A Comparative Study of Sex Distribution, Autoimmunity, Blood, and Inflammatory Parameters in Chronic Spontaneous Urticaria with Angioedema and Chronic Histaminergic Angioedema

Abstract

Recurrent idiopathic histaminergic angioedema is currently classified as a subtype of angioedema, as well as a subtype of chronic spontaneous urticaria (CSU), based on the fact that both are mast cell-mediated and respond to the same treatments. In the present work, we sought to verify whether chronic histaminergic angioedema (CHA) is an entity distinct from CSU or represents a CSU subtype that lacks hives. We performed a prospective study comparing 68 CHA patients, angioedema without hives, with 63 CSU patients, with hives and angioedema, from whom we collected demographic and clinical data, as well as blood and serum markers. We found key pathogenic features that differentiate CHA from CSU: gender distribution, basophil number, and antibodies against the IgE receptor. The male/female ratio in CHA was 0.78, whereas in CSU it was 0.36 (P= .0466). Basopenia was more often seen in CSU (n= 13 [20%]) than in CHA (n= 5 [7%]). Finally, 31.15% of CSU sera induced basophil activation, whereas no CHA sera were able to activate normal basophils. By contrast, nonspecific inflammation or immune markers, for example, erythrocyte sedimentation rate, C-reactive protein, or IgG antithyroid antibodies, were very similar between both groups. IgE anti-IL-24 could not be assessed because a control population did not differ from CSU. Inclusion of CHA as part of the spectrum of CSU is an assumption not evidence-based, and when studied separately, important differences were observed. Until there is further evidence, CHA and CSU should not necessarily be considered the same disorder, and it is our opinion that review articles and guidelines should reflect that possibility.