D1.418 - A complex case of recurrent spontaneous angioedema in a young teenager, ‘The Devil is in the details’
Case report
Recurrent episodes of angioedema with airway obstruction are clinically challenging to manage. The pathogenesis could be difficult to explain and the risk of misdiagnosis is high.
A 16-year-old White British female presented with acute-onset facial and tongue swelling, stridor and wheeze. Based on the clinical history, the probable diagnosis was probable anaphylaxis to Fusidic Acid eye drop. The patient had a squint surgery just before the onset of symptoms, and at recovery, she had stiffness of the upper limb. She received intramuscular adrenaline, an antihistamine and intravenous steroid without clinical improvement. The persistent tongue swelling and angioedema leading to upper airway obstruction requiring emergency tracheostomy. Because of a lack of response to standard treatment protocol, a possible clinical diagnosis of hereditary angioedema (HAE) was considered and was treated with fresh frozen plasma and C1-esterase inhibitor. The patient recovered from the acute episode but continued to have multiple episodes of milder angioedema leading to hospital attendance.
She had a previous unconfirmed diagnosis of possible multiple allergies, functional abdominal pain and recurrent urticarial rash as well as behavioural difficulties.
The assay for C3, C4, and C1 esterase inhibitor levels and functions were normal, ruling out HAE types 1 and 2, pointing to a diagnosis of type 3 HAE. There is no evidence of a mutation in factor XII, plasminogen (Ex9), or angiotensin-1 (Ex2) SERPING1 gene or spontaneous mutation in the factor XII hot spot (R368.1 panel). Subsequently, she fell pregnant and received pre-delivery pre-emptive C1-estarase without angioedema and successful delivery.
Discussion: The most important learning point from this ultra-rare and unusual presentation of HAE type III is the normal blood level and functionality of the C1-esterase inhibitor. In this extraordinary case, the absence of an abnormal genetic finding does not rule out HAE Type III and its pathogenesis is unknown; however, the pre-emptive use of the C1-esterase inhibitor mitigates acute angioedema during physiological stress like pregnancy and childbirth.
Conclusion: Recurrent severe angioedema, which is unresponsive to antihistamine and steroids, should raise clinical suspicion of HAE. Moreover, normal laboratory investigations and genetic tests do not rule out type III HAE. This condition is rare, and its pathogenesis is unknown. However, pre-emptive use of a C1-Esterase inhibitor during pregnancy mitigated the risk of angioedema during pregnancy and childbirth in this case.
