DISCUSSION
Pre-attack perceptions has been reported by HAE patient’s from the early
descriptions of this rare genetic disorder, but are still loosely
defined and therefore pose a clinical condundrum.7-12Some prodromes are charchterized by objective physical signs, even at
the same location of the attack, which helps to fortell its development
(i.e. Erythema Marginatum rash on the abdomen), but some are manifested
by subjective sensations reflecting high variability in individual
perceptions.8 At the present time, a large body of
evidence supports the observation that prodromes are an intergral part
of the edematous attacks, and may even represent a continuity of
pathophysiologic events invlovling the bradykinin-forming cascade as
well as the vascular endothelium. 14-17
HAE is a life-long illness and prodromes with its recurring nature are
having a profound effect on the patient’s perception of their
illness-trajectory and burden of disease.5,8 The
present study indicates that personal variables such as age, gender, and
experience in illness, can affect patient’s perception of prodromes and
their ability to predict oncoming attacks. So far the main obstacle to
the investigation of prodromes’ clinical significance has been the lack
of reliable scientific methods that can capture the essential elements
of the prodromes and their association with consequent attacks.9-12 Clearly, there is an unmet need for a unified
definition of prodromes, its temporal relations to attacks, its
predictive power as an early warning sign, and its use in mitigating
cosequences of attacks.
A newly developed disease-specific evaluation instrument (HAE Evaluarion
of Prodromes and Attacks, HAE-EPA), was chosen for this
study.13 This investigational tool is based on the
principles of patient-reported outcome measures (PRO) that have already
shown its effectiveness in clinical research and medical practice.18-19 HAE-EPA is the first tool to measure both
prodromes and attacks, while other HAE instruments are focusing on
either attack attributes, or disease-related quality of life (HRQoL) or
both (reviewed in ref. 13). The dimensions and domains selected for
evaluation of the attacks and prodromes in our study are meant to
authentically reflect the patients’ perception of disease severity and
its effect on their daily routine, and therefore represent their
real-life illness prespective.
The present study is an exploratory pilot which applied the HAE-EPA
instrument to a cohort of 66 patients who were willing to share their
experience on both prodromes and attacks, out of a total of 197 HAE
patients surveyed in Israel.20
The statistical analysis presented in this study demonstrates
significant differences in the dimensions of prodromes and attacks (i.e.
pain, severity, limitation, functionality) across all pre-defined body
domains (”clusters”). This means that patients could clearly distinguish
between these two events. The positive correlations support our basic
assumption that prodromes could predict attack location, severity and
degree of impairment and functionality. These correlations indicate that
high intensity prodromes can predict high severity of the subsequent
attacks, which was particulary emphasized in the abdominal location.
Moreover, the relationships seems not to be based on compensatory
response during the attack (i.e. intense prodrome results in mild
attack), but on a predictive principle (i.e intense prodrome predicts
intense attack). As expected, prodromes were far less intense than
attacks on all dimensions.
In this study we tried to comprehend how personal characteristics affect
the interactions between prodromes and attacks in individual patients.
Personal experience seems to be an essential asset when it comes to
coping with chronic illness.21 Even though prodromes
and attacks are unpredictable and vary in their manifestations,
experienced patients are more attentive to their body cues and capable
of finding some consistency and repetitiveness in the prodromes,
enabling them better coping skills than the less experienced patients
(i.e. newly diagnosed or with fewer attacks) who, according to our
study, perceive more intense prodromes and attacks. Experience in
illness is strongly associated with the patients’ ability of to predict
attacks, distinguish them from the prodromes and employ these insights
as a coping strategy. Experienced patients are expected to better endure
the challenges of the disease by using the prodromes as an early warning
sign and prepare to take preventative actions to mitigate the attacks.
These finding are in-line with the observation that experienced patients
are coping better with chronic disease and able to utilize their
individual resources more efficiently21. In chronic
diseases, patients develop their own perception of illness as a
limitation and cultivate their own individual coping
strategies. 22-23 More experienced and trained
patients can recognize the early warning signs and use them as an
efficient strategy in the management of attacks (i.e. timing of
self-administration of rescue medication). 24