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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 -
The Journal of the American Academy of... Feb 2016End-stage arthritis of the tibiotalar joint is disabling and causes substantial functional impairment. Most often it is the residual effect of a previous traumatic... (Review)
Review
End-stage arthritis of the tibiotalar joint is disabling and causes substantial functional impairment. Most often it is the residual effect of a previous traumatic injury. Nonsurgical treatment of end-stage arthritis of the ankle includes bracing, shoe-wear modifications, and selective joint injections. For patients who fail to respond to nonsurgical modalities, the two primary treatment options are arthroplasty and arthrodesis. Each has its proponents. Although no ideal treatment of ankle arthritis exists, high-quality studies can help guide treatment in patients of varying demographics. Inherent risks are linked with each treatment option, but those of greatest concern are early implant loosening that requires revision following arthroplasty and the acceleration of adjacent joint degeneration associated with arthrodesis.
Topics: Ankle Joint; Arthritis; Arthrodesis; Arthroplasty; Arthroscopy; Humans
PubMed: 26660651
DOI: 10.5435/JAAOS-D-15-00354 -
Expert Review of Clinical Immunology Jul 2021Psoriatic arthritis (PsA) and spondyloarthritis (SpA) are inflammatory arthritides associated with progressive damage, deformity and morbidity. Janus kinase (JAK)... (Review)
Review
INTRODUCTION
Psoriatic arthritis (PsA) and spondyloarthritis (SpA) are inflammatory arthritides associated with progressive damage, deformity and morbidity. Janus kinase (JAK) inhibitors block JAKs, cytoplasmic protein tyrosine kinases important in signal transduction and immune processes that are currently being studied as synthetic disease modifying anti-rheumatic drugs (tsDMARDs) in psoriatic arthritis and spondyloarthritis.
AREAS COVERED
This review evaluates published phase 2 and 3 clinical trial data for JAK kinase inhibitors for psoriatic arthritis and spondyloarthritis. A literature search using PubMed was conducted using the following keywords: 'psoriatic arthritis', 'ankylosing spondylitis', 'axial spondyloarthritis', 'non-radiographic axial spondyloarthritis', 'tofacitinib', 'baricitinib', 'filgotinib' and 'upadacitinib'. Mechanism of action, phase 2 and 3 clinical trial data, including efficacy and safety, are discussed.
EXPERT OPINION
JAK inhibitors are important orally administered agents conferring different degrees of selectivity toward JAK1, JAK2, and JAK3 which may have implications on efficacy and safety in PsA and SpA. Phase 2 and 3 clinical trials in PsA for tofacitinib and upadacitinib and phase 2 for filgotinib confirmed efficacy comparable to biologic DMARDs. In SpA, phase 2 and 2/3 studies confirmed significant efficacy of tofacitinib, filgotinib and upadacitinib compared to placebo. Safety was comparable to clinical trial, long-term extension, and registry data for rheumatoid arthritis.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Arthritis, Rheumatoid; Axial Spondyloarthritis; Humans; Janus Kinase Inhibitors
PubMed: 33944642
DOI: 10.1080/1744666X.2021.1925541 -
Nature Reviews. Rheumatology Feb 2017The past two decades have witnessed major advancements in the clinical management of inflammatory arthritis, with new treatment strategies in some cases providing a... (Review)
Review
The past two decades have witnessed major advancements in the clinical management of inflammatory arthritis, with new treatment strategies in some cases providing a marked improvement in patient outcomes. However, it is widely accepted that current strategies do not provide the 'total therapeutic solution', in view of the proportion of patients who do not respond to therapy, the important incidence of adverse effects and the development of an immune response against antibodies or fusion proteins used therapeutically. Moreover, although some therapeutic approaches can effectively bring about an end to inflammation, mechanisms to promote the recovery and/or repair of damage are required. Harnessing the concepts and mechanisms of the resolution of inflammation is a new approach to the treatment of inflammatory pathologies; this approach could help address the unmet need for new therapeutic approaches that not only control but also revert the course of inflammatory rheumatic diseases.
Topics: Arthritis; Humans; Immunotherapy; Inflammation
PubMed: 28053331
DOI: 10.1038/nrrheum.2016.193 -
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 -
Rheumatic Diseases Clinics of North... Aug 2018The prevalence of gout increases with age. After the serum concentration of urate exceeds the saturation or solubility point, it deposits in and around the joints.... (Review)
Review
The prevalence of gout increases with age. After the serum concentration of urate exceeds the saturation or solubility point, it deposits in and around the joints. Presentation in the elderly is often atypical and challenging to diagnose. Treatment depends on disease stage, health status, and comorbidities. Elderly patients often have several confounding issues; treatment decisions can be complicated and therapeutic options limited. To prevent recurrence, serum concentration of urate should be maintained well below the saturation threshold of 6.8 mg/dL, leading to dissolution of urate deposits and preventing recurrence.
Topics: Aged; Comorbidity; Geriatrics; Gout; Humans; Patient Care Management; Prevalence
PubMed: 30001788
DOI: 10.1016/j.rdc.2018.03.007 -
Translational Research : the Journal of... Dec 2019RNA interference (RNAi) is a cellular mechanism for post-transcriptional gene regulation mediated by small interfering RNA (siRNA) and microRNA. siRNA-based therapy... (Review)
Review
RNA interference (RNAi) is a cellular mechanism for post-transcriptional gene regulation mediated by small interfering RNA (siRNA) and microRNA. siRNA-based therapy holds significant promise for the treatment of a wide-range of arthritic diseases. siRNA selectively suppresses the expression of a gene product and can thus achieve the specificity that is lacking in small molecule inhibitors. The potential use of siRNA-based therapy in arthritis, however, has not progressed to clinical trials despite ample evidence for efficacy in preclinical studies. One of the main challenges to clinical translation is the lack of a suitable delivery vehicle to efficiently and safely access diverse pathologies. Moreover, the ideal targets in treatment of arthritides remain elusive given the complexity and heterogeneity of these disease pathogeneses. Herein, we review recent preclinical studies that use RNAi-based drug delivery systems to mitigate inflammation in models of rheumatoid arthritis and osteoarthritis. We discuss a self-assembling peptide-based nanostructure that demonstrates the potential of overcoming many of the critical barriers preventing the translation of this technology to the clinic.
Topics: Animals; Arthritis; Cell Engineering; Gene Transfer Techniques; Humans; Inflammation; RNA Interference; Signal Transduction
PubMed: 31351032
DOI: 10.1016/j.trsl.2019.07.002 -
The Journal of Knee Surgery Oct 2021This review investigated the potential value of computed tomography (CT) scans for the evaluation and management of knee arthritis and arthroplasty. Specifically, we... (Review)
Review
This review investigated the potential value of computed tomography (CT) scans for the evaluation and management of knee arthritis and arthroplasty. Specifically, we evaluated the following: (1) assessment of arthritis within knee compartments, (2) patellofemoral joint assessment, (3) implant sizing prediction, (4) component alignment, (5) soft-tissue protection, and (6) potential concerns with radiation exposure. To compare if CT or X-ray imaging is more accurate and clinically relevant, a search was performed using Boolean search operators and terms: "CT," "radiograph," "joint alignment," "knee," and "arthroplasty," which yielded 661 results. Studies were evaluated based on (1) assessment of arthritis within knee compartments, (2) patellofemoral joint assessment, (3) implant sizing prediction, (4) component alignment, (5) soft-tissue protection, and (6) potential concerns with radiation exposure. Correlative and comparative analyses of imaging modalities to pre-, intra-, and postoperative clinical and patient-related factors were performed for the 63 included studies. CT scans were found to better detect medial and lateral arthritic changes, bony deformities, subchondral cysts, and cartilage losses. CT scans were shown to 99% accurately predict prosthetic sizes preoperatively. CT scans can also help better visualize surrounding anatomy, such as the posterior cruciate ligament, and have therefore been linked to better soft tissue protection during total knee arthroplasty. Although radiation is a potential concern, newer imaging protocols have comparable exposure to plain radiographs. Compared with plain radiographs, CT scans were found to be more accurate and provide more clinically relevant data. Therefore, the authors recommend the use of CT for the evaluation of certain patients with arthritis and for preoperative planning for knee arthroplasty.
Topics: Arthritis; Arthroplasty, Replacement, Knee; Humans; Knee Joint; Knee Prosthesis; Osteoarthritis, Knee; Posterior Cruciate Ligament; Tomography, X-Ray Computed
PubMed: 32268407
DOI: 10.1055/s-0040-1708041 -
Current Rheumatology Reports Mar 2017The involvement of chemokines and their receptors in the genesis and perpetuation of rheumatoid arthritis, spondyloarthritis, and osteoarthritis has been clearly... (Review)
Review
PURPOSE OF REVIEW
The involvement of chemokines and their receptors in the genesis and perpetuation of rheumatoid arthritis, spondyloarthritis, and osteoarthritis has been clearly recognized for a long time. Nevertheless, the complexity of their contribution to these diseases is now becoming evident and this review focuses on published evidence on their mechanism of action.
RECENT FINDINGS
Studies performed on patients and in vivo models have identified a number of chemokine-mediated pathways involved in various aspects of arthritogenic processes. Chemokines promote leukocyte infiltration and activation, angiogenesis, osteoclast differentiation, and synoviocyte proliferation and activation and participate to the generation of pain by regulating the release of neurotransmitters. A number of chemokines are expressed in a timely controlled fashion in the joint during arthropathies, regulating all the aspects of inflammation as well as the equilibrium between damage and repair and between relief and pain. Thus, the targeting of specific chemokine/chemokine receptor interactions is considered a promising tool for therapeutic intervention.
Topics: Arthritis; Arthritis, Rheumatoid; Biological Products; Chemokines; Humans; Molecular Targeted Therapy; Osteoarthritis; Pain; Receptors, Chemokine; Spondylarthritis
PubMed: 28265846
DOI: 10.1007/s11926-017-0635-y -
Journal of Translational Medicine Aug 2016Only recently, the scientific community gained insights on the importance of the intestinal resident flora for the host's health and disease. Gut microbiota in fact... (Review)
Review
BACKGROUND
Only recently, the scientific community gained insights on the importance of the intestinal resident flora for the host's health and disease. Gut microbiota in fact plays a crucial role in modulating innate and acquired immune responses and thus interferes with the fragile balance inflammation versus tolerance.
MAIN BODY
Correlations between gut bacteria composition and the severity of inflammation have been studied in inflammatory bowel diseases. More recently similar alterations in the gut microbiota have been reported in patients with spondyloarthritis, whereas in rheumatoid arthritis an accumulating body of evidence evokes a pathogenic role for the altered oral microbiota in disease development and course. In the context of dysbiosis it is also important to remember that different environmental factors like stress, smoke and dietary components can induce strong bacterial changes and consequent exposure of the intestinal epithelium to a variety of different metabolites, many of which have an unknown function. In this perspective, and in complex disorders like autoimmune diseases, not only the genetic makeup, sex and immunologic context of the individual but also the structure of his microbial community should be taken into account.
CONCLUSIONS
Here we provide a review of the role of the microbiota in the onset, severity and progression of chronic inflammatory arthritis as well as its impact on the therapeutic management of these patients. Furthermore we point-out the complex interwoven link between gut-joint-brain and immune system by reviewing the most recent data on the literature on the importance of environmental factors such as diet, smoke and stress.
Topics: Animals; Arthritis; Chronic Disease; Environment; Humans; Inflammation; Microbiota
PubMed: 27492386
DOI: 10.1186/s12967-016-0989-3