Claire Wenham

The role of synovitis in osteoarthritis.

Osteoarthritis (OA) is the most common form of arthritis worldwide yet there is still a lack of effective treatments for this condition. Increasingly, attention has turned to the role of the synovium in OA as it is now recognized, in part from the use of modern imaging techniques, that synovitis is both common and associated with pain. This offers a target for treatment, for both symptom and potential structure modification. In this review we discuss the evidence for histological and imaging-detected synovitis and the current role of antisynovial therapies in OA.

Imaging the painful osteoarthritic knee joint: what have we learned?

Pain in the peripheral joints is an increasingly common problem, resulting in significant patient disability and health-care expenditure. Osteoarthritis (OA), a syndrome of joint pain with associated structural changes, is the most prevalent joint disease, yet the etiology of pain in OA is not entirely clear. Traditional assessment of the structure–pain relationship in knee OA has relied on conventional radiography, which has several limitations, not least the discrepancy between symptoms and radiographic findings. MRI has the capability to visualize all the structures within the knee joint, and there is a growing body of work using MRI to examine the correlation between structural findings and symptoms. In large cohort studies, synovial hypertrophy, synovial effusions, and abnormalities in the subchondral bone have been associated with knee pain. Advances in our understanding of the etiology of pain in OA will assist in the identification of further targets for treatment of this common and painful disease.

A randomized, double-blind, placebo-controlled trial of low-dose oral prednisolone for treating painful hand osteoarthritis

OBJECTIVE Anti-inflammatory therapies are effective analgesics for OA. This study determined whether low-dose oral prednisolone (PNL) was an effective analgesic for hand OA. METHODS This was a randomized, double-blind, placebo-controlled trial of people with ACR criteria hand OA and baseline hand pain visual analogue scale (VAS) of >40/100 mm. Participants received 5 mg PNL or placebo daily for 4 weeks. Pain VAS, disease activity VAS, Australian/Canadian Hand Osteoarthritis Index and joint counts were performed at baseline, 4 and 12 weeks. Primary outcome was the change in hand pain VAS at 4 weeks. Analysis of covariance was used for analysis, controlling for baseline values. To explore potential mechanism of action of PNL, non-contrast 0.2 Tesla MRI was performed on the most painful hand at baseline and 4 weeks. RESULTS A total of 70 participants were recruited (57 women, mean age 61 years, mean baseline pain VAS 61.5 mm); 75% had more than one joint with definite MRI synovitis/effusion. At 4 weeks the adjusted mean reduction in pain VAS was 19.9 mm (PNL group) and 16.8 mm (placebo group) (P = 0.54). There were no statistically significant differences in VAS, Australian/Canadian Hand Osteoarthritis Index or joint counts between placebo and PNL groups at 4 or 12 weeks. A total of 20 participants in each group achieved an Outcome Measures in Rheumatology-Osteoarthritis Research Society International response. Baseline synovitis/effusion did not predict response to treatment. CONCLUSION This is the first randomized controlled trial of low-dose corticosteroid alone for painful hand OA, which demonstrated that short-term low-dose oral PNL is not an effective analgesic treatment for hand OA. TRIAL REGISTRATION International Standard Randomised Controlled Trial Number Register, www.isrctn.org, Trial number 99697616.

Autoantibodies to Posttranslationally Modified Type II Collagen as Potential Biomarkers for Rheumatoid Arthritis

OBJECTIVE Type II collagen (CII) posttranslationally modified by reactive oxygen species (ROS-CII) that are present in the inflamed joint is an autoantigen in rheumatoid arthritis (RA). The aim of this study was to investigate the potential use of anti-ROS-CII autoantibodies as a biomarker of RA. METHODS CII was exposed to oxidants that are present in the rheumatoid joint. Autoreactivity to ROS-CII was assessed by enzyme-linked immunosorbent assays in synovial fluid (SF) and serum samples obtained from patients during various phases of RA. This group included disease-modifying antirheumatic drug (DMARD)-naive patients with early RA (n = 85 serum samples) and patients with established RA (n = 80 serum and 50 SF samples), who were categorized as either DMARD responders or DMARD nonresponders. Control subjects included anti-citrullinated protein antibody (ACPA)-positive patients with arthralgia (n = 58 serum samples), patients with osteoarthritis (OA; n = 49 serum and 52 SF samples), and healthy individuals (n = 51 serum samples). RESULTS Reactivity to ROS-CII among DMARD-naive patients with early RA was significantly higher than that among patients with ACPA-positive arthralgia, patients with OA, and healthy control subjects (P < 0.0001), with 92.9% of serum samples from the patients with early RA binding to anti-ROS-II. There was no significant difference in anti-ROS-CII reactivity between ACPA-positive and ACPA-negative patients with RA, with 93.8% and 91.6% of serum samples, respectively, binding to ROS-CII. The sensitivity and specificity of binding to ROS-CII in patients with early RA were 92% and 98%, respectively. Among patients with established RA, serum reactivity in DMARD nonresponders was significantly higher than that in DMARD responders (P < 0.01); 58.3% of serum samples from nonresponders and 7.6% of serum samples from responders bound to HOCl-ROS, while the respective values for SF were 70% and 60%. In patients with longstanding RA, autoreactivity to ROS-CII changed longitudinally. CONCLUSION Autoantibodies to ROS-CII have the potential to become diagnostic biomarkers of RA.

Methotrexate for pain relief in knee osteoarthritis: an open-label study

OBJECTIVE Synovitis is very common in knee OA and associated with pain. This open-label study evaluated an anti-synovitis therapy, MTX, for pain relief in knee OA. METHODS Inclusion criteria included pain visual analogue scale (VAS) >40/100 mm, ACR clinical criteria for knee OA and intolerance/inefficacy of NSAID and opioids. US at baseline and 24 weeks assessed effusion and synovial thickness. Patients received MTX up to 20 mg/week for 24 weeks. RESULTS Thirty participants were recruited; mean age 64.5 years, median pain VAS 68 mm. At 24 weeks, 13/30 (43%) achieved ≥30% reduction in pain VAS, 7 (23%) achieved ≥50% reduction and 4 (13%) had worsened. Thirteen achieved Osteoarthritis Research Society International (OARSI) responder criteria. All had effusion/synovitis at baseline. There was no correlation between change in imaging and change in pain scores at 24 weeks. CONCLUSION This open-label trial suggests analgesic efficacy for MTX in OA knee and suggests that a randomized controlled trial is warranted. Trial Registration. Current controlled trials, http://www.controlled-trials.com/, ISRCTN66676866.

New horizons in osteoarthritis

Osteoarthritis (OA) is the most common type of arthritis worldwide and rapidly increasing with ageing populations. It is a major source of pain and disability for individuals and economic burden for health economies. Modern imaging, in particular magnetic resonance imaging (MRI), has helped us to understand that OA is a dynamic remodelling process involving all the structures within the joint. Inflammation is common in OA, with a high prevalence of synovitis seen on imaging, and this has been associated with joint pain. MRI detected changes within the subchondral bone are also common and associated with pain and structural progression. Targeting individual pathologies may offer potential new therapeutic options for OA; this is particularly important given the current treatments are often limited by side effects or lack of efficacy. New approaches to understanding the pathology and pain pathways in OA offer hope of novel analgesic options, for example, monoclonal antibodies against nerve growth factor and centrally acting drugs such as duloxetine, tapentadol and bradykinin receptor antagonists have all recently undergone trials in OA. While treatment for OA has until now relied on symptom management, for the first time, recent trials suggest that structure modification may be possible by treating the subchondral bone.

Do non-steroidal anti-inflammatory drugs have a significant effect on detection and grading of ultrasound-detected synovitis in patients with rheumatoid arthritis? Results from a randomised study

Objectives To determine whether non-steroidal anti-inflammatory drugs (NSAIDs) have a significant effect on ultrasonographic (US) grey scale (GS) and power Doppler (PD) assessment of synovitis in rheumatoid arthritis (RA). Methods Patients with RA taking NSAIDs were randomised to either stopping (for a minimum of 5 drug half-lives) or continuing the drug. All patients had a clinical assessment and US examination of both hands and wrists before and after stopping/continuing the NSAID. Changes at follow-up were compared between groups using Mann–Whitney U tests. Results A total of 58 patients with RA were recruited. All the clinical assessment parameters (including disease activity, pain, general state of health and physician global visual analogue score and tender and swollen joints count) showed an increase in the group who stopped their NSAID treatment. The total GS and PD score showed median (first to third quartiles) increase of 9.5 (5.75 to 19.0) and 4.0 (2.0 to 6.0) per patient, respectively, in the patients who stopped their NSAID in comparison with 1.0 (–1.0 to 2.25) and 0.0 (–2.0 to 3.0), respectively, in the patients who continued their NSAID (p<0.001). There was an increase in the number of joints scoring >0 for GS and PD in the patients who stopped the NSAID. The inter- and intrareader agreement was good to excellent for the US examination. Conclusion NSAID usage may mask the GS and PD signal and result in lower scoring despite continuing disease activity. Consideration should be given to the NSAID effect in designing clinical studies which use US to assess response to therapeutic.

The role of imaging modalities in the diagnosis, differential diagnosis and clinical assessment of peripheral joint osteoarthritis

Peripheral joint osteoarthritis (OA) is predominantly a clinical diagnosis, though imaging may provide confirmation and aid with differential diagnosis where there is clinical doubt. Whilst radiographs (X-rays (XR)) are usually the first-line imaging modality selected, magnetic resonance imaging (MRI), ultrasound and computed tomography (CT) may all have a valuable role in assessing a person with OA, although each has its particular advantages and disadvantages. MRI is of particular use for diagnosing bone conditions that may cause a rapid increase in symptoms, such as avascular necrosis (AVN) or a subchondral insufficiency fracture (SIF), while providing concomitant soft tissue assessment. Ultrasound offers rapid assessment of peripheral joints and can easily assess for features of inflammatory arthritis. CT is faster to perform than MRI and can also image the subchondral bone, but does involve ionising radiation. Selecting the correct imaging modality, in the context of its advantages when visualising a specific joint (e.g., hand vs knee) and with clinical context in mind, will enhance the added value of imaging in clinical practice.

Biological therapies in osteoarthritis.

Given the paucity of effective therapies and the increasing prevalence of osteoarthritis (OA) with ageing and overweight populations, new therapies for this painful, life-impairing condition are desperately needed, for both symptom relief and structural modification. With a growing understanding that OA involves multiple tissue pathologies including inflammation, many more therapeutic targets have been identified. This review will provide a current overview on the role of biologics in OA, including anti-tumour necrosis factor agents, growth factors and interleukin-1 antagonists.

A case of reactive arthritis secondary to sexually acquired Shigella flexneri

Abstract We present the first documented case of reactive arthritis (ReA) secondary to sexually acquired Shigella flexneri infection. The case occurred in the context of a recent change in Shigella epidemiology in England where non-travel associated cases are now contributing the majority of diagnoses. Such non-travel associated cases are occurring predominantly in men who have sex with men with high sexual risk taking behaviour reflecting the importance of the sexual history when assessing a man with Shigella infection who has not travelled. We suggest Shigella can be thought of as a cause of sexually acquired ReA and not just a form of enteric ReA. Referral to sexual health services for further management is essential.