Background: Digital ulcers (DUs) are common in systemic sclerosis (SSc) patients and cause significant morbidity. They are often complicated by local infection which can lead to contiguous osteomyelitis (OM). The clinical and imaging diagnosis of OM is challenging. The interpretation of MRI images, the gold standard for OM diagnosis, is problematic due to digital flexion contractures and acro-osteolysis. In our center (tertiary referral center for SSc), we use 99m-Technetium-Tc-labeled white blood cells (WBC) scintigraphy, for diagnosing OM in complicated DU. Despite the high sensitivity and specificity, it may be inconclusive in certain cases and it is a costly modality.Musculoskeletal ultrasound (US) imaging was found to be an accurate tool for OM diagnosis. Objectives: We aimed to assess the accuracy of US imaging in diagnosing contiguous OM in SSc patients with DU, compared to WBC scintigraphy. Methods: SSc patients with complicated DU, clinically suspected for OM, who were referred to WBC scan, were concurrently referred to US of the suspected DU. The US was performed by a highly skilled musculoskeletal imaging specialist, blinded to WBC scan results. Examinations were performed using the GE ML6-15-D Matrix Linear Probe LOGIQE9:R4.3.0 Ultrasound Machine. The sonographic findings indicating OM were periosteal thickening, cortical erosions, increased flow within or around periosteum on power Doppler sonography and deep soft tissue swelling. All patients had baseline hands x-ray to rule out calcinosis or acro-osteolysis. Clinical reassessment of DU healing was performed within 1-3 months. Results: Seven patients (6 females, 8 US examinations) were included in the pilot study. The mean(SD) age was 64.6(12.8), disease duration 14.6(7.4) years, 5 patients had diffuse SSc. One patient had 2 US examinations for separate events of suspected OM, in different sites.The results of both imaging tests concurred ruling in 2 cases and ruling out OM in 3 others. In the remaining 3 cases, the WBC scan was inconclusive, but the US ruled out OM. Patients that tested negative for OM on WBC scans and/or US were treated accordingly, with significantly shorter courses of antibiotics. Healing of the complicated DUs was achieved in all of them. Conclusion: In our pilot study, US imaging was found to be reliable in confirming and ruling out OM in SSc patients with complicated infected DUs, even in patients with inconclusive WBC scans. Musculoskeletal US may serve as a feasible and less expensive imaging technique for diagnosing contiguous OM in SSc-related DUs. Larger studies are required to confirm these preliminary results. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: None declared.Figure 1

Background The 3rd booster of mRNA vaccines against SARS COV2 was highly efficient against delta variant but data regarding the efficacy of the 3rd and 4th boosters against the omicron variants, among AIRD pts are scarce. Objectives We aimed to assess the effect of the 3rd and 4th booster mRNA vaccines against SARS CoV2, in preventing severe COVID-19, in AIRD patients (pts) treated with immunomodulating drugs. Methods 212 pts (mean age(SD) 57(13), disease duration 11.2(7.4), who received the 3rd booster (Pfizer) were included in the study. We performed serology tests 24 weeks after the second dose of vaccine and 4-8 weeks after the 3rd booster. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay. The test was considered positive above 50 AU/ml. Data regarding COVID-19 infection during the 5th outbreak (omicron) were collected from the medical files. The length of observation period was defined as the time from the 3rd booster to the last hospital visit or COVID 19 diagnosis, whichever occurred first. Results The 3rd booster administration (Pfizer) significantly augmented the humoral response (from mean(SD) 1121(4723) AU/ml to 12153(13687)). 58 patients received the 4th booster and 18 the 5th booster. COVID-19 was diagnosed in 103 pts (49%) within mean(SD) 224.8(106.5) days after the 3rd booster vaccination. 109 pts remained free of disease during mean(SD) follow-up 230.6(133.9). Following the 4th booster, 26 (45%) out of 58pts contracted COVID-19 within mean(SD) 97.6(78.7) days after the vaccination. One 70 year old patient (vaccinated 3 times) died and 2 other pts (rituximab treated) had severe COVID-19. The IgG Ab titer after the 3rd booster was lower in pts who contracted COVID 19 compared to those uninfected (mean(SD), median 8777.9(11716.4),3475 AU/ml vs 15348.1(14649.1),10801, p=0.004). There were no statistically significant differences between the pts with COVID-19 and those without, regarding age, type of disease, treatment and humoral response 24 weeks after the 2nd vaccination. Conclusion Despite an enhanced humoral response obtained after the 3rd booster, 49% of AIRD pts vaccinated with 3 doses and 45% of pts vaccinated with 4 doses had COVID-19 during the omicron outbreaks. Higher humoral response to the 3rd booster was associated with a lower rate of COVID19. The booster vaccines conferred 99% protection against severe COVID-19. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

Background A growing body of evidence suggests that the gut microbiota plays a significant role in the development of autoimmune diseases. An altered microbiota composition has been associated with gastrointestinal and extraintestinal features in systemic sclerosis (SSc) patients. Objectives To characterize differences in the gut microbiota between SSc patients and rheumatoid arthritis (RA) patients and to look for associations between microbial profiles and SSc subtypes, disease manifestations and treatment. Methods SSc and RA patients seen at our center were recruited in a prospective study. The exclusion criteria included antibiotic or probiotic treatment during the month prior to recruitment, recent hospitalizations, BMI>30, diabetes mellitus or concomitant inflammatory bowel disease. Fecal samples were collected and processed and 16S rRNA gene sequences were analyzed using the QIIME2 package. Microbiome composition was determined, beta diversity and alpha diversity were calculated and ANCOM analyses was performed. Results During 7/2018-4/2022, 49 SSc patients (mean age [SD] 53.5[13.8] and disease duration 9.4 [8.0] years) and 21 RA patients (mean age [SD] 57.1[10.4] and disease duration 15.1[10.0] years) fulfilled the criteria and were willing to participate in the study. Significant differences in beta diversity (Unweighted q=0.019, and Weighted UniFrac q=0.005) were found between RA and SSc patients’ stool microbiota, but not in alpha diversity. Composition analysis revealed higher abundance of Actinomyces and relative paucity of Coprococcus Eutactus among SSc patients compared to RA. Significant variations in beta diversity (unweighted and weighted) were associated with the subtype of SSc (diffuse - 27 vs limited - 22 patients, p [weighted] = 0.01), occurrence of interstitial lung disease (22 patients, p=0.011), renal crisis (3 patients, p=0.016), immunomodulatory treatment (33 patients, p=0.018) and biological treatment (11 patients, p=0.017). Composition analysis revealed higher relative abundance of Firmicutes in patients with GAVE [12]. Patients on biologicals (11) had higher abundance of Synergistaceae and lower of Firmicutes. The changes were consistent in recurrent fecal samples. Conclusion Significant differences on beta diversity were found between RA and SSc patients’ gut microbiota, but not on alpha diversity. Diffuse SSc, interstitial lung disease, renal crisis and immunomodulatory treatment were associated with shifts in the microbiome of SSc patients. The impact of these changes on SSc disease progression needs further elucidation. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests None Declared.

Background AIRD patients (pts) may be more susceptible to severe COVID19. Objectives To determine the risk factors for severe COVID19 and the effect of vaccinations among AIRD pts followed at dedicated rheumatology clinics. Methods At the onset of the pandemic, we established a national registry of AIRD pts, diagnosed with COVID19, based on voluntary reporting by the treating rheumatologist. 12 centers from Israel participated in the study. COVID19 was confirmed by a positive SARS CoV2 PCR. The indications for PCR testing were clinical symptoms or close contact with an infected person. Severe illness was defined by SpO 2 <94% in room air, respiratory rate of >30 breaths/min, PaO 2 /FiO 2 <300 mm Hg, or lung infiltrates >50% on imaging. The registry included demographic data, AIRD diagnosis and duration, visceral involvement, co-morbidities, immunomodulatory treatment, date of diagnosis and severity of COVID19 disease, management, complications, duration of hospitalization, the dates of the mRNA vaccinations, lab results and outcome. We analyzed data from 1.3.2020 to 30.11.2021 Results During the study period we experienced 4 outbreaks of COVID19 infection. Initially social distancing, followed by a lockdown were imposed. The low number of cases led to relaxation of the measures. Two more severe outbreaks followed, which triggered 2 new lockdowns. The 3rd outbreak ended almost 2 months after vaccination started (BNT162b2 mRNA COVID19 vaccine). From March 1st 2020 to April 30, 2021, 298 AIRD pts (70.8% females, mean (SD) age 53.3(15.3)) with confirmed COVID19 infection were included. 43.3%(129) had visceral involvement due to the AIRD. 58.7%(175 pts) were on conventional synthetic disease modifying drugs (csDMARDs), 44.6% (133) on biologic/targeted DMARDs and 40% (120) on prednisone. Almost 2/3 of pts had at least one comorbidity. In a multivariate logistic regression analysis age, AIRD with pulmonary involvement, diabetes and treatment with prednisone, mycophenolate mofetil or JAK inhibitors were associated with hospitalization. Older age, renal and vascular involvement due to the AIRD, and congestive heart failure were associated with higher mortality. The 4th outbreak occurred 6 months after the introduction of vaccines, with spreading of the delta variant: 110 AIRD pts with COVID19 were recorded. Demographic data, clinical AIRD‘s characteristics, immunomodulatory treatment and comorbidities were similar to the previous outbreaks. However, during the 4th outbreak, the proportion of pts with severe COVID19, the hospitalization and mortality rate were significantly lower as compared to the first 3 outbreaks (15% vs 24%, 27% vs 53%, 6.7% vs 9.1%, respectively). Among COVID19 pts, 25% received a 3rd vaccine dose (booster), 56% contracted infection more than 5 months after the 2nd vaccine dose and 24% were unvaccinated. Most of the pts who received the booster contracted the disease within a week of vaccination. The odds ratio for hospitalization in vaccinated pts compared to unvaccinated was 0.11 (0.01 – 0.63 95% CI, p=0.041) in those vaccinated within the previous 1-5 months, and 0.38 (0.21-0.67 95% CI, p=0.001) in those vaccinated more than 6 months ago. 9 pts died, 5 were more than 6 months after the 2nd mRNA vaccine, 2 were unvaccinated and 1 patient received the booster on the same day of COVID19 diagnosis. Conclusion Before the vaccination campaign, the hospitalization and mortality rate in our cohort were similar to the data reported by other registries. COVID19 tends to be more severe, with increased mortality in patients with active AIIRD and visceral involvement (pulmonary, cardiac, renal), advanced age and co-morbidities. The delta outbreak occured 6 months after the implementation of vaccinations and was associated with significantly lower hospitalization and mortality rates, despite the increased aggressiveness of the variant. Vaccination of AIIRD pts with 3 doses of mRNA vaccines protects from severe COVID19 disease, hospitalization, and death. Acknowledgements Fadi Kharouf and Tali Eviatar had equal contribution Disclosure of Interests None declared

Background Previous studies proved that mRNA vaccinations against SARS CoV2 induced significant humoral responses in AIRD patients (pts). However, the humoral response was blunted in pts treated with CD20 depleting antibodies. There are limited data regarding the long-term outcome of the humoral response and the contribution of the booster vaccine, in immunosuppressed AIRD pts. Objectives To assess the long-term outcome of the humoral response to mRNA vaccine against SARS CoV2, in AIRD pts treated with immunomodulating drugs, and the contribution of the booster vaccination. Methods Consecutive pts treated at the Rheumatology Institute at Rambam Hospital who received their first SARS-CoV-2 (Pfizer) vaccine were recruited to the study, at their routine visit. The visit included AIRD activity assessment and questioning regarding vaccine side effects. We performed serology test 4-6 weeks and 24 weeks after receiving the second dose of vaccine. Pts who received the booster (3rd vaccine) were invited for serology tests 4-8 weeks afterwards. The immunomodulating treatment was not modified, either before or after the vaccination. IgG Antibodies (Ab) against SARS COV2 virus were detected using the SARS-Cov-2 IgG II Quant (Abbott) assay based on a chemiluminescent microparticle immunoassay (CMIA) on the ARCHITECT ci8200system from Abbott. This assay is measuring IgG antibodies against the spike receptor-binding domain (S-RBD) of the virus. The test was considered positive above 50 AU/ml. Results 262 pts (mean age(SD) 57(13), disease duration 11.2(7.4), were recruited. The cohort included 152 pts with inflammatory joint disease, 26 pts with systemic lupus erythematosus, 62 pts with other connective tissue disease and 22 pts with vasculitis; 27 % received csDMARDs only, 35% - b/tsDMARDs only, 30% - combined therapy (csDMARDs+b/tsDMARDs) and 26% received steroids. 225 pts (86%) were seropositive for IgG Ab against SARS CoV2 virus (median 2832.5 AU/ml, IQR 58-29499). 37 (14%) pts had negative tests, 23 (62.2%) of them were rituximab treated. The IgG levels correlated with the medication used to treat the AIRD, the patients’ age but not with the type of the AIRD (Figure 1). 24 weeks afterwards, the median IgG level dropped to 282 AU/ml and 15% of the pts with previous seropositive tests became negative. The booster administration (Pfizer) significantly augmented the humoral response (median 8328 AU/ml, IQR 375-40000). De novo serologic response was observed in 10 out of 37 pts (4/23 rituximab treated pts). Figure 1. The reported side effects of the vaccine were minor (muscle sore, headache, low grade fever). The AIRD remained stable in all pts following all three vaccinations. Conclusion Although the vast majority of AIRD pts developed a substantial humoral response following the administration of the second dose of the Pfizer mRNA vaccine against SARS CoV2 virus, the humoral response significantly declined 24 weeks afterwards. An enhanced response was obtained after the third booster vaccination. Only minor side effects were reported and no apparent impact on AIRD activity was noted. Notably, 62% of the non-responders were treated with B cell depleting agents. Acknowledgements We would like to thank Mrs Tsofnat Margi and Mrs Sarit Elkouby for organisational support. Disclosure of Interests None declared

Background: The epidemiology of COVID19 among patients with AIIRD may be influenced by a dysregulated immune system, immunosuppressive therapies and behavioral patterns. Data regarding the epidemiology of COVID19 among patients with AIIRD is scarce. Objectives: To assess the pattern of COVID19 pandemic among patients with AIIRD compared to the general population in Israel Methods: At the beginning of the COVID-19 pandemic, we established a national registry of patients with AIIRD, diagnosed with COVID-19, based on voluntary reporting by the treating rheumatologist. All the members of the Israeli Society of Rheumatology were encouraged to participate and repeatedly reminded to report any new cases. Rheumatology centers from 11 hospitals from the Northern and Central part of Israel participated in this study. The registry included demographic data, AIIRD diagnosis and duration, systemic organ involvement, co-morbidities, treatment (conventional synthetic disease modifying drugs (csDMARDs), biologic/targeted (b/ts) DMARDs, corticosteroids use, dose and treatment duration, date of COVID19 diagnosis, severity of the viral disease and complications, duration of hospitalization, if required, treatment for COVID 19, laboratory results and outcome. The diagnosis of COVID 19 was made by a positive SARS CoV2 PCR. The indications for SARS CoV2 PCR testing in Israel comprise clinical symptoms or exposure to a confirmed close contact. Severe illness was defined by SpO 2 <94% in room air, respiratory rate of >30 breaths/min, PaO 2 /FiO 2 <300 mm Hg, or lung infiltrates >50% on chest imaging. The epidemiological data regarding the number of COVID19 confirmed patients, the number of severe cases and the rate of mortality among the general population per day and per week, were extracted from the data dashboard of the Israeli Ministry of Health. We analyzed data from 02.2020 to 15.01.2021. Results: During the study period we experienced 3 waves of COVID 19 pandemic. The governmental management of COVID19 spread, at the beginning of the pandemic, included inforcement of severe travel restrictions and social distancing, followed eventually by a preventive lockdown, in spite of the relatively low number of cases. Easing of the restrictions, lifting the travel ban, opening of the commerce and schools led to 2 much more severe waves, which triggered 2 new lockdowns. Up to January 2021, 549763 Israelis had confirmed COVID19, 30% of whom had severe disease, 0.84% died (30% of the patients with severe disease). We identified 190 AIIRD patients (mean(SD) age 52(18), 30% males) who had confirmed COVID19. The weekly incidence curve of patients with rheumatic diseases correlated with the curve of the general population (Figure 1). Sixty-one % of the patients with AIIRD received csDMARDs, 41% were on b/tsDMARDs, 39% on chronic corticosteroids, 12% on ≥10mg prednisone. Forty-seven% of patients required hospitalization, 20% had severe COVID19. Sixteen patients (42% of patients with severe COVID19) (mean(SD), median age 64.7(15.4),67)) died (systemic sclerosis-4 patients, rheumatoid arthritis – 6, systemic lupus erythematosus – 2, antiphospholipid syndrome-2, granulomatous polyangiitis -1, polymyalgia rheumatica-1). The AIIRD was active in 56% of them, 50% received csDMARDs, none of them were on b/tsDMARDs, 31% received chronic prednisone>10 mg. All patients who died had at least 2 comorbidities. Conclusion: The pattern of spread of COVID19 in AIIRD patients is similar to the general population despite repeated mass media alerts for enhanced social distancing for elderly and immune suppressed patients. The disease tends to be more severe with enhanced mortality, especially in those with active AIIRD disease and organ involvement (lungs, heart, renal), older age and co-morbidities. A reporting bias cannot be excluded. Figure 1. Acknowledgements: Both first authors contributed equally to the manuscript. Disclosure of Interests: None declared.

Background: Musculoskeletal manifestations occur in 20-50% of patients (pts) with inflammatory bowel disease (IBD). A substantial number of patients complain of non-inflammatory musculoskeletal pain. Objectives: To assess the incidence of joint hypermobility (JHM), benign joint hypermobility syndrome (BJHS) among patients with inflammatory bowel disease (IBD) examined in the inter-disciplinary rheumatology service at a tertiary referral center and the impact on IBD manifestations and outcome. Methods: Medical records of 180 consecutive IBD pts referred to the inter-disciplinary clinic were retrospectively reviewed. Data regarding age, gender, diagnosis, disease duration, clinical and laboratory features, previous and current therapy, Harvey-Brandshaw Index were entered into a database and analyzed. Beighton’s scoring of ≥4/9 was used to define patients with JHM. The 1998 Brighton’s criteria were used to identify patients with BJHS. Outcome was defined as improvement of joint pain. The statistical methods used included descriptive statistics, T test, Spearman’s correlation and multiple logistic regression analysis. Results: Forty-six patients (mean(SD) age 36.2(12.4), disease duration 13.9(8.8) years) out of 180 IBD patients (mean(SD) age 40.4(14.3), disease duration 15.7(9.1) years) fulfilled the criteria for JHM. Twelve patients had active inflammatory joint disease (2 with axial involvement, 10 with peripheral joint disease and 2 with axial and peripheral joint involvement). The other 32 answered both major criteria for BJHS. The median Beighton scoring was 7 (range 5-9). Most of them were on biological treatment. Patients with JHM suffered frequently of arthralgia and abdominal pain, in spite of endoscopic remission and normal levels of calprotectin and inflammatory markers (p=0.02, r=0.17). JHM and BJHS were associated with poorer outcome (p=0.004, r=0.2). In a multiple logistic regression analysis, only JHM reached borderline significance for predicting worse outcome. Conclusion: Joint and abdominal pain did not improve with immunomodulatory therapy in IBD patients with JHM. JHM may have a negative impact on achievement of clinical remission, in a significant subset of IBD patients. Rheumatologists and gastroenterologists should be aware of this. Disclosure of Interests: : Haya Zidany: None declared, Matti Waterman: None declared, Kohava Toledano: None declared, Yehuda Chowers: None declared, Doron Markovits: None declared, Amir Karban: None declared, Alexandra Balbir-Gurman Consultant of: Novartis, Yolanda Braun-Moscovici: None declared

Background: A growing body of evidence suggests that the gut microbiota plays a significant role in the development of autoimmune diseases. Altered microbiota composition was associated with gastrointestinal and extraintestinal features in systemic sclerosis (SSc) patients. Objectives: To look for differences in gut microbiota between SSc patients regarding disease duration, disease subset and occurrence of digital ulcers (DU). Methods: SSc patients seen at our center were recruited in a prospective study. The exclusion criteria included antibiotic or probiotic treatment during the month prior to recruitment, recent hospitalization, BMI>30, diabetes mellitus or concomitant inflammatory bowel disease. Fecal samples were processed and 16S rRNA gene sequences were analyzed using the QIIME2 packageWeighted (quantitative) and unweighted (qualitative) UniFrac distances, alpha diversity for richness and homogeneity, taxa plots for species and phyla and ANCOM analyses were performed. Results: During July 2018-May 2019, 26 SSc patients (mean age [SD] 53[12.7] years) and disease duration 8.8 [7.1] years) fulfilled the criteria and were willing to participate in the study. Thirteen patients had diffuse SSc, 16 patients had active DU, 8 patients had Raynaud’s phenomenon only without DU, 2 patients had past DU. The microbiota was significantly more similar between patients without active DU compared to those with active DU (P=0.024), but species richness did not differ. Patients with SSc duration less than 6 years had significantly different microbiota compared to long-lasting SSc (unweighted PCoA – q=0.031). Significant variations concerning quantitative and qualitative UniFrac distances (q=0.063, q=0.005) and species richness (q=0.009) were found among patients with diffuse compared to limited SSc. Limited SSc was associated with greater species richness. Taxa plot analysis revealed higher relative abundance of Firmicutes in diffuse disease and of Actinobacteria and Bacteroidetes in limited SSc. Conclusion: Disease duration, disease subset and active DU were associated with shifts in the microbiome of SSc patients. The impact of these changes on disease progression needs further elucidation. Figure: Disclosure of Interests: Yolanda Braun-Moscovici: None declared, Shira Ben Simon: None declared, Katya Dolnikov: None declared, Sami Giryes: None declared, Doron Markovits: None declared, Yonit Tavor: None declared, Kohava Toledano: None declared, Alexandra Balbir-Gurman Consultant of: Novartis, Omry Koren: None declared

Background Muscle involvement in systemic sclerosis (SSc) has a significant impact on morbidity, functional capacity, and mortality. The muscle histopathology is heterogeneous including inflammatory and fibrotic changes. Currently there are no satisfactory means to diagnose inflammatory myopathy in SSc pts with normal creatine kinase (CK) and to assess the response to therapy. Objectives Our aim was to evaluate whether muscle magnetic resonance imaging (MRI) might be a tool to diagnose inflammatory myopathy in SSc patients (pts) and to assess the effect of muscle oriented- immunomodulatory therapy. Methods We retrospectively analysed the clinical data of 290 consecutive SSc pts seen at our centre between the years 2012–2017. Our cohort is part of the EUSTAR registry (centre 042). Pts with muscle weakness as defined by the Medsger muscle severity score of ≥1 and at least one MRI study were included. Clinical data analyzis included SSc subtype, disease duration, modified Rodnan skin score (mRSS), Medsger muscle severity score, CK, autoantibody profile, MRI and immunomodulatory treatment. Results 26 pts with muscle weakness answered the criteria of Medsger muscle severity score of ≥1 MRI data were available, in 17 of the pts. Muscle oedema and fasciitis were seen in MRI in 13 pts (10 diffuse subset, median: age 40, disease duration 1.25 years, mRSS 13.5). MRI was normal in 4 pts (2diffuse SSc, median: age 50 years, disease duration 6 years, mRSS 4). CK was normal in 10 pts with pathologic MRI. Anti-topoisomerase was positive in 6 pts, RNA polymerase 3 – in 3 pts, anti-centromere – in 2 pts and 6 pts were only ANA positive. Muscle biopsy results were available in 4 pts: Biopsy was compatible with myositis in 3 pts with pathologic MRI and revealed fibrosis in 1 pt with normal MRI. 14 pts received immunomodulatory treatment: rituximab (3 pts), rituximab and intravenous immunoglobulins (IVIG) (3 pts), IVIG and methotrexate/azathioprine/mycophenolate mofetil.8 A second MRI was performed in 6 pts with first pathologic MRI, after 12 months of treatment. Significant regression of muscle oedema and perifasciitis was observed in 5 pts and correlated with clinical amelioration, with improvement of muscle strength. No clinical and imaging improvement occurred in one patient, despite the treatment. No change in muscle strength was seen in the patient with normal MRI and evidence of fibrosis on muscle biopsy, although the skin score improved. Conclusions MRI might serve as a non-invasive tool for diagnosis of inflammatory myopathy in SSc pts with early disease, Medsger muscle severity score of ≥1 and normal CK and for assessment of treatment efficacy. Disclosure of Interest None declared

Material and Methods: This explorative study assesses the effectiveness and feasibility of two different exercise approaches designed to increase oral aperture. Both groups had to exercise for 10 minutes, 3 times/day during 3 months. Group A exercised with a passive jaw motion device (Therabite), and Group B did mouth-stretching exercises. Patients were contacted 4 times by telephone to address encountered problems. The subjects used an exercise diary to document compliance. Patients were evaluated at baseline, 3 months (period without intervention), 6 months (at the end of the treatment after 3 months of intervention) and 9 months (follow-up). The subjects were evaluated with The Short Form Health Survey, Scleroderma Health Assessment Questionnaire, modified Rodnan skin score, Abilhand-SSc, Mouth Handicap in Systemic Sclerosis Scale and mouth opening in millimeters. At the end of the study an individual qualitative interview is planned.

Background Skin ulcers, particularly digital ulcers occur in at least 50% of systemic sclerosis (SSc) patients (pts) and cause significant morbidity. They are often complicated by local infection which can lead to contiguous osteomyelitis. Objectives Our aims were to evaluate the accuracy of clinical diagnosis of osteomyelitis and to assess whether there are clinical parameters that may improve the precision of the clinical diagnosis. Methods We retrospectively analyzed the clinical data of consecutive SSc patients hospitalized for skin ulcers in a tertiary referral center for SSc. Our cohort is part of the EUSTAR cohort. The patients were evaluated by rheumathologists skilled in managing SSc skin lesions. All the patients with infected ulcers and suspected for contiguous involvement of underlying bone had bone scans. All the positive scans were followed with 99m-Technetium-Tc-labeled white blood cells (WBC) scintigraphy, in order to differentiate true osteomyelitis from acro-osteolysis or soft tissue infection. We collected demographic data, disease type, extent and severity, routine lab data (CBC, C-reactive protein -CRP, erythrocyte sedimentation rate (ESR), alkaline phosphatase (ALKP), albumin) and wound culture. Each hospitalization was considered a separate event. Statistical analysis: descriptive, student9s T test, Mann-Whitney test. Results During the years 2003–2016, 220 SSc pts with skin/digital ulcers were hospitalized in our department for ilomedin treatment (993 hospitalizations). Most of the pts were hospitalized several times due to recurrent ulcers. Tc bone scan was performed in 39 pts (59 admissions) with infected ulcers (32 females, mean (SD) age 48 (15), disease duration 9 (6.6) years, 25 with diffuse SSc, skin score (MRSS) 9.9 (8)). Osteomyelitis was confirmed in 18 pts on 23 occasions. Osteomyelitis occurred twice in 5 pts in different locations. No statistically significant differences were found between the group with positive scans and the group with negative scans regarding demographic, clinical and lab data. 9 pts had 25 admissions for infected ulcers, osteomyelitis was confirmed in 14 of the admissions. No statistically significant differences were found for CBC ESR CRP ALKP between the osteomyelitis events and superficial infected ulcer admissions in these pts. The causative infectious agents were similar between the 2 groups. Positive bone and WBC scans confirmed osteomyelitis in 39% of clinical suspected cases. WBC scans confirmed osteomyelitis in 75% or the patients with positive Tc bone scans. Conclusions The prevalence of osteomyelitis among our SSc pts admitted for digital ulcers was 10%. The prevalence of confirmed osteomyelitis by scintigraphy in clinically highly suspected cases was 39%. Even when contiguous osteomyelitis was suspected by highly skilled rheumathologists, bone scan ruled out the diagnosis in 61% of the cases, thus avoiding unnecessary prolonged antibiotic therapy. No clinical predictors to rule osteomyelitis in or out could be identified. Disclosure of Interest None declared

BackgroundBehcet9s disease is a multisystemic chronic relapsing inflammatory disease, classified among the vasculitides. The aetiology of Behcet9s disease is unknown. Several cytokines, among them TNF-α, are involved in the pathogenesis of the disease.ObjectivesWe aimed to assess efficacy and safety of Adalimumab (ADA) in patients with active Behcet9s arthritis not responding to one or more DMARDS and to assess the impact of treatment on the cytokine milieu.MethodsEligible patients (pts) with active arthritis were enrolled in a 24 weeks single center prospective open-label study. Pts who relapsed within 12 weeks following ADA discontinuation could enter a 3 year extension study. The efficacy was assessed by 68 tender and 66 swollen joint count, patient visual analogue scale (VAS) for pain, physician overall disease activity VAS, health assessment questionnaire (HAQ), Behçet9s Disease Current Activity Form (BDCAF), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). TNF-α,IL-1β, IL-6, INF-γ, IL-10 and IL-17a were evaluated at baseline, after 24 and 48 weeks of treatment, by ProcartaPlex Human High Sensitivity – Immunoassay kit. Trough ADA serum levels and anti-drug antibodies were measured at baseline, week 24 and 48.ResultsTen pts (6 females),age (mean, standard deviation –SD) 45 (8.4) years, with a disease duration of 11.6 (10) years, were enrolled and treated with subcutaneous ADA 40mg every 2 weeks for 24 weeks. The results are described in Table1. A statistically significant improvement was observed in swollen joint count, physician VAS and BDCAF and in IL-6 levels, but not in tender joint count or HAQ. Resolution of oral and urogenital ulcers was achieved in all pts. Significant reduction of pain was reported by 40% of pts. No relapse of uveitis or other disease manifestations occurred during the study. The reduction in IL-6 levels correlated with the physician VAS and BDCAF but not with HAQ. No correlation was found between change in IL-10 level and VAS pain. The levels of INF-γ, IL-17A, TNF-α were undetectable in all pts. IL-1β was elevated in 1 patient only. ADA serum trough levels were in the therapeutic range in 7/10 pts. One patient developed high antidrug antibodies titer and ADA serum trough level of 0 with a concomitant increase in VAS pain and IL-6 concentration. Another patient with low ADA trough levels and no antibodies improved after providing ADA weekly. The disease relapsed in 9/10 pts, within 4–6 weeks following ADA interruption, 7 pts enrolled into the extension study.ConclusionsADA treatment was well tolerated and achieved a significant improvement in arthritis and mucocutaneous manifestations and lowered IL-6 serum concentration in all study pts but only 40% reported significant pain reduction. A subset of pts with insufficient improvement in joint tenderness and generalized pain may require comprehensive pain management besides anti-inflammatory therapy.AcknowledgementsABBVIE donated the study medication and supported the lab workDisclosure of InterestNone declared

Background Behcet9s disease is a multisystemic chronic relapsing inflammatory disease, classified among the vasculitides. The clinical manifestations include mucocutaneous lesions, articular, ocular, vascular, gastrointestinal and/or central nervous system involvement. The aetiology of Behcet9s disease is unknown. TNF-α may play an important role in the pathogenesis of the disease. Short term studies reported the efficacy of anti-TNFα therapy, particularly regarding ocular and mucocutaneous involvement in Behcet9s. Objectives The primary end point was to assess efficacy and safety of Adalimumab (ADA) in patients with active Behcet9s arthritis not responding to one or more DMARDS. The secondary end point was to assess the impact of treatment on other disease manifestations. Methods Eligible patients with active arthritis were enrolled in a 24 weeks single center prospective open-label study. Patients who relapsed within 12 weeks following ADA discontinuation could enter a 3 year extension study. The efficacy was assessed by 68 tender and 66 swollen joint count, patient visual analogue scale (VAS) for pain, physician overall disease activity VAS, health assessment questionnaire (HAQ), Behçet9s Disease Current Activity Form (BDCAF), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Statistical methods: descriptive statistics, T test, Mann-Whitney U test. Results Ten patients (6 females),age (mean, standard deviation – SD) 45 (8.4) years, with a disease duration of 11.6 (10) years, met the inclusion, exclusion criteria and were treated with subcutaneous ADA 40mg every 2 weeks for 24 weeks. The clinical manifestations included arthritis, oral and urogenital aphtae in all patients, erythema nodosum (3 patients) and other skin involvement (3 patients), uveitis (1 patient) and deep vein thrombosis (1 patient). Prior to ADA therapy they failed treatment with3.2 (1.3) different DMARDs. A statistically significant improvement was observed in swollen joint count (mean (SD) at baseline 4.6 (4.2) vs 0.4 (0.6) at 24 weeks, p=0.006), physician VAS (51.5 (18.5) vs 24.5 (16), p=0.002) and BDCAF (5.4 (1.6) vs 2.1 (1.4), p=0.001), but not in tender joint count (19 (18.7) vs 10.9 (12.6), p=0.14) or HAQ (1.76 (0.85) vs 1.59 (0.99), p=0.14). Resolution of oral and urogenital ulcers was achieved in all patients. Significant reduction of pain was reported by 40% of patients. No relapse of uveitis or other disease manifestations occurred during the study. The treatment was well tolerated: there were no serious adverse events; there were no injection related site reactions. Four infective episodes (2 cases of pneumonia and 2 of sinusitis), were treated ambulatory and did not require ADA withdrawal. The disease relapsed in 9 out of 10 patients, within 4–6 weeks following ADA interruption, 7 patients enrolled into the extension study. Conclusions ADA treatment was well tolerated and achieved a significant improvement in arthritis and mucocutaneous manifestations in all study patients but only 40% reported significant pain reduction. A subset of patients with insufficient improvement in joint tenderness and generalized pain may require comprehensive pain management besides anti-inflammatory therapy. Acknowledgement ABBVIE donated the study medication Disclosure of Interest None declared

Background Hypocomplementemia was previously reported in patients (pts) with rheumatoid arthritis (RA) treated with tocilizumab (TCZ). Decreased complement (C3,C4) production was suggested as a possible mechanism. The long-term consequences concerning serious bacterial infections or autoimmune disorders (AID) have not been reported. Objectives To assess the long-term outcome of RA pts treated with TCZ who developed hypocomplementemia regarding serious bacterial infections or AID. Methods The charts of RA pts treated with TCZ at our center were reviewed retrospectively. Data regarding pts9 age, gender, disease duration, presence of rheumatoid factor (RF), antibodies to citrullinated peptide (ACPA), and nuclear antigens (ANA), previous and concomitant non-biological DMARDs, previous biological DMARDs, and TCZ treatment duration; laboratory parameters including leucocytes and thrombocytes count, liver enzymes, C3 and C4 levels at baseline and during TCZ treatment; episodes of infections, allergic reactions, and AID were captured and analyzed. Results Thirty five pts out of 85 RA pts treated with TCZ, at our center, had serial measurements of serum complement concentration. Fourteen pts (mean age 58.3 years, mean disease duration 8.6 years) developed low C4 levels (9 had also low C3). Mean TCZ treatment period was 4.6 years (range 1-10 years). All patients had normal complement levels at baseline. Seven pts developed persistent leukopenia, 3 pts had persistent thrombocytopenia, 3 pts developed liver enzymes elevation. No serious bacterial infections or new onset AID occurred during follow up. One patient developed a severe allergic reaction. Persistent leukopenia was observed only in 2 out of 21 pts with normal complement levels, as opposed to 5 out of 14 pts with hypocomplementemia. No patients with normal complement levels developed thrombocytopenia. No significant differences regarding previous biologic or concomitant DMARD9s treatment were found between the 2 groups of pts. Conclusions Long-term follow up of RA pts treated with TCZ who developed hypocomplementemia did not reveal an increased rate of serious bacterial infections or AID. Persistent leukopenia and thrombocytopenia were frequent in these pts; the relationship to hypocomplementemia needs to be further elucidated. Disclosure of Interest None declared

Background Musculoskeletal manifestations occur in 20-50% of patients (pts) with inflammatory bowel disease (IBD) and they have an impact on the clinical course and therapeutic approach. Objectives To summarize the rheumatologic manifestations of IBD pts referred to the rheumatology service in a tertiary referral center and to assess the impact of gastro-rheumatologic inter-disciplinary clinic on patient management. Methods Medical records of 100 consecutive IBD pts referred to rheumatology unit and the inter-disciplinary clinic were retrospectively reviewed. Data regarding age, gender, diagnosis, disease duration, clinical and laboratory features, previous and current therapy were entered into a database and analyzed. The statistical methods used included descriptive statistics, T test, Spearman9s correlation and multiple logistic regression analysis. Results Seventy pts suffered of Crohn9s disease, 29 of ulcerative colitis, and 1 patient of celiac disease. The mean (median) age was 43 (41.5) years, 68 pts were females, the mean (median) disease duration 7.7 (5) years, range 0-40 years. The referrals were for joint pain (73%), back pain (15%), myalgia (3%), fever (2%), and miscellaneous (7%). Spondyloarthropathy was diagnosed in 56 out of 88 pts referred for joint or back pain (35 pts with peripheral arthritis, 13 pts with axial involvement - symptomatic sacroiliitis or spondylitis, confirmed by imaging and 8 pts with enthesopathies). Hypermobility was found in 18 pts referred for joint pain. The other "musculoskeletal" entities included avascular necrosis of hips (2pts), Takayasu arteritis (1patient), IBD related myositis (1patient), steroid-induced myopathy (2pts), systemic lupus erythematosus (1patient), pseudogout (1patient), insufficiency fractures (1patient) osteoarthritis (2pts).Seventeen pts developed chronic peripheral arthritis which did not correlate to IBD activity and did not consistently respond to IBD-targeted immunomodulatory treatment, including anti-TNF agents, but responded to non anti-TNF biologicals. Nine pts had psoriasis or familial history of psoriasis; all of them developed chronic arthropathy (peripheral or axial). The assessment of the patients at the inter-disciplinary clinic had an important impact on the management in almost 70% of cases referred. Conclusions An accurate assessment of joint inflammation in the context of IBD activity may lead to changes in the use of disease modifying drugs or biological agents. Not every joint or back pain in IBD pts is arthritis or spondyloarthropathy. The treatment of IBD pts with chronic arthritis in whom the IBD is silent should be focused on articular inflammation. We suggest that multidisciplinary clinic might have an important role in correctly diagnosing and treating rheumatologic manifestations in IBD pts. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3629

Background The gastrointestinal tract is involved in nearly all patients with systemic sclerosis (SSc) and is a source of significant morbidity and even mortality. Objectives To assess whether there is correlation between upper gastrointestinal (UGI) endoscopy findings and mortality in SSc patients. Methods The records of 256 SSc patients seen in our rheumathologic clinic between 2003-2013 were reviewed. 140 patients who had at least one detailed upper endoscopy report and at least 6 months follow-up were included in the study. Patient data included demographics, type of SSc, disease duration, modified Rodnan skin score (mRSS), lung, cardiac, renal or musculoskeletal involvement, hemoglobin at endoscopy and type of antibodies. Endoscopic findings that were included in the analysis were esophagitis, ulcerations, tumors, gastric antral vascular ectasia (GAVE), gastric erosions, submucosal hemorrhages and lumenal blood. The statistical methods used included descriptive statistics, T test, bivariable analysis, cox regression analysis Results Forty seven patients (16 diffuse SSc) had evidence of GAVE or antral erosions and hemorrhage. The mortality rate in this group, during the follow up was 37% vs. 25% in the group of 93 (39 diffuse) SSc patients without GAVE or UGI bleeding (p=0.001). There were no statistical differences between the groups regarding mean ages (55) or Hb (10.87 in the group with the UGI bleeding vs 11.77). The mean mRSS score was higher in the group with UGI bleeding 8 vs.5.6 (p=0.019). Mean (median) disease duration was 6.9 (4.5) years in the group with UGI bleeding vs 10.4 (10) (p<0.001). Esophagitis was found in 90% of patients, despite use of PPI. Co-morbidity of myositis had a negative impact on survival. The mortality hazard ratio (95% CI) for UGI bleeding, myositis and interstitial lung disease were 5.9 (2.7-13.2), 4.9 (2-12.4) and 2.7 (1.3-5.8) respectively. Conclusions A diagnosis of GAVE or UGI bleeding on upper endoscopy was associated with significantly higher mortality. In our cohort of SSc patients, myositis was associated also with increased mortality. The long-term survival of patients with GAVE/UGI bleeding was similar to the patients with myositis that were free of such GI complications. The patients with both myositis and GI bleeding had a very poor prognosis. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.3613