D2.313 - Importance of non-itchy erythema marginatum as a prodromal symptom of hereditary angioedema attacks

Improvements in the treatment of hereditary angioedema caused by C1 inhibitor deficiency (C1-INH-HAE) have been made in the last few years. However, it is not unusual for this rare genetic disease to be misdiagnosed or to be diagnosed decades after the onset of symptoms,  Erythema marginatum (EM) in particular is problematic because, despite being a common prodrome of C1-INH-HAE attacks in children, it is frequently confused with urticaria. However, a close examination reveals that it is easily differentiated from urticaria, which is pruritic, temporary, and more widespread, frequently exhibiting smaller or larger elevated wheals. Intravenous injection of C1-inhibitor concentrate, which was authorized in Ukraine for the treatment of acute HAE attacks and permits early therapy, has markedly improved  HAE therapy.  EM is a known visible prodromal symptom that can occasionally appear before an angioedema attack.  Early HAE treatment depends on identifying the risk of an acute attack. The clinical signs of EM in  HAE were assessed in this study.

Clinical data on EM from patients with HAE was collected using  a  survey containing 10 questions developed at our institute. Information was gathered from  48 adult HAE patients, including 36 with HAE-1, 9 with  HAE-2 and 3 with  HAE-unknown origin.

53.3% of the patients with HAE-1 and HAE -2 had erythema marginatum, while 46.7 % did not. The forearm (45.8%), upper arm (29.1 %), and abdomen (25.1%), were the most common sites of EM. Of the HAE-1 and HAE-2 patients with EM, 58.3% always had continuation of EM during angioedema attacks, and 12.5% reported a dependency between the intensity of angioedema attacks and EM manifestation. The time between becoming aware of EM and the onset of angioedema was less than three hours in 41.7 % of HAE-1 and HAE-2 patients with EM. In 45.8% of HAE-1 and HAE-2 cases, non-itchy EM was the first symptom leading to a future HAE diagnosis.

EM is a prodromal symptom of an angioedema attack in approximatly 42% of Ukrainian adult patients with HAE-1 and HAE-2.  Patients with HAE should be informed by their doctors about the importance of EM in order to prepare them for any impending HAE attacks which need treatment.