BACKGROUND:Psoriasis is a chronic inflammatory skin disease associated with substantial patient burden. Symptoms often worsen later in the day, suggesting time-of-day (ToD)-dependent variation, although the underlying systemic immune correlates remain poorly understood. OBJECTIVE:To investigate ToD-dependent variation in immune parameters and inflammatory mediators in psoriasis and their associations with disease severity and treatment response. METHODS:Peripheral blood samples were collected in the morning and evening before and after anti-IL-23 therapy. Immune cell subsets, serum cytokines, and chemokines were quantified. Public skin transcriptomic datasets were analysed using the ZeitZeiger algorithm to infer sampling time and assess ToD-dependent inflammatory signatures. RESULTS:Patients with psoriasis exhibited attenuated time-of-day variation in circulating lymphocytes, largely driven by reduced evening lymphocyte counts. In parallel, patients showed an evening-biased inflammatory profile characterized by increased cytokines and chemokines involved in inflammation and leukocyte migration. Anti-IL-23 therapy reduced inflammatory mediator levels and partially restored disrupted diurnal immune dynamics, particularly at the evening time point. The extent of diurnal variation was associated with disease severity: ToD-dependent variation in IL-31 positively correlated with PASI, whereas variation in Th17 cells and the CD4+/CD8+ ratio showed negative correlations. Non-responders exhibited higher pre-treatment evening IL-31 levels and a more pro-inflammatory immune profile. Consistently, transcriptomic analyses revealed enhanced late-ToD inflammatory activity and immune cell infiltration in lesional psoriatic skin, both of which were attenuated after treatment. CONCLUSION:Psoriasis is characterized by altered time-of-day-dependent immune dynamics, including reduced ToD variation in circulating lymphocytes and a late-ToD pro-inflammatory profile. These findings suggest that temporal immune dysregulation is associated with disease activity and treatment response, and that anti-IL-23 therapy may partially restore disrupted time-of-day immune variation. Consideration of temporal immune context may improve biomarker interpretation and help inform future therapeutic strategies.

Objective To assess the real‐world long‐term treatment effectiveness of ixekizumab (IXE) in Chinese patients with moderate‐to‐severe psoriasis (msPsO). Methods This study used a Chinese national psoriasis registry database to retrospectively analyze data on patients initiating IXE treatment between 2020 and 2024. Baseline patient characteristics, treatment information, and treatment responses at Weeks 24, 48, 60, and 104 were extracted for data analysis. Descriptive statistics were used to summarize the baseline patient characteristics and treatment responses based on measures such as the Psoriasis Area and Severity Index (PASI). Multiple logistic regression analyses were conducted to explore associations between patient characteristics and PASI response outcomes, including PASI 75, PASI 90, and PASI 100, at each time point. Results A total of 415 msPsO patients from 44 hospitals were included (mean age ± standard deviation [SD]: 43.0 ± 14.8 years, male: 72.5%, overweight/obesity: 45.5%, and severe psoriasis: 83.9%). IXE showed sustained effectiveness across all four prespecified time points: PASI 75 response rates were 86.2% at Week 24 ( N = 311), 83.7% at Week 48 ( N = 178), 85.3% at Week 60 ( N = 136), and 87.1% at Week 104 ( N = 70); PASI 90 response rates were 74.3%, 71.9%, 71.3%, and 67.1%, respectively; and PASI 100 response rates were 58.5%, 57.9%, 56.6%, and 47.1%, respectively. Multiple logistic regression analyses showed that overweight/obesity (48‐week PASI 75: odds ratio [OR] = 0.313, p = 0.047), prior biologic therapy (48‐week PASI 75: OR = 0.045, p = 0.010; 60‐week PASI 75: OR = 0.046, p = 0.014), and urban employee basic medical insurance (48‐week PASI 75: OR = 4.263, p = 0.011; 48‐week PASI 90: OR = 2.841, p = 0.016; 60‐week PASI 90: OR = 2.597, p = 0.042; 60‐week PASI 100: OR = 2.384, p = 0.047) were significantly associated with PASI responses. At Week 104, no significant association was found between the baseline characteristics and PASI responses. Conclusion This real‐world study showed sustained reduction in psoriasis severity in the long term among IXE‐treated Chinese patients with msPsO, mirroring clinical trials.

BACKGROUND:Rheumatoid arthritis (RA) is an inflammation-mediated autoimmune disease. Tinosporine (TIN), derived from Tinospora sinensis (Lour.) Merr. has significant anti-inflammatory and immunosuppressive effects. However, the anti-RA effect and mechanism of TIN have not been fully elucidated. OBJECTIVE:This study elucidates the mechanism of TIN in alleviating collagen-induced arthritis (CIA) in rats based on the gut microbiome-metabolomic-immunity axis. MATERIALS AND METHODS:We established CIA rat model to evaluate the efficacy of TIN. Based on 16S rRNA sequencing analysis, fecal metabolomics profiling and the concentrations of short-chain fatty acids determination to investigate the effect of TIN on gut microbiota composition and metabolome changes. Histopathology showed that TIN protected the intestinal barrier, then use ELISA and flow cytometry to analyze the mechanism of TIN, and qRT-PCR and WB were employed for verification. RESULTS:TIN ameliorated joint damage and inflammation in CIA rats, histopathological observation confirmed that TIN had protective effect on intestinal barrier. 16S rRNA sequencing analysis and fecal metabolomics profiling confirmed that TIN intervention regulates the composition of gut microbiome and promote the propagation of probiotics, the abundance changes of 12 serum metabolites in the CIA group were reversed by TIN intervention. After intervention with TIN, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, and caproic acid rise significantly, but acetic acid cannot be reversed. Then ELISA and flow cytometry confirmed that TIN intervention could regulate the level of inflammatory factors, maintain the integrity of the intestinal barrier and restoring the imbalance of Th1/Th2 and Th17/Treg ratios in the colon of CIA rats. CONCLUSION:TIN inhibited the inflammatory response of CIA rats by regulating the gut microbiome-metabolome-immunity axis, reversed the abnormalities of intestinal flora and differential metabolites, and maintained the integrity of the intestinal barrier.

ObjectiveTo analyze the correlations between serum Nod-like receptor protein 3 （NLRP3）， cytoskeleton-associated protein 4 （CKAP4）， interleukin-37 （IL-37）， and vascular calcification in patients with uremia undergoing maintenance hemodialysis （MHD）.MethodsA total of 127 MHD patients admitted to Xianyang Hospital of Yan'an University from June 2021 to December 2023 were assessed for vascular calcification and divided into a calcification group （n=52） and a non-calcification group （n=75）. General characteristics， biochemical indices， and serum NLRP3， CKAP4， and IL-37 levels were compared between groups. Correlations with biochemical indices were assessed using Pearson coefficients. Logistic regression identified independent factors associated with vascular calcification. Receiver operating characteristic （ROC） curves evaluated the predictive performance of individual markers and their combination. Risk ratios （RRs） were calculated to assess risk stratification based on prespecified serum thresholds.ResultsCompared with the non-calcification group， the calcification group had higher serum phosphate， intact parathyroid hormone （iPTH）， NLRP3， and IL-37 levels and lower CKAP4 levels： Phosphate ［（1.97±0.44） mmol/L vs （1.75±0.40） mmol/L］， iPTH ［（355.16±62.43） ng/L vs （276.14±57.84） ng/L］， NLRP3 ［（116.47±14.02） ng/L vs （93.04±8.16） ng/L］， IL-37 ［（19.96±4.19） ng/L vs （17.58±3.51） ng/L］， and CKAP4 ［（135.29±16.34） ng/L vs （213.45±25.63） ng/L］； all P<0.05. Pearson analyses indicated that NLRP3 and IL-37 were positively correlated with serum phosphate and iPTH， whereas CKAP4 was negatively correlated （all P<0.05）. Logistic regression identified serum phosphate， iPTH， NLRP3， and IL-37 as independent risk factors for vascular calcification， with CKAP4 as an independent protective factor （P<0.05）. The combined marker panel （NLRP3+CKAP4+IL-37） yielded an area under the ROC curve （AUC） of 0.921， outperforming each individual marker. RR analyses showed that NLRP3>102.14 ng/L， CKAP4≤144.11 ng/L， and IL-37>18.71 ng/L were associated with higher risk of vascular calcification and effectively stratified risk in MHD patients （P<0.05）.ConclusionIn uremic patients receiving MHD， serum NLRP3， CKAP4， and IL-37 are independently associated with vascular calcification. Combined measurement of these markers provides high predictive value and may aid in risk assessment and guide clinical prevention and treatment.

BackgroundOur study aimed to clarify the impact of home quarantine on disease severity, quality of life, and mental health in psoriasis patients through the multidimensional analysis of the status of home quarantine, the severity of psoriasis, quality of life, and depression scores during the COVID-19 pandemic.MethodsFrom 2022 to 2023, we conducted telephone follow-up on 963 psoriasis patients. Participants’ demographic characteristics, psoriasis condition, home quarantine duration, quality of life and depression symptom scores were collected. The association between COVID-19 lockdown and patient-reported outcomes were investigated with pearson correlation and Spearman correlation.ResultsA total of 963 participants were recruited, finally 605 participants were enrolled. The mean values of age and disease duration was 43.63 years, 312.35 years, 67.6% were male. Patients with disease-related impaired quality of life (DLQI > 5) accounted for 7.44%. A total of 65 patients had varying degrees of depression symptoms (QIDS-SR16 > 5 points). The result of correlation analysis revealed a positive correlation between BSA and both DLQI and QIDS-SR16 scores (R = 0.27, p < 0.001; R = 0.08, p < 0.05).ConclusionOur results revealed that COVID-19 lockdown had a measurable impact on disease severity, quality of life, and mental health in psoriasis patients. Many individuals experienced varying degrees of symptoms aggravation during the lockdown. The severity of psoriasis was negatively correlated with quality of life and positively correlated with depression symptoms, with older adult patients being particularly vulnerable to depression. These findings highlight the importance for dermatologists to integrate mental health assessment and support into routine psoriasis management.

ABSTRACT POETYK PSO‐3, a 52‐week, double‐blind, phase 3 study, evaluated the efficacy and safety of deucravacitinib, an oral, selective, allosteric tyrosine kinase 2 inhibitor, in adult patients with moderate to severe plaque psoriasis in mainland China, Taiwan, and South Korea. Secondary and additional endpoints included improvement on two patient‐reported outcome measures: the Psoriasis Symptoms and Signs Diary (PSSD) total score and the Dermatology Life Quality Index (DLQI). Patients were randomized 1:2 to placebo or deucravacitinib 6 mg once daily; at week 16, patients receiving placebo crossed over to receive deucravacitinib. PSSD and DLQI score changes from baseline and response rates for achieving meaningful within‐patient change from baseline in PSSD total score (≥ 15 points) and DLQI of 0 or 1 (DLQI 0/1) were assessed over 52 weeks. In POETYK PSO‐3, 74 patients were randomized to placebo and 146 patients to deucravacitinib. At week 16, mean (95% confidence interval [CI]) PSSD total score changes from baseline were −1.9 (−6.9, 3.1) and −28.8 (−32.6, −25.0) in patients receiving placebo and deucravacitinib, respectively. At both weeks 16 and 52, the response rate for ≥ 15‐point meaningful change in PSSD total score (95% CI) was 73.3% (65.3, 80.3) in the group randomized to deucravacitinib. At week 16, mean (95% CI) DLQI changes from baseline were −1.7 (−3.1, −0.4) and −7.4 (−8.4, −6.4) in patients receiving placebo and deucravacitinib, respectively. In patients randomized to deucravacitinib, DLQI 0/1 response rates (95% CI) at weeks 16 and 52 were 36.4% (28.5, 44.4) and 44.7% (36.5, 52.9), respectively. Deucravacitinib was associated with meaningful and sustained improvements in psoriasis symptoms and signs and in quality of life in Asian patients with moderate to severe plaque psoriasis. Trial Registration: ClinicalTrials.gov identifier: NCT04167462

Background::Generalized pustular psoriasis (GPP), a rare and recurrent autoinflammatory disease, imposes a substantial burden on patients and society. Awareness of GPP in China remains limited.Methods::This cross-sectional survey, conducted between September 2021 and May 2023 across 14 hospitals in China, included GPP patients of all ages and disease phases. Data collected encompassed demographics, clinical characteristics, economic impact, disease severity, quality of life, and treatment-related complications. Risk factors for GPP recurrence were analyzed.Results::Among 127 patients (female/male ratio = 1.35:1), the mean age of disease onset was 25 years (1st quartile [Q1]–3rd quartile [Q3]: 11–44 years); 29.2% had experienced GPP for more than 10 years. Recurrence occurred in 75.6% of patients, and nearly half reported no identifiable triggers. Younger age at disease onset ( P = 0.021) and transitioning to plaque psoriasis ( P = 0.022) were associated with higher recurrence rates. The median diagnostic delay was 8 months (Q1–Q3: 2–41 months), and 32.3% of patients reported misdiagnoses. Comorbidities were present in 53.5% of patients, whereas 51.1% experienced systemic complications during treatment. Depression and anxiety affected 84.5% and 95.6% of patients, respectively. During GPP flares, the median Dermatology Life Quality Index score was 19.0 (Q1–Q3: 13.0–23.5). This score showed significant differences between patients with and without systemic symptoms; it demonstrated correlations with both depression and anxiety scores. Treatment costs caused financial hardship in 55.9% of patients, underscoring the burden associated with GPP. Conclusions::The substantial disease and economic burdens among Chinese GPP patients warrant increased attention. Patients with early onset disease and those transitioning to plaque psoriasis require targeted interventions to mitigate the high recurrence risk.

BACKGROUND:Psoriasis treatments that provide rapid and extensive itch relief as well as lesion clearance are currently inadequate. OBJECTIVES:To evaluate the efficacy and safety of the tyrosine kinase 2/Janus kinase 1 inhibitor TLL-018 in patients with moderate-to-severe psoriasis. METHODS:This phase Ib, double-blind, placebo-controlled study (NCT05342428) randomized participants to receive TLL-018 10 mg, 20 mg, 30 mg or placebo 2 : 2 : 2 : 1 orally twice daily for 12 weeks. The study included 73 patients with moderate-to-severe psoriasis. Eligible patients were aged 18-75 years and were diagnosed with moderate-to-severe psoriasis at least 6 months prior to screening, as defined by a Psoriasis Area and Severity Index (PASI) of ≥ 12, a body surface area ≥ 10% and a Physician's Global Assessment (PGA) of ≥ 3. The primary endpoint was safety of TLL-018. The efficacy endpoints were proportions of patients at week 12 achieving a ≥ 75% improvement from baseline in PASI (PASI 75), PGA of 0 or 1 (PGA 0/1) and Dermatology Life Quality Index of 0 or 1. RESULTS:A total of 73 participants were treated. TLL-018 was well tolerated, and most treatment-emergent adverse events were mild/moderate. At week 12, 40% of patients (8 of 20) achieved PASI 75 with TLL-018 10 mg, 48% (10 of 21) with 20 mg, 62% (13 of 21) with 30 mg and 9% (1 of 11) with placebo. The proportions of patients with PGA 0/1 were 35%, 43%, 71% and 0%, respectively. Of the 21 patients in the TLL-018 30-mg group, 10 (48%) achieved a ≥ 90% improvement from baseline in PASI. CONCLUSIONS:TLL-018 was well tolerated and showed promising efficacy at week 12 compared with placebo in patients with moderate-to-severe plaque psoriasis.

Psoriasis is a chronic inflammatory skin disease. It is associated with many autoimmune diseases such as rheumatoid arthritis, Crohn’s disease and thyroid diseases. Graves’ disease (GD) is a common organ-specific autoimmune disease characterized by diffuse goitre and thyrotoxicosis. Management of psoriasis patients with GD is challenging. This current report presents the case of a 34-year-old female patient with refractory psoriasis with GD who was hospitalized for drug eruption and then experienced new-onset erythema and scaling following treatment with adalimumab and secukinumab. Despite the sequential move to phototherapy, tofacitinib and ustekinumab, the erythema and scaling continued unabated and exacerbated. Finally, switching to guselkumab resulted in the psoriasis lesions significantly improving. These findings suggest that guselkumab might be an effective treatment option for refractory psoriasis combined with GD.

In this study we aimed to investigate the prevalence of SARS-CoV-2 infection in psoriasis patients, and outcomes of SARS-CoV-2 infection and associated risk factors. A cross-sectional survey was conducted from February 2023 to March 2023. Information was obtained with online questionnaire about psoriasis patients on demographic characteristics, clinical characteristics, SARS-CoV-2 infection and outcomes, vaccination, and routine protection against COVID-19. Logistic regression analysis was used to explore risk factors with SARS-CoV-2 infection and exacerbation of psoriasis. A total of 613 participants were recruited. 516 (84.2%) were infected, and associated factors were sex, working status, routine protection against COVID-19, COVID-19 vaccination, impaired nail, infection exacerbate psoriasis, and severity of psoriasis. Among the patients infected with SARS-CoV-2, 30 (5.8%) required hospitalization, 122 (23.6%) had psoriasis exacerbation due to SARS-CoV-2 infection, and associated factors were subtype of psoriasis, discontinuation of psoriasis treatment during SARS-CoV-2 infection, response following COVID-19 vaccination, and severity of psoriasis. Booster dose vaccination contributed a low probability of COVID-19 sequelae. COVID-19 vaccine’s effectiveness was unsatisfactory, while booster dose vaccination reduced the occurrence of COVID-19 sequelae in psoriasis patients of Southwest China. Patients treated with psoriasis shown to be safe, without a higher incidence of SARS-CoV-2 infection or COVID-19hospitalization compared to untreated patients. Stopping treatment during SARS-CoV-2 infection led to psoriasis exacerbation, so psoriasis treatment could be continued except severe adverse reaction.

BackgroundData on nail psoriasis (PsO) in China are scarce.ObjectivesTo provide nail PsO-related data regarding epidemiologic characteristics, manifestations, fungal infections, arthritic complaints and treatments that may facilitate improved patient management globally.MethodsFrom August 2021 to August 2022, patients with nail PsO were enrolled in a prospective multicentre observational study at 25 hospitals in China. We collected and analysed data concerning nail PsO demography, clinical signs, fungal detection, arthritic symptoms and treatment.ResultsA total of 817 patients with nail PsO were involved, with a mean body mass index of 24.13 +/- 2.93. In addition, 71.41% of the patients were male. The Nail PsO Severity Index score was weakly positively correlated with body surface area. The percentage of nail involvement was 95.29% for fingernails and 57.18% for toenails, with pitting (67.11%) and subungual hyperkeratosis (60.40%) being the most prevalent manifestations, respectively. Toenails showed a significantly higher frequency of nailfold scales, subungual hyperkeratosis and nail plate crumbling and a lower frequency of splinter haemorrhages, pitting and erythema of the lunula. A total of 13.26% of the PsO patients had onychomycosis, and 77.08% were observed in the toenails. Articular symptoms were reported by 12.17% of the patients, with the peripheral type being predominant. Significant associations between articular symptoms and nailfold swelling, subungual hyperkeratosis, nailfold scales, onycholysis and longitudinal ridges were found. Only 2.30% (20 out of 871) of patients with nail PsO received treatment. The most frequently employed therapy for cutaneous PsO with nail involvement was biologic therapy (n = 366).ConclusionsPsO showed distinct manifestations in the toenails and fingernails. Additionally, toenail PsO combined with onychomycosis requires special attention. Articular symptoms in psoriatic patients are associated with specific nail changes. It is important to research and advocate for more potent treatments for nail PsO.

Generalized pustular psoriasis (GPP) is a rare chronic inflammatory pustular dermatosis that presents as painful erythema with sterile pustules on nonacral skin. No unified standard and guideline for the treatment of GPP has been established. Several biologics have been tried for GPP, with varying success. Acrodermatitis continua of Hallopeau (ACH) is a very rare disabling variant of pustular psoriasis characterized by sterile pustules on the fingers and toes, including the nail bed. Comparatively, treating ACH is highly challenging due to its commonly therapy-resistant disease course. The pathogenic role of IL-36 signaling axis has been currently identified in GPP development. Spesolimab, the first anti-interleukin-36 receptor biologic, has been approved for treating GPP flares and shown promising results. In view of a shared pathogenesis between GPP and ACH, specolimab may be an effective treatment for ACH. Currently, there is no case and clinical trial data exist on this condition. Therefore, this case was aim to describe real-world experience of spesolimab use in ACH coexisting with GPP. We report an Asian patient with a 16-year-history of GPP and ACH with marked pustulosis on the nail bed and onychodystrophy. He received conventional systemic regimen acitretin, cyclosporine and biologics adalimumab and secukinumab, but experienced relapse for skin lesions and refractory for nail lesions. He was then treated with a single dose of spesolimab in combination with secukinumab, which resulted in skin clearance and nearly complete resolution of nail lesions over a 32-week period. Our observation suggests that spesolimab should be considered for the treatment of ACH, especially in the patients with intractable nail lesions and concomitant GPP.

Pemphigus vulgaris (PV) is an autoimmune skin disorder characterized by the loss of cell cohesion, with the histone deacetylase 1 (HDAC1) and lysine demethylase 1A (KDM1A) playing critical roles in its pathogenesis. This study aimed to elucidate the molecular mechanisms behind PV, focusing on the function of HDAC1 and KDM1A in disease onset and progression. Based on in vitro and in vivo PV models, we observed a significant increase in HDAC1 mRNA and protein levels in skin tissues of PV patients. Inhibition of HDAC1 ameliorated cell damage and reduced the loss of cell cohesion in human epidermal keratinocytes (HEKs) induced by PV-IgG. Our findings suggest that HDAC1 regulates KDM1A expression through deacetylation, with a notable deficiency in KDM1A expression in PV. Overexpression of KDM1A mitigated cell damage and cohesion loss. The extracellular signal-regulated kinase (ERK) pathway serves as a downstream executor of the HDAC1/KDM1A axis. Inhibiting HDAC1 and increasing KDM1A expression suppressed ERK phosphorylation, reducing PV-related apoptosis. These insights provide a new perspective on treating PV, highlighting the therapeutic potential of targeting HDAC1 expression. The regulatory mechanism of the HDAC1/KDM1A/ERK axis offers crucial clues for understanding PV pathogenesis and developing novel treatments.

To the Editor: Psoriasis is a common, chronic inflammatory skin disease occurring worldwide and presenting at any age.[1] Biologics are the most important therapeutic advances in psoriasis treatment.[2] With the development of 16S rRNA sequencing technology, the association between psoriasis and intestinal flora has been gradually revealed. Some bacteria secrete short-chain fatty acids (SCFAs) with anti-inflammatory properties, serving as active microbial metabolites that regulate the function of immune cells in the intestine and other tissues.[3] However, the impact of biological treatment on gut microbiota and related functional changes in psoriasis patients remains unclear. Our study aimed to explore the effects of biological treatments on the intestinal microbiota of psoriasis patients. This research was reviewed and approved by the Ethic Committee of The First Affiliated Hospital of Chongqing Medical University (No. 2023-433). Patients have given written informed consent to publication of their case details. Inclusion criteria and exclusion criteria are shown in Supplementary Materials, https://links.lww.com/CM9/C83. Finally, a total of 181 plaque psoriasis vulgaris patients were enrolled, and their fecal samples were collected. Participant's characteristics are presented in Supplementary Table 1, https://links.lww.com/CM9/C83. Biologics included tumor necrosis factor (TNF)-α inhibitors (adalimumab), interleukin (IL)-17A inhibitors (secukinumab and ixekizumab), IL-12/23 inhibitors (ustekinumab), and IL-23 inhibitors (guselkumab). Age, sex, and body mass index (BMI) were matched in non-bio-treated and bio-treated group [Supplementary Table 1, https://links.lww.com/CM9/C83]. According to our findings, there were no significant differences in alpha-diversity between the bio-treated and non-bio-treated groups [Supplementary Figure 1A–E, https://links.lww.com/CM9/C83]. Furthermore, no significant statistical differences in terms of the Firmicutes/Bacteroidetes (F/B) ratio between these two groups [Supplementary Figure 1F, https://links.lww.com/CM9/C83]. No significant clustering was observed based on Bray-Curtis dissimilarity [Supplementary Figure 1G,H, https://links.lww.com/CM9/C83]. We found that the fecal microbiota in both groups appeared to be dominated by Firmicutes and Actinobacteriota at the phylum level, and by Blautia and Faecalibacterium at the genus level [Supplementary Figure 1I,J, https://links.lww.com/CM9/C83]. To detect the specific bacteria's discrepancy, we analyzed the gut microbiota at genus level. Our results revealed a significantly higher relative abundance of Coprococcus (P = 0.0450) and Adlercreutzia (P = 0.0062), and a significantly lower relative abundance of Dialister (P = 0.0189), Veillonella (P = 0.0308), Eggerthella (P = 0.0102), and Erysipelatoclostridium (P = 0.0440) were observed in the bio-treated group [Supplementary Figure 2A, https://links.lww.com/CM9/C83]. We then conducted LEfSe comparison of these two groups. The structure and predominant bacteria of the microbiota were represented in a cladogram. The greatest difference in taxa from phylum to genus level was identified by the linear discriminant analysis (LDA) score. Coprococcus were enriched in fecal microbiota in the bio-treated group, while the top two in non-bio-treated group were Dialister and Veillonella at the genus level [Supplementary Figure 2B,C, https://links.lww.com/CM9/C83]. Heat map showed Enterococcus decreased in the bio-treated group [Supplementary Figure 2D,E, https://links.lww.com/CM9/C83]. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways are shown in Supplementary Figure 3, https://links.lww.com/CM9/C83. Subgroups (IL-12/23i, IL-17i, and IL-23i) of the bio-treated group were then analyzed. Results revealed that although the Sobs index had no significant differences at Operational Taxonomic Units (OTU) level, Chao index between the IL-12/23i group and IL-17i group displayed a significant difference in genus level (P = 0.0247) [Supplementary Figure 4A–E, https://links.lww.com/CM9/C83]. Beta-diversity analysis based on Principal Co-ordinates Analysis (PCoA) showed no significant differences among the three bio-treated groups. The F/B ratio of IL-12/23i, IL-17i, and IL-23i groups were decreased in turn, but there were no significant differences between the three groups [Supplementary Figure 4F, https://links.lww.com/CM9/C83]. The fecal microbiota in the three bio-treated groups appeared to be dominated by Firmicutes at phylum level, and by Blautia at genus level [Supplementary Figure 4G–J, https://links.lww.com/CM9/C83]. At genus level, the IL-12/23i group had a significantly higher relative abundance of Megamonas (P = 0.0408); the IL-17i group had a significantly higher relative abundance of, Rothia (P = 0.0216), and Granulicatella (P = 0.0495); and IL-23i had a significantly higher relative abundance of Alistipes (P = 0.0361), Oscillibacter (P = 0.0451) and Colidextribacter (P = 0.0453) [Supplementary Figure 5A, https://links.lww.com/CM9/C83]. Megamonas was enriched in the fecal microbiota of the IL-12/23i group, Rothia in the IL-17i group, and Alistipes in the IL-23i group in genus level [Supplementary Figure 5B,C, https://links.lww.com/CM9/C83]. The heatmap indicated an increase in Sarcina in the IL-23i group and an increase in CAG-352 in the IL-12/23i group compared with the other two groups at the genus level. [Supplementary Figure 5D,E, https://links.lww.com/CM9/C83]. To understand whether severity of skin lesions affects the changes in intestinal flora composition and abundance in psoriasis patients, we divided all patients into four different disease severity groups according to psoriasis area and severity index (PASI) score: mild (PASI <3; n = 9), moderate (3 ≤PASI <10; n = 36), severe (10 ≤PASI <30; n = 109), and extremely severe (PASI ≥30; n = 27). The relative abundance of Enterococcus (P = 0.0158) was higher in the mild and moderate groups, while the relative abundance of Anaerostipes (P = 0.0277) and Lachnospira (P = 0.0083) was higher in the severe and extremely severe groups [Figure 1A–C]. There was no significant difference in F/B values between the four groups [Figure 1D]. At the genus level, Enterococcus were enriched in the mild group, TM7x (a human oral Saccharibacteria isolate) in the moderate group, Anaerostipes in the severe group, and Lachnospira in the extremely severe group at the genus level [Supplementary Figure 6A,B, https://links.lww.com/CM9/C83]. The heatmap indicated Enterococcus increased in both the mild and moderate groups, while Akkermansia and Lactobacillus decreased in the mild group compared with the others [Supplementary Figure 6E,F, https://links.lww.com/CM9/C83].Figure 1: (A–C) Comparison of bacterial abundance at the genus level among PASI <3 (n = 9), 3 ≤PASI <10 (n = 36), 10 ≤PASI <30 (n = 109), and PASI ≥30 (n = 27) groups. The Kruskal–Wallis H test was applied. * P-value <0.05, † P <0.01 represent significant differences. (D) F/B ratio among PASI <3, 3 ≤PASI <10, 10 ≤PASI <30, and PASI ≥30 groups. (E,F) Heat map based on the abundance ranks of the phylum and genus level. Red and blue indicate high and low abundance, respectively. LDA: Linear discriminant analysis; LefSe: Linear discriminant analysis effect size; ns: Not significant; PASI: Psoriasis area and severity index.PASI improvement rate (PASI IR) was calculated according to the patients' skin lesions before treatment with biological agents and at the sampling time. The patients were divided into four groups: PASI IR <50 (n = 7), 50 ≤PASI IR <70 (n = 11), 70 ≤PASI IR <90 (n = 32), and PASI IR ≥90 (n = 69). The relative abundance of Butyricicoccus (P = 0.0179) and Adlercreutzia (P = 0.0191) decrease in turn in four groups [Supplementary Figure 7A,B, https://links.lww.com/CM9/C83]. There was no significant difference in F/B values between the four groups [Supplementary Figure 7C, https://links.lww.com/CM9/C83]. On genus level, Adlercreutzia and Butyricicoccus were enriched in the PASI IR <50 group, Brevundimonas was enriched in the 50 ≤PASI IR <70 group, and NK4A214_group was enriched in the 70 ≤PASI IR <90 group [Supplementary Figure 7D,E, https://links.lww.com/CM9/C83]. The microbiota communities of the four different PASI improvement groups were compared based on the relative abundance ranks of the phylum and genus levels. Heatmap showed that Lactobacillus decreased in the PASI IR <50 group, Akkermansia decreased in both PASI IR <50 and PASI IR ≥90 groups, and increased in the 50 ≤PASI IR <70 group [Supplementary Figure 7F,G, https://links.lww.com/CM9/C83]. In patients with BMI ≥25, the relative abundances of Christensenellaceae_R-7_group (P = 0.0368) and Coprococcus (P = 0.0193) increased with biological treatment [Supplementary Figure 8A,E, https://links.lww.com/CM9/C83]. The relative abundance of Coprococcus (P = 0.0077) increased in male patients with biological treatment, but that of Enterococcus (P = 0.0292) decreased in female patients with biological treatment [Supplementary Figure 8B,F, https://links.lww.com/CM9/C83]. In patients with biological treatment and comorbidities, the relative abundance of Coprococcus (P = 0.0312) was increased, while that of Enterococcus (P = 0.0008) was decreased [Supplementary Figure 8C,G, https://links.lww.com/CM9/C83]. Smoking patients with biological treatment had an increased relative abundance of Coprococcus (P = 0.0420) [Supplementary Figure 8D, https://links.lww.com/CM9/C83]. Moreover, the relative abundance of Prevotella (P = 0.0291) decreased in bio-treated patients <40 years old [Supplementary Figure 8H, https://links.lww.com/CM9/C83]. We found that patients with IL-12/23i treatment for less than 6 months showed the most significant increase in the relative abundance of Ruminococcus (P = 0.0443), and patients with IL-23i treatment for >6 months showed the most significant increase in the relative abundance of Butyricimonas (P = 0.0469) [Supplementary Figure 8I, J, https://links.lww.com/CM9/C83]. The Redundancy analysis/Canonical Correlation Analysis (RDA/CAA) environmental factor analysis are shown in Supplementary Figure 9, https://links.lww.com/CM9/C83. The 16s rRNA sequencing data of this article were deposited in GenBank (https://www.ncbi.nlm.nih.gov/bioproject/PRJNA1014805). Adlercreutzia is an anti-inflammatory bacterium, and Butyricicoccus is a butyrogenic bacterium. SCFAs play an anti-inflammatory role by down-regulating inflammatory cytokines such as IL-6 and IL-8.[4] In this study, as the PASI IR score increases, the relative abundance of Adlercreutzia and Butyricicoccus decreases in turn. The presence of butyrogenic bacteria seems to correlate with the intensity of the inflammatory response. A stronger inflammatory response in psoriasis seems linked to a higher abundance of anti-inflammatory gut bacteria, suggesting that gut microbiota could indicate the severity of inflammation. Our findings revealed that the gut microbiota of psoriasis patients with different lesion severity had different characteristics, and biological treatment changed the composition and structure of intestinal flora. There was a certain correlation between PASI IR and butyrogenic bacteria in psoriasis patients. Butyrogenic bacteria produce SCFAs with anti-inflammatory properties and modulate immune cell function in the intestine and other tissues. They might play a role in the intestinal immunoinflammatory response of psoriasis and could serve as a biomarker for its severity. However, further research into their mechanisms with larger sample sizes is necessary to strengthen the findings. In the course of psoriasis biological treatment, adjusting diet and lifestyle habits and paying attention to the increase and decrease of beneficial biomarkers of intestinal flora can contribute to disease prognosis and individualized treatment. Acknowledgment The authors are grateful to Ying Chen for her kindly help in this study. Funding This work was funded by grants from the National Natural Science Foundation of China (No. NSFC 82103733) and Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJQN202100412). Conflicts of interest None.

The skin and mucous membrane of cancer patients can be directly or indirectly impaired during the treatment of cancers, bringing about not physical but also psychological damages to cancer patients. A practical guideline is of great significance to improve the quality of life for patients suffered from cutaneous adverse events. This guideline was generated based on up-to-date evidence and the consensus of experts specialized in dermatology. The current guideline include the baseline screening of skin and mucosal membranes, the manifestations of injuries on skin, mucosa and appendages, along with the treatment of them. The causal anti-tumor management include chemotherapy, radiotherapy, immune therapy and surgery. This guideline can be helpful to reduce the risk of cutaneous adverse events during anti-cancer treatment and improve the quality of life of patients suffered from these adverse events.

BackgroundContinuous exposure to UVB is the main extrinsic cause of skin photodamage, which is associated with oxidative stress, DNA damage, apoptosis and degradation of collagen. Rapamycin, a mechanistic target inhibitor of rapamycin complex 1 (mTORC1), has been shown to play a crucial role anti-tumor and aging retardation, but its mechanism of action in UVB-induced photodamage still remains unknown. In this study, we investigated the role of rapamycin and Hspb2 (also known as Hsp27) in UVB-induced photodamage in mice.Methods and resultsWe constructed skin acute photodamage models on the ears of WT and Hspb2 KO mice, respectively, and administered rapamycin treatment. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels, with a significant increase in p53 levels and Bax/Bcl-2 ratio, a reduction in LC3II/I ratio and an increase in p62 levels in the KO mice compared to those in WT mice after the same dose of UVB irradiation. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-beta/Smad signaling pathway.ConclusionsRapamycin can alleviate skin photodamage from Hspb2 knockout to some extent. It may be a potential therapeutic drug for skin photodamage.Graphical abstractIn this study, we investigated the role of rapamycin and Hspb2 in UVB-induced photodamage in mice. Histological results showed that knockout of the hspb2 exacerbated the skin damage, as evidenced by thickening of the epidermis, breakage and disruption of collagen fibers and reduction in their number, which is reversed by rapamycin treatment. In addition, hspb2 knockout promoted UVB-induced apoptosis and reduced autophagy levels. Rapamycin was also found to inhibit collagen degradation induced by hspb2 knockdown through activation of the TGF-beta/Smad signaling pathway. We conclude that rapamycin and Hspb2 exert a synergistic protective effect in skin photodamage.

Toxic epidermal necrolysis (TEN) is a rare severe cutaneous adverse reaction that involves more than 30% of the body surface area. TEN can be accompanied by a series of systemic symptoms and has a high risk of death. Tumor necrosis factor (TNF)-α inhibitors such as adalimumab and etanercept have been shown to be safe and effective for the treatment of TEN in some cases. However, clinical data on the use of TNF-α inhibitors to treat TEN with severe systemic infection are scarce. In the present study, three adult patients who developed TEN with serious active infection were successfully treated with etanercept. One of the three patients had active open pulmonary tuberculosis, and the other two had septicemia and/or fungal sepsis. All patients’ skin lesions significantly improved after several days, and none of the patients developed emerging or re-emerging infectious diseases, adverse reactions, or a similar rash during follow-up. TNF-α inhibitors may be an effective treatment choice for TEN with severe systemic infection. However, further studies with large samples are still required for validation because clinical experience is limited.

BACKGROUND:Atopic-like dermatitis (ALD) is a common side effect of interleukin-17A (IL-17A) inhibitors. OBJECTIVE:To determine the prevalence, risk factors, outcomes and treatment of ALD in a cohort of psoriasis patients treated with IL-17A inhibitors. METHODS:This retrospective study included 226 psoriasis patients treated with an IL-17A inhibitor in our dermatology department between July 2020 and July 2022. The patients were reviewed over 2 years. A logistic regression model in rare events data (relogit) was used to predict the risk factors for ALD. RESULTS:Of the 226 patients, 14 had ALD. Data including age, body mass index, IL-17A inhibitor use, personal and family history of atopic disease, pet ownership history, and immunoglobulin E (IgE) levels were analysed using the relogit regression model. It indicated a personal history of atopic disease (odd ratio [OR] 27.830, 95% confidence interval [CI] 3.801-203.770; p = 0.001) and elevated IgE levels (OR 5.867, 95% CI 1.131-30.434; p = 0.035) as independent predictors of incident ALD. In one patient, anti-IL-17A therapy was discontinued, and treatment was switched to tofacitinib. Thirteen patients who continued with IL-17A inhibitor were treated with topical therapy and/or antihistamines, and their ALD was partially or completely resolved. CONCLUSION:In this study, the incidence rate of ALD was 6.19%. Elevated IgE levels and a personal history of atopic disease were found to be the risk factors for ALD. Our study findings suggest that treatment should be provided based on the severity of psoriasis and incident ALD. Prior to treatment, psoriasis patients who have the risk factors for ALD should be informed of the possible development of ALD, and alternative psoriatic therapeutic options should be considered if severe ALD develops.

Background and objectivePrevious studies have shown that patients with psoriasis are at higher risk of developing chronic kidney disease (CKD) and end-stage renal disease (ESRD) compared with general population; however, data on the differences in the occurrence of CKD and ESRD between patients with psoriasis and non-psoriatic controls are limited and inconsistent. The aim of this study was to carry out a comparison of the probability of suffering CKD and ESRD in patients with or without psoriasis by conducting a meta-analysis of cohort studies.MethodsCohort studies on PubMed, Web of Science, Embase and Cochrane Library by March, 2023 were searched for. The studies were screened according to pre-established inclusion criteria. Hazard ratios (HRs) and a 95% confidence intervals (CIs) for the renal outcomes among patients with psoriasis were calculated using the random-effect, generic inverse variance method. Subgroup analysis was related to the severity of psoriasis.ResultsA total of seven retrospective cohort studies were included, including 738,104 psoriasis patients and 3,443,438 non-psoriasis subjects, published from 2013 to 2020. Compared to controls without psoriasis, patients with psoriasis had an increased risk of CKD and ESRD, with pooled hazard ratios of 1.65 (95% CI, 1.29–2.12) and 1.37 (95% CI, 1.14–1.64), respectively. Besides, the incidence of CKD and ESRD is positively correlated with the severity of psoriasis.ConclusionThis study showed that compared to patients without psoriasis, patients with psoriasis, especially those with severe psoriasis, had a significantly increased risk of developing CKD and ESRD. Considering the limitations of this meta-analysis, more high-quality and well-designed studies are needed in the future to validate our findings.