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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 -
BMJ Open Ophthalmology Jun 2023This study aimed to review effectiveness studies comparing two biological anti-tumour necrosis factor agents, adalimumab (ADA) and infliximab (IFX), in the management of...
OBJECTIVE
This study aimed to review effectiveness studies comparing two biological anti-tumour necrosis factor agents, adalimumab (ADA) and infliximab (IFX), in the management of autoimmune uveitis.
METHODS
A systematic search was conducted across PubMed, Scopus, Web of Science and Google Scholar from 2014 until February 2022. The search included the following keywords "Adalimumab", "Infliximab", "Autoimmune", "Anterior", "Intermediate", "Posterior", "Panuveitis", "Refractory" and "Uveitis". Primary studies comparing both ADA and IFX in a population of autoimmune uveitis patients were considered. Outcomes of interest were measures of response to treatment and incidence of adverse events.
RESULTS
The preliminary literature search generated 7156 references. Six studies fulfilled the eligibility criteria and were included in the final analysis; all were non-randomised, retrospective or observational. The included studies found similar effectiveness and side effect profiles for both ADA and IFX in the management of autoimmune uveitis, however, one did not report effectiveness for each separately, and three were limited to Behcet's disease.
CONCLUSION
ADA and IFX seem to display comparable effectiveness and safety profiles. However, the available evidence remains scarce, of low quality and at high risk of bias. A direct comparison between ADA and IFX through large randomised controlled trials is needed to provide more substantial evidence of equivalence or superiority in uveitis.
Topics: Humans; Adalimumab; Infliximab; Retrospective Studies; Treatment Outcome; Uveitis; Tumor Necrosis Factor-alpha; Behcet Syndrome
PubMed: 37493653
DOI: 10.1136/bmjophth-2023-001303 -
Autoimmunity Reviews Sep 2013The objectives of this study are to review our current knowledge of the aetiopathogenesis of Vogt-Koyanagi-Harada syndrome, including viral infection, genetic factors... (Review)
Review
OBJECTIVES
The objectives of this study are to review our current knowledge of the aetiopathogenesis of Vogt-Koyanagi-Harada syndrome, including viral infection, genetic factors and immunomediated mechanisms, and to discuss pathogenesis and its relevance to pharmacotherapy.
SYSTEMATIC REVIEW METHODOLOGY
Relevant publications from 1965 to 2012 on the aetiopathogenesis and pharmacotherapy of VKHS were analysed.
RESULTS AND CONCLUSION
Vogt-Koyanagi-Harada syndrome (VKHS) is a rare multisystemic autoimmune disease that affects tissues containing melanin, including the eye, inner ear, meninges, and skin. The disease is characterised by bilateral uveitis associated with a varying constellation of auditory, neurological and cutaneous manifestations. The disease occurs more frequently among people with darker skin pigmentation. Asians, Native Americans, and Hispanics are most frequently affected. It predominates in patients aged between 20 and 50years, and females are affected more frequently, with a female:male ratio of 2:1. The classic clinical course is characterised by bilateral panuveitis, hypoacusis, and meningitis, in addition to cutaneous involvement with poliosis, vitiligo, and alopecia. Although the exact cause of VKH disease remains unknown, it is thought to be a T-cell-mediated autoimmune process directed against melanocytes. VKHS classically begins with vague systemic symptoms suggestive of a viral infection, although a clear association between a specific viral agent and the disease has not been established. Genetic factors may play an important role in the loss of self-tolerance in VKHS. The HLA-DRB1*0405 allele is the main susceptibility allele for VKHS. Early and aggressive systemic corticosteroids are still the primary initial therapy for VKHS. Ocular complications may require an intravitreous injection of corticosteroids. Despite proper treatment with steroids, a number of patients experience recurrent attacks or steroid-associated complications. Thus, non steroid immunomodulatory therapy (IMT) has become necessary for the treatment of VKHS.
Topics: Autoimmune Diseases; HLA-DRB1 Chains; Humans; Self Tolerance; Uveomeningoencephalitic Syndrome
PubMed: 23567866
DOI: 10.1016/j.autrev.2013.01.004 -
Health Technology Assessment... Nov 2017Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Non-infectious intermediate uveitis, posterior uveitis and panuveitis are a heterogeneous group of inflammatory eye disorders. Management includes local and systemic corticosteroids, immunosuppressants and biological drugs.
OBJECTIVES
To evaluate the clinical effectiveness and cost-effectiveness of subcutaneous adalimumab (Humira; AbbVie Ltd, Maidenhead, UK) and a dexamethasone intravitreal implant (Ozurdex; Allergan Ltd, Marlow, UK) in adults with non-infectious intermediate uveitis, posterior uveitis or panuveitis.
DATA SOURCES
Electronic databases and clinical trials registries including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and the World Health Organization's International Clinical Trials Registry Platform were searched to June 2016, with an update search carried out in October 2016.
REVIEW METHODS
Review methods followed published guidelines. A Markov model was developed to assess the cost-effectiveness of dexamethasone and adalimumab, each compared with current practice, from a NHS and Personal Social Services (PSS) perspective over a lifetime horizon, parameterised with published evidence. Costs and benefits were discounted at 3.5%. Substantial sensitivity analyses were undertaken.
RESULTS
Of the 134 full-text articles screened, three studies (four articles) were included in the clinical effectiveness review. Two randomised controlled trials (RCTs) [VISUAL I (active uveitis) and VISUAL II (inactive uveitis)] compared adalimumab with placebo, with limited standard care also provided in both arms. Time to treatment failure (reduced visual acuity, intraocular inflammation, new vascular lesions) was longer in the adalimumab group than in the placebo group, with a hazard ratio of 0.50 [95% confidence interval (CI) 0.36 to 0.70; < 0.001] in the VISUAL I trial and 0.57 (95% CI 0.39 to 0.84; = 0.004) in the VISUAL II trial. The adalimumab group showed a significantly greater improvement than the placebo group in the 25-item Visual Function Questionnaire (VFQ-25) composite score in the VISUAL I trial (mean difference 4.20; = 0.010) but not the VISUAL II trial (mean difference 2.12; = 0.16). Some systemic adverse effects occurred more frequently with adalimumab than with placebo. One RCT [HURON (active uveitis)] compared a single 0.7-mg dexamethasone implant against a sham procedure, with limited standard care also provided in both arms. Dexamethasone provided significant benefits over the sham procedure at 8 and 26 weeks in the percentage of patients with a vitreous haze score of zero ( < 0.014), the mean best corrected visual acuity improvement ( ≤ 0.002) and the percentage of patients with a ≥ 5-point improvement in VFQ-25 score ( < 0.05). Raised intraocular pressure and cataracts occurred more frequently with dexamethasone than with the sham procedure. The incremental cost-effectiveness ratio (ICER) for one dexamethasone implant in one eye for a combination of patients with unilateral and bilateral uveitis compared with limited current practice, as per the HURON trial, was estimated to be £19,509 per quality-adjusted life-year (QALY) gained. The ICER of adalimumab for patients with mainly bilateral uveitis compared with limited current practice, as per the VISUAL trials, was estimated to be £94,523 and £317,547 per QALY gained in active and inactive uveitis respectively. Sensitivity analyses suggested that the rate of blindness has the biggest impact on the model results. The interventions may be more cost-effective in populations in which there is a greater risk of blindness.
LIMITATIONS
The clinical trials did not fully reflect clinical practice. Thirteen additional studies of clinically relevant comparator treatments were identified; however, network meta-analysis was not feasible. The model results are highly uncertain because of the limited evidence base.
CONCLUSIONS
Two RCTs of systemic adalimumab and one RCT of a unilateral, single dexamethasone implant showed significant benefits over placebo or a sham procedure. The ICERs for adalimumab were estimated to be above generally accepted thresholds for cost-effectiveness. The cost-effectiveness of dexamethasone was estimated to fall below standard thresholds. However, there is substantial uncertainty around the model assumptions. In future work, primary research should compare dexamethasone and adalimumab with current treatments over the long term and in important subgroups and consider how short-term improvements relate to long-term effects on vision.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42016041799.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Adalimumab; Adult; Anti-Inflammatory Agents; Antibodies, Monoclonal, Humanized; Cost-Benefit Analysis; Dexamethasone; Humans; Quality-Adjusted Life Years; Technology Assessment, Biomedical; Uveitis, Intermediate; Uveitis, Posterior
PubMed: 29183563
DOI: 10.3310/hta21680 -
Arthritis Care & Research May 2023The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to update the current guidelines, and the objective here was to produce...
OBJECTIVE
The Multinational Interdisciplinary Working Group for Uveitis in Childhood identified the need to update the current guidelines, and the objective here was to produce this document to guide clinicians managing children with juvenile idiopathic arthritis-associated uveitis (JIAU) and idiopathic chronic anterior uveitis (CAU).
METHODS
The group analyzed the literature published between December 2014 and June 2020 after a systematic literature review conducted by 2 clinicians. Pediatric rheumatologists were paired with ophthalmologists to review the eligible 37 publications. The search criteria were selected to reflect those used for the 2018 Single Hub and Access point for pediatric Rheumatology in Europe (SHARE) recommendations, in order to provide an update, rather than a replacement for that publication. The summary of the current evidence for each SHARE recommendation was presented to the expert committee. These recommendations were then discussed and revised during a video consensus meeting on January 22, 2021, with 14 voting participants, using a nominal group technique to reach consensus.
RESULTS
JIAU treatment was extended to include CAU. Fourteen recommendations regarding treatment of JIAU und CAU with >90% agreement were accepted.
CONCLUSION
An update to the previous 2018 SHARE recommendations for the treatment of children with JIAU with the addition of CAU was created using an evidence-based consensus process. This guideline should help support clinicians to care for children and young people with CAU.
Topics: Child; Humans; Adolescent; Arthritis, Juvenile; Uveitis; Europe; Rheumatology; Uveitis, Anterior
PubMed: 35638697
DOI: 10.1002/acr.24963 -
Nephrology, Dialysis, Transplantation :... Apr 2022Tubulointerstitial nephritis and uveitis (TINU) syndrome is defined as the occurrence of tubulointerstitial nephritis (TIN) and uveitis in the absence of other systemic...
BACKGROUND
Tubulointerstitial nephritis and uveitis (TINU) syndrome is defined as the occurrence of tubulointerstitial nephritis (TIN) and uveitis in the absence of other systemic diseases. The most comprehensive review on this condition was published in 2001.
METHODS
We conducted a systematic review of the literature for cases of TINU syndrome. MEDLINE and Embase databases were screened. Full-length articles or letters reporting cases with both TIN and uveitis were selected. We investigated differences between males and females and paediatric and adult cases. Multivariate analysis was performed to identify potential risk factors for chronic kidney disease (CKD) development.
RESULTS
A total of 233 articles reporting 592 TINU cases were retained for the analysis. The median age of the included subjects was 17 years (interquartile range 13-46) with a female predominance (65%). Uveitis most frequently (52%) followed renal disease and was mostly anterior (65%) and bilateral (88%). Children tended to have more ocular relapses, while they were slightly less likely than adults to suffer from acute kidney injury and to develop CKD. Adult age as well as posterior or panuveitis were associated with an increased risk of developing CKD.
CONCLUSIONS
TINU affects both children and adults, with some differences between these two categories. Adult age and the presence of a posterior uveitis or panuveitis appear to be associated with the development of CKD.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Nephritis, Interstitial; Panuveitis; Renal Insufficiency, Chronic; Uveitis
PubMed: 33561271
DOI: 10.1093/ndt/gfab030 -
Seminars in Arthritis and Rheumatism Feb 2016To evaluate subclinical atherosclerosis in Behcet disease (BD), we performed a systematic review and meta-analysis of studies where atherosclerosis was determined by... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate subclinical atherosclerosis in Behcet disease (BD), we performed a systematic review and meta-analysis of studies where atherosclerosis was determined by flow-mediated dilatation (FMD) and endothelial-mediated dilatation (EMD) and by measurement of intima media thickness (IMT) of carotid arteries.
METHODS
Systematic search of EMBASE and PubMed databases from January 2000 to January 2014 according to PRISMA guidelines.
RESULTS
Nine studies met the inclusion criteria on FMD/EMD, 11 on IMT and 4 on both. BD had lower FMD than controls (SMD = -0.89, 95% CI: -0.660 to -1.11, p < 0.001), which was confirmed by subgroup analyses on active and inactive patients (SMD = -1.17, 95% CI: -1.45 to -0.89 and SMD = -0.72, 95% CI: -0.97 to -0.46, p = 0.0001 for both). EMD was lower in BD but with a large estimate (SMD = 0.38, 95% CI: -0.79 to -0.03, p = 0.06, I(2) = 82.2%). IMT was greater in BD and the large estimate (SMD = 0.95, 95% CI: 0.63-1.28, p < 0.0001, I(2) = 87.6%) persisted after subgroup analysis on active and inactive patients (I(2) = 88.4% and 86.7%, respectively). Pooling IMT studies by a Newcastle Ottawa Scale of 5 and 6/7 yielded lower estimates (SMD = 0.54, 95% CI: 0.32-0.75, p < 0.0001, I(2) = 58.7% and SMD = 1.72, 95% CI: 1.35-2.09 p < 0.05, I(2) = 48.6%).
CONCLUSIONS
FMD is impaired in BD even in inactive state and IMT is greater despite a degree of statistical heterogeneity that reflects the clinical heterogeneity of BD. Future prospective studies should account for risk stratification of atherosclerosis in BD.
Topics: Atherosclerosis; Behcet Syndrome; Carotid Arteries; Carotid Intima-Media Thickness; Endothelium, Vascular; Humans; Severity of Illness Index
PubMed: 26239908
DOI: 10.1016/j.semarthrit.2015.06.018 -
BMJ Clinical Evidence Apr 2010Anterior uveitis is rare, with an annual incidence of 12/100,000 population, although it is more common in Finland (annual incidence of 23/100,000), probably because of... (Review)
Review
INTRODUCTION
Anterior uveitis is rare, with an annual incidence of 12/100,000 population, although it is more common in Finland (annual incidence of 23/100,000), probably because of genetic factors, such as high frequency of HLA-B27 in the population. It is often self-limiting, but can, in some cases, lead to complications such as posterior synechiae, cataract, glaucoma, and chronic uveitis.
METHODS AND OUTCOMES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of anti-inflammatory eye drops on acute anterior uveitis? We searched: Medline, Embase, The Cochrane Library and other important databases up to November 2009 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found six systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: corticosteroids, mydriatics, and non-steroidal anti-inflammatory drug eye drops.
Topics: Acute Disease; Adrenal Cortex Hormones; Anti-Inflammatory Agents, Non-Steroidal; Evidence-Based Medicine; Humans; Incidence; Mydriatics; Ophthalmic Solutions; Uveitis, Anterior
PubMed: 21736765
DOI: No ID Found -
Survey of Ophthalmology 2022Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior... (Meta-Analysis)
Meta-Analysis Review
Cytomegalovirus (CMV) anterior uveitis is the most common form of ocular manifestation of CMV in immunocompetent individuals. The difficulty in diagnosing CMV anterior uveitis may delay adequate treatment and affect outcomes. We sought to review systemically the overall clinical characteristics and compare treatment outcomes in CMV anterior uveitis and endotheliitis. A literature search was performed, and studies describing clinical characteristics, treatment regimens, and outcomes that included more than 5 treated eyes were included. In these 23 studies, acute CMV anterior uveitis commonly presented with high intraocular pressure (95.31%, 95% CI 90.45-98.60) and mild anterior chamber inflammation (cells >2+ = 3.18%, 95% CI 0.21-0.54). About two-thirds of CMV endotheliitis cases presented with high intraocular pressure and coin-shaped corneal lesions. Acute CMV anterior uveitis showed good clinical response to topical 0.15% ganciclovir (GCV) gel or oral valganciclovir (VGCV) (90%, 95% CI 74-100% and 95%, 95% CI 88-100%, respectively). For chronic CMV anterior uveitis, both topical GCV and oral VGCV yielded comparable results. Topical 0.5-2% GCV or a combination of topical and oral VGCV for CMV endotheliitis both resulted in good clinical response. Recurrence of inflammation was common after cessation of maintenance therapy. Overall, topical GCV resulted in an optimal outcome for CMV anterior uveitis. Escalated concentration and frequency of usage are needed for chronic CMV anterior uveitis and endotheliitis. Adequate induction and maintenance phases of anti-CMV treatment seem necessary to prevent recurrences.
Topics: Antiviral Agents; Aqueous Humor; Cytomegalovirus; Cytomegalovirus Infections; DNA, Viral; Eye Infections, Viral; Ganciclovir; Glaucoma; Humans; Inflammation; Treatment Outcome; Uveitis, Anterior; Valganciclovir
PubMed: 34954093
DOI: 10.1016/j.survophthal.2021.12.006 -
Minerva Ginecologica Oct 2020Behcet's disease (BD) is a rare inflammatory, multisystemic, autoimmune disorder with unknown origin. BD is included in vasculitic disorders with a more frequent onset...
INTRODUCTION
Behcet's disease (BD) is a rare inflammatory, multisystemic, autoimmune disorder with unknown origin. BD is included in vasculitic disorders with a more frequent onset characterized by oral and genital ulcers associated with eye inflammation. However, BD has several clinical manifestations, and the most fearful complication is thrombotic involvement. BD occurs mainly in women of childbearing age, therefore it is important to identify the potential risks of pregnancy on the mother and fetus.
EVIDENCE ACQUISITION
The aim of our review is to identify, through the study of existing literature, the possible consequences of pregnancy on the course of this disease, the potential risks for the mother and fetus in gestation period and in puerperium, in order to identify a correct pregnancy management in patient affected by BD.
EVIDENCE SYNTHESIS
Currently, there are few studies that have analyzed the consequences of the disease on the course of pregnancy and pregnancy on the activity of the pathology. Some authors believe that pregnancy may worsen the symptoms of the disease, while others may even improve the course. Many authors believe that thromboembolic events are the main problems for which focus attention on these patients, both in pregnancy and in puerperium. Different opinions exist about pregnancy complications and neonatal outcomes, although events such as abortion, intrauterine growth restriction and C-section appear to have a higher incidence in BD patients.
CONCLUSIONS
There are no contraindications for the onset of pregnancy in BD patients. In most cases pregnancy can improve the course of the disease. However, in view of the potential adverse events, a thorough follow-up of the pregnancy is necessary in order to minimize any risks to the mother and fetus.
Topics: Abortion, Spontaneous; Behcet Syndrome; Female; Humans; Infant, Newborn; Postpartum Period; Pregnancy; Pregnancy Complications; Retrospective Studies
PubMed: 32403914
DOI: 10.23736/S0026-4784.20.04564-5