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Objective: The SARS-CoV-2 pandemic has induced an exceptional sanitary crisis, potentially having an impact on treatment continuation, for juvenile idiopathic arthritis (JIA) patients receiving immunosuppressive therapies. After national lockdowns, many patients were also concerned about their safety at school. We evaluated the impact of the pandemic on the optimal continuation of treatment and on the return to school in JIA patients.Methods: JIA patients under 18 years of age, usually treated with disease-modifying anti-rheumatic drugs (DMARDs) were prospectively included during their outpatient visit and completed a standardized questionnaire. The primary outcome was DMARD treatment modification in relation to the context of the pandemic but we also evaluated the pandemic's impact on the schooling.Results: One hundred and seventy three patients from 8 different expert centers were included between May and August 2020. Their mean age was 11.6 years (± 4.1 years), and most of them 31.2% (54/173) had a rheumatoid factor-negative polyarticular JIA. Fifty percent (86/172) were treated with methotrexate, and 72.5% (124/171) were treated with bDMARDs. DMARD treatment modification in relation to the pandemic was observed in 4.0% (7/173) of participants. 49.1% (81/165) of the patients did not return to school due to a personal/parental decision in 69.9% (55/81) of cases. Two patients were diagnosed positive for SARS-CoV-2 infection.Conclusion: This study suggests that JIA patients treated with DMARDs continued their treatment during the pandemic and were rarely affected by symptomatic COVID-19. In contrast, parents' reluctance was a major obstacle for returning to school. Therefore, more solidified school reopening strategies should be developed.

Summary Background Pompe disease is a rare, progressive neuromuscular disorder caused by deficiency of acid α-glucosidase (GAA) and accumulation of lysosomal glycogen. We assessed the safety and efficacy of avalglucosidase alfa, a recombinant human GAA enzyme replacement therapy specifically designed for enhanced mannose-6-phosphate-receptor targeting and enzyme uptake aimed at increased glycogen clearance, compared with the current approved standard of care, alglucosidase alfa, in patients with late-onset Pompe disease. Methods We did a randomised, double-blind, phase 3 trial at 55 sites in 20 countries. We enrolled individuals (aged ≥3 years) with enzymatically confirmed late-onset Pompe disease who had never received treatment. We used a centralised treatment allocation system to randomly allocate participants to either avalglucosidase alfa or alglucosidase alfa. Participants and investigators were unaware of their treatment allocation. The primary outcome measure was change from baseline to week 49 in upright forced vital capacity percent (FVC%) predicted. We used a hierarchical fixed sequential testing strategy, whereby non-inferiority of avalglucosidase alfa compared with alglucosidase alfa was assessed first, with a non-inferiority margin of 1·1. If non-inferiority was seen, then superiority was tested with a 5% significance level. The key secondary objective was effect on functional endurance, measured by the 6-minute walk test (6MWT). Safety was assessed, including treatment-emergent adverse events and infusion-associated reactions. The modified intent-to-treat population was the primary analysis population for all efficacy analyses. The safety population was the analysis population for safety analyses. This trial is registered with ClinicalTrials.gov , NCT02782741 . We report results of the 49-week primary analysis period. Findings Between Nov 2, 2016, and March 29, 2019, 100 participants were randomly allocated avalglucosidase alfa (n=51) or alglucosidase alfa (n=49). Treatment with avalglucosidase alfa resulted in a least-squares mean improvement in upright FVC% predicted of 2·89% (SE 0·88) compared with 0·46% (0·93) with alglucosidase alfa at week 49 (difference 2·43% [95% CI −0·13 to 4·99]). Non-inferiority was shown because the lower bound of the 95% CI for the difference far exceeded the predefined non-inferiority margin but did not exclude 0 (p=0·0074). Superiority was not reached (p=0·063), so formal testing was stopped, as per the testing hierarchy. Improvements were also seen in the 6MWT with avalglucosidase alfa compared with alglucosidase alfa, with greater increases in distance covered (difference 30·01 m [95% CI 1·33 to 58·69]) and percent predicted (4·71% [0·25 to 9·17]). Treatment-emergent adverse events potentially related to treatment were reported in 23 (45%) of 51 participants in the avalglucosidase alfa group and in 24 (49%) of 49 in the alglucosidase alfa group, and infusion-associated reactions were reported in 13 (26%) participants in the avalglucosidase alfa group and 16 (33%) in the alglucosidase alfa group. Of the five trial withdrawals, all in the alglucosidase alfa group, four were due to adverse events, including two infusion-associated reactions. Serious treatment-emergent adverse events were reported in eight (16%) participants who received avalglucosidase alfa and in 12 (25%) who received alglucosidase alfa. One participant treated with alglucosidase alfa died because of acute myocardial infarction determined to be unrelated to treatment. Antidrug antibody responses were similar in both groups. High and persistent titres (≥12 800) and neutralising antibodies were more common with alglucosidase alfa (in 16 [33%] participants) than with avalglucosidase alfa (ten [20%]). Interpretation We consider that this study provides evidence of clinically meaningful improvement with avalglucosidase alfa therapy over alglucosidase alfa in respiratory function, ambulation, and functional endurance, with no new safety signals reported. An open-label extended-treatment period is ongoing to confirm the long-term safety and efficacy of avalglucosidase alfa, with the aim for this therapy to become the new standard treatment in late-onset Pompe disease. Funding Sanofi Genzyme.

Introduction Oral administration of pilocarpine enhances salivary flow in sicca patients but its effect upstream on ultrasound (US) of salivary glands (SG) and downstream on periodontium remain unknown. Methods Sicca patients were prospectively included. Echostructural and vascularization of SG were assessed using B mode and pulsed Doppler (USPD). Vascularization of SG was measured using resistive index (RI) before and after stimulation by lemon juice. Echostructure (measure of glandular length in cm2, evaluation of parotid and submandibular glands parenchymal abnormalities) was assessed at baseline (M0) and after 3 months (M3) of treatment with pilocarpine. A dental consultation was performed at M0 and M3 to evaluate changes in unstimulated salivary flow (USSF), stimulated salivary flow (SSF), and periodontal parameters such as modified gingival index (Lobene), plaque index (Silness), bleeding index, pocket depth, and pH. Results Nineteen patients were included but only 11 received pilocarpine treatment for 3 months, as six stopped pilocarpine due to side effects and two were excluded for other causes. Among the 11 patients who completed the 3-month follow-up, five had primary Sjögren’s syndrome according to the American-European’s classification criteria. As expected, statistical differences were found concerning SSF (p = 0.018) and USSF (p = 0.027) between M0 and M3 while no statistical change in both SG echostructure and vascularization or periodontal evaluation was shown. Conclusions Pilocarpine improved SSF and USSF measurements in sicca syndrome but no ultrasonography of major salivary glands (SGUS) structural and vascular changes were detected as well as periodontal evaluation. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-020-00263-y.

Objectives To refine the prevalence, characteristics and response to treatment of myositis in primary SS (pSS). Methods The multicentre prospective Assessment of Systemic Signs and Evolution in Sjögren’s Syndrome (ASSESS) cohort of 395 pSS patients with ≥60 months’ follow-up was screened by the 2017 EULAR/ACR criteria for myositis. Extra-muscular complications, disease activity and patient-reported scores were analysed. Results Before enrolment and during the 5-year follow-up, myositis was suspected in 38 pSS patients and confirmed in 4 [1.0% (95% CI: 0.40, 2.6)]. Patients with suspected but not confirmed myositis had higher patient-reported scores and more frequent articular and peripheral nervous involvement than others. By contrast, disease duration in patients with confirmed myositis was 3-fold longer than without myositis. Two of the four myositis patients fulfilled criteria for sporadic IBM. Despite receiving three or more lines of treatment, they showed no muscle improvement, which further supported the sporadic IBM diagnosis. The two other patients did not feature characteristics of a myositis subtype, which suggested ‘pure’ pSS myositis. Steroids plus MTX was then efficient in achieving remission. Conclusions Myositis, frequently suspected, occurs in 1% of pSS patients. Especially when there is resistance to treatment, sporadic IBM should be considered and might be regarded as a late complication of this disease.

Objectives The aim of this study was to determine the prevalence and clinical significance of extra-articular manifestations (EAMs) at inclusion into a cohort of patients with recent-onset arthritis consistent with rheumatoid arthritis (RA). Methods The ESPOIR cohort included patients aged 18 to 70 years who had a definitive or probable diagnosis of RA. Symptoms consistent with EAMs were collected at baseline. We divided the patients into two groups, with vs. without baseline EAMs. We looked for associations linking the presence of EAMs at baseline to patient and disease characteristics at baseline and 5 years later, as well as to diagnostic certainty after 2 years. The analyses were adjusted for multiple comparisons using the Benjamini–Hochberg procedure to control the false discovery rate. Results Of 798 patients, 330 (41.4%) had at least one symptom consistent with EAM at baseline, with the most common being sicca syndrome (28.4%) and Raynaud's phenomenon (17.3%). The EAM+ group had a higher mean baseline DAS-28 value (5.3 ± 1.3 versus 5.0 ± 1.3; corrected p value = 0.005) compared to the EAM- group. The final diagnosis did not differ between the two groups. After 5 years, the EAM+ group had significantly higher values for the tender joint count (3.9 ± 6.4 versus 1.8 ± 3.3, corrected p value = 0.005) and swollen joint count (1.3 ± 2.8 versus 1.1 ± 2.3, corrected p value =0.0005) compared to the EAM- group. Conclusion EAMs, particularly sicca syndrome and Raynaud's phenomenon, are very common in patients with early arthritis consistent with RA. In this population, several parameters reflecting disease activity were higher among patients with EAMs, at baseline and after 5 years.

Ischiofemoral impingement syndrome (IFIS) is an unusual cause of hip pain. Certain strenuous sports can cause this impingement, such as dancing. We report the case of an 11-year-old ballet dancer with bilateral IFIS secondary to overtraining and hypertrophy of the quadratus femoris. This syndrome is frequently evoked in the field of orthopedics following hip replacement. Bilateral IFIS is rare and should be sought in the context of an intense sport such as dance when any other cause has been eliminated.

Background Myositis is recognized as a manifestation of primary Sjogren’s syndrome (pSS). Grading muscle involvement using the EULAR Sjogren Syndrome Disease Activity index (ESSDAI) does not require biopsy-proven active myositis or extensive immunological investigations. However, several studies have reported that a high proportion of pSS-associated myositis is either inclusion body myositis (IBM) or an overlap with idiopathic inflammatory myopathies. Objectives The objective of our study was to investigate the nature of inflammatory muscle involvement in a large sample of patients with pSS and concurrent myositis. Methods We conducted a French nation-wide survey among reference centers known for their experience in the field of systemic auto-immune diseases. Patients with physician-based diagnosis of pSS and inflammatory muscle involvement were included. They were categorized and subsequently described and compared according to the identification of an associated condition likely to explain inflammatory muscle involvement. Results 60 cases of myositis in patients with pSS were identified. Patients were mostly female (52/60) and pSS classification criteria were met in 43/60. Muscle biopsy was performed in 50/60 patients and showed inflammatory lesions in 80% of cases. An associated condition likely to explain myositis was identified in 31 patients: typical dermatomyositis rash (n=8), MCTD-specific antibodies (n=11), myositis specific antibodies (n=10), and systemic lupus erythematosus, scleroderma or ANCA associated vasculitis specific antibodies in favor of an overlap syndrome (n=7). Among the 29 patients without associated condition likely to explain myositis, 17 had a biopsy proven inflammatory muscle disease, showing histopathologic features consistent with IBM in 5 cases. 4 of the 5 patients with IBM histological features received corticosteroids and/or other immunosuppressive agents to treat muscle disease. Worsening of muscular involvement despite treatment was reported in these 4 patients. Comparative analysis showed a lower ESSDAI (p = 0.001) among patients without identified associated condition likely to explain myositis. Conclusion In most cases of concurrent pSS and myositis, inflammatory muscle involvement is explained by a context of overlap syndrome or has a histological pattern consistent with IBM. Extensive immunological investigations and muscle biopsy appear to be necessary in pSS patients with suspected inflammatory muscle involvement, in order to avoid misclassification and/or overtreatment. Disclosure of Interests Camille Houssais: None declared, Jean-baptiste Noury: None declared, Yves Allenbach: None declared, Laure Gallay: None declared, Florence Assan: None declared, Olivier Benveniste: None declared, Jonathan Broner: None declared, Pierre Duffau: None declared, Alexandra Espitia-Thibault: None declared, Anne Grasland: None declared, Sebastien SANGES: None declared, Gilles Hayem: None declared, Veronique LE GUERN: None declared, Nihal Martis: None declared, Kuberaka Marianpillai: None declared, Denis Mulleman Speakers bureau: Pfizer, Novartis, Grifols, Gaetane Nocturne: None declared, alain meyer: None declared, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Divi Cornec: None declared, Dewi Guellec: None declared

Objective To look for abnormalities in circulating B-cell subsets in patients with rheumatic symptoms of Whipple’s disease (WD). Method Consecutive patients seen between 2010 and 2016 for suspected inflammatory joint disease were identified retrospectively. Results of standardized immunological and serological tests and of peripheral-blood B-cell and T-cell subset analysis by flow cytometry were collected. Patients with criteria suggesting WD underwent PCR testing for Tropheryma whipplei, and those with diagnosis of WD (cases) were compared to those without diagnosis (controls). We used ROC curve analysis to evaluate the diagnostic value of flow cytometry findings for WD. Results Among 2917 patients seen for suspected inflammatory joint disease, 121 had suspected WD, including 9 (9/121, 7.4%) confirmed WD. Proportions of T cells and NK cells were similar between suspected and confirmed WD, whereas cases had a lower proportion of circulating memory B cells (IgD-CD38low, 18.0%±9.7% vs. 26.0%±14.2%, P = 0.041) and higher ratio of activated B cells over memory B cells (4.4±2.0 vs. 2.9±2.2, P = 0.023). Among peripheral-blood B-cells, the proportion of IgD+CD27- naive B cells was higher (66.2%±18.2% vs. 54.6%±18.4%, P = 0.047) and that of IgD-CD27+ switched memory B cells lower (13.3%±5.7% vs. 21.4%±11.9%, P = 0.023), in cases vs. controls. The criterion with the best diagnostic performance was a proportion of IgD+CD27- naive B cells above 70.5%, which had 73% sensitivity and 80% specificity. Conclusion Our study provides data on peripheral-blood B-cell disturbances that may have implications for the diagnosis and pathogenetic understanding of WD.

Objective.To assess the prevalence of myofascial inflammatory lesions visible by magnetic resonance imaging (MRI) and their changes after tocilizumab (TCZ) therapy in active polymyalgia rheumatica (PMR).Methods.We conducted a posthoc analysis of data from the TENOR study of TCZ monotherapy in PMR. The 18 patients each received TCZ injections at weeks 0, 4, and 8. The shoulder and pelvic girdles were assessed at baseline then at weeks 2 and 12 using T1- and T2- short-tau inversion recovery–weighted MRI. Radiologists blinded to patient data assessed each muscle group for localized myofascial inflammation on baseline, Week 2, and Week 12 MRI. Reproducibility was estimated by having 2 radiologists assess the Week 2 MRI of 13 patients, then computing the κ coefficient.Results.For myofascial lesion detection, intraobserver reproducibility was almost perfect (κ = 0.890) and interobserver reproducibility was substantial (κ = 0.758). At baseline, all patients had at least 1 inflammatory myofascial lesion; sites involved were the shoulder in 10 (71.4%) patients, hip in 13 (86.7%), ischial tuberosity in 9 (60.0%), and pubic symphysis in 12 (80.0%). Sites involved at Week 12 were the shoulder in 8 patients (53.3%), hip in 5 (33.3%), ischial tuberosity in 1, and pubic symphysis in 3 (20.0%). At Week 12, of 103 muscle groups studied in all, 43 (41.7%) had no inflammatory lesions, compared to 33 at baseline (p = 0.002); improvements were noted in 66 (64.1%) muscle groups, worsening in 2 (1.9%), no change in 35 (34.0%; p = 0.034).Conclusion.Localized myofascial inflammatory lesions are common in recent-onset PMR and improve during TCZ therapy. Clinicaltrials.gov (NCT01713842).

Objective Parotidomegaly is a criterion of the EULAR Primary Sjogren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous. The objective is to evaluate inter-observer reproducibility of parotid gland measurement by palpation, and to secondary evaluate its reliability compared to US assessment. Methods Outpatients with primary Sjogren Syndrome (pSS) or with a diagnostic suspicion, in a single reference centre, were included. They underwent clinical examination by two independent investigators (VDP and DC), evaluating: parotid gland swelling, parotid gland size (direct measurement with a decameter under the mandibular angle), and pain. Cohen's kappa coefficient was calculated to determine inter-observer concordance for parotid gland swelling, and intraclass correlation coefficient to determine inter-observer agreement of gland size measurement. Results Thirty-four patients (33 women, 1 man) were included. Clinical data were complete for 33 patients. Inter-observer concordance Kappa coefficient was 0.90 [0.76–1.00] for detection of parotidomegaly over 66 parotid glands. It was of 0.60 [0.42–0.73] for gland length measurement. For one observer, the median cut-off for defining parotidomegaly was 4.15 cm; for the second observer, it was of 4.92 cm. For submandibular glands palpation, no correlation was found between investigators. A significant association between clinical parotidomegaly and a larger echographic surface was found. Conclusion Clinical measurement of parotidomegaly was concordant between two observers on a binary mode (presence/absence). However, concordance on direct measurement was weak. US could be a complementary examination.

Background:The SARS-CoV-2 pandemic has induced an exceptional sanitary crisis, potentially having an impact on treatment continuation, for juvenile idiopathic arthritis (JIA) patients receiving immunosuppressive therapies. In France, after the first lockdown from March to May 2020, many parents and children were then also concerned about whether reopening plans for school could ensure the safety of students, despite data concerning children with COVID-19 seem reassuring, and very few of them develop severe forms of the disease (1, 2, 3).Objectives:Our objectives were to evaluate the impact of the COVID-19 pandemic on the therapeutic management of JIA, the frequency of returning to school after the first lockdown period and the prevalence of SARS-CoV-2 infection at the time of the survey.Methods:JIA patients under 18 years of age, usually treated with disease-modifying anti-rheumatic drugs (DMARDs) were prospectively included during their outpatient visit and completed a standardized questionnaire. Data regarding the general characteristics of the participants, medical history, SARS-CoV-2 infection, characteristics of JIA subtypes and treatment modifications were collected.Results:A total of 173 patients from 8 different expert centers were included between May and August 2020. Their mean age was 11.6 years (± 4.1 years), and most of them 31.2% (54/173) had a rheumatoid factor-negative polyarticular JIA. Fifty percent (86/172) were treated with methotrexate, and 72.5% (124/171) were treated with bDMARDs. DMARD treatment modification in relation to the pandemic was observed in 4.0% (7/173) of participants, our results reflect good adherence of the patient/parents to their immunosuppressive treatments. 49.1% (81/165) of the patients did not return to school due to a personal/parental decision in 69.9% (55/81) of cases, due to anxiety of the patient/parents regarding COVID-19. Two patients were diagnosed positive for SARS-CoV-2 infection.Conclusion:This study suggests that JIA patients treated with DMARDs continued their treatment during the pandemic. In contrast, parents’ reluctance was a major obstacle for returning to school. Therefore, more solidified school reopening strategies should be developed.References:[1]Filocamo G, et al. “Absence of severe complications from SARS-CoV-2 infection in children with rheumatic diseases treated with biologic drugs.” J Rheumatol. 25 avr 2020;[2]Tagarro A, et al. “Screening and Severity of Coronavirus Disease 2019 (COVID-19) in Children in Madrid, Spain.” JAMA Pediatr. 8 avr 2020;[3]Lu X, et al. « SARS-CoV-2 Infection in Children”. N Engl J Med. 23 avr 2020;382(17):1663-5.Acknowledgements:We would like to thank all the participants involved in this clinical research and six medical students who helped completing the forms: Margaux Blondel, Alice Bonnod, Marie Desval, Béatrice Dordain, Gabrielle Fagnet, and Madouc De Saint Martin Pernot.Disclosure of Interests:None declared

Background Myositis prevalence in primary Sjogren’s syndrome (pSS) and whether it is associated with peculiar extra-muscular involvement and/or a biological profile is unknown. Objectives To refine prevalence and characteristics of patients with pSS and myositis. Methods In the national multicenter prospective cohort ASSESS (395 patients with pSS with a 5 year-prospective follow-up), patients with suspected myositis were identified. Their charts were reviewed and the patients were compared with the rest of the cohort. Results Myositis was suspected in 38 patients (2 men, 36 women, 5829–78 yr old) because of myalgia and/or exercise intolerance (n=38) along with high blood CK level (n=28). As compared with the rest of the cohort, they had higher patient-reported signs including pain VAS, dryness VAS and patient reported index ESSPRI (6.3 vs 5.3, p=0.007). In contrast, proportion of systemic involvements (76.3% vs 70.9%, p=0.57) and systemic disease activity measured by the ESSDAI, without taking the muscular domain into account (2 vs 3, p=0.93), were not different from patients without suspected myositis. Demographic characteristics and disease duration were also similar. Electromyographic recording and/or muscle histology performed in these 38 patients objective muscular involvement in only 4 patients (1% of the cohort). - Three patients were diagnosed with inclusion body myositis (sIBM). Accordingly, age at first sign was 49 years,49–60 muscle disease had progressive onset as suggested by the 11 years1–28 delay between first muscle sign and diagnosis. CK level was - One pSS patient with myositis was a 39 years old woman with polymyositis. She developed proximal muscle weakness, CK was 750UI/L and muscle biopsy found endomysial infiltrate. Muscle force and CK level normalised with immunomodulatory drugs. Compared to the rest of the cohort, patient with myositis had longer disease duration at inclusion (15 vs 5 year, p=0.01) and tended to be younger at pSS diagnosis (41.5 vs 53 year, p=0.07). They had more frequent history of systemic manifestations (100% vs 65.0%, p=0.011) but ESSDAI at baseline (2 vs 3, p=0.56) and the biological characteristics were not different from patients without myositis. In contrast with the patients with suspected but not confirmed myositis, patient-reported signs (i.e. fatigue, pain, dryness and ESSPRI score) were similar to patients without myositis. Conclusions Myositis is frequently suspected in patients with pSS, especially when patients-reported signs are particularly disabling. Myositis occurs very infrequently (1% of the cohort), in patients with longer disease duration. sIBM was the most predominant subset of myositis in the present study. Disclosure of Interest None declared

Background In everyday practice, myofascial lesions are not usually evaluated on MRIs obtained for patients with PMR. Objectives To assess the prevalence of myofascial inflammatory lesions visible by magnetic resonance imaging (MRI) and their changes after tocilizumab therapy in active polymyalgia rheumatica (PMR). Methods We conducted a post hoc analysis of data from the TENOR study of tocilizumab monotherapy in PMR.1 The 18 patients each received tocilizumab injections at weeks 0, 4, and 8. The shoulder and pelvic girdles were assessed at baseline then at weeks 2 and 12 using T1- and T2-STIR-weighted MRI. Radiologists blinded to patient data assessed each muscle group for myositis and fasciitis on baseline, week-2, and week-12 MRIs. Reproducibility was estimated by having two radiologists assess the week-2 MRIs of 13 patients then computing the kappa coefficient. Results For myofascial lesion detection, intraobserver reproducibility was almost perfect (κ=0.890) and interobserver reproducibility was substantial (κ=0.758). At baseline, all patients had at least one inflammatory myofascial lesion (example on right shoulder fig 1); sites involved were the shoulder in 10 (71.4%) patients, hip in 13 (86.7%), ischial tuberosity in 9 (60.0%), and pubic symphysis in 12 (80.0%). Sites involved at week 12 were the shoulder in 8 (53.3%) patients, hip in 5 (33.3%), ischial tuberosity in 1, and pubic symphysis in 3 (20.0%). At week 12, of 103 muscle groups studied in all, 43 (41.7%) had no inflammatory lesions, compared to 33 at baseline (Mac Nemar; p Conclusions Myositis and fasciitis are common in recent-onset PMR and improve during tocilizumab therapy. They could be used for the diagnosis in routine practice and as criteria of outcome evaluation. References [1] Devauchelle-Pensec V, Berthelot JM, Cornec D, Renaudineau Y, Marhadour T, Jousse-Joulin S, et al. Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study. Ann Rheum Dis2016;75:1506–1510. Disclosure of Interest J. P. Laporte: None declared, F. Garrigues: None declared, A. Huwart: None declared, S. Jousse-Joulin: None declared, T. Marhadour: None declared, D. Guellec: None declared, D. Cornec: None declared, V. Devauchelle-Pensec: None declared, A. Saraux Grant/research support from: Chugai, Speakers bureau: Chugai

Background Technological advances have improved phenotypical characterisation of blood cells, and flow cytometry is currently used in haematology, infectious disease, systemic auto-immune diseases. Abnormalities of blood B cell subset profile might provide a useful diagnostic tool in systemic auto-immune diseases, especially for primary Sjogren’s Syndrome1 in which the activated B cells to memory B cells ratio is increased. Nevertheless, we observed that some patients suffering from chronic infection had lymphocytes disturbances similar to those observed in primary Sjogren’s Syndrome. Objectives Whipple’disease (WD) is a rare, systemic, disease caused by intracellular gram positive bacterium, Tropheryma Whipplei (TW). No previous study evaluated the role of B cells in WD. The aim of this study was to analyse whether the circulating blood B cell subset disturbances is characteristic of WD. Methods We collected characteristics of all patients coming for inflammatory rheumatism in our rheumatology department between April 2010 and December 2016. All of them had systematically routine examination, immunological tests, lymphocyte subsets in peripheral blood by flow cytometric analysis. We selected among this population those patients who also had PCR for TW for suspicion of WD, and compared the distribution of lymphocyte subsets of those with and without WD. Then, we evaluated their diagnostic value for WD using a ROC curve. Results Among 3494 patients with inflammatory rheumatism, 121 patients (212 visits) had a suspicion of WD and the diagnosis of WD was retained by an expert rheumatologist for 9 (7.4%) (22 visits). T cells and NK cells were not different whereas percentage of circulating memory B cells (IgD-CD38low) was lower (18.0%±9.7% vs 26.0±14.2%, p=0.041) and the ratio of activated B cells to memory B cells higher (4.4±2.0 vs 2.9±2.2, p=0.023), in patients compared with controls. More precisely, the analysis of the frequency of peripheral blood B cells showed that IgD +CD27 – naive B cells were higher (66.2%±18.2% vs 54.6±18.4%, p=0.047) and IgD-CD27 +switched memory B cells lower (13.3%±5.7% vs 21.4±11.9%, p=0.023), in patients compared with the controls. The best diagnostic value was obtained for the IgD +CD27- naive B cells (cut off 70.5, sensitivity 73%, specificity 80%). Conclusions Our study provides data on blood B cells disturbances and a first step towards understandings of immunological abnormalities in WD. These disturbances provide guidance for diagnosis and allow physiopathological hypothesis. Reference [1] Binard A, Le Pottier L, Devauchelle-Pensec V, Saraux A, Youinou P, Pers J-O. Is the blood B-cell subset profile diagnostic for Sjogren syndrome?Ann Rheum Dis2009;68(9):1447–52. Disclosure of Interest None declared

Background: Cerebral amyloid angiopathy–related inflammation is a rare condition with approximately 100 reported cases. Its clinical manifestations are varied. We report here a novel presentation of this disease. Case presentation: A 61-year-old Caucasian man presented with rapidly progressive paralysis of the IX, X, XI and XII right cranial nerves associated with right central facial nerve palsy. Brain computed tomography angiography and cerebral catheter angiography found a focal fusiform enlargement of the distal cervical portion of the right internal carotid artery, related to a pseudo-aneurysm suggesting an evolution of a dissection and intra-cranial vessel dysplasia. Brain magnetic resonance imaging showed multiple asymmetrical subcortical regions of hyperintensity on T2 fluid-attenuated inversion recovery sequences. Punctiform cortical hyposignals on T2-weighted gradient echo magnetic resonance imaging sequences were mostly congruent with the white matter hyperintensities. There was a decreased cerebral perfusion at the frontal hyperintense fluid-attenuated inversion recovery region. Spectrometry identified a lactate–lipid peak. A brain biopsy showed intravascular amyloid deposits. Corticosteroid therapy was initiated, leading to a dramatic improvement of both clinical condition and magnetic resonance imaging brain lesions. Conclusion: This case report suggests that extra-cranial vasculitis and dysplasia can exceptionally be found in patients satisfying cerebral amyloid angiopathy–related inflammation criteria.

To evaluate whether major salivary-gland ultrasonography (SGUS) abnormalities change over time in patients with suspected primary Sjögren's syndrome (pSS) during the natural course of the disease.We studied patients with suspected pSS who were included in the Brittany cohort of suspected pSS and underwent SGUS at least twice, as part of the routine diagnostic workup done at baseline then at least 1 year later as an additional investigation deemed appropriate by the physician. The evaluation criteria were the semi-quantitative SGUS score (0-4) for each parotid and submandibular gland, the highest SGUS score among the four glands, and the sum of SGUS scores for the four glands. These scores were compared in patients with and without pSS according to the workup at baseline, and their changes over time were assessed.Of 49 included patients, 29 received a diagnosis of pSS at baseline; none of the remaining 20 patients was diagnosed with pSS at either evaluation. The mean (SD) sum of SGUS scores at baseline was 8.9 (5.6) in patients with and 2.1 (2.9) in those without pSS (P0.01). Mean time between SGUSs was 1.9 (1.6) years. None of the evaluation criteria changed between the two SGUSs in the overall population, pSS group, or group without pSS. Similar results were found in the subgroup with recent-onset symptoms.SGUS abnormalities assessed using a semi-quantitative score did not change significantly during a follow-up of nearly 2 years after an initial evaluation for suspected pSS.

Background This study assessed inflammatory changes using ultrasound (US) and magnetic resonance imaging (MRI) in patients taking tocilizumab for polymyalgia rheumatica (PMR). Methods Eighteen patients were included in the prospective open-label TENOR study and received three tocilizumab infusions, without corticosteroids. B-mode and power Doppler US and MRI (T1 and T2-short time inversion recuperation weighted sequences) of the hips and shoulders were performed at weeks 0, 2, and 12. Subacromial, trochanteric, and iliopsoas bursitis and intraarticular glenohumeral and coxofemoral effusions/synovitis were scored from 0 to 3. Changes over time and US–MRI correlations were evaluated. Results At baseline, the proportions of shoulders and hips with bursitis were 93 and 100% by MRI and 61 and 13% by US; and the corresponding proportions for intraarticular effusions/synovitis were 100 and 100% by MRI and 57 and 53% by US. Imaging findings did not improve during the first two treatment weeks. From baseline to week 12, bursitis improved significantly at all four joints by MRI (P = 0.005) and US (P = 0.029) and intraarticular effusions/synovitis by US only (P = 0.001). The proportion of abnormalities that improved by week 12 was 42% by MRI and 37% by US. MRI detected bursitis in a larger proportion of hips (73% versus 13%) and US in a larger proportion of shoulders (57% versus 28%), whereas no difference was found for intraarticular effusions/synovitis. At baseline, agreement between US and MRI findings was poor. Conclusions US and MRI showed significant improvements in inflammatory lesions during tocilizumab treatment of PMR.

Neurological manifestations of primary Sjögren's syndrome are multiple and appear frequently. Depending on data analysis, patient recruitment, and diagnosis criteria used to defined primary Sjögren's syndrome or neurological manifestations, the estimated prevalence is between 0 and 70%. Peripheral neurological complications seem the most common, particularly sensory-motors axonal neuropathies. Neuronopathy seems to be the most specific neurological complication of primary Sjögren's syndrome. Central manifestations of primary Sjögren's syndrome are not uncommon, but the neurological complication's spectrum is not well defined. Neuromyelitis optica is regularly found among central complications. To conclude, although central and peripheral complications of primary Sjögren's syndrome are difficult to assess, partly because of the wide spectrum of possible manifestations, it is around 20%. Neuronopathy is still the most specific complication.

Background The objective was to evaluate concordance between 2002 American-European Consensus Group (AECG) and 2016 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for primary Sjögren’s syndrome (pSS) and to assess how salivary gland ultrasonography (SGUS) might improve the classification of patients. Methods Patients with suspected pSS underwent a standardised evaluation, including SGUS, at inclusion into the single-centre Brittany DIApSS cohort. Agreement between the two criteria sets was assessed using Cohen’s κ coefficient. Characteristics of discordantly categorised patients were detailed. Results We prospectively included 290 patients between 2006 and 2016, among whom 125 (43%) met ACR/EULAR criteria and 114 (39%) also met AECG criteria; thus, 11 (4%) patients fulfilled only ACR/EULAR, no patients AECG only, and 165 (57%) patients neither criteria set. Concordance was excellent (κ = 0.92). Compared to patients fulfilling both criteria sets, the 11 patients fulfilling only ACR/EULAR criteria had similar age and symptom duration but lower frequencies of xerophthalmia and xerostomia (p

Objective The PMR activity score (PMR-AS) includes the CRP value, which may be lacking or invalid owing to anti-IL-6 therapy. Our objective was to develop alternatives to PMR-AS that do not require CRP. Methods We used the Club Rhumatisme et Inflammation (CRI; 89 patients with PMR) and the Tolerance and Efficacy of tocilizumab iN pOlymyalgia Rheumatica (TENOR; 20 patients with recent-onset PMR naive to glucocorticoid who received three tocilizumab infusions, at weeks 0, 4 and 8, followed by prednisone from weeks 12 to 24) cohorts. In the CRI cohort, we evaluated correlations between PMR-AS items to select the best item for imputing CRP. Then we calculated the PMR-AS with (PMR-AS) and without (clin-PMR-AS) CRP and we used the linear regression between PMR-AS and clin-PMR-AS to obtain CRP-imputed (CRP-imp) PMR-AS. Finally, we evaluated agreement between clin-PMR-AS, CRP-imp PMR-AS, PMR-AS and ESR-PMR-AS in the TENOR cohort during tocilizumab therapy. Results In the CRI cohort, agreement between PMR-AS and clin-PMR-AS was excellent (κ = 0.90). Linear regression between PMR-AS and clin-PMR-AS [CRP-imp PMR-AS = 1.12(clin-PMR-AS)+0.26] allowed us to build the CRP-imp PMR-AS. Mean (s.d.) values were as follows: 8.40 (9.76) for PMR-AS, 7.24 (8.58) for clin-PMR-AS and 7.84 (9.61) for CRP-imp PMR-AS. CRP-imp PMR-AS agreed more closely with PMR-AS than did clin-PMR-AS. The results in the TENOR cohort confirmed that CRP-imp PMR-AS or ESR-PMR-AS could be used. Conclusion Alternatives to the PMR-AS obtained without CRP can be used to monitor PMR activity in everyday practice in patients without available CRP values and in those receiving IL-6 antagonist therapy.

Background New consensual classification criteria for primary Sjogren9s syndrome (pSS) have been recently developed and endorsed by ACR and EULAR. They differ substantially from previously used AECG criteria in that they consider systemic involvement (defined as ESSDAI score ≥1) as well as sicca symptoms as entry criteria before applying a weighted score. Evaluation of the concordance and differences between the two sets of criteria in independent patient populations is mandatory to establish how future clinical studies using the new criteria will be comparable to previously published studies. Major salivary gland ultrasonography (SGUS) has demonstrated promising diagnostic performance in previous studies, but was not included in these new classification criteria. Methods This cross-sectional study was conducted in the monocentric Brittany cohort (DIApSS cohort) of patients with suspected pSS (sicca symptoms, parotidomegaly or extraglandular manifestations suggestive of pSS). All patients had standardized clinical examination, basic biology, immunological tests and minor labial salivary gland biopsy. SGUS in mode B was performed by the same experienced operator, who was blinded to the diagnosis. Agreement between the two sets of criteria was assessed using Cohen9s κ coefficient and the characteristics of discordant patients were detailed. Results 290 patients were prospectively included between 2006 and 2016. Mean age was 55.6±13.2 years, 92.1% were female and mean duration of the symptoms 6.0±6.6 years. More patients fulfilled ACR/EULAR criteria (n=125, 43.1%) than AECG criteria (n=114, 39.3%). 114 patients (39.3%) fulfilled both criteria, 11 (3.8%) fulfilled ACR/EULAR only, 0 AECG only and 165 (56.9%) none of the criteria. Concordance between both criteria was good (kappa=0.9). Compared to patients fulfilling both criteria, patients fulfilling ACR/EULAR but not AECG criteria (n=11) had similar age, similar symptom duration, but less frequent sicca symptoms (eye dryness 18.2% versus 96.5%; mouth dryness 54.5% versus 97.4%, p Conclusions Agreement between AECG criteria and new ACR/EULAR criteria is good suggesting that they select quite similar patients. ACR/EULAR criteria display a slightly higher sensitivity and are able to detect more patients with systemic involvement, but some of these patients did not have pSS according to the physician diagnosis. As previously demonstrated for AECG criteria, SGUS inclusion into ACR/EULAR criteria may further enhance their sensitivity. Disclosure of Interest None declared

Background The ultrasonography of salivary glands (USSG) has proved its utility in diagnosing and following primary Sjogren patient9s (pSS) (1,2). The evaluation of disease activity is still of interest and can be studied by assessing the inflammatory status of SG using US Doppler. Objectives To evaluate the vascularization of salivary glands, and particularly the parotid gland (PG) using Pulsed Doppler color ultrasonography (USSGPD) in patients complaining of xerostomia before and after treatment by pilocarpine. Methods We prospectively included patients with objective dry mouth syndrome (using salivary flow rate) at Brest University Hospital (DiapSS cohort). The vascularization was assessed by the resistive index (RI) at the left parotid. Only patients with pathological RI ( Results Among the 19 patients included, 11 received pilocarpine treatment for the whole 3 months period, 6 of the 8 remaining patients stopped the pilocarpine due to side effects. Among the 11 patients with a follow-up evaluation at 3 months, 5 had pSS according to AECG criteria. The differences of RI before and after lemon stimulation were on average of -0.04 at baseline and -0.04 at M3. The sum of ultrasound9s grades average of the four glands was 3.47 at M0 and 4.18 at M3. The non-simulated salivary flow was on average of 1.96 mL/mn at M0 and 5.23 mL/mn at M3, whereas the average of stimulated salivary flow was 2.84 mL/mn at M0 and 8.51 mL/mn at M3. None of these observed differences were statistically significant before and after 3 months of treatment by Pilocarpine: RI before and after lemon stimulation (p=0.953), the sum of the four glands9 grades (p=0.858), the non-stimulated (p=0.26) and stimulated salivary flow (p=0.139). Concerning the 3 patients with Sjogren9s syndrome, there was no differences using RI before and after treatment but the RI was lower in this subgroup compared to the xerostomia patients.The study was marked by a large number of pilocarpine9s discontinuation (31%) due to adverse effects. Conclusions Preliminary results showed no significant differences between the 4 gland9s grade, ultrasound9s RI and salivary non and stimulated flow before and after three months of pilocarpine9s treatment. The vascularisation of salivary glands could be an opportunity to follow our treated patients with Sjogren9s syndrome or with xerostomia but more studies are needed to prove the interest of this procedure. References Cornec D, et al. Contribution of salivary gland ultrasonography to the diagnosis of Sjogren9s syndrome: toward new diagnostic criteria? Arthritis Rheum. 2013 Jan;65(1):216–25. Jousse-Joulin S et al. Brief Report: Ultrasonographic Assessment of Salivary Gland Response to Rituximab in Primary Sjogren9s Syndrome. Arthritis Rheumatol. 2015 Jun;67(6):1623–8. Acknowledgements We thank the Professor luc Bressollette and Muriel Korpet for their contribution in the study. Disclosure of Interest None declared

Objective The 2010 update of ASAS/EULAR recommendations for managing ankylosing spondylitis (AS) specify that continuous non-steroidal anti-inflammatory drug (NSAID) treatment should be preferred in patients with persistently active, symptomatic disease. Here, our objective was to assess whether continuous NSAID therapy improves disease control and influences radiographic progression compared to on-demand therapy. We also assessed the safety profiles of both regimens. Methods We performed a review by searching the PubMed and Embase databases using two MeSH term combinations to compare continuous and on-demand NSAID therapy in terms of disease control, radiographic progression, and safety. Results The only study evaluating the impact of continuous NSAID therapy on disease control showed no significant difference with on-demand therapy. In four studies, continuous treatment was associated with slower radiographic progression, as assessed in three studies using the modified Stoke Ankylosing Spondylitis Spinal Score (m-SASSS). Three studies compared the safety of continuous and on-demand celecoxib, two in osteoarthritis and one in AS, and found no significant differences regarding the usual side effects of Cox-2 inhibitors. Conclusions Several studies showed slower radiographic progression with continuous NSAID therapy in AS. No studies demonstrated superiority of continuous NSAID therapy regarding symptom control. Continuous NSAID therapy (at least with Cox-2 inhibitors) does not modify safety compared to on-demand therapy.

Primary Sjogren’s syndrome (pSS) is an autoimmune disease. Eleven classification or diagnostic criteria have been published for pSS since 1965. The American–European Consensus Group criteria have a better specificity than its predecessor; however, they have been criticized. New classification criteria for pSS were proposed by the ACR in 2012. The fact that two different criteria to classify patients with Sjogren’s syndrome could be available may introduce some difficulties. New criteria are being discussed by expert groups from the ACR and the European League Against Rheumatism to obtain consensual classification criteria. We describe the objective tests that are useful in practice for a positive diagnosis and assessment of pSS. Furthermore, we present other tests that might be included in future classification criteria.

International audience; OBJECTIVES: To assess the diagnostic value of minor salivary gland biopsy (MSGB) for primary Sjögren's syndrome (pSS). METHODS: Systematic review of studies retrieved from PUBMED and EMBASE using the terms 'salivary glands' AND 'Sjögren's syndrome' AND 'biopsy', conducted in patients with suspected pSS, and defining positive biopsies as a focus score (FS)≥1. Sensitivity and specificity of MSGB were abstracted from the articles or calculated when possible. RESULTS: Of 238 publications identified initially, 9 were included in the study. MSGB sensitivity ranged from 63.5% to 93.7% and specificity from 61.2% to 100%. Specificity was >89% in six studies. An attempt to separate patients with and without pSS without using MSGB findings or via clinical re-evaluation was made in only two studies, in 73 and 120 patients, respectively, with sicca syndrome in the first study and suspected pSS in the other. The reference standard for diagnosing pSS was a set of criteria that did not include MSGB in the first and patient re-evaluation by three experienced rheumatologists who were aware of MSGB findings in the other. In these studies, sensitivity was 63.9% and 85.7% and specificity was 91.9% and 89.7%, respectively. CONCLUSIONS: Few published studies have evaluated the diagnostic usefulness of MSGB in pSS. Only two studies used a methodology that precluded circular reasoning. Our study indicates a lack of information about the diagnostic value of MSGB. Specificity and positive predictive values (PPV) are high and sensitivity is variable.

Objectives Neurological manifestations seem common in primary Sjögren's syndrome (pSS) but their reported prevalences vary. We investigated the prevalence and epidemiology of neurological manifestations in a French nationwide multicentre prospective cohort of patients with pSS, the Assessment of Systemic Signs and Evolution in Sjögren's syndrome (ASSESS) cohort. Methods The ASSESS cohort, established in 2006, includes 395 patients fulfilling American–European Consensus Group criteria for pSS. Demographic and clinical data were compared between patient groups with and without neurological manifestations, and across patient groups with peripheral nervous system (PNS) manifestations, central nervous system (CNS) manifestations and no neurological manifestations. Results Data at inclusion were available for 392 patients, whose mean age was 58±12 years. Mean follow-up was 33.9 months. Neurological manifestations were present in 74/392 (18.9%) patients, including 63 (16%) with PNS manifestations and 14 (3.6%) with CNS manifestations. Prevalences were 9.2% for pure sensory neuropathy, 5.3% for sensorimotor neuropathy, 1.3% for cerebral vasculitis and 1.0% for myelitis. Neurological manifestations were associated with greater pSS activity as assessed using the ESSDAI (9.4±6.8 vs 4.3±4.8; p

Objectives Lyme disease may be considered by rheumatologists in patients with recent-onset arthritis, even in the absence of suggestive symptoms. The aim of this study was to determine the diagnostic impact of routine Lyme serology in a French cohort of patients with recent-onset arthritis affecting at least 2 joints. Methods We performed an ancillary study of a French prospective multicentre cohort established to monitor clinical, biological and radiographic data in patients with inflammatory arthritis in at least 2 joints, lasting for 6 weeks to 6 months. Borrelia IgM and IgG antibodies were sought routinely at baseline, using ELISA tests, independently from the physician's strategy for detecting a spirochetal infection. We recorded the proportion of patients with a final diagnosis of Lyme arthritis and evaluated the diagnostic performance of Lyme serology in this particular context. The clinical and biological characteristics of patients according to the Lyme serology results were analysed. Results Of 810 patients, 657 (81.1%) were negative for IgM and IgG antibodies, 91 (11.2%) had only IgM antibodies, 49 (6%) had only IgG antibodies, and 13 (1.6%) had IgG and IgM antibodies. Thus, 7.6% had IgG positivity, consistent with exposure to Borrelia infection. IgG positivity was significantly more prevalent in the North and North-East regions of France (χ2=14.6, p

Objectives To describe the clinical presentation, management and prognosis of patients diagnosed with both primary Sjogren's syndrome (pSS) and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Methods French nation-wide survey completed by a systematic literature review. Results This work identified 7 new cases of coexisting pSS and AAV: 2 microscopic polyangiitis (MPA), 2 granulomatosis with polyangiitis (GPA), 2 anti-myeloperoxidase (MPO)–ANCA renal-limited AAV, and 1 eosinophilic granulomatosis with polyangiitis (EGPA). The systematic literature search identified 15 previously published cases. Among the 22 patients, 19 were females. Mean age at diagnosis of AAV was 63.9 ± 9.8 years. All individuals with available information experienced at least one extra-glandular manifestation attributable to pSS. p-ANCA with anti-MPO specificity were found in 76.2% (16/21), c-ANCA with anti-PR3 specificity in 14.3% (3/21) and isolated c-ANCA in 13.6% (3/22). Vasculitis involved kidneys (n = 13), lungs (n = 8), skin (n = 6), peripheral nerves (n = 5), central nervous system (n = 2), small bowel (n = 1), muscle (n = 1), ear chondritis (n = 1) and sinuses (n = 1). The mean AAV follow-up was 73.5 (± 120.0) months. While on treatment, disease remission occurred in 77.3% of cases, and one death was reported in the first 6 months after diagnosis. Conclusion This work shows that AAV may occur in patients with pSS. These are most commonly p-ANCA associated vasculitis with anti-MPO specificity. AAV may reveal an underlying pSS or arise during its evolution, but did not precede pSS in any of these cases. AAV occurrence appears to be correlated with extra-glandular manifestations of pSS.

Objectives To determine the prevalence of eosinophilia in patients with recent-onset arthritis suggestive of rheumatoid arthritis (RA) and to describe their features and outcomes. Methods We performed an ancillary study of data from a French prospective multicentre cohort study monitoring clinical, laboratory and radiographic data in patients with inflammatory arthritis of 6 weeks to 6 months duration. We determined the proportion of patients with eosinophilia, defined as a count >500/mm3, at baseline and after 3 years. Features of patients with and without baseline eosinophilia were compared. Results Baseline eosinophilia was evidenced in 26 of 804 (3.2%) patients; their mean eosinophil count was 637.7±107/mm3. Baseline eosinophilia was ascribed to atopic syndrome in 6 of 26 (23.1%) patients. After 3 years, patients with eosinophilia had higher Health Assessment Questionnaire scores (0.9 vs 0.5, p=0.004), higher patient visual analogue scale activity score and morning stiffness intensity (p=0.05), and were more often taking disease-modifying antirheumatic drugs (p=0.02). Baseline eosinophilia was not associated with presence of extra-articular manifestations. Conclusions Eosinophilia is rare in recent-onset arthritis suggestive of RA, and is usually directly related to the rheumatic disease. Our data suggest that patients with mild eosinophilia at diagnosis could respond worse to the treatment than those without.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mardi 11 decembre 2012

Joint Bone Spine - In Press.Proof corrected by the author Available online since jeudi 26 juillet 2012

Background Primary Sjogren syndrome (pSS) is an autoimmune disease which may be associated to several systemic manifestations. Neurological manifestations seem to be frequent but prevalence is inconstant in literature (1). Objectives To assess neurological involvement prevalence in a national multi-center prospective cohort and to study epidemiological aspects of neurological involvement. Methods The ASSESS (Assessment of Systemic Signs and Evolution in Sjogren9s Syndrome) cohort is a French, multi-centre, prospective cohort, set up in 2006, including 395 pSS patients fulfilling American- European Consensus Criteria (AECG). Demographic and clinical data were compared between patients with and without neurological manifestations, and between patients with peripheral nervous system (PNS) manifestations, central nervous system manifestations (CNS) and no manifestations. Medical records of 26 patients with CNS manifestations and/or cranial nerve involvement were reviewed by both local investigator and our group to confirm or invalidate the association between pSS and the neurological manifestations. Results Data at inclusion were available for 392 patients. Mean follow-up was 33.8 months. Mean age at inclusion was 58 (±12) years. Mean age at diagnosis was 51 (±12) years. Seventy-four of 392 patients (65 females and 9 males) presented neurological manifestations (18.9%). Sixty-three had PNS manifestations (16%) and 14 had CNS manifestations (3.6%). Most frequent peripheral manifestations were pure sensitive neuropathy (9.2%) and sensory-motor neuropathy (5.3%). Only 2 patients (0.6%) had isolated ganglionopathy. Most frequent central manifestations were cerebral vasculitis (5 patients, 1.3%) and myelitis (4 patients, 1.0%) Patients with neurological involvement had more severe disease according to the ESSDAI scoring system, 8.9 (±6.6) versus 3.9 (±4.8). They had more frequently immunomodulatory/immunosuppressive drugs, 32.4% (24/74) versus 13.8% (44/318) (p=0003). Vasculitis was seen in 21 of 73 patients with neurological manifestations (28.8%) and in 30 of 318 patients without (9.4%) (p Conclusions The prevalence of neurological manifestations in the ASSESS cohort was about 20% and is comparable to data in the literature. Isolated ganglionopathy, which is frequently considered as the most specific neurological manifestation in pSS, was rare ( References Carvajal Alegria G et al. Joint Bone Spine. 2014 Jun 20 Disclosure of Interest None declared

Background Primary Sjogren9s syndrome (pSS) is a systemic autoimmune disease characterized by B-cell hyperactivation. In some patients, multiple autoantibodies develop, including anti-neutrophil cytoplasmic antibody (ANCA), which could lead to the development of ANCA-associated vasculitis (AAV). Objectives To describe clinical presentation, therapy and prognosis of patients diagnosed with both pSS and AAV. Methods Nation-wide survey in France collecting information on cases of AAV associated with pSS. The study was completed by a systematic review of the literature. Results This work identified 6 new cases of coexisting pSS and AAV: 2 microscopic polyangiitis (MPA), 2 MPO-ANCA renal-limited AAV, 1 granulomatosis with polyangiitis (GPA), and 1 eosinophilic granulomatosis with polyangiitis (EGPA). The systematic literature search identified 15 previously published cases. Among the 21 patients, 18 were females. Mean age at diagnosis of AAV was 64±10 years with mean pSS duration of 76±122 months. All individuals with pre-existent pSS experienced at least one extra-glandular manifestation attributable to pSS before AAV diagnosis. p-ANCA with anti-MPO specificity were found in 80% (16/20), c-ANCA with anti-PR3 specificity in 9.5% (2/20) and isolated c-ANCA in 14.3% (3/21). Vasculitis involved kidneys (n=13), lungs (n=6), peripheral nerves (n=5), skin (n=5), central nervous system (n=2), small bowel (n=1), muscle (n=1), and sinuses (n=1). The mean follow-up duration of AAV was 20.5 (±31.1) months. A favourable response to treatment was observed in 76.2% of cases (16/21), stabilization in 19% of cases (4/21) and one death was reported. Conclusions This work shows that AAV may occur in patients with pSS. These are most commonly p-ANCA associated vasculitis with anti-MPO specificity. The AAV may reveal an underlying pSS or arise during its evolution. In this latter case, its occurrence appears to be correlated with extra-glandular manifestations of pSS. Disclosure of Interest None declared

Background Osteoporosis (OP) is a frequent complication of ankylosing spondylitis (AS), even in early stages of the disease (1). Assessment of bone mineral density (BMD) remains complicated in these generally male and young patients and consequently, therapeutic indications and issues are not clear (2). Objectives The objective of this study is to assess the prevalence of low BMD and to detect the predictive clinical or biological parameters of OP in AS patients. Methods We searched Pubmed, EMBASE and Cochrane databases to perform a meta-analysis of prevalence of low bone mineral density in AS using data from new published observational studies or baseline data from longitudinal studies up to June 2014. The recommendations of PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) were applied (3). The outcome was the BMD measurement assessed with dual x-ray absorptiometry (DEXA) at the lumbar spine or femoral neck in absolute value or T-score. Our comparator population in case-control studies was composed by sex and age-matched healthy subjects. The standard difference in means between AS patients and controls were estimated using DerSimonian and Laird random-effects models. Results Fourty-six studies were included and concerned 3420 patients with AS. At the femoral neck, the mean BMD was at 0.813 g/cm 2 (IC95% 0.784 – 0.842 g/cm 2 ) with T-score at -1.055 SD (IC95% -1.325-0.785 SD). At the lumbar spine, the mean BMD was at 1.020 g/cm 2 (IC95% 0.999 – 1.040) with T-score at –0.904 SD (IC95% -1.085-0.723). BMD was correlated with age (p=0.02) and AS duration (p=0.007). None statistically significant correlation between BMD and gender (p=0.61), BASDAI (p=0.43), BASFI (p=0.51), CRP (p=0.32), ESR (p=0.64), Body Mass Index (p=0.68) was found. In 21 case-control studies, BMD in AS patients (n=1271) was significantly decreased comparing to control group (n=1858) at the femoral neck (-0.814±0.134; p Conclusions This first meta-analyses confirmed significant increase of low BMD at the femoral neck in patients with AS compared with age-and-sex-matched healthy controls. This difference disappears at the lumbar spine. Reflection about the OP, vertebral fracture assessment and about the benefit of the OP treatment in AS should be supported and should promote future prospective studies. References Will R, Palmer R, Bhalla AK et al. Osteoporosis in early ankylosing spondylitis: a primary pathological event? Lancet. 1989 Dec 23-30;2(8678-8679):1483-5. Karberg K, Zochling J, Sieper J et al. Bone loss is detected more frequently in patients with ankylosing spondylitis with syndesmophytes. J Rheumatol. 2005 Jul;32(7):1290-8. Moher D, Liberati A, Tetzlaff J et al; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.BMJ. 2009 Jul 21;339:b2535. Disclosure of Interest None declared

Background Congenital dislocation of the hip (CDH), which is one of the most common skeletal congenital anomalies, results from an abnormality of the seating of the femoral head in the acetabulum. Importance of misalignment of femoral head defines different phenotypes ranging from luxation to mild forms of acetabular dysplasia (AD). CDH is a multifactorial disease with a strong genetic component attested by ethnical predispositions and familial aggregation. Recently, several studies reported the association between functional polymorphism of the 59-untranslated region of GDF5 (Growth/Differentiation Factor 5) and CDH, a region that have also been reported to be associated with osteoarthritis. Objectives The main goal of our study was to assess whether GDF5 is associated with mild forms of AD in adult patients with hip osteoarthritis. Methods 131 Caucasian patients from the KHOALA (Knee or Hip Osteoarthritis Long Term Assessment) cohort with hip osteoarthritis were included in this study. All patients met both American College of Rheumatology and Kellgren and Lawrence (≥2) criteria for osteoarthritis. Patients underwent a morphological evaluation at both hips, based on standard anteroposterior and lateral X-rays. The morphological parameters retained here were the acetabular depth, VCE and HTE angles. Cut-off values to define AD were: VCE angle ≤20 °, HTE angle >12 °, or acetabular depth Results 45.8% (60/131) of patients had at least one morphological parameter consistent with AD. 29.8% (39/131) had abnormal HTE, 25.2% (33/131) had abnormal acetabular depth, and 17.6% (23/131) had abnormal VCE. The case-control study revealed a significant association between rs143383 variant and AD, when defined by insufficient acetabular depth. Individuals carrying CT genotype had a 5 fold higher prevalence of AD compared to those carrying CC genotype (95% CI: [0.95-35.63], p=0.030). Prevalence of AD was not significantly increased among patients carrying TT genotype (OR TT vs. CC =4.03, 95% CI: [0.72-29.33], p=0.138), whereas a significant association was observed under a dominant model (OR =4.57, 95% CI: 0.93-30.53], p=0.035). No significant association with out of range HTE and VCE values was observed. For each SNP, mean VCE, HTE, and acetabular depth values were compared among the three groups defined by their genotypes.For rs143383 variant, a significant difference in acetabular depth was observed among individuals presenting at least one morphological parameter consistent with AD (ANOVA: F =6.19, p=0.004 in the right hip and F =7.59, p=0.001 in the left hip). Conclusions This study confirms the association between GDF5 polymorphisms and CDH. It is the first publication to report an association between GDF5 and adult AD in context of hip osteoarthritis. Our results suggest an association between rs143383 and insufficient acetabular depth that should be assessed in further studies. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.2371

Background The minor salivary gland biopsy (MSGB) plays a preponderant role in the American European Consensus Group (AECG) criteria set for primary and secondary Sjogren’s syndrome (SS).However, its diagnostic value remains partially unclear and some authors have pointed out the lack of reproducibility of the results, and the lack of specificity of the test. Objectives To estimate the diagnostic value of MSGB for primary-SS, we performed a systematic review of published studies on MSGB for investigating SS. Methods PUBMED and EMBASE databases were searched. The following association of MeSh terms was used: “SJOGREN’S SYNDROME” in conjunction with “SALIVARY GLANDS” AND “BIOPSY”. All publications published between January 1966 and June 2011 were considered. Selected publications were screened for additional relevant studies. We selected studies that considered a Focus Score (FS) ≥1 (or equivalent) as cut-off for a positive biopsy and concerning patients addressed for suspected SS. Sensibility and specificity of MSGB were collected, or calculated when possible. Results From the 237 publications identified, 8 were finally included in the study (table 1). Among these 8 studies, sensitivity ranged from 63.5% to 93.7% and specificity from 61.2% to 100%. Specificity was >89% in 6 studies (Table 1). The differentiation between SS and non-SS patients was made without the help of MSGB or through a clinical reevaluation in only 2 studies. In these studies, sensitivity was respectively 63.9% and 85.7%, specificity was 91.9% and 89.7%. These 2 studies concerned 73 and 120 patients, evaluated for sicca symptoms in the first case and suspicion of primary-SS in the second. The gold standard for diagnosis of primary-SS was a set of criteria that did not include the MSGB in the first case and a reassessment of each patient by three experienced rheumatologists in the second (but not blinded to the MSGB). Conclusions Few studies are available in the literature to estimate the diagnostic value of MSGB for primary-SS. Only 2 studies used a methodology that avoids circular reasoning. Our study shows the lack of knowledge about the diagnostic value of MSGB, but confirm the good diagnosis value. The specificity of the test seems to be high, but the data about sensitivity is more heterogeneous. Disclosure of Interest None Declared

Background Early arthritis is often undifferentiated and may resolve spontaneously, remain undifferentiated, or progress to rheumatoid arthritis or to another chronic joint disease such as SpA. There is a need for improving the early diagnosis of ankylosing spondylitis (AS) and other spondyloarthritis (SpAs). Objectives To 1- assess the level of agreement between a SpA at baseline and 10 years later in a cohort of patients with recent-onset arthritis and 2- evaluate the ability of baseline clinical, laboratory, and radiographic features to predict a final diagnosis of SpA. Methods Patients with swelling of at least one joint between 1995 and 1997 were included. Ten years later, the physicians of each patient were contacted to determine the final diagnosis. Baseline pelvic radiographs were subjected to centralized blinded review. The statistical analysis used the chi-square test, Mann-Whitney test, and Cohen’s kappa coefficient. Results The diagnosis at baseline and 10 years later was known for 164 patients. At baseline, a diagnosis of SpA was suggested in 25 (15.2%) patients, of whom only 10 had a diagnosis of SpA 10 years later, in addition to 10 patients not diagnosed with SpA at baseline (20/164, 12.2%, Kappa=0.36±0.1). The 10-year diagnoses were ankylosing spondylitis (n=3), psoriatic arthritis (n=7), reactive arthritis (n=4), undifferentiated SpA (n=4), SAPHO syndrome, and Crohn’s disease (n=1). Of the 20 patients with a 10-year diagnosis of SpA, only 4 had inflammatory back pain at baseline (versus 11/144 non-SpA patients, p =0.72), 5 had psoriasis (versus 9/144 non-SpA patients, p =0.005), and 1 had uveitis ( p =0.12); 10 of the 20 SpA patients were HLA-B27-positive versus 8/144 non-SpA patients ( p Conclusions SpA is relatively rare and extremely challenging to diagnose in patients with early peripheral arthritis. Disclosure of Interest None Declared

Background Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular mortality and may therefore benefit from early atherosclerosis detection. Ankle brachial pressure index (ABPI) measurement can detect asymptomatic peripheral atherosclerosis, and isolated ABPI abnormalities can warrant treatment changes according to French recommendations. Objectives To evlauate the prevalence of ABPI abnormalities in RA in routine pratice. Methods We studied consecutive 100 patients meeting 1987 American College of Rheumatology criteria for RA when evaluated as inpatients or outpatients in November 2010 at a single rheumatology department. ABPI was measured routinely by a vascular physician. Patients were separated into three groups based on whether the ABPI was 1.3 (arterial stiffness). The three groups were compared using chi-square and Mann-Whitney tests. Results Of the 100 patients, 85 had normal ABPI values, 10 had DAF, and 5 had stiff arteries. Patients with DAF were older (69.1±12.6 years, P=0.002) and more often had a history of coronary artery disease (40%, P=0.004) compared to patients with normal arteries. The group with incompressible arteries had a larger proportion of patients with diabetes (40%, P=0.034) compared to the group with normal ABPI values. Conclusions The prevalence of DAF is relatively high in RA, especially in older patients. DAF is strongly associated with coronary artery disease in RA patients. Disclosure of Interest None Declared

BackgroundThe systemic antibody responses to SARS-CoV-2 in COVID-19 patients has been extensively studied. However, much less is known about the mucosal responses in the upper airways at the site of initial SARS-CoV-2 replication. Local antibody responses in the nasopharyngeal epithelium, that are likely to determine the course of infection, have not been analysed so far nor their correlation with antibody responses in serum.MethodsThe IgG and IgA antibody responses were analysed in the plasma as well as in nasopharyngeal swabs (NPS) from the first four COVID-19 patients confirmed by RT-qPCR in France. Two were pauci-symptomatic while two developed severe disease. Taking advantage of a comprehensive series of plasma and nasopharyngeal samples, we characterized their antibody profiles from the second week post symptoms onset, by using an in-house ELISA to detect anti-SARS-CoV-2 Nucleoprotein (N) IgG and IgA.ResultsAnti-N IgG and IgA antibodies were detected in the NPS of severe patients. Overall, the levels of IgA and IgG antibodies in plasma and NPS appeared specific to each patient.ConclusionsAnti-N IgG and IgA antibodies are detected in NPS, and their levels are related to antibody levels in plasma. The two patients with severe disease exhibited different antibody profiles that may reflect different disease outcome. For the pauci-symptomatic patients, one showed a low anti-N IgG and IgA response in the plasma only, while the other one did not exhibit overt serological response.