Immunological signature of chronic spontaneous urticaria (Review)

Abstract

Chronic urticaria (CU) is a condition characterized by intensely pruritic, edematous, erythematous papules lasting for more than 6 weeks. Over half of the cases have concomitant swelling of deeper tissues, known as angioedema. The socio-economic burden of the disease is significant. Unfortunately, patients with severe CU, refractory to conventional treatment, have limited and expensive therapeutic options. The pathogenesis of CU is not yet completely understood. Therefore, elucidating the pathophysiological mechanisms involved would potentially identify new therapeutic targets. It has been accepted in recent years that mast cells and their activation, followed by excessive degranulation represent the key pathophysiological events in chronic spontaneous urticaria (CSU). The triggering events and the complexity of the effector mechanisms, however, remain intensely debated topics with conflicting studies. One pathogenetic mechanism incriminated in chronic spontaneous urticaria is the response mediated by the high-affinity receptor for IgE (FcεRI) expressed on mast cells. Increasing recognition of chronic spontaneous urticaria as an autoimmune disease linked to the cytokine-chemokine network imbalance resulting from alteration of innate immune response is another pathogenetic explanation. It is likely that these different pathological mechanisms are more interconnected, both acting synergistically, rather than separately, to produce the clinical expression of CU. The discovery and understanding of pathogenic mechanisms represent the premise for the development of safe and effective immunomodulators and targeted biological treatment for severe, refractory CU.

Levels of Serum Inflammatory Cytokines and Their Correlations with Disease Severity in Patients with Chronic Spontaneous Urticaria

“…For instance, Zhou et al (2019) (18) proved that elevated IL-4 can promote B cell proliferation and immunoglobulin E production, leading to increased sensitivity to allergens and exacerbation of the disease. Similarly, Huo et al (2020) (19) reported a positive correlation between disease severity and the level of IL-17, as IL-17 can promote the release of in ammatory mediators and chemokines by skin cells, increase in ammation and vascular permeability, and thus exacerbate the formation of wheals and itching symptoms (20,21). Additionally, IL-31 can enhance itching reactions and exacerbate itching symptoms in urticaria patients.…”

Treatment of Urticaria Caused by Severe Cryptosporidiosis in a 17-Month-Old Child – A Case Report and Review of the Literature

“…Diagnosing urticaria is easy, but nding its cause is di cult and requires careful examination methods to discover diagnostic clues and rule out serious medical conditions. Several conditions have been found to be related to urticaria symptoms, whereas the term chronic idiopathic urticaria identi es the high percent of conditions in which a pathogenetic factor has not been found [9]. Identifying the cause of urticaria requires ruling out many other conditions.…”

“…Unfortunately, we do not know the exact mechanism of urticaria caused by Cryptosporidium. Anyway, various reasons have been discussed for the cause of urticaria caused by parasitic infections, such as the role of speci c IgE, Th2 cytokine skewing, eosinophil's and coagulation system and nally circulating immune complexes and complement system [9][10][11][12].…”

Functional connectivity impairment of thalamus-cerebellum-scratching neural circuits in pruritus of chronic spontaneous urticaria

“…UAS7 is recommended by the latest chronic urticaria activity guidelines and can be used to assess the number of urticaria and severity of pruritus over 7 days ( Zuberbier et al, 2022 ). Another important pathogenic mechanism of CSU is mediated by the IgE high-affinity receptor (FcεRI) expressed by mast cells ( Dobrican et al, 2022 ). Mast cells are activated upon antigenic stimulation, mediated by IgE, and release multiple mediators, including histamine, to initiate an inflammatory response.…”