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.