Pathogenesis of Chronic Urticaria: An Overview

Abstract

The pathogenesis of chronic urticaria is not well delineated and the treatment is palliative as it is not tied to the pathomechanism. The centrality of mast cells and their inappropriate activation and degranulation as the key pathophysiological event are well established. The triggering stimuli and the complexity of effector mechanisms remain speculative. Autoimmune origin of chronic urticaria, albeit controversial, is well documented. Numerical and behavioral alterations in basophils accompanied by changes in signaling molecule expression and function as well as aberrant activation of extrinsic pathway of coagulation are other alternative hypotheses. It is also probable that mast cells are involved in the pathogenesis through mechanisms that extend beyond high affinity IgE receptor stimulation. An increasing recognition of chronic urticaria as an immune mediated inflammatory disorder related to altered cytokine-chemokine network consequent to immune dysregulation resulting from disturbed innate immunity is emerging as yet another pathogenic explanation. It is likely that these different pathomechanisms are interlinked rather than independent cascades, acting either synergistically or sequentially to produce clinical expression of chronic urticaria. Insights into the complexities of pathogenesis may provide an impetus to develop safer, efficacious, and targeted immunomodulators and biological treatment for severe, refractory chronic urticaria.

Effectiveness of Autologous Whole-Blood Injections in Patients with Refractory Chronic Spontaneous Urticaria

“…It is well established that thrombin enhances vascular permeability, and activates and degranulates mast cells, thus generating anaphylatoxin C5a [21]. …”

The link between chronic spontaneous urticaria and metabolic syndrome

“…The autologous serum skin test (ASST) is a simple screening tool able to detect autoreactivity related to the presence of circulating histamine-releasing factors of any type, and not only of functional autoantibodies (1). Current evidence supports the possible contribution of other pathomechanisms, including the dysregulation of intracellular signalling pathways in basophils and mast cells, an abnormal innate immunity response, and the simultaneous activation of inflammatory response and coagulation system (2)(3)(4). With regard to the last aspect in more detail, significantly increased circulating levels of inflammatory markers [such as C-reactive protein (CRP) and interleukin (IL)-6], fibrin degradation products and D-dimer have been associated with the active phase of CSU, in correlation with disease severity (5).…”

Plasma Levels of Matrix Metalloproteinase-9 in Children With Chronic Spontaneous Urticaria

“…The presence of persistent activation of dermal mast cells is a hallmark of CSU pathogenesis, but the underlying mechanisms of mast cell activation are an enigma 118. Urticarial wheals are characterized by dermal edema, vasodilatation, and perivascular infiltrates comprising lymphocytes, monocytes, neutrophils, eosinophils, and basophils 1819. Altered numbers and imbalanced cytokine production of T cells have also been reported in patients with CSU 2021…”