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Current Clinical Microbiology Reports 2020The aim of this paper is to provide an overview about reactive arthritis, with an update regarding pathophysiology and therapeutic approach of the disease, outlining the... (Review)
Review
PURPOSE OF REVIEW
The aim of this paper is to provide an overview about reactive arthritis, with an update regarding pathophysiology and therapeutic approach of the disease, outlining the clinical features and diagnostic approach, based on recent literature review.
RECENT FINDINGS
Reactive arthritis is considered to be part of the spectrum of the spondyloarthritis. Its epidemiology is changing worldwide due to several reasons, among them are as follows: different diagnosis approach and clinical presentations, different grades of infection, microbiome changes, etc. The understanding of pathophysiological models is challenging, but recent studies contribute to elucidate the major factors involved in the development of the disease. The management of ReA depends on the triggering agent and the phase of disease, whether it is acute or chronic.
SUMMARY
The association between the microbiome changes and spondyloarthropathies (ReA) is becoming increasingly evident. The results regarding the biologic treatment on refectory ReA are promising.
PubMed: 33014690
DOI: 10.1007/s40588-020-00152-6 -
Seminars in Arthritis and Rheumatism Feb 2021C-reactive protein (CRP) is routinely assessed as a marker of systemic inflammation in rheumatoid arthritis (RA). However, it is also an immune regulator that plays an... (Review)
Review
C-reactive protein (CRP) is routinely assessed as a marker of systemic inflammation in rheumatoid arthritis (RA). However, it is also an immune regulator that plays an important role in inflammatory pathways associated with RA and promotes atherogenic effects. Comorbidities linked to systemic inflammation are common in RA, and CRP has been associated with the risk for cardiovascular disease, diabetes, metabolic syndrome, pulmonary diseases, and depression. The relationship between systemic inflammation, CRP, and comorbidities in RA is complex, and it is challenging to determine how changing CRP levels may affect the risk or progression of these comorbidities. We review the biological role of CRP in RA and its implications for disease activity and treatment response. We also discuss the impact of treatment on CRP levels and whether reducing systemic inflammation and inhibiting CRP-mediated inflammatory pathways may have an impact on conditions commonly comorbid with RA.
Topics: Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Cardiovascular Diseases; Humans; Inflammation
PubMed: 33385862
DOI: 10.1016/j.semarthrit.2020.11.005 -
Biomolecules Oct 2020Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis,... (Review)
Review
Spondyloarthritis comprises a group of inflammatory diseases of the joints and spine, with various clinical manifestations. The group includes ankylosing spondylitis, reactive arthritis, psoriatic arthritis, arthritis associated with inflammatory bowel disease, and undifferentiated spondyloarthritis. The exact etiology and pathogenesis of spondyloarthritis are still unknown, but five hypotheses explaining the pathogenesis exist. These hypotheses suggest that spondyloarthritis is caused by arthritogenic peptides, an unfolded protein response, HLA-B*27 homodimer formation, malfunctioning endoplasmic reticulum aminopeptidases, and, last but not least, gut inflammation and dysbiosis. Here we discuss the five hypotheses and the evidence supporting each. In all of these hypotheses, HLA-B*27 plays a central role. It is likely that a combination of these hypotheses, with HLA-B*27 taking center stage, will eventually explain the development of spondyloarthritis in predisposed individuals.
Topics: Arthritis, Psoriatic; Arthritis, Reactive; HLA-B27 Antigen; Humans; Inflammation; Inflammatory Bowel Diseases; Joints; Spine; Spondylarthritis; Spondylitis, Ankylosing; Unfolded Protein Response
PubMed: 33092023
DOI: 10.3390/biom10101461 -
Frontiers in Endocrinology 2022Investigating the causal relationship between rheumatoid arthritis (RA) and atlantoaxial subluxation (AAS) and identifying and quantifying the role of C-reactive protein...
OBJECTIVE
Investigating the causal relationship between rheumatoid arthritis (RA) and atlantoaxial subluxation (AAS) and identifying and quantifying the role of C-reactive protein (CRP) as a potential mediator.
METHODS
Using summary-level data from a genome-wide association study (GWAS), a two-sample Mendelian randomization (MR) analysis of genetically predicted rheumatoid arthritis (14,361 cases, and 43,923 controls) and AAS (141 cases, 227,388 controls) was performed. Furthermore, we used two-step MR to quantitate the proportion of the effect of c-reactive protein-mediated RA on AAS.
RESULTS
MR analysis identified higher genetically predicted rheumatoid arthritis (primary MR analysis odds ratio (OR) 0.61/SD increase, 95% confidence interval (CI) 1.36-1.90) increased risk of AAS. There was no strong evidence that genetically predicted AAS had an effect on rheumatoid arthritis risk (OR 1.001, 95% CI 0.97-1.03). The proportion of genetically predicted rheumatoid arthritis mediated by C-reactive protein was 3.7% (95%CI 0.1%-7.3%).
CONCLUSION
In conclusion, our study identified a causal relationship between RA and AAS, with a small proportion of the effect mediated by CRP, but a majority of the effect of RA on AAS remains unclear. Further research is needed on additional risk factors as potential mediators. In clinical practice, lesions of the upper cervical spine in RA patients need to be given more attention.
Topics: Humans; Arthritis, Rheumatoid; Atlanto-Axial Joint; C-Reactive Protein; Cervical Vertebrae; Genome-Wide Association Study; Joint Dislocations; Joint Instability
PubMed: 36589832
DOI: 10.3389/fendo.2022.1054206 -
Journal of Ophthalmic & Vision Research 2021The seronegative spondyloarthropathies are a group of autoimmune inflammatory diseases lacking rheumatoid factor or antinuclear antibody in their serum. They include... (Review)
Review
The seronegative spondyloarthropathies are a group of autoimmune inflammatory diseases lacking rheumatoid factor or antinuclear antibody in their serum. They include ankylosing spondylitis (AS), reactive arthritis, psoriatic arthritis, spondylitis associated with Crohn's disease and ulcerative colitis, and undifferentiated spondyloarthropathies. Inflammation mostly affects the axial joints, entheses, and extra-articular structures such as uveal tract, gastrointestinal tract, mucocutaneous tissue, and heart. Uveitis is the most common extra-articular manifestation. Spondyloarthropathies, especially AS, have a strong association with the presence of Human Leukocyte Antigen (HLA)-B27 gene. AS happens earlier in HLA-B27 patients and men are more prone to the disease. Uveitis, typically unilateral non-granulomatous acute anterior uveitis, occurs in up to 50% of the patients with AS. HLA-B27 positivity correlates with more frequent flare-ups. Conjunctivitis and scleritis are rare ocular manifestations of AS. To establish the diagnosis of AS, at least one clinical and one radiologic parameter are required for definitive diagnosis. Magnetic resonance imaging (MRI) or bone scan can help early detection of the axial skeleton inflammation. The course of eye and joint involvement are not correlated. Short-term treatment with topical corticosteroids and cycloplegic agents control the uveitis attack. In resistant cases, local or systemic therapy with corticosteroids are recommended. NSAIDs, disease-modifying anti-rheumatic drugs (DMARDs), methotrexate, azathioprine, anti-IL-17A monoclonal antibodies, and TNF-α antagonists are effective treatments for ocular and systemic manifestations of AS. If not treated adequately, uveitis may become recalcitrant and extend posteriorly. Functional impairment due to joint destruction can also occur as a result of under-treatment.
PubMed: 34394873
DOI: 10.18502/jovr.v16i3.9440 -
Nature Communications Feb 2022Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial...
Ferroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium. Data from single-cell RNA sequencing further identify two groups of fibroblasts that have distinct susceptibility to IKE-induced ferroptosis, with the ferroptosis-resistant fibroblasts associated with an increased TNF-related transcriptome. Mechanistically, TNF signaling promotes cystine uptake and biosynthesis of glutathione (GSH) to protect fibroblasts from ferroptosis. Lastly, low dose IKE together with etanercept, a TNF antagonist, induce ferroptosis in fibroblasts and attenuate arthritis progression in the CIA model. Our results thus imply that the combination of TNF inhibitors and ferroptosis inducers may serve as a potential candidate for RA therapy.
Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Cells, Cultured; Disease Models, Animal; Drug Therapy, Combination; Etanercept; Ferroptosis; Fibroblasts; Glutathione; Humans; Imidazoles; Ketones; Lipid Peroxidation; Mice; Piperazines; Reactive Oxygen Species; Synovial Membrane; Tumor Necrosis Factor Inhibitors
PubMed: 35115492
DOI: 10.1038/s41467-021-27948-4 -
World Journal of Gastroenterology Jan 2023Seronegative spondyloarthropathy (SpA) usually starts in the third decade of life with negative rheumatoid factor, human leukocyte antigen-B27 genetic marker and... (Review)
Review
Seronegative spondyloarthropathy (SpA) usually starts in the third decade of life with negative rheumatoid factor, human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations (EAMs). Cases can be classified as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, or juvenile-onset spondyloarthritis. Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease (IBD), with shared genetic and immunopathogenic mechanisms. IBD is a common EAM in SpA patients, while extraintestinal manifestations in IBD patients mostly affect the joints. Although individual protocols are available for the management of each disease, the standard therapeutic guidelines of SpA-associated IBD patients remain to be established. Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA, whereas their use is controversial in IBD due to associated disease flares. Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy. Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD, and a drug of choice for treating SpA-associated IBD. Janus kinase inhibitors, approved for treating SpA and ulcerative colitis, are promising therapeutics in SpA coexistent with ulcerative colitis. A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.
Topics: Humans; Colitis, Ulcerative; Spondylarthropathies; Spondylarthritis; Inflammatory Bowel Diseases; Tumor Necrosis Factor-alpha; Spondylitis, Ankylosing
PubMed: 36688014
DOI: 10.3748/wjg.v29.i3.450 -
Frontiers in Immunology 2022Ferroptosis is one of the newly discovered forms of cell-regulated death characterized by iron-dependent lipid peroxidation. Extensive research has focused on the roles... (Review)
Review
Ferroptosis is one of the newly discovered forms of cell-regulated death characterized by iron-dependent lipid peroxidation. Extensive research has focused on the roles of ferroptosis in tumors, blood diseases, and neurological diseases. Some recent findings have indicated that ferroptosis may also be related to the occurrence and development of inflammatory arthritis. Ferroptosis may be a potential therapeutic target, and few studies and animal models have shown implications in the pathogenesis of inflammatory arthritis. This mini review discussed the common features between ferroptosis and the pathogenesis of rheumatoid arthritis (RA), and evaluated therapeutic applications of ferroptosis regulators in preclinical and clinical research. Some critical issues worth paying attention to were also raised to guide future research efforts.
Topics: Animals; Arthritis, Rheumatoid; Ferroptosis; Humans; Inflammation; Iron; Lipid Peroxidation; Reactive Oxygen Species
PubMed: 35185879
DOI: 10.3389/fimmu.2022.779585 -
Current Rheumatology Reports Jul 2021This article presents a comprehensive narrative review of reactive arthritis (ReA) with focus on articles published between 2018 and 2020. We discuss the entire spectrum... (Review)
Review
PURPOSE OF REVIEW
This article presents a comprehensive narrative review of reactive arthritis (ReA) with focus on articles published between 2018 and 2020. We discuss the entire spectrum of microbial agents known to be the main causative agents of ReA, those reported to be rare infective agents, and those reported to be new candidates causing the disease. The discussion is set within the context of changing disease terminology, definition, and classification over time. Further, we include reports that present at least a hint of effective antimicrobial therapy for ReA as documented in case reports or in double-blind controlled studies. Additional information is included on microbial products detected in the joint, as well as on the positivity of HLA-B27.
RECENT FINDINGS
Recent reports of ReA cover several rare causative microorganism such as Neisseria meningitides, Clostridium difficile, Escherichia coli, Hafnia alvei, Blastocytosis, Giardia lamblia, Cryptosporidium, Cyclospora cayetanensis, Entamoeba histolytica/dispar, Strongyloides stercoralis, β-haemolytic Streptococci, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Mycobacterium bovis bacillus Calmette-Guerin, and Rickettsia rickettsii. The most prominent new infectious agents implicated as causative in ReA are Staphylococcus lugdunensis, placenta- and umbilical cord-derived Wharton's jelly, Rothia mucilaginosa, and most importantly the SARS-CoV-2 virus. In view of the increasingly large spectrum of causative agents, diagnostic consideration for the disease must include the entire panel of post-infectious arthritides termed ReA. Diagnostic procedures cannot be restricted to the well-known HLA-B27-associated group of ReA, but must also cover the large number of rare forms of arthritis following infections and vaccinations, as well as those elicited by the newly identified members of the ReA group summarized herein. Inclusion of these newly identified etiologic agents must necessitate increased research into the pathogenic mechanisms variously involved, which will engender important insights for treatment and management of ReA.
Topics: Arthritis, Reactive; Blastocystis Infections; COVID-19; Clostridium Infections; Cryptosporidiosis; Cyclosporiasis; Entamoebiasis; Enterobacteriaceae Infections; Escherichia coli Infections; Giardiasis; HLA-B27 Antigen; Humans; Meningococcal Infections; Pneumonia, Mycoplasma; Prohibitins; Rocky Mountain Spotted Fever; SARS-CoV-2; Staphylococcal Infections; Streptococcal Infections; Strongyloidiasis; Tuberculosis
PubMed: 34196842
DOI: 10.1007/s11926-021-01018-6