Upadacitinib for the management of bullous pemphigoid coexisting with psoriasis vulgaris: a case report and literature review.

Both bullous pemphigoid (BP) and psoriasis are common immune-related dermatological conditions in clinical practice, but the co-occurrence of these two diseases is rare. Currently, there is no consensus on the long-term safe and effective treatment for patients with both BP and psoriasis. JAK inhibitors are emerging as targeted therapeutic drugs that act by inhibiting Janus kinase activity, regulating the JAK/STAT pathway, blocking the transduction pathway of key proinflammatory cytokines, and influencing T-cell differentiation. These cytokines upstream of the JAK/STAT pathway play a pivotal role in the pathogenesis of numerous inflammatory and autoimmune disorders. Upadacitinib, a second-generation JAK inhibitor with high selectivity, demonstrates promising potential.This case report aims to provide a description of the successful treatment of bullous pemphigoid (BP) and psoriasis vulgaris by using upadacitinib, highlighting significant clinical outcomes. Additionally, we aim to analyze the underlying mechanism of upadacitinib in treating these two comorbidities by reviewing relevant literature from both domestic and international sources. Based on our clinical observations, upadacitinib appears to be a promising and well-tolerated therapeutic option for patients with concurrent BP and psoriasis, offering valuable insights for developing appropriate treatment strategies in clinical practice.

Serum LL-37 and inflammatory cytokines levels in psoriasis.

BACKGROUND: Psoriasis (PsO) is a T-cell-associated inflammatory autoimmune dermatitis. Leucine leucine-37 (LL-37) is upregulated in PsO patients and correlated with the area and severity of PsO. However, the exact relation between LL-37 and T cell-associated inflammation is not well understood. It is very important to clarify the relationship between LL-37 and inflammatory response for clinical diagnosis and treatment of PsO. This study investigated the serum levels of LL-37 and inflammatory cytokines, as well as correlations between them in PsO patients, which aimed to provide new ideas for the diagnosis and treatment of PsO. METHODS: PsO patients (n = 50) and healthy volunteers (n = 33) were recruited in this study. Skin specimens were stained with hematoxylin and eosin (H&E). The serum levels of LL-37, T-helper type 1 (Th1, IFN-γ), T-helper type 17 (Th17, IL-17), T-helper type 22 (Th22, IL-22), and T-helper type 2 cytokines (Th2, IL-4) were assessed by enzyme-linked immunosorbent assay. Some of the patients were re-recruited after treatment to evaluate LL-37 and cytokines levels. RESULTS: Pathological changes were observed in PsO skin lesions. LL-37, IFN-γ, IL-17, and IL-22 serum levels were much higher in PsO patients than those in healthy volunteers (p < .001), and posttreatment reduction was observed in five patients. However, no remarkable difference in IL-4 level (p > .05) was found. LL-37 level was positively correlated with IFN-γ, IL-17, and IL-22 levels (p < .001) in PsO patients. CONCLUSION: LL-37 expression was significantly associated with inflammatory response, which may provide us new ideas for diagnosing and monitoring disease activity of PsO.

Acitretin Promotes the Differentiation of Myeloid-Derived Suppressor Cells in the Treatment of Psoriasis.

Increased numbers of myeloid-derived suppressor cells (MDSCs) are involved in the development of psoriasis. Acitretin is used to treat psoriasis by regulating the proliferation and differentiation of keratinocytes, but little is known about the effect of acitretin on immune cells. Here, we reported that psoriasis patients had an expansion of MDSCs and monocytic-MDSCs (M-MDSCs) in peripheral blood and skin lesions. The number of MDSCs and M-MDSCs in peripheral blood correlated positively with disease severity. Acitretin could reduce the number of MDSCs and M-MDSCs in the peripheral blood of psoriasis patients as well as the spleen and skin lesions of IMQ-induced psoriasis-like model mice. Moreover, acitretin promoted the differentiation of MDSCs into macrophages, especially CD206+ M2 macrophages, and CD11c+MHC-II+ dendritic cells. Mechanically, acitretin dramatically increased the glutathione synthase (GSS) expression and glutathione (GSH) accumulation in MDSCs. Interruption of GSH synthesis abrogated the acitretin effect on MDSCs differentiation. Acitretin regulated GSS expression via activation of extracellular signal-regulated kinase 1/2. Thus, our data demonstrated a novel mechanism underlying the effects of acitretin on psoriasis by promoting MDSCs differentiation.

[Effect of methotrexate on regulation for the number of regulatory T cells and expression of Foxp3 in psoriasis].

OBJECTIVE: To explore the role of methotrexate (MTX) in regulating the number of regulatory T cells (Treg) and the mRNA expression of transcription factor Foxp3.
 Methods: 1) We analyzed the number of Treg and the mRNA expression of Foxp3 by flow cytometry (FCM) and quantitative real-time PCR (qRT-PCR) respectively in patients with psoriasis vulgaris, patients with psoriasis vulgaris after the 8-week treatment of MTX, and healthy people. 2) BALB/c female mice were smeared with imiquimod (IMQ) cream for 6 days. We recorded the change of the lesion in mice every day. The morphological changes of lesion in mice were evaluated by the psoriasis area and severity index (PASI) and HE staining. 3) The mouse model was randomly divided into a control group and an MTX group. The MTX group was treated with different doses of MTX (38.5 and 77.0 nmol/L) on the third day of this experiment. The morphological changes of lesion in mice were evaluated by PASI and HE staining. We tested the number of Treg and the expression level of Foxp3 mRNA in splenic lymphocytes.
 Results: 1) The number of Treg and the expression level of Foxp3 mRNA were lower in psoriasis vulgaris patients than those in the healthy control group (P<0.05). After 8-week treatment of MTX, the number of Treg was increased (P<0.05) and Foxp3 mRNA level was up-regulated (P<0.01). 2) Typical psoriasis-like skin lesions, such as red scaly skin plaque were found after topical application of IMQ. Both the number of Treg in the splenic lymphocytes of mice and the Foxp3 mRNA level of Treg were reduced by IMQ (P<0.01 and P<0.05). 3) Different doses of MTX for mice showed the ability to improve skin lesion, increase the number of Treg in the spleen of mice and Foxp3 mRNA level in psoriatic dermatitis of mice (P<0.05).
 Conclusion: MTX is able to regulate the number of Treg and Foxp3 mRNA expression in psoriasis.

Topical Sunitinib ointment alleviates Psoriasis-like inflammation by inhibiting the proliferation and apoptosis of keratinocytes.

Psoriasis is a chronic auto-immune inflammation disease with skin lesions and abnormal keratinocyte proliferation. Sunitinib, a multi-targeted tyrosine kinase inhibitor, is known to selectively inhibit several growth factor receptors, including vascular endothelial growth factor receptor, platelet-derived growth factor receptor and stem cell factor. It was reported that a patient with renal cell carcinoma (RCC) whose psoriatic lesion was resolved dramatically during treatment with Sunitinib, however, the mechanism is still unclear. We applied Sunitinib ointment to treat imiquimod-induced mouse model of psoriasis and found that Sunitinib ointment could alleviate imiquimod-induced psoriasis-like inflammation and reduce the Ki67 expression, while Sunitinib ointment couldn't reduce imiquimod-induced splenomegaly of the mouse model, then we concentrated on studying the effect of Sunitinib on the proliferation and apoptosis of keratinocytes, we cultivated HaCaT cells with epidermal growth factor (HaCaT/E cells) to represent as a state of highly proliferative psoriatic keratinocytes. We found that Sunitinib could inhibit the proliferation of Hacat/E cell in a time and concentration dependent manner by influencing the expression level of cell cycle protein D1, cycle protein E1, in addition, Sunitinib could induce the apoptosis of Hacat/E cell and up-regulate the expression of poly ADP-ribose polymerase (PARP). Sunitinib down-regulated the expression of phosphorylated signal transduction and activator of transcription 3 (p-Stat3) of Hacat/E cells significantly. We conclude that Sunitinib alleviates imiquimod-induced psoriasis-like inflammation by regulating the proliferation and apoptosis of HaCaT cells through inhibiting the expression of p-Stat3.