Throat Edema Unresponsive to Glucocorticoids and Antihistamines: A Warning for the Risk of Hereditary Angioedema

Hereditary angioedema (HAE) is a rare genetic disorder characterized by spontaneous, localized swelling of soft tissues. ¹ If swelling occurs in the respiratory tract, hypoxia and suffocation can rapidly develop. HAE is prone to misdiagnosis, leading to poor prognosis, especially in cases of initial diagnosis and lack of family or past medical history. This report presents a case of HAE to illustrate its clinical features and diagnostic challenges.

A 22-year-old man went to the emergency department due to facial and eyelid swelling several hours ago, which worsened after the use of anti-allergic drugs and medicinal facial masks, accompanied by swelling of lips and perioral areas. He denied other symptoms such as fever, palpitations, dyspnea, abdominal pain, or urticaria. He reported a history of recurrent facial and foreskin swelling that was relieved with anti-allergic treatment. He was considered allergic and received treatment with dexamethasone, oxygen inhalation, and electrocardiographic monitoring. Subsequently, he experienced mild respiratory obstruction and nasal congestion, and a physical examination revealed laryngeal edema. The otolaryngologist suggested endotracheal intubation or tracheotomy for treatment; however, his family refused. Approximately 10 minutes later, he suddenly experienced respiratory distress followed by cardiac arrest. Following rapid emergency interventions, including tracheal intubation, cardiac compression, and adrenaline injection, spontaneous heartbeat was restored, and the patient was admitted to the ICU. During hospitalization, a review of the patient’s medical records revealed that his father had a similar history of recurrent, unexplained abdominal pain, suggesting a potential familial link to HAE. In addition, a low complement C4 level (0.075 g/L; reference range 0.1-0.4 g/L) provided supportive evidence for the diagnosis of HAE. Unfortunately, he passed away 2 days later due to complications including cerebral edema, pulmonary infection, cerebral infarction, and central respiratory and circulatory failure. The results of the C1-INH test on his father and sister confirmed the diagnosis of HAE in their family. This case has obtained written consent from the patient’s family.

HAE is an autosomal dominant genetic disease caused by low level, dysfunction, or deficiency of C1 esterase inhibitors (C1-INH) in the serum. ² It is characterized by recurrent systemic skin and submucosal edema, which is more common in limbs, face, respiratory tract, and gastrointestinal tract. ³ The most life-threatening manifestation is upper respiratory mucosal edema, which can lead to breathing difficulties or suffocation due to the rapid progression of laryngeal edema. Although HAE can present with clinical features similar to acute epiglottitis and allergic edema, it is distinguished by its lack of response to glucocorticoids and antihistamines. The acute management of HAE focuses on symptom relief and includes C1-INH replacement therapy (plasma-derived or recombinant human C1-INH), the kallikrein inhibitor ecallantide, and the bradykinin B2 receptor antagonist icatibant. Long-term prophylactic options include C1-INH, lanadelumab, attenuated androgens, and antifibrinolytics such as tranexamic acid. In addition, it is crucial to identify and avoid potential triggering factors to prevent episodes. ⁴

Otolaryngologists should maintain a high level of vigilance for HAE in patients presenting with recurrent or unexplained edema, particularly when standard treatments with glucocorticoids or antihistamines are ineffective, a thorough review of the patient’s past and family history is crucial. Early recognition and airway management are key to preventing life-threatening complications.