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.