Severe CSU and activation of the coagulation/fibrinolysis system: clinical aspects

Abstract

Background. About 50% of patients with severe chronic spontaneous urticaria (CSU) show signs of activation of the coagulation/fibrinolysis system, but the clinical significance of this phenomenon is unclear. Objective. The present study compared patients with severe CSU showing and not showing elevated D-dimer plasma levels. Methods. 132 adult patients (m/f 44/88; mean age 51, 5 years; range 14-89 years) with severe CSU (UAS-7 > 30) were included in a cross-sectional, real life study. The study group was divided based on baseline D-dimer plasma levels, and compared for age, sex, disease duration, disease activity, CRP, thyroid autoimmunity, total IgE, and atopic status. Results. Identical numbers of patients showed elevated and normal D-dimer plasma levels (50% and 50%, respectively). Patients showing elevated D-dimer levels were slightly older (p < 0.05), were more frequently females (p < 0.05), had a longer disease duration (p < 0.01), and had a significantly higher prevalence of elevated PCR (26/66 vs 4/66; p < 0.001). Conclusions. Only 50% of patients with severe CSU show elevated D-dimer plasma levels. The activation of the coagulation/fibrinolysis system is associated with a systemic inflammatory milieu, suggesting the existence of a specific phenotype. Whether this reflects the existence of different endotypes in patients showing and not showing the activation of the coagulation cascade has still to be established. of D-dimer are not predictive of CSU patients' response to the humanized anti-IgE mAb, omalizumab (12), it nonetheless parallels the clinical response to this drug (13). Patients with severe CSU show a detectable activation of the coagulation cascade in about 50% of cases (12). What differentiates patients with severe CSU showing and not showing the activation of the coagulation / fibrinolysis system has not been established so far. The present study compared the clinical features in these two subsets of patients with CSU. Patients and methods Patients This cross-sectional, real life study included 132 patients (m/f 44/88; mean age 51, 5 years; range 14-89 years) with severe CSU (UAS-7 > 30) unresponsive to antihistamine treatment. The study group was divided based on baseline D-dimer plasma levels, which were measured by ELISA and expressed as ng/

Urticaria: Collegium Internationale Allergologicum (CIA) Update 2020

“…Recent reports [31][32][33][34][35] suggest that additional endotypes of CSU may exist, with evidence pointing to a role of factors of the coagulation pathway, ligands of the MASrelated G protein-coupled receptor X2 (MRGPRX2), ba-sophils, alarmins, and other signals in the pathogenesis of CSU. More research is needed to clarify whether mechanisms of skin MC degranulation other than type I and type IIb autoimmune activation support the existence of distinct and separate endotypes.…”

Intersecting pathways: evaluating inflammatory markers and metabolism in chronic spontaneous urticaria with a multi‐marker approach

“…27 On the other hand, Asero et al suggested that D-dimer levels are elevated in severe cases of CSU, but this elevation varies among individuals, attributed to distinct underlying mechanisms. 28,29 Similar to D-dimer, elevated fibrinogen levels were also observed in CSU. 15 Albumin acts as a negative acute phase reactant, and new studies emphasize that it can also function in both procoagulant and anticoagulant mechanisms.…”

“…On the other hand, Asero et al. suggested that D‐dimer levels are elevated in severe cases of CSU, but this elevation varies among individuals, attributed to distinct underlying mechanisms 28,29 . Similar to D‐dimer, elevated fibrinogen levels were also observed in CSU 15 …”

The Role of Anti-IgE Antibodies in Urticaria

“…CSU patients that take more than a month (late responders) to respond to omalizumab, probably underwent a type IIb autoimmunity, where the reduction of free IgE results in the slow loss of membrane-bound FcεRI from skin mast cells [46]. New endotypes of CSU have been proposed in addiction by recent reports, suggesting a key role of the coagulation pathway factors, ligands of the Mas-related G protein-coupled receptor X2, basophils, and other signals in the pathogenesis of CSU [47,48]. Moreover, other research to characterize better the role and the relevance of type I and type IIb autoimmunity in CSU and to support the existence of distinct and separate endotypes, are still in progress.…”