R.-M. Javier

Campylobacter fetus infection in three rheumatoid arthritis patients treated with rituximab

Campylobacter fetus osteoarticular or prosthetic material infection or cellulitis has been rarely described, mainly in immunocompromised patients. Among these cases, only two patients had inflammatory systemic diseases treated with rituximab (RTX).1 We report three patients with rheumatoid arthritis (RA) treated with RTX who developed osteoarticular or cutaneous infection due to C fetus . The patients were aged 71, 53 and 80 years with disease durations of 24, 13 and 19 years, respectively. All patients had a history of diabetes. Patients 1 and 3 had hypertensive cardiomyopathy, while patient 2 suffered from chronic obstructive pulmonary disease (COPD) and patient 3 from bronchiolitis obliterans organising pneumonia. All patients were co-treated with corticosteroids (10 mg/day) and disease-modifying antirheumatic …

AB0671 Vitamine D Serum Level Correlates with Quadriceps Muscle Strength in Inflammatory Myositis

Background Vitamin D has been involved in both inflammation and muscle strength. Inflammatory myopathies are characterized by muscle inflammation and weakness. Objectives We assessed whether vitamin D serum level is linked to muscle strength during inflammatory myopathies. Methods Fourteen consecutive patients with inflammatory myopathies (with the exclusion of inclusion boy myositis) were prospectively included. Muscle strength was recorded on dominant quadriceps using hand held dynamometer. 25-OH-vitamin D3 level was measured on a blood sample at the same time. Results Characteristic of the patients: 9 women and 5 men with a median age of 53.5 (13-71) were included. Duration of mysoitis at the time of muscle strength was 29 months (3-68). 11 patients were treated at the time of quadriceps strength measurements (corticosteroids n=11, methotrexate n=9, mycophenolate mofetil n=2, intraveinous immunoglobulin n=5). Vitamine D levels and quadriceps muscle strength: Median 25-OH-vitamine D3 level was 17.80μg/L (10.2-38.3) and median quadriceps strength (expressed as the percentage of the mean value recorded in healthy volunteers of the same age and sex) was 65% (14-107). 25-OH-vitamine D3 correlated with quadriceps muscle strength (figure: Spearman R =0.68, 95%CI: 0.22-0.89, p<0.01). Conclusions Our data suggests that vitamin D is involved in muscle strength during inflammatory myopathies. 25-OH-vitamin D3 might be monitored in these patients not only with the aim of protecting bone during corticosteroids treatments but also with the objective of improving muscle strength. Disclosure of Interest None declared

FRI0167 Anti-TNF do not modify the interferon signature in patients with rheumatoid arthritis and lupus (“rhupus”)

Background We recently reported the clinical efficacy and safety of anti-TNF-alpha in a cohort of 15 rhupus patients with rheumatoid arthris and systemic lupus (“rhupus”). TNF-alpha and type I interferon (IFN) were reported to be crossregulated in a gene expression study of patients with juvenile idiopathic arthritis. Treating with anti-TNF these patients could raise the concern of a potential overexpression of IFN-inducible genes and chemokines, which play a pathogenic role in SLE. Objectives To evaluate changes in levels of IFN-inducible genes and chemokines under treatment with anti-TNF for RA associated with SLE. Methods Among the 15 patients with RA and SLE, PBMCs and serum were collected before and after anti-TNF initiation (median: 8 months) in 6 patients. Total RNA was extracted from PBMC using the Nucleospin RNA II extraction kit according to the manufacturer’s instructions and reverse transcribed using the First Strand cDNA Synthesis Kit according to the manufacturer’s instructions (In Vitrogen). Real-time quantitative RT-PCR was performed in a total volume of 20 μl using SensiMix Plus SYBR kit (Quantace, Corbett Life Science)and gene specific primers for BAFF, IFTIMMX-1,PKR. Serum CXCL10, CCL2 and CCL19 levels were assessed using R&D ELISA. Results All 15 patients were women with a mean age of 51 years [20-75]. The mean duration of treatment was 34.7 and 33.7 (4-69) months with etanercept and adalimumab, respectively. 8.3 infections for 100 patient years occurred. No mycobacteria infection, no lymphoproliferation and no cancer were observed. Also, no cutaneous, renal or other systemic flare of SLE occurred. No death was observed. After 2 years of follow-up, the mean decrease of DAS 28 and SLEDAI was -3 [-0.75 to -4.89] -5.13 [0 – 6], respectively. Corticosteroid dosage significantly decreased from 10mg/d to 5mg/d. No statistical significant increase in gene expressions of 4 different IFN-inducible genes, BAFF (2.2 to 0 fold), MX1 (17.2 to 0 fold), IFITM (1.2 to 0 fold), and PKR (19.3 to 0 fold) Likewise, no significant change was observed in serum levels of 3 IFN-inducibles chemokines: CXCL10 (82 to 56.2 pg/ml, p=0.87), CCL2 (343.8 to 729.4 pg/ml, p=0.375) and CCL19 (316.3 to 335.9 pg/ml, p=0.875). Conclusions This study shows good short term tolerance and efficacy of anti-TNF in patients with SLE and RA (“rhupus”). The absence of increase in IFN-inducible genes and chemokines, which are validated prognostic markers of disease activity in SLE, might contribute to the absence of SLE flares observed in rhupus patients treated with anti-TNF. Disclosure of Interest None Declared

THU0412 Reactive hyperemia index (RHI) is associated with macrovascular disease and lung disease in systemic sclerosis

Background Vasomotor endothelial function is an emerging data in functional exploration. Its meaning is well established in cardiology, where it independently predicted the occurrence of cardiovascular events. It interest has been poorly assess in rheumatology. Recently it was shown that patients with rheumatoid arthritis (RA) and systemic sclerosis (SS) have impaired endothelial function compared to controls. In the SS, endothelial function was correlated with the microvascular disease observed in capillaroscopy (1,2). Methods Reactive hyperhemia index (RHI), a simple, reliable and non invasive method for endothelial function exploration (3), taken at the estimated maximal vasodilatation (1 min 30 s after release of occlusion) using digital pulse amplitude tonometry was performed on 21 patients with SSc, 14 patients with IR and 15 healthy subjects. In IR and SSc patients, DAS 28, Rodnan score, cardiac echography, spirometry, DLCO and 6 minute walk test were also performed. Results Characteristics of the 3 groups: Mean age of SSc was 57 years (28-75), sex ratio (SR) was 5/1 and mean disease duration was 4.5 years (0-22). 11 patients had limited form and 7 had diffuse form. The mean Rodnan score in 13 of 18 SSc patients was 10.2 (4-28). IA patients had a mean age of 60 years (38-73) and SR was 6/1. 11 patients had RA, 1 spondylarthropathy, one antisynthetase syndrome and one myositis with SRP antibody. Mean IR duration was 16 years (0-31). Mean DAS 28 in 11 of 14 IR patients was 4.45 (2.03-6.66) and 8 patients were treated with biologic treatments. Controls were 57 years old (53-64) and SR was 6/1. Patients mean weight was comparable: 67 kg (45-106), 67 kg (54-79) and 64 kg (54-91) in SSc, PR and controls respectively. Mean blood pressure was also similar (SSc: 127/73mmHg, PR: 128/76mmHg and controls: 130/75mmHg in SSc). One IR patient suffered of diabetes mellitus and had history of heart infarct. Results: Median RHI was significantly lower in SSc patients (median 1.45, range 1.00-3.18) compared with IA patients (median 2.01, range 1.35-3.02) (p=0.03) and was significantly lower in both SSc and IA patients compared with controls (median 2.60, range 1.40-3.05) (p=0.001 and p=0.049 respectively). In SSc patient but not in IA patients, RHI value significantly correlated with echocardiograhic PAPs (r: -0.75; p=0.037), DLCO (r: 0.53; p=0.017), total pulmonary capacity (r: 0.46; p=0.032), functional and maximal vital capacity (r: 0.48; p=0.032 and r: 0.48; p=0.033 respectively). Conclusions RHI, an easy and non invasive test, is associated with macroangiopathy and lung involvement in SSc. Further studies are necessary to determine whether RHI may represent disease activity and therapeutic response marker. References Rollando et al. J Rheumatol. 2010;37:1168-73. Hannawi et al. Arthritis Res Ther. 2009;11:R51. Hamburg et al. Trends Cardiovasc Med. 2009;19:6-11. Disclosure of Interest None Declared

AB0779 Eosinophilic myositis and rheumatoid arthritis as first manifestation in a patient carrying myotonic dystrophy type 2 (CCTG)n expenssion of ZNF9 gene

Background Eosinophilia myopathies (EM) are a heterogeneous group of disease characterized by eosinophlic infiltration muscles associated with peripheral blood and/or bone marrow hypereosinophilia. The diagnosis of idiopathic EM is usually retained after the exclusion of accepted EM aetiologies. Recently, mutations in the CAPN3 and SGCG genes, encoding calapain-3 and γ-sarcoglycan proteins, were identified in some patients with idiopathic EM. Objectives We report the first case of a patient with idiopathic EM and rheumatoid arthritis (RA) who carried CCTG expansion in intron 1 of the ZNF9 gene, a mutation characteristic of myotonic dystrophy type 2 (DM2). Results A 40 years old woman presented with arthromyalgia for 4 months. She had a 18 months history of hypereosinophilia. Physical examination showed a symmetrical oedematous polyarthritis. Proximal muscles were painful but there was no muscle weakness. Eosinophilic polynuclear count was 8,210/mm3. CRP amount was 11mg/L. Serum creatine kinase level was 406 IU/L. Serum tested positive for anti-citrullinated protein antibodiesand rheumatoid factor. There was no anti nuclear antibody nor ANCA. Fecal examination didn’t found any parasite. Serological tests for T spiralis, T canis, A lubricoides, E histolytica, A fumigatus, E granulosus, and VIH were negative. Osteomedular biopsy showed hypereosinophilc infiltration (30%). Karyotype on myelogram was normal. Molecular analysis didn’t detected Philadelphia chromosome, mutation in JAK2, KIT, PDGFRs genes nor clonal TCR rearrangement. Foots and hands radiographs, tomography of chest abdomen and pelvis, electrocardiogram and cardiac echography found no abnormality. Electromyography showed myogenic features. Muscle biopsy is presented on figure n°1. The diagnosis of idiopathic ME associated with RA was retained. The patient was successfully treated with non steroidal anti inflammatory drugs and methotrexate Ten years after, a patient’s sister was diagnosed with DM2. Quadruplet repeat primed-PCR performed on the patient’s blood sample found CCTG expansion in intron 1 of the ZNF9 gene. Expansion size measured with southern blot was 8 kb. At this time, there was no muscular symptom but a diabetes had appeared. Conclusions DM2 is typically characterized by muscle weakness, myotonia, cataract and diabetes but increasingly, incomplete or atypical phenotypes are encountered. A strong incidence of autoimmune diseases, including RA, was reported in DM2 patients. In this observation, EM symptoms disappeared with immunomodulatory therapy, that argue for an authentic immunologic driven process. One explanation might be that, contrary to calpainopathies and sarcoglycanopathies, genetic lesion in DM2 does not eliminate an essential muscle protein. Instead, it induces a defect of RNA processing that may impact many different pathways including inflammation. EM with RA might be inaugural manifestations of DM2. Disclosure of Interest None Declared

THU0064 Clinical signification of anti-ku antibody

Background The Ku autoantigen is a DNA binding factor consisting of 70 and 80 kDa protein which form a heterodimer involved in repair of ds DNA breaks. Since the original description of anti-Ku antibody in patients with polymyositis-scleroderma overlap syndrome, this antibody has been showed to be associated with several autoimmune diseases. Objectives To describe clinical features of 8 patients with anti-KU antibody. Methods ResultsAbstract THU0064 Table 1 Patient 1 2 3 4 5 6 7 8 Age (years) 28 40 44 30 66 41 67 74 ENA (ELISA) Ku/Ro Ku Ku/RNP/JO1 Ku Ku/proteinase3 Ku Ku Ku Clinical features Digital vasculitis Sicca syndrome, polyarthritis Myalgia, pulmonary fibrosis, sclerodactylia, raynaud’s phenomen Raynaud’s phenomen Extra-capillar glomerulonephritis, polyarthralgia, rectal carcinoma Polyarthritis Bronchopneumonia, Pulmonary embolism Hand’s oedema, prostatic cancer Diagnosis Lupus Sjögren syndrome Myositis-scleroderma Raynaud Wegener granulomatosis Rheumatoid arthritis Chronic obstructive lung disease Prostatic cancerRS3PE ? Conclusion anti-Ku antibody is not specific of a connective tissu disease and can also be observed in patients without any autoimmune disease (n°7). In addition to previous described association, anti-Ku antibody can also be present in Wegener granulomatosis and idiopathic Raynaud’s phenomen. Two of our patients had an evaluative cancer (n°5 and 8) and one (n°7) presented a stomach neoplasm 3 years before the detection of anti-Ku antibody. This finding needs further investigations to assess if anti-Ku antibody can be associated with or predictive of a neoplasm.