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O diagnostico clinico de dermatomiosite e muitas vezes dificil e desafiante. A presenca de uma historia clinica classica, aliada a um exame fisico completo e ao uso dos anticorpos especificos para miosite recentemente descritos, pode levar ao diagnostico mais precoce desta entidade. Desta forma e com o inicio atempado da terapeutica, minimiza-se o risco de progressao da doenca. Apresentamos o caso de uma doente com maos-de-mecânico e uma historia previa de toxidermia a hidroxicloroquina. Embora estes achados nao sejam patognomonicos de dermatomiosite, quando associados a uma historia clinica e exame fisico tipicos, sao ferramentas diagnosticas uteis.

BackgroundDifferent autoantibodies (Ab) have been associated with distinct systemic sclerosis (SSc) phenotypes. Most of these associations have not been confirmed in Portuguese patients.ObjectivesTo evaluate SSc immuno-clinical associations in the Rheumatic Diseases Portuguese Register (Reuma.pt) cohort.MethodsMulticentre open cohort study including adult SSc patients registered in Reuma.pt up to February 2021. The associations between Ab expression and clinical data were established using Chi-Square, Fischer’s Exact or Mann-Whitney U tests. The Bonferroni correction for multiple comparisons was applied to get α≤0.05. Definite associations were defined by p≤0.002, and likely associations by p≤0.05.Results1080 patients were included, with a mean age and disease duration of 60.2±14.6 and 12.4±10.0 years, respectively. Most were females (87.5%) and had white European ancestry (WEA, 93.2%). The most common disease subtypes were limited cutaneous (lcSSc, 57.4%), diffuse cutaneous (dcSSc, 17.7%), and very early diagnosis of SSc (VEDOSS, 12.3%). Most patients expressed antinuclear Ab (ANA, 93.4%), and the most frequent were anti-centromere (ACA, 54.6%), anti-topoisomerase I (Scl70, 21.8%), and anti-Pm/Scl Ab (PmScl, 4.7%).ACA had definite positive associations with female sex, older age at diagnosis, lcSSc, lower modified Rodnan skin score (mRSS, median 0 vs 4), and isolated sclerodactyly, and likely associations with a higher diagnosis delay, WEA and VEDOSS. ACA had definite inverse associations with flexion contractures (FC), myositis, digital ulcers (DU), and interstitial lung disease (ILD), and likely inverse associations with pitting scars (PS) and oesophageal involvement (OI).Scl70 had definite positive associations with male sex, dcSSc, higher mRSS, FC, DU, PS, ILD, and OI, and likely associations with younger age at diagnosis, tendon friction rubs, active scleroderma pattern in capillaroscopy, and heart involvement.PmScl had a definite association with myositis and likely associations with male sex, calcinosis, joints involvement, and ILD. Anti-U1RNP Ab had definite associations with younger age at diagnosis, MCTD and myositis, and likely associations with a lower diagnosis delay, African ancestry and joint involvement. Anti-RNA polymerase III Ab (RP3) had likely associations with higher mRSS and renal involvement. Anti-U3RNP Ab had a definite association with dcSSc and likely associations with calcinosis and renal involvement. Anti-Th/To Ab had likely associations with male sex and myositis. Anti-Ku Ab had likely associations with systemic lupus erythematosus and mixed connective tissue disease (MCTD) overlap syndromes.ConclusionThere was a higher prevalence of ACA and PmScl compared to other cohorts, most likely due to the high proportion of WEA patients. Most immuno-clinical associations described in the literature apply, including ACA with lcSSc and Scl70 with dcSSc, DU, PS and ILD. However, Scl70+ patients did not have an increased risk of renal involvement, and ACA+ patients did not have an increased risk for calcinosis, PAH or OI, contrary to what was described in the literature. New findings included the association of PmScl with ILD and Scl70 with an active pattern in capillaroscopy. Also, anti-U3RNP+ and Th/To+ patients did not have an increased risk of ILD or PAH, contrarily to what was previously reported. These nuances may be specific to the Portuguese SSc population or signal previously reported associations as geographically specific.Disclosure of InterestsNone declared

Cerrado vegetation is the main formation covering c.60% of the land surface of Maranhão, Brazil, with cerradão being the dominant physiognomy. To characterise the cerrado flora in Maranhão, 12 localities were selected across its distribution in the northeastern, central, southern and southeastern regions of the state. A total of 150 angiosperm species were identified, distributed across 105 genera and 43 families. Twelve are new occurrences in Maranhão, and of these, four are also new records for Northeast Brazil. Two distinct floristic regions were recognised: the cerrados of the northeastern and central regions, and the cerrados of the southern region. Three subgroups were recognised in the southern region: cerrados of the highest altitudes, medium-altitude cerrados and cerrados of variable altitudes. Floristic comparisons with the Brazilian cerrados suggest that the medium-altitude southern cerrados of Maranhão are similar to those of the central region of Brazil, whereas the northeastern, central and southern highest-altitude regions form a distinct floristic group.

Aims: This study aimed to assess age- and sex-related differences in management and 1-year risk for all-cause mortality and hospitalization in chronic heart failure (HF) patients. Methods and results: Of 16 354 patients included in the European Society of Cardiology Heart Failure Long-Term Registry, 9428 chronic HF patients were analysed [median age: 66 years; 28.5% women; mean left ventricular ejection fraction (LVEF) 37%]. Rates of use of guideline-directed medical therapy (GDMT) were high (angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers and mineralocorticoid receptor antagonists: 85.7%, 88.7% and 58.8%, respectively). Crude GDMT utilization rates were lower in women than in men (all differences: P ≤ 0.001), and GDMT use became lower with ageing in both sexes, at baseline and at 1-year follow-up. Sex was not an independent predictor of GDMT prescription; however, age >75 years was a significant predictor of GDMT underutilization. Rates of all-cause mortality were lower in women than in men (7.1% vs. 8.7%; P = 0.015), as were rates of all-cause hospitalization (21.9% vs. 27.3%; P 75 years. Conclusions: There was a decline in GDMT use with advanced age in both sexes. Sex was not an independent predictor of GDMT or adverse outcomes. However, age >75 years independently predicted lower GDMT use and higher all-cause mortality in patients with LVEF ≤45%. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology

Aims: We assessed the interplay between hyperkalaemia (HK) and renin–angiotensin–aldosterone system inhibitor (RAASi) use, dose and discontinuation, and their association with all-cause or cardiovascular death in patients with chronic heart failure (HF). We hypothesized that HK-associated increased death may be related to RAASi withdrawal. Methods and results: The ESC-HFA-EORP Heart Failure Long-Term Registry was used. Among 9222 outpatients (HF with reduced ejection fraction: 60.6%, HF with mid-range ejection fraction: 22.9%, HF with preserved ejection fraction: 16.5%) from 31 countries, 16.6% had HK (≥5.0 mmol/L) at baseline. Angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) was used in 88.3%, a mineralocorticoid receptor antagonist (MRA) in 58.7%, or a combination in 53.2%; of these, at ≥50% of target dose in ACEi: 61.8%; ARB: 64.7%; and MRA: 90.3%. At a median follow-up of 12.2 months, there were 789 deaths (8.6%). Both hypokalaemia and HK were independently. associated with higher mortality, and ACEi/ARB prescription at baseline with lower mortality. MRA prescription was not retained in the model. In multivariable analyses, HK at baseline was independently associated with MRA non-prescription at baseline and subsequent discontinuation. When considering subsequent discontinuation of RAASi (instead of baseline use), HK was no longer found associated with all-cause deaths. Importantly, all RAASi (ACEi, ARB, or MRA) discontinuations were strongly associated with mortality. Conclusions: In HF, hyper- and hypokalaemia were associated with mortality. However, when adjusting for RAASi discontinuation, HK was no longer associated with mortality, suggesting that HK may be a risk marker for RAASi discontinuation rather than a risk factor for worse outcomes. © 2020 European Society of Cardiology

Background:Systemic sclerosis (SSc) is a rare systemic rheumatic disease (SRD) characterized by small vessel inflammation and fibrosis of skin and internal organs. Pulmonary and cardiac involvement contribute to both morbidity and mortality associated with the disease. A multidisciplinary approach with strict monitoring is therefore key to attain clinical success.Objectives:To describe the organization and patient pathways of our SSc outpatient clinic.Methods:Observational study using data extracted from Reuma.pt/SSc (a subset of the Rheumatic Diseases Portuguese Register). Data extracted included demographic variables and clinical and immunological manifestations. The disease was classified according to the 2013 ACR/EULAR criteria. Our SSc clinic is managed by two dedicated Rheumatologists and up to two Rheumatology residents on a weekly basis, but it is a dynamic multidisciplinary clinic where various medical specialties collaborate closely. There are two associated subspecialty clinics (pulmonary hypertension and pulmonary fibrosis) where the Rheumatologists engage with pneumologists and cardiologists, allowing greater collaboration in the management of these patients. Patients’ data is systematically registered in Reuma.pt/SSc as a part of the routine activity of this clinic, contributing to real-world data on SSc.Results:A total of 220 patients were registered between July 2011 and June 2019. 196 (89.1%) were female, with a mean age of 58.9±14 years and a mean disease duration of 14.6±9 years. Ninety-seven patients (44.1%) had limited cutaneous SSc, 52 (23.6%) had diffuse cutaneous SSc, 35 (15.9%) had overlap SSc, 24 (10.9%) had preclinical SSc and 12 (5.4%) had SSc sine scleroderma. Raynaud phenomenon was present in 92% of the SSc patients and 40% had a history of digital ulcers. Gastrointestinal manifestations included esophageal dismotility in 39.5% of patients, gastric disease in 24.4% and intestinal involvement in 15.5%. Pulmonary involvement was found in 47.6% of SSc patients, heart disease in 43.6% and kidney involvement in only two patients. Antinuclear antibodies were positive in 92.2% of the patients, anti-centromere in 44.1%, anti-topoisomerase I antibodies in 39.1%, anti-U1RNP in 4.5% and only three patients had anti-PM-Scl and one had anti-RNA polymerase III. 31 patients were lost to follow-up and 32 died. 18 patients are currently being followed up in the pulmonary hypertension clinic and seven in the pulmonary fibrosis clinic.Conclusion:The implementation of a standardized approach with regular multidisciplinary work has proven very helpful in evaluating patients with SSc. The continuous registry of patients in Reuma.pt/SSc has been essential for patient care, research and healthcare planning.Disclosure of Interests:None declared

Background:In recent years more attention has been given to patients reported outcomes (PROs). Systemic sclerosis (SSc) is no exception. As there is no effective treatment or cure to SSc, it is important to recognize the relevance to patients of the different features of the disease to improve quality and enjoyment of life: the ultimate targets of therapy. Remarkably lacking in PROs is the evaluation of the overall perspective of subjective well being, equivalent to ‘happiness’ or “positive psychological dimensions”.Objectives:To examine the determinants of happiness and quality of life (QoL) in patients with SSc with emphasis on disease activity, disease impact and personality traits.Methods:This is an observational, cross-sectional and multicenter study from six rheumatology clinics in Portugal. A total of 113 patients with SSc with a complete set of data on disease activity, disease impact, personality, quality of life and happiness were included.Structural equation modelling (latent variable structural model) was used to estimate the association between the variables using a maximum likelihood estimation with Satorra-Bentler’s correction and performed with STATA® 15.0. Two hypotheses were pursued: H1 – Disease activity and impact of disease are negatively associated to overall QoL and happiness; H2 – ‘Positive’ personality traits are related to happiness both directly and indirectly through perceived disease impact.Results:Results obtained in the structural equation measurement model indicated a good fit [χ2/df=1.44; CFI=0.93; TLI=0.90; RMSEA=0.06] and supported all driving hypotheses (Figure 1). Happiness was positively related to ‘positive’ personality (β=0.45, p=0.01) and, to a lesser extent, negatively related with impact of disease (β=-0.32; p=0.01). This impact, in turn, was positively related to EUSTAR activity score (β=0.37; pConclusion:Optimization of Qol and happiness in people with SSc requires effective control of the disease process. Personality and its effects upon the patient´s perception of the disease impact, seems to play a pivotal mediating role in these relations and should deserve paramount attention if happiness and enjoyment of life is taken as the ultimate goal of health care.Disclosure of Interests:Tânia Santiago: None declared, Eduardo Santos: None declared, Ana Catarina Duarte: None declared, Patrícia Martins: None declared, Marlene Sousa: None declared, Franscisca Guimarães: None declared, Soraia Azevedo: None declared, Raquel Ferreira: None declared, Miguel Guerra: None declared, Ana Cordeiro Consultant of: Ana Cordeiro has acted as a consultant for Roche, Speakers bureau: Ana Cordeiro has received speaker fees from Boehringer Ingelheim, Lilly, and Vitoria, Inês Cordeiro: None declared, Sofia Pimenta: None declared, Patrícia Pinto: None declared, Maria Joao Salvador: None declared, José Antonio P. da Silva Grant/research support from: Pfizer, Abbvie, Consultant of: Pfizer, AbbVie, Roche, Lilly, Novartis

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., The coronavirus disease 2019 (COVID-19) pandemic has come with many challenges for healthcare providers and patients alike. In addition to the direct burden it has placed on societies and health systems, it had a significant impact in the care of patients with chronic diseases, as healthcare resources were deployed to fight the crisis, and major travel and social restrictions were adopted. In the field of rheumatology, this has required notable efforts from departments and clinicians to adapt to the novel status quo and assure the follow-up of patients with rheumatic and musculoskeletal diseases. In the present viewpoint, we provide a practical approach to tackle this reality. Key measures include setting up preventive team management strategies, optimising communication with patients and reorganising patient care in all its dimensions. We then anticipate the nuances of rheumatology practice as restrictive measures are progressively lifted, while an effective vaccine is still pending. This includes the need to reimpose the same strategy as further waves unfold. Finally, we look ahead and address the lessons we can incorporate into post-COVID-19 rheumatology.

Background:Antisynthetase syndrome (AS) may have different clinical phenotypes and outcomes associated with different anti-aminoacyl RNA-synthetase (anti-ARS). Patients may also present with incomplete/early phenotypes that do not fulfil the classification criteria.Objectives:To evaluate the clinical and demographic characteristics of patients positive for anti-ARS in our Myositis clinic.Methods:Observational study using data from the Portuguese Rheumatic Diseases Register (Reuma.pt/Myositis protocol). Data extracted included demographic variables, clinical features and immunological expression of the disease.Results:17 patients were identified. All met the criteria for AS according to Connors criteria, while 3 did not met according to the Solomon criteria. Mean age at diagnosis was 60.1 years (26 - 80) and 76.5% were female. Mean follow-up time was 2.8 (0.5-9) years. Only 3 patients had history of smoking in the past. The autoantibodies expressed were anti-Jo1 (n=12), anti-PL12 (n=2), anti-OJ (n=2) and anti-PL7 (n=1). 4 patients positive for anti-Jo-1 also expressed anti-Ro52. The clinical information and treatment are described in table 1. One patient presented as a paraneoplastic syndrome associated with anti-Jo-1.Table 1.Demographic and clinic characteristics of our cohort. AZA – azathioprine; CYC – Cyclophosphamide; DM – dermatomyositis; GS – Gottron’s sign; ILD – Interstitial lung disease; PM – Polymyositis; NSIP - Nonspecific interstitial pneumonia; MH – mechanic hands; MMF - Mycophenolate mofetil; MTX – Methotrexate; PDN – prednisolone; RP – Raynaud phenomenon; RTX – Rituximab; UIP - Usual interstitial pneumonia; Y – yes; N – no. Connors criteria – anti-ARS plus one or more of RP, MH, arthritis, ILD, fever. Solomon criteria – anti-ARS plus 2 major criteria or 1 major and 2 minor criteria. *induction therapy.CaseSerologyMajor criteria (ILD [NSIP/UIP/non-specific] or PM/DM)Minor criteria (Arthritis, MH, RP)Other manifestationsConnors (2010)/ Solomon (2011) criteriaPDNDMARDcs (MTX/MMF/AZA)CYC/RTX1Jo1PMMH, arthritisGSY/YYMMF-2Jo1NSIPRP, MHAstheniaY/YYAZA-3Jo1NSIPMH, arthritisCalcinosis, astheniaY/YYAZA-4Jo1NSIP; DM-GSY/YY--5Jo1/Ro52PMMH, arthritisGS, astheniaY/YYMTX-6Jo1UIPRP, arthritisAstheniaY/YY-RTX7Jo1/Ro52NSIP; PMarthritis-Y/YYMMFCYC*8Jo1NSIP; PM--Y/YYMMF-9Jo1/Ro52NSIP; PM--Y/YYAZA-10PL7-RP, arthritis, MHDysphagiaY/NY--11Jo1-RPAstheniaY/N---12Jo1/Ro52PMMH, arthritisGS, astheniaY/YYMMF-13PL12PMRP, arthritisGS, astheniaY/YYMMF-14Jo1UIPRP, arthritisWeight loss, astheniaY/YY-RTX15OJNon-specific pattern--Y/NYMMF-16OJNSIP--Y/YY--17PL12PMRP, MH-Y/Y---Conclusion:The most frequent autoantibody was anti-Jo-1, which is consistent with the literature. Interestingly, patients with anti-PL, usually described as having severe lung disease, in our series do not have it. Additionally, we found a trend for a younger age at diagnosis in Jo1 positive patients and remarkably more than half of these patients have been diagnosed with ILD, being the NSIP pattern the most frequently reported.Disclosure of Interests:None declared

© International League of Associations for Rheumatology (ILAR) 2019, Introduction/objectives: To evaluate rituximab (RTX) effectiveness and safety in patients with interstitial lung disease (ILD) related to connective tissue diseases (CTD). Methods: Retrospective multicenter cohort study, including patients with CTD-ILD, followed in six Portuguese rheumatology departments until November 2018. ILD diagnosis was based on high-resolution CT (HRCT) and/or lung biopsy. Results of HRCT, pulmonary function tests, and 6-min walking test before and after RTX were compared using the Wilcoxon matched pair test. Safety, including adverse events during treatment and reasons for RTX discontinuation, was also analyzed. Results: A total of 49 patients were included, with rheumatoid arthritis being the commonest CTD (61.2%). The median interval between CTD onset and ILD diagnosis was 4 years (IQR 1-9.5) and median ILD duration at first RTX administration was 1 year (IQR 0-4). The median RTX treatment duration until the last follow-up was 3 years (IQR 1-6). Usual interstitial pneumonia (UIP) and non-specific interstitial pneumonia (NSIP) were the commonest patterns, occurring in 20 and 18 patients, respectively. One year after RTX first administration, there was a stabilization in carbon monoxide diffusing capacity (DLCO; mean + 5.4%, p = 0.12) and improvement in forced vital capacity (FVC; mean + 4.3%, p = 0.03), particularly in patients with NSIP. Patients with UIP had less promising results, but at 1 year, pulmonary function tests remained stable (DLCO + 2.5%, p = 0.77; FVC + 4.2%, p = 0.16). Infection was the main reason for RTX discontinuation and led to two deaths. Conclusions: RTX seems to be a promising treatment for CTD-ILD patients, particularly when NSIP pattern is present. Key points • The use of rituximab in patients with interstitial lung disease related to connective tissue disease is associated with long-standing disease stability in a wide range of systemic rheumatic diseases. • Efficacy results were particularly impressive in patients with non-specific interstitial pneumonia pattern, although in a subgroup of patients with usual interstitial pneumonia pattern, disease progression was also hold with this treatment. • In a large number of patients, rituximab was used in monotherapy and as first-line treatment.

Aims: Classification of acute heart failure (AHF) patients into four clinical profiles defined by evidence of congestion and perfusion is advocated by the 2016 European Society of Cardiology (ESC)guidelines. Based on the ESC-EORP-HFA Heart Failure Long-Term Registry, we compared differences in baseline characteristics, in-hospital management and outcomes among congestion/perfusion profiles using this classification. Methods and results: We included 7865 AHF patients classified at admission as: ‘dry-warm’ (9.9%), ‘wet-warm’ (69.9%), ‘wet-cold’ (19.8%) and ‘dry-cold’ (0.4%). These groups differed significantly in terms of baseline characteristics, in-hospital management and outcomes. In-hospital mortality was 2.0% in ‘dry-warm’, 3.8% in ‘wet-warm’, 9.1% in ‘dry-cold’ and 12.1% in ‘wet-cold’ patients. Based on clinical classification at admission, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: ‘wet-warm’ vs. ‘dry-warm’ 1.78 (1.43–2.21) and ‘wet-cold’ vs. ‘wet-warm’ 1.33 (1.19–1.48). For profiles resulting from discharge classification, the adjusted hazard ratios (95% confidence interval) for 1-year mortality were: ‘wet-warm’ vs. ‘dry-warm’ 1.46 (1.31–1.63) and ‘wet-cold’ vs. ‘wet-warm’ 2.20 (1.89–2.56). Among patients discharged alive, 30.9% had residual congestion, and these patients had higher 1-year mortality compared to patients discharged without congestion (28.0 vs. 18.5%). Tricuspid regurgitation, diabetes, anaemia and high New York Heart Association class were independently associated with higher risk of congestion at discharge, while beta-blockers at admission, de novo heart failure, or any cardiovascular procedure during hospitalization were associated with lower risk of residual congestion. Conclusion: Classification based on congestion/perfusion status provides clinically relevant information at hospital admission and discharge. A better understanding of the clinical course of the two entities could play an important role towards the implementation of targeted strategies that may improve outcomes. © 2019 The Authors. European Journal of Heart Failure © 2019 European Society of Cardiology

Background The vasculitides are a group of relatively rare diseases with different manifestations and outcomes. New therapeutic options have led to the need for long-term registries. The Rheumatic Diseases Portuguese Register, Reuma.pt, is an electronic clinical record, created in 2008, which currently includes specific protocols for 11 diseases and >16000 patients registered from 79 national and international rheumatology centres. Since October 2014, a dedicated protocol to vasculitis has been created as part of the European Vasculitis Society initiative of having compatible European registries. Objectives To describe the structure of Reuma.pt/Vasculitis and characterize the patients registered over the last two years. Methods We developed a dedicated web-based software to enable prospective collection and central storage of anonymised data from patients with vasculitis. All Portuguese rheumatology centres were invited to participate. Data regarding demographics, diagnosis, classification criteria, imaging and laboratory tests, outcome measures of prognosis, damage, disease activity and quality of life, and treatment were collected. We performed a cross-sectional descriptive analysis of all patients registered up to January 2017. Results A total of 492 patients, with 1114 visits, from 11 centres were registered in Reuma.pt/Vasculitis. The mean age was 53±20 years at last visit; 68% were females. The diagnoses followed the 2012 Chapel Hill Consensus nomenclature (Table 1). The most common diagnoses were Behcet9s disease (BD) (39%) and giant cell arteritis (GCA) (20%). Patients with BD met the International Study Group 1990 criteria, the International Criteria for BD 2006 and 2013 in 84%, 95% and 95% of cases, respectively. Patients with GCA met the 1990 American College of Rheumatology criteria in 95% of cases. Data on vascular ultrasound was available in 74% of patients; 73% compatible with the diagnosis. Assessment of the Birmingham Vasculitis Activity Score (BVAS) and Vasculitis Damage Index (VDI) was available for all vasculitides and the Five Factor Score calculation of survival rate for ANCA associated vasculitis (AAV) and polyarteritis nodosa (PAN). The mean BVAS at first visit was 18±7 for AAV and 15±9 for PAN; the mean VDI at last visit was 3±2 for AAV and 2±2 for PAN. Health related quality of life assessments (SF-36, EQD5, FACIT and HADS) were also collected. Treatment registry with the disease assessment variables shown in graphics was available for all patients; only 6% were under biologic treatment. Conclusions Reuma.pt/Vasculitis is a registry adapted for routine care, allowing an efficient data repository at a national level with the potential to link with other international databases. It facilitates research, trials recruitment, service planning and benchmarking. Disclosure of Interest None declared

Background Risk of pulmonary embolism (PE) in systemic sclerosis (SSc) has been estimated between 2.51–3.47 fold higher when compared to non-SSc patients (pts). Proinflammatory state, vasculopathy and vascular injury may contribute to a prothrombotic state in SSc and increased risk for venous thromboembolism. Objectives Calculate frequency and identify possible risk factors for PE among SSc pts;analyse efficacy of longterm anticoagulation (ACO) in these pts. Methods We conducted a retrospective analysis of 110 pts with SSc followed in our Rheumatology department and selected those who performed lung ventilation/perfusion scintigraphy (V/Q scan) or CT pulmonary angiography due to worsening dyspnea/fatigue or isolated reduction of the carbon monoxide diffusing capacity (DLCO). We collected demographic features, comorbidities, age at SSc diagnosis, anti-nuclear antibody specificities, dyspnea according to New York Heart Association (NYHA) classes and results of cardiopulmonary exams. PE and related variables were assessed at baseline and after 12 months of ACO. Results PE was diagnosed in 12 out of 29 (41.4%) SSc pts that met inclusion criteria, with the majority presenting bilateral peripheral multisegmental defects. Most were females (91.7%), mean age of 59.4 (±12.7) years (yrs). Two thirds were diagnosed with limited SSc with mean disease duration of 13.3 (±12.9) yrs. Mean time between SSc and PE diagnosis was 8.5±8.2 yrs, although one third of the pts was diagnosed within the first year of SSc diagnosis. One patient was taking oral contraceptives and none had thrombophilia, previous surgery or cancer. One third was classified as having NYHA class≥3, with a mean N-terminal pro-brain natriuretic peptide (NTproBNP) of 1108pg/mL (19 to 8069). Six pts had concomitant interstitial lung disease (ILD) and 8 had an estimated pulmonary artery systolic pressure (PASP)≥35 mmHg (6 of them had concomitant ILD). From these only 2 had pulmonary hypertension confirmed by right heart catheterization and 1 died. When comparing SSc pts with and without PE, Scl70 positivity was more common in pts with PE (p=0.041). No significant associations were found between PE and several cardiovascular risk factors. From the 12 pts with PE, 10 were on longterm ACO:5 on rivaroxaban, 4 on warfarin and 1 on apixaban. Clinical reassessment after 12 months of ACO is shown in figure 1. Conclusions Our results suggest that PE is frequent in SSc and must be considered in the differential diagnosis of worsening fatigue and dyspnea and/or reduction of DLCO/PASP increase. PE may occur more frequently in Scl70 positive pts and early in disease course, probably due to vasculopathy and vascular injury being more prominent in the early phase of the disease. Although there is no consensus regarding the optimal ACO, the disease9s vasculopathy seems to be an important contributor, potentially preventing improvement in perfusion defects, regardless of the anticoagulant used. Disclosure of Interest None declared

Mutations in the gene that encodes Fibroblast Growth Factor Receptor 3 (FGFR3) are associated with Achondroplasia (MIM 100800), Hypochondroplasia (MIM 146000), Muenke Syndrome (MIM 602849), Thanatophoric Dysplasia (MIM 187600, MIM 187601) and Lacrimo-Auriculo-Dento-Digital Syndrome (MIM 149730).Here we report a clinical and molecular study in a large cohort of 125 Portuguese patients with these skeletal disorders. The identification of the P250R mutation allowed the confirmation of the Muenke Syndrome in 9 out of the 52 cases referred. Two known mutations were found in the Thanatophoric Dysplasia referred cases. No mutations were identified in the LADD syndrome patient. In Achondroplasia and Hypochondroplasia, genetic heterogeneity was present amongst the 70 clinically diagnosed patients with 5 different mutations identified. As in other studies, complex phenotypic heterogeneity amongst patients carrying the same gene defect was observed. In several cases, the new amino acids encoded, as a consequence of mutations, were related to the severity of patients' phenotype. The presence of 10 misdiagnosed cases emphasizes the importance of performing mutation analysis of the hotspot regions responsible for both dysplasias (Ach and Hch). For patients with an unquestionable clinical diagnosis, lacking the most common mutations, a complete screening of FGFR3 is necessary.

Eighty seven olive (Olea europaea ssp. sativa L.) cultivar accessions from Portugal were characterized by means of randomly amplified polymorphic DNA (RAPD) markers. Of the 11 arbitrary 10-mer primers tested a total of 92 polymorphic bands were obtained, representing 87.6 % of the total amplification products. Twenty nine different genotypes were clearly discriminated. Differences were not found among the amplification profiles from different individuals of the same cultivar. All the genotypes could be identified by the combination of three primers: OPR-1, OPK-14 and OPA-1, seven genotype-specific markers being detected. Genetic relationships were estimated by the unweighted pair-group method with arithmetic averaging (UPGMA). The genetic analysis of the results showed a gradual distance between the various cultivars, making it difficult to identify well-differentiated phylogenetic groups, although two clusters were distinguishable with 35 % similarity, in addition to three independent branches with lower similarity: Galega, Tentilheira and Redondal. The dendrogram reflect some relationships for most of the cultivars according to the use of the fruit and ecological adaptation.

O Síndroma de Williams tem uma expressão fenotípica variável, que inclui um fácies característico, atraso do desenvolvimento psicomotor, cardiopatia e outras anomalias, nomeadamente renais ou esqueléticas. Recentemente foi identificada nestes doentes a presença de uma microdelecção de dimensões variáveis no cromossoma 7 (7q11.23), que inclui o gene da elastina. O rastreio desta microdelecção, através da técnica de hibridização in situ com fluorescência, tem revelado uma taxa de concordância fenótipo/genótipo superior a 90%. É apresentada uma revisão das manifestações clínicas, alterações laboratoriais e genéticas deste síndroma. Foi reobservada a nossa série de doentes (n=8) com o diagnóstico clínico de Síndroma de Williams, e em todos pesquisada a delecção característica. Os objectivos que nos propusemos, de acordo com estes recentes avanços, foram os de confirmar ou infirmar o diagnóstico clínico e laboratorial, caracterizar a história natural da doença e avaliar a adequação da técnica de hibidização in situ com fluorescência. Verificámos em todos os doentes cujo fenótipo levou ao diagnóstico clínico de Síndroma de Williams a delecção do cromossoma 7, o que indica uma mesma etiologia e uma adequada classificação. São sugeridas algumas alterações fenotípicas que em conjunto são muito sugestivas de Síndroma de Williams, e outras que classicamente lhe são atribuídas e que por vezes estão ausentes. Concluímos que a técnica de hibridização in situ com fluorescência é um meio de diagnóstico laboratorial valioso, com especial interesse no diagnóstico precoce, quando o quadro clínico típico está incompleto., Portuguese Journal of Pediatrics, Vol 31 No 3 (2000)

Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p

Background Nailfold capillaroscopy (NCP) is a useful tool for the diagnosis and follow-up of systemic rheumatic diseases and represents one of the best methods to evaluate microvascular abnormalities. Objectives To characterize NCP findings of patients with Systemic Sclerosis (SSc), and understand how NCP associates with the presence of digital ulcers, gastrointestinal involvement, pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD). Methods NCP findings of adult patients with SSc followed-up in our center were reviewed. Demographic and clinical features were collected. Nonparametric tests were used to determine potential associations between capillaroscopy findings/patterns and the presence of digital ulcers, gastrointestinal involvement, PAH and ILD. Results In total, 52 out of 103 patients with SSc had at least one NCP result available. Forty five were female (86.5%) and seven male (13.5%), the age was 56.6 ±13.2 years and disease duration 10.9 ±10.5 years. Thirty one (59.6%) had limited cutaneous SSc, seven (13.5%) diffuse cutaneous SSc, ten (19,2%) VEDOSS, three (5.8%) overlap syndromes and one (1.9%) SSc sine scleroderma. (table 1). The most frequent NCP findings were hemorrhages (54.7%) megacapillaries (54.7%), and capillary dilatations (52.8%). We found that digital ulcers were significantly associated with the existence of avascular areas (p=0.02), and with neoangiogenesis (p=0.03) in univariate analysis, but were not associated with any capillaroscopy pattern. Looking to interstitial lung disease, there is a trend for association with the presence of avascular areas (p=0.056). Only one patient had PAH confirmed by right heart catheterization. In this case NCP showed giant capillaries, neoangiogenesis and avascular areas. There was also a trend for association between avascular areas and higher values of NT pro BNP (p=0.078). Gastrointestinal involvement was not significantly associated with NCP findings (table 2). Conclusions In our study the presence of avascular areas and neoangiogenesis in NCP was significantly associated with the existence of digital ulcers. Also, ILD and higher values of NT-proBNP were more common in patients who present avascular areas. These results suggest that abnormalities detected in the NCP might help predict organ involvement, although long term follow up and greater numbers of patients are needed in order to confirm the prognostic value of NCP findings. References Mannarino E, Pasqualini L, Fedeli F, Scricciolo V, Innocente S. Nailfold capillaroscopy in the screening and diagnosis of Raynaud9s phenomenon. Angiology 1994; 45: 37–42 Disclosure of Interest None declared

Background Systemic sclerosis (SSc) is a rheumatic disorder characterized by inflammation and fibrosis involving the skin as well as internal organs, including the lung. Objectives This study was conducted to characterize SSc patients with ILD and determine predictor features for the presence of ILD. Methods A retrospective evaluation of SSc patients from our Rheumatology department was undertaken. ILD was defined according to imaging findings in high-resolution CT (HRCT) combined with functional parameters. Demographic features, auto-antibodies, spirometry, diffusion capacity for carbon monoxide (DLCO) measurement, echocardiography and 6-minute walk test were compared between groups with and without ILD using parametric tests and non-parametric tests. Predictor factors were established by logistic regression analyses. Results One hundred and three SSc patients with current mean age of 60.2±14.1y and mean disease duration of 10.0±9.6y were evaluated. Thirty-four (35.8%) patients were diagnosed with ILD, of whom 13 had limited cutaneous SSc, 14 had diffuse cutaneous SSc, 2 sine sclerodema and 5 overlap syndroms. ANA was positive in 100% cases, anti-Scl70 was found in 55% and anti-centromere antibody positivity was found in 15% of patients. HRCT revealed diffuse parenchymal lung disease involvement >20% in 18 (53%) cases, with the majority showing a predominant honeycombing pattern. Spirometry showed a restrictive pattern in 8 patients and 1 had obstruction. The DLCOsb was abnormal in 7 patients. Three patients had pulmonary hypertension confirmed by right heart catheterization, 2 patients classified as group 1 and 3 and 1 patient of group 5. About 63% of ILD patients were ever treated with corticosteroids and 27% with cyclophosphamide, which were the most common drugs used. Two patients were also treated with rituximab. In this ILD-group, 5 deaths were recorded, 2 due to cancer, 1 abdominal sepsis, 1 pulmonary hypertension and 1 of unknown cause. Comparison of these ILD patients with non-ILD patients revealed some significantly differences (Table 1). Multivariate analysis showed that digital ulcers (OR=31.6, 95% CI 3.09 to 321.91), Anti-Scl70 antibody positivity (OR=10.1, 95% CI 1.19 to 85.74) and anti-centromere antibody negativity (OR=0.08, 95% CI 0.01 to 0.83) were independently associated with the presence of ILD. Conclusions This study is one of the first studies carried out in Portugal regarding lung involvement in SSc. About one third of the patients had ILD, whose main characteristics are in accordance with other European cohorts. We confirmed that anti-SCL70 positivity, presence of digital ulcers as well as the absence of anti-centromere antibody is independently associated with ILD Disclosure of Interest None declared

Background Nailfold capillaroscopy (NCP) is an easy, non-invasive and useful tool for the diagnosis and follow-up of Systemic Sclerosis (SSc) and other systemic rheumatic diseases. Objectives To present our single center experience with NCP, describing the main reasons for NCP request, and the major abnormalities detected in capillaroscopy. Methods Retrospective analysis of patients submitted to NCP assessment, from January 2013 to December 2015 in our center. We collected reasons for NCP request, demographic and clinical data, autoimmunity profile and NCP results. Results A total of 221 NPC, corresponding to 197 patients, 167 females (84.8%) and 30 males (15.2%) aged from 9 to 90 years were reviewed. One hundred and thirty eight (62.4%) patients had no definitive diagnosis, 53 patients (24%) had SSc, 7 (3.2%) had mixed connective tissue disease, 3 (1.4%) had dermatomyositis/polymyositis (DM/PM), and 3 (1.4%) antiphospholipid syndrome (APS). Raynaud9s phenomenon (RP) alone was the most frequent reason for requesting NCP (33% of the cases), and combined with ANA positivity accounted for another 30.8% of the requests. RP was present in 73.3% of the patients, acrocyanosis in 16.3%, livedo reticularis and puffy hands accounted for 8.6% each one. Anti-nuclear antibodies (ANA) were positive in 59.7%, anti-centromere antibodies were present in 21.3%, anti-topoisomerase I and SSA/SSB in 5.1% of the cases. One hundred and fifty nine (71.9%) NCP were considered abnormal. The most frequent specific disease pattern was the early one (Cuttolo) in 15%. The most frequent findings were: capillary tortuosity in 112 (71.8%) cases, capillary dilatations in 95 (60.9%), and hemorrhages in 85 (54.5%). NCP was abnormal in 79.4% of patients with RP and ANA, 41.2% of them displaying specific findings of rheumatic diseases (Table 1). In SSc patients the late and the early pattern (Cuttolo) were the most frequent, present in 15 and 13 NCP, respectively. Concerning specific NCP findings capillary dilatations (81%), hemorrhages (73.6%) and megacapillaries (71.7%) were the most frequent (Table 2). Of the 138 cases without definitive diagnosis, 61. 6% had abnormal NCP, although mostly with non-specific patterns (50%). In 10 (7.2%) patients NCP helped to establish the diagnosis: VEDOSS (Very Early Diagnosis of Systemic Sclerosis) in 6, antiphospholipid syndrome in 3 and DM in one case. Conclusions In our experience, NCP was helpful for the diagnosis of rheumatic systemic disease. Specific NCP findings were more frequent in patients with RP + ANA positivity, suggesting that this combination is associated with more disease incidence. Patients with isolated RF had less pathologic NCP findings than those with isolated. ANA positivity. The prospective follow up of those patients with abnormal NCP and no definitive diagnosis will help to establish the predictive value of observed alterations. References Cutolo M, Pizzorni C, Sulli A. Capillaroscopy. Best Pract Res Clin Rheumatol. 2005 Jun;19(3):437–52 Disclosure of Interest None declared

Background Systemic sclerosis (SSc) has a wide spectrum of cardiovascular manifestations, being pulmonary hypertension (PH) one of the most lethal complications. Echocardiography is a pivotal screening test for patients at risk for PH that allows prompt identification of those with high estimated pulmonary artery systolic pressure (PASP). Objectives We conducted a retrospective analysis of patients with SSc followed in our Rheumatology department aiming to characterize those with estimated PASP≥35 mmHg. Methods Clinical and laboratory features, including dyspnea according to New York Heart Association (NYHA) classes, N-terminal pro-Brain Natriuretic Peptide (NT-proBNP) serum levels, uricemia, anti-nuclear antibody (ANA) specificities, 6-minute walk test (6MWT), and right heart catheterization (RHC), if required, were assessed. Results In total, 87 out of 103 SSc patients had available echocardiography results (females 93.1%; mean age 57.8 years; mean disease duration 10.3 years). Eight patients were classified as having NYHA class≥3. The median value of NTproBNP was 104 pg/mL (19 to 15902). Twenty one (24%) had estimated PASP≥35 mmHg (in 16 patients PASP could not be estimated), of whom16 performed RHC. PH (mPAP≥25 mmHg) was confirmed in 7 (44%) cases; 3 were classified as group 1, 1 as group 2, 2 as group 3 and 1 as group 5, according to the ERS/ECS 2013 classification. The group with elevated PASP included 11 patients with limited SSc, 7 with diffuse SSc, 1 sine scleroderma and 2 overlap syndromes. Comparison of patients with PASP≥35 mmHg with those with PASP Conclusions PASP is elevated in one quarter of SSc patients. This subgroup present more frequently higher NYHA classes, elevated NTproBNP levels and Scl70 positivity. About 44% of them had restrictive pulmonary disease. It is essential to closely monitor cardiorespiratory function in order to rule out cardiac involvement as early as possible. Our results suggest that there is still need to increase physicians9 awareness of systematic cardiovascular screening, since fewer patients than are nowadays recommended had a complete evaluation. Acknowledgement Cardiology department Hospital Garcia de Orta Disclosure of Interest None declared

BACKGROUND Successful gametogenesis requires the establishment of an appropriate epigenetic state in developing germ cells. Nevertheless, an association between abnormal spermatogenesis and epigenetic disturbances in germline-specific genes remains to be demonstrated. METHODS In this study, the DNA methylation pattern of the promoter CpG island (CGI) of two germline regulator genes—DAZL and DAZ, was characterized by bisulphite genomic sequencing in quality-fractioned ejaculated sperm populations from normozoospermic (NZ) and oligoasthenoteratozoospermic (OAT) men. RESULTS OAT patients display increased methylation defects in the DAZL promoter CGI when compared with NZ controls. Such differences are recorded when analyzing sperm fractions enriched either in normal or defective germ cells (P< 0.001 in both cases). Significant differences in DNA methylation profiles are also observable when comparing the qualitatively distinct germ cell fractions inside the NZ and OAT groups (P= 0.003 and P= 0.007, respectively). Contrastingly, the unmethylation pattern of the DAZ promoter CGI remains correctly established in all experimental groups. CONCLUSIONS An association between disrupted DNA methylation of a key spermatogenesis gene and abnormal human sperm is described here for the first time. These results suggest that incorrect epigenetic marks in germline genes may be correlated with male gametogenic defects.

Introduccion. La neurofibromatosis tipo 1 y la esclerosis tuberosa son dos sindromes neurocutaneos distintos, resultado de la mutacion de genes supresores tumorales, que aumentan la propension a la genesis tumoral. Ambas tienen una herencia autosomica dominante y la mitad de los casos corresponden a nuevas mutaciones. Estas enfermedades raramente se presentan asociadas. Caso clinico. Nino sin antecedentes familiares de enfermedades neurocutaneas, que presenta caracteristicas de neurofibromatosis y de esclerosis tuberosa, principalmente manchas ?cafe con leche? (seis de ellas con un diametro superior a 0,5 cm), macrocefalia, glioma del nervio optico y alteraciones focales de vacuolizacion de la mielina en la sustancia blanca de los hemisferios cerebelosos, tronco cerebral y ganglios de la base, caracteristicas de la neurofibromatosis tipo 1. Por otro lado, presenta manchas hipopigmentadas, espasmos infantiles y evaluacion imaginologica de las areas de alteracion de la mielinizacion de la corteza para la sustancia blanca, calcificaciones en el surco talamocaudado a la izquierda, tuberosidades corticales, displasia cortical focal de Taylor y multiples nodulos subependimarios, caracteristicas que son compatibles con la esclerosis tuberosa. El nino tambien presenta retraso en el desarrollo psicomotor. Conclusion. El diagnostico de ambas enfermedades se confirmo gracias al estudio genetico. La evaluacion de los progenitores fue negativa, por lo que se puede confirmar la presencia de dos neomutaciones concomitantes, un hecho que es excepcionalmente raro.

Background Systemic Sclerosis (SSc) patients were recently described to have a higher risk of pulmonary embolism (PE) than healthy individuals 1 . Portuguese expert consensus 2 recommends screening for PE when respiratory distress cannot be explained by the presence of cardiovascular or pulmonary interstitial involvement (ILD). Objectives We present our 5-year experience with PE in SSc patients. Methods We included all adult SSc patients submitted to lung ventilation/perfusion scintigraphy (V/Q scan) or CT pulmonary angiography (AngioCT) due to worsening dyspnea/fatigue or isolated reduction of the carbon monoxide diffusing capacity (DLCO), from January 2010 to December 2014. We collected demographic data, functional class according to the World Health Organization (WHO-FC) classification, comorbidities, risk factors for PE and results from AngioCT and V/Q scans. A descriptive statistical analysis was performed. Results Eighteen patients were included: 15 females, with a mean age of 55±14 years and median disease duration 2 (IQR 2.5) years. Nine patients were diagnosed with PE, 8 of which by V/Q scan and 1 using AngioCT. Eight patients had bilateral peripheral multisegmental PE and 1 unisegmental PE. Five PE patients had a WHO-FC of 1-2. Three of the remaining 4 patients with WHO-FC >2 had concomitant extensive ILD, and one patient had pulmonary hypertension. No patient had thrombophilia, previous surgery or cancer. The frequency of hypertension, diabetes, smoking, obesity and dyslipidemia was similar to patients without PE. Anti-topoisomerase positive SSc patients (Anti-topo+) were slightly overrepresented in the PE group (5 vs 2 Anti-topo+ patients without PE). Other disease imunophenotypes were equally distributed between subgroups. Conclusions Oligosymptomatic PE is common in SSc patients. Traditional procoagulant risk factors do not account for this increased risk. Disease-specific risk factors, such as vascular endothelial dysfunction, may be involved. The impact of PE in disease prognosis is yet unknown. References Chung WS, Lin CL, Sung FC, Hsu WH, Yang WT, Lu CC, Kao CH. Systemic sclerosis increases the risks of deep vein thrombosis and pulmonary thromboembolism: a nationwide cohort study. Rheumatology (Oxford). 2014 Sep;53(9):1639-45. doi: 10.1093/rheumatology/keu133. Epub 2014 Apr 8. Grupo de Estudos de Doencas Reumaticas Sistemicas (GEDRESIS). Manual Pratico de Esclerose Sistemica. Sociedade Portuguesa de Reumatologia; 2014. Disclosure of Interest None declared

Background Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are chronic systemic illnesses that demand lifelong treatment. Adhesion to therapy is fundamental to achieve adequate disease control. Objectives We aimed to assess adherence to chronic therapy in RA and PsA patients and to identify reasons of non-adherence. Methods An anonymous written self-reported questionnaire was applied to consecutive RA and PsA patients followed-up in our Day Care Rheumatology Unit. Demographic and clinical characteristics were evaluated as well as chronic medication prescribed. Medication adherence was assessed using a qualitative 4-point scale. Patients were deemed adherent when stated that drug was always taken as prescribed. Reasons for non-adherence were collected. Presence and intensity of side effects was also investigated. Patients were asked to indicate one drug that they would like to stop and to specify the reasons for their choice. Variables independently associated with non-adherence where assessed by logistic regression analyses. Results One hundred and five participants were included: 83 females, 85 RA patients, with a mean age of 55±13 years and mean disease duration of 13±8 years. Drugs with lowest self-reported adherence were calcium supplements (58.3%, n=60) followed by hydroxychloroquine (62.5%, n=16) and the drugs with highest level of adherence were subcutaneous biologics (90.9% of patients, n=44) and leflunomide (85.7%, n=7). Forgetfulness was most often the perceived reason for non-adherence (67.8% of patients, n=59), followed by fear/presence of side effects (11.9% each). The drugs most frequently appointed for discontinuation were methotrexate (50% of patients, n=64) and glucocorticoids (23.4%), mainly due to fear of (69.4%, n=62) or presence of adverse events (27.4%). Methotrexate side effects most often indicated were nausea (25.3% of patients, n=87) and hair loss (18.4%). Younger age was associated with non-adherence to methotrexate and calcium supplement use (table 1). Conclusions We identified forgetfulness and fear/presence of side effects as the main barriers to adherence. Consequently, we are committed to improve doctor-nurse/patient communication, assuring a clear and individual explanation of the importance of maintaining adherence and possible side effects of each therapy at the beginning of treatment and at each consultation. Proactive management of side effects, even if mild, is encouraged. Additionally, health care professionals should encourage and implement group education sessions where rheumatic diseases and treatments are discussed with patients and where there will be the opportunity to clarify doubts and improve coping strategies. Disclosure of Interest None declared

Background The use of biological DMARDs to treat RA patients has increased over the past 15 years probably due to their efficacy and tolerability profile. Objectives Describe persistence (time between biological agent initiation and its discontinuation), the impact of biological therapy (BT) in clinical outcomes (DAS28) and the reasons for its discontinuation. Methods A retrospective study of RA patients (pts) followed at Hospital Garcia de Orta with 1st BT [abatacept (ABT), adalimumab (ADA), anakinra (ANA), etanercept (ETN), golimumab (GLM), infliximab (IFX), rituximab (RTX), and tocilizumab (TCZ)] starting between 1/1/2001 and 31/7/2014. Electronic clinical records (Reuma.pt database) were reviewed for all pts that have been treated at least 12 months previously to their recruitment. Available demographic, clinical and therapeutic data were collected. Survival methods were used to analyze time to an event. Results 97 RA pts with mean age at RA diagnosis of 45.4±13.4 years were included. 86% were women, 53% with erosive disease, 66% with positivity for rheumatoid factor and 70% with positivity for anti-CCP antibodies. The mean age at the beginning of BT was 53.0±12.7y. Concerning 1st BT, ETN was the most frequent one (36%), followed by IFX (30%), and ADA (27%). 61 pts discontinued their 1st BT, mainly due to secondary ineffectiveness (15 IFX, 10 ETN, 9 ADA, 2 ANA and 1 TCZ). The median time on 1st line was 59.6 months (plot 1). The treatment persistence was not significantly different between BT (p=0.6). Notwithstanding, ETN showed a higher median persistence (96.1 months) than the others (plot 2). Comparing with IFX, the adjusted risk of discontinuation was 42% and 33% inferior with ETN and ADA respectively, though statistical significance was not reached. More than 50% of pts discontinued 1st BT within first 5 years. 46 pts started a 2nd BT (19 ETN, 13 ADA, 5 IFX, 5 RTX and 4 others). Of these, 21 discontinued most due to secondary ineffectiveness (7 ADA, 3 IFX and 3 ETN). The median time on 2nd line was 43.2 months (plot 3). The differences between BT in persistence are fairly statistically significant (p=0.06). Again, ETN showed a higher median persistence (43.5 months) followed by ADA (11.5 months) (plot 4). ADA as 2nd BT presented an adjusted risk to discontinue almost 4 times higher than ETN (HR=3.98, p=0.02). 15 pts switched their 2nd BT (5 TCZ, 4 ABT, 4 RTX e 2 ETN). More than 50% of the pts discontinued their 2nd BT within 4 years after starting it. The adjusted risk for switching with ADA was 9 times higher than the risk for switching ETN (HR=9.06, p=0.004). Regarding evolution of DAS28 during 1st line, ETN presented the highest variation from the baseline at 3, 6, 12, 18 and 30 months compared with all other agents. Regarding 2nd BT, the longitudinal analysis revealed that all agents achieved response between 6 and 18 months after treatment initiation. Conclusions The analysis per BT suggests that ETN was the TNF antagonist with the highest persistence on treatment and efficacy profile. Comparing 1st and 2nd lines of biological therapy, there is a decrease of 16.4 months on persistence. Additionally, the probability of switch increases and the probability of end of treatment decreases from 1st to 2nd line. Disclosure of Interest None declared

Background The diagnostic1 and prognostic2 value of nailfold capillaroscopy (NCP) in patients with Raynaud9s phenomenon (RP) is well-established. However, its role in the assessment of patients without RP is still unclear. Objectives We aimed to assess the diagnostic role of NCP in suspected connective tissue disease (sCTD) without RP. Methods We included all patients with CTD or sCTD submitted to NCP assessment from January 2013 to December 2014. Clinical features were recorded, as well as the presence of antinuclear antibodies (ANA) and extractable nuclear antigens (ENA). NCP results were appraised according to capillary density, presence of dilatations, megacapillaries, hemorrhages, tortuosity, neovascularization and avascular areas. We classified NCP results as normal, nonspecific findings (NSF) and scleroderma pattern (SSP)3. Patients with sCTD were compared according to the presence/absence of RP, ANA/ENA and NCP findings. Results We included 112 patients: 95 (84.8%) female, with a mean age of 48±18 years. The most frequent CTDs were systemic sclerosis (SSc, n=33, 29.5%) and mixed CTD (n=6, 5.4%). Fifty-eight (51.8%) patients had sCTD – 37 (62.5%) had RP, 26 (55.3%) were ANA positive and 46 (86.8%) were ENA negative. Thirty-three (56.9%) had NSF; one sCTD patient exhibited SSP. Dilatations were present in 27 (51.9%), tortuosity in 40 (76.9%), hemorrhages in 22 (43.2%) and neovascularization in 8 (15.4%) individuals. Patients with and without RP were not different considering clinical features, ANA/ENA positivity and NCP findings (Table 1). The presence/absence of ANA and NCP findings were also not associated with distinct clinical features. Conclusions RP, ANA positivity and the presence of nonspecific findings in NCP were not discriminant in the short-term assessment of this patient group. Long term follow-up is needed in order to better understand the diagnostic and prognostic role of these NCP findings in both patients with and without RP. References Mannarino E, et al. Nailfold capillaroscopy in the screening and diagnosis of Raynaud9s phenomenon. Angiology 1994; 45: 37–42. Blockmans D, et al. Predictive value of nailfold capillaroscopy in the diagnosis of connective tissue diseases. Clin Rheumatol 1996; 15: 148–53. Cutolo M, et al. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol 2000; 27: 155–60. Disclosure of Interest None declared

Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive disorder characterised by craniofacial dysmorphism, mental retardation, multiple congenital anomalies, and increased levels of 7-dehydrocholesterol (7-DHC) in body tissues and fluids. SLO is caused by mutations in the DHCR7 gene which encodes 7-dehydrocholesterol reductase, the last enzyme of cholesterol biosynthesis pathway. In our investigation, we screened 682 dysmorphic/mentally retarded Portuguese patients for abnormal levels of 7-DHC in blood by UV spectrometry. We identified six unrelated patients with SLO (0.87% of total). Mutational analysis of the DHCR7 gene led to the identification of seven distinct mutations, three of which are new (F174S, H301R, and Q98X). The common IVS8-1G > C and T93M variants together with the H301R accounted for 70% of the all SLO alleles in our population. Our findings contribute to the variegate array of pathological changes in the DHCR7 gene among different European populations.

Robinow syndrome was found in two monozygotic twins. We describe the clinical and radiographic manifestations in these patients, both with normal stature and one with omphalocele, with a follow-up of 13 years. Families with Robinow syndrome of both autosomal dominant and recessive inheritance have been reported. We apply the criteria suggested to assign isolated cases to one of the two forms and conclude that autosomal dominant inheritance is more likely.