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Background:Hydroxychloroquine (HCQ) has attracted much attention especially during the COVID-19 pandemic. HCQ and closely related chloroquine (CQ) have known ocular and cardiac toxicity. However, although screening guidance now exists from the Royal College of Ophthalmologists for the former (RCOphth)1, little is known regarding predictors of both forms of toxicity.Objectives:To systematically explore the literature on predictors of toxicity limited to cardiac and ocular toxicity.Methods:A detailed search of the following databases was conducted: PubMed, Medline, Embase, Web of Science, The Cochrane library, EMCare and Academic Search Premier. Studies addressing predictors of HCQ toxicity with relevant search terms used were included. Exclusion criteria were: non-English articles, pre-clinical and paediatric studies. Three authors (SR, NC, PK) independently screened titles and abstracts for inclusion, ensuring each article was screened twice. Disagreement over inclusion was adjudicated by senior reviewers (EN, JG). Data extraction (SR, NC, PK) focused on predictors of toxicity.Results:The search strategy retrieved 3103 studies. 147 studies were included for data extraction, of which 92 were eventually excluded due to: not identifying predictors (n=17), reviews (n=19), not ocular or cardiovascular toxicity (n=18), case reports (n=3), paediatrics (n=1), screening articles that focused on detecting retinopathy (n=30), article unobtainable at time of abstract submission (n=4), leaving 55 studies for full review.Studies addressing cardiac toxicity (n=16) included: cohort, retrospective observational, a comparative pharmacovigilance, systematic monitoring protocol and a randomised control trial (RCT). The majority of these involved high-dose (>5mg/kg/day) use for acute COVID-19 infection. The main significant predictors identified were: Hydroxychloroquine (HCQ) use in combination with azithromycin (6/7 studies), cumulative dose (2 studies), pre-existing cardiovascular morbidity (2/3 studies) and prolonged baseline QTc (2 studies). Individual associations were also identified in the following: longer treatment duration, daily dosage, increased age, male gender, severe COVID-19 infection, abnormal liver function tests (LFTs) and concurrent use of loop-diuretics.Regarding predictors of ocular toxicity (n=39), only one study was a RCT. The remainder were observational studies: case-control, cohort, retrospective chart reviews and letters to the editor which included original patient data.Several predictors of retinopathy and maculopathy were examined in two or more studies and included: duration of use (16/18 studies), daily dosage (7/13 studies), cumulative dose (11/14 studies), increased age (10/11 studies), body weight or BMI (3/5 studies), renal impairment (5 studies), HCQ blood levels (2 studies), keratopathy (2 studies) and tamoxifen use (2 studies). Sex (2 studies) and history of cataract surgery (2 studies) were not found to be predictors of toxicity.Only few studies performed regression analysis presenting odds and/or hazard ratios with confidence intervals.Conclusion:The most recognised predictor of cardiac toxicity was co-administration with azithromycin. In ocular toxicity, commonly cited predictors included those already recognised by the RCOphth1, as well as cumulative dose, increased age, weight considerations, HCQ blood levels and keratopathy. Further research is warranted on better characterising predictors of cardiac and ocular toxicity in patients on HCQ and CQ therapy.References:[1]The Royal College of Ophthalmologists. Hydroxychloroquine and Chloroquine Retinopathy: Recommendations on Monitoring [Internet]. The Royal College of Ophthalmologists; 2020 [cited 2021 Jan 25].Disclosure of Interests:Natasha Citeroni: None declared, Sanketh Rampes: None declared, Pinky Kotecha: None declared, Jan Schoones: None declared, Elena Nikiphorou: None declared, James Galloway Speakers bureau: JG has received honoraria / speaker fees from Abbvie, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UCB.

Background:A growing number of professional societies in clinical and medically related disciplines investigate evidence, make recommendations, and take action to advance gender equity. Evidence on women’s advancement and leadership in the context of the European Alliance of Associations for Rheumatology, EULAR, is limited [1].Objectives:The objective of the EULAR Task Force on Gender Equity in Academic Rheumatology was to establish the extent of the unmet need for support of female rheumatologists, health professionals and non-clinical scientists in academic rheumatology and develop a framework to address this through EULAR and Emerging EULAR Network (EMEUNET).Methods:Potential interventions to accelerate gender-equitable career advancement in academic rheumatology were gathered from a narrative review of the relevant literature, expert opinion of a multi-disciplinary Task Force (comprised of 23 members from 11 countries), data from the surveys of EULAR scientific member society leaders, EULAR and EMEUNET members, and EULAR Executive Committee members. These interventions were rated by Task Force members, who ranked each according to perceived priority on a five-point numeric scale from 1 = very low to 5 = very high.Results:A framework of 29 potential interventions was formulated, which covers six thematic areas, namely, EULAR policies, advocacy and communication, EULAR Congress and associated symposia, training courses, mentoring/peer support, and EULAR funding (Figure 1).Figure 1.A framework of potential interventions with the levels of priority, mean and standard deviation (SD)Conclusion:The framework provides structured interventions for accelerating gender-equitable career advancement in academic rheumatology.References:[1]Andreoli L, Ovseiko PV, Hassan N, et al. Gender equity in clinical practice, research and training: Where do we stand in rheumatology? Joint Bone Spine 2019;86(6):669-72.Acknowledgements:The task force is grateful to EULAR for funding this activity under project number EPI 024.Disclosure of Interests:None declared

Background:Sick leave (SL) represents an often poorly studied adverse work outcome especially in early axSpA, with speculation around the potential role of clinical and socioeconomic (SE) factors.Objectives:To investigate the occurrence of SL and the impact of clinical and SE factors on SL in early axSpA.Methods:Patients with a clinical diagnosis of axSpA from the DESIR cohort up to 5 years of follow-up (6-month visits in the first 2 years, followed by annual visits) were studied. Time to SL and potential baseline and time-varying predictors were explored, with a focus on SE variables: age, gender, smoking status since last visit, ethnicity (Caucasian vs other), job type based on ‘collar’ (blue vs white), educational status (low vs high -university), marital status (married vs not) and parental status (number of children); and clinical factors including disease activity (ASDAS/BASDAI), function (BASFI), mobility (BASMI), at each time point. The incidence of SL was calculated as the number of SL events over the total number of person-days under observation. Univariable analyses, followed by collinearity and interaction tests, guided subsequent multivariable Cox survival model building.Results:In total, 704 axSpA patients with work-related data were included in this study: mean (SD) age 33.8 (8.6); 46% male. At baseline, 80% of patients were employed; of these, 5.7% reported being on SL, with people shifting in and out of different work states over time. The distribution of first and recurrent SL episodes over time is shown in the figure 1. The incidence of SL amongst those at risk (n=620, 88%) and across the five years of DESIR was 0.05 (95% CI 0.03, 0.06) per 1000 days calculated in a total of 913,559 observed person-days. In survival analyses, 7% (n=43) of those at risk developed SL at some point. Mean (SD) time to SL was 806 (595) days (min 175, max 2021 days). In people who developed SL, 25% did so at 364 days; 50% and 75% at 545 and 1172 days, respectively. Significant differences were seen between baseline socio-demographic, clinical variables and treatment in patients who developed SL at any point, compared to those who did not. In multivariable models (Table 1) older age, higher disease activity, smoking and use of TNFi, the latter likely a proxy to worse disease, were all significantly associated with more SL. Male gender and higher education were associated with less SL. There were no relevant interactions between SE factors and clinical variables.Table 1.Univariable and multivariable model analyses with Sick Leave as outcome.Type of analysisUnivariable analysisMultivariable modelHR (95% CI)HR (95% CI) (N = 614)Explanatory variablesAge1.04 (1.01, 1.08)1.05 (1.01, 1.09)Male gender0.37 (0.19, 0.74)0.41 (0.20, 0.86)High education0.33 (0.17, 0.61)0.48 (0.24, 0.95)Marital status2.44 (1.12, 5.27)NSASDAS (CRP)1.83 (1.34, 2.50)1.49 (1.04, 2.13)BASFI, 0-101.24 (1.09, 1.40)*BASMI, 0-101.76 (1.31, 2.38)*Comorbidity count1.77 (1.22, 2.57)NSHLA-B27 positive0.51 (0.28, 0.93)NSSmoking (current vs not)2.40 (1.31, 4.37)2.55 (1.32, 4.91)NSAID score last week, 0-4001.01 (1.00, 1.01)NSOral Corticosteroid use (vs no)3.90 (1.80, 8.46)NSTNF use2.86 (1.55, 5.28)2.41 (1.27, 4.58)*Variables tested in models separate from ASDAS. NS=Not significant in multivariable model.Figure 1.Distribution of first and recurrent sick leave episodes over time in the study population at risk.Conclusion:In this early axSpA cohort of young, working-age individuals, older age and worse disease activity were associated with more SL, whereas male gender and higher education were associated with less SL. The findings suggest a role of SE factors such as gender and level of education in adverse work outcomes, alongside active disease.Disclosure of Interests:None declared

Background:Work outcomes in spondyloarthritis (SpA) have mostly been studied in axSpA, less in peripheral SpA (pSpA) or PsA. The ASAS-COMOSPA study showed that lower education, female gender and lower healthcare expenditures (HCE) are associated with lower odds of employment in SpA. However, it is unknown whether country-level factors or SpA phenotype (axSpA/pSpA/PsA) modify the effect of individual-level socioeconomic factors.Objectives:To examine whether associations between socioeconomic factors and work outcomes differ across SpA phenotype and whether associations for individual-level socioeconomic factors are modified by country-level factors.Methods:Working age patients (18-65 years) from the ASAS-perSpA (peripheral involvement in SpA) study were included. Associations between individual- (age, gender, education, marital status) and country-level socioeconomic factors (Human Development Index (HDI), HCE) with work outcomes (employment status (binary), absenteeism, presenteeism (tertiles)) were assessed using mixed-effects logistic and ordinal logistic models. Models were adjusted for confounders. Separate models for ASDAS, BASFI and BASDAI were created in turn due to collinearity. Effect modification by SpA phenotype and country-level factors was tested using interaction terms.Results:A total of 3835 patients (mean age 42 years, 61% males) from 23 countries worldwide were included (66% axSpA, 10% pSpA, 23% PsA). Being employed was associated with gender (male vs female OR 2.5; 95%CI 1.9-3.2), education (university vs primary OR 3.7; 2.9-4.7) and being married (vs single OR 1.3; 1.04-1.6) (Table 1). University (vs primary) education was associated with lower odds of absenteeism (OR 0.7; 0.5-0.7) and presenteeism (OR 0.5; 0.3-0.7). Associations were not statistically different across SpA phenotypes. HCE was significantly associated with all work outcomes: employment (OR 2.5; 1.5-4.1), absenteeism (OR 0.6; 0.4-0.9) and presenteeism (OR 0.6; 0.3-0.9). HDI results were similar. Gender discrepancy in odds of employment was greater in countries with lower socioeconomic development; eg, males had 3.5 higher odds of employment than females in countries with low HCE, whereas the difference was 1.8 fold in high HCE countries.Table 1.Effect of individual socio-economic factors on work outcomes.Employment statusOR (95% CI)AbsenteeismOR (95% CI)PresenteeismOR (95% CI)N378022182127Age1.43 (1.36,1.51)1.00 (0.99,1.01)1.00 (0.99,1.01)Age20.996 (0.995, 0.996)NS - uniNS - uniMale (vs female)2.48 (1.92,3.21)1.22 (0.96,1.56)0.97 (0.78,1.20)EducationPrimaryrefrefrefSecondary1.86 (1.48,2.35)0.69 (0.49,0.99)0.69 (0.49,0.99)University3.68 (2.87,4.72)0.67 (0.47,0.96)0.49 (0.34,0.69)Marital statusSinglerefrefrefMarried1.27 (1.04,1.56)0.95 (0.73,1.22)0.98 (0.78,1.22)Divorced or Widowed1.39 (0.98,1.97)1.39 (0.88,2.18)1.16 (0.74,1.82)ASDAS0.78 (0.72,0.84)1.51 (1.33,1.72)2.31 (2.04,2.61)FatigueNS - multi1.14 (1.09,1.21)1.30 (1.24,1.36)Depression0.70 (0.59,0.82)1.45 (1.15,1.82)1.95 (1.59,2.39)FibromyalgiaNS - multi1.62 (1.11,2.35)1.58 (1.03,2.41)BMINS - multi0.99 (0.97,1.02)NS - multiDactylitis1.41 (1.12,1.76)NS - uniNS - uniUveitisNS - multi0.62 (0.46,0.84)NS - uniNSAIDsNS - multi1.53 (1.18,1.99)1.32 (1.07,1.64)bDMARDsNS - multiNS - uni1.23 (1.01,1.51)Models used ASDAS rather than BASDAI/BASFI, which are collinear. NS, not significant in the univariable or multivariable model.Conclusion:Individual- (lower education) and country-level socioeconomic factors (lower healthcare expenditure) were both associated with (lower) work participation, independently of SpA phenotype. The disadvantageous effect of female gender on employment is particularly strong in countries with lower socioeconomic development. This highlights the need for wider societal interventions, such as improving education and healthcare investment, to improve work outcomes.Disclosure of Interests:Sizheng Steven Zhao: None declared, Elena Nikiphorou Speakers bureau: Pfizer, Lilly, AbbVie, Annelies Boonen Consultant of: Yes, Grant/research support from: Yes, Clementina López-Medina: None declared, Maxime Dougados: None declared, Sofia Ramiro Speakers bureau: Lilly, MSD, Novartis, UCB, Consultant of: AbbVie, Lilly, MSD, Novartis, UCB, Sanofi, Grant/research support from: MSD.

Objective: To examine secular trends in demographic, clinical manifestations and comorbidity on first presentation of RA prior to DMARD treatment. Methods: 2701 patients were recruited over 25years to two UK-based RA inception cohorts: the Early RA Study (9 centres; 1986-2001) and the Early RA Network (23 centres; 2002-2012). Trends in demographic and baseline clinical/laboratory and radiographic variables and comorbidities were estimated using mixed effects models, including random effects for recruitment centre. Results: Age-at-onset increased from 53.2 to 57.7 years in 1990 and 2010 respectively (2.6 months/year; 95% CI 1.2-4.1). Gender-ratio, the proportion living in deprived areas and smoking status were unchanged (p>0.05) and there were no changes in the proportion seropositive or erosive at baseline (p>0.05). After controlling for treatment at the time of assessment, ESR reduced and haemoglobin increased over time (p 0.05). The overall prevalence of comorbidity increased from 29.0% in 1990 to 50.7% in 2010, mainly due to cardiovascular and non-cardiac vascular conditions including hypertension. There was a significant increase in BMI (0.15 units/year; 95% CI 0.11-0.18), resulting in an increase in the prevalence of obesity from 13.3% in 1990 to 33.6% in 2010. Conclusions: Age-at-onset and comorbidity burden, especially obesity have increased at RA presentation over 25 years, reflecting wider demographic trends at the population level. In contrast there were no accompanying changes in disease severity assessed by composite markers of disease activity, radiographic erosions, seropositivity or HAQ at presentation. Treatment strategies in early RA should take greater account of the impact of co-morbidity on outcomes. This article is protected by copyright. All rights reserved.

Objective. To evaluate, firstly, all published data on baseline and annual progression rates of radiographic damage from all longitudinal observational cohorts, and secondly, the association of standard clinical and laboratory parameters with long-term radiographic joint damage. Methods. A comprehensive search of the literature from 1975 to 2014, using PubMed, SCOPUS and Cochrane databases, identified a total of 28 studies that investigated long-term radiographic progression, and 41 studies investigating predictors of long-term radiographic progression. This was submitted and approved by PROSPERO in February 2014 (Registration Number: CRD42014007589). Results. Meta-analysis indicated an overall baseline rate of 2.02%, and a yearly increase of 1.08% of maximum damage. Stratified analysis found that baseline radiographic scores did not differ significantly between cohorts recruiting patients pre- and post-1990 (2.01% vs 2.03%; P > 0.01); however, the annual rate of progression was significantly reduced in the post-1990 cohorts (0.68% vs 1.50%; P < 0.05). High levels of acute phase markers, baseline radiographic damage, anti-CCP and RF positivity remain consistently predictive of long-term radiographic joint damage. Conclusion. Critical changes in treatment practices over the last three decades are likely to explain the reduction in the long-term progression of structural joint damage. Acute phase markers and presence of RF/anti-CCP are strongly associated with increased radiographic progression.

Opportunities within EMEUNET and BRiTs

Background:Intra-articular therapies (IAT) are widely used in clinical practice to treat patients with rheumatic and musculoskeletal diseases (RMDs). Many factors influence their efficacy and safety. There is a wide variation in the way IATs are delivered by health professionals. In an attempt to standardise these procedures, evidence-based recommendations are the right way forward.Objectives:To establish evidence-based recommendations to guide health professionals using IAT in adult patients with peripheral arthropathies.Methods:At a first face-to-face meeting, the results of an overview of systematic reviews were presented to the multidisciplinary task force of members from 8 countries. The aim, scope and outline of the taskforce were also established at this meeting. Thirty-two clinical questions ranked for priority (relevance for practice plus feasibility) drove the systematic reviews performed by two fellows. In addition, two surveys addressed to physicians, health professionals and patients throughout Europe were agreed to acquire more background information. At the second face-to-face meeting, the evidence for each research question was discussed, and each recommendation shaped and voted in a first Delphi round. Level of agreement was numerically scored 0 to 10 (0 completely disagree, 10 completely agree). All panellists voted anonymously using a sli.do app. Agreement needed to be greater than 80% to be included in a second Delphi round, which also allowed reformulation of statements. Finally, a third Delphi round was sent to the taskforce. The level of evidence was assigned to each recommendation according to the EULAR SOP for establishing recommendations.Results:Recommendations focus on practical aspects for daily practice to guide health professionals before, during and after IAT in adult patients with peripheral arthropathies. Five overarching principles were established, together with 11 recommendations that address the following issues: (1) patient information; (2) procedure and setting; (3) accuracy issues; (3) routine and special antiseptic care; (4) safety issues and precautions to be addressed in special populations; (5) efficacy and safety of repeated joint injections; (6) the usage of local anaesthetics; and (7) aftercare. The document includes the supporting evidence and results from the surveys, level of evidence and agreement.Conclusion:We have developed the first evidence and expert opinion based recommendations to guide health professionals using IAT.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Terence O’Neill: None declared, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Ingrid Möller: None declared, Valentina Vardanyan: None declared, Jenny de la Torre-Aboki: None declared, Lene Terslev: None declared, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Elena Nikiphorou: None declared, IRENE Pitsillidou: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Intra-articular therapies (IAT) are routinely used in rheumatic and musculoskeletal diseases (RMDs); however large variability exists regarding current practice of delivery amongst health professionals.Objectives:To inquire about common practice aspects to inform the EULAR Taskforce for the IAT of arthropathies.Methods:A steering committee prepared a 160-item questionnaire based on the information needs of the Taskforce. The survey was disseminated via EULAR professional associations and social media and it was open to any health professional treating persons with RMDs, regardless of using IAT personally.Results:The survey was answered by 186 health professionals from 26 countries, the large majority of whom (77%) were rheumatologists, followed by nurses (12%), general practitioners (2%) and orthopaedic surgeons (2%). The two collectives that perform IAT routinely are rheumatologists (97%) and orthopaedic surgeons (89%), with other professionals Conclusion:Although often performed in clinical practice for RMDs, there is apparent variability in several elements related to delivery of this treatment. This information, together with patient input, will help design current recommendations where research evidence is not available.Acknowledgments:Eular Taskforce grant CL109Disclosure of Interests:Jenny de la Torre-Aboki: None declared, IRENE Pitsillidou: None declared, Jacqueline Uson Jaeger: None declared, Esperanza Naredo: None declared, Lene Terslev: None declared, Mikael Boesen Consultant of: AbbVie, AstraZeneca, Eli Lilly, Esaote, Glenmark, Novartis, Pfizer, UCB, Paid instructor for: IAG, Image Analysis Group, AbbVie, Eli Lilly, AstraZeneca, esaote, Glenmark, Novartis, Pfizer, UCB (scientific advisor)., Speakers bureau: Eli Lilly, Esaote, Novartis, Pfizer, UCB, Hemant Pandit Grant/research support from: Glaxo Smith Kline (GSK) for work on Diclofenac Gel, Speakers bureau: Bristol Myers Squibb for teaching their employees about hip and knee replacement, Ingrid Möller: None declared, Maria Antonietta D’Agostino Consultant of: AbbVie, BMS, Novartis, and Roche, Speakers bureau: AbbVie, BMS, Novartis, and Roche, Willm Uwe Kampen: None declared, Terence O’Neill: None declared, Michael Doherty Grant/research support from: AstraZeneca funded the Nottingham Sons of Gout study, Consultant of: Advisory borads on gout for Grunenthal and Mallinckrodt, Francis Berenbaum Grant/research support from: TRB Chemedica (through institution), MSD (through institution), Pfizer (through institution), Consultant of: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Bone Therapeutics, Regulaxis, Peptinov, 4P Pharma, Paid instructor for: Sandoz, Speakers bureau: Novartis, MSD, Pfizer, Lilly, UCB, Abbvie, Roche, Servier, Sanofi-Aventis, Flexion Therapeutics, Expanscience, GSK, Biogen, Nordic, Sandoz, Regeneron, Gilead, Sandoz, Valentina Vardanyan: None declared, Elena Nikiphorou: None declared, Sebastian C Rodriguez-García Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme España, S.A., Sanofi Aventis, UCB Pharma, Raul Castellanos-Moreira: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme España, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution)

Background:Women represent an increasing proportion of the overall rheumatology workforce, but are underrepresented in academic rheumatology, especially in leadership roles [1].Objectives:The EULAR Task Force on Gender Equity in Academic Rheumatology has been convened to establish the extent of the unmet need for support of female rheumatologists, health professionals and non-clinical scientists in academic rheumatology and develop a framework to address this through EULAR and EMEUNET.Methods:To investigate gender equity in academic rheumatology, an anonymous web-based survey was targeted at the membership of EULAR and Emerging EULAR Network (EMEUNET) and their wider networks. The survey was developed based on a narrative literature review [1], best practice from The Association of Women in Rheumatology, a survey of task force members and face-to-face task force discussions. Personal experiences were explored and 24 potential interventions to aid career advancement were ranked. Statistics were descriptive with significance testing for male/female responses compared using chi-squared/t-tests. The level of significance was set at pResults:A total of 301 respondents from 24 countries fully completed the survey. By profession, 290 (86.4%) were rheumatologists, 19 (6.3%) health professionals, and 22 (7.3%) non-clinical scientists. By gender, 217 (72.1%) were women, 83 (27.6%) men, and 1 (0.3%) third gender. By age, 203 (67.5%) were 40 or under. By ethnicity, 30 (10.0%) identified themselves as ethnic minority. A high proportion of respondents reported having experienced gender discrimination (47.2% total: 58.1% for women and 18.1% for men) and sexual harassment (26.2%: 31.8% and 10.8% respectively) (Figure 1). Chi-squared tests on the numbers on which these proportions were based showed statistically significant differences between women and men in having experienced gender discrimination (Χ2=36.959 (df=1), p Figure 1.Perceived gender discrimination and sexual harassment, 301 responsesFigure 2.Mean perceived utility of potential interventions for career advancement by gender and statistically significant gender differences (pConclusion:The results of the survey will inform the development of task force policy proposals for interventions to support career advancement among EULAR and EMEUNET members. The identified interventions have potential to support career advancement of all rheumatologists, health professionals and non-clinical scientists regardless of gender.References:[1]Andreoli L, Ovseiko PV, Hassan N, Kiltz U, van Mens L, Gossec L, et al. Gender equity in clinical practice, research and training: Where do we stand in rheumatology? Joint, Bone, Spine: Revue du Rhumatisme. 2019;86(6):669-672.Acknowledgments:We gratefully acknowledge the rheumatologists, health professionals and non-clinical scientists who responded to the survey.Disclosure of Interests:Pavel V Ovseiko: None declared, Laure Gossec Grant/research support from: Lilly, Mylan, Pfizer, Sandoz, Consultant of: AbbVie, Amgen, Biogen, Celgene, Janssen, Lilly, Novartis, Pfizer, Sandoz, Sanofi-Aventis, UCB, Laura Andreoli: None declared, Uta Kiltz Grant/research support from: AbbVie, Amgen, Biogen, Novartis, Pfizer, Consultant of: AbbVie, Biocad, Eli Lilly and Company, Grünenthal, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, MSD, Novartis, Pfizer, Roche, UCB, Leonieke van Mens: None declared, Neelam Hassan: None declared, Marike van der Leeden: None declared, Heidi J Siddle: None declared, Alessia Alunno: None declared, Iain McInnes Grant/research support from: Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Janssen, and UCB, Consultant of: AbbVie, Bristol-Myers Squibb, Celgene, Eli Lilly and Company, Gilead, Janssen, Novartis, Pfizer, and UCB, Nemanja Damjanov Grant/research support from: from AbbVie, Pfizer, and Roche, Consultant of: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Speakers bureau: AbbVie, Gedeon Richter, Merck, Novartis, Pfizer, and Roche, Florence Apparailly: None declared, Caroline Ospelt Consultant of: Consultancy fees from Gilead Sciences., Irene van der Horst-Bruinsma Grant/research support from: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Consultant of: AbbVie, Novartis, Eli Lilly, Bristol-Myers Squibb, MSD, Pfizer, UCB Pharma, Elena Nikiphorou: None declared, Katie Druce Speakers bureau: Pfizer and Lilly, Zoltán Szekanecz Grant/research support from: Pfizer, UCB, Consultant of: Sanofi, MSD, Abbvie, Pfizer, Roche, Novertis, Lilly, Gedeon Richter, Amgen, Alexandre Sepriano: None declared, Tadej Avcin: None declared, George Bertsias Grant/research support from: GSK, Consultant of: Novartis, Georg Schett Speakers bureau: AbbVie, BMS, Celgene, Janssen, Eli Lilly, Novartis, Roche and UCB, Anne Maree Keenan: None declared, Laura C Coates: None declared

Background:In clinical training, a portfolio is expected to stimulate learning and encourage critical reflection. Some, but not all, European countries use a portfolio in rheumatology training, and their scope varies widely. A EULAR portfolio for Rheumatology trainees could contribute to improve overall training, raise educational standards, foster the setting of common goals and harmonize rheumatology training across countries.Objectives:Develop key components that should be included in a EULAR portfolio of Rheumatology.Methods:A working group (WG) composed of 9 rheumatologists and 1 educationalist was established. A systematic literature review (SLR) was conducted in November 2018, according to the PIM structure: Population: trainees; Instrument of interest: portfolio; Measurement of properties of interest: content portfolio. A survey was disseminated among the WG group and WG members of the EMerging EUlar NETwork (EMEUNET), inquiring about the content and structure of existing national portfolios. Portfolio materials of selected countries were reviewed. Last, the WG elected the key components of the portfolio.Results:13/2,034 articles were included in the SLR (12 high/1 moderate risk of bias). Information on direct observation of procedural skills (DOPS) (9/13), personal reflections (8/13), learning goals (5/13) and multisource feedback (5/13) were most often included in the portfolio. Twenty-five respondents filled out the survey (response rate ≈ 50%). Reflective writing (n=7), learning goals (n=4) and feedback (n=4) were considered the most useful components of a portfolio. About half indicated that a portfolio was a bureaucratic burden; 4 respondents mentioned lack of feedback by supervisors as a barrier. Portfolio materials of 7 European countries were reviewed. Several portfolios (Germany, Italy, Greece and Spain) were logbooks, i.e. a record of clinical activities. Other portfolios (UK, Denmark, The Netherlands) also included information on workplace-based assessments, learning goals, and personal reflections. The proposed key components of the portfolio are included in Table 1.Table 1.Key components of the EULAR portfolio of Rheumatology.Key componentContentCurriculum vitaePersonal record of achievements, experiences, knowledge and skillsPersonal Development PlanLearning goals and action planClinical workInformation on managing patients (e.g. rheumatoid arthritis)Skills (e.g. joint aspiration)Assessments (summative and formative)Personal reflectionsProfessional behaviourMultisource feedbackPersonal reflectionsEducationContinuing professional development, list of formal and non-formal learning activitiesAssessments (e.g. teaching assessment, evidence based medicine assignment)Personal reflectionsResearchList of abstracts, published articlesInformation on research funding, scholarships, bursaries, academic postsConclusion:This initiative resulted in the establishment of a list of key components to be included in a EULAR portfolio of Rheumatology. Assessment forms for each key portfolio component are currently being developed. Portfolio implementation, particularly in countries that do not use it yet, may contribute significantly to promote a higher standard of patient care across Europe.Disclosure of Interests:Marloes van Onna: None declared, Sofia Ramiro Grant/research support from: MSD, Consultant of: Abbvie, Lilly, Novartis, Sanofi Genzyme, Speakers bureau: Lilly, MSD, Novartis, Catherine Haines: None declared, M. Holland-Fischer: None declared, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis, Jean Dudler: None declared, Christopher Edwards Grant/research support from: Abbvie, Biogen, Roche, Consultant of: Abbvie, Samsung, Speakers bureau: Abbvie, BMS, Biogen, Celgene, Fresenius, Gilead, Janssen, Lilly, Mundipharma, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB,Alessia Alunno: None declared, Elena Nikiphorou: None declared, L. Falzon: None declared, Francisca Sivera: None declared

Background: Respiratory tract infections are among the leading causes of hospitalization in rheumatoid arthritis (RA) and Streptococcus Pneumoniae (Sp) is one of the most frequent pathogens involved. For these patients, the CDC recommends a combined vaccination scheme (CVS) using two types of Sp vaccines but evidence on its effectiveness remains insufficient.1 Objectives: To assess the impact of the combined vaccination scheme on the incidence of Sp infections in patients with RA treated with DMARD. Methods: A cohort was nested in a register including patients with RA who were prescribed a bDMARD or tsDMARD -either naive or switch- from 2000 to March 2019. The target outcomes were invasive pneumococcal disease (IPD) and all-cause community-acquired pneumonia (CAP), as defined by relevant MedDRA codes. Demographic and clinical features were also retrieved. Each participant centre informed about the date when they implemented a systematic Sp vaccination protocol and whether they were using the CVS. Those not adopting this practice were excluded from the analysis. Crude incidence rates (IRs) were calculated for each outcome as well as for its combination (combined variable defined as “Sp infections”). Exposure was split into two periods, considering the date when the CVS was officially recommended in Spain (May 2015). The incidence rate ratio (IRR) comparing pre and post implementation periods was estimated with a Poisson regression model adjusted for sex, age and comorbidities (Charlson Index). Results: 1704 patients were included, their characteristics are shown in table 1. One centre was excluded for not using any Sp vaccination protocol while the remaining ones reported using the CVS. Crude IRs by periods (pre and post CVS implementation) and age groups are shown in table 2. The IRR of the post-vaccination period after adjusting for age, sex and comorbidities (Charlson index) was 0.40 (95% CI: 0.29 - 0.56), p Conclusion: The incidence of Sp infections experienced a decrease in RA patients taking bDMARD or tsDMARD after the introduction of the stepwise combined vaccination scheme that is not related to age, sex or comorbidities. References: [1] Furer V, et al. Ann Rheum Dis 2019;0:1–14 Disclosure of Interests: Sebastian C Rodriguez-Garcia Speakers bureau: Novartis Farmaceutica, S.A., Merck Sharp & Dohme Espana, S.A., Sanofi Aventis, UCB Pharma, Carlos Sanchez-Piedra: None declared, Raul Castellanos-Moreira Speakers bureau: Lilly, MSD, Sanofi, UCB, Dolores Ruiz-Montesinos: None declared, Victoria Hernandez: None declared, Manuel Pombo: None declared, Fernando Sanchez-Alonso: None declared, Loreto Carmona Grant/research support from: Novartis Farmaceutica, SA, Pfizer, S.L.U., Merck Sharp & Dohme Espana, S.A., Roche Farma, S.A, Sanofi Aventis, AbbVie Spain, S.L.U., and Laboratorios Gebro Pharma, SA (All trhough institution), Juan Jesus Gomez-Reino: None declared

Accumulating research evidence suggests that individual dietary factors and dietary patterns might be implicated in the risk of development of rheumatoid arthritis (RA). This narrative review aims to present this evidence and provide nutritional recommendations for reducing RA risk in susceptible individuals. Overall, a 'Western' type diet rich in energy intake, total and saturated fat, an unbalanced ratio of n-3 to n-6 fatty acids, high in refined carbohydrates and sugar and low in fiber and antioxidants might increase the risk of RA both directly through increasing inflammation and indirectly through increasing insulin resistance and obesity, with the latter being a known risk factor for RA. On the contrary, consumption of long-chain omega-3 polyunsaturated fatty acids, derived from fish and fish oil, is associated with a reduced risk of RA probably due to their anti-inflammatory properties. The Mediterranean diet (MD), rich in plant-based foods such as wholegrains, legumes, fruit, vegetables, extra-virgin olive oil and low in red meat consumption, might have the potential to reduce the risk of RA. Based on current research evidence, it is suggested that adherence to the MD enhanced with an increased consumption of fatty fish, reduced consumption of sugar-sweetened drinks and maintenance of a normal body weight, contributes to reducing the risk of RA. Further research on RA susceptibility will allow for more specific dietary recommendations to be made.

The impact of dietary interventions such as specific types of diet or nutritional supplements in rheumatoid arthritis (RA) has been subject to increased attention in recent years. The recognition of the unmet need to better understand the effects of specific dietary interventions on disease outcomes in RA, along with the growing patient interest on lifestyle interventions beyond pharmacotherapy, have informed the undertaking of this narrative literature review. The benefits of the Mediterranean Diet (MD) have been shown in various studies, although only a limited number of trials focus specifically on RA. Based on the studies reviewed, the MD may provide benefits in reducing pain and swollen and tender joints in RA patients. There is more and better evidence that n-3 polyunsaturated fat (PUFA) supplementation has the potential to reduce inflammation and provide clinical benefit, possibly slowing progression to pharmacotherapy. Yet, many of these studies to date are limited in their methodology; this being partly a reflection of the complexity of the research questions being addressed. Consequently, the conclusions that can be robustly drawn from their results are restricted. With a focus on clinical trials on the MD and fish oil supplementation, this review critically appraises the evidence, discussing the findings of studies in the wider context of impact on RA outcomes, methodological challenges, and practical points to consider as part of the routine care of RA patients.

ObjectivesTo explore the role of individual and country level socioeconomic (SE) factors on employment, absenteeism and presenteeism in patients with spondyloarthritis (SpA) across 22 countries worldwide.MethodsPatients with a clinical diagnosis of SpA fulfilling the ASAS classification criteria and in working age (≤65 years) from COMOSPA were included. Outcomes of interest were employment status, absenteeism and presenteeism, assessed by the Work Productivity and Activity Impairment Specific General Health questionnaire. Three multivariable models were built (one per outcome) using mixed-effects binomial (for work status) or ordinal regressions (for absenteeism and presenteeism), with country as random effect. The contribution of SE factors at the individual-level (eg, gender, education, marital status) and country-level (healthcare expenditure (HCE) per capita, Human Development Index (HDI) and gross domestic product per capita) SE factors, independent of clinical factors, was assessed.ResultsIn total, 3114 patients with SpA were included of which 1943 (62%) were employed. Physical function and comorbidities were related to all work outcomes in expected directions and disease activity also with absenteeism and presenteeism. Higher education (OR 4.2 (95% CI 3.1 to 5.6)) or living in a country with higher HCE (OR 2.3 (1.5 to 3.6)) or HDI (OR 1.9 (1.2 to 3.3)) was positively associated with being employed. Higher disease activity was associated with higher odds for absenteeism (OR 1.5 (1.3 to 1.7)) and presenteeism (OR 2.1 (1.8 to 2.4)). No significant association between individual-level and country-level SE factors and absenteeism or presenteeism was found.ConclusionsHigher education level and higher country SE welfare are associated with a higher likelihood of keeping patients with SpA employed. Absenteeism and presenteeism are only associated with clinical but not with individual-level or country-level SE factors.

The Oxford Handbook of Rheumatology, 4th edition, includes a chapter on the hereditary diseases of connective tissue. Of importance, up-to-date genetic information and classification of subtypes of osteogenesis imperfecta is reviewed. There is a summary of a broad range of diseases of connective tissue including Marfan syndrome, Stickler disease, and arthrogryposis—conditions encountered occasionally by the rheumatologist. The chapter details the new 2017 criteria for Ehlers–Danlos syndrome and outlines the new classification for the hypermobility spectrum disorders and the distinction between generalized, localized, and regional hypermobility and hypermobility Ehlers–Danlos syndrome, both in adults and in children.

The Oxford Handbook of Rheumatology, 4th edition, takes the reader through a pragmatic and realistic way of assessing musculoskeletal and rheumatological disease presentation in its first four chapters. The text reflects real life, with differential diagnoses suggested as information becomes available through the details from history, then examination, then investigations. The chapters focus on patterns of, and focal regional, symptoms in adults and children. In this chapter, the book considers musculoskeletal and rheumatic conditions which occur in, or are closely associated with, other conditions of the skin, eye, heart, lung, kidney, and in hormonal, neurological, and gastrointestinal systems. Such an approach should help general practitioners and rheumatology trainees caring for their patients across their medical comorbidities and in general medicine. There is also a section on musculoskeletal–rheumatological features in patients with neoplasia. The chapter focuses primarily on adult disease.

The Oxford Handbook of Rheumatology 4th edition, has been extensively updated to thoroughly review aspects of musculoskeletal pain. Pain pathophysiology is reviewed. Chronic pain and fibromyalgia in adults and in children and adolescents is dealt with in detail. The reader is advised to cross reference from this chapter to Chapters 1–3 in the Handbook, where regional musculoskeletal pain conditions are listed and reviewed. In localized pain syndromes, the chapter has an overview of complex regional pain syndrome (CRPS), which is not infrequently encountered in rheumatology and musculoskeletal clinics. Included in detail for this edition, is the assessment and management of pain in children, which is a highly specialized clinical area of medicine and will be of use to the adult rheumatologist and general practitioner as well as paediatric specialists. Readers should cross reference to Chapter 23 on medications, for ‘pain medications’ in the Handbook

This chapter describes the clinical and laboratory classification criteria for antiphospholipid syndrome. It highlights the complexity and diagnostic challenges of antiphospholipid syndrome and discusses potential mimics of the disease that need to be excluded. Current therapeutic targets as well as novel therapeutic avenues are explored. The chapter finishes with a section on catastrophic antiphospholipid syndrome, which constitutes a rheumatological emergency. The clinical presentation, laboratory features, treatment, and outcomes of this life-threatening presentation of antiphospholipid syndrome are also discussed.

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This chapter describes the epidemiology, aetiopathogenesis, presenting features, clinical manifestations, and management of osteoarthritis. Commonly used investigations for osteoarthritis, their indication, and interpretation are described. A summary of the commonly used drugs for the treatment of osteoarthritis, their mechanism of action, and key points for starting are included. Non-pharmacological holistic management is also discussed. Exciting emerging therapies that could change the future landscape of osteoarthritis management are introduced.

This extensive chapter facilitates a focused regional musculoskeletal assessment with additional detail specific to children and adolescents. Taking each region or joint in turn, the reader is supported with (1) tables of differential diagnoses; (2) detailed descriptions of anatomy including reference ranges; (3) lines of enquiry that identify work- or sport-related injury; (4) examination that recognizes radiation, neuropathy, impingement, myopathy, and stress; (5) functional assessment; and (6) specific tests. In children, there is an additional focus on developmental or normal variants and dysplasia. The chapter also draws attention to common errors in assessment and mimics, the relative merits of investigation, and, when not covered elsewhere, treatments of joint-specific problems. The chapter is thorough, although not exhaustive, and supplements general enquiry.

This chapter focuses on Sjögren’s syndrome and covers epidemiological, pathophysiological, and clinical aspects of disease. It discusses classification criteria and disease-specific features, along with potential differential diagnoses. The chapter also includes a section on the extra-glandular (systemic) manifestations of disease, illustrating its potential for multiorgan involvement. The chapter provides a guide to the reader regarding how to best approach a patient presenting with related symptoms and signs. Furthermore, it discusses relevant investigations for the key manifestations of disease, the sicca symptoms, and describes common biopsy findings. The chapter closes with the treatment of Sjögren’s syndrome and a note on prognosis.

This chapter explores the epidemiology and pathophysiology of idiopathic inflammatory myopathies. The chapter takes a focus on polymyositis and dermatomyositis and describes relevant diagnostic criteria, clinical presentations, investigations, and therapeutic options. Other inflammatory myopathies discussed include inclusion-body myositis and other (adult) inflammatory myopathies such as those induced by drugs. The chapter closes with a description of juvenile idiopathic inflammatory myopathies, a heterogeneous group of inflammatory muscle conditions affecting young people and consisting of juvenile dermatomyositis and amyopathic juvenile dermatomyositis among others.

The multisystem, autoimmune nature of systemic lupus erythematosus (SLE) and its broad spectrum of presenting clinical manifestations are explored in detail in this chapter. Important comorbidities and associations between SLE and the antiphospholipid syndrome and pregnancy are also discussed. The chapter details the various autoantibodies associated with the disease, along with their prevalence and associated clinical features. In addition, it provides a detailed review of the management of SLE, starting from conservative measures through to disease-modifying, immunosuppressive therapy to plasma exchange and stem cell transplantation. Novel therapeutic agents are also summarized, along with a note on prognosis. The chapter includes a section on childhood and neonatal SLE, covering presentation, relevant investigations, and treatment.

General rheumatological assessment is for musculoskeletal pain, stiffness or swelling, weakness, fever, rashes, and fatigue. This chapter describes both the nature of those symptoms helpful in making a diagnosis and also the subjective elements influenced by exertion, loss of function, anxiety, cultural norms, and other symptoms. In children and adolescents, symptoms are also influenced by developmental stage and may present simply as a limp or loss of limb function. Other referrals are for symptom complexes (such as Raynaud’s disease) or isolated abnormal investigations (such as elevated erythrocyte sedimentation rate or antinuclear antibody). Both paediatric and adult assessment requires the effective use of the (p)GALS screening examination tool described here. The nature of symptoms requiring rheumatological assessment varies according to diagnosis and has a subjective element influenced by exertion, impact, anxiety, cultural norms, and associated symptoms. They include musculoskeletal pain and stiffness, weakness or loss of limb function, fever, and also fatigue. Other referrals require assessment of symptom complexes or isolated abnormal investigations.

This chapter describes large, medium, and small vessel primary vasculitides. The 2012 Chapel Hill Consensus Conference nomenclature of vasculitis is introduced, and acts as a framework for more detailed descriptions of polymyalgia rheumatic and giant cell arteritis, polyarteritis nodosa (systemic and cutaneous), granulomatosis with polyangiitis, microscopic polyangiitis, eosinophilic granulomatosis with polyangiitis, Takayasu arteritis, childhood-onset vasculitis, Kawasaki disease, Henoch–Schönlein purpura, and leucocytoclastic vasculitis. Other antineutrophil cytoplasmic antibody-associated vasculitides and primary angiitis of central nervous system in children are also covered. The epidemiology, aetiopathogenesis, classification criteria, presenting features, clinical manifestations, and management of these diseases are presented. In particular, diagnostic criteria for and mimics of polymyalgia rheumatic and giant cell arteritis are discussed in detail to permit rheumatologists and non-rheumatologists to confidently manage them.

The Oxford Handbook of Rheumatology, 4th edition, includes a chapter on spondyloarthritis (SpA) conditions. These conditions are axial spondyloarthritis, including ankylosing spondylitis, psoriatic arthritis, reactive arthritis, and inflammatory bowel disease-related arthritis. It summarizes evidence for pathogenetic mechanisms either common to all conditions, or specific for each condition, highlights current disease classifications, and emphasizes clinical features common to all SpAs, such as inflammatory back pain and enthesitis. There is an expanded section on treatments including biologic disease-modifying antirheumatic drugs (bDMARDs; ‘biologics’) such as anti-tumour necrosis factor-α‎, ustekinumab, and secukinumab, and new to this edition of the Handbook, an expanded section on juvenile spondyloarthritis.

Mesenteric panniculitis (MP) is a rare chronic disease characterized by inflammation and subsequently fibrosis of adipose tissue of the omentum. Only recently it has been associated with IgG4-related disease. Cancer antigen 125 (CA-125) is a high-molecular mass glycoprotein, traditionally associated with ovarian cancer, although it can be elevated in other conditions. Herein we describe a case of a 56-year-old man with IgG4 related mesenteric panniculitis associated with very high levels of CA-125 at the onset of disease. The CA-125 levels corresponded to clinical disease activity and improved with steroid therapy and rituximab. A literature review was performed concerning possible association of MP, IgG4-related disease and CA-125. The review of literature suggests that high levels of CA-125 can be raised in non-malignant, inflammatory conditions including IgG4-related mesenteritis and can improve with treatment.

The Oxford Handbook of Rheumatology, 4th edition, chapter on ‘Spinal disorders and back pain’ brings together a pragmatic approach to categorizing back pain, how to investigate disorders presenting with back pain, and how to treat adults, children, and adolescents with back pain. In the chapter, the management of back pain is separated into acute, subacute, and chronic presenting scenarios and the text makes reference to other chapters in the book where there may be some additional useful information (e.g. spondyloarthritis-associated back pain in Chapter 8 and chronic pain syndromes in Chapter 22). Notably the chapter is best read in conjunction with relevant sections in Chapter 3 (‘Regional musculoskeletal symptoms: making a working diagnosis’). The chapter makes reference to the need for a rigorous diagnostic approach to all the conditions which cause back pain, and at whatever age. There are subsections on how to assess paediatric spinal disorders and how to take a broad holistic approach to managing chronic back pain where there is no specific diagnosis.

The Oxford Handbook of Rheumatology, 4th edition, includes a chapter on metabolic bone diseases with an extensive review of the modern management of all forms of osteoporosis and fracture risk assessment including glucocorticoid-induced osteoporosis, idiopathic juvenile osteoporosis, and DXA scanning. The chapter outlines the salient features of other less common and occasionally encountered bone diseases found in rheumatological practice including vitamin D deficiency, osteomalacia and rickets, hypercalcaemia, parathyroid disease, Paget’s disease of bone, SAPHO syndrome, osteochondroses, osteonecrosis, fibrous dysplasia, sclerosing bone dysplasias, and bone tumours. New to this Handbook edition is a section on the main childhood autoinflammatory conditions manifest as skeletal disease under the umbrella term chronic non-bacterial osteomyelitis.

This chapter covers commonly encountered rheumatological emergencies, including septic arthritis (for both adults and paediatrics), infections in patients taking biologic therapy, acute systemic lupus erythematosus (SLE), systemic vasculitis, systemic sclerosis-related crises, methotrexate-induced pneumonitis, macrophage activation syndrome (MAS), and paediatric osteomyelitis. Malignancies presenting with musculoskeletal symptoms in children are also covered. Several of these topics are covered in more detail in other chapters of this handbook, with links provided from this chapter as appropriate.

Infectious agents have been linked directly and indirectly to a number of acute and chronic inflammatory rheumatological diseases. This chapter introduces some examples of the organism-specific and autoimmune responses leading to rheumatic disease. The epidemiology, aetiopathogenesis, classification criteria, clinical presentation, and management of septic arthritis (pyogenic non-gonococcal arthritis and gonococcal arthritis), Mycobacterium tuberculosis arthritis, osteomyelitis, Lyme disease, rheumatic fever, septic bursitis, and atypical mycobacterial infection are presented.

This chapter provides a systematic approach to rare autoimmune and autoinflammatory or monogenetic genetic conditions. These conditions typically present with characteristic fevers such as familial Mediterranean fever, TRAPS, cryopyrin-associated periodic syndromes, and adult-onset Still’s disease; characteristic skin manifestations such as panniculitis, neutrophilic dermatoses, and eosinophilic fasciitis; or with refractory synovial disease or polychondritis. Rare multisystem conditions of unknown aetiology including sarcoidosis, Behçet’s disease, amyloidosis, and immunoglobulin G4-related disease are described in terms of organ or system involvement.

The Oxford Handbook of Rheumatology, 4th edition, includes a chapter on glucocorticoid (‘steroid’) injection therapy. Soft tissue, tendon sheath, tendon insertion (enthesis), and joint injections are commonly carried out by rheumatologists in outpatient clinics. The chapter outlines the principles of injection techniques referring to the utility of both image-guided and non-imaging-guided injection procedures and cross-refers to line drawings of joint and tendons elsewhere in the book. The chapter focuses also on the use of injections in the context of managing specific disorders such as tennis elbow, plantar fasciitis, carpal tunnel syndrome, and greater trochanter pain syndrome, thus placing injection therapy in the context of alternatively available therapies.

The Oxford Handbook of Rheumatology, 4th edition, emphasizes the importance of evidence-based therapeutics and therefore devotes a whole chapter to medications used to treat rheumatological and bone disease (‘Drugs used in rheumatological disease’). Details about treatments are cross-referenced to specific use of medications for specific diseases and conditions elsewhere in the book. There are chapter sections on analgesics including opiate-based medications, NSAIDs, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, intravenous immunoglobulin, and other immunosuppressants. There is a specific focus in the chapter on drugs used for Raynaud’s disease, osteoporosis (e.g. bisphosphonates), pulmonary hypertension, gout, and hyperuricaemia. Overall there is reference to both adult and paediatric disease treatments in the chapter.

This chapter describes the presenting features, clinical manifestations, and management of rheumatoid arthritis. Commonly used investigations, their indication and interpretation, as well as the holistic treatment of rheumatoid arthritis are outlined. A summary of the commonly used drugs for the treatment of rheumatoid arthritis, their mechanism of action, and key points for starting and monitoring their use is included. Special circumstances including the management of rheumatoid arthritis in pregnancy, surgery, vaccinations, and during infections are also discussed.

This chapter focuses on systemic sclerosis, a generalized autoimmune connective tissue disease. It describes the epidemiology and classification of systemic sclerosis, along with its pathophysiology and potential triggers of disease. It also discusses the condition’s broad spectrum of clinical manifestations and highlights its potential for multiorgan involvement and life-threatening complications. Furthermore, the chapter provides insights into the definitions for related conditions such as morphoea and its different subtypes. Complexities around the treatment and a discussion on the prognosis and outcomes of systemic sclerosis and related conditions are also included.

The key to a rheumatological diagnosis and formulation of an effective management plan is a structured history and thorough examination that assesses the extent or impact of disease, screens for asymptomatic components, and tests for any red flags and incongruence. This, in turn, focuses the use of investigations, which alone rarely provide a diagnosis. Our structured approach aims to identify (1) those conditions not be missed; (2) normal variants; (3) inflammatory and non-inflammatory causes of pain, including chronic pain; (4) mono/oligo articular diagnoses; (5) multi/polyarticular or widespread presentations; and (6) diagnoses with systemic features. Assessment of the child and adolescent acknowledges the impact of musculoskeletal development on presentation and a parental-derived history. All assessment includes evaluation of infectious causes of musculoskeletal pain, gait, limp, muscle weakness and polysymptomatology.

This chapter describes crystal-induced musculoskeletal disease, which encompasses gout, hyperuricaemia, calcium pyrophosphate dihydrate disease, basic calcium phosphate-associated disease, and calcium oxalate arthritis. Their epidemiology, aetiopathogenesis, classification criteria, presenting features, clinical manifestations, and management are discussed. Diet, lifestyle, non-pharmacological and pharmacological approaches to their management are considered. User-friendly algorithms for the management of gout and calcium pyrophosphate dihydrate disease are provided, allowing both rheumatologists and non-rheumatologists to confidently manage these diseases in clinic, ward, or community settings.

The presentation and natural history of juvenile idiopathic arthritis (JIA) differs from that of the adult inflammatory arthritides and this chapter describes the key features and differentials that need to be considered. In making a diagnosis, this chapter should be used in association with Part I of the Handbook. The chapter conveys information useful for explaining JIA to parents, national guidelines and other routine therapeutic practices, analysis of subtypes of JIA, and uveitis commonly associated with JIA. The description of systemic-onset JIA includes its differential and association with macrophage activation syndrome. As an archetypal long-term musculoskeletal condition, the key features of transition and age-appropriate care are also discussed here.

Background Treat-to-target (T2T) principles in rheumatoid arthritis (RA) are now widely recognised as effective in achieving optimal disease outcomes. Objectives To examine for differences in outcomes between low (LDAS) and remission (RDAS) disease activity score (DAS) categories, addressing the question: is LDAS a ‘good enough’ treatment target in RA? Methods Data from two consecutive UK multi-centre RA inception cohorts with similar design were used: the Early RA Study (ERAS) and Early RA Network (ERAN). Recruitment figures/median follow up for ERAS and ERAN were 1465/10 years (maximum 25 years), and 1236/6 years (maximum 10 years) respectively. Standard demographic and clinical variables were recorded at baseline and then annually until the end of study follow up. Disease activity was categorised by mean DAS28 score between years 1–5 as remission [mRDAS Results Out of 2701 patients, 468 (17%) were in mRDAS, 284 (11%) in mLDAS in the first five years of disease. Lower proportions had achieved sRDAS (8%), sLDAS (6%) and Boolean (2%) remission. Mean age was similar across categories; more women were in low vs remission DAS. Compared to mLDAS or sLDAS, inflammatory markers, DAS, functional (HAQ, PCS) and mental (MCS) scores tended to be better in the mRDAs, sRDAS or Boolean remission categories (figure 1). Significant differences (p Conclusions The results demonstrate striking differences between remission and low DAS categories, suggesting worse functional and SF36 outcomes over time in the low DAS categories. This supports that remission should be the primary T2T goal in in RA. Disclosure of Interest None declared

Background Young clinicians and researchers frequently work alongside other medical specialists in order to share expertise, knowledge and skills. Multidisciplinary work is worthwhile but may be sometimes challenging. Objectives To describe current clinical and research collaboration among young specialists and to identify some perspectives to develop such collaborations. Methods An online survey was disseminated by email and social media (facebook and twitter) to members of the Emerging European League Against Rheumatism Network (EMEUNET), the Young Nephrologists’ Platform (YNP), the Paediatric Rheumatology European Society Emerging Rheumatologists and Researchers (PReS EMERGE), and the European Academy of Allergy and Clinical Immunology Junior Members (EAACI JM). Results Of 354 respondents from 40 countries, 60% were female, 23% were aged below 30 years and 67% 31–40 years. Young rheumatologists were the most represented (36%), followed by young nephrologists (24%), young paediatricians (18%), young allergologists (11%) then young internists (3%) and several other specialties (as clinical immunology, dermatology, pulmonology, orthopaedics). 60% were certified specialists, 34% in training and 6% were researchers without clinical work. Overall, the top 3 specialties for clinical collaboration in daily practice were radiology, cardiology and dermatology. Collaborations were reported frequently by phone and email, also by various combined clinics while common local multidisciplinary meetings were uncommon. Of note, 71% of respondents found collaboration with young colleagues easier than with senior specialists. Research collaboration usually started by knowing other specialists (73%) and/or by attending common meetings (39%). 96% would like to develop clinical research collaborations and 69% basic research collaborations. The majority of young specialists would be interested in online (84%) and/or 1–2 days (86%) common courses including cases discussion (80%) and training workshops (84%), as well as webinars recorded with several specialists on a specific disease (96%). Respondents were a bit less enthusiastic with developing collaboration through social media (facebook 61%, twitter 58%) but interested in common apps (71%). Conclusions This collaborative initiative highlighted wishes from young specialists for developing 1) regular local multidisciplinary meetings to discuss complex patients 2) clinical research collaboration with combined grants and 3) multidisciplinary online projects such as common courses, webinars and apps. Acknowledgements We thank all members of young organisations for their active participation. Disclosure of Interest None declared

Background Mobile health (mHealth) is exponentially growing in the current era, providing new potential and transforming the face of healthcare delivery. While the increasing availability of applications (apps) may enable people with rheumatic and musculoskeletal diseases (RMDs) to better self-manage their health, there is a general lack of evidence on ways to ensure appropriate development and evaluation of apps. Objectives To obtain an overview of existing mHealth apps for self-management in patients with RMDs, regarding content and development methods in particular, through a systematic literature review. Methods A search was performed up to December 2017 using EMBASE, Pubmed, Cochrane library, Web of Science and Psychinfo databases, with relevant key words and MeSH terms addressing three key domains: RMDs, self-management and mHealth. Double screening was performed on 15% of all abstracts against agreed inclusion criteria. For each publication relevant to an app for RMDs, the content, the aims, the target population of the apps and their development strategies were noted. The analysis was descriptive. Results Of 562 abstracts, 57 full text were screened. 39 articles were included in the analysis. 13 articles referred to an app linked to a connected device. Most of the apps targeted rheumatoid arthritis patients (n=11), juvenile idiopathic arthritis (n=7) and osteoarthritis (n=8). The development process of the app was poorly described in 19/39 (48.7%) of the studies (figure 1). Only 6/39 (15.4%) included patients, and 14/39 (35.9%) included health professionals or physicians in the development of such apps. Moreover, a qualitative phase occurred in only 6/39 (15.4%) of the cases. The app was tested and evaluated by physicians in 6/39 (15.4%). Patients were more frequently involved in app evaluation (29/39, 74.4%) but mostly indirectly through their adherence to the app. Only few of the apps published on were commercially available (5/39, 12.8%), 4/5 are free. One app is currently under development. Conclusions The development process of most apps was poorly described and potentially not satisfying in many studies. Despite patient willingness to use mHealth apps for self-management of their RMDs, a strong effort needs to be made to provide a standard and ensure quality and safety of newly-developed apps. This work will further inform EULAR points to consider for development, evaluation and implementation of mobile health applications for self-management of RMDs by patients. Disclosure of Interest None declared

This lecture will focus on the case of a psoriatic arthritis (PsA) patient presenting primarily with entheseal disease rather than the usual poly-articular phenotype. The case discusses issues around misinterpretation of signs and symptoms leading to inappropriate diagnoses and failure to early disease recognition and therefore treatment. Consequences of delayed treatment and less typical presentations of PsA will be discussed in greater detail during the session, highlighting important diagnostic and management aspects of disease, relevant to routine clinical practice. Disclosure of Interest None declared

Background The treat-to-target (T2T) approach, with earlier, aggressive treatment has resulted in improvements in rheumatoid arthritis (RA) outcomes 1,2 . Whether these improvements have translated into improvements in patient reported outcomes is less clear. Studies have indicated declines in pain and function as well as depression and anxiety. However, these studies are limited to short follow-up periods or were restricted to cross-sectional, rather than longitudinal analyses. Objectives To assess changes in 5 year progression rates for disease activity and patient reported outcomes in a prospective cohort of early RA patients between 2002 and 2011. Methods The Early RA Network (ERAN) is a longitudinal prospective cohort study that recruited 1236 early RA patients from 2002 to 2011. DAS-28 and SF-36 were measured at baseline, 6 months, 12 months and then yearly. Multi-level linear regression were used to model 5 year progression rates of both DAS-28 and SF-36 in patients recruited between 2002–2011. Models controlled for sex and age and seropostivity at baseline. DMARD use at baseline was controlled for using propensity score weighting. Year of diagnosis was entered as a continuous variable, allowing for the mean of the outcome variables to be estimated for 2002 and 2011. Restricted cubic splines were used to account for non-linear progression over time. Results Disease activity for patients diagnosed in 2011 demonstrated a statistically significant decrease at year 5 compared to patients diagnosed in 2002 (5 year estimated mean difference −0.35; 95% CI 0.22–0.49, p 0.05). Mental health was similar to the normalised population mean of 50, irrespective of year diagnosed. However, levels of vitality/fatigue, function and pain remain less favourable for all early RA patients over the first 5 years. Conclusions Although disease activity has shown a marked decline at 5 years between 2002 and 2011, there is little evidence that this has led to improvements of an equivalent magnitude in function, pain, fatigue and mental health. Treatment should also focus on improved function, pain management, fatigue and mental health as part of the T2T protocol. References [1] Twigg S, et al. Fatigue, older age, higher body mass index and female gender predict worse disability in early rheumatoid arthritis despite treatment to target: A comparison of two observational cohort studies from the United Kingdom. Arthritis Care Res. (Hoboken). 2017. doi:10.1002/acr.23281 [2] Carpenter L, et al. Reductions in Radiographic Progression in Early Rheumatoid Arthritis Over Twenty-Five Years: Changing Contribution from Rheumatoid Factor in Two Multicenter UK Inception Cohorts. Arthritis Care Res. 2017;69. Disclosure of Interest None declared

Background Treatment of Sjogren’s syndrome (SS) has traditionally focused on conventional synthetic DMARDs (csDMARDs), with encouraging evidence on the benefit of biologic therapies emerging, mainly for treatment of SS extraglandular manifestations. Overlapping autoimmune diseases in SS are poorly studied; yet evidence primarily from case reports suggest a beneficial effect with biologics. Objectives To systematically review the literature on the treatment of SS with biologics, taking a focus on case reports and overlapping autoimmune conditions or extraglandular manifestations (defined here as those described in the EULAR SS disease activity index - ESSDAI). Methods A literature review was performed independently by two reviewers, using Pubmed and the following search terms: “Sjogren” or “Sjogren’s” AND any of the following: “biologics”, “Etanercept”, “Adalimumab”, “Infliximab”, “Golimumab”, “Certolizumab”, “Tocilizumab”, “Abatacept”, “Rituximab”, “Belimumab”, “Secukinumab”, “Ustekinumab” and “Anakinra”. Inclusion criteria were: articles in English; published until January 2018; case reports of patients with primary or secondary SS. Initial screening was based on title/abstract, followed by full-text review for articles fulfilling inclusion criteria. For articles written in a different language, information was obtained from abstract if available, otherwise excluded. Concordance in article screening was 95% across the two reviewers. Data extraction focused on reporting overlapping autoimmune diseases and extraglandular manifestations, treatment and response data. Results Out of 679 papers screened, 39 articles were included. 22 overlapping autoimmune conditions were reported in 22 SS patients (table 1). Most of the patients were treated with Rituximab (63.6%), while TNF-inhibitors (22.7%), Tocilizumab (9.1%) and Ustekinumab (4.5%) were also used. Concurrent treatment with csDMARDs and steroids was used in 28.6% and 42.9% of the cases, respectively. 61.9% and 13.6% of the patients were csDMARDs- and biologic- experienced, respectively. Good response of overlapping condition was seen in 86.4% of them, while in 13.6%, control or partial response was reported. Although, most of the studies do not mention the effect of biologic treatment on SS, general ‘improvement’ was mentioned in 4 cases, while arthritis was improved in 6 patients, 4 of which had secondary SS. In terms of extraglandular manifestations (e.g cryoglobulinemic vasculitis, interstitial nephritis) 18 were reported. 16 (88.8%) patients received Rituximab (one of them in combination with Belimumab), while 2 (11.1%) were treated with TNF-inhibitors. 11.1% and 61.1% of them received concurrent treatment with csDMARDS and steroids, respectively. 55.5% and 11.1% of the patients were csDMARDs- and biologics- experienced, respectively. Extraglandular manifestations responded well in the majority (83.3%) of the patients, with the remaining having partial or late response. SS and arthritis ‘improvement’ was mentioned in 5 and 1 patients, respectively. Table 1 Biologic treatments used for overlapping autoimmune conditions in SS patients. csDMARDs: conventional synthetic Disease Modifying Antirheumatic Drugs, NA: Not Applicable, Joints: improvement of arthritis. ^SS response was defined as clinical improvement of sicca symptomatology or improvement in ESSDAI. Improvement of arthritis was reported separately. † cases of secondary Sjogren’s syndrome (3 cases co-existing with RA and one case with SLE) Conclusions Treatment with biologic DMARDs, sometimes accompanied by steroids, appears to be beneficial also in treating overlapping autoimmune diseases as well as some extraglandular manifestations in SS patients. Disclosure of Interest None declared

Background Mesenteric panniculitis (MP), a rare fibrotic inflammatory disease of the bowel mesentery, can be a rare manifestation of IgG4-related disease (IgG4-RD). IgG4-RD is a chronic inflammatory disease most commonly affecting the pancreas, characterised by infiltration of IgG4-positive plasma cells and lymphocytes into various organs.1 We recently encountered a male patient with IgG4-related MP who was incidentally found to have a very high level of CA-125, which correlated with CRP levels and normalised after steroid treatment. This prompted a systematic literature review (SLR) to better understand this unexpected phenomenon. Objectives To investigate for associations between CA-125, MP and/or IGG4-RD, understand possible common pathophysiological mechanisms and explore potential clinical implications. Methods The SLR was performed using MEDLINE, EMBASE, Web of Science, and Scopus, looking for literature on either MP and CA-125 or IgG4-RD and CA-125 up to January 8 2018, using a comprehensive search strategy with relevant mesh terms and keywords linked to the above broad categories. Literature screening was performed by two independent reviewers. Results 24 unique citations were found, of which 13 were unanimously identified as relevant by the two reviewers. The final selected articles included: 8 case reports, 3 conference abstracts of case reports, 1 cohort study of 22 patients, and a retrospective study of 7 patients (table 1). CA-125 was raised in 22/40 patients in the identified reports (shown in red), including males, and was often the only elevated tumour marker (yellow). We also report on the presence of effusions (blue), as this may be linked to the causal mechanism. Table 1 The clinical and laboratory characteristics of cases of IgG4-RD and MP AI Autoimmune, AIH: Autoimmune Hepatitis, AIP: Autoimmune Pancreatitis, SM: Sclerosing Mesenteritis, ↑: Raised, ↔: Normal Conclusions To our knowledge, this is the first SLR exploring the association between CA-125 and IgG4-RD and MP. Despite the small sample, our results do indicate that CA-125 was raised in more than 50% of reported cases, the majority of which also had some kind of effusion. Although traditionally a marker of ovarian cancer, this report highlights that a raised CA-125 can be found in other, non-malignant, inflammatory conditions, and potentially correlates with inflammatory burden. CA-125 in this setting may thus represent a useful biomarker and have a role in monitoring treatment response. Reference [1] Minato H, Shimizu J, Arano Y, et al. IgG4-related sclerosing mesenteritis: a rare mesenteric disease of unknown etiology. Pathol Int. 2012;62:281–6. Disclosure of Interest None declared