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Frontiers in Immunology 2024Osteoarthritis (OA) and Rheumatoid Arthritis (RA) are significant health concerns with notable prevalence and economic impact. RA, affecting 0.5% to 1.0% of the global... (Review)
Review
Osteoarthritis (OA) and Rheumatoid Arthritis (RA) are significant health concerns with notable prevalence and economic impact. RA, affecting 0.5% to 1.0% of the global population, leads to chronic joint damage and comorbidities. OA, primarily afflicting the elderly, results in joint degradation and severe pain. Both conditions incur substantial healthcare expenses and productivity losses. The cGAS-STING pathway, consisting of cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING), is a crucial component of mammalian immunity. This pathway is responsible for detecting foreign DNA, particularly double-stranded DNA (dsDNA), triggering innate immune defense responses. When cGAS recognizes dsDNA, it catalyzes the synthesis of cyclic GMP-AMP (cGAMP), which then binds to and activates STING. Activated STING, in turn, initiates downstream signaling events leading to the production of interferons and other immune mediators. The cGAS-STING pathway is essential for defending against viral infections and maintaining cellular balance. Dysregulation of this pathway has been implicated in various inflammatory diseases, including arthritis, making it a target for potential therapeutic interventions. Understanding the intricate molecular signaling network of cGAS-STING in these arthritis forms offers potential avenues for targeted therapies. Addressing these challenges through improved early detection, comprehensive management, and interventions targeting the cGAS-STING pathway is crucial for alleviating the impact of OA and RA on individuals and healthcare systems. This review offers an up-to-date comprehension of the cGAS-STING pathway's role in the development and therapeutic approaches for these arthritis types.
Topics: Humans; Nucleotidyltransferases; Membrane Proteins; Arthritis, Rheumatoid; Signal Transduction; Osteoarthritis; Animals
PubMed: 38765007
DOI: 10.3389/fimmu.2024.1384372 -
BMC Musculoskeletal Disorders Apr 2021Arthritis, regardless of cause, has significant physical, social and psychological impacts on patients. We aimed to identify the non-healthcare needs perceived by... (Review)
Review
BACKGROUND
Arthritis, regardless of cause, has significant physical, social and psychological impacts on patients. We aimed to identify the non-healthcare needs perceived by patients with inflammatory arthritis (IA) and osteoarthritis (OA), and to determine if these differ.
METHODS
We electronically searched MEDLINE, PsycINFO, EMBASE and CINAHL (1990-2020) systematically to identify non-healthcare-related needs of people with IA or OA. All citations were screened and quality appraised by two reviewers. Data was extracted by a single reviewer.
RESULTS
The search identified 7853 citations, with 31 studies included (12 for OA, 20 for IA). Six areas of need emerged and these were similar in both group These were: 1) Assistance with activities of daily living especially related to a lack of independence; 2) Social connectedness: need for social participation; 3) Financial security: worry about financial security and increased costs of health-seeking behaviours; 4) Occupational needs: desire to continue work for financial and social reasons, facilitated by flexibility of workplace conditions/environment; 5) Exercise and leisure: including limitation due to pain; 6) Transportation: limitations in ability to drive and take public transport due to mobility concerns. Many areas of need were linked; e.g. loss of employment and requiring support from family was associated with a sense of "failure" and loss of identity, as social isolation.
CONCLUSIONS
This review highlights the pervasive impact of arthritis on peoples' lives, regardless of aetiology, albeit with a limited evidence base. Improved identification and targeting of non-healthcare needs of people with arthritis is likely to improve person-centred care.
Topics: Activities of Daily Living; Delivery of Health Care; Employment; Humans; Osteoarthritis; Workplace
PubMed: 33836697
DOI: 10.1186/s12891-021-04190-z -
Disability and Health Journal Jun 2022Growing concerns about opioid overprescribing, opioid use disorder (OUD), and overdose led to opioid misuse prevention practices that may impact the lives of people with...
BACKGROUND
Growing concerns about opioid overprescribing, opioid use disorder (OUD), and overdose led to opioid misuse prevention practices that may impact the lives of people with disability (PWD) and chronic pain.
OBJECTIVE
To investigate the experiences of providers and people with arthritis related disability with opioid prescribing and monitoring following release of the Centers for Disease Control and Prevention Guideline for prescribing opioids for chronic pain.
METHODS
We conducted semi-structured interviews with 24 specialists and primary care providers and 24PWD. Providers were required to prescribe opioids to people with arthritis-disability. PWD were required to have arthritis-disability causing chronic pain and to be on chronic opioid therapy (COT) or have been treated for OUD. We used a deductive and inductive analytic approach to develop themes.
RESULTS
Providers recommended COT when other pain treatment options were exhausted or unaffordable. PWD reported their provider recently reduced their opioid treatment intensity and frequent visits were required. PWD didn't remember or recalled hearing limited information about opioid risks and benefits. Some PWD were unsure if the benefits of opioids outweighed the risks. Few providers identified chronic pain care considerations specific to PWD.
CONCLUSIONS
Our findings facilitate a better understanding of the challenges faced by PWD living with chronic pain and their providers related to COT. The findings show the need for better informing PWD about the risks and benefits of opioids prior to initiating treatment, training on person-centered care tailored to PWD's unique needs and improved coverage of nonopioid treatments for chronic pain.
Topics: Analgesics, Opioid; Arthritis; Chronic Pain; Disabled Persons; Humans; Opioid-Related Disorders; Practice Patterns, Physicians'
PubMed: 35422404
DOI: 10.1016/j.dhjo.2022.101294 -
International Journal of Molecular... Jan 2020Arthritis, including osteoarthritis (OA) and rheumatoid arthritis (RA), is the leading cause of years lived with disability (YLD) worldwide. Although pain is the... (Review)
Review
Arthritis, including osteoarthritis (OA) and rheumatoid arthritis (RA), is the leading cause of years lived with disability (YLD) worldwide. Although pain is the cardinal symptom of arthritis, which is directly related to function and quality of life, the elucidation of the mechanism underlying the pathogenesis of pain in arthritis has lagged behind other areas, such as inflammation control and regulation of autoimmunity. The lack of therapeutics for optimal pain management is partially responsible for the current epidemic of opioid and narcotic abuse. Recent advances in animal experimentation and molecular biology have led to significant progress in our understanding of arthritis pain. Despite the inherent problems in the extrapolation of data gained from animal pain studies to arthritis in human patients, the critical assessment of molecular mediators and translational studies would help to define the relevance of novel therapeutic targets for the treatment of arthritis pain. This review discusses biological and molecular mechanisms underlying the pathogenesis of arthritis pain determined in animal models of OA and RA, along with the methodologies used.
Topics: Animals; Arthritis; Arthritis, Rheumatoid; Biomarkers; Disease Models, Animal; Disease Susceptibility; Osteoarthritis; Pain; Pain Management; Pain Measurement
PubMed: 31947680
DOI: 10.3390/ijms21020533 -
Frontiers in Immunology 2022T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in...
T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides.
Topics: Humans; Autoantibodies; Arthritis, Rheumatoid; T-Lymphocytes, Helper-Inducer; Arthritis, Juvenile; B-Lymphocytes
PubMed: 36685593
DOI: 10.3389/fimmu.2022.1068399 -
Arthritis Care & Research Sep 2019Exposure to inhaled mineral dust, in particular silica, is associated with increased odds of rheumatoid arthritis (RA) and other autoimmune diseases. We studied the...
OBJECTIVE
Exposure to inhaled mineral dust, in particular silica, is associated with increased odds of rheumatoid arthritis (RA) and other autoimmune diseases. We studied the association of RA with work-related coal and silica exposure in the Appalachian region of the US.
METHODS
We carried out a random-digit dialed telephone survey in selected counties in Appalachia that had elevated coal workers' pneumoconiosis mortality. Our study cohort included men ages ≥50 with any employment history, and we assessed exposure to coal mining employment, other work-related dust, and ergonomic factors. We ascertained self-reported physician diagnosis of any arthritis and of RA with glucocorticoid treatment. We used multivariable logistic regression analysis to estimate the odds ratios (ORs) and associated population attributable fraction (PAF) estimates.
RESULTS
Among the 973 men who met study entry criteria (mean ± SD ages 66 ± 10 years; 54% ever smokers), 266 (27%) reported coal mining work and 189 (19%) reported other work-related silica exposure. There were 517 men (53%), who reported any arthritis and 112 (12%) whose disease met the study definition of RA. Adjusting for covariates, coal mining was associated with elevated odds of RA (OR 3.6 [95% confidence interval (95% CI) 2.1-6.2]), which accounted for a PAF of 33% (95% CI 26-40%) of the men studied. For any arthritis, the coal mining-associated OR was 2.3 (95% CI 1.6-3.2), with an associated PAF of 20% (95% CI 14-25%).
CONCLUSION
In this population of older males living in a coal mining region, we estimated that 20% of arthritis and 33% of RA may be attributable to coal mining work.
Topics: Age Factors; Aged; Appalachian Region; Arthritis; Arthritis, Rheumatoid; Coal Mining; Humans; Male; Middle Aged; Occupational Diseases; Occupational Exposure; Odds Ratio; Prevalence; Risk Assessment; Silicon Dioxide; Surveys and Questionnaires; United States
PubMed: 30875457
DOI: 10.1002/acr.23874 -
Frontiers in Immunology 2023Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)-a rare...
Mutations in nucleotide binding oligomerization domain containing 2 receptor (NOD2) are associated with Blau syndrome (also known as early-onset sarcoidosis)-a rare autosomal dominant, chronic granulomatous disease that typically presents before 5 years of age. Blau syndrome is characterized by the clinical triad of arthritis, granulomatous dermatitis, and recurrent uveitis. Here, we report a case of NOD2-mutation-associated early-onset sarcoidosis in which a combination of methotrexate and hydroxychloroquine was used to achieve improvement in arthritis, granulomatous dermatitis, and uveitis. A 13-month-old boy presented with a sudden-onset cutaneous eruption affecting the face, trunk, and extremities that initially mimicked papular atopic dermatitis but progressively worsened despite topical steroid therapy. The patient had no other known medical comorbidities or abnormalities except for heterochromia of the right eye. However, prior to presentation to dermatology, the patient began experiencing frequent falls, conjunctival injection, and apparent eye and joint pain. Skin biopsy from the right shoulder demonstrated rounded aggregates of epithelioid histiocytes and multinucleated giant cells without a significant lymphocytic component ("naked granulomas"), consistent with sarcoidal granulomatous dermatitis. Given the concern for Blau syndrome, the patient was sent for evaluation by ophthalmology and was found to have bilateral subconjunctival nodules. Our patient underwent genetic testing and was found to have a mutation in codon 1000 C > T (protein R334W) in the NOD2 gene. The patient responded to oral prednisolone 2 mg/kg/day for 8 weeks, but quickly relapsed, requiring a second 8-week course with taper upon starting methotrexate 7.5 mg subcutaneously weekly with 1 mg folic acid orally daily. After 8 weeks on methotrexate, due to persistent arthritis, conjunctival injection, and pruritus, and in consultation with rheumatology, the patient was started on hydroxychloroquine 75 mg orally daily along with continuation of 7.5 mg methotrexate subcutaneously weekly for 8 weeks, achieving significant reduction in arthritis, pruritus, and uveitis. After 8 weeks of this combination therapy, due to concerns of long-term macular toxicity, hydroxychloroquine was discontinued in favor of continuing methotrexate alone. The patient has remained free of significant side effects and stable with good disease control on 7.5 mg methotrexate weekly injected subcutaneously.
Topics: Humans; Infant; Male; Arthritis; Dermatitis; Granuloma; Hydroxychloroquine; Methotrexate; Mutation; Nod2 Signaling Adaptor Protein; Pruritus; Uveitis
PubMed: 37868966
DOI: 10.3389/fimmu.2023.1279329 -
Nature Reviews. Rheumatology Jan 2018Early treatment is associated with improved outcomes in patients with rheumatoid arthritis (RA), suggesting that a 'window of opportunity', in which the disease is most... (Review)
Review
Early treatment is associated with improved outcomes in patients with rheumatoid arthritis (RA), suggesting that a 'window of opportunity', in which the disease is most susceptible to disease-modifying treatment, exists. Autoantibodies and markers of systemic inflammation can be present long before clinical arthritis, and maturation of the immune response seems to coincide with the development of RA. The pre-arthritis phase associated with symptoms such as as joint pain without clinical arthritis (athralgia) is now hypothesized to fall within the aforementioned window of opportunity. Consequently, disease modulation in this phase might prevent the occurrence of clinically apparent arthritis, which would result in a persistent disease course if untreated. Several ongoing proof-of-concept trials are now testing this hypothesis. This Review highlights the importance of adequate risk prediction for the correct design, execution and interpretation of results of these prevention trials, as well as considerations when translating these findings into clinical practice. The patients' perspectives are discussed, and the accuracy with which RA development can be predicted in patients presenting with arthralgia is evaluated. Currently, the best starting position for preventive studies is proposed to be the inclusion of patients with an increased risk of RA, such as those identified as fulfilling the EULAR definition of 'arthralgia suspicious for progression to RA'.
Topics: Animals; Anti-Citrullinated Protein Antibodies; Arthralgia; Arthritis; Arthritis, Rheumatoid; Autoantibodies; Autoimmunity; Biomarkers; Disease Progression; Humans; Immunosuppressive Agents; Inflammation; Mice; Predictive Value of Tests; Risk Factors; Secondary Prevention
PubMed: 29118439
DOI: 10.1038/nrrheum.2017.185 -
Revista Da Associacao Medica Brasileira... Jan 2018Chikungunya (CHIK) is a tropical arbovirus, transmitted by the female mosquito Aedes aegypti and Aedes albopictus. In Brazil, there have been cases reported since 2014.... (Review)
Review
INTRODUCTION
Chikungunya (CHIK) is a tropical arbovirus, transmitted by the female mosquito Aedes aegypti and Aedes albopictus. In Brazil, there have been cases reported since 2014. The initial manifestations of this virus are sudden onset high fever, headache, chills, rashes, myalgia and intense joint pain. Usually, CHIK presents the acute and chronic phases, the latter characterized by bilateral polyarthralgia, which can last for months or even years. During this period, autoimmune diseases can be triggered, making the picture even more complicated.
METHOD
A systematic review was performed on the PubMed and Scielo databases in January 2017. Clinical trials, cohorts, case-control and case reports were included in the study. Expert opinions, societal consensuses and literary reviews were exclusion criteria. Studies were conducted in English, Spanish and Portuguese. The studies were descriptively analyzed and the data was grouped according to methodological similarity.
RESULTS
Twenty-four (24) articles were selected and, in compliance with the inclusion and exclusion criteria, 18 were eliminated, with six studies remaining in the present review: five clinical trials and one case report.
CONCLUSION
When the manifestations of CHIK become chronic and, the longer they last, more complications arise. Polyarthralgia can be immaterial, distancing individuals from their daily-life activities. Anti-inflammatory drugs (either steroid or not), in addition to immunosuppressants, homeopathy and physiotherapy are measures of treatment that, according to the literature, have been successful in relieving or extinguishing symptoms. However, it is fundamental that studies of CHIK treatment be further developed.
Topics: Animals; Arthritis; Arthritis, Infectious; Chikungunya Fever; Chikungunya virus; Humans
PubMed: 29561944
DOI: 10.1590/1806-9282.64.01.63 -
Turkish Journal of Medical Sciences 2023Craniocervical junction (CCJ) can be involved in inflammatory arthritis. We aimed to define types of CCJ involvement in rheumatoid arthritis (RA), spondyloarthritis...
BACKGROUND/AIM
Craniocervical junction (CCJ) can be involved in inflammatory arthritis. We aimed to define types of CCJ involvement in rheumatoid arthritis (RA), spondyloarthritis (SpA), and psoriatic arthritis (PsA) and compare them with patients without inflammatory arthritides.
MATERIALS AND METHODS
In this retrospective analysis, cervical CT or MRIs of patients with RA, SpA, or PsA, taken for any reason between 2010 and 2020, according to ICD-10 codes, were scanned. Demographic data of the patients were recorded. CCJ involvements (atlantoaxial, vertical, or subaxial subluxation, odontoid process involvement) were reevaluated by an experienced radiologist. The control group consisted of consecutive patients without inflammatory arthritis.
RESULTS
Exactly 459 patients (204 RA, 200 SpA, and 55 PsA) and 78 patients in the control group were included in the study. CCJ involvement was detected in 101 (49.5%) RA, 53 (26.5%) SpA, 10 (18.2%) PsA, and 4 patients (5.1%) in the control group (p < 0.001). The odontoid process was one of the main targets, especially in RA patients (69 (33.8%)), which was significantly higher than in the SpA, PsA, and control groups. Although vertical subluxation (VS) was numerically higher in the RA and SpA groups compared to the control group, VS-related brainstem compression was relatively uncommon: 6 (2.9%) in RA, 1 (0.5%) in AS, and none in the PsA and control groups.
CONCLUSION
CCJ involvement can often be detected in patients with inflammatory arthritis, especially in RA and SpA patients. The odontoid process is the main target of inflammation.
Topics: Humans; Female; Male; Middle Aged; Retrospective Studies; Arthritis, Rheumatoid; Adult; Magnetic Resonance Imaging; Tomography, X-Ray Computed; Spondylarthritis; Aged; Arthritis, Psoriatic; Atlanto-Axial Joint; Cervical Vertebrae; Odontoid Process
PubMed: 38813511
DOI: 10.55730/1300-0144.5740