Most patients with hereditary angioedema (HAE) who have experienced a prodrome can predict when symptoms or swelling will occur, according to a preprint published in Authorea.

Moreover, the study suggests that early treatment of HAE attacks may help reduce medication-related burden among patients with HAE.

“We hope that our findings will stimulate further interest in how prodromes can contribute to management of HAE,” the study’s authors said. “Better characterization and understanding of prodromal symptoms may help patients recognize that an attack is developing and institute preventative behavioural or treatment measures to mitigate swellings and lessen the impact of the disease on their day-to-day life.”

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According to the results, 60% of responders were often or always aware of prodromal signs and symptoms, which included tiredness/fatigue (64%), pressure or tightness in the skin (53%), abdominal pressure (52%), and widespread pain in the abdomen (48%). Furthermore, over one-third of responders experienced skin rash.

Read more about HAE prognosis

Responders have noticed prodromes within 2 hours (38%), between 2 and 6 hours (27%), and more than 6 hours (29%) before the swelling has started. Swelling mostly occurred in the abdomen (89%), followed by hands (71%), feet (63%), and face (40%).

Most (59%) responders said they took medication when they experienced an early prodromal sign/symptom. There were, however, different reactions. While most participants in the UK took some kind of medication, most participants in Spain often preferred to “watch and wait,” try to relax, go to bed, or take a bath.

In addition, the analysis of the surveys suggest that early treatment may reduce the use of medication during HAE attacks. The proportions of responders requiring 1, 2, or 3 injections to treat an HAE attack were 55%, 29%, and 5%, respectively. When taking medication at the onset of early signs/symptoms and before the swelling has started, 65% of responders typically needed 1 injection to treat an HAE attack, 21% needed 2 injections, and 6% needed 3 injections.

Most (70%) responders said their healthcare provider has advised them to “treat early,” although the understanding of the best time to take their medication was not unanimous. For 60% of responders, it meant as soon as they experience an early prodromal sign/symptom, for 26% it meant taking medication if the early signs/symptoms persisted or progressed, and for 13% it meant as soon as the swelling started.

The study enrolled 208 patients with HAE (mean age, 46 years, 65% females) from the UK (61%) or Spain (39%). Participants responded to a survey questionnaire assessing their experience with prodromal signs/symptoms.


Mar G and Yong P. Prodromal symptoms of hereditary angioedema (HAE) attacks: a patient survey in UK & Spain. Authorea. Published online May 4, 2023. doi:10.22541/au.168317302.29518030/v1