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To analyse ultrasound (US) differences between rheumatoid arthritis (RA) patients according to autoantibody status and characterise the clinical and radiological features associated with the US pattern of seropositive patients.We collected demographic and clinical data and bilateral hand US images of RA patients. We defined an extreme proliferative US pattern, encompassing synovial hypertrophy grade II-III with Power Doppler signal, which we called US proliferative synovitis (US PS). To better characterise US PS, MRI of the dominant hand and immunostaining of synovial biopsies were made in subgroups of 42 and 23 patients, respectively.We included 205 RA patients (84.8% seropositive). No significant differences in disease activity were found according to autoantibody status. US PS was found in 55.5% of seropositive and 16.1% of seronegative patients (p=0.0001). In the multivariate analysis, erosions [OR 4.90 95% CI (2.17-11.07), p=0.0001] and ACPA [OR 3.5 95% CI (1.39-10.7), p=0.009] but not RF status [OR 0.74 95% CI (0.31-1.71), p=0.483] were independently associated with US PS. After a mean follow-up of 46 months, US PS was independently associated with changes in therapy (OR 2.63, 95% CI 1.20-5.77, p=0.016). Ninety-four per cent of joints with US PS had RAMRIS synovitis sub-index grade 2-3. US PS was significantly associated with higher synovial vessel density (p=0.042).In RA patients, US PS was associated with ACPA status, erosive disease and an enhanced need to change disease-modifying anti-rheumatic drug therapy in the long-term. At synovial level, this US pattern was characterised by higher vessel density. more...

Objectives: To analyze ultrasound (US) differences between rheumatoid arthritis (RA) patients according to their autoantibody status and characterize the clinical, immunological and radiological features associated with the US pattern of seropositive patients.Methods: We collected clinical and immunological data along with bilateral hand US images of RA patients. Serum biomarkers, MRI of dominant hand and immunostaining of synovial biopsies were performed.Results: Two hundred and five RA patients were collected (84.8% seropositive). No significant differences in disease activity/therapy were found according to autoantibodies status. An extreme proliferative US pattern, encompassing synovial hypertrophy grade II-III with Power Doppler signal that we called US Proliferative Synovitis (US PS) was present in 55.5% of seropositive and 16.1% of seronegative patients, (p=0.0001). In the multivariate analysis, erosions [OR 4.90 CI 95% (2.17-11.07). p=0.0001] and ACPA [OR 3.5 CI 95% (1.39-10.7), p=0.09] but not RF status [OR 0.74 CI 95% (0.31-1.71), p=0.483] were independently associated with the presence of US PS. Ninety-four per cent of joints with US PS scored 2-3 in RAMRIS synovitis sub-index. At synovial level, US PS was significantly associated with higher density of vessels (p=0.042). Moreover, significantly higher serum levels of angiogenic and inflammatory cytokines were found in patients with US PS. After a mean of 46 months of follow-up, US PS was independently associated with change of therapy (OR 2.63, 95% CI 1.20-5.77, p=0.016).Conclusions: ACPA+ RA was associated with US PS. This US pattern significantly detected erosive disease and an enhanced need to change therapy in the long-term. more...

Background In the context of the COVID-19 pandemic the risk of misdiagnosis of other causes of respiratory infection is likely. In this work we aim to describe the clinical characteristics, treatment and outcome of pneumococcal infection in COVID-19 patients. Patients and methods Every COVID-19 patient presenting with concomitant pneumococcal pneumonia during March 2020 in a tertiary teaching Hospital In Barcelona, Spain. Results Five patients with PCR confirmed COVID19 or clinical and radiological suspicion were diagnosed of pneumococcal infection. In all cases chest X-ray were abnormal, with unilateral or bilateral infiltrates. Procalcitonin showed to be not sensitive enough to detect pneumococcal infection. Antibiotherapy was promptly started in all five cases with subsequent satisfactory evolution. Conclusion International guidelines do not include the universal screening for bacterial co-infection. Radiological pattern of COVID-19 can be indistinguishable from that of pneumococcus pneumonia and frequency of co-infection is not well stablished, therefore clinicians should be aware of the possible SARS-CoV-2-pneumococcus association to avoid misdiagnosis and delay antibiotic therapy. more...

Background:Seronegative (sero-) and seropositive (sero+) Rheumatoid Arthritis (RA) have different genetic, immunopathological and vascular morphology features, but no previous studies have analyzed if US characteristics differ between sero+ or sero- RA. Our preliminary studies suggest that sero+ RA is associated with an expansive synovitis pattern that we have called “proliferative synovitis” (PS)Objectives:To analyze potential differences between patients with RA according to their autoantibody status by using ultrasonography (US). We aimed to assess whether PS is associated with ACPA+ ptsMethods:We collected clinical, epidemiological data and bilateral carpal and hand US images of pts with RA. Synovial hypertrophy (SH), Power Doppler signal (PD) and total score (sum of scores of SH and PD) in wrist and hand (1-5 metacarpophalangeal) were assessed. We evaluated the presence of PS, defined as expansive synovial growth encompassing the concepts of synovial SH grade II and III. We performed synovial biopsies of a subgroup of pts using arthroscopy or US guided in order to see immunohistochemistry differences between “proliferative” and “flat” (non-proliferative) synovitis. Serum levels of angiogenic and inflammatory biomarkers were performedResults:Two hundred and five RA patients were collected. Overall, 173 (84.8%) pts were sero+ for RF (68.7%) or ACPA (74.6%), general characteristics are summarized in Table. No significant differences between sero+ and sero- pts in terms of disease activity or therapy were found. PS was present in 55.5% of sero+ pts (55.3% in RF+ and 58.2% in ACPA+ pts) and 16.1% of sero- pts (p=0.0001). Globally, 101 pts (49.2%) had PS. Ninety-six (95.0%) were RF or ACPA positive. Only 5 pts with sero- RA had PS (p=0.001). In the univariate analysis, significantly more pts with PS had erosive disease (72.3% vs 35.0% p=0.0001), higher US scores (p=0.0001) and more of them were taking conventional synthetic Disease-modifying anti-rheumatic drugs (csDMARD) (81.8% vs 69.6% p=0.05). No differences regarding disease activity were found.In the multivariate analysis erosions [OR 4.90 CI 95% (2.17-11.07) p=0.0001] and ACPA [OR 3.5 CI 95% (1.39-10.7) p=0.09] but not RF status [OR 0.74 CI 95% (0.31-1.71) p=0.483] were independently associated with the presence of PS.We immunostained synovial biopsies from 23 pts with PS (13 pts) or non-PS (10 pts). PS was significantly associated with higher density of vessels (p=0.042) and a strong trend to a higher density of B, T, Mast cells and macrophages (figure 1). Significantly higher serum levels of angiogenic (Activin A, bFGF, IL18, IL20, PIGF, SDF-1 and VEGF-D) and pro-inflammatory (IL23) cytokines were found in patients with PS (figure 2).Conclusion:The presence of “proliferative Synovitis” was significantly associated with ACPA and erosive disease in patients with RA. PS pattern also was associated with higher density of synovial vessels and higher serum levels of angiogenic and inflammatory mediatorsTable .Total US pattern p valueN=205Proliferative (N=101)Non proliferative (N=104)Female, n (%)162 (79.4)79 (78.2)83 (80.6)0.57Age, mean (SD) years57.1 (± 14,1)56.3 (± 12.0)58.0 (± 15.9)0.40Current Smoker, n (%)47 (26.9)22 (25.6)25 (28.1)0.73Disease duration, mean (SD) months113.3 (± 105.7)127.7 (± 111.1)99.3 (± 99.3)0.05Erosion, n (%)108 (53.7)73 (72.3)35 (35.0)0.00ACPA, n (%)153 (75.4)89 (89)64 (62.1)0.00RF, n (%)99 (68.3)78 (78)63 (61.2)0.01DAS 28–CRP, mean (SD)2.55 (±1.03)2.66 (±1.04)2.44 (±1.02)0.17GC, n (%)99 (49.3)45 (45.5)54 (52.9)0.32cDMARDs, n (%)152 (75.6)81 (81.8)71 (69.6)0.05bDMARD, n (%)69 (34.3)35 (35.4)34 (33.3)0.76Total US score14.9 (± 11.5)18.8 (± 11.8)11.1 (± 9.9)0.00*ACPA anti-citrullinated protein antibodies, RF rheumatoid factor, DAS28-CRP Disease Activity Score 28-joint count, CRP C-reactive protein, GC glucocorticoids, bDMARD biological disease-modifying antirheumatic drugsDisclosure of Interests:Ana Belén Azuaga-Piñango: None declared, Beatriz Frade-Sosa: None declared, Roberto Gumucio: None declared, Katherine Cajiao: None declared, Andrea Cuervo: None declared, Raquel Celis: None declared, Jose A. Gómez-Puerta Speakers bureau: Abbvie, BMS, GSK, Lilly, Pfizer, Roche, Raimón Sanmartí Speakers bureau: Abbvie, Eli Lilly, BMS, Roche and Pfizer, Juan de Dios Cañete: None declared, Julio Ramirez: None declared more...

Background Immune checkpoint inhibitors (ICI) against CTLA-4 or PD-1/PD-L1 improve the survival of patients with advanced malignancies including melanoma, lung cancer among other tumours. Because of its mechanism of action, ICI are prone to produce different immune-related adverse events (irAEs), including musculo-skeletal manifestations. Objectives Our aim was to describe the experience with rheumatic irAEs in two tertiary centres. Methods All adult patients referred to the Rheumatology department from 2015 to 2018 because of the onset of musculo-skeletal symptoms following treatment with an ICI were included. Data collected comprised demographic features as well as ICI indication and type, history of rheumatic disease, disease manifestations at irAE onset, laboratory tests, ultrasound findings and treatment. Diagnostic and treatment approach was done according clinical judgment and in a daily clinical practice setting. Results 20 patients were included, 50% female, with a mean age of 61,5 years (range 32-83). The indication for ICI was melanoma in 10 cases, lung cancer in 5, urothelial neoplasia in 2 and squamous skin, breast and head and neck cancer in 1 case each. Pembrolizumab was the most used ICI accounting for 9 cases (1 combined with epacadostat), 8 patients were treated with Nivolumab (4 combined with Ipilimumab), 2 wit Atezolizumab (1 combined with Ibatasertib) and 1 Ipilimumab in monotherapy. A history of previous rheumatic disease was reported in 8 patients (1 seropositive RA, 1 Spondyloarthritis, 1 SLE, 1 gout, 1 chondrocalcinosis, 1 fibromyalgia, 1 De Quervain tendinitis, 1 hand osteoarthritis) and 1 had psoriasis. The most frequent irAE presentation was arthritis with 8 cases (40%), arthralgia in 4 cases (20%), 1 case of myalgia, 2 presented PMR-like symptoms, 1 tenosynovitis and 2 paraesthesia (1 with associated dysesthesia). After assessment, 7 patients were diagnosed as undifferentiated arthritis, 1 leukocytoclastic vasculitis, 1 small-vessel vasculitis, 2 psoriatic-like arthritis, 1 tenosynovitis, 2 PMR and 6 were classified as having non-inflammatory symptoms. Antibody status was analyzed in 16 patients. Anticitrullinated-peptide antibodies, rheumatoid factor and HLA B27 were negative in all cases (except for 1 patient with seropositive RA), ANAs were positive in 4 (including 1 patient with previous SLE) but without any specificities (i.e. ENAs) and ANCA were negative in one case with small-vessel vasculitis. Ultrasound assessment was performed in 6 patients, 3 presented synovial hypertrophy with positive power Doppler (1 with tenosynovitis associated), 1 peritendinous fluid collection, 1 elbow joint effusion and 1 bilateral supraspinatus calcified tendinopathy. Most patients were treated with glucocorticoids 12 (60%) and NSAID 6 (30%) and only 3 patients had to discontinue ICI treatment due to irAEs. Conclusion Our results were in line with previous studies showing that musculo-skeletal irAEs associated to ICI may present as a flare of a previous known rheumatic disease or as a de novo symptom. Most patients presented with asymmetric mono or oligoarthritis having a good response to GC and NSAID without the need of adding DMARD or withdraw of ICI therapy.. Disclosure of Interests Sebastian C Rodriguez-Garcia: None declared, DAVID LOBO: None declared, Raul Castellanos-Moreira Speakers bureau: MSD, Lilly, Ana Milena Millan Arciniegas: None declared, Roberto Gumucio: None declared, Ana Laiz Consultant for: Lilly, Novartis, AbbVvie, MSD, UCB and Janssen, Speakers bureau: Lilly, Novartis, Abvvie, MSD, UCB and Janssen, Virginia Ruiz-Esquide Speakers bureau: Sanofi, Lilly, MSD, Berta Magallares: None declared, Cesar Diaz-Torne: None declared, Patricia Moya: None declared, Ivan Castellvi Consultant for: I received fees less than 5000USD as a consultant for Kern and Actelion, Paid instructor for: I received fees less than 2000USD as a instructor for Boehringer -Ingelheim, Novartis and Gebro, Speakers bureau: ND, Hector Corominas: None declared, Jose A. Gomez-Puerta Consultant for: Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen, MSD, Pfizer, Roche more...

Background Community-acquired pneumonia (CAP), the most common pneumococcal infection, is a leading cause of morbidity and mortality among immunocompromised hosts. Although vaccination against Streptococcus Pneumoniae is recommended by international guidelines, most studies report a sub-optimal coverage. Objectives To describe the pneumococcal vaccination coverage, predictors for vaccination uptake and frequency of severe CAP and invasive pneumococcal disease during the study period. Methods We performed a cross-sectional study using electronic medical record data from October 2000 to October 2018, including patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and Ankylosing Spondylitis (AS), treated with biologic (bDMARD) and conventional synthetic DMARD (csDMARD) with or without glucocorticoids (GC), followed-up at a referral centre. Since pneumococcal vaccination guidelines have changed during the study period, patients who received at least one dose of any of the available vaccines were defined as being “ever-vaccinated” whereas those who received a complete scheme defined as one dose of conjugated vaccine and one of polysaccharide vaccine 8 weeks apart were defined as having “optimal vaccination”. Predictors of vaccination were analyzed using logistic regression modelling using a set of covariates selected according to the literature. Model assessment was done using Akaike information criterion. To analyze the frequency of severe infections we defined two outcomes: Severe CAP: An episode requiring hospitalization or intravenous antibiotic treatment Invasive pneumococcal disease (IPD): an infection confirmed by the isolation of the micro–organism from a normally sterile site (i.e. blood). Results A total of 279 patients were included, their main clinical features are shown in Table 1. The vaccination coverage was 38.7% and 13.3% overall when analyzing as “ever-vaccinated” and having “optimal vaccination” respectively. A 66% of patients were vaccinated in primary care with a 7% of optimal vaccination whereas the remaining ones received vaccination in referral centres with an 85.3% of optimal vaccination. After adjustment in a multivariate model, age, presence of bronchiectasis, history of severe CAP, current use of csDMARD or GC were predictors of being ever-vaccinated against Streptococcus Pneumoniae. (Table 2) During the study period, 27 (10%) episodes of severe CAP and 4 of IPD were identified, 8 of the former with evidence of pneumococcal infection (either positive urine antigens or isolation in sputum). Conclusion Pneumococcal vaccination coverage remains lower than expected with most patients vaccinated in primary care and not receiving the current recommended scheme. Age, bronchiectasis, history of severe CAP and current use of csDMARD or GC were independent predictors of receiving vaccination. The frequency of severe CAP and IPD was 10% and 1,43% within this cohort. Disclosure of Interests Sebastian C Rodriguez-Garcia: None declared, Raul Castellanos-Moreira Speakers bureau: MSD, Lilly, Victoria Hernandez: None declared, Roberto Gumucio: None declared, Anna Vilella: None declared, Carolina Garcia-Vidal Speakers bureau: Lilly, Pfizer, Juan D. Canete: None declared, Julio Ramirez: None declared, Raimon Sanmarti Speakers bureau: PFIZER, SANOFI, LILLY, MSD, UCB, NOVARTIS, JANSSEN, Jose A. Gomez-Puerta Consultant for: Pfizer, Roche, Speakers bureau: Abbvie, BMS, Janssen, MSD, Pfizer, Roche more...

Background:Immune checkpoint inhibitors (ICI), such as anti-CTLA-4and anti-PD1/PD-L1 monoclonal antibodies, have produced impressive clinical results in different types of cancer. However, immune-related adverse events (irAEs) may develop a wide spectrum of disabling syndromes. Knowledge of different rheumatic irAEs induced by ICI is increasing over the last years, however clinical patterns, time to onset of different irAEs according to treatment and follow-up are less well known.Objectives:To describe different clinical patterns of rheumatic irAEs induced by ICI and their rheumatic and oncologic outcomes.Methods:We included consecutive patients with rheumatic irAEs from 3 different referral centers in Barcelona with special emphasis in articular irAEs. Four main clinical syndromes were identified: inflammatory arthritis (IA), non-inflammatory arthralgias (NIA), psoriatic arthritis (PsA)-like and polymialgia (PMR)-like. We conducted a baseline visit and then follow-up in order to determine their clinical pattern, treatment response and outcome. Longitudinal visits were done from January 2017 to January 2020. Patients with other non–articular diagnosis were not included in the follow-up analysis.Results:We included 55 patients. A total of 34 patients were male (61.8%) with a mean age of 65.0 ± 11.4 years. Oncologic underlying diagnosis was lung carcinoma in 24 (43.6%) patients, followed by melanoma in 17 (29%), urothelial cancer in 4 (7.3%), breast in 2 (3.6%) and 2 (3.6%) acute myeloid leukemia among others. Seven (12.7%) patients received ICI as combined therapy. Different ICI were used including: Pembrolizumab in 21 (38.2%), Nivolumab 13 (23.6 %), Atezolizumab 6 (10.9%), Nivolumab + ipilimumab 5 (9.0%), Durvalumab 3 (5.5%), Pembrolizumab + epacadostat in 2 (3.6%), 2 anti TIM3, Atezolizumab+ Ibatasertib, Avelumab and Ipilimumab in one case each. 12 out of 55 patients had an underlying rheumatic disease before ICI treatment. Eleven patients developed other irAEs before or at the same time as rheumatic syndromes (mainly colitis and thyroiditis). Main rheumatic irAE included: IA in 23 (41.8%), NIA in 16 (29.1%), PsA-like in 6 (10.9%), PMR-like in 5 (9.1%) among others. Time from ICI to irAEs was 8.3 ± 8.4 months(mo). irAE presented earlier in patients with combined ICI therapy than in patients with monotherapy (6.5 ± 4.0 vs 8.6 ± 8.9 mo, p=NS, Figure 1A). Time (in mo) from ICI initiation to irAE onset was different according to treatments. For Nivolumab 10.0 ± 10.6, Anti TIM3 10.0 ± 1.4, Durvalumab 9.0 ± 2.0, Ipilimumab 7.98 ± 9.21, Pembrolizumab 7.28 ± 7.53, Avelumab 6.0 and Atezolizumab 4.4 ± 5.38 mo (Figure 1B). Time from ICI initiation and onset also differs among rheumatic irAEs (Figure 2). Mean time follow-up was 13.4 ± 10.9 mo. At the last visit, 45% were under GC, mean dose of 3.6 mg/d (range 0-40). DMARD were needed in 15% of patients (6 patients MTX, 1 with LEF and 1 SFZ). At the last visit, 11 (22.9%) patients remain with persistent arthritis, 25% intermittent flares and 52% had a self-limited pattern. Regarding oncologic outcome, 30.2% were on remission, 30.2% in partial response and 39.6% with tumor progression. Eleven (20%) of patients died.Conclusion:We described different clinical patterns according treatment and irAEs. Combined ICI therapy and patients treated with Atezolizumab had earlier onset of symptoms. Vasculitis and PMR-like syndromes appear in earlier phases. After a mean follow-up of around 1 year, one-quarter of the patients remain with persistent arthritis and 15% require DMARD therapy.Disclosure of Interests:Jose A. Gómez-Puerta Speakers bureau: Abbvie, BMS, GSK, Lilly, Pfizer, Roche, Carolina Perez-Garcia: None declared, David Lobo Prat: None declared, Roberto Gumucio: None declared, Fabiola Ojeda: None declared, Ana Milena Millán Arciniegas: None declared, Sebastian Rodriguez Garcia: None declared, Virginia Ruiz Speakers bureau: Lilly, Pfizer, Héctor Corominas Speakers bureau: Abbvie, Lilly, Pfizer, Roche more...