Abstract Introduction Although very rare, with an annual incidence of approximately 1 in 1 million, Takayasu arteritis (TAK) predominantly affects affects younger females. This makes issues related to child bearing particularly relevant to the management of the condition. The heterogenous nature of the condition, difficulty in assessing the degree of active vasculitis, and lack of guidelines specific for TAK in pregnancy make management challenging. We describe two cases managed in a district general hospital (DGH) with close interdepartmental and tertiary centre support which highlight these difficulties, though happily resulted in successful pregnancies. Case description Case 1: TAK diagnosed in 2015 age 23. Presented with headaches and hypertension. MRA: focal and irregular stenosis of the abdominal aorta in the region of the renal arteries with focal stenosis of the left renal artery. Stenosis coeliac axis and superior mesenteric artery origins. Lupus anticoagulant positive (no thrombotic episodes). Initial management: prednisolone, mycophenolate 1 g bd, with rapid normalisation of CRP and weaning of prednisolone. Triple antihypertensive treatment. Joint management with tertiary centre. 2018: unsuccessful left renal angioplasty. Developed lower limb claudication. Despite normal PET-CT activity, concern that TA was active. MMF switched to MTX + tocilizumab. MDT decision to hold off reconstructive vascular surgery. 2019: unplanned ectopic pregnancy, managed with MTX. Following this MTX was switched to AZA. 2020: successful pregnancy - normal vaginal delivery with epidural on tocilizumab, AZA, prednisolone 5 mg daily, aspirin 75 mg daily. 2021: further successful pregnancy - elective LSCS at 39/40. Both deliveries at DGH. Case 2: TAK diagnosed 2011 age 14 in Nepal. 2013: ascending aortic arch and hemi-arch surgery. Immigrated to the UK and seen by our team in 2023 at 23/40 gestation. Managed jointly with a tertiary centre. She remained on a long-term regimen of prednisolone 5 mg, metoprolol was increased from 12.5 mg daily to 25 mg daily and aspirin 75 mg daily was given. MRA showed mild dilatation from the distal aortic arch to the suprarenal aorta and diffuse narrowing of the both external iliac and superficial femoral arteries, left subclavian stenosis. Echocardiogram: moderate aortic incompetence. She developed gestational diabetes in the second trimester, growth scans showed no IUGR. Delivery was managed at a tertiary centre, with elective LSCS at term. There were no complications to mother or baby. Post delivery there was a mild increase in her moderate aortic incompetence. Discussion TAK itself does not appear to affect fertility, nor does pregnancy affect TAK activity. However, pregnancy is high risk in TAK. A literature review of 505 pregnancies in 373 patients found life threatening complications in 5% and death in three cases. 35% developed hypertension, 16% births were premature, 15% had IUGR and there was a 12% foetal loss rate. Active TAK is associated with poor outcomes. In this sense both our patients were fortunate that, despite significant arterial abnormalities, their diseases were well controlled and they were able to proceed to term, delivering healthy babies. In Case 1 there was concern that the distal aortic stenosis could lead to reduced uterine blood flow; the successful outcome in both pregnancies suggests blood supply was adequate. Case 1 required adjustment of potentially teratogenic medicines but illustrates that tocilizumab can be continued through pregnancy. Pre-existing hypertension increases the risk of superimposed preeclampsia by 25%, necessitating the initiation of low-dose aspirin. Case 1 continued amlodipine 5 mg and doxazosin 4 mg twice daily during pregnancy. Amlodipine is a safe calcium channel blocker in pregnancy. Although limited data exist for doxazosin, one study indicated low foetal concentrations even when crossing the placenta at doses up to 8 mg, confirming the safety of our patient’s dose. Case 2 involved a less complex treatment scenario, where continuous therapy with prednisolone was sufficient to maintain disease stability. However, post-pregnancy assessments indicated slight disease progression, necessitating ongoing vigilance. MRA was utilised for monitoring disease activity, emphasising the importance of selecting imaging modalities that minimise radiation exposure to the foetus. The use of steroids can increase the risks associated with pregnancy, such as gestational diabetes, preeclampsia, preterm delivery, IUGR, and foetal loss. Fortunately, both patients were able to be managed on low dose prednisolone. Key learning points • Pre-conception counselling is important in TAK, a disease often affecting females of child bearing age. This also guides choice of treatment and investigation. Both these patients were managed with very close collaboration between secondary and tertiary care centres. Unfortunately none of the centres had linked health records, highlighting the need for the continued development of nationally linked health IT systems. • The lack of formal guidelines for TAK in pregnancy means that expert reviews are vital. We are fortunate that there are comprehensive UK guidelines on medication in pregnancy, as well as very supportive tertiary centres. • The importance of a multidisciplinary team, including obstetricians and rheumatologists, is highlighted. Close monitoring and early referral to a tertiary centre are essential for managing complicated pregnancies. • The relative rarity of TAK with pregnancy suggests the usefulness of a national registry for such cases.

Abstract Background Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), function, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) or RA. Methods Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in patients from the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F. PROMs were compared across CSA, UA and RA and with population averages from the HSE with descriptive statistics. Multivariate linear regression assessed associations between PROMs and clinical and sociodemographic variables. Results Of 838 patients included in the analysis, 484 had RA, 200 had CSA and 154 had UA. Patients with RA reported worse outcomes for all PROMs than those with CSA or UA. However, “mean EQ-5D utilities were 0.65 (95%CI: 0.61 to 0.69) in CSA, 0.61 (0.56 to 0.66) in UA and 0.47 (0.44 to 0.50) in RA, which was lower than in general and older (≥ 65 years) background populations.” In patients with CSA or UA, HRQoL was comparable to chronic conditions such as heart failure, severe COPD or mild angina. Higher BMI and older age (≥ 60 years) predicted worse depression (PHQ-9: -2.47 (-3.85 to -1.09), P < 0.001) and fatigue (FACIT-F: 5.05 (2.37 to 7.73), P < 0.001). Women were more likely to report worse function (HAQ-DI: 0.13 (0.03 to 0.21), P = 0.01) and fatigue (FACIT-F: -3.64 (-5.59 to -1.70), P < 0.001), and residents of more deprived areas experienced decreased function (HAQ-DI: 0.23 (0.10 to 0.36), P = 0.001), greater depression (PHQ-9: 1.89 (0.59 to 3.18), P = 0.004) and fatigue (FACIT-F: -2.60 (-5.11 to 0.09), P = 0.04). After adjustments for confounding factors, diagnostic category was not associated with PROMs, but disease activity and polypharmacy were associated with poorer performance across all PROMs. Conclusions Patient-reported outcomes were associated with disease activity and sociodemographic characteristics. Patients presenting with RA reported a higher health burden than those with CSA or UA, however HRQoL in the pre-RA groups was significantly lower than population averages.

This is a correction to: Ilfita Sahbudin, Ruchir Singh, Paola De Pablo, Elizabeth Rankin, Benjamin Rhodes, Elizabeth Justice, Emma Derrett-Smith, Nicole Amft, Nehal Narayan, Catherine McGrath, Sangeetha Baskar, Jeanette Trickey, Mark Maybury, Karim Raza, Andrew Filer, The value of ultrasound-defined tenosynovitis and synovitis in the prediction of persistent arthritis, Rheumatology, 2022, keac199, https://doi.org/10.1093/rheumatology/keac199 In the originally published version of this manuscript, there was an error in the eleventh author’s surname. The eleventh author’s surname should read “Baskar” instead of “Baskhar”.

Abstract Background/Aims Rheumatoid arthritis (RA) is often preceded by symptomatic phases during which classification criteria are not fulfilled. The health burden of these “at-risk” stages is not well described. This study assessed health-related quality of life (HRQoL), functioning, fatigue and depression in newly presenting patients with clinically suspect arthralgia (CSA), unclassified arthritis (UA) and RA. Methods Cross-sectional analysis of baseline Patient-Reported Outcome Measures (PROMs) was conducted in 838 patients with CSA, UA or RA recruited to the Birmingham Early Arthritis Cohort. HRQoL, function, depression and fatigue at presentation were assessed using EQ-5D, HAQ-DI, PHQ-9 and FACIT-F, respectively. Descriptive statistics and multivariate linear regression were performed to assess associations between clinical/demographic variables and PROMs. Results Patients with RA at initial presentation had worse PROMs than those with CSA or UA. However, HRQoL was decreased in all groups. In patients with CSA/UA, HRQoL was comparable to data relating to chronic conditions such as heart failure, severe COPD or mild angina from the Health Survey for England (HSE). Associations between predictor variables and PROMs are summarised in Table 1. Increased functional disability was associated with female sex, older age, obesity, lower quintiles of social deprivation, increased disease activity and polypharmacy. HRQoL was associated with increased disease activity and polypharmacy. The severity of depression (PHQ-9) increased with older age, increasing BMI, living in areas with the lowest quintile of social deprivation, increased disease activity and polypharmacy. Fatigue (FACIT-F) was associated with female sex, increasing BMI, disease activity and polypharmacy. After adjusting for the demographic and clinical factors, the diagnosis assigned at baseline did not affect any of the studied PROMs, but disease activity and polypharmacy were strongly linked to poorer scores across all PROMs. Conclusion Patients with musculoskeletal symptoms who are at risk of RA present with a high health burden. Early intervention may be needed to improve quality of life from initial presentation. Disclosure B. Torlinska: Corporate appointments; BT is employed by Visible Analytics Ltd.. Grants/research support; BT receives funding from the NIHR. K. Raza: Consultancies; KR declares personal fees from Abbvie and Sanofi outside of the submitted work. Grants/research support; KR declares funding from Bristol Myers Squibb outside of the submitted work, KR is supported by the NIHR Birmingham Biomedical Research Centre, the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research and the Research into Inflammatory Arthritis Centre Versus Arthritis, University of Birmingham, UK. A. Filer: Grants/research support; AF is supported by the NIHR Birmingham Biomedical Research Centre, the MRC Versus Arthritis Centre for Musculoskeletal Ageing Research and the Research into Inflammatory Arthritis Centre Versus Arthritis, University of Birmingham, UK, AF declares funding outside of the submitted work from Abbvie, Roche, Janssen, UCB, Nascient, Mestag, GSK. G. Jutley: None. I. Sahbudin: None. R. Singh: None. P. de Pablo: None. E. Rankin: None. B. Rhodes: None. N. Amft: None. E. Justice: None. C. McGrath: None. S. Baskar: None. J. Trickey: None. M. Calvert: Consultancies; MC has received personal fees outside of the submitted work from Astellas, Aparito Ltd., CIS Oncology, Takeda, Merck, Daiichi Sanko, Glaukos, GSK, and the Patient-Centered Outcomes Research Institute. Grants/research support; MC is Director of the Birmingham Health Partners Centre for Regulatory Science and Innovation, Director of the Centre for Patient Reported Outcomes Research and is a NIHR Senior Investigator, MC receives funding from NIHR, UKRI, NIHR Birmingham Biomedical Research Centre, NIHR Surgical Reconstruction and Microbiology Research Centre, NIHR ARC West Midlands, UK Spine and Health Data Research at the University of Birmingham and University Hospitals Birmingham, UK, Innovate UK (part of UK Research and InnovatioRin), Macmillan Cancer Support, UCB Pharma, Janssen, GSK, and Gilead. M. Falahee: None.

Plain English summary Patient and public involvement (PPI) improves the quality of health research and ensures that research is relevant to patients’ needs. Though PPI is increasingly evident in clinical and health services research, there are few examples in the research literature of effective PPI in translational and laboratory-based research. In this paper, we describe the development and evaluation of PPI in a multi-centre European project (EuroTEAM – Towards Early biomarkers in Arthritis Management) that included both translational and laboratory-based and psychosocial research. We found that although most PPI in EuroTEAM was centred around the psychosocial research, there were examples of PPI in the laboratory studies. As the project evolved, researchers became better at accommodating PPI and identifying PPI opportunities. It was generally agreed that PPI had a positive impact on the project overall, particularly on public engagement with the research. We concluded that the inclusion of both psychosocial and laboratory-based research in the same project facilitated PPI across all aspects of the research. In future projects, we would try to specify individual PPI activities in more detail at the project-planning stage, and better accommodate patient partners who are not native speakers of English. Abstract Background Patient and public involvement (PPI) enhances research quality and relevance and is central to contemporary health policy. The value of PPI has been recognised in rheumatology research, though there are limited examples of PPI in basic and translational science. The EU FP7 funded ‘EuroTEAM’ (Towards Early biomarkers in Arthritis Management) project was established to develop biomarker-based approaches to predict the future development of rheumatoid arthritis and incorporated psychosocial research to investigate the perceptions of ‘at risk’ individuals about predictive testing, and to develop informational resources about rheumatoid arthritis (RA) risk. Patient involvement was central to EuroTEAM from the inception of the project. The objective of this paper is to describe the development of PPI in EuroTEAM, formatively assess the impact of PPI from the perspectives of researchers and patient research partners (PRPs), reflect on successes and lessons learned, and formulate recommendations to guide future projects. Methods Two mixed-methods surveys (for PRPs and researchers) and a teleconference were undertaken to assess the impact of PPI on individual work packages and on EuroTEAM overall. Results There was consensus about the positive impact of PPI on the research and on the experiences of those involved. In particular, the positive impact of PPI on the personal development of researchers, and on effective public engagement with EuroTEAM research were highlighted. Researchers described adapting their practice in future projects to facilitate PPI. Spin-off projects and ongoing collaborations between PRPs and researchers reflected the value of PPI to participants. PPI was more frequently integrated in psychosocial research, though examples of PPI in laboratory/translational science were also described. PRPs asked for more opportunities to contribute meaningfully to basic scientific research and for more extensive feedback on their contributions. Conclusions The findings were used to formulate recommendations to guide effective involvement of patients in future similar projects, including identifying specific training requirements for PRPs and researchers, the identification of PRP focused tasks/deliverables at the project planning stage, and supporting access to involvement for all PRPs. Importantly, the distinctive multidisciplinary approach of EuroTEAM, incorporating both basic science and psychosocial research, facilitated patient involvement in the project overall.

Abstract Introduction Melanoma differentiation-associated gene 5 (MDA5) is a myositis-associated autoantibody. It is increasingly being recognised that this antibody presents with typical skin lesions and the potential for a rapidly progressive interstitial lung disease but without muscle involvement. We present two cases of patients with MDA5 positive dermatomyositis who both developed rapidly progressive lung disease and despite intensive treatment passed away. Case description A previously well 48-year-old Caucasian man presented with a few months history of inflammatory arthritis, Raynaud’s and Gottron’s papules. He also described exertional breathlessness and was found to have fine inspiratory crackles bibasally. An HRCT scan showed cryptogenic organising pneumonia (COP). Inflammatory markers and creatine kinase were normal but an extended myositis panel showed positive anti-MDA5 antibodies consistent with a diagnosis of amyopathic dermatomyositis. He was started on cyclophosphamide as part of a research trial, given iloprost and sildenafil for worsening digital ischaemia and commenced on home oxygen. He was admitted with worsening shortness of breath after the second cycle of cyclophosphamide and found to have pneumocystis jirovecii (PCP) positive sputum. He developed pyrexia with a positive influenza A swab and increasing oxygen requirements requiring transfer to ITU. Despite further antibiotics, antivirals, steroids, IV immunoglobulin and rituximab infusion he deteriorated further and died 13 days later. The second patient was a 45-year-old Asian man. He was initially seen by dermatology with alopecia and a scaly rash on his face, elbow and hands. He was then diagnosed with early inflammatory arthritis and commenced steroids and methotrexate. He developed skin ulceration and respiratory symptoms with a CT chest showing features of COP. He was ANA negative but anti-Ro and anti-Scl-70 positive. He was given antibiotics, methylprednisolone and switched to mycophenolate mofetil. Whilst abroad he was admitted to hospital, diagnosed with anti-MDA5 positive amyopathic dermatomyositis and given methylprednisolone and cyclophosphamide. Cyclophosphamide was continued on his return to the UK, with PCP prophylaxis but he also required home oxygen. He was admitted to hospital with increasing breathlessness and given further methylprednisolone and treatment dose co-trimoxazole. Two weeks later he deteriorated further and repeat CT scan showed a pneumomediastinum. He received antibiotics, antifungals and rituximab but died after three days on ITU. Discussion Although in both cases it was recognised the patients had some form of inflammatory condition the diagnosis of anti-MDA5 positive dermatomyositis took some time. The lack of muscle involvement is typical and means clinicians need to give more thought to the possible diagnosis particularly when patients present with skin lesions and look specifically for MDA5 antibodies. These cases also show how rapidly the lung disease can progress. Being aware that a patient is MDA5 positive gives important information to the clinical team regarding the potential prognosis and in these cases it has been questioned whether these concerns were entirely relayed to the patients and their families. High serum ferritin, ground-glass opacities in all six lung fields and worsening of pulmonary infiltrates during therapy have been suggested as further poor prognostic factors. Both patients presented particular challenges in trying to decide whether their deterioration was due to infection in the context of immunosuppression, disease progression or both and consequently full infection screens were performed including bronchoscopies at various points. Given how unwell both patients were all available treatments were considered. Once it was recognised how rapidly the lung disease was progressing they both received cyclophosphamide and rituximab. IV immunoglobulin was requested for both patients but only agreed for the first patient as he had proven PCP pneumonia. Key learning points Anti-MDA5 positive dermatomyositis commonly presents with typical mucocutaneous lesions (such as cutaneous ulceration, alopecia and oral ulcers) which can differ from those seen in classical dermatomyositis. It is important to consider the possibility of anti-MDA5 positive dermatomyositis in a patient with skin abnormalities and a normal CK, and in such circumstances request an extended myositis screen ensuring MDA5 is included. Patients who are MDA5 positive and have lung involvement often have rapidly progressive interstitial lung disease. Prognosis is especially poor when patients are admitted to ITU and worse than patients with anti-synthetase syndrome. Spontaneous pneumomediastinum can be a feature when the outcome is almost always poor in a ventilated patient. Treatment options are limited, generally aggressive immunosuppression is recommended when there is lung involvement and induction therapy with cyclophosphamide or rituximab has been tried. There are emerging reports of JAK inhibitors being used in dermatomyositis and so this may be something to consider in this subset of difficult to treat patients. Consideration should be given to vaccinating against influenza and pneumococcal infections as soon as possible, together with PCP prophylaxis and aggressive treatment of superadded infections. When appropriate patients and relatives should be made aware of the potentially poor prognosis. It is important to work closely with other specialities such as dermatology, respiratory and when necessary ITU. Due to the complexity and severity of this condition an MDT approach is recommended. Conflict of interest The authors declare no conflicts of interest.

Objectives. We aimed to conduct a large audit of routine care for patients with ANCA-associated vasculitis. Methods. We invited all 34 hospitals within one health region in England to undertake a retrospective case note audit of all patients newly diagnosed or treated with CYC or rituximab (RTX) for ANCA-associated vasculitis from April 2013 to December 2014. We compared clinical practice to the British Society for Rheumatology guidelines for the management of adults with ANCA-associated vasculitis and the use of RTX with the National Health Service (NHS) England commissioning policy and National Institute for Health and Care Excellence (NICE) technology appraisal. Results. We received data from 213 patients. Among 130 newly diagnosed patients, delay from admission to diagnosis ranged from 0 to 53 days (median 6, interquartile range 3-10.5) for those diagnosed as inpatients. BVAS was recorded in 8% of patients at diagnosis. Remission at 6 months was achieved in 83% of patients. The 1-year survival was 91.5%. A total of 130 patients received CYC for new diagnosis or relapse. The correct dose of i.v. CYC (within 100 mg of the target dose calculated for age, weight and creatinine) was administered in 58% of patients. A total of 25% of patients had an infection requiring hospital admission during or within 6 months of completing their CYC therapy. Seventy-six patients received RTX for new diagnosis or relapse. A total of 97% of patients met the NHS England or NICE eligibility criteria. Pneumocystis jiroveci pneumonia prophylaxis (recommended in the summary of product characteristics) was given in only 65% of patients. Conclusion. We identified opportunities to improve care, including compliance with safety standards for delivery of CYC. Development of a national treatment protocol/checklist to reduce this heterogeneity in care should be considered as a priority.

Objectives. We aimed to conduct a large audit of routine care for patients with ANCA-associated vasculitis. Methods. We invited all 34 hospitals within one health region in England to undertake a retrospective case note audit of all patients newly diagnosed or treated with CYC or rituximab (RTX) for ANCAassociated vasculitis from April 2013 to December 2014. We compared clinical practice to the British Society for Rheumatology guidelines for the management of adults with ANCA-associated vasculitis and the use of RTX with the National Health Service (NHS) England commissioning policy and National Institute for Health and Care Excellence (NICE) technology appraisal. Results. We received data from 213 patients. Among 130 newly diagnosed patients, delay from admission to diagnosis ranged from 0 to 53 days (median 6, interquartile range 3–10.5) for those diagnosed as inpatients. BVAS was recorded in 8% of patients at diagnosis. Remission at 6 months was achieved in 83% of patients. The 1-year survival was 91.5%. A total of 130 patients received CYC for new diagnosis or relapse. The correct dose of i.v. CYC (within 100 mg of the target dose calculated for age, weight and creatinine) was administered in 58% of patients. A total of 25% of patients had an infection requiring hospital admission during or within 6 months of completing their CYC therapy. Seventy-six patients received RTX for new diagnosis or relapse. A total of 97% of patients met the NHS England or NICE eligibility criteria. Pneumocystis jiroveci pneumonia prophylaxis (recommended in the summary of product characteristics) was given in only 65% of patients. Conclusion. We identified opportunities to improve care, including compliance with safety standards for delivery of CYC. Development of a national treatment protocol/checklist to reduce this heterogeneity in care should be considered as a priority.

common site of pathology, with decreasing incidence at the distal extremityofthelowerlimb.Inourcase,onlythefootandankleregionwas affected,withbothfeetbeingaffectedatdifferentpointsoftime.Recurrenceofepisodeshavebeendescribedintheliterature,andcan affectdifferentanatomicalsites.Thiswasthecaseforourpatient,butspecificallyaffectedthedistallimboneachoccasionratherthanmore commonproximalsites.Episodeshadbeenrelativelyfrequentalsoinourpatient,withmultipleepisodesoverthepreceding1tenyears-whichalso appearstobeanatypicalphenomenon.Duetothelocationofsymptomsatthepatient’sfeet,herrecurrentepisodeshadbeenessentiallymisdiag-nosedasprolongedgoutflares,thusleadingtodelayeddiagnosis.Unfortunately,basedontheliterature,thisisamorecommonexperience inpatientswithfootinvolvementduetoitslowerfrequencyandnon-specificnature.Assuch,patientsareatriskofpersistentbonepainsymp-tomswhichcanaffectfunctionandsubsequentqualityoflife. Key LearningPoints: Bone marrow oedemasyndromeisarare condi-tionthatcanoftenbemissed.Symptomscanbetransientinnaturewith patientsnotpresenting,orbeingmisdiagnosedwithalternativecondi-tions.Inourdescribedcase,thepatient’sepisodewasprolongedthus allowingappropriateinvestigation.Casesaregenerallymanagedcon-servatively,howevergradualresolutioncantakeweekstomonthsto occur.Literatureislimitedinregardingmedicaltherapy,howeveruseofbisphosphonateshasbeendescribedandwasutilisedinthiscase.Our

Shifts in cellular metabolism are central to activation, differentiation and proliferation of inflammatory cells and can contribute to the pathogenesis of inflammatory diseases. Integrating metabolomics data with other omics data is a major challenge but might enable clinicians to stratify stages of disease and response to therapy in patients with rheumatoid arthritis.

Background: Rituximab (RTX), a monoclonal anti-CD20 B-cell depleting antibody, is a treatment option in severe active rheumatoid arthritis (RA).Maintenance regimes for RTX in RA are debated with trials of ultra-low RTX protocols while the European license is of two 1000 mg infusions two weeks apart.Dosing schedules from 1 x 50mg up to 1 x 1000mg show evidence of B-cell depletion and have benefits of convenience for the patient as well as cost effectiveness.We conducted a baseline audit in 2013 in our trust to assess usage of RTX in RA with 72 RTX (2 x 1000 mg) cycles administered in 67 patients.In 2014, after internal approval, we implemented a single 1 x 1000mg dose maintenance RTX regimen in RA.After 18 months, we initiated a review of the outcome data presented here.Methods: Data logs from the medical infusion suite were accessed to create a working list of patients receiving RTX in the audit period (year to April 2017) and cross-referenced with pharmacy prescription data as well as review of patient letters to confirm diagnosis and review patient outcomes.Data collection continued for a further six months after the audit period for data on ongoing drug efficacy.Factors considered predictive of a better clinical response of RTX in RA such as rheumatoid factor seropositivity and number of previous biological agents were recorded.Results: Data from 116 patients with RA scheduled to receive RTX in the year up to April 2017 are reported with 156 RTX cycles (one or two infusions) administered.101 (87%) were female and 15 (13%) male.Median age was 59.5 years (range 27-85 years).15 patients (13%) had a diagnosis of RA for <5 years, 27 patients (24%) for 5-10 years and the majority, 74 patients (64%) more than 10 years.Rheumatoid Factor was negative in 18 patients (15%), not known in 18 patients (16%) and was positive in the remaining 81 patients (69%).Anti-cyclic citrullinated peptide (anti-CCP) status not known in 45 patients (39%), negative in 11 patients (9%) and positive in 60 patients (53%).108 out of 116 patients (93%) remained on RTX with a median number of RTX cycles of 4 (range 1-12).88 patients switched to single infusions remain on this regimen while 28 patients who had at least one cycle of single RTX infusion have continued with cycles of two infusions.Conclusion: These data suggest that after an initial two RTX infusions, maintenance single infusions of rituximab can be effective in RA.Further analysis to understand the reasons affecting success of single infusion cycles are underway.

providing him with appropriate supplements through the hospital pharmacy.He is currently on regular probenacid with overall significant improvement.Discussion: Though, this is a straight forward case of gout, this case posed several practical challenges in the primary and secondary care management.The following are some of the important highlights: 1.As gout in itself is a recognised cardiovascular risk factor, tight control of hyperuricaemia and gouty flares is crucial in this gentleman's overall management.2. Multiple drug intolerance for urate lowering therapy should be carefully evaluated as true or partial intolerance.Clinicians should carefully evaluate symptoms before swapping medications.3. Significant co-morbidities and drug interactions limit our choice of medications.4. Drug availability at the hospital and community level is a continuing challenge, particularly for some of the infrequently used medications.5. Drug adherence is key in managing chronic conditions particularly Gout as reflected in this case.Adequate counselling at primary and secondary care levels about ULT is essential.Key learning points: This was an interesting case which highlighted several important learning points.1. Drug intolerances to be carefully evaluated and addressed 2. Drug interactions of ULT particularly with polypharmacy should be assessed effectively by the treating clinicians.3. Education and counselling patients regarding ULT to optimise adherence.

Classification criteria for the ANCA-associated vasculitides (AAV) were developed in the 1980s, prior to the routine use of ANCA testing. The Diagnostic and Classification of the Systemic Vasculitides (DCVAS) study is an international collaborative project to update classification criteria for each type of systemic vasculitis. Provisional classification criteria for granulomatosis with polyangiitis (GPA) have been developed.

assessment and a personalized treatment approach in managing fibromyalgia.Moreover, it is very important to assess patients' expectations in order to guide interventions and set realistic achievable goals which are acceptable to both patients and clinicians.Patients' expectations are an important patient reported outcome measure which need to be assessed.

to help ensure aplanned and safe pregnancy.

The musculoskeletal system is a highly active metabolic system. Energy consumption is driven by the combined demands of skeletal muscle, turnover and remodelling of bone, cartilage and other structural components in response to changing levels of loading. The high-energy respiratory chain is estimated to result in the turnover of 65 kg/day of adenosine triphosphate for the whole body, increasing during periods of activity [1]. With skeletal muscle accounting for 30% of body mass in a postmenopausal woman (and more in men), it is perhaps not surprising then that changes in metabolic activity are observed in musculoskeletal disease. Overall resting energy use is increased by 8% in RA patients and, interestingly, a similar increase in metabolic activity is seen in patients who smoke, a well-established risk factor for the development of RA [2]. The mechanism underlying this increase in energy metabolism is unclear, but the active role of the immune system in the inflammatory processes in RA suggests that immune cell activation and turnover may contribute. There are also significant changes in liver metabolism as a result of the acute phase response and large shifts in systemic metabolism as a result of rheumatoid cachexia, where muscle degradation occurs along with the related increase in the mass of body fat. Many of these metabolic changes can pre-date obvious joint symptoms, and metabolic pathways may change in response to therapy. It is not surprising therefore that there is increasing interest in using altered metabolites as biomarkers of disease activity and response to therapy. These studies may also provide novel insights into the pathological processes driving complex musculoskeletal diseases. RA was first associated with altered levels of individual metabolites in a report from 1962 describing changes in the metabolism of tryptophan [3]. In recent years a more broad-ranging approach, metabolomics, has been applied to assessment of the disease. Metabolomics is the new kid on the omics block and comparable in scope to genomics, transcriptomics and proteomics. Through the study of small molecules (<1500 Da) within specific or multiple compartments (blood, urine, joints, saliva, eyes, tears, cerebrospinal fluid, intact cells), metabolite profiles or fingerprints, each containing thousands of metabolites, can be identified. In individuals at risk due to genetics, their environment or both, disruptive pathological processes can result in altered metabolite profiles long before overt signs and symptoms of disease appear. The metabolites themselves can be identified and quantified using NMR spectroscopy or mass spectrometry. Metabolite identification is done by reference to metabolite databases or by direct metabolite assay. The Human Metabolome Database lists >41 000 metabolite entries in the latest version, however, just 3000 have been linked with diseases to date [4]. In common with other omics approaches, metabolomics experiments generate prodigious amounts of data, but this is amenable to multivariate analysis techniques, including principal components analysis, partial least squares discriminant analysis, regression methods and genetic algorithms. Metabolomics studies have been reported for virtually all of the main rheumatologic diseases, although notably none yet for SSc [5]. Our own group has demonstrated the use of urinary metabolic fingerprint analysis to predict responses to anti-TNF [6], and we have suggested that metabolites resulting from TNF-driven cachexia are among the useful predictive biomarkers. Serum metabolic profiling can differentiate four types of human arthritis [7], and we have shown the predictive value of the serum metabolite profile in early synovitis patients, with differences between those with self-limiting disease and those who went on to develop persistent RA [8]. The value of combining omics approaches has been demonstrated in a study using proteomics and metabolomics to show alterations in both vitamin D3 metabolites and proteins in patients with AS [9]. The combination of genetic and metabolomic data [10] has shown the potential to identify genotype-influenced metabotypes in a number of chronic diseases. Different cells types vary in their energy and metabolic requirements, with cells undergoing proliferation being very different from those in a stable steady state. This applies to tissue cells such as synovial stroma and to immune cells including macrophages and T lymphocytes. Thus the state of immune activation and tissue hyperplasia may be strongly reflected in the metabolic profiles observed in tissues and in biofluids from patients, providing useful insights into the state of the disease and its aetiopathology. Comprehensive clinical assessment approaches used by BILAG and SLEDAI offer a clinical approach to individualized systems medicine by objectively quantifying components in a disease. Transcriptomics, proteomics and metabolomics are the biological equivalents of these clinical assessments. However, the sole analysis of tissues from the specific site of disease will miss the systemic changes commonly associated with complex diseases that may be responsible for driving the persistence and much of the associated co-morbidity.