Explore the vast range of titles available.

Rheumatoid arthritis (RA) and periodontitis are both chronic inflammatory diseases, which demonstrate similarities in terms of mechanism, histopathology, and demography. An association between these conditions has been demonstrated previously but has been called into question more recently. The published databases, such as MEDLINE, EMBASE, and PsycINFO, were searched using search terms related to RA and periodontitis. Articles were selected if they included data on the number of people with RA diagnosed with periodontitis (or periodontal disease parameters) compared to a control comparison group. Review articles, case reports, animal model studies, non-English language, and articles with unavailable abstracts were excluded. Data were extracted, critically appraised using the Downs and Black tool, and a random-effect Mantel-Haenszel meta-analysis was performed. Twenty-one papers met the eligibility criteria and provided data for the meta-analysis; 17 studies (including a total of 153,492 participants) comparing RA to healthy controls and 4 (including a total of 1378 participants) comparing RA to osteoarthritis (OA). There was a significantly increased risk of periodontitis in people with RA compared to healthy controls (relative risk: 1.13; 95% CI: 1.04, 1.23; p = 0.006; N = 153,277) with a significantly raised mean probing depth, risk of bleeding on probing (BOP), and absolute value of clinical attachment loss in those with RA. When comparing RA and OA, there was no significant difference in the prevalence of periodontitis; however, the risk of BOP was greater in OA than RA. A significant association between RA and periodontitis is supported by the results of our systematic review and meta-analysis of studies comparing RA to healthy controls. In our meta-analysis, however, this is not replicated when comparing RA to OA controls.

ObjectiveBone marrow lesions (BMLs) are well described in osteoarthritis (OA) using MRI and are associated with pain, but little is known about their pathological characteristics and gene expression. We evaluated BMLs using novel tissue analysis tools to gain a deeper understanding of their cellular and molecular expression.MethodsWe recruited 98 participants, 72 with advanced OA requiring total knee replacement (TKR), 12 with mild OA and 14 non-OA controls. Participants were assessed for pain (using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) and with a knee MRI (using MOAKS). Tissue was then harvested at TKR for BML analysis using histology and tissue microarray.ResultsThe mean (SD) WOMAC pain scores were significantly increased in advanced OA 59.4 (21.3) and mild OA 30.9 (20.3) compared with controls 0.5 (1.28) (p<0.0001). MOAKS showed all TKR tissue analysed had BMLs, and within these lesions, bone marrow volume was starkly reduced being replaced by dense fibrous connective tissue, new blood vessels, hyaline cartilage and fibrocartilage. Microarray comparing OA BML and normal bone found a significant difference in expression of 218 genes (p<0.05). The most upregulated genes included stathmin 2, thrombospondin 4, matrix metalloproteinase 13 and Wnt/Notch/catenin/chemokine signalling molecules that are known to constitute neuronal, osteogenic and chondrogenic pathways.ConclusionOur study is the first to employ detailed histological analysis and microarray techniques to investigate knee OA BMLs. BMLs demonstrated areas of high metabolic activity expressing pain sensitisation, neuronal, extracellular matrix and proinflammatory signalling genes that may explain their strong association with pain.

Background Giant cell arteritis is a large vessel vasculitis of the arteries in the head and neck. The mainstay of management is with high-dose corticosteroids, and patients often face difficulties stopping or reducing steroids without recurrence of symptoms. Corticosteroids are well established to have numerous associated side effects, including osteoporosis, weight gain, and diabetes. Therefore, when tocilizumab was approved for up to 1 year for cases of relapsing or refractory giant cell arteritis by the National Institute of Health and Care Excellence (NICE) in April 2018, this offered an opportunity to benefit from new funding and to reduce steroid burden. Case presentation This case series describes the impact of the establishment of a new hub and spoke referral pathway for the use of tocilizumab in refractory or relapsing giant cell arteritis, with case examples from consecutive patients who accessed the funding between August 2018 and April 2021. A total of 16 patients were identified: 11 female and 5 male, with an average age of 72.4 (range 61–82) years, with a majority of 11 ethnically white. The central assessing hub is St George’s University Hospitals NHS Foundation Trust Hospital, serving a population of 1.3 million in the south of England. This is the first large case series looking into the impact of the establishment of a regional clinical pathway for the new tocilizumab funding. Conclusions The case series demonstrates that the use of tocilizumab has reduced both the duration and the dose of corticosteroids in these 16 cases (mean prednisolone reduction 20.4 mg: 95% CI 13.0–27.8 mg), with 50% of patients continuing on tocilizumab after the initial 12 month funding period. The disease course, patterns of response, and maintenance of remission are discussed, and we describe the benefits of replicating this hub and spoke tocilizumab pathway in other centers.

Background Treatment guidelines for psoriasis and psoriatic arthritis consider all skin and joint domains and recommend collaborative multidisciplinary team (MDT) working. The uptake of joint working in clinical practice for psoriatic disease management has not been well studied. Objectives This United Kingdom (UK) study aimed to provide a better understanding of current working patterns and collaborating specialities, as well as benefits and challenges of combined clinics. Methods An online survey was emailed to dermatology and rheumatology healthcare professionals (HCPs) using professional networks. Results Responses were received between October 2020 and April 2021 (N = 80); 60.0% of respondents worked in dermatology and 40.0% in rheumatology. Use of combined clinics with dermatology was reported by 40.6% of rheumatology HCPs, including joint (25.0%), parallel (3.1%) and virtual clinics (6.3%), and MDT meetings (6.2%). Similarly, 50.1% of dermatology HCPs reported use of joint (25.0%), parallel (4.2%) and virtual clinics (2.1%), single visits (2.1%), and MDT meetings (16.7%) with rheumatology. Around one‐quarter of respondents collaborated via email, which was also the main method of collaboration with other specialists. Overall, one‐quarter of respondents reported no collaboration in psoriatic disease management. Perceived benefits of combined clinics included shared knowledge, improved patient outcomes and increased patient satisfaction. Challenges included difficulties in aligning clinician time and geographical location, as well as limited ‘buy‐in’ from senior management. Most respondents felt that the COVID‐19 pandemic had partially or significantly impacted combined clinics. Conclusions This study is one of the first to survey collaborative working in psoriatic disease management and the first in the UK. These findings demonstrate the variety of approaches used and a lack of collaborative working by one‐quarter of respondents. Despite the benefits, numerous challenges in establishing formal arrangements exist. More evidence is needed to demonstrate improved patient outcomes with collaborative working and to standardise best practice.

ObjectivesThis study establishes research priorities for medically not yet explained symptoms (MNYES), also known as persistent physical symptoms or medically unexplained symptoms, from the perspective of patients, caregivers and clinicians, in a priority setting partnership (PSP) following the James Lind Alliance (JLA) approach. Research into such symptoms in general has been poorly funded over the years and so far has been primarily researcher-led with minimal input from patients, caregivers and clinicians; and sometimes has been controversial.DesignJLA PSP method. The PSP termed these symptoms MNYES.MethodsThe study was conducted according to the JLA’s detailed methodology for conducting priority setting exercises. It involved five key stages: defining the appropriate term for the conditions under study by the PSP Steering Group; gathering questions on MNYES from patients, caregivers and clinicians in a publicly accessible survey; checking these research questions against existing evidence; interim prioritisation in a second survey; and a final multi-stakeholder consensus meeting to determine the top 10 unanswered research questions using the modified nominal group methodology.ResultsOver 700 responses from UK patients, caregivers and clinicians were identified in the two surveys and charities contributed from a broad range of medical specialties and primary care. The final top 10 unanswered research questions cover, among others: treatment strategies, personalisation of treatment, collaborative care pathways, training for clinicians and outcomes that matter to patients.InterpretationThe top 10 unanswered research questions are expected to generate much needed, relevant and impactful research into MNYES.

Introduction Historically, idiopathic recurrent pericarditis (IRP) has been considered challenging to treat, with underlying pathological mechanisms being incompletely understood. Over the last few years, there has been a growing body of evidence to support IRP as an autoinflammatory disease. Consequentially, the use of interleukin-1 receptor antagonists in refractory disease is becoming increasingly common. Our case describes a patient with three distinct presentations of severe pericarditis associated with pleural effusions and systemic inflammation, despite treatment with high-dose NSAIDs and colchicine. Following initiation of anakinra, he had complete sustained symptomatic, biochemical and radiographical resolution of disease, with no further episodes. Case description A 40-year-old Caucasian previously fit and well male presented to his local hospital with two weeks of pericarditic chest pain despite ibuprofen use. He was found to have a large pericardial effusion requiring pericardiocentesis, suspected to be secondary to viral pericarditis. On discharge his symptoms and effusion had resolved. Two months later, his pericarditic chest pain recurred with general malaise and pyrexia. An episode of postural syncope precipitated local admission. He had no joint pain, rashes, or other symptoms or signs of connective tissue disease. He had no significant family, travel or occupational history. A CTPA showed recurrent pericardial effusion with a left-sided pleural effusion, prompting transfer to our centre for pericardiocentesis. Blood tests revealed raised inflammatory markers (CRP 302 mg/L; WCC 14.2x10*9/L), but were otherwise unremarkable including troponin. An ECG showed sinus tachycardia only. An echocardiogram confirmed recurrence. Pericardiocentesis was attempted but unsuccessful. Pericardial fluid from his first admission revealed scanty white cells, but no growth on bacterial or tuberculosis cultures. Pleural fluid aspiration revealed an exudative effusion. Extensive infection screening was negative. He was treated with antibiotics, high-dose aspirin and colchicine, with clinical improvement, normalisation of inflammatory markers and resolution of his pericardial effusion on repeat echocardiogram. Four weeks later, he presented with a further collapse, recurrent chest pain and fevers. His inflammatory markers were raised (CRP 227 mg/L) and a repeat echocardiogram showed a bright, thickened pericardium with small-volume effusion. Immunology, including ANA, ANCA, rheumatoid factor, anti-CCP, anticardiolipin antibodies and serum ACE were all negative. Serum ferritin was mildly raised (653ug/L). A diagnosis of IRP was made. Anakinra was commenced with excellent clinical response and resolution of all changes on echocardiogram. An attempt to switch to alternative maintenance therapy was not tolerated. Anakinra was continued through the national centre. He remains well with no further episodes of pericarditis. Discussion Recurrent pericarditis is defined as a further episode of pericarditis occurring after a symptom-free interval of at least 4 weeks. Recurrence occurs in 15 to 30% of cases, with the majority being idiopathic. An immune-mediated pathogenesis has long been postulated with treatment centred around anti-inflammatory medications. While the exact disease mechanism remains elusive, recently IRP has been increasingly conceptualised as an autoinflammatory phenomenon. Autoinflammatory disease encompasses a group of conditions driven by innate immune system overactivity with no identifiable extrinsic trigger, autoreactive antibodies or antigen-specific T-cells. The prototypical autoinflammatory conditions are monogenic disorders characterised by recurrent spontaneous episodes of systemic inflammation underpinned by disruption of interleukin-1 signalling. There is accumulating evidence that autoinflammatory and autoimmune disease form a spectrum, with monogenic disorders sitting at the extremes. Conditions, including gout, psoriasis, and IRP, are being reconsidered as predominantly autoinflammatory disorders. One UK study compared IRP patients to those with monogenic autoinflammatory disorders. They found that IRP most frequently manifests with evidence of systemic inflammation and extrapericardial effusions, as illustrated here. Comparatively, pericarditis was a feature of monogenic disease but was uncommon, and never the initial complaint. Genetic analysis of IRP patients revealed an increased frequency of rare deleterious variants of four monogenic autoinflammatory disease genes involved in interleukin-1β processing. These clinical and genetic bridges strengthen the hypothesis that IRP is an autoinflammatory disease. Identification of effective IRP treatments has enabled understanding of an autoinflammatory mechanism and vice versa. The effectiveness of colchicine has been used as evidence of IRP as an interleukin-1 driven process. The poor outcomes associated with corticosteroid dependence in refractory IRP has led to exploration of targeted interleukin-1 therapy. The AIRTRIP trial demonstrated a significant reduction in pericarditis recurrence with anakinra versus standard care in IRP. Similarly, this case shows rapid disease control with anakinra, avoiding corticosteroid use. Key learning points • Autoinflammatory and autoimmune disease are increasingly being considered on a spectrum, with prototypical monogenic autoinflammatory disease being one extreme of this. There is accumulating evidence that polygenic conditions, such as IRP, sit under the umbrella of autoinflammatory disease. This is based on clinical and genetic similarities between IRP and monogenic disorders. Additionally, interleukin-1, a key innate immune system mediator has been identified as fundamental in IRP pathogenesis, demonstrated by the effectiveness of interleukin-1 blockade in preventing further IRP disease flares. • The differential for pericarditis is broad and includes infective causes such as certain viruses, bacteria or tuberculosis, autoimmune causes, malignancy, and autoinflammatory disease. To make a diagnosis of IRP alternative causes need to be ruled out sufficiently. While IRP does present predominantly with pericarditis, systemic inflammation and extrapericardial effusions are other key features. Pericarditis can be a feature of monogenic autoinflammatory disease, but is not usually the predominant complaint. • There is significant morbidity associated with use of corticosteroids in IRP that is refractory to initial management with colchicine and NSAIDs. In these patients, targeted therapy, such as anakinra, should be considered and may be used in preference to corticosteroids. This case highlights that the use of anakinra can result in complete and sustained disease remission. This fuels the case that there is a need for broader access to anakinra for treatment of IRP. Further research is needed to fully understand the pathogenesis of IRP, with the hope that this would help identify additional treatment options to a historically difficult-to-treat, debilitating disease.

A woman in her mid-60s presented to transient ischaemic attack (TIA) clinic with a 3-year history of intermittent sensory changes and white discolouration affecting the left side of her tongue. Following extensive investigation, a provisional diagnosis of posterior circulation TIA was made, and the patient was commenced on clopidogrel therapy. Despite anti-platelet treatment, she continued to have identical episodic symptoms. She was referred to the rheumatology team for assessment of possible underlying autoimmune pathology. On rheumatology assessment, the patient reported colour changes on the tongue, associated with numbness, followed by paraesthesia of the affected area. A comprehensive assessment excluded secondary causes and a diagnosis of primary Raynaud’s phenomenon of the tongue was made. The diagnosis of TIA was revoked. This case illustrates a rare presentation of a common condition and highlights the sensory symptoms which are associated with Raynaud’s phenomenon.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein–Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future. Systemic lupus erythematosus is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Here, Kaul et al . highlight the heterogeneity of the disease, the management approaches and provide an outlook on the future research directions.

IntroductionSystemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder that affects many different organ systems with significantly more women affected than men. This study was carried out to assess the prevalence of Functional gastrointestinal disorders(FGID) in patients diagnosed with SLE.MethodsData was collected from patients with a confirmed diagnosis of SLE and no organic gastrointestinal disorder using SF36 RAND and Rome IV Diagnostic questionnaire and compared to a control group to assess the burden of GI symptoms in these patients. Data analysis was carried out using Microsoft Excel and SPSS version 25 (IBM Corporation, America).Results101 SLE patients (all female; age range 31–56 years, mean 41) and 108 female controls (range 21–60 mean age 42.4), were included. 71 (70.29%) SLE patients reported abdominal symptoms which met the criteria for diagnosis of at least 1 FGID according to Rome IV diagnostic criteria compared to 37% of controls (OR 4.97: 95% CI:2.7025 to 9.1401 p<0.0001). Both upper and lower FGIDs were frequently reported with 37 patients (36%) meeting the criteria for more than 1 FGID.All SLE patients with FGID scored lower (statistically significant p<0.01) on the mean scores of the eight parameters (physical functioning, role limitations due to physical health, role limitations due to emotional health, energy/fatigue, emotional wellbeing, social functioning, pain, general health) measured by the RAND SF36 as compared to the control group. (mean scores 59.62 vs 71.23, U-value 0, Z-Score −2.50672, p-value.00604).ConclusionsFunctional gastrointestinal disorders are very common in patients with SLE and adversely affect the overall quality of life. Treatment of these disorders with a multi-disciplinary approach may help in improving the quality of life for these patients.