Immunomodulatory Effects of Probiotics on Th17-Mediated Immune Responses in Psoriasis: A Systematic Review and Meta-Analysis

Psoriasis is a chronic immune-mediated skin disease that is increasingly associated with alterations in gut microbiota through the gut-skin axis. This systematic review assessed the efficacy of probiotic supplementation in managing psoriasis. A comprehensive search was performed across PubMed, Scopus, and the Cochrane Library for studies published between 2010 and 2025. After screening 688 unique records and removing duplicates and incomplete entries, 10 studies were found relevant, and eight with accessible full texts were included for qualitative synthesis. Across included randomized controlled and observational studies, probiotic or synbiotic supplementation either alone or as an adjunct to topical or systemic therapy was associated with reductions in Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores. Several included studies also reported improvements in inflammatory biomarkers and gut microbiota composition, which were narratively presented in this review. Due to heterogeneity in study designs and interventions, findings were synthesized narratively. Multistrain formulations containing Lactobacillus, Bifidobacterium, or Lactiplantibacillus plantarum consistently demonstrated clinical benefits, whereas single-strain products yielded variable outcomes. All interventions were well tolerated, with only mild gastrointestinal discomfort noted in a small minority of participants. The available evidence suggests that probiotic supplementation may reduce disease severity, improve quality of life, and support immune and barrier function in individuals with psoriasis. The therapeutic effect appears strain-dependent and more pronounced in mild-to-moderate disease. Larger, well-controlled trials with standardized probiotic strains, defined dosages, and longer follow-up are needed to clarify the long-term clinical value of probiotics as adjunctive therapy in psoriasis management.

Psoriasis is a common, chronic inflammatory skin disease which typically follows a relapsing and remitting course, and is associated with joint disease in approximately 25% of patients.1 The significant reduction in quality of life and the psychosocial disability suffered by patients underline the need for prompt, effective treatment, and long-term disease control (reviewed2, 3). Localized, limited disease can usually be managed satisfactorily with topical agents. Those with moderate to severe disease often require systemic treatment. Phototherapy and traditional 'standard' systemic therapies, while often effective, can be associated with long-term toxicity; some are expensive, and some patients have treatment-resistant disease.4 Also, phototherapy is not available to many due to geographical, logistical or other constraints. Patients themselves demonstrate high levels of dissatisfaction with standard approaches to treatment.5, 6 Biologic therapies for psoriasis utilize molecules designed to block specific molecular steps important in the pathogenesis of psoriasis and now comprise a number of well-established, licensed, treatment options for patients with severe disease. Since 2005, when the British Association of Dermatologists (BAD) first published guidance on the use of biologic therapies in psoriasis,7 much has changed. There is a substantial body of new evidence pertinent to the clinical use of these treatments, the U.K. National Institute for Health and Clinical Excellence (NICE) has approved the use of a number of biologic therapies in severe chronic plaque psoriasis and the BAD Biologic Interventions Register (BADBIR) has been successfully launched. Despite these developments, use of biologic therapy in clinical practice remains limited in the U.K., with a shortfall in funding cited as a significant obstacle to prescribing in approximately 40% of units recently surveyed.8 These guidelines have been revised and updated in accordance with a predetermined scope. This is based on the original scope used in 2005, and extended to include additional areas of practice. Recommendations in this guideline supersede those in the 2005 guideline. The overall objective of these guidelines is to provide up-to-date, evidence-based recommendations on use of biologic therapies (infliximab, adalimumab, etanercept, ustekinumab) in adults and children with all types of psoriasis and, where relevant, psoriatic arthritis, for clinical staff involved in the care of patients treated with biologic therapies. Efalizumab remains in the scope of the guideline in relation to safety only, given that the European Medicines Agency has withdrawn the marketing authorization of this drug because of concerns over the development of progressive multifocal leukoencephalopathy (PML). This guidance does not cover agents licensed outside the U.K. (alefacept) or use of biologic therapies for indications other than psoriasis and psoriatic arthritis. The guideline working group represents all relevant stakeholders including dermatologists, nurses, rheumatologists and patients. Draft guidance was made available for consultation and review by patients, the BAD membership and the British Dermatological Nursing Group (BDNG). Advice relating to tuberculosis was reviewed and approved by the British Thoracic Society. The guideline has been developed using the BAD's recommended methodology9 and with reference to the AGREE (Appraisal of Guidelines Research and Evaluation) instrument.10 Recommendations were developed for implementation in the National Health Service using a process of considered judgment based on the evidence and an awareness of the European product licence of the various treatments. Cochrane, EMBASE and Medline databases were searched between 1990 and June 2009 for clinical trials involving adalimumab, efalizumab, etanercept, infliximab and ustekinumab using an agreed protocol. Two reviewers screened all titles and abstracts independently, and full papers of relevant material were obtained. In relation to efficacy, only randomized controlled trials (RCTs) of high quality (1+ or more; see Appendix 1) were included for chronic plaque psoriasis, whereas in other clinical phenotypes, given the paucity of published data, all data were included. Data from each paper were extracted by two members of the guideline group using standardized literature evaluation forms in order to create evidence tables. Evidence on safety was extracted from literature on use of biologic agents for any indication in view of the relatively limited data specifically relating to use in psoriasis. The methodological limitations of the safety analysis are detailed in section 15. The guideline was peer reviewed by the Clinical Standards Unit of the BAD (made up of the Therapy & Guidelines and Audit & Clinical Standards Subcommittees) prior to publication. These guidelines have been prepared on behalf of the BAD and reflect the best data available at the time the report was prepared. Caution should be exercised in interpreting the data; the results of future studies may require alteration of the conclusions or recommendations in this report. It may be necessary or even desirable to depart from the guidelines in the interests of specific patients and special circumstances. Just as adherence to guidelines may not constitute defence against a claim of negligence, so deviation from them should not necessarily be deemed negligent. This field of psoriasis biologic therapeutics is in a rapid phase of development, and revision of the scope and content of the guidelines will therefore occur on an annual basis. Where necessary, the guideline will be updated via the BAD website, and a fully revised version is planned for 2012. Most patients with moderate to severe disease achieve satisfactory disease control (i.e. significant or complete clearing of disease) in the short term with at least one of the systemic agents currently available.4 Long-term disease control frequently requires some form of continuous therapy and consequent, predictable risks of toxicity. At present, the risks and benefits of biologic therapies relative to standard systemic therapy are largely unknown. Widespread use of these agents in uncomplicated moderate to severe psoriasis is inappropriate and is not supported by the licensed indications for these drugs. Eligibility criteria should encompass both objective measures of disease severity and the impact the disease has on quality of life. All existing disease severity assessment tools are imperfect11-13 and most require some training to complete. The Psoriasis Area and Severity Index (PASI) is a measure of disease severity in chronic plaque psoriasis12 and has been chosen for the purposes of this guideline as it has been widely used in clinical trials including those investigating biologic therapies, and has also been adopted by NICE. A PASI score of ≥ 10 (range 0–72) has been shown to correlate with a number of indicators commonly associated with severe disease such as need for hospital admission or use of systemic therapy,14 and reflects the minimal level of disease severity required for patient inclusion in most of the clinical trials of biologic therapies to date. Where the PASI is not applicable (e.g. pustular psoriasis), body surface area (BSA) affected should be used, with severe disease defined as > 10% BSA affected.14 The Dermatology Life Quality Index (DLQI) is a validated tool for the measurement of quality of life across all skin diseases, including psoriasis, and has been used in both trial and clinical practice settings.13, 15 A score of > 10 (range 0–30) has been shown to correlate with at least 'a very large effect' on an individual's quality of life.12, 14, 16 When using the PASI and DLQI to determine whether or not a patient should be considered for biologic therapy, clinicians should take into account the applicability of these measures to each individual patient. There are circumstances where the use of these tools fails to give a sufficiently accurate assessment of the clinical situation. With respect to the PASI, this is especially pertinent in patients with localized disease that involves special 'high-impact' sites (genitalia, hands, feet, head and neck) where highly significant functional and/or psychosocial morbidity may exist with a PASI < 10. The DLQI may be a poor indicator of emotional disabilities resulting from psoriasis and the validity of the DLQI (and of other quality of life measures) may also be undermined due to linguistic or other communication difficulties.13 Patients with psoriasis may be considered eligible to receive treatment with any of the licensed biologic interventions when they fulfil the eligibility criteria set out below. However, the decision to proceed with treatment must be made in collaboration with the patient and include a careful assessment of the associated risks and benefits17 Eligibility criteria To be considered eligible for treatment, patients must have severe disease as defined in (a) and fulfil one of the clinical categories outlined in (b): (a) Severe disease defined as a PASI score of 10 or more (or a BSA of 10% or greater where PASI is not applicable) and a DLQI > 10. In exceptional circumstances (for example, disease affecting high-impact sites with associated significant functional or psychological morbidity such as acral psoriasis), patients with severe disease may fall outside this definition but should be considered for treatment (Strength of recommendation D; level of evidence 3) AND (b) Fulfil at least one of the following clinical categories (Strength of recommendation D; level of evidence 3, and formal consensus) where phototherapya and alternative standard systemic therapyb are contraindicated or cannot be used due to the development of, or risk of developing, clinically important treatment-related toxicity. are intolerant to standard systemic therapy are unresponsive to standard systemic therapyb have significant, coexistent, unrelated comorbidity which precludes use of systemic agents such as ciclosporin or methotrexate have severe, unstable, life-threatening disease Eligibility criteria for patients with skin and joint disease patients with active psoriatic arthritis or skin disease that fulfils defined British Society for Rheumatology (BSR)18 or BAD guideline criteria, respectively patients with severe skin psoriasis and psoriatic arthritis who have failed or cannot use methotrexate may need to be considered for biologic treatment given the potential benefit of such treatment on both components of psoriatic disease aPhototherapy may be inappropriate in patients (i) who have exceeded safe exposure limits (150–200 treatments for PUVA, 350 treatments for narrowband UVB19, 20), (ii) who are nonresponsive or relapse rapidly, (iii) who have a history of skin cancer or repeated episodes of severe sunburn, (iv) who are intolerant of UV exposure, especially if skin phototype I (sun-sensitive), or (v) for logistical reasons bStandard systemic therapy includes ciclosporin (2·5 mg kg−1 daily; up to 5 mg kg−1 daily), and in men, and women not at risk of pregnancy, methotrexate [single dose (oral, subcutaneous, intramuscular) of 15 mg weekly; max 25 mg weekly] and acitretin (25–50 mg daily) An adequate response to treatment is defined as either (i) a 50% or greater reduction in baseline PASI (PASI 50 response) (or % BSA where the PASI is not applicable) and a 5-point or greater improvement in DLQI4, 21-23or (ii) a 75% reduction in PASI score compared with baseline (PASI 75 response). Initial response to therapy should be assessed at time points appropriate for the drug in question (Table 1). For patients on tumour necrosis factor (TNF) antagonist treatment with psoriasis and psoriatic arthritis, treatment may be continued if there has been a sufficient response in at least one of these components (see BSR guidelines18 for definition of disease response in psoriatic arthritis). TNF is a proinflammatory cytokine produced by a wide variety of cell types including keratinocytes. It plays a central role in the pathogenesis of psoriasis, psoriatic arthritis and a number of other disease states. TNF is released from cells as a soluble cytokine (sTNF) following cleavage from its cell surface-bound precursor (transmembrane TNF, tmTNF). Both sTNF and tmTNF are biologically active, and bind to either of two distinct receptors: TNF receptor 1 (TNFR1, p55) and TNF receptor 2 (TNFR2, p75). This leads to NF-κB activation (which promotes inflammation) and/or cell apoptosis. In addition, tmTNF can itself act as a ligand (via a process of reverse signalling) to induce cell activation, cytokine suppression or apoptosis of the tmTNF-bearing cell. Soluble forms of the TNF receptors also exist and, by binding and neutralizing sTNF, may act as natural TNF antagonists. There are currently two approved groups of biologic agents that target TNF: anti-TNF monoclonal antibodies (adalimumab and infliximab), and sTNF receptors (etanercept). Infliximab is a chimeric human–murine monoclonal antibody (∼ 25% mouse-derived protein) whereas adalimumab is fully human. Etanercept is a genetically engineered fusion protein composed of a dimer of the extracellular portions of human TNFR2 (p75) fused to the Fc domain of human IgG1. All three agents specifically bind both soluble and transmembrane forms of TNF and act by (i) blocking TNFR-mediated mechanisms and (ii) inducing tmTNF (reverse-signalling) events. Etanercept also binds members of the lymphotoxin family [LTα3 (also known as TNF-β) and LTα2β1] although the biological significance of this is unclear. Aside from the latter, there are important differences between the three agents with respect to pharmacokinetics, immunogenicity and structure-based mechanisms of action (only some of which are completely understood).24 It is likely that these differences, in the context of the highly complex biology of TNF, account for observed differences in the efficacy and adverse events profile of TNF antagonists. Lymphocyte function-associated antigen-1 (LFA-1) is a cell surface protein that binds to intracellular adhesion molecule (ICAM) 1–3 and plays a key role in T-lymphocyte recirculation, trafficking to sites of inflammation, antigen presentation by dendritic cells and other activated cells including keratinocytes, and T-cell costimulation. Efalizumab is a recombinant humanized IgG1 monoclonal antibody that binds specifically to the CD11a subunit of LFA-1, which by interfering with LFA-1/ICAM binding inhibits several key steps important in the pathogenesis of psoriasis including T-cell migration into the skin and T-cell activation. More recently, in vivo data have shown that efalizumab induces a state of reversible T-cell 'hyporesponsiveness' including downregulation of a number of T-cell surface molecules unrelated to LFA-1 both in the circulation and in psoriatic plaques.25, 26 Interleukin (IL)-12 and IL-23 are heterodimeric cytokines secreted by activated antigen-presenting cells, and share a common protein subunit, p40. Of relevance to psoriasis, IL-12 activates CD4 and natural killer cells to induce expression of type 1 cytokines (TNF and interferon-γ) while IL-23 stimulates survival and proliferation of a subset of T cells that produce IL-17 (Th17 cells). Recent immunological27 and genetic studies indicate a central role for IL-23 in the pathogenesis of psoriasis.28Ustekinumab is a fully human IgG1κ monoclonal antibody which acts as an IL inhibitor by binding with high affinity and specificity to the p40 protein subunit. It thus prevents IL-12 and IL-23 from binding to their IL-12Rβ1 receptor protein expressed on the surface of immune cells. Three large RCTs demonstrate that etanercept is effective in chronic plaque psoriasis.29-31 Onset of action is slower than that seen with the monoclonal antibodies, with clinically significant improvement in disease severity scores evident between 4 and 8 weeks after initiation of treatment.30 Response is dose related, with 34% (25 mg biweekly) and 48% (50 mg biweekly) of patients achieving PASI 75 by 12 weeks (Table 2). Continuing therapy up to 6 months improves response rates further (43% and 57% for 25 mg biweekly and 50 mg biweekly, respectively).29, 30, 32 While there are no RCT data establishing efficacy beyond 6 months, data from a 2-year, open-label etanercept 50 mg biweekly extension study32 (following the phase III study reported by Tyring et al.31) suggest that efficacy is maintained for up to 1 year, with approximately 75% of patients maintaining their PASI 75 response over the ensuing year. Overall, continuous therapy provides better disease control and higher levels of patient satisfaction compared with interrupted therapy. When treatment is stopped, disease relapses slowly: median time to disease relapse as defined by loss of PASI 50 in those who achieved PASI 75 after 24 weeks of continuous etanercept 25 or 50 mg biweekly, was 85 and 91 days, with no evidence of disease PASI scores were with the of patients achieving efficacy after 12 further weeks (i.e. and of PASI 75 achieved this level of efficacy on Aside from objective measures of disease improvement studies also report associated clinically in quality of life reduction in and and of patients in analysis of two of these RCTs that response rates in those over were the as those although in the group were The 25 mg and 50 mg are given that their are that the number of patients achieving PASI 75 at 12 weeks following etanercept 50 mg an RCT compared with was with that seen in other RCTs investigating etanercept 25 mg biweekly and that no significant differences were observed in PASI or DLQI in a of patients open-label etanercept 25 mg biweekly and etanercept 50 mg In the RCTs the of adverse events or adverse events in patients etanercept was no greater than in the control patients, with the of in each treatment RCT has shown efficacy of etanercept 25 mg compared with acitretin mg kg−1 at 24 weeks (see the role of TNF in levels of TNF in patients, and the used for etanercept, response rates may occur in patients, with This is in by published RCT and data cited in the study by et The of etanercept and methotrexate has been shown to be more effective in arthritis than either with no significant additional toxicity. data suggest that the of methotrexate may also etanercept efficacy in psoriasis. A RCT the efficacy and safety of etanercept (25 mg biweekly) in patients on and reported of patients or at 24 weeks on therapy, as compared with those in methotrexate was A reported both efficacy with the of methotrexate in patients on etanercept and loss of efficacy on of methotrexate from patients on Data from a RCT reported that the of etanercept 25 mg with acitretin mg kg−1 is as effective as etanercept 25 mg and that both these interventions are more effective that acitretin These data suggest that in the short term at the may additional efficacy as there is no additional associated toxicity. The patient in the cited RCTs may not be of patients likely to be treated in clinical practice as to the studies required patients only to be considered or have or systemic therapy. However, objective disease severity criteria were the as those currently recommended by the BAD and and PASI scores on to studies were higher from 16 to studies of practice report response rates in patients who have failed systemic therapies, all of which that data from the RCTs can be to clinical 50 There is a of long-term RCT data beyond 6 months, and only limited data on the two published studies one is and both report following one of treatment RCT data indicate that 50 mg biweekly is more effective than 25 mg biweekly, but there are no trial data whether the dose to 50 mg biweekly in patients who to achieve or adequate on 25 mg biweekly results in disease This is especially pertinent given guidance which currently limits treatment to the 25 mg biweekly dose (see Etanercept is licensed for use in moderate to severe psoriasis at either 50 or 25 mg biweekly for the first months, and 25 mg biweekly for up to 24 therapy beyond 24 weeks may be appropriate for some patients has approved use of etanercept in severe plaque psoriasis to defined disease at the 25 mg biweekly dose only, and not the 50 mg dose effective, with therapy to be continued only in those patients achieving disease response at months (Table 1). Etanercept is recommended for the treatment of patients with severe psoriasis who fulfil the disease severity criteria to section (Strength of recommendation level of evidence Etanercept therapy may be at either 50 or 25 mg and disease response assessed at months (Strength of recommendation level of evidence The of which dose to use will on clinical disease body and, in the U.K., the dose that will be (Strength of recommendation level of evidence Patients on etanercept 25 mg may to to etanercept 50 mg as these two are in of efficacy (Strength of recommendation level of evidence In patients who treatment may be continued to clinical although long-term data on efficacy are limited to 2 (Strength of recommendation level of evidence may be risk of disease although there may be a response on therapy (Strength of recommendation level of evidence may be recommended in clinical where it is required for associated or to efficacy (Strength of recommendation level of evidence Three large indicate that infliximab therapy is highly effective in chronic plaque psoriasis (Table Onset of action is with evidence of significant improvement the first 2 weeks of treatment and benefit by 10 when of patients achieve PASI 75 (Table (and in DLQI of This response is largely maintained over time with and achieving PASI 75 at 6 and 12 months, respectively (Table 2). of efficacy with development of antibodies to which in of patients continuous therapy and 5 mg following a standard 2 and 6 continuous therapy at 5 mg kg−1 8 weeks achieved to relapse in the by loss of PASI was as and in the of although data were not An that 50% patients relapse of PASI by There are no published trial data beyond 1 year. study assessed disease using the Psoriasis Severity Index to a a improvement in from baseline was observed at 10 with a of improvement reported at This was maintained of patients with complete of disease the target continued to between weeks 24 and 50 and There are no RCT data on use of methotrexate in with infliximab in psoriasis. In both and psoriatic arthritis, with methotrexate is a licensed and response rates and are at least in these disease levels of infliximab have been reported with methotrexate which may in of mg also the of antibodies to The patient in the cited RCTs may not be of patients likely to be treated in clinical practice. The PASI at baseline was ≥ 10 in all the studies However, of systemic therapy was not an in that most studies required patients to be for systemic therapy and/or failed A of patients in the study by et indicate that baseline PASI > and the of treatments two or more systemic therapies, or biologic no on treatment The of the study investigating continuous infliximab therapy is in that study at patients randomized to receive therapy receive infliximab at PASI 75 was not and in both were reported as Infliximab is licensed for use mg kg−1 8 in moderate to severe plaque psoriasis. has approved use of infliximab in patients with severe (PASI ≥ DLQI ≥ with treatment beyond 10 weeks recommended only in those who achieve response Infliximab is recommended for the treatment of patients with severe psoriasis who fulfil the disease severity criteria to section (Strength of recommendation level of evidence Infliximab therapy should be at a dose of 5 mg kg−1 at weeks 2 and 6 and disease response assessed at months (Strength of recommendation level of evidence In patients who mg should be given at to disease control although long-term data are available only up to 1 (Strength of recommendation level of evidence therapy should be given the associated risk of and disease control (Strength of recommendation level of evidence may be recommended in clinical where it is required for associated to efficacy or to the development of antibodies to infliximab (Strength of recommendation D; level of evidence 3) Three large RCTs demonstrate that adalimumab is a highly effective treatment for chronic plaque psoriasis (Table Onset of action is with significant in disease severity evident 2 weeks of treatment and disease response seen between weeks 12 and Response is dose with of patients achieving PASI 75 at 12 with adalimumab mg other (i.e. the licensed dose for psoriasis), and achieving PASI 75 with adalimumab mg relevant in quality of life indicators are also In one a subset of patients who failed to achieve PASI 50 following at least 24 weeks of adalimumab other was to the dose for the of the study 40% of this PASI 50 that dose may further data are available up to 1 year, with no evidence of significant loss of response over time in those patients who and are continued on of response on treatment was also in the phase of the study reported by et those who maintained PASI 75 by were to receive either or a further weeks of adalimumab While time to relapse was not of patients PASI 50 response relative to baseline with a of a in PASI score relative to compared with relapse in those on adalimumab by of this patients who

SummaryBackgroundThe ‘treat to target’ paradigm improves outcomes and reduces costs in chronic disease management but is not yet established in psoriasis.ObjectivesTo identify treatment targets in psoriasis using two common measures of disease activity: Psoriasis Area and Severity Index (PASI) and Physician's Global Assessment (PGA).MethodsData from a multicentre longitudinal U.K. cohort of patients with psoriasis receiving systemic or biologic therapies (British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR) were used to identify absolute PASI thresholds for 90% (PASI 90) and 75% (PASI 75) improvements in baseline disease activity, using receiver operating characteristic curves. The relationship between PGA (clear, almost clear, mild, moderate, moderate–severe, severe) and PASI (range 0–72) was described, and the concordance between absolute and relative definitions of response was determined. The same approach was used to establish treatment response and eligibility definitions based on PGA.ResultsData from 13 422 patients were available (58% male, 91% white ethnicity, mean age 44·9 years), including over 23 000 longitudinal PASI and PGA scores. An absolute PASI ≤ 2 was concordant with PASI 90 and an absolute PASI ≤ 4 was concordant with PASI 75 in 90% and 88% of cases, respectively. These findings were robust to subgroups of timing of assessment, baseline disease severity and treatment modality. PASI and PGA were strongly correlated (Spearman's rank correlation coefficient 0·92). The median PASI increased from 0 (interquartile range 0–0, range 0–23) to 19 (interquartile range 15–25, range 0–64) for PGA clear to severe, respectively. PGA clear/almost clear was concordant with PASI ≤ 2 in 90% of cases, and PGA moderate–severe severe was concordant with the National Institute for Health and Care Excellence PASI eligibility criteria for biologics in 81% of cases.ConclusionsAn absolute PASI ≤ 2 and PGA clear/almost clear represent relevant disease end points to inform treat‐to‐target management strategies in psoriasis. What's already known about this topic? The most commonly used relative disease activity measure in psoriasis is ≥ 90% improvement in Psoriasis Area and Severity Index (PASI 90); however, it has several limitations including dependency on a baseline severity assessment.Defining an absolute target disease activity end point in psoriasis has the potential to improve patient outcomes and reduce costs, as demonstrated by treat‐to‐target approaches in other chronic diseases such as hypertension and diabetes.The Physician's Global Assessment (PGA) is a popular alternative measure of psoriasis severity in daily practice; however, its utility has not been formally assessed with respect to PASI. What does this study add? An absolute PASI ≤ 2 corresponds with PASI 90 response and is a relevant disease end point for treat‐to‐target approaches in psoriasis.There is a strong correlation between PASI and PGA.PGA moderate–severe/severe may serve as an alternative eligibility criterion for biologics to PASI‐based definitions, and PGA clear/almost clear is an appropriate alternative absolute treatment end point. What are the clinical implications of this work? Absolute PASI ≤ 2 and PGA clear/almost clear represent relevant disease end points to inform treat‐to‐target management strategies in psoriasis.

Introduction: Psoriasis is a chronic inflammatory skin disease that exhibits a strong association with metabolic syndrome (MetS). The involvement of various proinflammatory cytokines in MetS is thought to play a critical role in the pathogenesis of psoriasis. This study aims to evaluate the impact of MetS on immunological markers (IL-17, IL-23, and FOXP3+ regulatory T cells), disease severity, and quality of life (QoL) among patients with psoriasis.Methods: This cross-sectional study involved 42 psoriasis patients, divided into two groups: 29 without MetS (Pso) and 13 with MetS (Pso-MetS). Clinical parameters such as blood pressure, fasting blood glucose, and triglyceride levels were measured. Immunological markers (IL-17, IL-23, and FOXP3+) were analyzed using ELISA. Psoriasis severity was assessed using the Psoriasis Area and Severity Index (PASI), and QoL was evaluated with the Dermatology Life Quality Index (DLQI).Results: The Pso-MetS group was significantly older than the Pso group (p value = 0.003). Higher systolic (p value < 0.001), fasting glucose (p value = 0.002), and triglycerides (p value < 0.001) were observed in the Pso-MetS group. Lower HDL observed in the Pso-MetS group (p value = 0.004). FOXP3+ expression was significantly lower in the Pso-MetS group (p=0.02), while waist circumference, diastolic blood pressure, IL-17, IL-23, PASI, and DLQI scores levels showed no significant differences.Conclusions: MetS is associated with immune dysregulation, evidenced by reduced FOXP3+ expression in psoriasis patients. Further studies are needed to explore the immunological link between psoriasis and MetS.

BackgroundPsoriasis is a chronic inflammatory skin disease with metabolic abnormalities serving as important contributors for pathogenesis and progression. Polyunsaturated fatty acids (PUFAs) have been found to be associated with human diseases, including psoriasis. However, differences and controversies exist regarding their content and roles.MethodsPlasma PUFAs concentrations were measured in 296 patients with moderate-to-severe plaque psoriasis from the Shanghai Psoriasis Effectiveness Evaluation CoHort. Disease severity was assessed using Clinician-Reported Outcomes (ClinROs), including Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA) and Physician Global Assessment (PGA), as well as Patient-Reported Outcomes (PROs), including Patient Global Assessment (PtGA) and Dermatology Life Quality Index (DLQI). Multivariate generalized linear regression models (GLMs), subgroup and interaction analysis, and restricted cubic spline were used to estimate the cross-sectional associations between PUFAs concentrations and disease severity. Longitudinal assessments of PASI scores and PASI response were conducted at a 12-week follow-up. Associations between baseline plasma PUFAs levels and prospective PASI scores or PASI response were assessed using multivariate GLMs or logistic regression models.ResultsMales suffered severer psoriasis and presented lower plasma docosahexaenoic acid (DHA) and arachidonic acid (ARA) levels compared to females. Among males, plasma eicosadienoic acid (EDA) level was positively associated with PASI, BSA and PGA scores, while total Omega-3 PUFAs and/or eicosapentaenoic acid (EPA) levels exhibited non-linear associations with PASI and/or BSA scores. α-Linolenic acid (ALA) was negatively, whereas ARA was positively, associated with DLQI scores. In females, Omega-3 PUFAs, including EPA, DHA, and total Omega-3 PUFAs, showed inverse associations with PASI and BSA scores. Longitudinally, plasma total Omega-6 PUFAs were positively associated with the likelihood of achieving PASI 100 at 12 weeks in males. In females, concentrations of dohomo-γ-linolenic acid were prospectively associated with an increase in PASI scores, and DHA was associated with the likelihood of achieving PASI 75 and PASI 90 decline.ConclusionsSex differences cross-sectionally exist in disease severity and plasma PUFAs levels. The association between PUFAs and psoriasis severity also varies cross-sectionally and longitudinally between males and females. Sex differences should be considered when studying the function and clinical application of PUFAs in psoriasis.

Psoriasis is a chronic inflammatory skin disease that significantly impacts patients' quality of life (QoL). While the Psoriasis Area and Severity Index (PASI) has traditionally been used to assess disease severity and treatment response, achieving substantial improvement in QoL has become an increasingly important therapeutic goal. Recent advances in biologic therapies have enabled higher rates of PASI 90 and PASI 100 responses; however, PASI 75 is no longer considered sufficient for optimal patient outcomes. Calculating PASI improvement rates in daily practice remains challenging, shifting focus toward absolute PASI values as a practical indicator of disease control. In this study, we analyzed 235 psoriasis patients treated with biologics at Nagoya City University Hospital, evaluating 3526 data points collected over a maximum of 288 weeks. We found that PASI positively correlated with DLQI (r = 0.5696, p < 0.001), and that an absolute PASI score of ≤2.2 was associated with DLQI remission (AUC = 0.8140). Notably, 82.6% of patients achieving PASI 100 also achieved DLQI 0/1 status. However, 1.0% of patients with a PASI score of 0 still reported a DLQI ≥10, suggesting that factors beyond skin lesions, such as stigma or residual damage, may contribute to impaired QoL. These findings underscore the importance of evaluating absolute PASI values to guide treatment decisions and achieve DLQI remission. Additionally, the psychosocial burden of psoriasis must be addressed to ensure comprehensive care and sustained improvements in QoL.

BackgroundPsoriasis is a chronic inflammatory skin disease, and as all inflammatory processes, it could induce osteoclast activation1 ending up with osteoporosis. It is well known that a recognised contributing factor...

A 58-year-old woman presented in 2013 with a 30-year history of psoriasis vulgaris. She had a medical history of mild degree of bronchial asthma (not on any medications) and anxiety disorder for which she was on a course of 30 mg/day mirtazapine. Clinically, the patient had a well-defined, erythematous scaly plaques affecting the scalp, trunk, and extremities (Psoriasis Area and Severity Index (PASI): 16.8). The rest of the examination was regular except for a mild degree of arthralgia affecting small joints of both hands. She had received 15 mg/week of methotrexate and 25 mg/day of acitretin, intermittently over months, with an unsatisfactory response. In 2014, while she was on acitretin, multiple disseminated urticarial wheals were noted but no angioedema (Urticaria Activity Score (UAS7): 35). Urticaria was controlled on antihistaminics; however, no complete remission could be achieved. In October 2020, omalizumab (300 mg/28 days) was started as a second-line due to the poor response to higher doses of antihistaminics. In November 2020, she was switched from methotrexate to secukinumab (300 mg at 0, 1, 2, 3, and 4 weeks, followed by a monthly maintenance dose every 4 weeks) due to a lack of psoriasis improvement by cyclosporin and adalimumab. The patient was kept on omalizumab for 18 months and secukinumab for 20 months. Urticaria went into remission (UAS7:0) while psoriasis achieved nearly complete clearance of lesions (PASI:1) without reporting any side effects (Figure 1). Omalizumab (OMZ) is a recombinant humanized monoclonal anti-IgE antibody approved for managing chronic asthma and chronic spontaneous urticaria (CSU) refractory to high doses of H1-antihistamines. Additionally, OMZ has anti-inflammatory effects beyond anti-IgE activity.1 The treatment of CSU with OMZ results in a normalized IL-31 serum level—a cytokine involved in the initiation of chronic skin inflammation—in both CSU and psoriasis patients.2 Binding of high-affinity IgE to the FceRI receptor of mast cells (MCs) would lead to degranulation and immediate release of the preformed chemical mediators, such as tryptase, and tumor necrosis factor (TNF) from the granules.1 Paolino et al.3 recently reported a possible correlation between serum tryptase, as an inflammatory biomarker, and psoriasis. That supports the role of “activated” MCs in the pathogenesis of psoriasis. Interestingly, increased IgE might be an early parameter of poor/unsatisfactory response of psoriasis patients to biologics.4 Fougerousse et al.5 noted that combination of biologics with OMZ in 10 patients with different inflammatory conditions, 7 of them had psoriasis, was well tolerated, and not associated with adverse events, such as infections, or hospital admission for any reason. Concomitant use of guselkumab and OMZ for psoriasis and CSU showed no clinically significant side effects during an extended treatment course of 21 months.6 OMZ combined with biologics may achieve a better outcome in psoriasis than biologics.6-8 Since all published articles were limited to case reports, the relation between psoriasis and urticaria remains uncertain (Table 1). Based on a single case of psoriasis remission on CSU exacerbation, Magen and Chikovani thought CSU would be found at a lower frequency in patients with psoriasis and vice versa, if more evidence exist.9 However, we think the association of both disorders might be under-reported. Patients with treatment-refractory psoriasis may have, for instance, hyper-IL-23 that would induce concomitant urticarial manifestation.8 Therefore, combined therapy would mutually restore the cytokine imbalance of the two conditions.7, 8 Safety profile of the drug as a potential therapy for psoriasis in-combination with other anti-psoriatic lines, namely biologics, may warrant further studies, particularly for psoriasis with pruritic symptoms. -Diffuse urticarial wheals UAS7:31, -Generalized plaque psoriasis(PASI:32) -Acitretin -Methotrexate -Adalimuma- -Etanercept -Infliximab -Secukinumab -Ustekinumab -Levocetiriz- -Guselkumab -Omalizumab UAS7:0 PASI: ≌ 1 -Diffuse urticarial wheals, -Generalized plaques psoriasis -NBUVB -Cyclosporine -Methotrexate -Adalimumab -Secukinumab -Omalizumab -Diffuse urticarial wheals(UAS7:40) -Generalized plaque psoriasis(PASI:25) -Corticosteroid -NBUVB -Cyclosporine -Methotrexate -Apremilast Tildrakizumab- Omalizumab- -Diffuse urticarial wheals (UAS7:35) -Generalized psoriasis plaques (PASI:16.8) -Cyclosporin -Methotrexate -Adalimumab -Acitretin -Secukinumab Omalizumab- Selami Aykut Temiz, Munise Daye, and Sibel Yavuz managed and followed up the case. Uwe Wollina, Torrllo Lotti, and Recep Dursun shared in literature review. Uwe Wollina reviewed the initial draft. Ayman Abdelmaksoud reviewed the literature, wrote the initial draft, and submitted the final draft. All the authors approved the final draft for submission. An informed consent has been obtained from the patient. The patient agreed for publishing her data in an international journal. The data that support the findings of this study are available from the corresponding author upon reasonable request.

Background/Aim: Psoriasis is a chronic inflammatory skin disease that is associated with a higher prevalence of cardiovascular (CV) risk factors. The effect of vitamin D on bone health has been long known, but its extraskeletal role especially in cardiovascular disease and skin disease, is the subject of recent research. This study aimed to assess the influence of high-dose vitamin D supplementation on the Psoriasis Area and Severity Index (PASI) score and lipid profile in patients with psoriasis. Methods: The study included 20 adult patients with chronic plaque psoriasis. They received vitamin D capsules in a daily dose of 5,000 IU over 12 weeks. Measured serum concentrations of lipid metabolism parameters were triglycerides (TG), total cholesterol (TC), low-density lipoproteins (LDL) and high-density lipoproteins (HDL). PASI was used to determine the severity of the disease. Results: High-doses vitamin D supplementation had a significant influence on reduction in PASI score in all patients (17.99 ± 12.42 vs 10.27 ± 8.53; p &lt; 0.001). The supplementation of high dose vitamin D induced statistically significant lowering of the TC, LDL-C and TG in the psoriatic patients (p &lt; 0.05). Furthermore, significant increase in serum HDL-C level was observed. The change of PASI score showed week positive correlation with the changes in serum TC and LDL-C (r = 0.303, p = 0.03 and r = 0.357 p = 0.013). Conclusion: High-dose vitamin D supplementation had a positive impact on clinical status of the chronic plaque psoriasis patients, measured by PASI score. It also improved the serum lipid profile of these patients. Double-blinded prospective studies are needed in order to get more comprehensive data related to vitamin D, lipid metabolism and severity of psoriasis.

The psoriasis area and severity index (PASI) is the gold standard for assessing psoriasis severity but is time-consuming, subjective, poorly reproducible, and requires face-to-face interaction between clinician and patient. Automating PASI assessments using deep learning-based image analysis may provide a more objective, efficient measure of disease severity in trial and real-world settings. Most studies have used Convolutional Neural Networks.1 However, Vision Transformers (ViTs) are sophisticated deep learning models that have shown unprecedented capabilities in image analysis, including classifying skin lesions from dermoscopic images and 3D image (computed tomography/magnetic resonance imaging scan) analysis. We sought to develop and evaluate a ViT model for automated PASI using images. Following consent, adults with chronic plaque psoriasis were recruited via a UK national specialized psoriasis service (04/2021–05/2024). Professional studio photographs (five standardized views) and self-taken photographs (three views) were captured. Two blinded, independent face-to-face physician PASI measures were recorded, with the first rater used as the primary reference value. Fitzpatrick Skin Type and Physician Global Assessment (PGA) were also noted. We trained our ‘MultiViT’ model over 300 epochs and tested using an 80:20 split of the participants. MultiViT advances beyond standard ViTs by handling multiple images and resolutions simultaneously. Mean absolute error (MAE) was used to assess prediction accuracy and compare the standard ViT models with the MultiViT. We captured 1109 images from 152 participants; 63% were male, median age of 45.5 years [interquartile range (IQR) 33.75–57.0], median body mass index of 29.68, 84% Fitzpatrick Skin Types I–IV, and 16% V and VI. The majority (76%) had mild-to-moderate disease (PGA ≤3); median PASI was 8.2 (IQR 5.7–12.7). The MultiViT model demonstrated an MAE of 3.88 for predicting PASI from skin images vs. 5.13 for the standard ViT. When stratified by skin type, I–IV performed better than V and VI (MAE of 2.80 and 8.17, respectively), and by disease severity, PGA ≤3 performed better than PGA &amp;gt;3 (MAE of 1.97 and 9.13, respectively). Our findings suggest the MultiViT model offers potential for automated psoriasis severity assessments from skin images, with favourable prediction accuracy despite a small dataset. An expanded and more diverse (Fitzpatrick Skin Type, severity) dataset will enable further refinement, validation and testing of the MultiViT model in trial and real-world settings. Future integration into a smartphone application will facilitate self-monitoring of psoriasis and healthcare efficiency for improved health and cost outcomes in psoriasis.

BackgroundPsoriasis is a chronic immune-mediated inflammatory skin disease for which biologics are effective treatments. Dose reduction (DR) of the first generation biologics seems a promising way for more efficient use of expensive biologics. A substantial part of patients on tumor necrosis factor (TNF)-alfa inhibitors and ustekinumab could successfully lower their dose, after following a tightly controlled DR strategy. The objective of this study is to assess whether controlled DR of interleukin (IL)-17 and IL-23 inhibitors in psoriasis patients with low disease activity is non-inferior (NI) to usual care (UC).MethodsThis is an international, prospective, multicenter, pragmatic, randomized, non-inferiority trial. A total of 244 patients with stable low disease activity (Psoriasis Area and Severity Index (PASI) ≤ 5) for at least 6 months and using secukinumab, ixekizumab, brodalumab, guselkumab, risankizumab, or tildrakizumab in the standard dose, together with stable low disease activity, defined as a PASI ≤ 5 and Dermatology Life Quality Index (DLQI) ≤ 5 at the moment of inclusion, will be randomized 2:1 to DR or UC. In the DR group, dosing intervals will be prolonged stepwise to achieve 66% and 50% of the original dose. Disease activity is monitored every 3 months by PASI and DLQI. In case of disease flare (i.e., PASI and/or DLQI increase), treatment is adjusted to the previous effective dose. The primary outcome is the incidence proportion of persistent flares (PASI > 5 for ≥ 3 months), which will be compared between arms. Secondary outcomes include proportion of patients with successful DR, (course of) PASI and DLQI, serious adverse events (SAEs), health-related quality of life, costs, and pharmacokinetic profile. Outcomes of DR will be compared to UC.DiscussionWith this study, we aim to assess whether DR of IL-17 and IL-23 inhibiting biologics can be achieved for psoriasis patients with low disease activity, without losing disease control. Reducing the dose may lead to more efficient use of biologics.Trial registrationClinicalTrials.govNCT04340076. Registered on April 9 2020.

THU0438 Is Skin Disease More Important to Patients or Physicians in the Assessment of Disease Activity in Psoriatic Arthritis?

This research aimed to evaluate the impact of probiotic supplementation on the severity of psoriasis symptoms and its association with the risk of developing the disease. We analyzed the association between probiotic usage and psoriasis among 21,942 participants from the 2009–2014 NHANES, employing advanced machine learning techniques for data analysis. A separate meta-analysis was conducted to assess the effects of probiotics on the severity, life quality, and some related inflammation factors. Dichotomous data were analyzed using odds ratios (ORs) corresponding to the 95% confidence interval (CI). Analysis of NHANES data did not reveal a statistically significant association between probiotic intake and the risk of psoriasis. However, the meta-analysis indicated that probiotic supplementation significantly lowers Psoriasis Area and Severity Index (PASI) scores both for change in PASI score and post-data change, and enhances PASI 75 (OR = 4.80, 95% CI = 2.92–7.89) and clearance responses (OR = 3.14, 95% CI = 1.99–4.96), as well as reduced levels of inflammatory markers. While the improvement of life quality was only observed in the post-treatment data. While probiotic supplements do not appear to reduce the risk of psoriasis, they have a significant positive effect on reducing disease severity. Registered on PROSPERO: Registration number CRD42023484417.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12602-024-10418-w.

Background/Objectives: Psoriasis and periodontitis share inflammatory pathways. Current evidence suggests a bidirectional non-causal relation. However, the evidence on the effects of periodontal treatment on psoriasis outcomes (severity, inflammatory markers, quality of life) is limited. This study aims to synthetize the available clinical and preclinical evidence of periodontal treatment effects on psoriasis outcomes, in patients with comorbid psoriasis and periodontitis (CRD420261298145). Methods: Several databases (PubMed, WebOfScience, ScienceDirect, ProQuest and GoogleScholar) were searched for relevant articles, without language or time restrictions. We included randomised and non-randomised clinical studies on humans, and controlled animal experiments. Interventions included periodontal treatment (surgical and non-surgical). Outcomes were the Psoriasis Area and Severity Index and dermatology-specific quality of life scores; secondary outcomes included inflammatory biomarkers and periodontal parameters. Studies were screened in duplicate, data extracted independently and risk of bias was assessed using Cochrane RoB 2, ROBINS I, NOS and SYRCLE. Results: A total of five studies were included in this systematic review (four clinical studies and one preclinical studies). Three studies directly assessed post-treatment psoriasis outcomes, with two studies investigating inflammation mediators as secondary outcomes. Two studies directly assessed PASI (Psoriasis Area and Severity Index) modifications, both studies confirming PASI scores decreasing post-periodontal treatment; one study also reported DLQI (Dermatology Life Quality Index). Typical follow-up durations ranged from 8 to 10 weeks for interventional studies, to 5 years for one cohort study. Conclusions: Although momentarily limited by the small number of available studies, the results of this review suggest that periodontal treatment may be associated with improvements in psoriasis outcomes. Further studies on larger samples, with longer follow-up periods would be necessary to confirm and possibly strengthen the existing results.

Introduction: Psoriasis is a chronic inflammatory disease of skin associated with various metabolic derangements. These metabolic derangements increases the risk of cardiovascular diseases in psoriatic patients. Aim: To study the metabolic parameters- Fasting Blood Glucose (FBS), serum lipid profile, serum uric acid, C-Reactive Protein (CRP) in psoriatic patients in relation to clinical disease severity- Psoriasis Area Severity Index (PASI) score. Materials and Methods: The study was a hospital based cross-sectional observational study carried out over a period of 18 months in Department of Dermatology at Government Medical College and Rajindra Hospital, Patiala that included 250 psoriatic patients. Their percentage Body Surface Area (BSA) involved and PASI score were calculated as per the standard guidelines. The severity of psoriasis was divided into mild (PASI&lt;7), moderate (PASI 7-12) and severe (PASI &gt;12) disease based on PASI score. Serum lipid profile was measured by enzymatic method, blood glucose by glucose oxidase method, serum uric acid by uricase method and CRP by latex slide agglutination method and the values obtained were compared with severity of psoriasis. Results: There was a rise in the value of FBS, serum lipid profile, serum uric acid and CRP as PASI score increased and the difference between these values was statistically highly significant (p-value &lt;0.001). Conclusion: There was a significantly higher derangement of metabolic parameters in patients with higher PASI scores. So, patients with severe psoriasis have a higher risk of metabolic complications and cardiovascular diseases as compared to patients with mild disease. These patients should be advised lifestyle modifications and should be regularly monitored so that the metabolic derangements can be detected earlier and metabolic complications can be avoided.