# Understanding the Intricate Pathophysiology of Psoriasis and Related Skin Disorders
## 3 Pathogenic Pathways Across Soriasis Subtypes
Multiple types of IL-17 are produced by various cell types, including hematopoietic cells such as CD8+ T cells (Tc17), invariant NKT cells, \(\gamma\)$ T cells, and non-T non-B lymphocytes (known as type 3 innate lymphoid cells), as well as neutrophils. Inflammatory responses are regulated by IL-17A-F cytokines. It has been established that the most critical signaling in psoriasis is mediated by a receptor activated by two cytokines, IL-17A and IL-17F, with IL-17A displaying a stronger effect. Additionally, some intracellular kinases are activated, leading to the expression of pro-inflammatory cytokines, chemokines, and antimicrobial peptides. Th1 and Th2 cytokines operate through Janus kinase (JAK)-STAT signaling pathways, whereas Th17 responses are mediated by ACT1 and NF\(\kappa\)B. Interestingly, \(\gamma\)$ T cells can produce IL-17A independently of the IL-23 stimulus [4; 5]. The second most common type of psoriasis is pustular psoriasis, which is marked by multiple coalescing sterile pustules. In plaque psoriasis, the adaptive immune system plays a greater role in pathogenesis, with promising results from therapies targeting these elements. In contrast, the innate immune system appears to play a more significant role in pustular psoriasis, making therapies used for plaque psoriasis less effective. There are significant differences in the general pathogenesis of these types of psoriasis, despite some shared metabolic pathways. Generalized pustular psoriasis (GPP) presents with an acute and rapidly progressive course, characterized by widespread redness and subcorneal pustules, often accompanied by systemic symptoms. GPP seems to primarily depend on the activities of keratinocytes, neutrophils, and monocytes, with increased expression of IL-1\(\beta\), IL-36\(\alpha\), and IL-36\(\gamma\) observed in pustular psoriasis compared to plaque psoriasis. This overexpression of IL-36 appears to be a central mechanism promoting neutrophil accumulation in the epidermis. The significant presence of neutrophil chemokines CXCL1, CXCL2, and CXCL8 (IL-8) aligns with the proposed pathogenesis of GPP [4]. Another less common type is guttate psoriasis, characterized by small erythemat plaques and more commonly seen in children and teenagers. There is currently no evidence demonstrating any differences in the pathophysioc mechanisms compared to plaque-type psoriasis. It has been suggested that streptococcal superantigens may stimulate the proliferation of T cells in the skin in individuals with guttate psoriasis. Notably, some homology exists between streptococcal proteins and keratin proteins involved in pathways regulated by IL-17. Molecular mimicry may also play a significant role in patients with the major histocompatibility allele HLA-Cw6, as CD8+ T cell IFN-\(\gamma\) responses can be triggered by K17 and M6 peptides in these patients. Inverse psoriasis is a less common type characterized by affecting intertriginous areas and is generally more erosive than the erythematosus plaques seen in plaque psoriasis. Currently, no existing data shows any differences in the pathophysiologic mechanisms between common psoriasis and inverse psoriasis. However, it is speculated that there is a decrease in the number of specific immune cells in the plaques of inverse psoriasis, potentially due to the constant microenvironmental influences. Erythrodermic psoriasis is an acute condition in which the entire body surface is erythematous and inflamed and is accompanied by serious hemodynamic and metabolic disturbances. However, there is no data to reveal differences between the pathophysiologic mechanism of erythrodermic psoriasis versus common psoriasis [4].