Introduction
Hereditary angioedema (HAE) is a rare, potentially life-threatening disease with an estimated worldwide prevalence of 1:50 000.1 HAE is characterized by recurrent, transient episodes of subcutaneous or submucosal nonpruritic swelling that resolve spontaneously in 2-5 days.2–5The areas typically affected include the extremities, gastrointestinal tract, face, genitals, as well as larynx.1,5–10 The frequency, location and severity of attacks vary unpredictably and the clinical phenotype differs from patient to patient.8
Emotional distress, physical trauma, infections or changes in oestrogen levels have been identified as the most frequent precipitating factors although 50% of attacks do not have recognized triggers.7,8,11 The number of attacks differs from patient to patient, but when not treated, attacks can appear every 7 to 14 days on average with frequency ranging from virtually never to every 3 days. Usually, the swelling worsens progressively over the first 24 hours, then slowly subsides over the subsequent 48 to 72 hours.1 Aside from significant disruptions to everyday life, severe episodes can be extremely painful and disabling; and laryngeal swellings can cause asphyxiation or permanent brain damage.12–14
Recent data suggests that more than 80% of HAE patients may experience prodromes, also referred to as early symptoms or signs, that precede the swelling attack.15,16 The most common include tiredness, irritability, erythema marginatum (EM), tight or tingling sensation in the skin, abdominal discomfort, and nausea.1,11,16,17 Previous studies confirmed that prodromes are more frequent than initially realized and a significant correlation was shown between the perception of prodrome and the ability to predict an oncoming swelling.18 Of all the above-mentioned early symptoms, EM is the only objective phenomenon. Pathophysiological changes, such as elevation of D-dimer levels begin during EM development and thus, EM may actually be regarded as the initial phase of an HAE attack, not a separate entity.17
These findings are of importance considering the widespread availability of treatments for on-demand use, such as C1 esterase inhibitor (C1-INH) concentrate and icatibant, which can be administered at home by the patient.4,19Early treatment of HAE attacks with icatibant, particularly within the first hour of attack onset, significantly reduced attack duration and time to attack resolution.20 Accordingly, prodromes may alert patients of forthcoming attacks and allow them to deploy therapeutic strategies to avoid or shorten them. Unfortunately, limited research has been done on prodromes in HAE and they remain mostly subjective with their contribution to treatment disputed.21
This article presents the results of a patient-focused survey, which sought to characterize levels of awareness of prodromal symptoms amongst HAE patients to understand what kind of symptoms HAE patients may experience prior to swellings and how patients managed early signs and symptoms.