# Understanding the Intricate Pathophysiology of Psoriasis and Related Skin Disorders
## 4 Sporiasis and Associated Dermatologic Disorders
The Th2 pathway in morphea and the Th1 pathway in psoriasis, both intersect with the Th17 path way. Thus, it is postulated that dysregulation of this pathway may lead to the coexistence of these conditions in the same patient [51]. [PERSON] et al. reported the case of a patient who developed biopsy-proven scleroderma after initiation of secukinumab for her psoriatic arthritis. The administration of secukinumab is temporally associated with skin changes without the influence of any confounding medications. The duration between drug exposure and the onset of skin lesions was 19 months [51]. To understand the cause of their dual presentation, it is important to have additional reports of similar cases that demonstrate the coexistence of psoriasis and morphea in patients treated or not with biologics, as well as an improved understanding of their pathophysiology. Sporiasis and atopic dermatitis (AD) are common inflammatory skin conditions with distinct clinical features and immunological profiles. Overlapping conditions could be classified into mainly psoriasis lesions with AD features or vice versa, concomitant psoriasis and AD, or disease transformation as a result of biologics treatment. Psoriasis typically affects the scalp and extensor surfaces, while AD varies with age: it affects the extensor surfaces of extremities and the face in infancy, and the flexural surfaces and hands in adolescents and adults. In terms of disease progression, psoriasis often begins around ages 20 to 30, with many patients experiencing lifelong symptoms. In contrast, AD typically starts in early childhood, often improving before adolescence (approximately 80% of the cases). Interestingly, studies show that individuals with psoriasis have a 25-fold lower prevalence of AD. There are shared genetic profiles, immune pathways, pathologic changes, and comorbidities for these two dermatological conditions (Figure 1). Additionally, it seems that individuals with abnormalities in their skin barriers and immune responses may be more prone to exhibiting the overlapping symptoms of psoriasis and AD [54]. In AD, exposure to various allergens triggers a systemic Th2 immune inflammation termed epithelial susceptibility. Furthermore, the interaction between Th2/Th17-related cytokines and skin structures or Kupffer cell cytokines determines a cycle or loop of skin barrier-inflammatory cytokine interactions. The overlap between AD and psoriasis starts with a Th2 inflammatory activation following the breakdown of the skin barrier due to genetic or other factors. In psoriasis, the skin barrier function may be compromised due to trauma (intense scratching), a genetic mutation affecting epidermal barrier integrity,  
Figure 1: Shared features between psoriasis and atopic dermatitis. and the downregulation of barrier-related proteins because of dysregulated Th17-related cytokines [55]. Both psoriasis and AD show significant genetic influences, evidenced by familial patterns and greater disease risk in identical twins compared to fraternal twins. Numerous genetic loci have been identified for each condition, highlighting their genetic diversity. The most common susceptibility gene for psoriasis is HLA-Cw*0602, located on PSORS1 at 6p21, while null mutations in the filaggrin (FLG) gene represent the strongest genetic risk factor for developing atopic dermatitis. The epidermal differentiation complex on chromosome 1q2l.3 contains FLG gene mutations for AD, and it seems to increase the risk of developing psoriasis in Taiwanese and Chinese populations [56; 57]. Another common genomic region is located on chromosome 5q3l.1-q33.1, where IL-13 has been linked to both AD and psoriasis [58]. Psoriasis primarily involves the TNF-\(\alpha\) and the IL23-Th17-IL17 pathway, while AD is associated with a Th2 response driven by IL-4 and IL-13. However, the Asian, pediatric, and intrinsic forms of AD also show Th17 involvement. Research on psoriasis susceptibility genes found that there is a 1.18-fold increase in loci related to IL-4/IL-13 signaling.