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Background Dilated cardiomyopathy (DCM), a well-known complication of cardiac neonatal lupus, is associated with high mortality rate. Its risk factors remain unclear. Methods We analyzed occurrence of postnatal DCM among children with high-degree congenital heart block (CHB) and mothers with anti-SSA and/or anti-SSB antibodies. Results Among 187 neonates with CHB, 35 (18.8%, one missing data) had DCM and 22 (11.8%) died during a median follow-up of 7years [range: birth–36years]. On multivariate analysis, factors associated with postnatal DCM were in utero DCM ( P =0.0199; HR=3.13 [95% CI: 1.20–8.16]), non-European origin ( P =0.0052; HR=4.10 [95% CI: 1.81–9.28]) and pacemaker implantation ( P =0.0013; HR=5.48 [95% CI: 1.94–15.47]). Postnatal DCM could be categorized in two subgroups: neonatal DCM (n=13, diagnosed at a median age of 0day [birth–4days]) and late-onset DCM (n=22, diagnosed at a median age of 15.2months [3.6months–22.8years]). Factors associated with neonatal DCM were in utero DCM, hydrops, endocardial fibroelastosis and pericardial effusion, whereas those associated with late-onset DCM were non-European origin, in utero mitral valve insufficiency, and pacemaker implantation. Fluorinated steroids showed no protective effect against late-onset DCM ( P =0.27; HR=1.65 [95% CI: 0.63–4.25]). Probability of survival at 10years was 23.1% for newborns diagnosed neonatally with DCM, 53.9% for those who developed late-onset DCM, and 98.6% for those without DCM. Conclusion Neonatal and late-onset DCM appear to be two different entities. None of the known risk factors associated with neonatal DCM predicted late-onset DCM. Long-term follow-up of cardiac function is warranted in all children with CHB.

Cardiac neonatal lupus syndrome is due to anti-SSA or SSB antibodies and mainly includes congenital heart block (CHB) and dilated cardiomyopathy (DCM). Its optimal management is still debated. We report a large series of autoimmune high degree CHB.Inclusion criteria in this retrospective study were fetuses or neonates with high-degree CHB associated with maternal anti-SSA/SSB antibodies.214 CHB were included: 202 detected in utero at a median term of 23 weeks' gestation (WG) [range 16 to 39 WG] and 12 neonatal cases diagnosed at a median age of 0 days [range birth to 8 days]. The 214 cases of CHB included 202 (94.4%) third-degree CHB, 8 (3.7%) second-degree CHB, and 4 (1.9%) intermittent CHB. In multivariate analysis, the factors associated with feto-neonatal deaths (15.7%) were hydrops (p0.001; hazard ratio [HR] 12.4 [95% confidence interval (95%CI) 4.7-32.7]) and prematurity (p=0.002; HR 17.1 [95%CI 2.8-103.1]). During a median follow-up of 7 years [birth to 36 years], 148 of 187 children born alive (79.1%) had a pacemaker, 35 (18.8%, one missing data) had DCM, and 22 (11.8%) died. In multivariate analysis, factors associated with child death were in utero DCM (p=0.0157; HR 6.37 [95%CI: 1.25-32.44]), postnatal DCM (p0.0001; HR 227.58[95%CI: 24.33-2128.46]) and pacemaker implantation (p=0.0035; HR 0.11[95%CI: 0.02-0.51]). The use of fluorinated steroids was neither associated with survival nor with regression of 2nd degree CHB.In this second largest series of CHB, we confirm some of the previous results. We were unable to find data supporting the routine use of in utero fluorinated steroids.

Primary Sjögren's syndrome is a systemic autoimmune disease, characterized by a lymphocytic exocrinopathy. Oral and ocular dryness, asthenia and pain represent hallmarks of the disease. Systemic manifestations concern a third of patients, including lymphoma in 5% of the patients. The American European Consensus Group classification criteria have been used in current practice and clinical trials since 2002. New classification criteria were recently proposed by the American Congress of Rheumatology. A group of international experts are currently working to reach a new consensus between the American European Consensus Group classification criteria and the American Congress of Rheumatology proposal for disease classification. In addition, international consensus disease activity scores were recently established. Regarding treatment modalities, symptomatic treatments remain the cornerstone of therapy in pSS, but new biologic treatments are currently evaluated.

Antisynthetase syndrome (ASS) is a rare systemic inflammatory disease associated with myositis, polyarthritis, interstitial lung disease, Raynaud’s phenomenon and the presence of auto-antibodies targeting aminoacyl-tRNA-synthetase enzymes [1]. We recently diagnosed amyloidosis in one patient with ASS. To better characterize this unusual association, we retrospectively assessed amyloidosis frequency in a monocentric cohort of 30 patients with ASS and performed a systematic review of the literature. The charts of the patients followed at Strasbourg University Hospital who serum tested positive for aminoacyltRNA-synthetase antibody using immunodot (Euroimmun, Germany and/or D-Tek, Belgium) between 1994 and 2011 were systematically reviewed. Patients were diagnosed with ASS if they had myositis according to Bohan and Peter criteria [2] and/or interstitial lung disease (ILD) diagnosed on chest computed tomography (CT). Diagnosis of amyloidosis was made if extracellular deposit stained with Congo Red was demonstrated in a biopsy. Monoclonal mouse antibodies against human AA protein, polyclonal rabbit antibodies against κ and λ light chains used for amyloidosis typing were purchased from Dako, Denmark. Thirty-three patients tested positive for aminoacyl-tRNAsynthetase antibodies. Charts were available for 30 patients who all had ASS. Patients tested positive for PL-7 (n = 4), PL-12 (n = 4), Jo-1 (n = 22) antibodies. Median follow-up was 6 years (range 1 month–16 years). Amyloidosis occurred in two patients with ASS.

Recently, the use and evaluation of biologics increased in systemic lupus erythematosus (SLE). However, no international recommendation is available concerning the use of biologics with regards to the subset of patients who should be treated, the optimal time to treat, the objective of treatment and the manner to discontinue it. To address these complex questions, we focused on biologics already evaluated in at least two published randomized controlled trials. We summarized the results of these trials and available observational data in registries. Taking into account the clinical evidence, we proposed some guidance on the way biologics could be used in SLE. Many areas of uncertainty persist and require intensifying efforts from the academic world to set up new trials, and develop international recommendations.

Chronic meningococcaemia is an unusual clinical presentation of Neisseria meningitidis infection. We describe the case of a patient, who presented with total IgA deficiency and partial IgM deficiency with a low switched memory B cells count, suggestive of a borderline form of common variable immunodeficiency (CVID). The role of IgA in the protection against Neisseria meningitidis, and the link between IgA deficiency and CVID are discussed.

Background Neonatal lupus syndrome (NLS) includes congenital heart block (CHB) and cardiomyopathies. Its optimal management is debated. Objectives We analyzed the mortality and morbidity of CHB, with special focus on risk factors. Methods This was a retrospective study of the French national registry of NLS. Inclusion criteria were high-degree CHB associated with maternal anti-SSA/SSB antibodies. Results 214 CHB were included (202 in utero cases and 12 neonatal cases). These 214 fetuses or children were born to 195 mothers anti-SSA (99.5%) and/or anti-SSB antibodies (60%) positive. 51 mothers (26.2%) fulfilled the classification criteria for an autoimmune disease: systemic lupus erythematosus (n=23), Sjogren syndrome (n=14), undifferentiated connective tissue disease (n=7), or other autoimmune disease (n=7). The factors associated with feto-neonatal deaths (15.7%) were hydrops (p During a median follow-up of 7 years [birth to 36.1 years], 148 of 187 surviving children (79.1%) had a pacemaker, 35 (18.8%, one missing data) had dilated cardiomyopathy (DCM), and 22 (11.8%) died. DCM was neonatal (n=13) or late-onset (n=22, diagnosed at a median age of 15.2 months [3.6 months-22.8 years]). Factors associated with neonatal DCM were maternal treatment with hydroxychloroquine, in utero cardiomegaly, in utero DCM, and hydrops. By contrast, only non-white race origin and significant in utero valvulopathy were associated with late-onset DCM. On multivariate analysis, only in utero DCM was associated with neonatal DCM (p=0.0001; HR 15.99 [95%CI: 3.93-65.01]), whereas non-white race origin was associated with late-onset DCM (p=0.0147; HR 3.65 [95%CI: 1.28-10.0]). For children who survived the neonatal period (n=179), the risk of death during follow-up was 7.8%. On multivariate analysis, the only factor associated with late mortality was postnatal DCM (neonatal and late-onset DCM) (p Fluorinated steroid in utero treatment was not associated with CHB regression, survival or absence of late-onset DCM. Conclusions The factors associated with late-onset DCM differ completely from those associated with neonatal DCM. Our findings do not support the use of fluorinated steroids for CHB. Disclosure of Interest None declared

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 …

Revue du rhumatisme - In Press.Proof corrected by the author Available online since samedi 25 janvier 2014

Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 1 mars 2014

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

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

Background Anti-Jo-1 has been negatively associated with cancer. Accordingly, only few reports described the co-existence of anti-Jo-1 positive myositis and malignancy. Despite the apparent rarity of this association, Jo-1 has been shown to be over express by a variety of tumors and it has been proposed that this could lead in some cases to tolerance breakdown. Methods We retrospectively determined the frequency of cancer-associated myositis (CM) in a cohort of 20 anti-Jo-1 positive myositis diagnosed between January 1st 1994 and January 1st 2011 at the Strasbourg University Hospital were reviewed. CM was defined as cancer occurring within the 3 years of myositis diagnosis and, if the cancer is cured, the cure of the myositis as well (as per the modified Bohan and Peter classification of Troyanov et al. (6). To better address the question of a fortuitous or a paraneoplasic link between cancer and anti-Jo-1 positive myositis, we assessed the expression of Jo-1 in available tumor and healthy tissues by immunohistochemistery with monoclonal anti-Jo-1 antibody (Abcam). Results A CM was diagnosed in one patient (5%). A 55 year old woman, smoker, presented a antisynthetase syndrome complicated with myocardial injury. After 3 solumedrol bolus, oral corticosteroids (1.5 mg/kg/day), mycophenolate mofetil (2 g/d) infusion of rituximab (1g) and an infusion of immunoglobulins (2 g/kg), evolution was only mildly favorable. Concomitantly, a nodule of the right breast was found, the biopsy revealed an infiltrating ductal carcinoma. There was no other location. Right mastectomy was performed, followed by chemotherapy, radiotherapy and hormone therapy. Within 4 weeks following surgery, the symptoms disappeared dramatically. 6 months after the mastectomy all immunomodulatory therapy, including corticosteroids, was stopped. 1 year after stopping treatment, myositis was still in remission. Immunohistochemical study of the specimen showed an overexpression of Jo-1 in the cytoplasm of tumor cells compared to normal cells. Conclusions It cannot be ruled out that chemotherapy had an immunomodulatory effect by itself on myositis. anti-Jo-1 myositis were characterised by a chronic course and all patients relapsed within the year following the steroid taper to 5mg or less (7). One year and half after the stop of cortiocosteroids therapy, our patient myositis was still in remission. Moreover, Jo-1 antibodies disappeared. All together, these data suggest that anti-Jo-1 positive myositis was an authentic paraneoplasic syndrome in this patient. For the first time, we studied expression of Jo-1 antigen in a patient with anti-Jo-1 positive CM. Immunohistochemistery assays showed that Jo-1 was over expressed in tumor cells. This result corroborates the hypothesis of a triggering role of the tumour on autoimmune process. The positivity of Jo-1 antibodies may not be an exclusion criterion for the diagnosis of cancer-associated myositis. A thorough age-appropriate malignancy work up may be indicated in all patients with a new diagnosis of myositis, despite the presence of anti-Jo-1 antibodies. Disclosure of Interest None Declared