COVID-19-Induced Flare of Hereditary Angioedema in a Twelve-Year-Old Female Patient

Aman Kalkat1, Irfan Amir2, Sarah Azzi3

  • 1Allergy and Immunology, Case Western Reserve University/University Hospitals Cleveland Medical Center Program, Cleveland, USA.

Cureus
|September 3, 2025
PubMed

Hereditary angioedema (HAE) is a rare disorder characterized by recurrent episodes of angioedema, most often due to a deficiency or dysfunction of C1 esterase inhibitor. This deficiency leads to an accumulation of bradykinin, a pro-inflammatory peptide that increases vascular permeability and causes localized swelling. Although some HAE flares occur spontaneously, known triggers include trauma, stress, and infection. Clinical manifestations typically involve swelling of the skin, gastrointestinal tract, and upper airway. SARS-CoV-2, the virus responsible for COVID-19, enters host cells via angiotensin-converting enzyme 2 (ACE2). Viral binding and subsequent ACE2 depletion impair bradykinin degradation, leading to increased bradykinin levels, a mechanism that mirrors the pathophysiology of HAE. This shared pathway may contribute to HAE exacerbations during COVID-19 infections. We report the case of a pediatric patient with known HAE who experienced a disease flare triggered by COVID-19. While bradykinin-driven swelling in adult HAE patients with COVID-19 has been documented, pediatric reports are exceedingly rare. To our knowledge, this is the first published case detailing the symptom progression and treatment timeline of a confirmed pediatric HAE patient following SARS-CoV-2 infection. This case aims to raise awareness of COVID-19 as a potential trigger for HAE flares in children and emphasizes the need for healthcare providers to educate families of pediatric HAE patients about flare management and preparedness in the context of COVID-19, especially given its continued global circulation.

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