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JCI Insight Mar 2019Inflammatory arthritis encompasses a set of common diseases characterized by immune-mediated attack on joint tissues. Most but not all affected patients manifest... (Review)
Review
Inflammatory arthritis encompasses a set of common diseases characterized by immune-mediated attack on joint tissues. Most but not all affected patients manifest circulating autoantibodies. Decades of study in human and animal arthritis have identified key roles for autoantibodies in immune complexes and through direct modulation of articular biology. However, joint inflammation can arise because of pathogenic T cells and other pathways that are antibody-independent. Here we review the evidence for these parallel tracks, in animal models and in humans, to explore the range of mechanisms engaged in the pathophysiology of arthritis and to highlight opportunities for targeted therapeutic intervention.
Topics: Animals; Antigen-Antibody Complex; Arthritis; Arthritis, Rheumatoid; Autoantibodies; Disease Models, Animal; Glycosylation; Humans; Immunoglobulin G; T-Lymphocytes
PubMed: 30843881
DOI: 10.1172/jci.insight.125278 -
Trends in Molecular Medicine Oct 2017Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including... (Review)
Review
Arthritis represents a family of complex joint pathologies responsible for the majority of musculoskeletal conditions. Nearly all diseases within this family, including osteoarthritis, rheumatoid arthritis, and juvenile idiopathic arthritis, are chronic conditions with few or no disease-modifying therapeutics available. Advances in genome engineering technology, most recently with CRISPR-Cas9, have revolutionized our ability to interrogate and validate genetic and epigenetic elements associated with chronic diseases such as arthritis. These technologies, together with cell reprogramming methods, including the use of induced pluripotent stem cells, provide a platform for human disease modeling. We summarize new evidence from genome-wide association studies and genomics that substantiates a genetic basis for arthritis pathogenesis. We also review the potential contributions of genome engineering in the development of new arthritis therapeutics.
Topics: Animals; Arthritis; CRISPR-Cas Systems; Gene Editing; Genome, Human; Genome-Wide Association Study; Humans; Precision Medicine
PubMed: 28887050
DOI: 10.1016/j.molmed.2017.08.002 -
RMD Open Feb 2024It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases... (Review)
Review
It is known that metabolic shifts and tissue remodelling precede the development of visible inflammation and structural organ damage in inflammatory rheumatic diseases such as the inflammatory arthritides. As such, visualising and measuring metabolic tissue activity could be useful to identify biomarkers of disease activity already in a very early phase. Recent advances in imaging have led to the development of so-called 'metabolic imaging' tools that can detect these changes in metabolism in an increasingly accurate manner and non-invasively.Nuclear imaging techniques such as F-D-glucose and fibroblast activation protein inhibitor-labelled positron emission tomography are increasingly used and have yielded impressing results in the visualisation (including whole-body staging) of inflammatory changes in both early and established arthritis. Furthermore, optical imaging-based bedside techniques such as multispectral optoacoustic tomography and fluorescence optical imaging are advancing our understanding of arthritis by identifying intra-articular metabolic changes that correlate with the onset of inflammation with high precision and without the need of ionising radiation.Metabolic imaging holds great potential for improving the management of patients with inflammatory arthritis by contributing to early disease interception and improving diagnostic accuracy, thereby paving the way for a more personalised approach to therapy strategies including preventive strategies. In this narrative review, we discuss state-of-the-art metabolic imaging methods used in the assessment of arthritis and inflammation, and we advocate for more extensive research endeavours to elucidate their full field of application in rheumatology.
Topics: Humans; Arthritis; Inflammation; Tomography, X-Ray Computed; Positron-Emission Tomography; Molecular Imaging
PubMed: 38341194
DOI: 10.1136/rmdopen-2023-003880 -
Rheumatology (Oxford, England) Mar 2024Biologic and targeted synthetic DMARDs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Among these, polyarticular JIA... (Review)
Review
Biologic and targeted synthetic DMARDs (b/tsDMARDs) have revolutionized the management of multiple rheumatic inflammatory conditions. Among these, polyarticular JIA (pJIA) and RA display similarities in terms of disease pathophysiology and response pattern to b/tsDMARDs. Indeed, the therapeutic efficacy of novel targeted drugs is variable among individual patients, in both RA and pJIA. The mechanisms and determinants of this heterogeneous response are diverse and complex, such that the development of true 'precision'-medicine strategies has proven highly challenging. In this review, we will discuss pathophysiological, patient-specific, drug-specific and environmental factors contributing to individual therapeutic response in pJIA in comparison with what is known in RA. Although some biomarkers have been identified that stratify with respect to the likelihood of either therapeutic response or non-response, few have proved useful in clinical practice so far, likely due to the complexity of treatment-response mechanisms. Consequently, we propose a pragmatic, patient-centred and clinically based approach, i.e. personalized instead of biomarker-based precision medicine in JIA.
Topics: Adult; Humans; Arthritis; Precision Medicine; Inflammation; Antirheumatic Agents
PubMed: 37725352
DOI: 10.1093/rheumatology/kead490 -
Clinical and Experimental Rheumatology 2016Musculoskeletal ultrasound (MSUS) has become a relevant part of rheumatology practice and research because it substantially allows us to optimize management of rheumatic... (Review)
Review
Musculoskeletal ultrasound (MSUS) has become a relevant part of rheumatology practice and research because it substantially allows us to optimize management of rheumatic and musculoskeletal diseases. This non-invasive imaging modality is a valuable point-of-care tool to accurately evaluate intra-articular and periarticular structures involved in a wide range of rheumatic diseases in adults and children. In addition, MSUS is an invaluable bedside aid for guiding accurate and safe musculoskeletal aspirations, injections and biopsies. This review provides an overview of the literature of the last year on the role of MSUS in arthritis.
Topics: Adult; Arthritis; Arthritis, Juvenile; Arthritis, Rheumatoid; Child; Echocardiography, Doppler; Humans; Musculoskeletal System; Osteoarthritis; Point-of-Care Systems; Point-of-Care Testing; Predictive Value of Tests; Prognosis; Reproducibility of Results; Severity of Illness Index
PubMed: 26892798
DOI: No ID Found -
Current Opinion in Rheumatology Sep 2015To review recent advances in the management strategies of polyarticular course juvenile idiopathic arthritis (JIA) and identify unanswered questions and avenues for... (Review)
Review
PURPOSE OF REVIEW
To review recent advances in the management strategies of polyarticular course juvenile idiopathic arthritis (JIA) and identify unanswered questions and avenues for further research.
RECENT FINDINGS
There is evidence for an early, aggressive, treat-to-target approach for polyarticular JIA. Clinical disease activity criteria have been recently defined and validated, including criteria for inactive disease and the juvenile arthritis disease activity score (JADAS). There is a need for evidence-based, defined disease targets and biomarkers for prediction of response, including targets for remission induction, and guidelines on drug withdrawal. Recent treatment consensus plans and guidelines are discussed and compared, including the 2015 NHS England clinical policy statement, the 2014 Childhood Arthritis and Rheumatology Research Alliance (CARRA) treatment plans and the 2011 American College of Rheumatology (ACR) guidelines. Evidence for new agents such as tocilizumab, rituximab, golimumab, ustekinumab, certolizumab and tofacitinib is promising: the recent clinical trials are summarized here. Stratification of individual patient treatment remains a goal, and predictive biomarkers have been shown to predict success in the withdrawal of methotrexate therapy.
SUMMARY
There are promising advances in the treatment approaches, disease activity criteria, clinical guidelines, pharmaceutical choices and individually stratified therapy choices for polyarticular JIA.
Topics: Antibodies, Monoclonal; Arthritis; Arthritis, Juvenile; Child; Enzyme Inhibitors; Guidelines as Topic; Humans; Treatment Outcome
PubMed: 26147756
DOI: 10.1097/BOR.0000000000000206 -
Arthritis & Rheumatology (Hoboken, N.J.) Jan 2018Current classification of primary inflammatory arthritis begins from the assumption that adults and children are different. No form of juvenile idiopathic arthritis... (Review)
Review
Current classification of primary inflammatory arthritis begins from the assumption that adults and children are different. No form of juvenile idiopathic arthritis bears the same name as an adult arthritis, a nomenclature gap with implications for both clinical care and research. Recent genetic data have raised questions regarding this adult/pediatric divide, revealing instead broad patterns that span the age spectrum. Combining these genetic patterns with demographic and clinical data, we propose that inflammatory arthritis can be segregated into 4 main clusters, largely irrespective of pediatric or adult onset: seropositive, seronegative (likely including a distinct group that usually begins in early childhood), spondyloarthritis, and systemic. Each of these broad clusters is internally heterogeneous, highlighting the need for further study to resolve etiologically discrete entities. Eliminating divisions based on arbitrary age cutoffs will enhance opportunities for collaboration between adult and pediatric rheumatologists, thereby helping to promote the understanding and treatment of arthritis.
Topics: Adult; Arthritis; Child; Child, Preschool; Diagnosis, Differential; Female; Genetic Predisposition to Disease; Humans; Male
PubMed: 29024575
DOI: 10.1002/art.40350 -
BioMed Research International 2022This study aimed to investigate the clinical characteristics and risk factors of fever in hospitalised patients with acute gouty arthritis (AGA).
OBJECTIVES
This study aimed to investigate the clinical characteristics and risk factors of fever in hospitalised patients with acute gouty arthritis (AGA).
METHODS
The clinical data of 167 hospitalised patients with AGA who met the inclusion criteria were retrospectively analysed. The demographic, clinical, and medication data of patients with and without fever were compared, and risk factors associated with fever were identified via logistic regression analysis.
RESULTS
The incidence of fever in hospitalised patients with AGA was 31.1%, with low-grade fever being predominant. Visual analogue scale (VAS) scores, white blood cell counts, neutrophil proportion, C-reactive protein (CRP) levels, and erythrocyte sedimentation rate (ESR) were higher in the fever group than in the non-fever group ( < 0.05 for all). In addition, the incidence rates of arthritis of single knee and polyarthritis were higher in patients in the fever group ( < 0.05). The proportion of patients who received betamethasone injection and combination therapy were higher in the fever group ( < 0.05). However, no significant differences were observed in age; sex; uric acid (UA) levels; and the incidence rate of hypertension, diabetes mellitus, cardiovascular disease, and renal function abnormalities between the two groups. Logistic regression analysis revealed that arthritis of single knee, polyarthritis, age of ≥65 years, CRP levels, and VAS scores were risk factors for concomitant AGA and fever. Among these factors, CRP levels and VAS scores were identified as independent risk factors (odds ratio [OR], 1.014 and 1.686, respectively; 95% confidence interval [CI], 1.004-1.025 and 1.115-2.549, respectively; < 0.05 for both).
CONCLUSION
The incidence of fever is high in hospitalised patients with AGA. Elderly patients, patients with arthritis affecting only one knee, and those with polyarthritis are predisposed to fever. In addition, the risk of developing fever increases with increasing VAS scores and CRP levels, and patients presenting with fever require enhanced anti-inflammatory and analgesic therapy.
Topics: Aged; Anti-Inflammatory Agents; Arthritis, Gouty; Betamethasone; Blood Sedimentation; C-Reactive Protein; Fever; Humans; Retrospective Studies; Risk Factors; Uric Acid
PubMed: 36225982
DOI: 10.1155/2022/8798838 -
Biological Chemistry Aug 2015Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the... (Review)
Review
Cathepsin S is a member of the cysteine cathepsin protease family. It is a lysosomal protease which can promote degradation of damaged or unwanted proteins in the endo-lysosomal pathway. Additionally, it has more specific roles such as MHC class II antigen presentation, where it is important in the degradation of the invariant chain. Unsurprisingly, mis-regulation has implicated cathepsin S in a variety of pathological processes including arthritis, cancer, and cardiovascular disease, where it becomes secreted and can act on extracellular substrates. In comparison to many other cysteine cathepsin family members, cathepsin S has uniquely restricted tissue expression and is more stable at a neutral pH, which supports its involvement and importance in localised disease microenvironments. In this review, we examine the known involvement of cathepsin S in disease, particularly with respect to recent work indicating its role in mediating pain, diabetes, and cystic fibrosis. We provide an overview of current literature with regards cathepsin S as a therapeutic target, as well as its role and potential as a predictive diagnostic and/or prognostic marker in these diseases.
Topics: Animals; Arthritis; Cardiovascular Diseases; Cathepsins; Humans; Hydrogen-Ion Concentration; Neoplasms; Prognosis
PubMed: 25872877
DOI: 10.1515/hsz-2015-0114 -
Rheumatology (Oxford, England) Jan 2021Ankle arthritis is a useful clinical signpost to differential diagnosis in rheumatic disease. Biomechanical features and differences in cartilage physiology compared... (Review)
Review
Ankle arthritis is a useful clinical signpost to differential diagnosis in rheumatic disease. Biomechanical features and differences in cartilage physiology compared with the knee may confer protection of the ankle joint from factors predisposing to certain arthritides. The prevalence of ankle OA is low, and usually secondary to trauma. Primary OA of the ankle should be investigated for underlying causes, especially haemochromatosis. New presentations of inflammatory mono/oligo arthritis involving the ankle are more likely due to undifferentiated arthritis or spondyloarthritis than RA, and gout over CPPD. The ankle is often involved in bacterial and viral causes of septic arthritis, especially bacterial, chikungunya and HIV infection, but rarely tuberculosis. Periarticular hind foot swelling can be confused with ankle arthritis, exemplified by Lofgren's syndrome and hypertrophic osteoarthropathy where swelling is due to subcutaneous oedema and osteitis respectively, and the ankle joint is rarely involved.
Topics: Ankle Joint; Arthritis; Diagnosis, Differential; Humans
PubMed: 33097958
DOI: 10.1093/rheumatology/keaa531