Our case has some interesting clinical points [7]. First, the patient’s initial presentation was a pruritic erythema marginatum-like rash, followed by fever, abdominal pain, and AE on the hands and feet the next day. Fortunately, we did not miss the patient’s medical history of recurrent arm swelling for one year and checked her complement level, which led to confirmation of the diagnosis without delay at 4 years of age. HAE does not accompany pruritis or urticarial wheal, but it shows erythema marginatum-like prodromal skin rashes in 60% of cases that can interfere with and delay the HAE diagnosis by years [8]. Second, the patient’s mother developed symptoms of HAE 5 years later during breast cancer chemotherapy. HAE can be fatal due to laryngeal or gastrointestinal involvement, so its early diagnosis and treatment are essential [2]. The reported mean delay to diagnosis after the initial presentation was 8–13 years, but this patient and her mother were diagnosed without delay. The World Allergy Organization/European Academy of Allergy and Clinical Immunology (WAO/EAACI) guidelines for HAE [2] recommend that all patients with suspected HAE undergo the assessment of serum levels of C4 and C1-INH proteins as well as C1-INH function. If any of the levels are abnormally low, the tests should be repeated to confirm the diagnosis of HAE. The WAO/EAACI guidelines also recommend that all family members, including grandparents, parents, siblings, children, and grandchildren of HAE-1/2 patients, be screened due to the possibility of autosomal dominant inheritance and delayed diagnosis leading to morbidity, since the first AE event can be fatal due to airway involvement. Therefore, when a patient has suspected HAE at 4 years of age, the test should be repeated for confirmation and family screenings should be performed immediately. All early testing performed for the offspring of HAE-1/2 patients should be repeated after 1 year of age; the measurement of C4 was not useful for diagnosing HAE-1/2 in children younger than 12 months since C4 levels are frequently low in healthy infants. However, genetic testing increases the diagnostic reliability in children and may be helpful [2].

Third, in our case, AE did not recur after the first admission, and the recurrent abdominal pain improved spontaneously after 6 years of age; her mother’s symptoms disappeared after the discontinuation of tamoxifen, suggesting mild severity despite the early age at onset [7]. However, HAE is known to worsen around puberty and persist throughout life with unpredictable severity [5]. This case should be followed closely according to the recommendation that all patients have an action plan, avoid possible triggers that may induce HAE attacks, and be taught to self-administer medications [2,6]. The treatment of HAE is divided into treatments for acute attacks; maintenance therapy (long-term prophylaxis); and preprocedural prophylaxis (short-term prophylaxis) for surgical trauma, dental surgery, and endoscopy. All patients must have sufficient medication for the on-demand treatment of 2 attacks and carry on-demand medication at all times [2,6]. C1-INH should be used to treat HAE attacks in children under the age of 12 years [6]. In Korea, C1-INH and bradykinin B2 receptor antagonist icatibant (≥2 years of age) are available, while the oral kallikrein inhibitor for long-term prophylaxis is currently in clinical trial [9].