# Understanding the Intricate Pathophysiology of Psoriasis and Related Skin Disorders
## 4 Sporiasis and Associated Dermatologic Disorders
Additionally, both conditions involve Th1 and Th22 responses. Interestingly, despite elevated IL-22 levels in both diseases, it seems that blocking IL-22 lacks efficacy in psoriasis and has modest results in AD treatment [59]. Overlapping manifestations and phenotypes between psoriasis and AD have been increasingly reported. Immunopathogenesis, common to both conditions, is supported by clinical features. IgE is commonly used as a marker for AD. However, total IgE levels are notably higher in psoriasis patients compared to healthy individuals. Moreover, those with long-standing psoriasis also show a significant increase in total IgE levels. In vitro studies show that scratch injuries in both conditions lead to CCL20 production by keratinocytes, which, in turn, attracts IL17-producing immune cells, contributing to the elevated IL-17 levels observed in AD as well. However, the mechanisms behind itch differ between the two diseases. In psoriasis, pruritus involves Substance P, IL-2, calcitonin gene-related peptide (CGRP), \(\mu\)-opioid receptors (OPRM), and \(\kappa\)-opioid receptors (OPRK), while in AD pruritus is linked to thymic stromal lymphopoietin (TSLP), CGRP, IL-4, IL-13, and IL-31. In psoriasis, pruritus is primarily driven by the transient receptor potential vanilloid 1 (TRPV1) channel, whereas AD itch is largely mediated by the transient receptor potential anskyrin 1 (TRPA1) channel [60]. There is evidence that prostanoids and leukotrienes (LTs) are produced at significantly higher levels in the lesional skin of chronic inflammatory conditions like AD and psoriasis. These lipid mediators are generated when arachidonic acid, released from membrane phospholipids in response to various pathophysiological stimuli such as trauma, is converted into prostanoids and LTs. Specifically, compounds like PGE2, LTB4, and CysLTE4 have been detected in the lesional skin or urine of patients with AD, suggesting their involvement in the disease's progression. The pathological processes underlying AD can be categorized into three main components: (i) disruption of type 2 immunity; (ii) impairment of the skin barrier; and (iii) presence of itch. In AD, there is a notable elevation of type 2 cytokines like IL-4 and IL-13, which contribute to various clinical manifestations such as barrier dysfunction and itch. For instance, IL-4 and IL-13 are known to impede the production of filaggrin, a crucial protein for maintaining skin barrier function, in keratinocytes. Additionally, signaling from IL-4 and IL-13 receptors in neurons is crucial for sustaining chronic itch. In AD lesions, IL-4 and IL-13 are mainly secreted by Th2 cells, although other innate cells like group 2 innate lymphoid cells (ILC2), basophils, and mast cells also contribute to type 2 cytokineproduction in the skin. Studies have shown the involvement of prostanoids in the induction of Th2 cells in AD models. For instance, the absence of COX-2 or inhibition of its activity led to enhanced eosinophil infiltration and increased IL-4 levels, indicating a regulatory role of prostanoids in type 2 immune responses [61]. Epicutaneous sensitization with protein antigens highlights the significant role of Langerhans cells (LCs) in inducing allergic responses. The modulation of prostaglandin (PG) receptors during sensitization influences the development of AD-like skin lesions, suggesting the regulatory role of PG signaling in AD pathogenesis. Various prostanoids and receptors are implicated in the fine-tuning of T-cell differentiation in AD. IL-22 is suspected to contribute to epidermal hyperplasia in AD lesions, and PGE2-EP4 signaling has been shown to regulate IL-22 production. Moreover, CCL17/TARC production, a key Th2 chemokine in AD, is promoted by PGE2, showcasing the diverse functions of prostanoids in AD pathogenesis. Prostanoids like PGD2 play a role in recruiting type 2 immune cells to AD skin lesions through CRTH2 signaling. LTs, particularly LTB4 acting on BLT1 receptors, are involved in Th2 cell infiltration in AD lesions.