# Understanding the Intricate Pathophysiology of Psoriasis and Related Skin Disorders
## 4 Sporiasis and Associated Dermatologic Disorders
Since the JAK1-STAT pathway plays a critical role in psoriasis and DM, upadacitinib, a highly selective JAK1 inhibitor, may be an effective and safe option for treating refractory concomitant skin autoimmune diseases with JAK1- STAT pathway activation [48]. Due to the complexity of autoimmune diseases and the rarity of such cases, further studies are required to find the optimal treatment in patients suffering from both DM and psoriasis. Systemic sclerosis (SSc) is an uncommon autoimmune condition marked by a characteristic triad: vasculopathy, skin and internal organs fibrosis, and immunologic dysfunction. Although clinical signs and symptoms such as [PERSON]'s phenomenon are prototypical of SSc, this disease globally exhibits a wide range of clinical manifestations with a high inter-individual variability [49]. Localized scleroderma, also known as morphea, is an autoimmune disease characterized by fibrosis, primarily affecting the skin and subcutaneous tissue, with occasional involvement of the underlying bone. The association between psoriasis and morphea is currently unknown, and the co-occurrence of these conditions is believed to be quite uncommon, with only 22 cases documented in the literature. Psoriasis has been confirmed in 11.6% of documented immune-mediated conditions seen in conjunction with morphea, making it one of the most common co-occurring autoimmune conditions [50]. Cases of co-existing SSc and psoriasis have been also reported, suggesting a possible association between the two conditions. The possible link between SSc and psoriasis has been further evaluated in a cohort study from Israel. In that research, 2431 patients with SSc were evaluated with 12,710 age- and sex-matched controls. Psoriasis was more common in patients with SSc (1.9%) than in controls without SSc (1.2%) [51]. Several hypotheses or mechanisms have been proposed to explain the potential link between SSc and psoriasis. Studies have shown associations between MHC-I molecules--particularly HLA-B*08:01--in both SSc and psoriasis, specifically psoriatic arthritis, due to shared genetic background. Furthermore, both diseases share certain immunopathogenic aspects. In psoriasis, skin inflammation is dominated by CD4+ and CD8+ T-cells, with CD8+ T-cells emerging as key players. In SSc, CD4+ T-cells, including follicular helper T-cells, may drive autoantibody production and interactions between CD4+ Th2 T-cells and fibroblasts releasing profibrotic mediators (IL-4, IL-6, IL-13), which may contribute to the skin phenotype [50]. The development of both conditions has been linked to type I interferon pathways, as described in studies involving patients who received intense interferon therapy for hepatitis C infection, multiple sclerosis, and myeloproliferative diseases. Another significant mechanism connecting SSc and psoriasis is the skin target tissue damage, such as radiation and direct trauma, which exposes neo-autoantigens to the immune system and may initiate local adaptive immune reactions [52]. Cases of biologic treatment-induced morphea are a rare complication, with only 10 cases reported in the literature, 2 of which involved patients treated with ustekinumab. [PERSON] et al. presented a patient who received ustekinumab treatment for psoriasis with resolution but exhibited subsequent development of sclero nodules consistent with morphea and whose lesions resolved once the medication was stopped. The disease mechanism is not fully known but is likely related to the profibrotic activity of Th2 cells [52]. [PERSON] et al. described a patient with long-standing plaque psoriasis under ustekinumab who developed morphea under a plaque of psoriasis [53]. Both morphea and psoriasis have a common immunologic basis involving inappropriate immune activation against self-antigens, which provides a possible explanation for their coexistence. The Th17 pathway and cytokines IL-17, IL-21, and IL-23 are believed to significantly impact the pathogenesis of inflammatory autoimmune conditions.