# Understanding the Intricate Pathophysiology of Psoriasis and Related Skin Disorders
## 3 Pathogenic Pathways Across Soriasis Subtypes
In patients diagnosed with drug-related psoriasis, suspected medications should be discontinued and replaced with alternative treatments [3]. The development of psoriatic inflammation is influenced by both innate and adaptive immune responses, with innate responses playing a more significant role in chronic plaque psoriasis. One accepted mechanism involves the overexpression of antimicrobial peptides in psoriatic skin, which act as triggers and contribute to the ongoing maintenance of the condition. LL-37, \(\beta\)-defensins, and specific proteins are some of the most studied markers of psoriasis. In the early stages, there is an abnormal reduction in LL-37 and various antimicrobial peptides produced by keratinocytes under stress conditions, such as physical injury. LL-37 is released by damaged keratinocytes and forms complexes with other molecules--mostly genetic material from altered cells around the keratinocyte. \begin{table}
\begin{tabular}{c} \hline \hline \multicolumn{2}{c}{**Medications Involved in Triggering and/or Exacerbating Soriasis**} \\ \hline \hline \multicolumn{2}{c}{Beta-blockers} \\ \hline \hline \multicolumn{2}{c}{Angiotensin-converting enzyme inhibitors} \\ \hline \hline \multicolumn{2}{c}{Nonsteroidal anti-inflammatory drugs} \\ \hline \hline \multicolumn{2}{c}{Antimalarials} \\ \hline \hline \multicolumn{2}{c}{Lithium} \\ \hline \hline \multicolumn{2}{c}{Interferons} \\ \hline \hline \multicolumn{2}{c}{Tetracycline} \\ \hline \hline \multicolumn{2}{c}{Terbinafine} \\ \hline \hline \multicolumn{2}{c}{Imiquimod} \\ \hline \hline \multicolumn{2}{c}{Fibrate drugs} \\ \hline \hline \multicolumn{2}{c}{Biologic therapy} \\ \hline \hline \end{tabular}
\end{table} 
Table 2: Systemic medication associated with the onset and exacerbation of psoriasis. LL-37 has been recognized as a participant in the pathogenesis of psoriasis, particularly through its role in activating plasmonic dendritic cells. This activation stimulates the production of type I interferon (IFN), which plays a crucial role in the phenotypic maturation of myeloid dendritic cells and is important for the differentiation and function of T-helper 1 (Th1) and T-helper 17 (Th17) cells. Th17 cells are specialized populations of CD4+ T cells that produce several key cytokines, including IL-17, IL-22, IL-21, and TNF-\(\alpha\)[4]. Cytokines such as IL-6, IL-1\(\beta\), and IL-23 play a crucial role in activating Th17 cells. These cytokines can lead to chronic inflammation and autoimmunity. However, Th17 cells that are activated by transforming growth factor-beta (TGF-\(\beta\)) and IL-6 are generally less pathogenic; they mainly help maintain tissue integrity and provide defense against pathogens. Additionally, the migration of myeloid dendritic cells into lymph nodes is observed, which is associated with an increase in the production of TNF-\(\alpha\), IL-23, and IL-12. The maintenance phase of psoriatic inflammation is driven by the activation of adaptive immune responses through specific T cell subsets. Keratinocyte proliferation in the epidermis occurs through two pathways: inflammation mediated by TNF-\(\alpha\), IL-17, and IFN-\(\gamma\), and the action of LL-37 complexed with DNA, leading to increased production of type I IFNs. These mediators further enhance keratinocyte activation, resulting in the production of LL-37, pro-inflammatory cytokines (including TNF-\(\alpha\), IL-1\(\beta\), and IL-6), chemokines, and antimicrobial peptides, which together perpetuate chronic inflammation [4]. This cascade promotes keratinocyte proliferation and the production of antimicrobial peptides and chemokines that recruit neutrophils, sustaining skin inflammation. Plaque-type psoriasis is characterized by an inflammatory pathway involving TNF-\(\alpha\), IL-23, and Th17 cells.