# Understanding the Intricate Pathophysiology of Psoriasis and Related Skin Disorders
## 3 Pathogenic Pathways Across Soriasis Subtypes  
Various triggering factors can elicit the onset of psoriasis in genetically predisposed individuals and may also facilitate consequent exacerbations of the disease. These may be grouped into extrinsic and intrinsic factors (Table 1) [3]. Drug-related psoriasis refers to the onset or worsening of psoriasis linked to certain medications. Some drugs can exacerbate existing psoriasis, induce psoriatic lesions on previously unaffected skin in patients who already have the condition, or even trigger the disease in individuals without a family history of psoriasis and those who are predisposed to it. Identifying drug-related causes of psoriasis can be challenging in clinical settings due to significant variability in the latency period between medication initiation and psoriatic skin lesions' appearance. Clinically and histopathological, drug-related psoriasis may closely resemble typical psoriasis. Drug-related psoriasis can present in various forms including plaque-type, palmoplantar, nail, scalp, pustular, and erythrodermic psoriasis. In most cases, the histopathological findings in drug-related psoriasis are nearly indistinguishable from those of conventional psoriasis. However, eosinophilic infiltrates in the dermis and lichenoid reactions can sometimes indicate drug-related psoriasis. Unlike non-drug-related psoriasis, in which the capillaries in the upper dermis appear convoluted and tortuous, this characteristic may not be evident in drug-related psoriasis. Additionally, there may be differences in the formation of neutrophic micro-abscesses in the stratum corneum of the epidermis. While these clues can guide the diagnosis, they are not the most crucial indicators. \begin{table}
\begin{tabular}{c c} \hline \hline
**Intrinsic Factors** & **Extrinsic Factors** \\ \hline Metabolic syndrome & Mechanical trauma (Köbner phenomenon) \\ \hline Emotional stress & Alcohol \\ \hline Dyslipidemia & Smoking \\ \hline Hypertension & Infection \\ \hline Diabetes & Vaccination \\ \hline Obesity & Drugs \\ \hline \hline \end{tabular}
\end{table} 
Table 1: Risk factors associated with both the onset and exacerbation of psoriasis. Commonly recognized drugs that can trigger the onset or flare-up of psoriasis include \(\beta\)-blockers, lithium, antimalarial drugs, and interferons, as well as angiotensin-converting enzyme inhibitors, among others (Table 2) [3]. The pathways responsible for drug-related psoriasis are highly complex, but the exact mechanisms remain elusive. Certain medications have been shown to affect keratinocyte hyperproliferation and the IL-23/IL-17 signaling pathway. Cyclic adenosine monophosphate (cAMP) acts as an intracellular messenger that stimulates proteins responsible for cellular differentiation and inhibits proliferation; \(\beta\)-blockers can lead to a decrease in intraperitoneal cAMP, resulting in keratinocyte hyperproliferation. Imiquimod-induced skin inflammation is a well-accepted model of psoriasis in animal studies. Imiquimod activates toll-like receptors 7/8, which can induce and exacerbate psoriasis, primarily through the IL-23/IL-17 axis. Recently, immune checkpoint inhibitors and molecular inhibitors have been used in the treatment of malignancies and autoimmune diseases, and these drugs may influence the immune system, potentially leading to the development of psoriasis. Although psoriasis symptoms are rarely worsened during biologic therapy, they can still be triggered by biologics, resulting in what are known as paradoxical reactions. While most reported paradoxical reactions have been associated with tumor necrosis factor (TNF)-\(\alpha\) inhibitors, there is a growing incidence of reactions associated with biologics targeting IL-23 and IL-17. These biologics block immune signaling pathways, potentially causing cytokine imbalances. Paradoxical reactions are believed to result from an imbalance in cytokine production, leading to overproduction of interferon-\(\alpha\) and altered lymphocyte recruitment and migration.