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Ana Teresa Melo,1,2,* Eduardo Dourado,1,2,* Raquel Campanilho-Marques,1,2,* Matilde Bandeira,1,2 Sofia C Barreira,1,2 José Costa,3 Rita Pimenta,4 Sofia Antunes-Duarte,4 Inês Cordeiro,1,2 João E Fonseca1,2 1Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal; 2Rheumatology Investigation Unit, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Centro Académico de Medicina de Lisboa, Lisbon, Portugal; 3Physical Medicine and Rehabilitation Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal; 4Dermatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Centro Académico de Medicina de Lisboa, Lisbon, Portugal*These authors contributed equally to this workCorrespondence: Ana Teresa Melo, Serviço de Reumatologia, Centro Hospitalar Universitário Lisboa Norte, Hospital de Santa Maria, EPE, R. Prof. Egas Moniz, Lisboa, 1700, Portugal, Tel +351 217805139, Email anateresamelo@campus.ul.ptBackground: Idiopathic inflammatory myopathies (IIM) are a rare heterogeneous group of diseases characterised by chronic skeletal muscle inflammation, but other organs are also frequently involved. IMM represent a diagnostic challenge and a multidisciplinary approach is important to ensure successful diagnosis and adequate follow-up of these patients.Objective: To describe the general functioning of our multidisciplinary myositis clinic, highlighting the benefits of multidisciplinary team management in patients with confirmed or suspected IIM and to characterise our clinical experience.Methods: Description of the organization of a dedicated multidisciplinary myositis outpatient clinic, supported by IMM specific electronic assessment tools and protocols based on our Portuguese Register - Reuma.pt. In addition, an overview of our activity between 2017 and 2022 is provided.Results: An IIM multidisciplinary care clinic, based on a close collaboration between Rheumatologists, Dermatologists and Physiatrist is detailed in this paper. One hundred and eighty-five patients were assessed in our myositis clinic; 138 (75%) of those were female, with a median age of 58 [45– 70] years. At the last appointment, 130 patients had a confirmed IIM diagnosis, and the mean disease duration was 4 [2– 6] years. The most frequent diagnosis was dermatomyositis (n = 34, 26.2%), followed by antisynthetase syndrome (n = 27, 20.8%) and clinically amyopathic/paucimyopathic dermatomyositis (n = 18, 13.8%). Twenty-four patients (18.5%) were on monotherapy and 94 (72.3%) were on combination therapy.Conclusion: A multidisciplinary approach is important to ensure the correct diagnosis and follow-up of these patients. A myositis clinic, with a standardised practice at a tertiary hospital level, contributes to a standardization of care and opens research opportunities.Keywords: inflammatory myopathies, rheumatology, dermatology, rehabilitation medicine, multidisciplinary clinic

Patient centred care is an increasingly important paradigm. Applying a treat-to-target strategy to the impact of the disease in patients' lives seems a very promising tool to serve this purpose. We aimed to evaluate if maximum acceptable impact scores (target-values) defined at the population level provide an appropriate representation for most individual patients. To determine if the individually established target values of impact are consistent enough to be used in a treat-to-target strategy.Consecutive patients with rheumatoid arthritis were asked to indicate, in two consecutive visits, the maximum severity of impact they considered acceptable to live with for the rest of their lives, in the seven domains of Rheumatoid Arthritis Impact of Disease score. The individual adequacy of population-based reference values was assessed by measures of dispersion. Stability of individual target-values were evaluated through intraclass correlation coefficient. Socio-demographic, clinical and psychological features were tested as co-factors of stability.299 patients were included. The dispersion of targets was wide (CV0.68), thus limiting the use of any population-based single values as targets for the individual patients. Although the mean target values were very similar in both visits for all domains, reliability was poor in all cases (ICCs: 0.37-0.47). Only 25-30% of the patients selected the same target value in the 2 visits. No explanatory factors for (non-)stability were identified.Quantified impact targets defined at population level are not appropriate for individual patient care. Research on alternative tools to support patient-centred, target-oriented management strategies is warranted.

© Copyright Clinical and Experimental Rheumatology 2022, Objectives: The purpose of this study was to review the frequency and clinical presentation of the rarest clinical manifestations of systemic lupus erythematosus (SLE). Methods: A list of 6 rare SLE manifestations were defined: gastrointestinal, liver, pulmonary, cardiac, ocular and neurological manifestations. Each topic was assigned to a pair of authors to perform a literature search and article review. Results: In total, 149 articles were included in the literature review: 37 for gastrointestinal manifestations, 6 for liver manifestations, 27 for pulmonary manifestations, 50 for cardiac manifestations, 16 for ocular manifestations, 13 for neurological manifestations. Gastrointestinal disorders included several clinical presentations with variable frequency (from 0.5% to 10.7% of the cases); liver involvement included lupus-related hepatitis (9.3%) and autoimmune hepatitis (2.3%). The rarest pulmonary manifestations identified were shrinking lung syndrome, described in 1.5% of patients, while interstitial lung disease and lupus pneumonia were reported in 4% and 3% of patients respectively. Myocarditis and pulmonary hypertension were also rarely described in SLE patients although ranging from 0.4-16% and 1-14% respectively, depending on the methodology used for its identification. Ocular manifestations in SLE included some rare manifestations (reported in less than 5% of patients) and lupus retinopathy that is described in 1.2-28.8% of patients depending on methods of ascertainment. Aseptic meningitis and chorea were also confirmed as very rare manifestations being reported in less than 1% and in 0.3-2.4% of cases respectively. Conclusions: The results of this literature review provide the basis for a better understanding of some less-known manifestations of SLE and for stressing the need for a higher awareness in diagnostic and therapeutic protocols regarding these rare disease aspects.

BackgroundThe definitions of remission play a crucial role in the treat-to-target strategy in rheumatoid arthritis.The patient’s and physician’s global assessment (PGA|PhGA) of disease activity are considered in current definitions, but PGA has been criticized for its poor relationship with actual disease activity. This leads to a considerable risk of overtreatment in patients who are otherwise in remission but fail this target solely because of PGA: PGA-near-remission. A dual-target strategy, excluding PGA from the definition of biological remission and the creation of a second target focused on disease impact has been proposed.1 Another proposal is to substitute PGA by PhGA with the purpose of strengthening the definition with a fourth variable capable of conveying relevant unaccounted factors, such as comorbidity.2ObjectivesTo assess the relationship of PGA and PhGA with objective measures of disease activity (DAS3v) and their impact upon near-remission and risk of overtreatment.MethodsThis is a cross-sectional analysis of data from RAID.PT, an observational, prospective and multicenter study, including adult patients fulfilling RA classification criteria. Tender (TJC28) and swollen (SJC28) 28 joint counts, C-Reactive Protein (CRP), Pain score, Health Assessment Questionnaire (HAQ), the Rheumatoid Arthritis Impact of Disease (RAID) total score, Hospital Anxiety and Depression Scale (HADS) scores, PGA and PhGA were collected. Disease Activity Score (DAS28-3v-CRP) was calculated and taken as the reference measure of current disease activity. Correlation between PGA and PhGA with other continuous variables was evaluated through Pearson´s Correlation Coefficient and variables with pResultsWe included 299 patients, 81.3% women, mean age of 57.4±12.0 years and disease duration 9.4±9.5 years. Average DAS28-3v-PCR 2.4 (±1.9).DAS3v-CRP is the strongest factor associated with PhGA, explaining 45% of its variance. Inversely, it only explains 2% of the variance of PGA, which is more affected by disease impact.In this clinical cohort, 13% of patients were in full Boolean remission and 41% in PGA-near-remission. Only 49 of 123 patients in the latter group had a PhGA >1.Considering PhGA instead of PGA in the Boolean definition of remission would increase the proportion of remission from 13 to 37.5% of the whole cohort.Table 1.Factors Associated with PGA and PhGA in multivariate regression analysisPGAPhGA(β, 95% CI)(β, 95% CI)(β, 95% CI)ΔR2ΔR2DAS28-3v-CRP3.7 (1.9-5.5)10.9 (9.4 to12.5)0.020.45RAID7.7 (6.7-8.8)3.4 (2.5 to 4.3)0.610.09HAQ5.6 (1.0-8.1)-3.4 (-6.4 to -0.4)0.010.01R20.64*0.55*DAS28-3v-CRP: Disease Activity Score-3 variables C-Reactive Protein. PGA: Patient global assessment; PhGA: Physician Global Assessment; HAQ (health assessment questionnaire); RAID: Rheumatoid Arthritis Impact Disease score. ΔR2 change of R2associated with the inclusion of the variable in the model. *pConclusionPhGA is a closer representation of actual disease activity than PGA, thus providing a more valid basis for treatment decisions aimed at disease activity. These observations support the substitution of PGA by PhGA in the Boolean definition of remission as it would strengthen the representation of disease activity and significantly reduce the risk of overtreatment in comparison to current definitions. The consequences of this change upon the prediction of long-term function and structural stability warrant evaluation. The patient’s perspective will remain central to disease management in the form of a distinct target.References[1]Ferreira et al. Ann Rheum Dis 2019 Oct;78(10):e109.doi: 10.1136/annrheumdis-2018-214199[2]Pazmino et al. J Rheumatol. 2021 Feb;48(2):174-178.doi: 10.3899/jrheum.200758Disclosure of InterestsNone declared.

BackgroundGiant cell arteritis (GCA) is the most common form of primary systemic vasculitis in patients aged >50 years. It predominantly affects the cranial arteries; however, extra-cranial disease involving the aorta and its major branches can also be present. Currently, ultrasound of the temporal (TA) and axillary (AX) arteries is the first imaging modality recommended in patients with suspected predominantly cranial GCA. Nevertheless, other arteries such as facial (FA), occipital (OC), subclavian (SC), and common carotid (CC) arteries can also show vasculitic changes on ultrasound. However, there are still conflicting data to support the inclusion of these arteries in the routine ultrasound assessment of patients with suspected GCA.ObjectivesTo assess the value of adding the evaluation of the FAs, OCs, SCs and CCs in the ultrasonographic diagnosis of patients with GCA.MethodsSingle-center observational retrospective study, using data from patients diagnosed with GCA registered at the Rheumatic Diseases Portuguese Registry (Reuma.pt). All patients underwent ultrasound of the TAs and AXs ± FAs, OCs, SCs or CCs at the time of diagnosis. The halo sign was considered a positive ultrasonographic finding for GCA. Only patients with the presence of halo sign in at least one of the arterial segments evaluated were included. Binary logistic regression modelling was performed to explore associations between the presence of halo sign in different arterial segments.ResultsWe included 84 patients, 57 (67.9%) females, with a mean ± standard deviation age at diagnosis of 75.6 ± 8.8 years. Halo sign was found in the TAs of 66/84 (78.6%) patients, AXs of 40/84 (47.6%) patients, FAs of 37/74 (50.0%) patients, OCs of 15/61 (24.6%) patients, SCs of 30/49 (61.2%) patients and CCs of 13/60 (21.7%) patients. Of the 18/84 patients with GCA without the presence of TA halo, 17/18 (94.4%) showed halo in the AXs, 1/18 (5.6%) in the FAs, 3/18 (16.7%) in the OCs, 15/17 (88.2%) in the SCs and 6/16 (37.5%) in the CCs. Of the 44/84 patients with GCA without the presence of AX halo, 43/44 (97.7%) showed halo in the TAs, 24/39 (61.5%) in the FAs, 12/32 (37.5%) in the OCs, 4/18 (22.2%) in the SCs and 3/33 (9.1%) in the CCs. A total of 83/84 (98.8%) patients had halo sign on the ultrasound of either the TA or AX arteries. The patient with normal TA and AX ultrasound had the presence of halo sign in the SCs. Table 1 shows the proportion of patients with positive TA and AX ultrasounds according to the presence of halo in the FA, OC, SC or CC arteries. Patients with involvement of the cranial arteries were more likely to have a TA halo (FA: OR 30.6, 95%CI 3.8-247.3; OC: OR not applicable) and less likely to have an AX halo (FA: OR 0.37, 95%CI 0.14-0.95; OC: OR 0.19, 95%CI 0.05-0.77). As opposed to patients with involvement of the extra-cranial arteries in whom the halo sign was more frequently found in the AXs (SC: OR 18.2, 95%CI 4.2-78.9; CC: OR 5.9, 95%CI 1.4-24.4) but not in the TAs (SC: OR 0.12, 95%CI 0.02-0.60; CC: OR 0.32, 95%CI 0.09-1.15).Table 1.Differences in the presence of halo sign in the temporal and axillary arteries according to the arterial segment affected.Arterial segment with haloTemporal arteries with haloAxillary arteries with haloFacial arteries (n=37)36/37 (97.3%)13/37 (35.1%)Occipital arteries (n=15)15/15 (100.0%)3/15 (20.0%)Subclavian arteries (n=30)15/30 (50.0%)26/30 (86.7%)Common carotid arteries (n=13)7/13 (53.8%)10/13 (76.9%)ConclusionOur results support the need to assess both TAs and AXs in patients with suspected GCA, resulting in a diagnostic sensitivity of 99%. Only by adding the evaluation of the SCs to the already recommended TAs and AXs increased the diagnostic sensitivity of ultrasound to 100%. All patients with a positive FA, OC or CC ultrasound for GCA also showed a halo sign in either the TAs or AXs. Hence, the additional assessment of these arteries did not improve the diagnostic yield of ultrasound and, therefore, should not be recommended in routine practice.Disclosure of InterestsNone declared

BackgroundThere is growing interest in reproductive issues in patients with Spondyloarthritis (SpA) and Psoriatic arthritis (PsA).ObjectivesTo describe a real-life cohort of prospectively-followed pregnancies in SpA and PsA patients, focusing on obstetric outcome and on flare during pregnancies and post-partum.MethodsData on SpA and PsA pregnancies prospectively-followed in 2 European pregnancy clinics from 2010 to 2021 were retrospectively analysed.Disease activity was assessed using ASDAS-CRP or DAS28-CRP according to the main involvement (peripheral or axial). Disease flare was defined as the need to treatment modification (introduction or increase ≥5mg/day of prednisone, introduction of cDMARD or bDMARD). Miscarriages were excluded from the analysis of flares.ResultsData on 122 pregnancies (53 PsA and 69 ‘other SpA’: 39 axialSpA, 20 undifferentiated SpA, 6 IBD-related SpA, 4 reactive arthritis) in 102 patients (median age at conception: 34 [IQR: 31-36] years; median disease duration: 72 [24-132] months) were collected.We recorded 98 (86%) live births and 16 (14%) miscarriages (8 missing data).Cesarean section was performed in 15/98 (15%) cases. Median week of gestation at delivery was 39 [38-40]; 8 preterm births (Fourty-two pregnancies (40%) had at least 1 flare during pregnancy; 7 pregnancies had more than 1 flare. Overall, there were 13, 24 and 12 flares in the 1st, 2nd and 3rd trimester, respectively.A higher frequency of patients with axial involvement was observed in the ‘flare’ group as compared to pregnancies without flare (83% vs 59%, p=0.02) (Table 1).Table 1.Comparison between ‘flare’ and ‘without flare’ groups.FLARE (42)WITHOUT FLARE (64)pAge at conception (years)33 (31-37)33 (31-35)0.88Disease duration at conception (months)71 (24-120)60 (24-137)0.74PsA13 (31%)31 (48%)0.11‘Other SpA’29 (69%)33 (52%)0.11Axial involvement35 (83%)38 (59%)0.02Peripheral involvement30 (%)54 (%)0.17bDMARD useAny time before pregnancy16 (38%)19 (30%)0.49Stop at + pregnancy test/1st trimester8 (19%)4 (6%)0.09Start/continue 1st trimester7 (17%)10 (16%)0.89Start in 2ndtrimester5 (12%)00.02Start in 3rd trimester2 (5%)00.30Post-partum flare11/34 (32%)22/49 (45%)0.36Continuous variables were compared using Mann-Whitney test; categorical variables were compared using Chi-square with Yates’ correction or Fisher’s exact test.Medications resumed to treat flare were steroids (29 pregnancies), csDMARDs (14 pregnancies) and TNF-inhibitors (7 pregnancies: 5 during the 2nd and 2 during the 3rd trimester).A post-partum flare was registered in 33/83 (40%) of cases, without difference between ‘flare’ group vs ‘without flare’ group (Table 1), as well as between PsA vs ‘other SpA’ pregnancies (47% vs 33%, p=0.2).ConclusionIn this cohort of SpA pregnancies, 40% experienced a flare during pregnancy and 40% during post-partum. Flares occurred more frequently in the 2nd trimester and especially in patients with axial involvement, requiring the start of a TNF-inhibitor during the 2nd or the 3rd trimester in 7 pregnancies. Having a flare during pregnancy was not associated with a post-partum flare.Disclosure of InterestsNone declared

BackgroundThe idiopathic inflammatory myopathies (IMM) module of the Rheumatic Diseases Portuguese Register (Reuma.pt/Myositis) is a tool used to systematically evaluate IIM patients.ObjectivesTo clinically characterise the Reuma.pt/Myositis cohort.MethodsMulticentre open cohort study, including IIM patients registered in Reuma.pt up to January 2022. Data collected included demographic, clinical, and treatment data and patient-reported outcomes. Data were presented as frequencies and median (interquartile range) for categorical and continuous variables, respectively.Results280 patients were included, 71.4% female, 89.4% Caucasian, with a median age at diagnosis and disease duration of 48.9 (33.6-59.3) and 5.3 (3.0-9.8) years, respectively. Patients were classified as having definite (N=57/118, 48.3%; N=35/224, 15.6%), likely (N=23/118, 19.5%; N=50/224, 22.3%), or possible (N=2/118, 1.7%; N=46/224, 20.5%) IIM by 2017 EULAR/ACR and Bohan-Peter criteria, respectively. Disease subtypes included dermatomyositis (DM, N=122/280, 43.6%), polymyositis (N=59/280, 21.1%), myositis in overlap syndromes (N=41/280, 14.6%), clinically amyopathic DM (N=17/280, 6.1%), nonspecific myositis (N=13/280, 4.6%), mixed connective tissue disease (N=12/280, 4.3%), immune-mediated necrotizing myositis (N=9/280, 3.2%), and inclusion bodies myopathy (N=7/280, 2.5%). Over the course of the disease, the most common symptoms were proximal muscle weakness (N=180/215, 83.7%), arthralgia (N=127/249, 52.9%), erythema (N=63/166, 38.0%), fatigue (N=47/127, 37.0%), Raynaud’s phenomenon (N=76/234, 32.5%), and dysphagia (N=33/121, 27.3%), and the most common clinical signs were Gottron’s sign (N=75/184, 40.8%), heliotrope rash (N=101/252, 40.1%), Gottron’s papules (N=93/237, 39.2%), and arthritis (N=38/98, 38.8%). Organ involvement included lung (N=78/230, 33.9%), oesophageal (N=40/221, 18.1%), and heart (N=11/229, 4.8%) involvements. Most patients expressed myositis-specific (MSA, N=158/242, 65.3%) and/or myositis-associated (MAA, 112/242, 46.3%) antibodies. The most frequent antibodies were anti-SSA/SSB (N=70/231, 30.3%), anti-Jo1 (N=56/236, 23.7%), and anti-Mi2 (N=31/212, 14.6%). Most patients had a myopathic pattern on electromyogram (N=101/138, 73.2%), muscle oedema in magnetic resonance (N=33/62, 53.2%), and high CK (N=154/200, 55.0%) and aldolase levels (N=74/135, 54.8%) at diagnosis, with median highest CK levels of 1308 (518-3172) and aldolase of 42 (12-121) mg/dL. Neoplasia was found in 11/127 patients (8.7%), most commonly breast (N=3/11, 27.3%), non-melanoma skin (N=2/11, 18.2%), and colorectal (N=2/11, 18.2%) cancer (Table 1). Most patients with cancer-associated myositis had DM (N=8/11, 72.7%) and expressed MSA (N=6/11) and/or MAA (N=3/11). The most used drugs over the course of disease were glucocorticoids (N=201/280, 71.8%), methotrexate (N=117/280, 41.8%), hydroxychloroquine (N=87/280, 31.1%), azathioprine (N=85/280, 30.4%), mycophenolate mofetil (N=56/280, 20.0%), intravenous immunoglobulin (N=55/280, 19.6%), and rituximab (N=45/280, 16.1%). At the last follow-up, there was a median MMT8 of 150 (142-150), modified DAS skin of 0 (0-1), global VAS of 10 (0-50) mm, and HAQ of 0.125 (0.000-1.125).Table 1.Autoantibodies in cancer-associated myositisCancerIIMAutoantibodiesBreastDM (3)Mi2, SRP (+ SSA/SSB), Pm/SclSkin (non-melanoma)Clinically amyopathic DM, PMJo1, SAE1 (+SSA/SSB)ColorectalDM (2)Mi2 (2)KidneyDM-LungDM-LymphomaInclusion bodies myopathy-UnknownDM-ConclusionReuma.pt/Myositis adequately captures the main features of inflammatory myopathies’ patients, depicting in this first report a heterogeneous population, with frequent muscle, joint, skin and lung involvements. Of interest, most patients reached low disease activity at the last follow-up appointment.Disclosure of InterestsNone declared

Background:Lupus nephritis (LN) is one of the most severe manifestations of Systemic Lupus Erythematosus.Objectives:1) To compare proliferative (PLN), membranous (MLN) and mixed LN regarding clinical and laboratory presentation. 2) To investigate predictors of progression to chronic kidney disease (CKD).Methods:Multicentre observational study, with retrospective analysis of a prospective cohort, using data from the Portuguese registry of rheumatic diseases – Reuma.pt. Patients with biopsy-proven PLN, MLN and mixed LN were included. Groups were compared using Pearson’s Chi-Square for categorical variables and One-Way ANOVA or Kruskal-Wallis for numerical variables. COX regression analysis was used to investigate predictors of CKD (defined as estimated glomerular filtration rate [eGFR] lower than 60 mL/min/1.73m2for at least 3 months) and Kaplan-Meier curves were drawn.Results:236 patients were included. Median follow-up was 8 years (IQR 11; maximum 35 years). As seen in table 1, the level of proteinuria did not differ between groups; however, MLN patients presented with significantly lower serum creatinine. Levels of complement C3 and C4 were reduced in PLN but normal in MLN patients, and there were fewer patients with positive anti-dsDNA antibodies in the MLN group (pTable 1.Comparative description of the Reuma.pt cohort of patients with proliferative, membranous and mixed LNPLNMLNMixedPTotal, N186428Females, N (%)157 (85)39 (95)4 (50)0.004EthnicityWhite European, N (%)163 (90)31 (78)7 (88)0.115Other, N (%)19 (10)9 (23)1 (13)Age LN diagnosis(y), median (IQR)30 (20)34 (16)42 (25)0.409SLEDAI at LN diagnosis, median (IQR)16 (9)10 (10)21 (17)0.006*uPCR at LN diagnosis, median (IQR)1675 (2598)1698 (2153)2160 (3320)0.629Creatinine at LN diagnosis, median (IQR)0.80 (0.32)0.70 (0.20)1.00 (0.95)0.006*eGFR at LN diagnosis, mean ± SD98 ± 33112 ± 1782 ± 450.019*Albumin at LN diagnosis, mean ± SD34 ± 734 ± 730 ± 60.390C3 at LN diagnosis, mean ± SD0.65 ± 0.260.90 ± 0.350.53 ± 0.30Positive anti-dsDNA LN diagnosis, N (%)115 (91)11 (48)6 (86)Use of antimalarials, N (%)166 (94)36 (92)8 (100)0.688Use of immunosuppressants, N (%)163 (94)33 (87)8 (100)0.245Use of corticosteroids, N (%)145 (84)33 (85)7 (100)0.511CKD after LN diagnosis, N (%)27 (15)1 (3)3 (38)0.018*ESRD, N (%)7 (4)1 (3)2 (25)0.016Deaths, N (%)14 (8)2 (5)00.610uPCR: urinary protein-creatinine ratio, mg/g; y: years; Creatinine presented in mg/dL, eGFR in mL/min/1.73m2,albumin in g/L and C3 in g/LNote: Baseline data (LN diagnosis) in grey; other data refer to the course of disease*Significant difference between the proliferative and membranous groupsFigure 1.Kaplan-Meir curves showing cumulative survival free of CKD in patients with PLN, MLN and mixed LNConclusion:Our results support previous findings from single-centre studies suggesting that MLN has a different serological profile than PLN, possibly reflecting different pathogenesis. Renal function at one year predicts long-term outcome in LN.Disclosure of Interests:Filipa Farinha: None declared, Sofia C Barreira: None declared, Maura Couto: None declared, Margarida Cunha: None declared, Diogo Fonseca: None declared, Raquel Freitas: None declared, Luís Inês: None declared, Mariana Luis: None declared, Carla Macieira: None declared, Ana Rita Prata: None declared, Joana Rodrigues: None declared, Bernardo Santos: None declared, Rita Pinheiro Torres: None declared, Ruth J. Pepper: None declared, Anisur Rahman: None declared, Maria Jose Santos Speakers bureau: Novartis and Pfizer

Background:It has been common practice to start a second TNF inhibitor (TNFi) in patients with axial spondyloarthritis (axSpA) who discontinue their first TNFi. It remains unclear if the reason for discontinuation of the first TNFi influences the response to the second.Objectives:To assess if the reason of discontinuation of the first TNFi influences the response to the second TNFi.Methods:Patients with axSpA from the ReumaPt registry, who discontinued their first TNFi and started a second TNFi and who had complete data on Ankylosing Spondylitis Disease Activity Score (ASDAS) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) at baseline, 3 and 6 months for their first TNFi were included. Then, they were followed every 6 months up to 12 years. The main outcome was the ASDAS clinically important improvement (ASDAS CII). Secondary outcomes were ASDAS major important improvement (ASDAS MI); ASDAS low disease activity (ASDAS LDA); ASDAS inactive disease (ASDAS ID) and BASDAI 50. The reason for discontinuation of the first TNFi was defined as: i) Primary failure, ASDAS CII was not achieved at 3 or 6 months; ii) Secondary failure, ASDAS CII achieved at 3 or 6 months but lost in ≥1 follow-up visit; iii) Adverse events; iv) Other (e.g. pregnancy, surgery). The response to the first TNFi at 3 and 6 months was compared to the response to the second TNFi at the same visits, adjusting for age, gender and C-reactive protein (CRP). The association between the reason of discontinuation of the first TNFi and response the second TNFi over time was tested in generalized estimating equations (GEE) models, adjusted for age, gender and CRP.Results:In total, 193 patients (53% male, mean age 45 (SD:11) years) were included, with a median follow-up time on the second TNFi of 1.5 years. Patients had a lower response to the second TNFi compared to the first TNFi according to the main outcome (ASDAS CII) at 3 months (41% vs 51%) and 6 months (35% vs 56%). There was an association between the reason to discontinue the first TNFi and response to the second TNFi as defined by the most stringent outcomes (ASDAS MI and ASDAS ID), but not for ASDAS CII (Table). Compared to patients who discontinued their first TNFi due to primary failure, patients were more likely to achieve ASDAS ID with the second TNFi when they discontinued their first TNFi due to secondary failure (OR: 7.3 [(95%CI: 1.9; 27.7]), adverse events (OR: 9.1 [2.5; 33.3]), or other reasons (OR: 7.7 [1.6; 37.9]).Conclusion:In axSpA, response to the second TNFi is worse compared to the first TNFi. Patients with a secondary failure to the first TNFi have a better response to the second TNFi compared to those discontinuing the first TNFi due to primary failure, particularly for most stringent outcomes.Table.Association between the reason for discontinuation of the first TNFi and response to the second TNFiReason to discontinue first TNFi*Outcome for the second TNFiOR (95% CI)ASDAS-CII (N=135)ASDAS-MII (N=135)ASDAS-LDA (N=166)ASDAS-ID (N=166)BASDAI50 (N=147)(ref Primary failure) -Secondary failure1.9 (0.7;4.8)4.8 (1.3;18.2)1.2 (0.6;2.4)7.3 (1.9;27.7)1.4 (0.6;3.0) -Adverse events1.5 (0.6;3.5)2.4 (0.6;9.6)0.9 (0.5;1.7)9.1 (2.5;33.3)1.1 (0.5;2.3) -Other1.0 (0.3;3.8)1.7 (0.1;19.4)1.0 (0.4;2.4)7.7 (1.6;37.9)0.5 (0.1;1.7)*GEE models with the reason of discontinuation of the first TNFi as predictor (reference category: primary failure); all models adjusted for age, gender and C-reactive protein. OR in bold are statistically significant (pDisclosure of Interests:Santiago Rodrigues-Manica Speakers bureau: Jansse, MSD, Novartis, Alexandre Sepriano: None declared, Fernando Pimentel dos Santos Speakers bureau: Novartis, Pfizer, Biogen, Vitoria,, Nélia Gouveia: None declared, Anabela Barcelos Speakers bureau: Bene, Eli-Lilly, Pfizer, MSD, Novartis, Jaime Branco Speakers bureau: Vitoria, Miguel Bernardes Speakers bureau: Abbvie, Amgen, Biogen, Eli-Lilly, Glaxo-Smith-Kline, Pfizer, Janssen, Novartis, Raquel Ferreira: None declared, Elsa Vieira-Sousa: None declared, Sofia C Barreira: None declared, Filipe Vinagre: None declared, Raquel Roque: None declared, Helena Santos Speakers bureau: AbbVie, Eli-Lilly, Janssen, Pfizer, Novartis, Nathalie Madeira: None declared, João Rovisco: None declared, Alexandra Daniel: None declared, Sofia Ramiro Grant/research support from: MSD, Consultant of: Abbvie, Lilly, Novartis, Sanofi Genzyme, Speakers bureau: Lilly, MSD, Novartis

Background Evidence suggests that social protection policies such as Brazil’s Bolsa Família Programme (BFP), a governmental conditional cash transfer, may play a role in tuberculosis (TB) elimination. However, study limitations hamper conclusions. This paper uses a quasi-experimental approach to more rigorously evaluate the effect of BFP on TB treatment success rate. Methods Propensity scores were estimated from a complete-case logistic regression using covariates from a linked data set, including the Brazil’s TB notification system (SINAN), linked to the national registry of those in poverty (CadUnico) and the BFP payroll. Results The average effect of treatment on the treated was estimated as the difference in TB treatment success rate between matched groups (ie, the control and exposed patients, n=2167). Patients with TB receiving BFP showed a treatment success rate of 10.58 percentage points higher (95% CI 4.39 to 16.77) than patients with TB not receiving BFP. This association was robust to sensitivity analyses. Conclusions This study further confirms a positive relationship between the provision of conditional cash transfers and TB treatment success rate. Further research is needed to understand how to enhance access to social protection so to optimise public health impact.

The transition from paediatric to adult health care has been recognised as a priority in recent years. Health care transition (HCT) is defined as the process of moving from a paediatric to an adult model of health care with or without a transfer of follow up to a different clinician. In our centre, the transition begins around 11 years, when the patient education process starts and at the same time enable adolescents and young adults (AYA) to acquire knowledge to manage their disease. By the age of 18 the transfer to adult care is made. This study aims to evaluate the transition process and the transfer from paediatric to adult rheumatology care at our centre. We included 126 patients, 78 (61%) were female, with a mean age of 23.1±3.2 years. 104 patients (83%) were transferred to a young adult clinic. In our centre, the transition of care was associated with a high degree of satisfaction, with just a 10% decrease in patient satisfaction between paediatric and adult care. We had low drop out rate, which was associated with longer disease duration. Few patients had worsening of disease activity. Our data reinforce that education and training in transitional care and having a transition program are important to optimize health outcomes in AYA with chronic diseases.

The goal of this research was to characterize the interior acoustics of high schools sports facilities using objective parameters. In situ measurements were done in 68 school gymnasiums in Portugal (Volume from 450 to 16,190 m3 with a median of 4,720 m3) regarding LAeqBN (background noise without gym classes), LAeqPE (ongoing Physical Education classes), RT, and RASTI. The results for LAeqBN were from 30 to 59 dB with a median of 42 dB. For the LAeqPE were found values from 68 to 90 dB with a median of 80 dB. For the RT(500/1k/2k), room values from 2.5 to 8.1 s with a median of 4.8 s, were measured. The room average RASTI values were from 0.26 to 0.54 with a median of 0.34. These sports rooms proved to be highly reverberant, almost without sound absorbing materials, which might be harmful, especially for the PE teachers. The subjective perception of the PE teachers was analyzed through questionnaires where it was verified that they feel most discomfort when it comes for noise conditions. This was supported by the objective results obtained. A multicriteria method to assess the overall acoustic quality of school gymnasiums is presented. Ideal values for those acoustic parameters are presented.

Radiologically diagnosed postmenopausal osteoporotic patients with at least one nontraumatic vertebral flattening were treated for one year with either oral pamidronate (APD), 300 mg/day plus calcium 1 g/day (n=39) or with calcium alone (n=21). Bone mineral density (BMD) was assessed in lumbar spine, femoral neck, trochanter and Ward's triangle by dual X-ray absorptiometry in order to determine the number of responders at each site. As no densitometric inclusion criteria were stipulated, wide inter- and intra-individual variations in both regional basal BMD and response to therapy were found. However, the APD-treated group showed significant mean BMD increases in spine (+3.1%; p < 0.001) and femoral neck (+3.2%; p < 0.002) versus basal level, whereas the calcium only group failed to exhibit significant differences. The entire 60-strong population was then split into two groups, according to whether individual BMD content was greater or less than the mean basal value for each skeletal site evaluated. For either treatment, subpopulations with lower basal BMD tended to achieve greater bone gain, though statistically significant differences were only disclosed at trochanter (p < 0.004) with APD and at femoral neck (p < 0.002) in the calcium only group. Globally speaking, increases in BMD were observed in 60-80% of patients receiving either treatment - who were thus defined as responders - at each particular skeletal area assessed. However, when only skeletal areas with low basal BMD were considered, the number of responders reached 60-100%. Responsive sites varied among patients: out of 56 cases, 9 (24%) on APD and 6 (32%) on calcium alone responded in all 4 areas evaluated, while a single case on the latter treatment failed to show BMD response at any site. Overall, the mean number of responsive sites was 2.7. Odds ratios were calculated considering treatment modality and high or low basal BMD as parameters, but no significant differences were found in the number of responders. It may be concluded that APD induces moderate lumbar and femoral neck bone mass gain in severe postmenopausal osteoporosis, whereas calcium alone leads to non significant variations, both findings being in agreement with reported data. Therefore, evaluated APD doses enhance mineralization in responsive sites alone, but fail to increase the total number of responders. Interestingly, responsive sites seem to be those relitively spared by the course of the disease.

Numerous studies have reported health and disease related problems in offspring with fetal alcohol spectrum disorders (FASD). Indeed, offspring exposed to alcohol during fetal development have problems ranging from stress disorders (Hellemans et al., 2010; Schneider et al., 2011), altered metabolic functioning (Chen et al., 2003), impairment in the immune response (Arjona et al, 2006), and disruptions in circadian rhythms (Chen et al., 2006; Handa et al., 2007). A critical component for regulation of stress, metabolic and immune functions is the proopiomelanocortin gene (POMC) (Boyadjieva et al., 2009; Sarkar et al., 2008), which has been shown to be a target of alcohol and clock genes (Agapito et al., 2010; Chen et al., 2006). Therefore, the resulting phenotypes of altered stress and metabolic responses due to developmental alcohol exposure may be in part due to effects on POMC producing neurons in the hypothalamus. Once transcribed, the POMC gene becomes a precursor for several bioactive peptides by posttranslational processing, including β-endorphin, adrenocorticotrophin (ACTH) and α-, β, and γ-melanocyte stimulating hormones (MSH), which are involved in regulation of food intake, metabolism, stress response (Millington, 2007) and immune regulation (Boyadjieva et al., 2006). POMC gene expression abnormalities are associated with obesity, hyperphagia, diabetes (Baker et al., 2005; Chen et al., 2005; Mizuno et al., 2003) and cancer (Sarkar et al., 2008). Thus POMC neurons are a key component regulating the metabolic signaling in the brain. Within the hypothalamus, several key genes, including signal transducer and activator of transcription 3 (Stat3), ankyrin repeat and suppressor of cytokine signaling (SOCS) box-containing 4 (Asb4), sirtuin 1 (Sirt1), and peroxisome proliferator-activated receptor gamma coactivator1α (Pgc1α), are associated with POMC function and play regulatory roles in metabolism. For example, Stat3 regulates POMC gene expression (Xu et al., 2007), and the mutation of this gene is associated with a severe obesity phenotype (Gao et al., 2004). Sirt1 is another key metabolic signaling gene that orchestrates adaptation to changing metabolic states in peripheral tissues (Cohen et al., 2004). Recently, Sirt1 has been found to localize in the arcuate nucleus of the hypothalamus and colocalizes with POMC producing neurons (Ramadori et al., 2008). In the liver both Sirt1 and Pgc1α peptides play a role to mediate the NAD+ mechanism. Interestingly, Pgc1α also colocalizes in POMC neurons, however the role that it plays in these neurons is unknown. Furthermore, gene expression levels of Sirt1 and Pgc1α are altered by alcohol exposure in the livers of adult rats (Lieber et al., 2008). Little is known about the function of Asb4, however, recent literature has indicated that Asb4 is expressed in the hypothalamic areas typically specific to regulating metabolic function. In POMC producing hypothalamic neurons, food intake regulates the gene expression level of Asb4 (Li et al., 2007), thus indicating its importance in metabolic sensing in the brain. Metabolic genes, in particular POMC and Sirt1, are expressed in a circadian manner, and are involved in core molecular clock function. (Chen et al., 2006; Grimaldi et al., 2009). Recently, clock genes have been connected to formation and progression of many diseases related to metabolic disorders (Ando et al., 2009; Bass et al., 2010). Clock genes, such as negative regulators, Period (Per1,2,3), and Cryptochrome (Cry1,2), and positive regulators, Clock and Bmal1, act in two tightly coupled transcriptional and translational feedback loops that are able to self-sustain a circadian rhythm (Ko and Takahashi, 2006). Interestingly, it appears that Per2 gene is a putative target of alcohol and may be linked to metabolic disease. Initial support for this notion stems from the evidence showing that alcohol exposure in adulthood or during fetal development alters the circadian expression of Per genes in the hypothalamus and peripheral tissues (Arjona et al, 2006; Chen et al., 2006). Additionally, Per2 gene mutant (Per2Brdm1) mice display enhanced alcohol consumption and preference (Spanagel et al., 2005), whereas Per1Brdm1 mutant mice do not show such an enhancement in alcohol drinking behavior (Zghoul et al., 2007). Evidence has shown, alcoholics with a specific set of polymorphisms in the Per2 gene consume less alcohol than alcoholics without the polymorphisms (Spanagel et al., 2005). Furthermore, under a metabolic disease state, the expression of Per genes is altered in peripheral tissues (Garaulet et al., 2010). However, there are no data available that connect Per genes in the mediation of ethanol’s programming of POMC-regulated metabolic functions. Therefore, we sought to determine whether postnatal alcohol exposure altered the expression levels of key metabolic genes in the hypothalamus of adult male and female mice.

Introduction Spondyloarthritis (SpA) includes a group of diseases that share immunogenetic, clinical and radiologic findings, with a particular involvement of the axial skeleton and the entheses. Methods SpA patients attending ambulatory care in 11 rheumatology services located in 6 Argentine provinces were included in a prospective, observational multicentre cohort of SpA in Argentina (Iberoamerican Spondyloarthritis Registry [RESPONDIA]). Data collected were transmitted online and stored in the Spanish spondyloarthritis registry (REGISPONSER) Web site. Sociodemographic, clinical features and diagnosis, disease activity, functional status, quality of life, work status, radiographic changes and treatment data were collected by means of validated tools. Results A total of 402 patients were included; 59% were male, with median age of 48.3 years and median disease duration of 8 years; 68.7% of patients belonged to middle and lower-middle social classes. Eighty-six patients were diagnosed with ankylosing spondylitis (AS), 242 with psoriatic arthritis, 25 with reactive arthritis, 10 with SpA associated with inflammatory bowel disease, 33 with undifferentiated SpA and 6 with juvenile AS. The median score was 2.6 for the Bath AS Functional Index, 3.8 for the Bath AS Disease Activity Index and 5 for the Bath AS Radiology Index. The lower social class patients achieved a worse Bath AS Functional Index than other social classes and a worse Bath AS Disease Activity Index, compared with upper-middle class. Conclusions The sociodemographic distribution pattern observed in these SpA patients was similar to that expected in the general population of Argentina, with worse functional capacity and higher disease activity observed in the lower social classes.

Palindromic rheumatism is characterized by multiple recurrent episodes of arthritis and periarthritis (mono or oligoarticular) that may last hours or days, disappearing without sequels. We report a 69-year-old male with a history of hypertension and a presumptive diagnosis of gout due to recurrent episodes of arthritis and periarthritis in the last thirty years. They involved at least two joints, lasted few days and were self limited. The patient was admitted due to arthritis and periarthritis of both wrists, knees, ankles, elbows and hands. He presented with fever (38-39 degrees C), intense articular pain and anorexia. With a presumptive diagnosis of palindromic rheumatism and the lack of response to non steroidal anti inflammatory drugs, methylprednisolone 20 mg/od per os was started, with an excellent response.

To analyze the factors associated with mortality, survival and causes of death in patients with systemic lupus erythematosus (SLE) in Argentina.A series of 366 patients with SLE (45 men and 321 women), mean age 29 y (range 11-70 y) and mean disease duration 6 y, was evaluated from 1990 to 1998. A total of 57 clinical, serological and therapeutic variables were studied.Five- and 10-year survival was 91% and 85% respectively. Forty four patients died (12%): 54% due to sepsis and 32% due to active SLE. Mortality risk factors included heart involvement CRR 3.82), hyperlipidemia (RR 2.72), renal damage (RR 2. 62), infections (RR 2.44), lung disease (RR 2.20) and myositis (RR 2. 07). High-dose prednisone (RR 3.4) or cyclophosphamide (RR 9.19) treatments increased the risk of sepsis (P=0.003) as a cause of death. However, corticosteroids, antimalarial agents and accumulated cyclophosphamide doses proved to be protective factors in overall mortality figures (RR1).The main risk factors of death in SLE were heart involvement, hyperlipidemia and renal damage. Treatment with steroids, antimalarial agents and cyclophosphamide improved survival. High-dose corticosteroids and cyclophosphamide were associated with sepsis as a cause of death.

The activity of olpadronate labelled with technetium-99m(99mTc) was monitored in plasma and urine samples after single oral (925 MBq 99mTc/10 mg, coadministered with 50 mg cold drug) and intravenous (925 MBq 99mTc/5 mg) administrations to two groups of patients with different rates of bone turnover. The first group comprised high bone turnover (HBTO) patients suffering from Paget's bone disease; the second group comprised patients with normal to low bone turnover (NBTO) having the diagnosis of rheumatoid arthritis and secondary osteoporosis. Kinetic variables were correlated with anthropomorphometric variables, biological markers of bone metabolism and plasma proteins. Data were also obtained after repeatedly dosing the HBTO patients. Additionally, Paget's bone and healthy bone (PB/HB) uptake before and after low-dose oral treatment were assessed by means of scintigraphy. Results showed that most of the kinetic variables did not differ between the two groups of patients, except for a greater V ss and smaller blood area under the curve AUC in the patients with HBTO. After a repeated-dose administration period, the blood AUC activity and Whole Body Retention (WBR) of the HBTO patients tended to be similar to those of the NBTO patients. In both groups, after oral dosing, the C max was 20 times lower than the C 0.5 after i.v. injection, and the oral bioavailability ranged from 3% to 4%. Finally, the plasma t 1/2β ranged from 9 to 14 h. Correlation coefficients were obtained from multiple regression analysis; kinetic variables showed very low correlations with anthropomorphometric measurements. In contrast the V ss and WBR were significantly correlated with serum alkaline phosphatase levels and the V ss also with urine hydroxyproline levels. Plasma protein concentration was also correlated with excretion parameters such as CLP and plasma t 1/2β after an oral dose. Scintigraphic studies in the HBTO group allowed bone selectivity to be seen through skeletal drug uptake. The 15 Pagetic lesions analysed in the HBTO group showed a decrease in PB/HB ratio from 3.8 in the basal study to 2.7 after olpadronate administration for 30 days at the rate of 50 mg/day. In conclusion, the kinetic profile of 99mTc-labelled olpadronate, mainly AUC and WBR, showed a dependence upon bone metabolism and seemed unrelated to body size variables. HBTO patients showed a lower blood AUC but a higher V ss. Both variables may have been reflecting the fact that the drug binds selectively with calcified tissues and, in turn, with the target compartment. Scintigraphy confirmed the labelled-compound bone selectivity as a desirable feature for a bone-scanning agent.

Longterm administration of steroid drugs, particularly prednisone, is known to induce osteoporosis, as well as bone growth inhibition and delayed fracture union. Recently deflazacort, an oxazoline prednisone derivative, has been developed to reduce such deleterious effects. We carried out a comparative study in premenopausal patients with rheumatoid arthritis (RA). Sixteen cases whose mean age was 36.5 years and mean disease duration 29 months, all fulfilling ARA criteria, were evaluated in a randomized, double blind trial. Visually identical deflazacort or prednisone capsules were given and patients were instructed to maintain an adequate calcium intake. Laboratory tests focussed on bone mineral density in lumbar spine, femoral neck and Ward's triangle and whole body mineral content. Differences between baseline and 12-month values were processed statistically. Persistent synovitis control proved similar for both drugs and features suggestive of Cushing's syndrome were only found in the prednisone group. The difference in whole body bone mineral content between the deflazacort and prednisone groups just failed to reach statistical significance. In the deflazacort group, the difference between the nonsignificant bone mineral density increase at the femoral neck and the significant decrease in the prednisone group proved statistically significant. Ward's triangle was the most sensitive area to bone mineral density changes in patients receiving prednisone, with a highly significant intergroup difference (p0.01). We believe this is the first study on corticosteroid induced osteoporosis, as evaluated by whole body mineral content measurements in premenopausal patients with short term RA, showing that deflazacort is a promising alternative in cases severe enough to require steroid therapy.

Degenerative arthropathy was experimentally induced in the right knee of 24 rabbits. The animals were randomly divided in 3 groups of 8 rabbits each. S-Adenosyl-L-Methionine (SAMe) was administered intramuscularly to 2 groups. One group received 30 and 60 mg/kg/day i.m. The remaining group was a control and received only a diluent. After 12 weeks of therapy rabbits were sacrificed and tibial and femoral cartilage specimens of both knees were taken. The latter was stained with hematoxylin -eosine, Masson's trichromic and Safranine 0 stains and was microscopically studied. The thickness and cell density of the lesioned cartilages were significantly greater in both groups treated with SAMe than the group control (p less than 0.001). Statistical differences (p less than 0.05) were found within 60 and 30 mg/kg/day of SAMe. A greater concentration of proteoglycans in the cartilage matrix was found in animals treated were as, a severe reduction was found in controls. The severity of the lesions, based on the histologic-histochemical analysis, was significantly lower in rabbits receiving SAMe (p less than 0.0005). These differences were correlated with the administration of SAMe and the possible mechanisms of action are discussed.

Twenty-four rabbits with surgically induced osteoarthritis of the knee were allocated into three treatment groups (placebo, S-adenosylmethionine (SAMe) 30 mg/kg per day, and SAMe 60 mg/kg per day). Intramuscular administration of drug or placebo was begun immediately after surgery and continued for 12 consecutive weeks. At the end of the treatment period, animals were killed, and the articular surfaces of the knees were studied using histologic and histochemical techniques. Microscopic studies showed that the number of cells and the depth of the cartilage were significantly (p less than 0.001) increased in SAMe-treated rabbits in comparison with placebo-treated animals. No difference was found in comparing data in animals given SAMe at the two dosage levels. In conclusion, these results suggest a chondroprotective effect of SAMe in animals with experimental osteoarthritis.

Excerpt To the editor: Solomon and associates (1) recently reported the case of a patient with eosinophilic fasciitis who showed a prompt and complete response to treatment with cimetidine, and the...