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Nottingham, United Kingdom

Courtney P.,Nottingham City Hospital | Doherty M.,Academic Rheumatology
Best Practice and Research: Clinical Rheumatology

Joint aspiration/injection and synovial fluid (SF) analysis are both invaluable procedures for the diagnosis and treatment of joint disease. This chapter addresses (1) the indications, technical principles, expected benefits and risks of aspiration and injection of intra-articular corticosteroid and (2) practical aspects relating to SF analysis, especially in relation to crystal identification. Intra-articular injection of long-acting insoluble corticosteroids is a well-established procedure that produces rapid pain relief and resolution of inflammation in most injected joints. The knee is the most common site to require aspiration although any non-axial joint is accessible for obtaining SF. The technique involves only knowledge of basic anatomy and should not be unduly painful for the patient. Provided sterile equipment and a sensible, aseptic approach are used, it is very safe. Analysis of aspirated SF is helpful in the differential diagnosis of arthritis and is the definitive method for diagnosis of septic arthritis and crystal arthritis. The gross appearance of SF can provide useful diagnostic information in terms of the degree of joint inflammation and presence of haemarthrosis. Microbiological studies of SF are the key to the confirmation of infectious conditions. Increasing joint inflammation associates with increased SF volume, reduced viscosity, increasing turbidity and cell count and increasing ratio of polymorphonuclear:mononuclear cells, but such changes are non-specific and must be interpreted in the clinical setting. However, detection of SF monosodium urate and calcium pyrophosphate dihydrate crystals, even from un-inflamed joints during intercritical periods, allows a precise diagnosis of gout and calcium pyrophosphate crystal-related arthritis. © 2013 Elsevier Ltd. All rights reserved. Source

Fernandes G.S.,Academic Rheumatology | Valdes A.M.,Academic Rheumatology
European Journal of Clinical Investigation

Background: Osteoarthritis (OA) and cardiovascular disease (CVD) are the two most prevalent conditions in the population aged over 70 in developed countries. Both conditions share common risk factors, in particular age and body mass index. However, the very high level of co-occurrence of both diseases cannot be accounted by common risk factors alone. Materials and Methods: We reviewed the recent literature published in English in PubMed for articles relating to osteoarthritis and cardiovascular disease. Results: On the one hand, the disability caused by OA increases the risk of CVD and in particular of ischemic events and mortality beyond what can be explained by known common risk factors, such as ageing and obesity. Moreover, the presence of OA has a synergistic effect on CVD symptoms considerably worsening them. On the other hand, at least in women, there appears to be a common pathogenic mechanism underlying atherosclerosis (but not hypertension) and actual joint damage. Conclusion: There are some possible molecular mechanisms underlying both diseases, in particular relating to low grade inflammation and female hormones. However, the data available to date also indicate that OA may be considered as an indirect cause of CVD by increasing walking disability and the use of analgesic medication such as NSAIDs. We discuss future directions that need to be taken to address these highly prevalent, costly and disabling morbidities. © 2015 Stichting European Society for Clinical Investigation Journal Foundation. Source

Valdes A.M.,Academic Rheumatology | Suokas A.K.,Academic Rheumatology | Suokas A.K.,University of Nottingham | Doherty S.A.,Academic Rheumatology | And 2 more authors.
Seminars in Arthritis and Rheumatism

Objective: Neuropathic pain (NP) mechanisms contribute to the pain experience in osteoarthritis (OA). We aimed to characterise the factors that contribute to NP-like symptoms in knee OA patients. Patients and methods: A total of 139 patients with knee OA were recruited from secondary care, and completed a nurse- administered PainDetect questionnaire (PD-Q), a visual analogue scale (VAS) for pain intensity, and the Western Ontario MacMaster questionnaire (WOMAC). Cases with any previous history of total joint replacement were excluded. Results: Almost 75% of patients had non-zero PD-Q scores, and 34% had PD-Q scores corresponding to possible NP. No association was seen between PD-Q scores and duration of symptoms, gender, and radiographic severity. Possible NP was strongly associated (p < 1 × 10-3) with worse quality of life scores, worse sleep scores, higher pain intensity, worse WOMAC pain, stiffness and function scores. A history of previous knee surgery (arthroscopy, ligament repair or meniscectomy) was strongly associated with possible NP (odds ratio [OR] = 6.86; 95% CI = 1.78-26.43; p < 0.005). This association remained statistically significant after adjustment for pain intensity (OR = 6.37; 95% CI = 1.55-26.11; p < 0.010) whereas an association between history of knee surgery and the other measures of pain was found to be mediated by PD-Q scores. Conclusions: NP-like symptoms are highly prevalent in patients with clinically severe painful OA and are a significant contributor to decreased quality of life and higher pain intensity. The cross-sectional association with previous history of knee surgery suggests that some of the NP-like symptoms may result from nerve damage. © 2014 The Authors. Source

Panoutsopoulou K.,Wellcome Trust Sanger Institute | Metrustry S.,Kings College London | Doherty S.A.,Academic Rheumatology | Laslett L.L.,Menzies Research Institute | And 13 more authors.
Annals of the Rheumatic Diseases

Objective: Variation in the fat mass and obesity-associated (FTO) gene influences susceptibility to obesity. A variant in the FTO gene has been implicated in genetic risk to osteoarthritis (OA). We examined the role of the FTO polymorphism rs8044769 in risk of knee and hip OA in cases and controls incorporating body mass index (BMI) information. Methods: 5409 knee OA patients, 4355 hip OA patients and up to 5362 healthy controls from 7 independent cohorts from the UK and Australia were genotyped for rs8044769. The association of the FTO variant with OA was investigated in case/control analyses with and without BMI adjustment and in analyses matched for BMI category. A mendelian randomisation approach was employed using the FTO variant as the instrumental variable to evaluate the role of overweight on OA. Results: In the meta-analysis of all overweight (BMI≥25) samples versus normal-weight controls irrespective of OA status the association of rs8044769 with overweight is highly significant (OR[CIs] for allele G=1.14 [01.08 to 1.19], p=7.5×10-7). A significant association with knee OA is present in the analysis without BMI adjustment (OR[CIs]=1.08[1.02 to 1.14], p=0.009) but the signal fully attenuates after BMI adjustment (OR[CIs]=0.99[0.93 to 1.05], p=0.666). We observe no evidence for association in the BMI-matched meta-analyses. Using mendelian randomisation approaches we confirm the causal role of overweight on OA. Conclusions: Our data highlight the contribution of genetic risk to overweight in defining risk to OA but the association is exclusively mediated by the effect on BMI. This is consistent with what is known of the biology of the FTO gene and supports the causative role of high BMI in OA. © 2013 BMJ Publishing Group Ltd & European League Against Rheumatism. Source

Kerkhof H.J.M.,Erasmus Medical Center | Doherty M.,Academic Rheumatology | Arden N.K.,University of Southampton | Arden N.K.,University of Oxford | And 34 more authors.
Osteoarthritis and Cartilage

Objective: To clarify the role of common genetic variation in the Interleukin-1β (IL1B) and Interleukin-1R antagonist (IL1RN) genes on risk of knee and hip osteoarthritis (OA) and severity of knee OA by means of large-scale meta-analyses. Methods: We searched PubMed for articles assessing the role of IL1B and IL1RN polymorphisms/haplotypes on the risk of hip and/or knee OA. Novel data were included from eight unpublished studies. Meta-analyses were performed using fixed- and random-effects models with a total of 3595 hip OA and 5013 knee OA cases, and 6559 and 9132 controls respectively. The role of ILRN haplotypes on radiographic severity of knee OA was tested in 1918 cases with Kellgren-Lawrence (K/L) 1 or 2 compared to 199 cases with K/L 3 or 4. Results: The meta-analysis of six published studies retrieved from the literature search and eight unpublished studies showed no evidence of association between common genetic variation in the IL1B or IL1RN genes and risk of hip OA or knee OA (P>0.05 for rs16944, rs1143634, rs419598 and haplotype C-G-C (rs1143634, rs16944 and rs419598) previously implicated in risk of hip OA). The C-T-A haplotype formed by rs419598, rs315952 and rs9005, previously implicated in radiographic severity of knee OA, was associated with reduced severity of knee OA (odds ratio (OR)=0.71 95%CI 0.56-0.91; P=0.006, I2=74%), and achieved borderline statistical significance in a random-effects model (OR=0.61 95%CI 0.35-1.06 P=0.08). Conclusion: Common genetic variation in the Interleukin-1 region is not associated with prevalence of hip or knee OA but our data suggest that IL1RN might have a role in severity of knee OA. © 2010 Osteoarthritis Research Society International. Source

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