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Objectives To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of clinical features predicting US synovitis/tenosynovitis. Methods In a longitudinal multicentre study, SLE patients with physician-diagnosed inflammatory joint pain received intramuscular methylprednisolone 120 mg once. Clinical assessments, patient-reported outcomes and bilateral hand/wrist USs were collected at 0, 2 and 6 weeks. The primary outcome (determined via internal pilot) was the early morning stiffness visual analogue scale (EMS-VAS) at 2 weeks, adjusted for baseline, comparing patients with positive (greyscale ≥2 and/or power Doppler ≥1) and negative US. Post hoc analyses excluded FM. Results Of 133 patients, 78 had a positive US. Only 53 (68%) of these had one or more swollen joint. Of 66 patients with one or more swollen joint, 20% had a negative US. A positive US was associated with joint swelling, symmetrical small joint distribution and serology. The primary endpoint was not met: in the full analysis set (N = 133) there was no difference in baseline-adjusted EMS-VAS at week 2 [−7.7 mm (95% CI −19.0, 3.5); P = 0.178]. After excluding 32 patients with FM, response was significantly better in patients with a positive US at baseline [baseline-adjusted EMS-VAS at 2 weeks −12.1 mm (95% CI −22.2, −0.1); P = 0.049]. This difference was greater when adjusted for treatment [−12.8 mm (95% CI −22, −3); P = 0.007]. BILAG and SLEDAI responses were higher in US-positive patients. Conclusion In SLE patients without FM, those with a positive US had a better clinical response to therapy. Imaging-detected synovitis/tenosynovitis may be considered to decide on therapy and enrich clinical trials.

BackgroundThe MSK components of the BILAG and SLEDAI have limited sensitivity, specificity and responsiveness.ObjectivesTo develop a better disease activity tool for MSK lupus.Methods“LAMDA” was derived using data from the multicentre USEFUL study (PMID:33792659); 133 patients with inflammatory MSK pain received intramuscular depomedrone then were assessed for 66/68 SJC/TJC, BILAG-2004, SLEDAI-2K, physician MSK-VAS, inflammatory markers, patient pain and disease-activity-VAS and MSK-ultrasound. Baseline variables were modelled against US using penalized (Lasso) regression. For validation we evaluated: (i) responsiveness at week 6 in USEFUL and (ii) association with quality of life and treatment decision in an independent study (n=100).ResultsLAMDA was a composite of SJC, patient-MSK-pain-VAS, physician-MSK-disease-activity-VAS and ESR ranging from 0 to 26.5. Response effect size was greater for the LAMDA (0.37) than the BILAG-MSK (0.31), SLEDAI-MSK (0.27) and total US score (0.33). With active US at baseline, LAMDA’s effect size was 0.42.In the validation study LAMDA score correlated with better physical function (R = -0.49, pConclusionLAMDA is a continuous disease activity instrument for MSK lupus that is sensitive to imaging-synovitis without swelling, more responsive than other instruments and correlates with quality of life and treatment decision. LAMDA may improve the ability of clinicians to monitor and treat MSK lupus, and determine the efficacy of therapies in clinical trials.AcknowledgementsFunding: Lupus UK and NIHRDisclosure of InterestsKhaled Mahmoud: None declared, Ahmed Zayat: None declared, Md Yuzaiful Md Yusof: None declared, Lee-Suan Teh: None declared, Shah Khan: None declared, Chee-Seng Yee: None declared, David D’Cruz: None declared, Nora Ng: None declared, David Isenberg: None declared, Coziana Ciurtin: None declared, Philip G Conaghan: None declared, Paul Emery: None declared, Christopher John Edwards: None declared, Elizabeth Hensor: None declared, Edward Vital Speakers bureau: GSK, AstraZeneca, Consultant of: GSK, AstraZeneca, Roche, Aurinia, Lilly, ILTOO, Novartis, Grant/research support from: AstraZeneca, Sandoz

ObjectiveTo determine whether SLE patients with inflammatory joint symptoms and ultrasound-synovitis achieve better clinical responses to glucocorticoid compared to patients with normal scans. Secondary objectives included identification of clinical features predicting ultrasound-synovitis.MethodsA longitudinal muticentre study of SLE patients with physician-diagnosed inflammatory joint pain was undertaken. Clinical assessments, patient-reported outcomes, and bilateral hands and wrist ultrasound were collected at 0-, 2- and 6-weeks after intramuscular methylprednisolone 120mg. The primary outcome (determined via internal pilot analysis) was EMS-VAS at 2-weeks, adjusted for the baseline value, comparing patients with positive (GS≥2 and/or PD≥1) and negative ultrasound. Post-hoc analyses adjusting for fibromyalgia were performed.ResultsOf 133 patients recruited, 78/133 had positive ultrasound, but only 68% of these had ≥1 swollen joint. Of 66/133 patients with ≥1 swollen joint, 20% had negative ultrasound. Positive ultrasound was associated with joint swelling, symmetrical small joint distribution and serology. In full analysis set (n=133) there was no difference in baseline-adjusted EMS-VAS at week 2 (−7.7mm 95% CI − 19.0mm, 3.5mm, p=0.178). After excluding 32 fibromyalgia patients, response was significantly better in patients with positive ultrasound at baseline (baseline-adjusted EMS-VAS at 2-weeks - 12.1 mm, 95% CI −22.2mm, −0.1mm, p=0.049). This difference was greater when adjusted for treatment (−12.8mm (95% CI −22mm, −3mm), p=0.007). BILAG and SLEDAI responses were higher in ultrasound-positive patients.ConclusionsIn SLE patients without fibromyalgia, those with positive ultrasound had a better clinical response to therapy. Imaging-detected synovitis should be used to select SLE patients for therapy and enrich clinical trials.

Background In SLE, musculoskeletal manifestations have an impact on quality of life, disability and clinical trial outcomes, but are harder to assess than in RA and PsA. We previously showed that joint swelling lacks sensitivity, specificity and responsiveness compared to ultrasound. USEFUL was a multicentre longitudinal study to determine clinical features predicting ultrasound synovitis and whether patients with ultrasound synovitis respond better to therapy.\ud \ud Methods SLE patients were recruited if the referring physician deemed they had inflammatory pain warranting treatment. Swollen joints were not required. At baseline, physicians recorded the features that led them to diagnose inflammatory pain and features of concurrent fibromyalgia and osteoarthritis. Stable doses of prednisolone (≤5 mg/day), antimalarials or immunosuppressants were allowed. Participants received depomedrone 120 mg IM then were assessed at 0, 2 and 6 weeks for 66/68 swollen and tender joint counts, BILAG-2004, SLEDAI-2K, physician global and MSK-VAS, inflammatory markers, patient pain and disease activity-VAS, HAQ-DI, LupusQoL, ultrasound of hands and wrists (blinded to patient and clinical assessor). An internal pilot determined the primary endpoint: EMS-VAS at 2 weeks (adjusted for baseline) between patients with ultrasound-synovitis vs. normal ultrasound at baseline. Sensitivity analyses adjusted for prednisolone and immunosuppressants.\ud \ud Results 122/133 patients recruited completed all visits. There was significant disagreement between clinical examination and ultrasound. 78/133 had ultrasound synovitis; 68% of these had ≥1 swollen joint. Of 66/133 patients with ≥ 1 swollen joint, 20% had normal ultrasound.\ud \ud Ultrasound-synovitis was more likely with joint swelling, a symmetrical small joint distribution and active serology. Physician-determined EMS, other lupus features or prior response to therapy were not associated. Fibromyalgia or osteoarthritis did not reduce the probability of ultrasound synovitis.\ud \ud In the full analysis set (n=133) there was no difference in EMS VAS at 2 weeks according to ultrasound synovial status as baseline (difference -8 mm, 95% CI -19, 4 mm, p=0.178). 32 patients had fibromyalgia. After excluding these patients, we found a statistically and clinically significantly better clinical response to depomedrone in patients with ultrasound-synovitis at baseline (baseline-adjusted EMS VAS at 2 weeks -12 mm, 95% CI -24, 0 mm, p=0.049). This difference was greater in the treatment-adjusted sensitivity analysis (-12.8 (95% CI -22, -3 mm), p=0.007) and the per-protocol-adjusted sensitivity analysis (-14.8 mm (95% CI -20.8, -8.8 mm), p

Background:In SLE, musculoskeletal manifestations impact on quality of life and trial outcomes. We previously showed that assessments based on joint swelling lack sensitivity, specificity and responsiveness compared to ultrasound (US).Objectives:To determine clinical features predicting US synovitis and whether patients with US synovitis respond better to therapyMethods:SLE patients were recruited if the referring physician deemed they had inflammatory pain warranting treatment. Swollen joints were not required. At baseline, physicians recorded features of inflammation, concurrent fibromyalgia and osteoarthritis. Stable doses of prednisolone (≤5mg/day), antimalarials or immunosuppressants were allowed. Participants received depomedrone 120mg IM then were assessed at 0, 2 and 6 weeks for 66/68 swollen and tender joint counts, BILAG-2004, SLEDAI-2K, physician global and MSK-VAS, inflammatory markers, patient pain and disease activity-VAS, HAQ-DI, LupusQoL, US of hands and wrists (blinded to patient and clinical assessor). An internal pilot determined the primary endpoint:(Early Morning stiffness-VAS (EMS-VAS) at 2 weeks (adjusted for baseline) between patients with US-synovitis (GS≥2 or PD≥1 in ≥1 joint) vs. normal US at baseline. 20% difference was considered clinically meaningful. Sensitivity analyses adjusted for prednisolone and immunosuppressants.Results:122/133 patients completed all visits. There was significant disagreement between clinical examination and US. 78/133 had US synovitis; 68% of these had ≥1 swollen joint. Of 66/133 patients with ≥ 1 swollen joint, 20% had normal US. US-synovitis was more likely with joint swelling, a symmetrical small joint distribution and active serology. Physician-determined EMS, other lupus features or prior response to therapy were not associated. Fibromyalgia or osteoarthritis did not reduce the probability of US synovitis.In the full analysis set (n=133) there was no difference in EMS VAS at 2 weeks according to US synovial status at baseline (difference -8mm, 95% CI -19, 4mm, p=0.178). 32 patients had fibromyalgia. After excluding them, we found a statistically and clinically significantly better clinical response to depomedrone in patients with US-synovitis at baseline (baseline-adjusted EMS VAS at 2 weeks -12mm, 95% CI -24, 0mm, p=0.049). This difference was greater in the treatment-adjusted sensitivity analysis (-12.8 (95% CI -22, -3mm), p=0.007) and the per-protocol-adjusted sensitivity analysis (-14.8mm (95% CI -20.8, -8.8mm), pConclusion:In lupus arthritis, distribution and serology, but not other features, help identify US-synovitis. US-synovitis was independent of features of fibromyalgia, but fibromyalgia confounded assessment of clinical response. US should be used to select SLE arthritis patients for therapy and clinical trials, especially when there are inflammatory symptoms without swollen joints.Acknowledgments:The Project was funded by Lupus-UKDisclosure of Interests:Khaled Mahmoud: None declared, Ahmed Zayat: None declared, Md Yuzaiful Md Yusof: None declared, Katherine Dutton: None declared, Lee-Suan Teh: None declared, Chee-Seng Yee: None declared, David d’cruz Grant/research support from: GlaxoSmithKline, Nora Ng: None declared, David Isenberg Consultant of: Study Investigator and Consultant to Genentech, Coziana Ciurtin Grant/research support from: Pfizer, Consultant of: Roche, Modern Biosciences, Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), 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, Elizabeth Hensor: None declared, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK

ObjectiveThe aim of this study was to investigate whether foot and lower limb related symptoms were associated with work participation and poor mobility in people with Systemic Lupus Erythematosus (SLE).MethodA quantitative, cross-sectional, self-reported survey design was utilised. People with SLE from six United Kingdom (UK) treatment centres and a national register were invited to complete a survey about lower limb and foot health, work participation and mobility. Data collected included work status and the prevalence of foot symptoms. The focus of the analyses was to explore potential associations between poor foot health work non-participation.ResultsIn total, 182 useable surveys were returned. Seventy-nine respondents reported themselves as employed and 32 reported work non-participation. The remaining were retired due to age or reported work non-participation for other reasons. Work non-participation due to foot symptoms was significantly associated with difficulty walking (p = 0.024), past episodes of foot swelling (p = 0.041), and past episodes of foot ulceration (p = 0.018). There was a significant increase in foot disability scores amongst those not working (mean 18.13, 95% CI: 14.85–21.41) compared to those employed (mean 10.16, 95% CI: 8.11–12.21).ConclusionsTwenty-nine% of people with SLE reported work non-participation because of lower limb or foot problems. Our results suggest that foot health and mobility may be important contributors to a persons’ ability to remain in work and should be considered as part of a clinical assessment.

Background:There had been very limited data on the development of damage and mortality in an inception cohort of SLE patients who were recruited very soon after diagnosis.Objectives:This study aimed to analyse the development of damage and death in an inception cohort of SLE patients recruited within 1 year of diagnosis with up to 13 years of follow-up.Methods:This was a prospective multi-centre longitudinal study in the UK of SLE patients recruited within 12 months of achieving 1997 ACR revised criteria for SLE. Data were collected on BILAG-2004, BILAG2004-Pregnancy Index (during pregnancy), SLICC/ACR DI (SDI), cumulative drug exposure and death at every visit. Information on cardiovascular risk factors and antiphospholipid syndrome status were also collected. This study ran from 1st January 2005 to 31st December 2017. Mortality and development of damage were analysed.Results:There were 273 patients recruited (91.2% female, 59.3% Caucasian, 17.2% African/Caribbean, 17.2% South Asian) with mean age at recruitment of 38.5 years (SD 14.8). 97.8% had no damage at recruitment (2.2% had SDI score of 1). Median follow-up was 73.4 months (range: 1.8, 153.8) with total follow-up of 1767 patient-years.There were 13 deaths (4.8%): 76.9% female, 84.6% Caucasian, 15.4% South Asian, mean age 62.6 years (± SD 15.8) and mean disease duration 3 years (± SD 1.8). Causes of death were cancer in 5 (38.5%), infection in 3 (23.1%), ischaemic heart disease in 1 (7.7%) and unknown in 4 (30.8%).114 new damage items in 83 patients occurred during follow-up. The distribution of damage was musculoskeletal (21, 18.4%), ophthalmic (18, 15.8%), neuropsychiatric (18, 15.8%), renal (14, 12.3%), malignancy (12, 10.5%), cutaneous (7, 6.1%), GIT (7, 6.1%), cardiac (6, 5.3%), pulmonary (4, 3.5%), diabetes mellitus (4, 3.5%) and vascular (3, 2.6%). The rate of development of damage appears to be higher in the first 3 years which subsequently stabilised (Table 1).Table 1.Incidence rate of development of damage over period of follow-up at 3 yearly intervalsPeriod of follow-up (year)Person-years at riskNumber of new items of damageIncidence rate, per 1000 person-years (95% CI)0 – 3753.46079.6 (61.8, 102.6)3 – 6534.03158.1 (40.8, 82.6)6 – 9321.21237.4 (21.2, 35.8)9 – 12152.5532.8 (13.6, 78.7)> 125.90-Conclusion:Mortality is uncommon during the first 12 years of follow-up for newly diagnosed SLE patients. However, development of damage appears to be higher in the first 3 years before stabilizing to a lower rate subsequently.Acknowledgements:Versus Arthritis, VIfor PharmaDisclosure of Interests:Chee-Seng Yee Consultant of: Bristol Myer Squibb, ImmuPharma, Grant/research support from: Vifor Pharma, Vernon Farewell: None declared, Mohammed Akil: None declared, Peter Lanyon: None declared, Christopher John Edwards Consultant of: Glaxo Smith Kline, Roche, Grant/research support from: Glaxo Smith Kline, Roche, David Isenberg: None declared, Anisur Rahman: None declared, Lee-Suan Teh: None declared, Sofia Tosounidou: None declared, Robert Stevens: None declared, Ahtiveer Prabu: None declared, Bridget Griffiths: None declared, Neil McHugh: None declared, Ian N. Bruce: None declared, Yasmeen Ahmad: None declared, Munther Khamashta: None declared, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MGP, Sanofi and UCB

Background:Low disease activity state has been defined using SLEDAI and used as treatment target in SLE. However, there has not been any such definition using BILAG-2004 index (BILAG-2004).Objectives:This study was to determine if low disease activity state according to BILAG-2004 is valid for use as treatment target in SLE. We also assessed disease activity longitudinally using BILAG-2004 systems tally (BST). BST is an alternative way of representing BILAG-2004 scores that combines the flexibility and simplification of numerical scoring of BILAG-2004 with the clinical intuitiveness of BILAG-2004 structure.Methods:This was a prospective multi-centre longitudinal study in the UK of an inception cohort of SLE patients (recruited within 12 months of achieving 1997 ACR revised criteria for SLE). Data were collected on disease activity (BILAG-2004 and BILAG2004-Pregnancy Index during pregnancy), SLICC/ACR DI (SDI), cumulative drug exposure and death at every visit. This study ran from 1st January 2005 to 31st December 2017. Four low disease activity states (LDA) were defined using BILAG-2004: 1) BILAG-2004 LDA when all 9 systems had scores of C, D or E on assessment (no Grade A or B), 2) BST LDA when there was persistent score of C, D or E in all 9 systems between 2 consecutive visits (equivalent to 2 consecutive visits with BILAG-2004 LDA), 3) BILAG-2004 Remission when all 9 systems had scores of D or E on assessment and 4) Persistent Remission when there was persistent score of D or E in all 9 systems between 2 consecutive visits. Longitudinal analysis using Poisson regression with random effects model was used with development of new damage as the outcome of interest. Gender, cardiovascular risk factors, antiphospholipid syndrome status and most drugs (except hydroxychloroquine, glucocorticoids, mycophenolate and cyclophosphamide) were excluded from the model as they were not associated with development of damage in univariate analysis.Results:273 patients were recruited (91.2% female, 59.3% Caucasian, 17.2% African/Caribbean, 17.2% South Asian) with mean age at recruitment of 38.5 years (SD 14.8). 97.8% had no damage at recruitment (2.2% had SDI score of 1). Median follow-up was 73.4 months (range: 1.8, 153.8) with total follow-up of 1767 patient-years. There were 13 deaths and 114 new damage items occurred during follow-up. There were 6674 assessments with disease activity score: 319 assessments with Grade A activity in 95 patients (84.6% had only 1 system with grade A, range: 1 - 4) and 1704 assessments with Grade A or B activity in 239 patients (78.7% had only 1 system with Grade A or B, range: 1 - 5).BILAG-2004 LDA was achieved in 74.5% of assessments (from 271 patients). BILAG-2004 Remission occurred in 28.2% of assessments (from 234 patients).6401 observations with BST were available (1 observation derived from change in activity between 2 consecutive assessments) and 63.7% were in BST LDA. There was no observation with Persistent Remission between consecutive visits.Table 1 summarises multivariate analysis which showed BILAG-2004 LDA to be inversely associated with damage. Similar results were obtained with BILAG-2004 Remission (RR 0.60 with 95% CI 0.38, 0.96) and BST LDA (RR 0.65 with 95% CI 0.43, 0.99). Cumulative drug exposure since recruitment for mycophenolate was protective against new damage (RR 0.99 with 95% CI 0.99, 0.99).Table 1.VariableRelative Risk (95% CI) for New DamageEthnicityAfro-Caribbean1.22 (0.68, 2.18)South Asian1.81 (0.97, 3.38)Others2.22 (0.63, 7.85)Age at diagnosis1.06 (1.04, 1.08)Prior SDI score0.68 (0.43, 1.06)BILAG-2004 LDA0.60 (0.39, 0.94)Hydroxychloroquine since last visit (per g)0.99 (0.98, 0.99)Steroids since last visit (per 100mg)1.02 (1.01, 1.03)Cyclophosphamide since last visit (per g)1.67 (1.15, 2.41)Conclusion:BILAG-2004 LDA and BST LDA are valid treatment targets in SLE. BILAG-2004 Remission and Persistent Remission are uncommon, which make them unrealistic as a treatment target.References:[1]Yee C. S., et al. The BILAG-2004 systems tally – a novel way of representing the BILAG-2004 index scores longitudinally. Rheumatology (Oxford) 2012; 51[11]: 2099-2105.Acknowledgements :Versus Arthritis, Vifor PharmaDisclosure of Interests:Chee-Seng Yee Consultant of: Bristol Myers Squibb, ImmuPharma, Grant/research support from: Vifor Pharma, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MGP, Sanofi and UCB, Mohammed Akil: None declared, Peter Lanyon: None declared, Christopher John Edwards Consultant of: Glaxo Smith Kline, Roche, Grant/research support from: Glaxo Smith Kline, Roche, David Isenberg: None declared, Anisur Rahman: None declared, Lee-Suan Teh: None declared, Sofia Tosounidou: None declared, Robert Stevens: None declared, Ahtiveer Prabu: None declared, Bridget Griffiths: None declared, Neil McHugh: None declared, Ian N. Bruce: None declared, Yasmeen Ahmad: None declared, Munther Khamashta: None declared, Vernon Farewell: None declared

Background:SLE disease activity tools do not optimally define disease activity and response. The SLEDAI arthritis item is common, and sufficient to define SRI response. Lupus patients with arthralgia often have no swelling. Glossary definitions of arthritis in different versions of the SLEDAI have included: swelling, swelling between visits, effusion, tenderness, warmth and erythema. MSK ultrasound in SLE can identify synovitis without swelling, ultrasound synovitis is associated with worse symptoms and serology, predicts response to therapy, and is more responsive to therapy than clinical variables.Objectives:To validate different glossary definitions for SLEDAI arthritis using musculoskeletal ultrasound.Methods:We analysed baseline data from a multicentre longitudinal study. Physicians scored SLEDAI-2K in 133 patients with joint pain that was considered inflammatory, but not necessarily swelling. Stable immunosuppressants and prednisolone =2, and in tendons as >=1 tendon with GS >=1, and abnormal power Doppler as >=1 joint or tendon with PD >=1.Results:78/133 patients had arthritis scored on SLEDAI-2K. In 21/78, swelling was not a reason for that decision. These 21 patients had either tenderness (16/21), swelling reported between visits (4/21) or both of these (1/21). No patient was scored for warmth, erythema or effusion alone. Comparison of SLEDAI definitions and ultrasound is shown in Table 1. Of 57 patients with SLEDAI arthritis scored due to swelling, 90% had an abnormal ultrasound. The positive predictive value was 89% (95% CI 79 – 94). Of 21 patients with SLEDAI arthritis scored without swelling, 48% had an abnormal ultrasound. The positive predictive value was 48% (95% CI 31 – 67). There was no substantive difference in clinical and serological variables comparing patients with SLEDAI arthritis without swelling and patients without SLEDAI arthritis. In contrast, patients with SLEDAI arthritis with swelling had worse ESR (p=0.0003), Physician MSK disease activity VAS (pConclusion:Although ultrasound proven synovitis in the absence of swelling is not uncommon, it is not reliably identified using other signs or symptoms. The arthritis item of the SLEDAI was likely to be associated with ultrasound synovitis if scored because of swelling, but not if scored because of tenderness or swelling between visits. Our results support raising the threshold criteria for arthritis so that it should only be scored when there is joint swelling. Previous clinical trial datasets could be re-analysed excluding SLEDAI arthritis scores not confirmed by a swollen joint count greater than one.SLEDAI-2K at baselineUltrasound Abnormalities at BaselineTest statistics for any ultrasound abnormalityGS jointsn/N (%)PD jointsn/N (%)GS tendonsn/N (%)PD tendonsn/N (%)Any abnormalityn/N (%)Sensitivity% (95% CI)Specificity% (95% CI)PPV% (95% CI)NPV% (95% CI)All patients (n=133)77/133 (58)33/133 (25)36/133 (27)27/106 (20)83/133 (62)----MSK SLEDAI = No (n=55)20/55 (36)2/55 (4)9/55 (16)3/55 (6)22/55 (40)----MSK SLEDAI = Yes (n=78)57/78 (73)31/78 (40)27/78 (35)24/78 (31)61/78 (78)73 (62, 82)b66 (51, 78) b78 (70, 84) b60 (49, 69) b-Due to swelling (n=57)48/57 (84)28/57 (49)21/57 (37)19/57 (33)51/57 (90)61 (50, 71)c88 (75, 95) c89 (79, 94) c57 (50, 64) c-Without swelling (n=21)a9/21 (43)3/21 (14)6/21 (29)5/21 (24)10/21 (48)31 (16, 50) d75 (60, 87) d48 (31, 67) d60 (45, 68) dDisclosure of Interests:Khaled Mahmoud: None declared, Ahmed Zayat: None declared, Md Yuzaiful Md Yusof: None declared, Katherine Dutton: None declared, Lee-Suan Teh: None declared, Chee-Seng Yee: None declared, David d’cruz: None declared, Nora Ng: None declared, David Isenberg: None declared, Coziana Ciurtin: None declared, Philip G Conaghan: None declared, Paul Emery: None declared, Christopher John Edwards Shareholder of: Research grant support from; Abbvie, Biogen, Pfizer, Consultant of: Personal fee from; Abbvie, BMS, Biogen, Celgene, Celltrion, Fresenius, Gilead, GSK, Janssen, Lilly, Mundipharma, Pfizer, MSD, Novartis, Roche, Samsung, Sanofi, UCB, Grant/research support from: Research grant support from; Abbvie, Biogen, Pfizer, Elizabeth Hensor: None declared, Edward Vital Speakers bureau: AstraZeneca, Genentech, Aurinia, Lilly, Modus, Consultant of: AstraZeneca, Genentech, Aurinia, Lilly, Modus, Grant/research support from: Sandoz, AstraZeneca

Background:BILAG-2004 Index (BILAG-2004) has undergone construct and criterion validity and is used to assess disease activity in SLE. However, its predictive validity has yet to be established.Objectives:This study was to determine if disease activity according to BILAG-2004 was predictive of development of damage in an inception cohort.Methods:This was a prospective multi-centre longitudinal study in the UK of an inception cohort of SLE patients (recruited within 12 months of achieving 1997 ACR revised criteria for SLE). Data were collected on disease activity (BILAG-2004 and BILAG2004-Pregnancy Index during pregnancy), SLICC/ACR DI (SDI), cumulative drug exposure and death at every visit. Information on cardiovascular risk factors (hypertension, diabetes mellitus, hypercholesterolaemia and smoking status) and antiphospholipid syndrome status were also collected. This study ran from 1st January 2005 to 31st December 2017. Longitudinal analysis using Poisson regression with random effects model was used to determine predictors of development of new damage. Death was not included in the analysis due to small numbers.Results:273 patients were recruited (91.2% female, 59.3% Caucasian, 17.2% African/Caribbean, 17.2% South Asian) with mean age at recruitment of 38.5 years (SD 14.8). 97.8% had no damage at recruitment (2.2% had SDI score of 1). Median follow-up was 73.4 months (range: 1.8, 153.8) with total follow-up of 1767 patient-years. Prevalence of risk factors during follow-up were: hypertension 23.1%, hypercholesterolaemia 35.5%, diabetes mellitus 5.5%, smoker or ex-smoker 44% and antiphospholipid syndrome 7%. There were 13 deaths and 114 new damage items occurred during follow-up.There were 6674 assessments with disease activity score: 293 assessments with Grade A activity in 95 patients (92.4% had only 1 system with grade A, range: 1 - 4) and 1704 assessments with Grade A or B activity in 239 patients (78.7% had only 1 system with Grade A or B, range: 1 - 5).Univariate analysis showed that gender, cardiovascular risk factors, antiphospholipid syndrome and most drug exposure (except hydroxychloroquine, glucocorticoids, mycophenolate and cyclophosphamide) were not associated with new damage (they were not included in the multivariate analysis).Table 1 summarises multivariate analysis. Similar results were obtained when the disease activity variable was changed to Number of Systems with Grade A per assessment (RR 2.04 with 95% CI: 1.05, 3.94). Analysis using BILAG-2004 systems tally showed that persistent minimal disease was protective of development of damage (RR 0.74 with 95% CI: 0.57, 0.95). Cumulative drug exposure since recruitment for mycophenolate was protective against new damage (RR 0.99 with 95% CI 0.99, 0.99) but not cumulative drug exposure since last visit.VariableRisk Ratio (95% CI) for New DamageEthnicity Afro-Caribbean1.21 (0.68, 2.17) South Asian1.81 (0.97, 3.36) Others2.37 (0.68, 8.20)Age at diagnosis1.06 (1.04, 1.08)Prior SDI score0.69 (0.44, 1.08)Constitutional A or Bunreliable estimate due to low numbersMucocutaneous A or B1.80 (1.04, 3.14)Neuropsychiatric A or B4.68 (1.68, 13.05)Musculoskeletal A or B0.76 (0.33, 1.73)Cardiorespiratory A or B0.35 (0.05, 2.59)GIT A or Bunreliable estimate due to low numbersOphthalmic A or Bunreliable estimate due to low numbersRenal A or B2.08 (0.99, 4.40)Haematological A or B4.37 (1.15, 16.65)Hydroxychloroquine since last visit (per g)0.99 (0.98, 0.99)Prednisolone since last visit (per 100mg)1.01 (1.00, 1.02)Cyclophosphamide since last visit (per g)1.42 (0.94, 2.14)Conclusion:Active disease (Grade A or B) according to BILAG-2004 index is predictive of development of new damage in SLE patients.References:[1]Yee C. S., et al. The BILAG-2004 systems tally – a novel way of representing the BILAG-2004 index scores longitudinally. Rheumatology (Oxford) 2012; 51[11]: 2099-2105.Acknowledgements:Versus Arthritis and Vifor PharmaDisclosure of Interests:Chee-Seng Yee Consultant of: Bristol Myers Squibb, ImmuPharma, Grant/research support from: Vifor Pharma, Vernon Farewell: None declared, Mohammed Akil: None declared, Peter Lanyon: None declared, Christopher John Edwards Consultant of: Glaxo Smith Kline, Roche, Grant/research support from: Glaxo Smith Kline, Roche, David Isenberg: None declared, Anisur Rahman: None declared, Lee-Suan Teh: None declared, Sofia Tosounidou: None declared, Robert Stevens: None declared, Ahtiveer Prabu: None declared, Bridget Griffiths: None declared, Neil McHugh: None declared, Ian N. Bruce: None declared, Yasmeen Ahmad: None declared, Munther Khamashta: None declared, Caroline Gordon Speakers bureau: UCB, Consultant of: Center for Disease Control, Astra-Zeneca, MGP, Sanofi and UCB

Objective The main aim of this survey was to determine the frequency of self-reported lower limb or foot and ankle complications experienced by participants with systemic lupus erythematosus (SLE). A secondary aim was to determine the frequency of treatments that have been received or that participants with SLE may like to receive if offered. Method A quantitative, cross-sectional, self-reported survey design was utilized. The developed survey was checked for face and content validity prior to patient partner cognitive debriefing in order to ensure usability, understanding of the process of completion and of the questions posed. The full protocol for survey development has been published previously. Results This is the first comprehensive national UK survey of lower limb and foot health problems reported by participants with SLE. A high prevalence of vascular, dermatological and musculoskeletal complications was reported by survey respondents. Additionally, whilst the relative prevalence of sensory loss was low, a quarter of people reported having had a fall related to changes in foot sensation demonstrating a previously unknown rate and cause of falls. Conclusion Complications related to vascular, dermatological and musculoskeletal health are identified as particularly prevalent in participants with SLE. Further, there is a suggestion that the provision of interventions to maintain lower limb health is highly varied and lacks national standardization, despite there being a strong indication of participant reported need. The findings of this work can be used to inform care guideline development in addition to identifying areas for future research.

Background:Musculoskeletal (MSK) disease is the commonest manifestation of SLE. We showed that the MSK components of the BILAG index and SLEDAI have limited sensitivity, specificity and responsiveness compared to ultrasound (US) synovitis. The USEFUL study evaluated response to glucocorticoids in SLE patients with inflammatory pain.Objectives:To develop a disease activity tool for lupus MSK manifestations that is continuous, responsive, sensitive, and correlates with US-synovitisMethods:133 patients who received depomedrone 120mg IM were assessed at 0, 2 and 6 weeks for 66/68 swollen and tender joint counts, BILAG2004 index, SLEDAI-2K, physician global and MSK-VAS, inflammatory markers, patient pain and disease activity-VAS. Total US score (OMERACT-EULAR) in the hands and wrists was calculated blinded to patient and clinical assessor. Patients reported overall response using a Likert scale.The LAMDA was developed by modelling a core set of clinical variables against total US score using penalized (Lasso) regression. Responsiveness was compared between LAMDA and other variables at week 6 using effect sizes. Minimum clinically important difference (MCID) was explored using the SEM and minimal disease activity threshold using ROC.Results:The variables selected for the LAMDA score were swollen joint count, patient MSK pain VAS, physician MSK disease activity VAS and ESR. A continuous score was derived. This had a theoretical range from 0 to 26.5 based on maximum ESR of 100. The highest value observed in USEFUL was 15. LAMDA was significantly higher in patients with active US (mean (SD) 5.71 (2.67), n=78) compared to patients with normal US (3.27 (1.77), n=55; difference (95% CI) -2.45 (-3.26, -1.63), t=-5.93, pEffect size was greater for the LAMDA (0.37) than the BILAG-MSK (0.31), SLEDAI-MSK (0.27) and total US score (0.33). In patients with active US at baseline, LAMDA’s effect size was 0.42.The MCID was 0.71 and correlated with patient-reported change in pain. A threshold for minimal disease activity of 3.23 optimized sensitivity (0.77 (0.65, 0.89)) and specificity (0.80 (0.68, 0.92)) against US score >0.Conclusion:The LAMDA score is a novel continuous disease activity instrument for MSK manifestations of SLE derived from variables familiar to rheumatologists. The LAMDA score is sensitive to imaging detected synovitis without swelling and more responsive than other instruments. . LAMDA may improve the ability of clinicians to accurately determine therapeutic efficacy in clinical trials and practice. Future work will validate the LAMDA score in independent cohorts and randomized trials.Acknowledgements:This project was funded by Lupus UKDisclosure of Interests:Khaled Mahmoud: None declared, Ahmed Zayat: None declared, Md Yuzaiful Md Yusof: None declared, Coziana Ciurtin Grant/research support from: Pfizer, Consultant of: Roche, Modern Biosciences, Chee-Seng Yee: None declared, David Isenberg Consultant of: Study Investigator and Consultant to Genentech, Lee-Suan Teh: None declared, Katherine Dutton: None declared, David d’cruz Grant/research support from: GlaxoSmithKline, Nora Ng: None declared, Philip G Conaghan Consultant of: AbbVie, BMS, Eli Lilly, EMD Serono, Flexion Therapeutics, Galapagos, GSK, Novartis, Pfizer, Speakers bureau: AbbVie, Eli Lilly, Novartis, Pfizer, Paul Emery Grant/research support from: AbbVie, Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, Roche (all paid to employer), Consultant of: AbbVie (consultant, clinical trials, advisor), Bristol-Myers Squibb (consultant, clinical trials, advisor), Lilly (clinical trials, advisor), Merck Sharp & Dohme (consultant, clinical trials, advisor), Novartis (consultant, clinical trials, advisor), Pfizer (consultant, clinical trials, advisor), Roche (consultant, clinical trials, advisor), Samsung (clinical trials, advisor), Sandoz (clinical trials, advisor), UCB (consultant, clinical trials, advisor), 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, Elizabeth Hensor: None declared, Edward Vital Grant/research support from: AstraZeneca, Roche/Genentech, and Sandoz, Consultant of: AstraZeneca, GSK, Roche/Genentech, and Sandoz, Speakers bureau: Becton Dickinson and GSK

Background Systemic lupus erythematosus (SLE) can present with a variety of symptoms. Previous research has shown there is a high prevalence of lower limb and foot problems in patients with SLE associated with the musculoskeletal, vascular and neurological changes. Furthermore, there is a high prevalence of infections affecting the feet and a range of common skin and nail problems. However, it is not known how these foot problems impact upon people’s lives. Therefore, we aimed to explore this using a qualitative approach. Method Following ethical approval, 12 participants were recruited who had a diagnosis of SLE, current and/or past experience of foot problems and were over 18 years in age. Following consent, interviews were carried out with an interpretivist phenomenological approach to both data collection and analysis. Results Seven themes provide insight into: foot problems and symptoms; the impact of these foot problems and symptoms on activities; disclosure and diagnosis of foot problems; treatment of foot problems and symptoms; perceived barriers to professional footcare; unanswered questions about feet and footcare; and identification of the need for professional footcare and footcare advice. Conclusion These participants tend to “self-treat” rather than disclose that they may need professional footcare. A lack of focus upon foot health within a medical consultation is attributed to the participant’s belief that it is not within the doctor’s role, even though it is noted to contribute to reduced daily activity. There is a need for feet to be included as a part of patient monitoring and for foot health management to be made accessible for people with SLE.

Background and aims Systemic lupus erythematosus (SLE) is characterised by relapses and remissions. This study describes the frequency, type and time to flare in a cohort of SLE patients. Methods SLE patients with one or more “A” or “B” BILAG2004 systems meeting flare criteria (items that were “new” or “worse”) and requiring an increase in immunosuppressive therapy were recruited from nine UK centres and assessed at baseline and monthly for nine months. Flares were defined as: severe (“A” flare/s irrespective of number of “B” flares), moderate (2 or more “B” flares without any “A” flares and mild (one “B” flare). Results Of the 100 patients, 94% were female, 61% white Caucasians, mean age (SD) was 40.7 years (12.7) and mean disease duration (SD) 9.3 years (8.1). A total of 195 flares occurred in 76 patients over 781 monthly assessments, giving a flare rate of 0.25/month. There were 37 severe flares (22 patients), 32 moderate flares (19 patients) and 126 mild flares (67 patients) [Table 1]. The median time to any “A” or “B” flare was 4 months (95% CI 2.7 to 5.3 months). Figure 1 shows the time to the first mild/moderate/severe flare (Curve 1), moderate/severe flare (Curve 2) and severe flare (Curve 3). Table 2 shows that severe and moderate flares tend to be in the system/s affected at baseline whereas mild flares are more likely to affect any system. Conclusions This real world cohort will share similarities with populations recruited to clinical studies so these results may inform future trial design.

Background and aims Systemic Lupus Erythematosus (SLE) is a multisystem disease and patients may benefit from non-pharmacological interventions. We explored the utility of the LupusQoL in identifying patients who may benefit from physical, occupational or psychological support. Methods The LupusQoL is a disease-specific health-related quality of life (HRQoL) questionnaire with eight domains (physical health, pain, planning, intimate relationship, burden to others, emotional health, body image and fatigue). For each domain the scores range from 0 to 100 (higher score better health). SLE patients sequentially attending an outpatient clinic over a 6 month period, who were able to complete the questionnaire in English, were asked to complete the questionnaire. Patients who scored Results 40 patients (97.5% females, 75% Caucasians; 17.5% South-Asians; 5% Afro-Caribbean; mean age 52.2 years) completed the LupusQoL over 6 months. Table 1 shows the number of patients who were eligible, the numbers who were referred and the numbers who attended the different support services. All domains of the LupusQol were impaired, with fatigue (45.19) being the worst affected and emotional health (68.60) being the least. Conclusions Following attendance for physical, occupational and psychological support, we intend to re-administer the LupusQoL to determine if these non-pharmacological interventions have improved HRQoL. The appropriateness of the LupusQoL threshold used to identify the intervention need will also be evaluated.

Objectives. We aimed to examine the strength of association between traditional cardiovascular risk factors and carotid plaque development in systemic lupus erythematosus (SLE) patients and controls. We also aimed to determine which lupus-related factors are associated with carotid plaque and whether SLE sensitizes patients to the effects of traditional factors. Methods. We studied 200 women with SLE and 100 controls. Demographic and risk factor data were collected and SLE features, including autoantibody profiles and therapy were noted. All subjects had B- mode ultrasound of their carotid arteries examined for the presence and distribution of plaque. Results. SLE patients

Health-related quality of life (HRQoL) is an important outcome measure in patients with systemic lupus erythematosus (SLE). A review was undertaken of the literature relating to HRQoL in SLE. MEDLINE, EMBASE, CINAHL, Allied and Complimentary Medicine were searched to locate full papers in the English language reporting on HRQoL in adult SLE patients published between 1990 and 2005. In total 53 papers were included and the review was subdivided into: 1) description of HRQoL in SLE patients; 2) HRQoL and disease activity and/or damage; 3) the impact of other variables on HRQoL; and 4) HRQoL measures used in clinical trials in SLE patients. The findings were as follows: HRQoL is reduced in SLE patients; HRQoL is not correlated to disease activity or damage; age appears to have a negative impact on HRQoL especially physical health but the effect of disease duration is unclear; other potentially modifiable variables such as fatigue and psychosocial factors impact on HRQoL in a complex manner; and HRQoL measures which are sensitive to change should be an essential outcome measure in all clinical trials on SLE patients.

OBJECTIVE: To devise a more discriminating version of the British Isles Lupus Assessment Group (BILAG) disease activity index and to show that it is reliable. METHODS: A nominal consensus approach was undertaken by members of BILAG to update and improve the BILAG lupus disease activity index. The index has been revised following intense consultations over a 1-yr period. It has been assessed in two real-patient exercises. These involved patients with diverse clinical features of SLE, including gastrointestinal, hepatic and ophthalmic problems, which the earlier versions of the index did not fully take into account. Reliability in terms of the ability to differentiate patients was assessed by calculating intraclass correlation coefficients. The level of agreement between physicians was determined by calculating the ratio of estimates of the standard error (SE) attributable to the physicians to the SE attributable to the patients. RESULTS: Good reliability and high levels of physician agreement were observed in one or both exercises in the constitutional, mucocutaneous, neurological, cardiorespiratory, renal, ophthalmic and haematological systems. In contrast, the musculoskeletal system did not score as well, although providing more clear-cut glossary definitions should greatly improve the situation. CONCLUSIONS: Some significant changes in the BILAG disease activity index to assess patients with SLE are proposed. The process of demonstrating validity and reliability has started with these two exercises assessing real patients. Further validation studies are under way. BILAG 2004 is likely to be valuable in clinical trials assessing new therapies for the treatment of SLE, as it provides a more comprehensive system-based disease activity measure than has been available previously.

This paper presents stress intensity factor (SIF) solutions for edge cracks emanating from semicircular notches using the composition of SIF weight functions. The method isolates and combines the geometrical influences defined by constitutive SIF weight functions to yield SIFs for semicircular notches in finite thickness bodies. Finite element analysis was employed to obtain the required stress distributions and to generate reference constitutive SIFs. Problems encountered with curve fitting high gradient stress distributions were addressed and a robust mathematical solution for these was formulated. The new SIF solutions were verified by comparison with published solutions showing a high degree of accuracy and reliability. The composition model was demonstrated to allow rapid generation of SIFs for mode I cracks in complex geometries where the relevant simple constitutive solutions are available. These new solutions expressed as SIF weight functions allow interpolation between the geometrical parameters for which they are valid and also to include the effect of complex stress distributions such as those due to residual stresses.

Linear elastic fracture mechanics (LEFM) is the science frequently used to understand the stable and progressive fatigue crack growth that often occurs in engineering components under varying applied stress. The stress intensity factor (SIF) is its basis and describes the stress state at the crack tip. This can be used with the appropriate material properties to calculate the rate at which the crack will propagate in a linear elastic manner. Unfortunately, the SIF is difficult to compute or measure, particularly if the crack is situated in a complex three-dimensional geometry or subjected to a non-simple stress state. This is because the SIF is not only a function of the crack and component geometry but is also dependent on the applied stress field. In the last 20 years, the SIF weight function has gained prominence as a method for calculating and presenting SIFs independent of applied stress. This paper demonstrates that the real promise of the SIF weight Function lies in its use to rapidly generate SIF solutions for cracks in complex geometries by simple composition of geometric influences from reference constituent solutions.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased mortality and significant personal, psychological and socioeconomic consequences. An agreed definition of remission is needed and lacking. We sought to visualize ‘remission in SLE’ in European patients considered by their physicians to be ‘in remission’ by comparing the reported symptom burden as reported by treating physicians for patients considered to be ‘in remission’ and those not considered to be ‘in remission’. Data for 1227 patients drawn from a multinational, real-world survey of patients with SLE consulting practising rheumatologists and nephrologists in France, Germany, Italy, Spain, and the UK show that physicians classed their patients as ‘in remission’ despite a considerable ongoing symptom burden and intensive immunosuppressive medication. Patients considered to be ‘in remission’ still had a mean of 2.68 current symptoms vs 5.48 for those considered to be not ‘in remission’ ( p

Objective The objective of this paper is to assess the validity of a linguistically validated version of the Lupus Quality of Life (LupusQoL©) in Italian patients affected by systemic lupus erythematosus (SLE). Methods Consecutive SLE patients completed the Italian version of the LupusQoL© and the Short Form (SF)-36. Disease activity was evaluated by the SLE disease activity Index-2000 (SLEDAI-2 K), and chronic damage by the Systemic Lupus International Collaborating Clinics/American College Rheumatology (ACR) Damage Index score (SDI). Internal consistency and test-retest reliability, convergent and discriminant validity were examined. Factor analysis with varimax rotation was performed. Results A total of 117 Italian SLE patients (M:F 13:104; mean age 40.6 ± 11.6 years, mean disease duration 127.5 ± 94.1 months) were recruited into the study. The Italian version of the LupusQoL© demonstrated substantial evidence of convergent validity in these patients when compared with equivalent items of the SF-36. In addition, the LupusQoL© discriminated between patients with different degrees of disease activity as measured by the SLEDAI-2 K. SLE patients with higher disease activity (SLEDAI-2K ≥4) showed poor QoL compared with those with lower disease activity (SLEDAI-2K 2/degree of freedom (df) 2.26, χ2 = 1128.6 ( p Conclusion The Italian version of the LupusQoL© is a valid tool for adult patients with SLE.

Genetic susceptibility to systemic lupus erythematosus (SLE) may vary amongst different populations. In UK patients, genes encoded in the HLA class II (DQA*0501/DRB1*0301) and class III [C4A*Q0 and tumour necrosis factor (TNF) polymorphisms] subregions appear to contribute to disease susceptibility. We have examined HLA-DRB1, C4 and TNF microsatellites in 50 Spanish SLE patients and 48 matched controls. HLA-DRB1*0301 was increased in patients but did not achieve statistical significance (41% vs. 25.5%). C4A*Q0 was not increased in patients, but C4B*Q0 allele frequency was significantly increased compared with the controls (29% vs. 6%; OR: 6.0). TNF c2 microsatellite allele frequency was also increased in SLE patients. The C4B null allele (C4B*Q0) appears to play an important role in SLE susceptibility in the Spanish population.

BackgroundThe manifestations of systemic lupus erythematosus (SLE) vary between individuals, from the severe and life-threatening renal and central nervous system involvement, to the involvement of skin, musculoskeletal and vascular system, and the complications of infection influencing the quality of life. However, as specific manifestations affecting the lower limb are perceived as receiving little focus, the purpose of this narrative literature review is to identify the specific factors associated with SLE that may have implications for lower limb and foot morbidity.MethodA structured search of databases was conducted. The inclusion was restricted to publications in the English language, those that specifically investigate the feet as affected with SLE. No restriction on year of publication was imposed to reduce publication bias and to capture as many publication in relation to feet.ResultsEleven papers fulfilled the inclusion criteria. There were seven additional papers that made observations related to the articular or vascular complications of the feet. This narrative review provides some information on how SLE affects the lower limb and foot in relation to the musculoskeletal and vascular systems. However, there is a lack of literature that specifically focuses on all the manifestations of SLE and the complications associated with its management.DiscussionThere are indications that SLE affects lower limb and foot morbidity but the scale of these problems is unclear and this is partly because of the absence of research and the lack of a ‘gold standard’ framework for the assessment of the lower limb and foot. In addition to clinical foot health assessment, ultrasonography may be a useful alternative to plain film radiography or magnetic resonance imaging (MRI) in capturing the extent of articular and extra-articular manifestations. Further, the Ankle Brachial Pressure Index (ABPI) may be useful in identifying those with atherosclerosis and ischaemia.ConclusionThere are indications that SLE affects lower limb and foot morbidity but the scale of these problems and effective management of them is unclear. Therefore, further research is warranted in order to better understand the impact of SLE on the foot and lower limb and its impact on quality of life.

Systemic lupus erythematosus (SLE) is associated with an increased risk of coronary heart disease (CHD) not fully explained by classic risk factors. Metabolic syndrome (MetS) is associated with an increased risk of CHD in the general population and whilst its prevalence is increased in SLE, its phenotypic expression may differ. We studied 200 women with SLE and 100 controls and compared the prevalence of MetS and its individual components. We examined whether any SLE features were associated with MetS and whether MetS in SLE patients was associated with carotid plaque. Patients with SLE were more likely to meet the MetS criteria (age-adjusted OR 2.1 (1.1–3.8)). However, this was not due to increased central obesity (median waist circumference 84 cm vs. 82 cm, p = 0.65) but rather increased prevalence of hypertension ( p

We sought to understand the patients’ ‘lived experiences of systemic lupus erythematosus (SLE)’ by exploring, describing and clarifying the patients’ perspective of how they felt about having SLE and how the disease impacted on their lives, both positively and/or negatively. An interpretative phenomenological approach was employed. Semi-structured interviews were undertaken with 30 females with SLE across a wide range of age (21 to 75 years), disease characteristics, disease duration (1 to 28 years) and ethnicity (Whites, South Asians). Eleven themes emerged as important to the patients: prognosis and course of disease; body image; effects of treatment; emotional difficulties; inability to plan due to disease unpredictability; fatigue; pain; career prospects and loss of income; memory loss/concentration; reliance on others to assist with everyday tasks; and pregnancy issues. Most patients reported a negative impact of SLE on their lives although a few patients found positive aspects to having SLE. The findings of this study identified themes important to patients with SLE and these themes will inform clinicians on the patients’ perspective of having SLE.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that exhibits extensive clinical heterogeneity. Several studies have suggested a role for tumor necrosis factor alpha (TNFalpha) in SLE and recently, the locus encompassing the TNF receptor II (TNFRII), which is a mediator of TNF effect, was amongst the candidate loci suggested by genetic linkage studies of multi-case SLE families. Komata et al. reported an association between a polymorphism at position 196 (R allele) of TNFR II and SLE in Japanese patients. We have typed SLE patients from two different ethnic populations, Spanish and UK Caucasoids, for this polymorphism using a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)-based technique. No significant differences in allele or genotype frequencies were found between cases and matched controls in either population. The TNFRII 196R allele does not appear to be associated with SLE susceptibility in either Spanish or UK populations.

We tested the hypothesis that carotid atherosclerosis in systemic lupus erythematosus (SLE) is associated with poor health-related quality of life (HRQOL), which is independent of any association with traditional risk factors (TRFs), lifestyle and socioeconomic factors. Women with SLE completed the RAND Medical Outcome Study 36-Item Short-Form Health Survey version 1 (MOS SF-36). B-mode Doppler examination of the carotid arteries determined the presence of atherosclerotic plaque. The association between carotid plaque and HRQOL domains was analysed using logistic regression models with sequential adjustments for age, TRFs, education level and employment status. We studied 181 women, 47 (26%) of whom had carotid plaque. Carotid plaque was significantly associated with lower levels of physical functioning (p = 0.047), vitality (p = 0.04), role emotional (p = 0.04) and mental health subscales (p = 0.01) and lower mental component summary score (MCS) (p = 0.03). These associations were no longer significant after adjustment for age and TRFs, especially smoking. Smokers had lower physical functioning, vitality and mental health and more bodily pain. The association between carotid plaque and HRQOL was not independent of TRFs and smoking was a key mediator of the associations found. Poor HRQOL in smokers will need addressing as part of any smoking cessation strategies in SLE patients.

Psoriatic spondyloarthropathy (PSA) can occasionally be complicated by AA amyloid, and renal amyloidosis should be suspected in patients with PSA who have unexplained proteinuria. The diagnosis of amyloidosis can be made either histologically or by radiolabelled serum amyloid P component (SAP) scintigraphy. Prognosis is determined by the extent of organ involvement and associated impairment of function, and by the degree of response of the underlying disease to anti-inflammatory therapy. A review of the literature identified less than a dozen cases of AA amyloidosis complicating PSA, and the outcome in most cases was poor. We report here the favourable clinical course of a middle-aged Caucasian male patient with severe PSA who developed renal AA amyloidosis, in whom treatment with oral chlorambucil led to stabilization of the amyloid deposits and resolution of the associated nephrotic syndrome. We review the diagnosis and treatment of AA amyloidosis, including the management of patients with underlying inflammatory spondyloarthropathies, and propose the possible role of a therapeutic trial of anti-tumour necrosis factor alpha in patients with amyloid complicating inflammatory rheumatic diseases.

Background Azathiopine (AZA) is commonly used to ensure SLE disease control during pregnancy. There is little information regarding long term outcomes of these children. Objectives We aimed to assess if AZA exposure during pregnancy and lactation was associated with adverse outcomes for children born to mothers with lupus. Methods Women attending lupus clinics, with available pregnancy data, were consented to take part. A standard questionnaire developed for a multi-centre study was used to collect the data. Results Complete data was available for 287 children born alive to 200 women: 66% Caucasian, 15% South Asian, 10% Afro-Caribbean, 1% Chinese, 1% Hispanic, 4% other and 4% not stated. The median (range) age of women at delivery was 32 (19-44) yrs, and duration of disease was 6 (0.5-27) yrs. Two groups were studied: 89 children exposed to AZA during pregnancy &/or breast-feeding (group A) vs 198 children unexposed (group NA). Maternal renal disease (group A 38/67, 57% vs group NA 28/175, 16%), use of maternal prednisolone (group A 78/89, 87% vs group NA 93/198, 47%) and aspirin (group A 70/84, 83% vs group NA 132/200, 66%) were significantly increased in group A compared with group NA (p There was no significant difference in maternal pre-eclampsiaa, hypertension, anti Ro and/or anti-La antibodies, between the two groups. The presence of maternal lupus anticoagulant and/or anticardiolipin antibodies (ACA) was statistically higher in group A 44/73 (60%) vs group NA 79/178 (49%), p=0.03. However the presence of the antibodies individually was not different. Median age of children at enrolment in group A was 3.2, (range 0-17.1) vs group NA 3.1 (0-16.2) years. The median birth weight in group A was 2.8 (0.6-4.4)kg vs 3.1 (0.7-4.7) kg in group NA and gestational age in group A was 36.3 (27-42) wks vs 38 (25-42) wks in NA. These were both statistically significant. Using univariate analysis children exposed to AZA had a significantly increased rate of hospital admissions for infection (group A 25/89, 28% vs group NA 28/198, 14%, p=0.005), but not for overall hospital admissions (group A 29/84, 35% vs group NA 45/192, 23%, p=0.07) or out- patient visits. When the effect of AZA was adjusted by multifactor logistic regression for maternal renal disease and prednisolone use, the relationship became non-significant (OR 1.73 (0.85-3.5), p=0.13, however, due to the lower sample size its power was Conclusions This study shows that women with SLE who take AZA during pregnancy are more likely to have had renal disease, ACA and/or lupus anticoagulant and to use prednisolone. The median birthweight and duration of pregnancy was lower. There appeared to be an increased risk of hospital admission due to infection in the children of group A mothers. However, after adjusting for markers of maternal lupus disease severity this relationship disappeared. Disclosure of Interest : None declared DOI 10.1136/annrheumdis-2014-eular.1616

OBJECTIVE: Mannose binding lectin (MBL) and FcgammaRII (CD32) polymorphisms have both been implicated as candidate susceptibility genes in systemic lupus erythematosus (SLE). The aim of this study was to evaluate the relationship of these polymorphisms with SLE. METHODS: We studied a cohort of 125 SLE patients from Barcelona, Spain and 138 geographically matched controls. Sequence-specific primer-polymerase chain reaction (SSP-PCR) amplification was used to determine CD32 and MBL structural polymorphisms. MBL haplotypes were established using sequence-specific oligonucleotide probing techniques. RESULTS: Patients carried the MBL codon 54 mutant allele more frequently than controls [odds ratio (OR) 2.2; 95% confidence interval (CI) 1.2-4.0; P=0.007] and the haplotype HY W52 W54 W57 was found to be significantly lower in cases compared with controls (OR 0.6; 95% CI 0.4-0.9; P=0.016). CONCLUSION: The MBL gene codon 54 mutant allele appears to be a risk factor for SLE, whilst haplotypes encoding for high levels of MBL are protective against the disease. Differences between controls and patients were not significant when considering the FcgammaRIIa polymorphisms; similar results were observed for renal affectation.

Rheumatoid arthritis (RA) is associated with HLA-DR4, which is encoded by the DRB1 gene. This genetic predisposition has been shown to lie within the sequence motif present in the third hypervariable region of the DRB1 gene.1 This sequence of amino acids has been called the “disease epitope” and can be encoded by DR4 subtypes as well as non-DR4 alleles; DR1 subtypes, DR10 and DR14 subtypes .1 Hence, it is also termed the shared epitope. In addition to imparting susceptibility to RA, HLA-DR4 has also been shown to be associated with the severity of the rheumatoid disease, including destructive erosive joint disease, rheumatoid factor positivity,2 and extra-articular manifestations, such as rheumatoid nodules, vasculitis, and Felty's syndrome.3 4HLA-DQ genes are in linkage disequilibrium with HLA-DR and subjects who are DR4 positive may either be DQB1*0301 or *0302 positive; certain extra-articular features of RA have been shown to be associated with HLA-DQB1*0301.4 5 Synovial fluid cytology in RA is heterogeneous both with respect to total white cell count and to the proportions of polymorphs, lymphocytes, and ragocytes.6 Ragocytes are leucocytes containing intracytoplasmic granules and have been shown to be present in higher percentages in the joints of patients with RA.6Davis et al showed that when a patient with RA has a relapse affecting the same joint, the proportions of cell types remain similar, though the total white cell count may differ.7 The same study also found a significantly poorer outcome in patients with persistently high ragocyte counts as assessed by the necessity for subsequent joint replacement or synovectomy. As both synovial cytology and genetic factors have been shown independently to …

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that exhibits extensive clinical heterogeneity. Several studies have suggested a role for tumor necrosis factor alpha (TNFalpha) in SLE and recently, the locus encompassing the TNF receptor II (TNFRII), which is a mediator of TNF effect, was amongst the candidate loci suggested by genetic linkage studies of multi-case SLE families. Komata et al. reported an association between a polymorphism at position 196 (R allele) of TNFR II and SLE in Japanese patients. We have typed SLE patients from two different ethnic populations, Spanish and UK Caucasoids, for this polymorphism using a polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP)-based technique. No significant differences in allele or genotype frequencies were found between cases and matched controls in either population. The TNFRII 196R allele does not appear to be associated with SLE susceptibility in either Spanish or UK populations.

Genetic susceptibility to systemic lupus erythematosus (SLE) may vary amongst different populations. In UK patients, genes encoded in the HLA class II (DQA*0501/DRB1*0301) and class III [C4A*Q0 and tumour necrosis factor (TNF) polymorphisms] subregions appear to contribute to disease susceptibility. We have examined HLA-DRB1, C4 and TNF microsatellites in 50 Spanish SLE patients and 48 matched controls. HLA-DRB1*0301 was increased in patients but did not achieve statistical significance (41% vs. 25.5%). C4A*Q0 was not increased in patients, but C4B*Q0 allele frequency was significantly increased compared with the controls (29% vs. 6%; OR: 6.0). TNF c2 microsatellite allele frequency was also increased in SLE patients. The C4B null allele (C4B*Q0) appears to play an important role in SLE susceptibility in the Spanish population.

To investigate whether reduced circulating levels of ascorbic acid in patients with systemic sclerosis (SSc) are a result of malabsorption.Eight patients with SSc, but with no evidence of bacterial overgrowth, and 8 healthy controls were recruited. On the first day of study, each subject was given orally an aliquot of [14C] ascorbic acid, which was then "flushed out" by oral intake of unlabeled ascorbic acid for the following 7 days. Plasma samples were collected at specified intervals and urine was collected continuously over the 8 day study period. [14C] content of plasma and urine were measured by scintillation counting. For each subject, a plasma [14C] decay curve was drawn. Each subject's ascorbic acid absorption was assessed using the area under the curve (AUC) and the apparent renal clearance (CLr[app]). Ascorbic acid intake was assessed using dietary history and food composition tables.There were no differences in the dietary intake of vitamin C (p = 0.16) and body mass indices (p = 0.91) between patients and controls. The plasma [14C] AUC and CLr(app) were similar between patients and controls [AUC patient mean (standard deviation, SD) = 37.1 (6.8), AUC control mean (SD) = 38.6 (9.9), p = 0.74; CLr(app) patient mean (SD) = 0.57 (0.24), CLr(app) control mean (SD) = 0.47 (0.27), p = 0.45].There was no evidence of impaired absorption of ascorbic acid in patients with SSc without bacterial overgrowth compared to healthy controls.

Background Certain immunosuppressive agents are used in pregnancy in SLE patients to prevent flare and ensure optimal outcome for mother and child. There is little literature regarding long term outcomes of children.US data suggested a link between azathioprine(AZA) and infection 1 , and between anticardiolipin antibodies(abs) and developmental delay 2 have been suggested. Objectives To assess if potential risk factors including maternal disease, autoantibodies, immunosuppression or other medication exposure influence health and behaviour of children. The following will be addressed:1)Does exposure to AZA in pregnancy &/or lactation increase risk of serious infections defined as requiring hospital assessment in the exposed children 2)Do immunosuppressive drugs or anti-phospholipid abs increase risk of developmental problems (delay±special needs±attention deficit disorder(ADD)±special educational needs). Methods A cross sectional, retrospective study recruited women with 4 SLE ACR criteria attending 8 specialist UK clinics with pregnancy data for children under 17yrs born after maternal SLE diagnosis. A standard questionnaire developed for this multi-centre study and used in US was used to collect data. Potential factors influencing infection and developmental problems, assessed were AZA, prednisolone, hydroxychloroquine, aspirin or heparin use in pregnancy, antiphospholipid syndrome, lupus anticoagulant &/or anticardiolipin (IgG&/orIgM) abs. Potential confounders assessed were pregnancy duration, pre-eclampsia, intra-uterine growth restriction, low birth weight, child age at assessment, maternal age at delivery, disease duration, prior renal biopsy and smoking. Results Complete data was available for 288 children born alive to 200 women: 66% Caucasian, 15% South Asian, 10% Afro-Caribbean,1% Chinese, 1% Hispanic 4% other and 4% not stated. The median (range) age of women at delivery was 32 (19-44) yrs, and duration of maternal disease was 6 (0-27) yrs. Infections were reported in 45(16%) of children. The odds ratio (OR) for infection in children with exposure to AZA was 1.63 (95%CI 0.84-3.15, p=0.15). In total 14(4%) of children were reported to have developmental delays, 7(2.5%) special needs, 3(1%) ADD and 6(2%) special educational needs. OR for developmental problems with AZA exposure was 1.22, 95%CI 0.44-3.42, and if mothers had antiphospholipid abs was 0.73, 95%CI 0.22-2.35. The age of child at assessment was associated with a small increased risk of developmental problems OR 1.15, 95%CI 1.05-1.26, p=0.003. No other potential risk factors were associated with infections or developmental problems. Conclusions No risk factors were identified for infection requiring hospital assessment, and only age of child at assessment was associated with increased risk of developmental problems. This study provides data to counsel women with SLE. References Akhtaret al. Maternal Anticardiolipin Affects Childhood Development.A&R.2008.57:9,443 Marderet al. In utero AZA exposure and increased utilization of special educational services in children born to mothers with SLE.A&R.2012:8:288 Acknowledgements LupusUK Disclosure of Interest : None Declared

Background Patients with systemic lupus erythematosus (SLE) are at increased risk of cardiovascular disease. This is thought to be due to both increased incidence of classical risk factors and SLE related risk factors (1). Objectives To investigate the incidence of cardiovascular events (CVEs) in SLE patients and the association with classical risk factors and SLE disease features. Methods Cardiovascular risk factors and SLE disease characteristics were evaluated in 200 female SLE patients. A subgroup was followed up at 5 years and CVEs (defined as myocardial infarction, angina, coronary angioplasty, coronary artery bypass surgery, stroke, transient ischaemic attack or peripheral vascular disease) were recorded. 5 year risk of CVE at baseline was calculated using the Framingham risk equation (2) and association of baseline measurements with subsequent CVEs were tested using non-parametric tests and linear regression models, adjusting for age. Results 124 patients were followed up at a median (IQR) of 5.8 (5.2, 6.3) years. At follow up, median (IQR) age was 55.6 (49.8, 62.4) years and disease duration was 16.3 (9.8, 23.5) years. At baseline, median (IQR) SLEDAI disease activity score was 1 (0, 4) and SLICC damage index was 0 (0, 1). 12 patients had suffered prior CVEs. The only significant difference at baseline between those who were and were not followed up was systolic blood pressure (132.2mmHg vs 124.7mmHg, p=0.015). At follow up, 12 patients had suffered a CVE giving a 10.2% 5 year CVE rate. Baseline predictors of CVEs (OR [CI 95%]) were hypertension (6.19[1.50,25.47]), prior CVE (4.89[1.15,20.65]), triglyceride levels (2.92[1.30,6.46]), cyclophosphamide exposure (4.20[1.77, 35.0]) and SLICC damage index (1.77[1.15, 2.62]). Venous thromboembolism (2.51[0.95,6.66]), azathioprine exposure (3.30[0.94,11.58]), metabolic syndrome (3.26[0.95, 11.28]) and disease duration (1.04[0.97, 1.43]) showed at trend towards significance. 8 of the 12 patients had no prior history of CVEs, giving a 7% 5 year primary CVE rate, this compared to our estimated median (IQR) 5 year risk using the Framingham risk equation of 1 (1, 3)%. Estimated risk was not significantly associated with subsequent CVE (OR 1.09 [CI95%0.88, 1.35]) and point estimates for cyclophosphamide exposure and triglyceride levels remained similar to in the population free of CVEs at baseline (4.20 [1.77, 35.0] vs 4.96 [0.77, 31] and 2.92 [1.3, 6.65] vs 2.55 [0.95, 6.8] respectively). Conclusions Our SLE cohort had a 7-fold increased risk of CVEs compared to what is predicted from the Framingham risk scores.The associations of cyclophosphamide exposure and SLICC damage index with future CVEs suggests disease severity may contribute to risk. We also noted that dyslipidaemia may contribute to CVE risk in SLE. Patients with more severe disease may be particularly at risk of future cardiovascular disease. References Bruce IN. “Not only ... but also”: factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus. Rheumatology (Oxford) 2005 Dec;44(12):1492-502. Anderson KM, Wilson PW, Odell PM, Kannel WB. An updated coronary risk profile. A statement for health professionals. Circulation 1991 Jan;83(1):356-62. Disclosure of Interest None Declared

Background Recent Canadian data suggested an increased male:female ratio in children born to women with SLE 1 . However results combined from PROMISSE and RRNL data demonstrated no ignificant gender difference 2 but reported hydroxychloroquine(HCQ) was protective against cardiac neonatal lupus(NL) in subsequent pregnancies in mothers with anti-Ro/La antibodies and a prior child with cardiac-NL 3 Objectives To address the following questions in UK cohort of children born to mothers with SLE: 1)Does HCQ protect against NL? 2)Is there an increased M:F ratio? Methods A cross sectional, retrospective study recruited women with 4 SLE ACR criteria attending 8 specialist UK clinics with available pregnancy data for children under 17 yrs born after maternal SLE diagnosis. A standard questionnaire developed for multi-centre study was used to collect data on each pregnancy and the child outcome. Data collected included ethnicity, age of mother, disease duration, autoantibody profile, exposure to HCQ and immunosuppressive drugs during pregnancy/lactation, age and gender of child, and medical conditions assessed at a hospital in the child. Results Complete data was available for 288 children born alive to 200 women: 66% Caucasian, 15% South Asian, 10% Afro-Caribbean, 1% Chinese, 1% Hispanic 4% other and 4% not stated. The median (range) age of women at delivery was 32 (19-44) yrs, and duration of disease was 6 (0-27) yrs. There were 128 (44%) male and 160 (56%) female children with M:F gender ratio of 0.80 (95% CI 0.63-1.01). In total 136 (47%) of children were exposed to HCQ and 152 (53%) were unexposed during pregnancy. Congenital heart block (CHB) was observed in 7 (2.5%) children and cutaneous NL was reported in 6 (2%) children. The frequency of CHB or cutaneous NL, was not significantly different in children exposed to HCQ versus those not exposed, OR 1.27 for all types of NL, 95%CI 0.39-4.08 (p=0.69). As expected the only significant risk factor associated with cardiac and cutaneous NL was anti-Ro±La antibodies, OR15.1, 95%CI 1.90-119.8 (p=0.01), which remained significant on multivariate analysis OR16.4 (p=0.01). There were no other significant potential risk or protective factors associated with cardiac or cutaneous NL; none of the other immunosuppressive drugs offered protection. Conclusions Gender ratio was almost equal and consistent with PROMISSE and RRNL data, in contrast to previously published Canadian data. . In contrast to published registry data that HCQ may be protective against recurrence of cardiac NL in subsequent pregnancies, HCQ was not protective against CHB &/or cutaneous NL in this UK cross sectional study. References: Vinet et al. Increased M:F Ratio in Children Born to Women with SLE.A&R.2013. Letter.[Epub ahead of print] Lockshin et al. Sex ratios of children of lupus pregnancies.A&R.2013.65:282 Izmirly et al. Maternal use of HCQ is associated with a reduced risk of recurrent anti-Ro-antibody-associated cardiac manifestations of NL.Circulation.2012:126:76-82 Acknowledgements Lupus UK Disclosure of Interest : None Declared

OBJECTIVE: To perform a clinical and immunological study of patients with rheumatoid arthritis who develop subnormal serum immunoglobulins on gold treatment; to clarify the nature of the defect in antibody production and determine the natural history of this adverse reaction; to use this information to suggest guidelines for the detection, investigation, and management of this complication. METHODS: 22 patients who developed subnormal levels of one or more immunoglobulin isotypes while receiving gold treatment were recruited over a 10 year period from the practice of a single rheumatologist. Antibody production was assessed by measurement of total immunoglobulins and of specific antibody production against polysaccharide and protein antigens, with test immunisation if necessary. RESULTS: Two broad patterns of antibody deficiency were identified: (1) (n = 11) mild, affecting only one immunoglobulin isotype and with normal specific antibody production. These patients were in general able to continue gold without further deterioration in antibody production. (2) (n = 11) severe, affecting two or three immunoglobulin isotypes, with defective specific antibody production. Six patients developed significant infections and were treated with immunoglobulin. Gold was discontinued in all. Normal antibody production recovered in nine patients, and in all but one followed for more than one year. No relation was seen between duration/dose of gold and antibody deficiency. CONCLUSIONS: Gold-induced antibody deficiency may be more common than usually recognised. A spectrum of deficiency exists, with some patients developing infective complications. Antibody production should be monitored in patients on gold treatment.

A randomized, double-blind, placebo controlled, cross-over study was conducted to determine the clinical efficacy of and patient tolerance to sustained-release glyceryl trinitrate (GTN) patches in the treatment of Raynaud's phenomenon. The patients studied were those with primary Raynaud's disease (n = 21) and patients with Raynaud's phenomenon secondary to systemic sclerosis (n = 21). GTN patches (0.2 mg/h) were found to be effective in reducing the number (P0.05) and severity of Raynaud's attacks (P0.05) in both groups of patients. Objective assessments by infrared thermography did not show any significant improvement when the patients were on GTN patches (P0.05). Headaches, refractory to treatment, led to the withdrawal of eight patients from the study and occurred in approximately 80% of the remaining patients. Thus, in spite of the subjective efficacy, the frequent headaches will limit the use of GTN patches in Raynaud's phenomenon. Elucidating the mechanism of action of the beneficial and adverse effects of GTN at the molecular level may shed light on the pathogenesis of Raynaud's phenomenon and its treatment.

In a cross-sectional study, 62 patients with systemic lupus erythematosus were assessed using standardized psychiatric and psychological methods; systemic disease activity was scored using the British Isles Lupus Assessment Group and the Lupus Activity Criteria Count indices. IgG and IgM anti-P antibodies were measured by ELISA using a synthetic 22 amino acid peptide as the relevant antigen. IgG and IgM anti-P antibodies were significantly associated with neuropsychiatric disorders (psychiatric and neurological) but failed to distinguish patients with psychiatric disorders from those with neurological disorders. These antibodies were not associated with cognitive impairment or systemic disease activity.

A synthetic peptide was used to develop an enzyme linked immunosorbent assay (ELISA) to detect antibodies to the ribosomal proteins P0, P1, and P2. Significantly increased levels of IgG antibodies to protein P were found in 16% (18/116) of patients with systemic lupus erythematosus but slightly increased levels were detected in 2% (2/98) of patients with rheumatoid arthritis and one normal control subject. No association was observed between the presence of IgG antibodies to protein P and either lupus psychosis or depression. Sequential studies in individual patients failed to show an association between antibody levels and the development of psychosis.

Antibodies to the ribosomal P protein are specific for SLE but their prevalence varies in different ethnic groups. In a group of Chinese SLE patients from Malaysia who have a high prevalence of this antibody, we have found an increased frequency of an uncharacterized HLA-DRB gene allele, DR16X, in patients who are positive for anti-P antibodies compared to antibody negative patients (31.3% vs 3.2%, P < 0.01, Pcorr not significant, relative risk = 13.6). DR16X has only been found in south east Asian populations and may be a genetic factor which influences the high prevalence of anti-P antibodies in Chinese.

Two patients with Behçet's syndrome and intracranial hypertension are reported. One developed a recurrence of papilloedema while receiving treatment but eventually made a full recovery, whereas the other developed optic atrophy within three months of onset despite treatment.