Psoriasis (Auckland, N.Z.)最新文献

Purpose: Harnessing helminth-induced immunomodulation offers a novel therapeutic avenue for autoimmune and inflammatory diseases; however, research on helminths against psoriasis remains limited. This study evaluates the effects of the peptide SJMHE1 from Schistosoma japonicum (S. japonicum) on the inflammatory response in imiquimod (IMQ)-induced psoriasis mice and LPS-stimulated keratinocytes, as well as the efficacy of SJMHE1-loaded hydrogel on psoriasis in mice.

Methods: SJMHE1 was administered to mice with IMQ-induced psoriasis via topical administration or subcutaneous injection, and effects were evaluated by detecting the skin inflammation of mice. LPS-stimulated HaCaT cells were used to assess the regulatory effects of SJMHE1 in vitro. Additionally, the effects of Poloxamer 407 (P407)-loaded SJMHE1 were evaluated in mice with IMQ-induced psoriasis through topical application.

Results: Topical administration and subcutaneous injection of SJMHE1 alleviated psoriasis-like skin lesions, improved PASI scores, reduced epidermal thickness and dermal inflammatory cell infiltration, and decreased expression of Ki67, a marker of keratinocyte proliferation or differentiation. SJMHE1 modulated pro-inflammatory and anti-inflammatory cytokine expression in LPS-treated HaCaT cells, down-regulating NF-κB and STAT3 activation. Both SJMHE1-loaded hydrogel and SJMHE1 treatment alleviated IMQ-induced psoriasis-like skin lesions, improved PASI scores, reduced the number of Ki67-positive epidermal cells, decreased the spleen index and T-cell infiltration, increased the proportion of regulatory T cells (Tregs), and decreased the percentage of Th17 cells, alongside reducing inflammatory cytokine expression and NF-κB and STAT3 activation in skin lesions. Notably, weight changes in the SJMHE1-loaded gel group were less than those in the betamethasone-positive control group on days 6, 7, and 8 post-IMQ administration.

Conclusion: SJMHE1-loaded hydrogel and SJMHE1 treatment inhibited NF-κB and STAT3 activation in skin lesions, improved Th17/Treg balance, and reduced inflammatory cytokine expression in psoriasis mice, thereby ameliorating psoriatic lesion symptoms. Furthermore, SJMHE1-loaded hydrogel exhibited fewer side effects compared to betamethasone, positioning it as a promising strategy against psoriasis.

Introduction: The emergence of IL-17A inhibitors, has led to improvements in psoriasis treatment. However, comparative studies addressing their long-term efficacy and drug survival with associated predictors are scarce. The study aimed to compare the characteristics of patients treated with secukinumab or ixekizumab and in addition to analyze associated factors and independent predictors of drug survival in a real-world setting.

Methods: This study was designed as a single-center retrospective study. Kaplan-Meier analysis was used to assess drug survival. Log rank test and Cox regression analysis were performed to identify associated factors and possible independent predictors for drug discontinuation.

Results: 81 patients have been included in the study. Ixekizumab showed a trend toward faster and higher Psoriasis Area and Severity Index (PASI) 75 and 90 response rates compared to secukinumab at weeks 52 (74.6% versus 55.4%) and 104 (41.5% versus 31.1%). Overall, drug survival rates for ixekizumab were always higher than secukinumab, although the differences were not statistically significant (P = 0.26). Four predictors were identified. For secukinumab, nail psoriasis (hazard ratio [HR]: 0.27, 95% confidence interval [CI]: 0.09-0.83; P = 0.02) was assessed to be a protective factor favoring drug continuation, while five or more previous therapies (HR: 5.52, 95% CI: 1.98-15.40, P = 0.007) were considered a risk factor for discontinuation. In the ixekizumab group, psoriasis inversa was identified as a protective factor (HR: 0.15, 95% CI: 0.03-0.72; P = 0.02), and female sex (HR: 3.47, 95% CI: 1.09-10.99, P = 0.03) was considered a risk factor.

Conclusion: Ixekizumab exhibited a non-significant trend toward better long-term efficacy and drug survival compared to secukinumab with slightly lower tolerability. Patient characteristics, including nail psoriasis and treatment history, influenced drug survival differently for each treatment. These findings underscore the importance of personalized treatment strategies in managing psoriasis.

In our manuscript, we present a case study of siblings with Generalized Pustular Psoriasis (GPP) and Acrodermatitis Continua of Hallopeau (ACH), both harboring IL36RN gene mutations. The 3-year-old proband exhibited systemic pustules leading to a GPP diagnosis, while his 6-year-old sister developed nail ulcers and subungual pustules characteristic of ACH. Despite standard treatments, their conditions were refractory. Genetic analysis revealed a homozygous splice variant c.115+6 T>C, with heterozygous parents. This case underscores the role of IL36RN mutations in pustular psoriasis and supports ACH as a localized form of the disease. The distinct subtypes in siblings with identical mutations suggest a complex pathogenesis influenced by additional factors. Our findings highlight the importance of genetic testing in pustular psoriasis and warrant further investigation into the phenotypic variability of IL36RN-related disease.

Background: Psoriasis is a refractory inflammatory disease affecting people worldwide. Currently, the prevalent guideline-recommended regimen is based on psoriasis severity; however, no corresponding studies have been conducted on the hierarchical selection of integrated Chinese and Western medicine treatments.

Objective: To explore the optimal implementation of psoriasis treatment by integrating Chinese and Western medicine.

Methods: We conducted a 16-week multicenter single-blind randomized controlled trial in China between December 2019 and July 2022. Patients with mild-to-moderate psoriasis (n=107) were randomized to receive oral Jueyin granules (JYG) or moving cupping treatment for 4 weeks, and then transferred to combine the internal or external TCM treatment for another 4 weeks base on the Psoriasis Area and Severity Index (PASI) score. Patients with severe psoriasis (n=193) were randomized to receive treatment with JYG and moving cupping (Group C), narrow-band ultraviolet B (Group D), or JYG, moving cupping and narrow-band ultraviolet B (Group E). Corresponding placebo therapies are applied to ensure single blind implementation. The primary outcome was the effective rate at week 8 and the incidence of relapse at week 16.

Results: The mild-to-moderate psoriasis group showed no differences in the efficacy or relapse resulting from the sequence of internal or external TCM treatment. However, both groups showed significant improvements in PASI score at week 8 compared to baseline (P < 0.001). The severe psoriasis group showed no significant difference in effective rates. While, more participants of Group E achieved PASI 75 (26.79%, P=0.02) at week 8, and Group D had a higher relapse rate at week 16 (21.57%, P=0.03).

Conclusion: Patients with mild-to-moderate psoriasis whether start with internal or external TCM treatment would be viable alternative. Integrated Chinese and Western medicine treatment favors patients with severe psoriasis in the improvement of skin lesions and reduction of recurrence.

Clinicaltrialsgov listing: NCT03941431.

Purpose: Psoriasis is an inflammatory disease linked to gut microbiome dysbiosis. However, the mechanisms underlying gut microbiome changes caused by dietary habits in psoriasis remain unclear.

Patients and methods: We performed a case-control study including 64 psoriasis patients and 64 age-, sex-, and body mass index (BMI)-matched controls. Stool samples were collected for metagenomics sequencing. The differential abundance analysis was performed to identify differentially abundant taxa between psoriasis and control groups. The dietary intake frequency information of each included subject was obtained through face-to-face interviews. Mediation analysis was used to identify potential mediators of the gut microbiome alterations in psoriasis.

Results: The gut microbiome of psoriasis patients was significantly alterated when compared to controls. Anaerostipes Hadrus, Blautia Wexlerae, and the other six species may be beneficial to psoriasis. However, Prevotella Copri and Eggerthellaceae could be pathogenic bacteria. The study also identified correlations between specific dietary habits and psoriasis, with the largest correlation observed between poultry consumption and psoriasis (OR=0.735, P=0.001), followed by red meat (OR=0.784, P=0.007) and fresh vegetables (OR=0.794, P=0.028). Mediation analysis revealed that Anaerostipes hadrus, Dorea longicatena, and Eggerthella lenta mediated the association between poultry and psoriasis.

Conclusion: The characteristics of intestinal flora in psoriasis patients were significantly different from controls. Intestinal flora mediated the association between diet and psoriasis to some extent. This study provides new insights for adjuvant treatments of psoriasis through dietary and intestinal microbiota interventions.

Purpose: Modern systemic therapies offer a high probability of significant improvement for psoriasis. However, elevated liver function tests (LFTs) may cause physicians to be reluctant to initiate systemic treatment. Especially considering the already increased risk of liver disease in patients with psoriasis, clinicians are often concerned about potential further liver damage caused by systemic therapies. The aim of this study was to provide real-world evidence to address this issue.

Patients and methods: This study retrospectively analyzed the treatment courses of N = 278 patients with psoriasis who received systemic anti-psoriatic therapy with secukinumab, ixekizumab, adalimumab, or apremilast in clinical routine. The cohort was divided into two subgroups based on normal or elevated LFTs prior to the start of therapy. AST, ALT, and GGT levels as well as Fibrosis-4 score (FIB-4) were measured at baseline, after 3 months, and after 6 months of therapy.

Results: The subgroup of patients with elevated LFTs had a higher mean PASI (Psoriasis Area and Severity Index), were more likely to be male, and had a higher prevalence of metabolic syndrome comorbidities compared to the subgroup with normal LFTs. During the follow-up period, there were no significant changes in LFTs and FIB-4 for the subgroup with normal LFTs at baseline. In the group of patients with initially elevated LFTs, all LFTs decreased significantly over time, whereas FIB-4 scores demonstrated no significant change. Drug survival, discontinuation rates, and PASI-75 response did not significantly differ between subgroups.

Conclusion: This study provides real world evidence that systemic therapy with secukinumab, ixekizumab, adalimumab, or apremilast does not present a general risk, but rather an opportunity for patients with psoriasis with elevated LFTs at baseline.

Linear psoriasis (LP) represents a rare variant of psoriasis. The clinical presentation includes erythematous plaques distributed along the Blaschko lines, reflecting the presence of embryological mosaicism. The clinical and histopathological features of this condition show many similarities with inflammatory linear verrucous epidermal nevus (ILVEN), which presents a challenge in differential diagnosis. Currently there is no disease-specific treatment guidelines causing a challenge in the therapeutic management. In this case report we describe a 28-year-old patient with LP. Clinically characterized by persistent, psoriasiform lesions that proved refractory to treatment with topical corticosteroids, vitamin D analogs, and systemic dimethyl fumarate. The histopathological findings showed psoriasiform epidermal hyperplasia with alternating ortho- and parakeratosis, subepidermal capillary dilatation, and perivascular lymphocytic infiltrates, confirming the diagnosis. Ixekizumab, a IL-17A antagonist, was administered leading to a rapid and significant reduction in disease severity within the first 16 weeks. The Psoriasis Area and Severity Index (PASI) decreased from 12.5 to 1.0 and as well as the Dermatology Life Quality Index (DLQI) improved to 1. Both scores prove significant improvement in quality of life and clinical severity. This case report shows the importance of histological confirmation in differentiating LP from clinically similar appearing diseases like ILVEN and highlights the potential therapeutic benefit of IL-17 blockade in LP. In addition, the findings emphasize the need for systematic studies to develop evidence-based treatment strategies for this rare psoriasis phenotype.

Purpose: Patients' treatment expectations significantly influence the effectiveness of medical and pharmacological treatments. This clinical proof-of-concept study aimed to enhance treatment outcomes by targeting positive treatment expectations of psoriasis patients beginning systemic anti-psoriatic therapy with secukinumab, an interleukin (IL)-17A antagonist.

Patients and methods: We randomly assigned patients to three groups: a treatment as usual (TAU) group receiving the standard 300mg dose of secukinumab, a dose-control (DC) group with 75% dose reduction and an experimental (EXP) group receiving the same reduced dose along with a "cover story" designed to positively influence treatment expectations. We evaluated skin symptoms using the Psoriasis Area and Severity Index (PASI), the Dermatology Life Quality Index (DLQI), perceived itch, mood and plasma IL-17A levels at baseline and at 1, 2, 3, 4, 8, 12, and 16 weeks post intervention.

Results: The study included N = 120 patients (average age = 45.78 years, 34% female). A high baseline expectation level (8.1 of 10 points) was observed across all groups which could not be further increased by the EXP-group's "cover story". The EXP and DC groups did not differ with regard to reaching 75% improvement in PASI scores (PASI75), a DLQI score of 0 or 1 or at least 4 points improvement in itch. Over time, the EXP-group showed a faster decline in PASI scores and anxiety symptoms compared to the DC-group, but less improvement in quality of life. IL-17A levels significantly increased throughout the treatment, with no significant differences between groups despite the 75% dose reduction.

Conclusion: This study demonstrates an attempt to modify patients' treatment expectations to enhance the effectiveness of pharmacological therapy with secukinumab in psoriasis patients. However, verbal suggestion alone did not significantly improve clinical outcomes, suggesting that future studies should explore alternative approaches to leverage placebo effects to the benefit of patients with psoriasis.

Background: Biological therapies, including TNF-alpha, IL12/23, IL17 and IL23 antagonists, adequately control a very high number of patients with moderate-to-severe psoriasis with an excellent long-term safety profile. However, on occasion, patients on biological therapy with stabilized disease or complete remission report episodes of sudden breakthrough psoriasis.

Aim: To study prospectively in a monocentric tertiary setting, the clinical characteristics of patients presenting a sudden breakthrough psoriasis although completely stabilized (PASI 90-100) under biological therapy.

Materials and methods: Psoriasis patients treated by biological therapies achieving PASI 90-100 and with stabilized disease for at least 6 months were invited to enter the follow-up study for 5 years. The clinical features of patients presenting a breakthrough psoriasis were described as well as the rescue therapies and outcomes.

Results: From the total cohort of 1121 patients with psoriasis receiving biologicals, 985 patients responded to the inclusion criteria. After 5 years, 10/882 cases (1,13%) of breakthrough psoriasis were identified. Two cases were induced by the Köbner phenomenon and 8 cases by severe psychological stress. Rescue therapies included topical very potent corticosteroids or additional injections of the biological. Two patients recovered spontaneously when the stressful event was resolved. In none of the cases, there was a consistency between the breakthrough event and the next scheduled injection, nor the duration of the exposure to the treatment. No biological class or agent could be systematically incriminated.

Conclusion: Breakthrough psoriasis is an exceptional event among patients with stabilized psoriasis using biologicals, either triggered by the Köbner phenomenon or by severe psychological stress. The pathogenesis of the breakthrough events could be linked to stress- or Köbner-related immunomodulation, permitting breakthrough psoriasis lesions to appear.

Psoriasis is a chronic inflammatory disease with a complex pathogenesis. Hyperplasia of glycolytic-dependent epidermal keratinocytes (KCs) is a new hallmark of psoriasis pathogenesis. Meanwhile, immune cells undergo metabolic reprogramming similar to KCs. Glycolysis provides energy for the proliferation of KCs, while it also releases lactic acid to facilitate the differentiation of immune cells. In turn, differentiated immune cells further promote KCs glycolysis by releasing inflammatory factors, thus forming an immunometabolism loop. The interaction between immune response and metabolic pathways jointly promotes the sustained proliferation of KCs and the secretion of various inflammatory factors by immune cells. Understanding the role of glycolysis in immunometabolism of psoriasis may provide new ideas for non-immunosuppressive treatment of psoriasis. This article aims to review the role of glycolysis in the pathogenesis of psoriasis and attempts to summarize the key enzymes and regulatory factors involved in psoriasis glycolysis, as well as their interactions. Finally, we discuss the pharmacological modulators of glycolysis in psoriasis.