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Clinical and Experimental Rheumatology Oct 2023The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the... (Review)
Review
The aim of this review was to describe the changes in the microbiota of patients with Behçet's disease (BD) and the mechanisms involved in the relationship between the microbiome and immunity in BD. A systematic search for relevant articles was made on PubMed and the Cochrane Library database using the following terms: "microbiota AND Behçet's disease" or "microbiome AND Behçet's disease". Sixteen articles were included in a qualitative synthesis. This systematic review on the microbiome and Behçet's disease underlines the presence of gut dysbiosis in BD patients. This dysbiosis is marked by (i) a decrease in butyrate-producing bacteria, which could affect T cell differentiation and epigenetic regulation of immune-related genes, (ii) a modification of tryptophan-metabolising bacteria, which could be linked to dysregulated IL-22 secretion, and (iii) a decrease in bacteria known to have anti-inflammatory properties. Regarding oral microbiota, this review underlines the possible role of Streptococcus sanguinis through molecular mimicry and NETosis. Clinical studies of BD have shown that (i) need for dentistry is associated with a more severe course in BD, and (ii) antibiotic-supplemented mouthwash reduces pain and ulcers. Fecal transplantation of BD patients' microbiota into mouse models led to decreased SCFA production, neutrophil activation, and Th1/Th17 responses.Recipient mice showed exacerbated experimental autoimmune uveitis (EAU) and experimental autoimmune encephalomyelitis (EAE). In Herpes Virus Simplex-1 (HSV-1) infected mice mimicking BD, administration of butyrateproducing bacteria improved symptoms and immune variables. The microbiome may thus be involved in BD through immunity regulation and epigenetic modifications.
Topics: Humans; Animals; Mice; Behcet Syndrome; Dysbiosis; Epigenesis, Genetic; Uveitis; Microbiota; Bacteria
PubMed: 37382445
DOI: 10.55563/clinexprheumatol/zbt4gx -
Arthritis Research & Therapy Jul 2021Anterior uveitis (AU) is the most frequent extra-articular feature of axial spondyloarthritis (axSpA). We aimed to assess and compare the incidence of AU in axSpA... (Meta-Analysis)
Meta-Analysis
Incidence of anterior uveitis in patients with axial spondyloarthritis treated with anti-TNF or anti-IL17A: a systematic review, a pairwise and network meta-analysis of randomized controlled trials.
BACKGROUND
Anterior uveitis (AU) is the most frequent extra-articular feature of axial spondyloarthritis (axSpA). We aimed to assess and compare the incidence of AU in axSpA patients treated with anti-TNF or anti-IL17A.
METHODS
We systematically reviewed PubMed, EMBase, and Cochrane from inception to May 3, 2020, and searched for placebo-controlled and head-to-head randomized controlled trials (RCTs) assessing anti-TNF monoclonal antibodies (mAb) or soluble receptor fusion protein or anti-IL17A in patients with axSpA according to ASAS criteria and reporting safety data on AU. Data were extracted following a predefined protocol. We did pairwise and network meta-analyses for the primary outcome of AU flares (relapse or de novo) incidence and estimated summary odds ratios (ORs). We assessed the quality of evidence using the Cochrane risk-of-bias 2.0 tool. We ranked treatments according to their effectiveness in preventing AU flare using the P-score.
RESULTS
We identified 752 citations and included 33 RCTs, comprising 4544 treated patients (anti-TNF mAb 2101, etanercept [ETN] 699, anti-IL17A 1744) and 2497 placebo-receiving patients. Incidence of uveitis was lower with anti-TNF mAb versus placebo (OR = 0.46; CI 95% [0.24; 0.90]) and versus anti-IL17A (OR = 0.34; CI 95% [0.12; 0.92]. According to the P-score, the ranking from the most to the least preventive treatment of uveitis flare was as follows: anti-TNF mAb, ETN, placebo, and anti-IL17A.
CONCLUSION
In RCTs assessing anti-TNF and anti-IL17A in axSpA, incident uveitis are rare events. However, this network meta-analysis demonstrates that anti-TNF mAb are associated with a lower incidence of uveitis compared to placebo and anti-IL17A.
Topics: Humans; Incidence; Network Meta-Analysis; Randomized Controlled Trials as Topic; Spondylarthritis; Tumor Necrosis Factor-alpha; Uveitis, Anterior
PubMed: 34271991
DOI: 10.1186/s13075-021-02549-0 -
Annals of the Rheumatic Diseases Jul 2008Uveitis is reported to be the most common extra-articular manifestation in spondyloarthritis (SpA); however, its prevalence and characteristics are not well established. (Review)
Review
BACKGROUND
Uveitis is reported to be the most common extra-articular manifestation in spondyloarthritis (SpA); however, its prevalence and characteristics are not well established.
OBJECTIVE
To perform a systematic literature review in order to examine these topics.
METHODS
A systematic literature analysis was conducted in the Medline database up to October 2006 and in the abstracts of rheumatology scientific meetings for the years 2004, 2005 and 2006. A hand search of references was also performed. Articles were analysed if they reported the prevalence or characteristics of uveitis in SpA. Data abstraction was standardised. Statistical analysis was mainly descriptive.
RESULTS
Among the 957 articles selected by the search, 126 articles (29,877 patients) allowed a calculation of the prevalence of uveitis in SpA; 36 articles (1989 patients) described its characteristics. The mean (SD) prevalence of uveitis was 32.7 (0.5)%; it varied with the type of SpA--for example, 33.2 (0.8)% for ankylosing spondylitis versus 25.1 (2.3)% for psoriatic arthritis. This prevalence increased with mean disease duration and was higher in HLA-B27-positive patients with an odds ratio of 4.2. Uveitis was acute in 88.7 (2.5)%, anterior in 90.5 (2.0)%, unilateral in 87.3 (2.8)%. Recurrence occurred in 50.6 (2.6)% and a reduction of visual acuity was observed in 8.3 (3.8)%.
CONCLUSION
The prevalence of uveitis varies with disease duration and according to the type of SpA. Reduction of visual acuity is not exceptional. Because of recent promising data about the effects of anti-tumour necrosis factor therapy on uveitis flares in SpA, it was important to determine this baseline prevalence.
Topics: Acute Disease; Adult; Female; Humans; Male; Middle Aged; Prevalence; Recurrence; Spondylarthritis; Uveitis; Uveitis, Anterior
PubMed: 17962239
DOI: 10.1136/ard.2007.075754 -
Medicina Clinica Dec 2017To develop recommendations on the use of immunodepressors in patients with non-infectious, non-neoplastic anterior uveitis (AU) based on best evidence and experience.
BACKGROUND AND OBJECTIVE
To develop recommendations on the use of immunodepressors in patients with non-infectious, non-neoplastic anterior uveitis (AU) based on best evidence and experience.
MATERIAL AND METHODS
A multidisciplinary panel of five experts was established, who, in the first nominal group meeting defined the scope, users, and chapters of the document. A systematic literature review was performed to assess the efficacy and safety of immunosuppressors in patients with non-infectious, non-neoplastic AU. All the above was discussed in a second nominal group meeting and 33 recommendations were generated. Through the Delphi methodology, the degree of agreement with the recommendations was tested also by 25 more experts. Recommendations were voted on from one (total disagreement) to 10 (total agreement). We defined agreement if at least 70% voted ≥7. The level of evidence and degree of recommendation was assessed using the Oxford Centre for Evidence-based Medicine's Levels of Evidence.
RESULTS
The 33 recommendations were accepted. They include specific recommendations on patients with non-infectious, non-neoplastic AU, as well as different treatment lines.
CONCLUSIONS
In patients with non-infectious, non-neoplastic AU, these recommendations on the use of immunosuppressors might be a guide in order to help in the treatment decision making, due to the lack of robust evidence or other globally accepted algorithms.
Topics: Clinical Decision-Making; Delphi Technique; Drug Administration Schedule; Humans; Immunosuppressive Agents; Uveitis, Anterior
PubMed: 28911893
DOI: 10.1016/j.medcli.2017.06.059 -
Seminars in Arthritis and Rheumatism Feb 2011To analyze the effectiveness of immunosuppressants and biological therapies in autoimmune posterior uveitis, chronic anterior uveitis associated with juvenile idiopathic... (Review)
Review
OBJECTIVES
To analyze the effectiveness of immunosuppressants and biological therapies in autoimmune posterior uveitis, chronic anterior uveitis associated with juvenile idiopathic arthritis, and macular edema.
METHODS
Systematic review. We conducted a sensitive literature search in Medline (from 1961) and EMBASE (from 1980) until October 2007. Selection criteria were as follows: (1) population: autoimmune posterior uveitis, chronic anterior uveitis in juvenile idiopathic arthritis, and macular edema; (2) intervention: immunosuppressive and biologic therapies; (3) outcomes: visual acuity, Tyndall, vitreous haze, macular edema, pars planitis, and retinal vasculitis. There were no limitations regarding study design. The quality of each study was evaluated using the Jadad's scale and Oxford Levels of Evidence.
RESULTS
Two hundred sixty-five articles were selected for detailed review of the 4235 found in the initial search: 128 records were on immunosuppressants, 105 on biological therapies, and 32 on macular edema. Overall, both the immunosuppressive and the biologic therapies appeared effective in the treatment of autoimmune posterior uveitis, except for daclizumab in uveitis related to Behçet's disease, and for etanercept in any uveitis. In the treatment of macular edema, the drugs tested were also effective.
CONCLUSIONS
Based on the evidence collated, immunosuppressants and biological therapies (except for daclizumab in Behçet and etanercept) may be effective in autoimmune uveitis and macular edema. No superiority may be inferred from this review.
Topics: Antibodies, Monoclonal; Arthritis, Juvenile; Autoimmune Diseases; Humans; Immunosuppressive Agents; Macular Edema; Treatment Outcome; Uveitis, Anterior; Uveitis, Posterior
PubMed: 20656330
DOI: 10.1016/j.semarthrit.2010.05.008 -
Orphanet Journal of Rare Diseases Aug 2012Uveitis is an autoimmune disease of the eye that refers to any of a number of intraocular inflammatory conditions. Because it is a rare disease, uveitis is often... (Review)
Review
BACKGROUND
Uveitis is an autoimmune disease of the eye that refers to any of a number of intraocular inflammatory conditions. Because it is a rare disease, uveitis is often overlooked, and the possible associations between uveitis and extra-ocular disease manifestations are not well known. The aim of this study was to characterize uveitis in a large sample of patients and to evaluate the relationship between uveitis and systemic diseases.
METHODS
The present study is a cross-sectional study of a cohort of patients with uveitis. Records from consecutive uveitis patients who were seen by the Uveitis Service in the Department of Ophthalmology at the Medical University of Vienna between 1995 and 2009 were selected from the clinical databases. The cases were classified according to the Standardization of Uveitis Nomenclature Study Group criteria for Uveitis.
RESULTS
Data were available for 2619 patients, of whom 59.9% suffered from anterior, 14.8% from intermediate, 18.3% from posterior and 7.0% from panuveitis. 37.2% of all cases showed an association between uveitis and extra-organ diseases; diseases with primarily arthritic manifestations were seen in 10.1% of all cases, non-infectious systemic diseases (i.e., Behçet´s disease, sarcoidosis or multiple sclerosis) in 8.4% and infectious uveitis in 18.7%. 49.4% of subjects suffering from anterior uveitis tested positively for the HLA-B27 antigen. In posterior uveitis cases 29% were caused by ocular toxoplasmosis and 17.7% by multifocal choroiditis.
CONCLUSION
Ophthalmologists, rheumatologists, infectiologists, neurologists and general practitioners should be familiar with the differential diagnosis of uveitis. A better interdisciplinary approach could help in tailoring of the work-up, earlier diagnosis of co-existing diseases and management of uveitis patients.
Topics: Age of Onset; Cohort Studies; Cross-Sectional Studies; Female; Humans; Male; Rare Diseases; Uveitis
PubMed: 22932001
DOI: 10.1186/1750-1172-7-57 -
Ocular Immunology and Inflammation Aug 2020New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify...
PURPOSE
New instrument-based techniques for anterior chamber (AC) cell counting can offer automation and objectivity above clinician assessment. This review aims to identify such instruments and its correlation with clinician estimates.
METHODS
Using standard systematic review methodology, we identified and tabulated the outcomes of studies reporting reliability and correlation between instrument-based measurements and clinician AC cell grading.
RESULTS
From 3470 studies, 6 reported correlation between an instrument-based AC cell count to clinician grading. The two instruments were optical coherence tomography (OCT) and laser flare-cell photometry (LFCP). Correlation between clinician grading and LFCP was 0.66-0.87 and 0.06-0.97 between clinician grading and OCT. OCT volume scans demonstrated correlation between 0.75 and 0.78. Line scans in the middle AC demonstrated higher correlation (0.73-0.97) than in the inferior AC (0.06-0.56).
CONCLUSION
AC cell count by OCT and LFP can achieve high levels of correlation with clinician grading, whilst offering additional advantages of speed, automation, and objectivity.
Topics: Anterior Chamber; Cell Count; Humans; Photometry; Tomography, Optical Coherence; Uveitis
PubMed: 31418609
DOI: 10.1080/09273948.2019.1640883 -
Frontiers in Pharmacology 2021Patients with noninfectious uveitis (NIU) are at risk of systemic side effects of long-term glucocorticoid therapy and uncontrolled inflammatory complications. In... (Review)
Review
Patients with noninfectious uveitis (NIU) are at risk of systemic side effects of long-term glucocorticoid therapy and uncontrolled inflammatory complications. In urgent need to identify more aggressive therapies, adalimumab (ADA) may be the right choice. To summarize the current evidence from randomized controlled trials (RCTs) regarding the efficacy and safety of ADA in the treatment of NIU. We searched Pubmed, Embase, Web of Science, Cochrane Library databases, and Clinical Trials Registry for qualifying articles from their inception to November 19, 2020, with no language restriction. Randomized controlled trials comparing ADA with conventional routine treatment in noninfectious uveitis patients of any age, gender, or ethnicity were included. The primary outcome was the time to treatment failure (TF). The secondary outcomes were the change in best-corrected visual acuity (BCVA), change in the anterior chamber (AC) cell grade, change in vitreous haze (VH) grade, and adverse events (AEs). The six studies comprised 605 participants in all, and the sample size of each study ranged from 16 to 225. The overall pooled results of the primary outcome (HR = 0.51; 95% CI, 0.41 to -0.63) showed that ADA nearly halved the risk of treatment failure compared to placebo for NIU patients. The pooled mean difference of change in BCVA was -0.05 (95% CI, -0.07 to -0.02). The pooled mean difference of change in AC cell grade and VH grade was -0.29 (95% CI, -0.62 to -0.05) and -0.21 (95% CI, -0.32 to -0.11), respectively. The incidence of AEs in the ADA group was numerically higher than that of AEs in the placebo group (2,237 events and 9.40 events per patient-year, equivalent to 1,257 events and 7.79 events per patient-year). This meta-analysis of six RCTs further confirmed that ADA considerably lowered the risk of treatment failure or visual loss, and moderately reduced AC cell grades and VH grades with slightly more AEs, as compared to placebo. ADA is both effective and safe in treating NIU. [https://clinicaltrials.gov], identifier [CRD42020217909].
PubMed: 33981245
DOI: 10.3389/fphar.2021.673984 -
Arthritis & Rheumatology (Hoboken, N.J.) May 2024Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Anterior uveitis is a common extra-articular manifestation of axial spondyloarthritis (AxSpA). We set to evaluate the risk of anterior uveitis (AU) with biologics and synthetic disease-modifying drugs in AxSpA.
METHODS
We conducted a systematic review and meta-analysis to identify phase II/III double-blinded randomized controlled trials of anti-tumor necrosis factor (TNF) monoclonal antibodies (mAb), anti-interleukin-17 (anti-IL-17), and Janus kinase inhibitors (JAKi) in AxSpA. Patient-exposure years (PEY) were calculated using the per-protocol approach. Incidence rate (IR) of AU/100 person-years were calculated by treatment group using the random effects approach. Network meta-analysis (NMA) was used to estimate risk of AU in treatment groups, expressed as IR ratios (IRRs). Bias was assessed using the Cochrane Risk of Bias-2 tool.
RESULTS
Forty-four trials were included: 17 anti-TNF mAb (1,004 PEY), 9 etanercept (180 PEY), 13 anti-IL-17 (1,834 PEY), and 6 JAKi (331 PEY). The IR of AU were as follows for anti-TNF mAb: 4.1, 95% confidence interval (CI) 0-8.5; etanercept: 5.4, 95% CI 0-16.0; anti-IL-17: 2.8, 95% CI 1.6-4.1; JAKi: 1.5, 95% CI 0.0-3.0; and placebo: 10.8, 95% CI 7.4-14.1. In NMA, IRRs of treatments compared with placebo were as follows for anti-TNF mAb: 0.32, 95% CI 0.10-1.04; etanercept 0.42, 95% CI 0.08-2.38; anti-IL-17: 0.43, 95% CI 0.19-0.98; and JAKi: 0.32, 95% CI 0.06-1.67. Comparisons between anti-TNF mAb, anti-IL-17, and JAKi did not demonstrate any significant difference in AU risk. Using the surface under the cumulative ranking curve approach to rank AU risk, anti-TNF mAbs were associated with the lowest risk followed by JAKi, anti-IL-17, and etanercept. All treatments were ranked superior to placebo.
CONCLUSION
Anti-TNF mAbs, JAKi, and anti-IL-17 appear protective against AU events in individuals with AxSpA, with no significant differences in risk of AU between treatments.
Topics: Humans; Biological Products; Incidence; Antirheumatic Agents; Network Meta-Analysis; Axial Spondyloarthritis; Antibodies, Monoclonal; Interleukin-17; Etanercept; Janus Kinase Inhibitors; Uveitis, Anterior; Tumor Necrosis Factor-alpha; Randomized Controlled Trials as Topic; Uveitis
PubMed: 38116697
DOI: 10.1002/art.42788 -
Ocular Immunology and Inflammation Jul 2021: Anterior chamber (AC) flare is a key sign for anterior uveitis. New instrument-based techniques for measuring AC flare can offer automation and objectivity. This...
: Anterior chamber (AC) flare is a key sign for anterior uveitis. New instrument-based techniques for measuring AC flare can offer automation and objectivity. This review aims to identify objective instrument-based measures for AC flare.: In this systematic review, we identified studies reporting correlation between instrument-based tests versus clinician AC flare grading, and/or aqueous protein concentration, as well as test reliability.: Four index tests were identified in 11 studies: laser-flare photometry (LFP), optical coherence tomography, ocular flare analysis meter (OFAM) and the double-pass technique. The correlation between LFP and clinician grading was 0.40-0.93 and 0.87-0.94 for LFP and protein concentration. The double-pass technique showed no correlation with clinician grading and insufficient information was available for OFAM.: LFP shows moderate to strong correlation with clinician grading and aqueous protein concentration. LFP could be a superior reference test compared to clinician AC flare grading for validating new index tests.
Topics: Anterior Chamber; Aqueous Humor; Diagnostic Techniques, Ophthalmological; Eye Proteins; Humans; Photometry; Tomography, Optical Coherence; Uveitis, Anterior
PubMed: 32255392
DOI: 10.1080/09273948.2019.1709650