Showing papers in "Rheumatology in 2018"

The British Society for Rheumatology guideline for the management of systemic lupus erythematosus in adults

Abstract: NICE has accredited the process used by the BSR to produce its guidance on the management of systemic lupus erythematosus in adults. Accreditation is valid for 5 years from 10 June 2013. More information on accreditation can be viewed at www.nice.org.uk/accreditation. For full details on our accreditation visit: www.nice.org.uk/accreditation. Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Rheumatology Department, City Hospital, Sandwell and West Birmingham Hospitals NHS Trust, Rheumatology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, Royal National Hospital for Rheumatic Diseases, Bath, Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, Institute for Inflammation and Repair, University of Manchester, Manchester Academic Health Sciences Centre, The Kellgren Centre for Rheumatology, NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester, Louise Coote Lupus Unit, Guy’s Hospital, London, Laurie Pike Health Centre, Modality Partnership, Birmingham, Department of Rheumatology, Freeman Hospital, Newcastle upon Tyne, Department of Medicine, University of Cambridge, Lupus and Vasculitis Unit, Addenbrooke’s Hospital, Cambridge, Lupus Research Unit, The Rayne Institute, St Thomas’ Hospital, Division of Women’s Health, King’s College London, Section of Renal Medicine and Vascular Inflammation, Division of Immunology and Inflammation, Department of Medicine, Imperial College London, London, LUPUS UK, Romford, Essex and Centre for Rheumatology, University College London, London, UK

Osteoarthritis: the genesis of pain.

Abstract: OA is a painful joint disease that predominantly affects the elderly. Pain is the primary symptom of OA, and it can present as either intermittent or constant. OA pain mechanisms are complex and have only recently been determined. Both peripheral and central processes are involved in creating the OA pain experience, making targeted therapy problematic. Nociceptive, inflammatory and neuropathic pains are all known to occur in OA, but to varying degrees in a patient- and time-specific manner. A better understanding of these multifactorial components of OA pain will lead to the development of more effective and safer pain treatments.

Update on colchicine, 2017.

Abstract: Colchicine is an ancient medication that is currently approved for the treatment of gout and FMF. However, colchicine has a wide range of anti-inflammatory activities, and studies indicate that it may be beneficial in a variety of other conditions. This paper reviews the evidence for the well-established use of colchicine in gout, as well as several other rheumatic diseases. In addition, we highlight the potential benefit of colchicine in cardiac disease, including coronary artery disease in patients both with and without gout.

Tofacitinib for refractory interstitial lung diseases in anti-melanoma differentiation-associated 5 gene antibody-positive dermatomyositis.

Abstract: Objective We aimed to determine the outcome of combination therapy with tofacitinib (TOF) in a case series of refractory rapidly progressive interstitial lung disease (ILD) associated with anti-melanoma differentiation-associated 5 gene (MDA5) antibody-positive (Ab+) DM. Patients who had poor prognostic factors and failed to respond to immunosuppressive therapy were selected for TOF treatment. Methods Five patients with anti-MDA5 Ab+ DM-ILD who failed to respond to triple therapy with high dose glucocorticoids, CSA and CYC were given additional TOF (10 mg/day). To identify the poor prognostic factors, data from 15 consecutive patients (seven survived and eight died) with anti-MDA5 Ab+ DM-ILD before induction of TOF were analysed. Results Three poor prognostic factors were identified: serum ferritin level >1000 ng/ml before therapy; ground-glass opacities in all six lung fields before therapy; and worsening of pulmonary infiltrates during therapy. All six patients who had all of the three factors and received triple therapy died before TOF therapy. There were five patients who had all of the three prognostic factors and failed to respond to triple therapy, but were able to receive the combination therapy with TOF; among them, three survived and two died. The survival rate of patients who received TOF was significantly better than that of the historical controls with immunosuppressive therapy before TOF. The patients who received TOF experienced complicated adverse events, particularly viral infection. Conclusion Combination therapy with TOF might have the potential to control refractory anti-MDA5 Ab+ DM-ILD.

Intravenous cyclophosphamide vs rituximab for the treatment of early diffuse scleroderma lung disease: open label, randomized, controlled trial

Abstract: Objectives SSc is characterized by fibrotic changes in the skin and lung, and the mainstay of treatment has been CYC. B cell involvement suggests that rituximab (RTX) may also be of therapeutic benefit. The aim of the study was to compare the efficacy and safety of RTX compared with CYC in retarding the progression of interstitial lung disease and skin manifestations of primary SSc. Methods We randomly assigned 60 patients of dcSSc, age 18-60 years with skin and lung involvement, to monthly pulses of CYC 500 mg/m2 or RTX 1000 mg × 2 doses at 0, 15 days. Primary outcomes were forced vital capacity (FVC) percent predicted at 6 months. Secondary outcomes were: absolute change in litres (FVC-l) at 6 months; modified Rodnan skin scores at 6 months, 6-min walk test, Medsgers score and new onset or worsening of existing pulmonary hypertension by echocardiographic criteria. Results The FVC [%mean (s.d.)] in the RTX group improved from 61.30 (11.28) to 67.52 (13.59), while in the CYC group it declined from 59.25 (12.96) to 58.06 (11.23) at 6 months (P = 0.003). The change of FVC was 1.51 (0.45) l to 1.65 (0.47) l in the RTX group, compared with 1.42 (0.49) to 1.42 (0.46) l in the CYC group. The mRSS changed from 21.77 (9.86) to 12.10 (10.14) in the RTX group and 23.83 (9.28) to 18.33 (7.69) in the CYC group after 6 months. Serious adverse events were more common in the CYC group. Conclusion RTX is a safe and effective alternative to CYC in the primary therapy of skin and lung manifestations of scleroderma. Trial registration Clinical Trials Registry - India, www.ctri.nic.in, CTRI/2017/07/009152.

Large-vessel giant cell arteritis: diagnosis, monitoring and management

Abstract: GCA is a chronic, idiopathic, granulomatous vasculitis of medium and large arteries. It comprises overlapping phenotypes including classic cranial arteritis and extra-cranial GCA, otherwise termed large-vessel GCA (LV-GCA). Vascular complications associated with LV-GCA may be due, in part, to delayed diagnosis, highlighting the importance of early identification and prompt initiation of effective therapy. Advancements in imaging techniques, including magnetic resonance angiography, CT angiography, PET and colour duplex ultrasonography, have led to improvements in the diagnosis of LV-GCA; however, the role imaging modalities play in the assessment of disease activity and long-term outcomes remains unclear. Glucocorticoids are the mainstay of therapy in LV-GCA, but their prolonged use is associated with multiple, sometimes serious, adverse effects. Recent data suggest that biologic therapies, such as tocilizumab, may be effective and safe steroid-sparing options for patients with GCA. However, data specifically evaluating the management of LV-GCA are limited.

Ultrasound in the diagnosis and management of giant cell arteritis.

Abstract: US has become an important diagnostic tool for musculoskeletal diseases. Because of its wide availability in rheumatology practice, US has also been applied in other rheumatic diseases such as GCA. In acute GCA, US displays a non-compressible, hypoechoic, most commonly concentric arterial wall thickening. Temporal and axillary arteries should be examined in patients with suspected GCA and PMR. Additionally, almost all other large arteries, with the exception of the thoracic aorta, can be easily delineated by US. Many studies and several meta-analyses have been conducted to evaluate the diagnostic performance of US. US is more sensitive than temporal artery biopsy (TAB) because TAB evaluates only a limited anatomical region in a systemic disease. Most US studies arrive at specificities between 90 and 100% compared with the final clinical diagnosis. Reliability for reading US images and videos is excellent and comparable to reliability for reading TAB specimens. The advantage of US over other imaging techniques in GCA is its availability, safety and tolerability and its high resolution of 0.1 mm. Rheumatology departments are increasingly establishing fast-track clinics. Physicians can refer patients with suspected GCA within 24 h. Patients receive clinical and US examination by experienced specialists, establishing a clear diagnosis either before TAB or without the need for TAB. The introduction of fast-track clinics has led to a significant reduction of permanent vision loss. Furthermore, a process that primarily includes US is significantly more cost-effective than TAB.

What is the evidence for a role for diet and nutrition in osteoarthritis

Abstract: As current treatment options in OA are very limited, OA patients would benefit greatly from some ability to self-manage their condition. Since diet may potentially affect OA, we reviewed the literature on the relationship between nutrition and OA risk or progression, aiming to provide guidance for clinicians. For overweight/obese patients, weight reduction, ideally incorporating exercise, is paramount. The association between metabolic syndrome, type-2 diabetes and OA risk or progression may partly explain the apparent benefit of dietary-lipid modification resulting from increased consumption of long-chain omega-3 fatty-acids from oily fish/fish oil supplements. A strong association between OA and raised serum cholesterol together with clinical effects in statin users suggests a potential benefit of reduction of cholesterol by dietary means. Patients should ensure that they meet the recommended intakes for micronutrients such as vitamin K, which has a role in bone/cartilage mineralization. Evidence for a role of vitamin D supplementation in OA is unconvincing.

Gout: state of the art after a decade of developments.

Abstract: This review article summarizes the relevant English literature on gout from 2010 through April 2017. It emphasizes that the current epidemiology of gout indicates a rising prevalence worldwide, not only in Western countries but also in Southeast Asia, in close relationship with the obesity and metabolic syndrome epidemics. New pathogenic mechanisms of chronic hyperuricaemia focus on the gut (microbiota, ABCG2 expression) after the kidney. Cardiovascular and renal comorbidities are the key points to consider in terms of management. New imaging tools are available, including US with key features and dual-energy CT rendering it able to reveal deposits of urate crystals. These deposits are now included in new diagnostic and classification criteria. Overall, half of the patients with gout are readily treated with allopurinol, the recommended xanthine oxidase inhibitor (XOI), with prophylaxis for flares with low-dose daily colchicine. The main management issues are related to patient adherence, because gout patients have the lowest rate of medication possession ratio at 1 year, but they also include clinical inertia by physicians, meaning XOI dosage is not titrated according to regular serum uric acid level measurements for targeting serum uric acid levels for uncomplicated (6.0 mg/dl) and complicated gout, or the British Society for Rheumatology recommended target (5.0 mg/dl). Difficult-to-treat gout encompasses polyarticular flares, and mostly patients with comorbidities, renal or heart failure, leading to contraindications or side effects of standard-of-care drugs (colchicine, NSAIDs, oral steroids) for flares; and tophaceous and/or destructive arthropathies, leading to switching between XOIs (febuxostat) or to combining XOI and uricosurics.

The use of ultrasound to assess giant cell arteritis: review of the current evidence and practical guide for the rheumatologist.

Abstract: Colour duplex sonography (CDS) of temporal arteries and large vessels is an emerging diagnostic tool for GCA. CDS can detect wall oedema, known as a halo, throughout the length of the vessel and shows higher sensitivity compared with biopsy. Specificity reaches 100% in case of bilateral halos. A positive compression sign has been demonstrated to be a robust marker with excellent inter-observer agreement. The assessment of other large vessels, particularly the axillary arteries, is recognized to further increase the sensitivity and to reliably represent extra-cranial involvement in other areas. Nevertheless, CDS use is still not widespread in routine clinical practice and requires skilled sonographers. Moreover, its role in the follow-up of patients still needs to be defined. The aim of this review is to provide the current evidence and technical parameters to support the rheumatologist in the CDS evaluation of patients with suspected GCA.

The multifaceted presentation of chronic recurrent multifocal osteomyelitis: a series of 486 cases from the Eurofever international registry

Abstract: Objectives Chronic non-bacterial osteomyelitis (CNO) or chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory disorder characterized by sterile bone osteolytic lesions. The aim of this study was to evaluate the demographic data and clinical, instrumental and therapeutic features at baseline in a large series of CNO/CRMO patients enrolled in the Eurofever registry. Methods A web-based registry collected retrospective data on patients affected by CRMO/CNO. Both paediatric and adult centres were involved. Results Complete baseline information on 486 patients was available (176 male, 310 female). The mean age of onset was 9.9 years. Adult onset (>18 years of age) was observed in 31 (6.3%) patients. The mean time from disease onset to final diagnosis was 1 year (range 0-15). MRI was performed at baseline in 426 patients (88%), revealing a mean number of 4.1 lesions. More frequent manifestations not directly related to bone involvement were myalgia (12%), mucocutaneous manifestations (5% acne, 5% palmoplantar pustulosis, 4% psoriasis, 3% papulopustular lesions, 2% urticarial rash) and gastrointestinal symptoms (8%). A total of 361 patients have been treated with NSAIDs, 112 with glucocorticoids, 61 with bisphosphonates, 58 with MTX, 47 with SSZ, 26 with anti-TNF and 4 with anakinra, with a variable response. Conclusion This is the largest reported case series of CNO patients, showing that the range of associated clinical manifestations is rather heterogeneous. The study confirms that the disease usually presents with an early teenage onset, but it may also occur in adults, even in the absence of mucocutaneous manifestations.

Gastrointestinal Manifestations of Systemic Sclerosis

Abstract: Systemic sclerosis (SSc) is a rare autoimmune disease characterized by fibroproliferative alterations of the microvasculature leading to fibrosis and loss of function of the skin and internal organs. Gastrointestinal manifestations of SSc are the most commonly encountered complications of the disease affecting nearly 90% of the SSc population. Among these complications, the esophagus and the anorectum are the most commonly affected. However, this devastating disorder does not spare any part of the gastrointestinal tract (GIT), and includes the oral cavity, esophagus, stomach, small and large bowels as well as the liver and pancreas. In this review, we present the current understanding of the pathophysiologic mechanisms of SSc including vasculopathy, endothelial to mesenchymal transformation as well as the autoimmune pathogenetic pathways. We also discuss the clinical presentation and diagnosis of each part of the GIT affected by SSc. Finally, we highlight the latest developments in the management of this disease, addressing the severe malnutrition that affects this vulnerable patient population and ways to assess and improve the nutritional status of the patients.

Ophthalmic manifestations of giant cell arteritis.

Abstract: GCA, the most common systemic arteritis, affects medium-sized and larger extradural arteries that have the internal elastic lamina. Involvement of the ophthalmic artery and its branches results in visual loss, which is often complete but is usually painless. Visual loss may be monocular or binocular developing simultaneously or sequentially. Rarely, it stems from occipital lobe infarct that result in homonymous hemianopia, a visual field defect involving the two identical halves (right or left) of the visual fields of both eyes. Visual hallucinations and diplopia are less common. All visual symptoms, including those that are transient, require urgent ophthalmological evaluation and treatment with high-dose glucocorticoids to avoid permanent visual loss.

Progress in our understanding of the pathogenesis of ankylosing spondylitis.

Abstract: AS is a common rheumatic condition characterized by inflammation and new bone formation. The pathogenesis of AS is likely multifactorial and has not been fully elucidated to date. A major genetic role has been demonstrated. The strongest genetic association is with HLA B27. Numerous other associated genetic polymorphisms have been identified, including those affecting the type 17 immune pathway, although the precise link between genetics and pathogenesis remains unexplained. Several immunological alterations, together with recent therapeutic advances, support a central role for IL-23- and IL-17-producing immune cells in disease pathogenesis. Recently, perturbations of gut microbiota of AS patients have further catalysed research and offer potential for future therapeutic intervention. In this review we outline the genetic basis of AS and describe the current hypotheses for disease pathogenesis. We synthesize recent experimental research data and clinical studies to support a central role for the type 17/23 immune axis in AS.

Physiological effects of modulating the interleukin-6 axis.

Abstract: IL-6 is a pleiotropic cytokine involved in many biological functions that affect tissues beyond the immune system and the vasculature. This multifunctional cytokine exerts its actions via the classic signalling pathway when it binds to the transmembrane IL-6 receptor (IL-6R) or via the trans-signalling pathway upon binding to the soluble form of IL-6R (sIL-6R). In general, classic IL-6 signalling is responsible for the anti-inflammatory properties of IL-6, whereas trans-signalling is responsible for the pro-inflammatory actions of IL-6. As a result, dysregulation of the IL-6 axis can lead to the onset or development of several disease states, particularly autoimmune and inflammatory disorders, including RA and GCA. This pathological role of IL-6 means that pharmacologic modulation of the IL-6 axis is a rational therapeutic approach; however, multiple predictable, but often underappreciated, effects on tissues and organs beyond the blood vessels may also occur.

Unchanging premature mortality trends in systemic lupus erythematosus: a general population-based study (1999-2014).

Abstract: Objective Patients with SLE have increased morbidity and premature mortality. Whether this mortality gap has improved in recent years, as in RA, is unknown. Methods We conducted a population-based cohort study using a medical records database representative of the general population of the UK. We identified incident SLE cases and matched non-SLE controls between 1999 and 2014, divided into two subgroups based on year of SLE diagnosis, forming the early cohort (1999-2006) and late cohort (2007-14). We compared the mortality rates and hazard ratios, adjusting for potential confounders. Results We identified 1470 and 1666 incident SLE cases in the early and late cohorts, respectively. In both cohorts, SLE patients had similar levels of excess mortality compared with their matched comparators [15.9 vs 7.9 deaths/1000 person-years (PY) in the early cohort and 13.8 vs 7.0 deaths/1000 PY in the late cohort]. The corresponding mortality hazard ratios were 2.15 (95% CI 1.63, 2.83) and 2.12 (95% CI 1.61, 2.80) in the early and late cohorts, respectively (P-value for interaction = 0.95). The absolute mortality differences were 8.0 (95% CI 4.3, 11.8) and 6.8 (95% CI 3.5, 10.0) deaths/1000 PY, respectively (P-value for interaction = 0.61). Conclusion This general population-based cohort study suggests that excess mortality has not improved among SLE patients in recent years, remaining greater than double that of comparators, unlike RA during the same period. This highlights a critical unmet need for the development of new therapeutic agents and improved management strategies for SLE and its comorbidities.

Anti-interleukin 6 receptor tocilizumab in refractory uveitis associated with Behçet's disease: multicentre retrospective study.

Abstract: Objective To assess the efficacy of tocilizumab (TCZ) in refractory uveitis of Behcet's disease (BD). Methods Multicentre study of patients with BD-associated uveitis. Patients were refractory to conventional and biologic immunosuppressive drugs. The main outcome measures were intraocular inflammation, macular thickness, visual acuity and corticosteroid-sparing effects. Results We studied 11 patients (7 men) (20 affected eyes); median age 35 years. Uveitis was bilateral in nine patients. The patterns of ocular involvement were panuveitis (n = 8, with retinal vasculitis in 4), anterior uveitis (n = 2) and posterior uveitis (n = 1). Cystoid macular oedema was present in seven patients. The clinical course was recurrent (n = 7) or chronic (n = 4). Before TCZ, patients had received systemic corticosteroids, conventional immunosuppressants and the following biologic agents: adalimumab (n = 8), infliximab (n = 4), canakimumab (n = 1), golimumab (n = 3), etanercept (n = 1). TCZ was used as monotherapy or combined with conventional immunosuppressants at 8 mg/kg/i.v./4 weeks (n = 10) or 162 mg/s.c./week (n = 1). At TCZ onset the following extraocular manifestations were present: oral and/or genital ulcers (n = 7), arthritis (n = 4), folliculitis/pseudofolliculitis (n = 4), erythema nodosum (n = 2), livedo reticularis (n = 1) and neurological involvement (n = 2). TCZ yielded rapid and maintained improvement in all ocular parameters of the patients, with complete remission in eight of them. However, this was not the case for the extraocular manifestations, since TCZ was only effective in three of them. After a mean (s.d.) follow-up of 9.5 (8.05) months, TCZ was withdrawn in two cases, due to a severe infusion reaction and arthritis impairment, respectively. Conclusion TCZ could be a therapeutic option in patients with BD and refractory uveitis.

Difficult-to-treat rheumatoid arthritis : an area of unmet clinical need

Abstract: Increased effectiveness of pharmacological treatments in early RA has led many to believe that difficult-to-treat, established RA is a condition of the past. However, there are still plenty of RA patients who continue to have signs and symptoms suggestive of inflammatory disease activity, despite consecutive treatment with multiple conventional synthetic and biological DMARDs. We argue that difficult-to-treat RA constitutes an area of unmet clinical need and propose a definition of this concept. An overview of what is known about the multiple contributory factors varying for each individual patient, and an approach towards improved patient-tailored management are presented. This management approach involves thorough assessment to determine whether persistence of signs and symptoms is based on inflammatory disease activity, and the role of comorbidities. Furthermore, it addresses medication-related issues, such as non-adherence, patient beliefs and expectations, and setting of realistic treatment goals.

Initial predictors of poor survival in myositis-associated interstitial lung disease: a multicentre cohort of 497 patients

Abstract: OBJECTIVE To identify initial predictors of poor survival in patients with PM/DM-associated interstitial lung disease (ILD). METHODS We established a multicentre retrospective cohort of incident cases of PM/DM-associated ILD from 44 institutions across Japan (Multicentre Retrospective Cohort of Japanese Patients with Myositis-associated ILD, JAMI). Inclusion criteria were an onset age ⩾16 years; PM/DM or clinically amyopathic DM according to the published criteria; imaging evidence of ILD; and availability of serum samples for assays of autoantibodies such as anti-melanoma differentiation-associated gene 5 and anti-aminoacyl tRNA synthetase. We collected demographic data and clinical characteristics recorded at the time of diagnosis, as well as follow-up survival data. Predictors of ILD-related mortality were identified by univariate and multivariate analyses. RESULTS JAMI enrolled a cohort of 497 patients with PM (15%), classic DM (32%) and clinically amyopathic DM (53%). During the observation period (median 20 months), 76 died of respiratory insufficiency directly related to ILD. Univariate analysis revealed several initial parameters associated with ILD mortality, including demographic, clinical, laboratory, imaging and autoantibody variables. We used multivariate analysis with a stepwise selection of parameters to generate an appropriate predictive model, and identified the following independent risk factors for ILD mortality: age at onset ⩾60 years [hazard ratio (HR) = 4.3, 95% CI: 2.4, 7.5], CRP ⩾1 mg/dl (HR = 2.6, 95% CI: 1.5, 4.8), peripheral capillary oxygen saturation <95% (HR = 2.0, 95% CI: 1.2, 3.4) and anti-melanoma differentiation-associated gene 5 antibody (HR = 7.5, 95% CI: 2.8, 20.2). CONCLUSION We established a large cohort of incident cases of PM/DM-associated ILD, and successfully identified independent predictors of short-term ILD mortality.

Is osteoarthritis one disease or a collection of many

Abstract: OA is a multifaceted and heterogeneous syndrome that may be amenable to tailored treatment. There has been an increasing focus within the OA research community on the identification of meaningful OA phenotypes with potential implications for prognosis and treatment. Experimental and clinical data combined with sophisticated statistical approaches have been used to characterize and define phenotypes from the symptomatic and structural perspectives. An improved understanding of the existing phenotypes based on underlying disease mechanisms may shed light on the distinct entities that make up the disease. This narrative review provides an updated summary of the most recent advances in this field as well as limitations from previous approaches that can be addressed in future studies.

Tumour TIF1 mutations and loss of heterozygosity related to cancer-associated myositis.

Abstract: Objectives To analyse the influence of genetic alterations and differential expression of transcription intermediary factor 1 (TIF1) genes in the pathophysiology of cancer-associated myositis (CAM). Methods Paired blood and tumour DNA samples from patients with anti-TIF1γ-positive CAM and from controls were analysed by whole-exome sequencing for the presence of somatic mutations and loss of heterozygosity (LOH) in their TIF1 genes. The genesis and maintenance of the autoimmune process were investigated immunohistochemically by studying TIF1γ expression in the different tissues involved in CAM (skin, muscle and tumour) based on the immunohistochemical H-score. Results From seven patients with anti-TIF1γ-positive CAM, we detected one somatic mutation and five cases of LOH in one or more of the four TIF1 genes compared with just one case of LOH in tumours from TIF1γ-negative myositis patients (86% vs 17%; P = 0.03). Compared with type-matched control tumours from non-myositis patients, TIF1γ staining was more intense in tumours from anti-TIF1γ-positive patients (H-score 255 vs 196; P = 0.01). Also, TIF1γ staining in muscle was slightly more intense in anti-TIF1γ-positive than in anti-TIF1γ-negative myositis (H-score 22 vs 5; P = 0.03). In contrast, intense TIF1γ staining was detected in the skin of both myositis and control patients. Conclusion Tumours from paraneoplastic anti-TIF1γ-positive patients showed an increased number of genetic alterations, such as mutations and LOH, in TIF1 genes. These genetic alterations, in the context of a high expression of TIF1γ in the tumour, muscle and skin of these patients may be key to understanding the genesis of paraneoplastic myositis.

Concomitant fibromyalgia complicating chronic inflammatory arthritis: a systematic review and meta-analysis.

Abstract: Objectives This systematic review and meta-analysis will describe the prevalence of concomitant FM in adults with inflammatory arthritis and quantify the impact of FM on DAS. Methods Cochrane library, MEDLINE, Psychinfo, PubMed, Scopus and Web of Science were searched using key terms and predefined exclusion criteria. As appropriate, proportional and pairwise meta-analysis methods were used to pool results. Results Forty articles were identified. In RA the prevalence of FM ranged from 4.9 to 52.4% (21% pooled). In axSpA the range was 4.11-25.2% (13% pooled in AS only). In PsA the range was 9.6-27.2% (18% pooled). The presence of concomitant FM was related to higher DAS in patients with RA and AS (DAS28 mean difference 1.24, 95% CI: 1.10, 1.37 in RA; BASDAI mean difference 2.22, 95% CI: 1.86, 2.58 in AS). Concomitant FM was also associated with higher DAS in existing PsA studies. Self-reported, rather than objective, components of DAS appear to be raised in the presence of FM (e.g. tender joint count and Visual Analogue Scale (VAS) pain scores). Conclusion FM is common in RA, AxSpA and PsA. Comorbid FM appears to amplify DAS and could therefore influence management of these rheumatic conditions.

Systemic interferon type I and type II signatures in primary Sjögren's syndrome reveal differences in biological disease activity

Abstract: Objective To assess the relationships between systemic IFN type I (IFN-I) and II (IFN-II) activity and disease manifestations in primary SS (pSS). Methods RT-PCR of multiple IFN-induced genes followed by principal component analysis of whole blood RNA of 50 pSS patients was used to identify indicator genes of systemic IFN-I and IFN-II activities. Systemic IFN activation levels were analysed in two independent European cohorts (n = 86 and 55, respectively) and their relationships with clinical features were analysed. Results Three groups could be stratified according to systemic IFN activity: IFN inactive (19-47%), IFN-I (53-81%) and IFN-I + II (35-55%). No patient had isolated IFN-II activation. IgG levels were highest in patients with IFN-I + II, followed by IFN-I and IFN inactive patients. The prevalence of anti-SSA and anti-SSB was higher among those with IFN activation. There was no difference in total-EULAR SS Disease Activity Index (ESSDAI) or ClinESSDAI between the three subject groups. For individual ESSDAI domains, only the biological domain scores differed between the three groups (higher among the IFN active groups). For patient reported outcomes, there were no differences in EULAR Sjogren's syndrome patient reported index (ESSPRI), fatigue or dryness between groups, but pain scores were lower in the IFN active groups. Systemic IFN-I but not IFN-I + II activity appeared to be relatively stable over time. Conclusions Systemic IFN activation is associated with higher activity only in the ESSDAI biological domain but not in other domains or the total score. Our data raise the possibility that the ESSDAI biological domain score may be a more sensitive endpoint for trials targeting either IFN pathway.

Effect of mechanical stress on magnetic resonance imaging of the sacroiliac joints: assessment of military recruits by magnetic resonance imaging study

Abstract: Objective To assess the baseline condition of the SI joints (SIJs) in healthy individuals without symptoms of back pain and to study the effect of mechanical stress caused by intense physical training on MRI of the SIJs. Methods Twenty-two military recruits underwent an MRI of the SIJs before and after 6 weeks of intense standardized physical training. Bone marrow oedema and structural lesions were scored based on the Spondyloarthritis Research Consortium of Canada (SPARCC) method, by three trained readers blinded for time sequence and clinical findings. Additionally, fulfilment of the Assessment of SpondyloArthritis international Society (ASAS) definition of a positive MRI was evaluated. Results At baseline, 9/22 recruits (40.9%) already presented a SPARCC score ⩾1; this number increased to 11/22 (50.0%) at week 6 (P = 0.625). In these patients, the mean (SD) SPARCC score was 2.4 (0.4) at baseline, compared to 3.7 (1.3) at week 6. Overall, the mean (SD) change in SPARCC score over time in all 22 patients was 0.9 (0.6) (P = 0.109). A positive MRI according to the ASAS definition was present in 5/22 recruits (22.7%) at baseline, which increased to 8/22 (36.4%) at follow-up (P = 0.375). Structural lesions were present in 6/22 subjects (27.3%), both at baseline and after 6 weeks of training. Conclusion A substantial proportion of healthy active individuals without any symptoms of back pain displayed bone marrow oedema lesions on MRI at baseline. However, MRI lesions did not increase significantly after 6 weeks of intensive physical training. Our study underscores the necessity to interpret MRI findings of the SIJs in the appropriate clinical context, even in a young active population.

Divergent roles of immune cells and their mediators in pain

Abstract: Chronic pain is a major debilitating condition that is difficult to treat. Although chronic pain may appear to be a disorder of the nervous system, crucial roles for immune cells and their mediators have been identified as important contributors in various types of pain. This review focuses on how the immune system regulates pain and discusses the emerging roles of immune cells in the initiation or maintenance of chronic pain. We highlight which immune cells infiltrate damaged nerves, the dorsal root ganglia, spinal cord and tissues around free nerve endings and discuss through which mechanisms they control pain. Finally we discuss emerging roles of the immune system in resolving pain and how the immune system contributes to the transition from acute to chronic pain. We propose that targeting some of these immune processes may provide novel therapeutic opportunities for the treatment of chronic pain.

Management of major organ involvement of Behçet’s syndrome: a systematic review for update of the EULAR recommendations

Abstract: Objective To assess the efficacy and safety of treatment modalities for major organ involvement of Behcet's syndrome (BS), in order to inform the update of the EULAR recommendations for the management of BS. Methods A systematic literature review of all randomized controlled trials, controlled clinical trials, or open label trials assessing eye, vascular, nervous system or gastrointestinal system involvement of BS was performed. If controlled trials were not available for answering a specific research question, uncontrolled studies or case series were also included. Results We reviewed the titles and abstracts of 3927 references and 161 studies met our inclusion criteria. There were only nine randomized controlled trials. Observational studies with IFN-α and monoclonal anti-TNF antibodies showed beneficial results for refractory uveitis. Meta-analysis of case-control studies showed that immunosuppressives decreased the recurrence rate of deep vein thrombosis significantly whereas anticoagulants did not. CYC and high dose glucocorticoids decreased mortality in pulmonary arterial aneurysms and postoperative complications in peripheral artery aneurysms. Beneficial results for gastrointestinal involvement were obtained with 5-ASA derivatives and AZA as first line treatment and with thalidomide and/or monoclonal anti-TNF antibodies in refractory cases. Observational studies for nervous system involvement showed improved outcome with immunosuppressives and glucocorticoids. Meta-analysis of case-control studies showed an increased risk of developing nervous system involvement with ciclosporin-A. Conclusion The majority of studies related to major organ involvement that informed the updated EULAR recommendations for the management of BS were observational studies.

Opportunistic infections in rheumatoid arthritis patients exposed to biologic therapy: Results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis

Abstract: Objectives This analysis set out to estimate the risk of opportunistic infection (OI) among patients with RA by biologic class. Methods The British Society for Rheumatology Biologics Register for Rheumatoid Arthritis is a prospective observational cohort study established to evaluate safety of biologic therapies. The population included adults commencing biologic therapy for RA. The primary outcome was any serious OI excluding tuberculosis (TB). Event rates were compared across biologic classes using Cox proportional hazards with adjustment for potential confounders identified a priori. Analysis of the incidence of TB was performed separately. Results In total, 19 282 patients with 106 347 years of follow-up were studied; 142 non-TB OI were identified at a rate of 134 cases/100 000 patient years (pyrs). The overall incidence of OI was not significantly different between the different drug classes; however, the rate of Pneumocystis infection was significantly higher with rituximab than with anti-TNF therapy (adjusted hazard ratio = 3.2, 95% CI: 1.4, 7.5). The rate of TB fell dramatically over the study period (783 cases/100 000 pyrs in 2002 to 38 cases/100 000 pyrs in 2015). The incidence of TB was significantly lower among rituximab users than anti-TNF users, with 12 cases/100 000 pyrs compared with 65 cases/100 000 pyrs. Conclusions The overall rate of OI was not significantly different between drug classes; however, a subtle difference in the pattern of OI was seen between the cohorts. Patient factors such as age, gender and comorbidity were the most important predictors of OI.

Magnetic resonance angiography in giant cell arteritis: results of a randomized controlled trial of tocilizumab in giant cell arteritis.

Abstract: Objective. To analyse magnetic resonance angiographic (MRA) vessel wall signals from a randomized controlled trial of tocilizumab (TCZ) to treat GCA. Methods. Participants were assigned in a 2:1 ratio to receive either TCZ + glucocorticoids (GCs) or placebo +GC infusions at 4-week intervals for 52 weeks. GCs were started at 1 mg/kg/day, then tapered to 0.1 mg/kg/day at week 12 and thereafter down to zero. Patients with initial positive MRA findings underwent control MRA at weeks 12 and 52. Vessel wall signals were scored from 0 (normal) to 3 (intense late enhancement). Outcomes were the number of patients with complete MRA remission at weeks 12 and 52, and changes in vasculitis score, vessel anatomy and atherosclerosis. Results. Of the 30 randomized participants, nine TCZ and two placebo patients had no vessel wall enhancement on initial MRA. At week 12, MRAs were performed in nine TCZ and four placebo patients (nine and three in clinical remission, respectively). Three (33%) TCZ patients showed normalization of vessel wall signals compared with one (25%) placebo patient. At week 52, there was additional MRA improvement in some TCZ patients, but one-third showed persistent or increased late vessel wall enhancement. There was no formation of aneurysms or stenosis and no increase in atherosclerosis. Conclusions. Although TCZ resulted in complete clinical and laboratory remission of GCA over 52 weeks, MRA signals in vessel walls normalized in only one-third of patients. Whether these signals are of prognostic importance remains to be determined.

The role of fat and inflammation in the pathogenesis and management of osteoarthritis.

Abstract: OA is a complex disease involving mechanical, metabolic and inflammatory contributions to its aetiology. A key risk factor, obesity, is becoming an increasing focus of research due to its multiple potential impacts on OA incidence, progression and symptom severity. An increased load due to an increase in body mass has been well established as a mechanical contribution to the pathophysiology of OA. However, evidence of obesity-linked to OA in non-weight-bearing joints has implicated the biological role of adipose inflammation and metabolic abnormalities in OA. The identification of inflammatory mediators such as adipokines (adipose-derived molecules) in OA has further incriminated the role of adiposity. This narrative review aims to discuss the role of adipose-derived inflammation in OA, with a focus on the contrast between systemic and local adipose tissue, and potential treatment applications targeting the adipo-inflammatory aspects of the disease.

Neuroendocrine and neurophysiological effects of interleukin 6 in rheumatoid arthritis

Abstract: RA is a chronic, systemic, autoimmune disease characterized by inflammation and degradation of the joints, causing significant negative impact on quality of life. In addition to joint disease, symptoms and co-morbidities associated with RA—namely pain, fatigue and mood disorders—are often as debilitating as the disease itself. The pro-inflammatory cytokine IL-6 plays a critical role in RA-associated pathology. However, a greater understanding of the translational effects of IL-6 outside of the immune system is needed. This review discusses our current understanding of emerging aspects of IL-6 in RA-associated pain, fatigue and mood disorders such as depression and anxiety. This review also describes the clinical effects of IL-6 inhibition on these symptoms and co-morbidities in patients with RA.