Introduction
Angioedema (AE) is defined as localized and self-limited swelling of the
deep dermis and subcutaneous or submucosal tissues due to a rapid-onset
increase in vascular permeability, causing local plasma extravasation
secondary to the release of vasoactive mediators.1,2
According to the indicated vasoactive mediator, AE can be classified
into two types: histamine-mediated AE (induced by mast cell activation
and basophil degranulation) and bradykinin-mediated AE (due to excessive
bradykinin), as observed in hereditary angioedema, acquired angioedema
with C1 inhibitor deficiency (related to lymphoproliferative and
autoimmune diseases) and angioedema related to angiotensin-converting
enzyme (ACE) inhibitors.3,4
Histamine-mediated AE is the most frequent form of
angioedema,2 and it is classified as chronic
histaminergic acquired angioedema (CHA) when allergies or other causes
have been excluded and positive treatment responses to antihistamines,
corticosteroids, adrenaline, or omalizumab5 have been
reported. Histamine-mediated AE can occur isolated as CHA or associated
with wheals in chronic spontaneous urticaria (CSU). Classically, CSU is
characterized by the presence of recurrent episodes of wheals (hives)
with or without angioedema for at least 6 weeks.6Approximately 33–67% of all patients with CSU present with wheals and
angioedema.7 For this reason and because CHA responds
to urticaria treatments, CHA is typically considered a subtype of CSU
without wheals. However, a recent study8 found several
features that differentiate CHA from CSU, suggesting that CHA should be
considered a separate entity.
Angioedema can be disfiguring, limit daily activities and have a
significant impact on quality of life.9,10 AE impacts
on quality of life (QoL) have been largely explored in
bradykinin-related AE11,12; however, specific QoL
studies for CHA have not been performed, except for those carried out in
the context of CSU associated with angioedema
attacks.13
We previously reported differences in cellular activation and
autoimmunity parameters between CHA and CSU8 in the
same cohort of patients. The aim of this study was to describe the
burden of the disease and the impact on QoL in patients with CHA and
compare the disease severity and quality of life of angioedema in
patients suffering from chronic urticaria (CSU-AE).
Finally, due to a growing interest in identifying biomarkers to monitor
disease activity and response to treatment, we selected several
previously reported potential biomarkers for CSU
activity14-16 and assessed them in our study
population as well as their relationship with disease activity and
quality of life.