Psoriasis is a complex chronic inflammatory disease with cutaneous manifestations, driven by intricate interactions between genetic, immunological, and metabolic dysregulations. However, the integrated molecular networks connecting transcriptional alterations to metabolic reprogramming remain incompletely elucidated. We performed a comprehensive integrated analysis of transcriptomics and targeted metabolomics using serum samples from 11 psoriasis vulgaris patients and 11 healthy controls to dissect the core gene-metabolite regulatory axes underlying psoriasis. RNA sequencing identified 5,186 differentially expressed genes (DEGs), with a striking predominance of downregulation (5,147 DEGs), and targeted metabolomic profiling detected 208 significantly altered metabolites, including upregulated propanoic acid and downregulated L-allysine. KEGG pathway enrichment analysis revealed six dysregulated metabolic pathways shared by DEGs and altered metabolites, notably lysine degradation, propanoate metabolism, and central carbon metabolism in cancer—with the latter identified as a novel pathogenic pathway in psoriasis vulgaris. Weighted Gene Co-expression Network Analysis (WGCNA) further delineated strong correlations between core genes (TP53, MTOR, AKT3) and key metabolites (propanoic acid, L-allysine), forming a functional network that links cellular energy metabolism to immune-inflammatory responses. Protein-protein interaction network analysis confirmed these core genes as hub regulators within the dysregulated pathways. In this exploratory pilot study, integrated transcriptomic and metabolomic profiling revealed preliminary associations between lysine degradation, propanoate metabolism, and psoriasis status. The observed crosstalk with central carbon metabolism, potentially involving TP53, MTOR, and AKT3, generates hypotheses that require validation in independent, larger cohorts before any clinical or mechanistic inferences can be drawn.
Atopic dermatitis (AD) presents as a prevalent chronic, relapsing, inflammatory skin condition. While dupilumab has proven effective in treating moderate-to-severe AD, some patients still experience unsatisfactory outcomes with this therapy in clinical settings. Patients with AD receiving dupilumab were selected for inclusion in the present study for prospective observations. Over an 8-week period, the patients underwent monitoring and changes in serum biomarkers and circulating T helper (Th) cell levels were analyzed using questionnaires, ELISA and flow cytometry. The Scoring Atopic Dermatitis (SCORAD), Objective-SCORAD, Itch Numeric Rating Scale (NRS), Dermatology Life Quality Index, Patient Oriented Eczema measure and Atopic Dermatitis Control Tools scores in patients with AD significantly decreased at week 8 compared with those before treatment (P<0.05). Moderate positive correlations were demonstrated between serum thymus and activation-regulated chemokine (TARC) and human β-defensin 2 levels and Eczema Area and Severity Index (EASI) and SCORAD scores (P<0.05). A weak negative correlation was shown between serum IgE against Staphylococcus aureus enterotoxin A level and the EASI and SCORAD scores, although these were not statistically significant (P>0.05). There was a notable increase in the proportion of Th2 cells in peripheral blood at week 2 (P<0.05). The proportion of Th22 cells in the peripheral blood was weakly correlated with the NRS score (P>0.05). Patients were categorized into rapid or slow groups depending on whether they achieved EASI-75 scores by week 8. The proportion of Th17 cells in peripheral blood in the rapid group at week 8 of treatment was lower than that compared with the slow group at week 2 (P<0.05). The SCORAD scores of the rapid group were significantly lower compared with those of the slow group at week 8 of treatment (P<0.05). The conventional dupilumab treatment regimen led to a marked remission in patients with exogenous AD after 8 weeks of therapy. Significant correlations were observed between serum TARC levels and clinical disease scores (P<0.05), which changed notably during treatment and remained valuable for monitoring disease progression at follow-up. Additionally, the elevated ratio of Th17 cells in peripheral blood at week 2 of treatment showed potential for predicting the attainment of EASI-75 by week 8 after treatment.
Biologic therapies have been successfully applied in the treatment of psoriasis and atopic dermatitis, however, unique phenomena of immunophenotypic switching have also been constantly reported. This review summarizes the current status and mechanisms of immunophenotypic switching among patients with psoriasis or atopic dermatitis during the treatment with biologics, in order to promote the full understanding of this new abnormal immune reaction.
BACKGROUND:Although efficacy and safety of Upadacitinib and Dupilumab in moderate to severe atopic dermatitis (AD) have been shown in clinical trials, real world data are still limited. The aim of this retrospective study is to indirectly compare the efficacy and safety of Upadacitinib and Dupilumab in patients with moderate to severe AD in real world practice. METHODS:A single-center retrospective cohort study was conducted. The study included patients with moderate to severe AD, who were enrolled from May 2022 to March 2024, to indirectly compare the efficacy and safety of Upadacitinib and Dupilumab over 12 weeks duration. RESULTS:Eighty-seven patients were included (46 received Upadacitinib and 41 Dupilumab). Compared with week 0, there was a significant decrease in EASI score, ADCT score and NRS score in patients of both groups in weeks 4, 8, and 12. In week 4, the reduction in EASI score, ADCT score and NRS score was significantly greater in patients of Upadacitinib group compared to those in Dupilumab group. Compared to baseline, in week 12, the decrease in IL-4, IL-13, and IL-31 level in the serum of patients in Upadacitinib group was significantly greater than that of patients in Dupilumab group. The total IgE of patients in Dupilumab group decreased significantly, while there was no significant change in patients of Upadacitinib group. Although Upadacitinib group reported more adverse events than Dupilumab group, no serious adverse events were observed. CONCLUSIONS:Both Upadacitinib and Dupilumab groups showed effective trend in patients with moderate to severe AD. Upadacitinib has better efficacy and rapid onset in the treatment of patients with moderate to severe AD.
Background: Psoriasis is an immune-mediated inflammatory, chronic, recurrent skin disease associated with a high risk of developing psychiatric disorders, especially depression and suicidal ideation, leading to functional disability and poor quality of life. Objective: To comprehensively review and assess the epidemiologic association between psoriasis and the risk ratios (RRs) of depression or suicidal ideation. Methods: Five databases (PubMed, Wanfang Database, CNKI, The Cochrane Library, and EMBASE) were searched for prospective cohort studies on the prevalence of depression and/or suicidal ideation in patients with psoriasis updated to 2 February 2023. Two independent reviewers evaluated and extracted the data, which were then pooled into a summary RR with corresponding 95% confidence interval (CI) using random-effects models in Stata/MP14.0. Results: Sixteen cohort studies comprising 1,166,840 patients with psoriasis and 3,294,205 controls were eligible for the final analysis. The pooled RR for depression was 1.43 (95% CI = 1.13–1.81) in patients with psoriasis and1.55 (95% CI = 1.40–1.71) in patients with psoriatic arthritis. In the subgroup analysis, Asian patients with psoriasis (RR=1.38, 95% CI =1.17–1.63) had a lower pooled RR for depression than non-Asian patients (RR=1.45, 95% CI = 1.07–1.97), and patients with moderate to severe psoriasis (RR=1.69, 95% CI = 1.15–2.50) showed a higher RR for depression than patients with mild psoriasis (RR=1.60, 95% CI= 1.06–2.42). We also found no increase in the RR for suicidal ideation among people with psoriasis (RR=1.25, 95% CI =0.95–1.65). Conclusions: Patients with psoriasis are at increased risk of depression. Among patients with psoriasis, those with psoriatic arthritis, those who are non-Asian, and those with moderate to severe psoriasis are at higher risk for depression. However, the available evidence does not support an association between psoriasis and suicidal ideation.
Photoaggravated dermatoses (PD) are diseases that occur without ultraviolet (UV) radiation but are sometimes or frequently exacerbated by UV radiation. The clinical manifestations of PD are varied, some patients may present with pruritic nodular lesions at the site of light exposure, which possibly through a light-induced type 2 inflammatory response. Some cases may be difficult to treat, safe and effective treatment methods are constantly being explored. Here, we reported five patients with moderate to severe PD with skin nodules as main manifestations successfully treated with dupilumab, who were previously resistant to conventional treatment. After the 16-week treatment period, dupilumab showed good efficacy and safety in PD mainly characterized by nodules.
银屑病是由免疫介导为主的慢性炎症性复发性疾病,而光疗因疗效确切、不良反应少,是治疗银屑病常用的治疗手段之一。光疗包括紫外线、可见光、激光、红外线等,其中紫外线光疗特别是窄谱中波紫外线(NB-UVB)、靶向中波紫外线(UVB)(308 nm准分子激光、308 nm准分子光)、补骨脂素光化学治疗UVA(PUVA)较为常用,而脉冲染料激光等激光疗法对甲银屑病和掌跖部位银屑病有良好疗效。本文将介绍适用于银屑病的光疗种类及其作用机制、适应证、疗效、联合治疗、不良反应及注意事项等。通过进一步认识光疗治疗银屑病的应用及研究进展,为银屑病患者提供更优更安全的个体化治疗方案,对确保安全性、改善皮损、提高患者生活质量有重要的指导意义。
51岁女性患者,右侧颧骨外侧皮肤肿物伴瘙痒6个月,搔抓后肿物表面易出血.右侧颧部外侧皮肤见一直径约1 cm的类圆形微隆起的红褐色斑块,边界清晰,表面粗糙覆有雾状透明细鳞屑,可见毛细血管扩张和针尖大小新鲜出血点,压之褪色.组织病理示:皮损与两侧正常上皮分界清晰,表皮角化不全,皮突融合延长,棘层规则肥厚,细胞富含糖原、细胞质呈透明状,皮突与真皮交界处大量淋巴细胞及散在浆细胞、嗜酸粒细胞浸润.棘层细胞胞质PAS染色阳性,人乳头瘤病毒(HPV)免疫组化阴性.诊断:透明细胞棘皮瘤.完整切除术后随访1年未见复发.该例未发现恶性证据,仍考虑为良性表皮肿瘤.
Most available options for the treatment of warts are limited by the potential for scarring, pain, lack of response, or recurrences, and the patients are often unable to tolerate and accept those experiences. The aim of this study was to evaluate the clinical efficacy and safety of oral systemic acitretin monotherapy in patients with extensive/recalcitrant cutaneous warts. The patients were given a dose of acitretin of 0.8 mg kg(-1) day(-1), and the clinical efficacy and safety of acitretin was assessed every 2 weeks for 2 months. A total of 14 patients (12 males and 2 females) were included, with an age of 14-60 years (mean 33 +/- 14.7 years) and a course of 4-48 months (mean 21.6 +/- 13.4 months). After 2 months of acitretin treatment, 42.9% (6/14) of patients (including warts of the feet, legs, and hands) exhibited complete response, 28.6% (4/14) excellent response, and 28.6% (4/14) good response. All patients demonstrated significant improvement, and the drug was well tolerated, with no patients discontinuing therapy due to side effects. Common mild side effects included dry skin and cheilitis. There were no recurrences during a follow-up period of 6 months. Acitretin monotherapy is an effective, safe, and well-tolerated treatment for patients with extensive/recalcitrant cutaneous warts who are unsuitable for or unwilling to accept traditional treatment methods.
Abstract Background Erythrokeratodermia variabilis et progressiva (EKVP, OMIM 133200) is a rare hereditary disorder characterized by varies from transient, fast moving erythema to persistent brown hyperkeratotic plaques. Recently, mutations in the genes gap junction alpha 1 gene (GJA1), GJB3, and GJB4 have been reported to cause EKVP. Here, we report the identification of two de novo missense mutations in the GJA1 gene in two unrelated individuals with EKVP. Methods The patients and his family members were subjected to mutation detection in the candidate gene GJA1, GJB3, and GJB4 by Sanger sequencing. The expression of connexin (Cx) 43 was detected by immunohistochemistry and immunofluorescence (IF) studies in the lesions. Results A 12‐year‐old boy presented with multiple hyperkeratotic plaques on the face, neck, elbows, wrists, limbs, knees, inguinal region, hands, and feet. A 7‐year‐old girl presented with symmetrical erythematous, plaques on the hands, feet, wrists, and ankles. A novel heterozygous missense mutation c.848C > T (p.P283L) in exon 2 of the GJA1 gene was identified in both patients. A novel heterozygous missense mutation c.869C > A (p.T290N) in exon 2 of the GJA1 gene was also identified in the boy. These mutations were not found in the unaffected family members and 100 normal controls. In the patients’ lesions, Cx43 protein was located to the cytomembrane and cytoplasm in the stratum corneum, and granular layer. Compound heterozygous mutations in the boy showed a more severe clinical phenotype and cytoplasmic mislocalization. Conclusions The novel mutations c.848C > T (p.P283L) and c.869C > A(p.T290N) arose de novo and were considered as the cause of two Chinese EKVP. GJA1 P283L and T290N mutations lead to Cx43 protein cytoplasmic mislocalization. Our finding expands the mutant spectrum of GJA1 gene and adds new understanding of the genotype‐phenotype correlation.
儿童银屑病是一种常见的炎症性皮肤病, 而儿童脓疱型银屑病 (Childhood pustular psoriasis, CPP) 较为少见, 是一种发生于儿童的全身性炎症性伴皮肤功能障碍的银屑病类型.CPP顽固且易复发, 对患儿及其父母生活质量及发展都影响颇大.对于CPP, 皮肤的局部治疗是必不可少的基础, 维甲酸类、甲氨蝶呤、环孢素、生物制剂等为系统治疗中的常用药物, 脓疱型银屑病儿童通常对光疗有较好的反应.此文介绍了目前针对于儿童脓疱型银屑病的治疗共识与经验, 为现在的治疗进展进行了概括.
Background: Vitiligo is an acquired depigmentation skin disorder mainly caused by the destruction of melanocytes. There are many therapeutic options available for vitiligo, but the options are not uniformly effective. Objectives: This study aimed to explore the clinical effect of the autologous non-cultured epidermal cell suspension (NCES) technique in the treatment of patients with stable vitiligo. Methods: A retrospective study of before-after comparisons was undertaken with 41 patients with stable vitiligo who received treatment with the NCES technique. The percentage of repigmentation area was evaluated using image analysis of the appearance before and 6-9 months after operation. Results: A total of 41 patients (18 males and 23 females) with a duration of clinical stability for ranging from 1 to 10 years (mean 1.6 +/- 1.9) were included. The mean age was 20.2 years (range, 8-50) and 4 (9.8%) were children under the age of 14 years. After 6-9 months of follow-up, 80.5% (33/41) of the patients showed good response; among these patients, 17.1% (7/41) showed complete or almost complete repigmentation. Interestingly, all 4 children showed very good response (more than 76% repigmentation). There were no significant differences in the efficacy of treatment between the different transplantation areas of the facial neck, trunk, and distal limbs and there were no adverse effects such as infection or scar formation. Limitation: This study included only a single center with a small sample size. Conclusions: Our study shows that the NCES technique has a high therapeutic effect, is safe for patients with stable vitiligo, and may be a very promising potential option for treating children.
目的 分析26例白色萎缩患者的临床、组织病理表现,以提高早期诊治水平.方法 通过临床资料回顾性分析,将广州医科大学皮肤病研究所诊治的26例白色萎缩患者的临床表现、实验室及组织病理检查、治疗情况进行总结.结果 患病具有青年女性倾向,皮损好发于双小腿及远端部位,主要表现为红斑、紫癜、瘀斑、痛性溃疡,遗留白色萎缩和色素沉着,易反复发作.皮肤组织病理检查发现大多数皮损真皮内血管壁纤维蛋白样坏死、透明血栓形成.小剂量阿司匹林、双嘧达莫及糖皮质激素治疗效果较好.结论 根据典型病史、临床表现及组织病理学检查即可诊断白色萎缩,临床上应提高对白色萎缩的早期诊断、早期治疗.
The roles of IL-22 in the pathomechanisms of psoriasis have been well demonstrated. Gap junctional intercellular communication (GJIC) is widely known for its involvement in multiple biological and pathological processes such as growth-related events, cell differentiation, and inflammation. Here, we show that IL-22 significantly decreased GJIC and down-regulated Cx43 expression in HaCaT cells. Cx43 overexpression markedly inhibited the proliferation of and increased GJIC in HaCaT cells, but the silencing of Cx43 exerted the opposite effects. Additionally, Cx43 overexpression effectively rescued the IL-22-induced decrease in GJIC in HaCaT cells. The IL-22-induced down-regulation of Cx43 expression and decrease in GJIC can be significantly blocked by the JNK inhibitor SP600125 and by the overexpression of IL-22RA2 (which specifically binds to IL-22 and inhibits its activity), but not by the NF-κB inhibitor BAY11-7082, in HaCaT cells. Furthermore, the IL-22-induced down-regulation of Cx43 expression mediated by the JNK signaling pathway was confirmed in a mouse model of IL-22-induced psoriasis-like dermatitis. Similarly, Cx43 expression was significantly lower in the lesional skin than in the nonlesional skin of patients with psoriasis. These results suggest that IL-22 decreases GJIC by activating the JNK signaling pathway, which down-regulates Cx43 expression; this process is a possible pathomechanism of keratinocyte hyperproliferation in psoriasis.
Abstract Background: There is a few evidence-based information regarding the efficacy and safety of acitretin treatment in children with pustular psoriasis (PP). Objective: This study aimed to provide an additional evidence for this field. Methods: A retrospective study was undertaken for 15 children with PP who received acitretin in doses of 0.6–1.0 mg/kg/day for 4–6 weeks, the transition dose of 0.2–0.4 mg/kg/day for 4–6 weeks and maintenance dose of 0.2–0.3 mg/kg/day. Additionally, a literature review on this topic is conducted. Results: Of 15 children with generalized PP (GPP, n = 10), palmoplantar psoriasis (PPP, n = 3), and acrodermatitis continua of Hallopeau (ACH, n = 2), 93.3% (14/15) showed good response, only one case with ACH exhibited moderate response. During the 10–32 months of follow-up, acitrerin monotherapy for children cases with PP overall showed good efficacy and safety. In the literature review, a total of 107 childhood PP cases treated with acitretin in 21 studies were included in the analysis. The clinical effectiveness was obtained in 88.8% (95/107) patients treated with acitretin as monotherapy or combination therapy, and most of cases (92.6%, 100/107) treated by acitretin did not report side effects during the treatment and follow-up of acitretin. Limitation: This study is just included a small sample sizes and no standardized studies were used in the literature. Conclusion: Acitretin therapy for children with PP (monotherapy or combination therapy), all showed a satisfactory therapeutic effect and safety, independent of the short or long-tern therapeutic procedures.
Background: Interleukin 4 (IL-4) -590C/T polymorphism has been reported to influence atopic dermatitis (AD) susceptibility, but the results are controversial.Objective: This meta-analysis was performed to study the association between IL-4 -590C/T polymorphism and AD susceptibility.Methods: The PubMed, Embase, and China National Knowledge Infrastructure databases were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were performed to estimate the strength of the association.Results: Ten studies comprising 923 cases and 1215 controls were included. The overall population revealed significant associations between IL-4 -590C/T polymorphism and AD susceptibility under the allele (OR, 1.19; 95% CI, 1.03Y1.38; I-2 = 0.0%), recessive (OR, 1.27; 95% CI, 1.002Y1.61; I-2 = 0.0%), and dominant (OR, 1.33; 95% CI, 1.003Y1.76; I-2 = 0.0%) models; similar results were found under the allele (OR, 1.19; 95% CI,1.01Y1.39; I-2 = 0.0%) and recessive (OR, 1.27; 95% CI, 1.001Y1.62; I-2 = 0.0%) models after excluding not-inYHardy-Weinberg equilibrium studies. However, subgroup analyses by ethnicity showed no significant associationin Asians or whites. Subgroup analyses by age indicateda significant association inchildren under the allele(OR, 1.30; 95% CI, 1.06Y1.60; I-2 = 0.0%) and dominant (OR, 1.42; 95% CI, 1.02Y1.97; I-2 = 0.0%) models, children in articles with Hardy-Weinberg equilibriumunder the allelemodel (OR, 1.33; 95% CI, 1.05Y1.69; I-2 = 0.0%), and Asian children under the allele model (OR, 1.41; 95% CI, 1.02Y1.95; I-2 = 0.0%) but not in white children.Conclusions: The IL-4 -590C/T polymorphism may contribute to AD susceptibility in the overall population and children, especially for Asian children, but large well-designed studies are warranted to confirm this conclusion.
反向银屑病又称间擦银屑病或屈侧银屑病,是银屑病的一种特殊表现类型,在中国人群中发病率占银屑病的3.2%~7%.同寻常型银屑病相比,在发病部位上,主要为体表褶皱部位;在临床表现上,表现为境界清楚的红斑,其上覆少量鳞屑或无鳞屑,炎症更明显,同形反应更敏感;在发病机制上,皮损中CD161+表达量明显下降,与微生物定植相关;在治疗上,局限性反向银屑病以局部治疗为主,重症或伴发其他类型银屑病需系统治疗.本文就反向银屑病的流行病学、临床特征、发病机制及治疗等方面进行详细的综述.