Urgent diagnosis of hereditary angioedema in the ICU and ED: the critical role of rapid complement testing - a case report.

BACKGROUND: Hereditary angioedema (HAE) affects 1.22 people per 100,000 worldwide, and can cause fatal airway obstruction due to laryngeal oedema. Diagnosis is often delayed by several years, due to rarity, and similarity to more common histamine-mediated angioedema. Approximately 20-25% of cases have a de novo genetic variant, and no family history. Clinically, HAE is characterised by recurrent, non-pruritic swelling of the skin and mucosal tissues, without urticaria, which does not respond to antihistamines, corticosteroids or adrenaline. Definitive diagnosis requires demonstration of reduced C1inhibitor levels or function, which cannot be provided on an emergency basis. Complement C4 levels are always reduced during acute attacks, and awareness of this surrogate test in an appropriate clinical setting allows appropriate management of previously undiagnosed patients, in emergency settings. CASE PRESENTATION: A female in her thirties presented to the emergency department (ED) with a 36-hour history of progressive facial swelling, including lip, tongue and uvular oedema, with concerns for airway compromise, requiring ICU admission for airway monitoring. She reported three similar previous episodes, and exhibited no urticaria or features of an allergic reaction. Treatments for histaminergic angioedema were ineffective. Given slowly-evolving episodes of angioedema, absence of urticaria or response to therapy, HAE was suspected. Urgent complement testing showed a markedly reduced C4 level with a result available in 1 h. Based on the patient's presentation and very low C4, a presumptive diagnosis of an acute HAE attack was made, and treatment with Icatibant was given. The patient responded rapidly to treatment, with full resolution of symptoms. Subsequent testing confirmed a diagnosis of HAE with C1 esterase inhibitor deficiency. CONCLUSION: This case highlights the importance of considering HAE in patients presenting with unexplained slowly-evolving angioedema without urticaria, when traditional histamine-directed therapies fail, especially when airway compromise is imminent. Awareness that C4 levels are universally low during HAE attacks, is key. C4 testing is widely available and prompt communication with biochemistry or immunology laboratories facilitates rapid turnaround. Urgent presumptive diagnosis facilitates appropriate emergency management and prompt referral for definitive diagnosis and management. Early identification and management of HAE can significantly reduce morbidity and mortality associated with this condition.