of HAE with C1 inhibitor deficiency or dysfunction (HAE-C1INH) were identified.

Final diagnoses included mast cell–mediated angioedema (n=7, including suspected cases), pollen–food allergy syndrome (n=1), suspected inducible laryngeal obstruction (n=1), granulomatous cheilitis associated with Crohn’s disease (n=1), Kimura disease (n=1), suspected HAE with normal C1 inhibitor (HAE-nC1INH; n=2), and idiopathic non–mast cell–mediated angioedema (n=1). Three patients showed poor response to antihistamines and corticosteroids and were initially suspected of having HAE-nC1INH. Genetic panel testing was performed in two of these patients and revealed no pathogenic variants. A family history of angioedema was present in two patients, whereas the remaining patient, without a family history, was diagnosed with idiopathic non–mast cell–mediated angioedema.

In this Japanese paediatric study, mast cell–mediated angioedema was the most frequent diagnosis among children referred for suspected HAE, and no cases of HAE-C1INH were identified. Careful assessment of treatment response and clinical course was critical for differential diagnosis, even in patients with a family history suggestive of HAE.