M. Almirall

Alopecia areata as another immune-mediated disease developed in patients treated with tumour necrosis factor-α blocker agents: Report of five cases and review of the literature.

Background  Tumour necrosis factor antagonists (anti‐TNF‐α) have demonstrated the efficacy in different chronic immune inflammatory disorders. Within the spectrum of adverse events, autoimmune diseases have been observed, including cases of alopecia areata (AA).

Rapid reduction in tenosynovitis of the wrist and fingers evaluated by MRI in patients with rheumatoid arthritis after treatment with etanercept

Objective To assess the efficacy of etanercept in reducing tenosynovitis evaluated by MRI of the hand (h-MRI) in patients with active rheumatoid arthritis (RA) refractory to disease-modifying antirheumatic drug (DMARD) after 6 weeks of treatment. Methods 31 patients with active RA defined by a disease activity score (DAS28) >3.2 and synovitis in the hands were randomised into two groups: 19 patients received 50 mg weekly subcutaneous etanercept added to previous DMARD treatment and 12 patients continued with previous DMARD therapy. Clinical evaluation, blood tests, functional capacity evaluation and h-MRI were performed at the start of the investigation and at week 6. Tenosynovitis was evaluated on T1-weighted sequences with fat suppression after gadolinium as the presence of a peritendinous signal enhancement on axial images using a new method including wrist and finger tendons. The reliability, sensitivity to change and responsiveness of this method were also evaluated. Results Scores for tenosynovitis showed a significant reduction in the etanercept group compared with placebo (p=0.01) after 6 weeks of treatment. Adding MRI joint synovitis to tenosynovitis scores gave an even higher significant reduction in the etanercept group (p=0.007). A positive and statistically significant correlation between tenosynovitis and DAS28, erythrocyte sedimentation rate and C-reactive protein was found, but not with functional capacity. Responsiveness for tenosynovitis was small but was higher when joint synovitis scores were added. Conclusion Addition of etanercept significantly reduced MRI tenosynovitis of the wrist and fingers in patients with active RA refractory to DMARD treatment. The method of scoring tenosynovitis showed good reliability and moderate responsiveness.

Association of Bone Edema with the Progression of Bone Erosions Quantified by Hand Magnetic Resonance Imaging in Patients with Rheumatoid Arthritis in Remission

Objective. To evaluate the association of synovitis, bone marrow edema (BME), and tenosynovitis in the progression of erosions quantified by hand magnetic resonance imaging (MRI) at 1 year in patients with early rheumatoid arthritis (RA) in remission. Methods. A total of 56 of 196 patients with early RA in remission at 1 year and with available MRI data at baseline and at 12 months were included. MRI images were assessed according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) system. Persistent remission was defined as 28-joint Disease Activity Score-erythrocyte sedimentation rate ≤ 2.6 and/or Simplified Disease Activity Index ≤ 3.3 and/or the new boolean American College of Rheumatology/European League Against Rheumatism remission criteria for a continuous period of at least 6 months. Progression of bone erosions was defined as an increase of 1 or more units in annual RAMRIS score for erosions compared to baseline. Results. At 1 year, the majority of patients with RA in sustained remission showed some inflammatory activity on MRI (94.6% synovitis, 46.4% BME, and 58.9% tenosynovitis) and 19 of the 56 patients (33.9%) showed MRI progression of bone erosions. A significant difference was observed in MRI BME at 1 year, with higher mean score in patients with progression compared to nonprogression of erosions (4.8 ± 5.6 and 1.4 ± 2.6, p = 0.03). Conclusion. Subclinical inflammation was identified by MRI in 96.4% of patients with RA in sustained clinical remission. Significantly higher scores of BME after sustained remission were observed in patients with progression of erosions compared to patients with no progression. The persistence of higher scores of BME may explain the progression of bone erosions in patients with persistent clinical remission.

Variation at interleukin-6 receptor gene is associated to joint damage in rheumatoid arthritis.

IntroductionInterleukin-6 (IL-6) cytokine signaling is key in Rheumatoid Arthritis (RA) pathophysiology. Blocking IL-6 receptor (IL6R) has proven to be a highly effective treatment to prevent joint damage. This study was performed to investigate the association between the genetic variation at IL6R gene and the severity of joint damage in RA.MethodsIL6R gene tagging SNPs (n = 5) were genotyped in a discovery group of 527 RA patients from 5 different university hospitals from Spain. For each marker, a linear regression analysis was performed using an additive model and adjusting for the years of evolution of the disease, autoantibody status, gender and age. Haplotypes combining the SNPs were also estimated and tested for association with the level of joint destruction. Using an independent cohort of 705 RA patients from 6 university hospitals we performed a validation study of the SNPs associated in the discovery phase.ResultsIn the discovery group we found a highly significant association between IL6R SNP rs4845618 and the level of joint destruction in RA (P = 0.0058, Pcorrected = 0.026), and a moderate association with SNP rs4453032 (P = 0.02, Pcorrected = 0.05). The resulting haplotype from both SNPs was more significantly associated with joint damage (P = 0.0037, Pcorrected = 0.011). Using the validation cohort, we replicated the association between the two IL-6R SNPs with the degree of joint destruction in RA (P = 0.007 and P = 0.04, meta-analysis P = 0.00011 and P = 0.0021, respectively), and the haplotype association (P = 0.0058, meta-analysis P = 6.64 e-5).ConclusionsGenetic variation at IL6R gene is associated with joint damage in RA.

Síndrome poliadenopático en lupus eritematoso sistémico: ¿es la enfermedad de Kikuchi-Fujimoto?

Lymphadenopathy syndrome is a common manifestation of systemic lupus erythematosus (SLE). In general, enlarged lymph nodes are small and can be found in the cervical, inguinal and axillary regions. Lymph node involvement is present in up to 25% of the patients and normally appears in the first stages of the disease or during relapses.1 The differential diagnosis of lymphadenopathy syndrome in SLE includes histiocytic necrotizing lymphadenitis or Kikuchi-Fujimoto disease (KFD), Castleman’s disease, syphilis, tuberculosis, sarcoidosis, infectious mononucleosis (Epstein–Barr virus [EBV], cytomegalovirus), herpes simplex, human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), other infections and lymphoma.2 Kikuchi-Fujimoto disease, or histiocytic necrotizing lymphadenitis, is a rare clinical disorder characterized by lymph node involvement (generally cervical), fever, night sweats and

ACR/EULAR Definitions of Remission Are Associated with Lower Residual Inflammatory Activity Compared with DAS28 Remission on Hand MRI in Rheumatoid Arthritis

Objective. To determine the level of residual inflammation [synovitis, bone marrow edema (BME), tenosynovitis, and total inflammation] quantified by hand magnetic resonance imaging (h-MRI) in patients with rheumatoid arthritis (RA) in remission according to 3 different definitions of clinical remission, and to compare these remission definitions. Methods. A cross-sectional study. To assess the level of residual MRI inflammation in remission, cutoff levels associated to remission and median scores of MRI residual inflammatory lesions were calculated. Data from an MRI register of patients with RA who have various levels of disease activity were used. These were used for the analyses: synovitis, BME according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system, tenosynovitis, total inflammation, and disease activity composite measures recorded at the time of MRI. Receiver-operating characteristic analysis was used to identify the best cutoffs associated with remission for each inflammatory lesion on h-MRI. Median values of each inflammatory lesion for each definition of remission were also calculated. Results. A total of 388 h-MRI sets of patients with RA with different levels of disease activity, 130 in remission, were included. Cutoff values associated with remission according to the Simplified Disease Activity Index (SDAI) ≤ 3.3 and the Boolean American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) definitions for BME and tenosynovitis (1 and 3, respectively) were lower than BME and tenosynovitis (2 and 5, respectively) for the Disease Activity Score on 28 joints (DAS28) ≤ 2.6. Median scores for synovitis, BME, and total inflammation were also lower for the SDAI and Boolean ACR/EULAR remission criteria compared with DAS28. Conclusion. Patients with RA in remission according to the SDAI and Boolean ACR/EULAR definitions showed lower levels of MRI-detected residual inflammation compared with DAS28.

THU0461-HPR Global assessment of disease by the patient in the new ACR/EULAR remission criteria: Why do not fulfil the remission?

Background Recently, new criteria has been described for assessing Rheumatoid Arthritis (RA) remission. However, in clinical practice, patients who may be in remission by these criteria (ACR/EULAR 2011), ofter fail to meet patient’s global assessment (PtGA) scale of 0 to 10 with a value less than or equal to 1. Objectives To evaluate in patients with rheumatoid arthritis (RA), the reasons for non compliance with the new remission criteria ACR/EULAR due to a high PtGA and not related to the activity of the RA. Methods We included consecutively from April to December 2011 all patients with RA in remission for the composite index of activity, simplified disease activity index (SDAI) ≤3.3 and swollen joint count (SJC) ≤1, tender joint count (TJC) ≤1, C-reactive protein (CRP) ≤1 mg/dl but with PtGA >1 cm. Demographic variables (date of birth, sex, educational level), disease (date of diagnosis of RA, presence of radiological erosions, serum levels of RF and ACPA), activity DAS28, VAS pain (0-10 cm), PtGA (0-10 cm), functional disability by HAQ, treatment (corticosteroids, DMARDs and/or tumor necrosis factor (anti-TNF), and comorbidity not associated with RA as possible causes of a PtGA>1 cm. Data were analyzed with SPSS v.15. Results 55 patients (87.3% women) with a mean age of 57.8±12.7 years and a mean disease duration of 4.2±3.1 years were included. 60% were seropositive for rheumatoid factor (RF), 61.8% for Anti-citrullinated protein antibodies (ACPA) and 87.3% had radiographic erosions. 20% of patients had basic studiesand only 16.4% medium-high level. The mean HAQ was 0.483±0.387. 80% were treated with DMARDs (47.3% methotrexate), a 34.5% anti-TNF with or whithout DMARDs, 52.8% were taken corticosteroids (mean dose to prednisone equivalent of 2.1±2.2 mg per day). The mean DAS28 was 2.3±0.5, the pain VAS 3.6±1.8 cm and 3.7 ± PtGA was 1.2 cm. Acute phase reactants were both below normal level (ESR=16.5±14.7 (normal <37 mm/h) and CRP=0.3±0.2 (normal <0.8mg/dl). The reasons why patients considered to be in remission (new ACR/EULAR criteria) did not meet a PtGA ≤1 cm is shown in Table 1. Table 1. Main causes of PtGA of >1 cm in patients with RA and in remission Causes No. of patients (%) Osteoarthritis 24 (43.7%) Fibromyalgia 3 (5.4%) Soft Tissue Rheumatism 9 (16.4%) Intercurrent Process (surgery, trauma, infection ...) 5 (9.1%) Psychological disorder 3 (5.4%) Awareness of chronic disease 6 (10.9%) Comorbidity not associated 5 (9.1%) Conclusions In our series, 65.5% of the patients on remission by other components if the new ACR/EULAR criteria, reported a PtGA >1 cm due to a non-RA joint disease, osteoarthritis and soft tissue rheumatism being most prevalent disorders. The Rheumatology nurse should ensure proper completion of visual analog scales especially the PtGA in patients with RA as it is an important variable in the index of activity and remission of the disease. Disclosure of Interest None Declared

FRI0582 Could MRI of the Hand Improve the Accuracy of the 2010 ACR/EULAR Criteria for Rheumatoid Arthritis?

Objectives To analyze whether the addition of inflammatory findings or erosions on hand MRI improve the accuracy of ACR/ EULAR 2010 RA classification criteria in early arthritis. Methods Cross-sectional study of patients with early arthritis (defined as the presence of at least one inflamed joint, less than a year since the start of the first symptoms and without meeting the ACR/EULAR 2010 criteria) referred to the Early Arthritis Clinic at Hospital Mar (PSMAR, Barcelona). At baseline, demographic (age, gender), disease-related (median of disease duration in months, serum levels of RF U/ml and ACPA U/ml, presence of radiological erosions on hands and feet) and previous treatments (NSAIDs, glucocorticoids (GCs) and synthetic DMARDs) were recorded. Clinical data, laboratory tests and functional disability were collected. MRI of the dominant hand (h-MRI) was performed and score according to the OMERACT RAMRIS recommendations (RAMRIS-synovitis (0-21), RAMRIS-bone edema (0-69) RAMRIS-erosions (0-230)), tenosynovitis (0-26) and total inflammation (sinovitis plus bone edema plus tenosynovitis, 0-116) in wrist and 2nd to 5th MCP joints were recorded. We used the presence of any lesion on h-MRI added 2010 RA criteria to improve the diagnostic accuracy of these criteria. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of the ACR/EULAR 2010 criteria alone and associated with h-MRI parameters were analyzed using fulfillment of the ACR 1987 criteria at one year follow-up as standard reference. All data was analyzed using the SPSS v.18. Results Sixty-one patients with early arthritis out of 199 (30.6%) who did not fulfilled the ACR/EULAR 2010 criteria for the diagnosis of RA at baseline and with avalaible data of h-MRI were included. Demographic, clinical and h-MRI data at baseline will be shown in an additional Table. The mean (±SD) RAMRIS score for synovitis was 4.86 (±2.61), for RAMRIS bone-edema was 6.81 (±3.61), for RAMRIS-erosions was 4.42 (±4.84), for tenosynovitis was 4.63 (±5.3), total inflammation was 10.6 (±13.11) and Total RAMRIS of 12.98±11.25). The table showed the sensitivity, specificity, PPV, NPV and diagnostic accuracy of the ACR/EULAR 2010 criteria alone or associated with MRI parameters using as reference standard fulfil the 1987 RA criteria at one year. Sensitivity Specificity PPV NPV Accuracy ACR/EULAR 2010 criteria alone 0.91 0.78 0.93 0.74 0.88 ACR/EULAR 2010 criteria plus h-MRI parameters  RAMRIS Synovitis 1 0.09 0.78 1 0.80  RAMRIS Bone edema 0.96 0.40 0.84 0.76 0.83  RAMRIS Erosions 0.99 0.17 0.79 0.89 0.80  Total RAMRIS 0.99 0.15 0.82 0.93 0.81  Total Inflammation 1 0.06 0.78 1 0.78  Tenosynovitis 0.99 0.25 0.81 0.92 0.81 Conclusions Our results suggest that including baseline inflammatory findings and erosions from h-MRI in the ACR/EULAR 2010 criteria using the 1987 ACR criteria as a reference at one year, does not improve the diagnostic accuracy in our patients with early arthritis. References Tamai M et al. Ann Rheum Dis 2014;73:2219-20. Nieuwenhuis WP et al. Ann Rheum Dis 2014;0:1-2. Disclosure of Interest None declared

FRI0564 RA and Remission: Acceptable Inflammatory Activity in Magnetic Resonance Imaging Associated with Absence of Progression of Erosions at One Year

Objectives To analyze the predictive value of inflammatory findings in hand MRI (h-MRI) and establish cutoff values of these inflammatory lesions at baseline (“acceptable inflammatory activity”) associated with absence of progression of erosions in h-RM after one year follow-up in RA remission patients Methods Prospective study of RA patients (fulfilling ACR 1987 revised criteria) in clinical remission (defined as DAS28-ESR ≤2.6 for at least 6 months and without changes of treatment 3 months before study) and with avaliable data of h-MRI at baseline and at one year. At baseline and every 3 months clinical and laboratory evaluation was performed according to established protocol. MRI of the dominant hand were obtained at entry of study and one year after. MRI images were read by 2 experienced readers following RAMRIS recommendations. Inflammatory MRI findings (bone edema, synovitis, tenosynovitis, sum of all inflammatory lesions) and bone erosions were recorded. “Acceptable inflammatory activity in h-MRI”, was defined as the inflammatory MRI findings associated with no progression of erosions at the annual h-MRI. “No progression of erosions on h-MRI” was defined as the change in annual RAMRIS <1 point from baseline erosion score. Statistical analysis included logistic regression analysis and receiver operating characteristic (ROC). Data evaluation and statistical analysis were performed using SPSS v.18. Results Fifty patients with RA (44 women, age 54.2±11.7 years, mean disease duration 8.2±7.1 years) and in clinical remission (mean of DAS28-ESR 1.72±0.60 and with a mean duration of remission 20.7±12.1 months) were included. Forty patients (80%) did not show progression of erosions on annual h-MRI.Univariate analysis showed a significant association between h-MRI progression of erosions at one year with disease duration, (OR 1.13, 95%CI 1.02 a 1.25, p=0.013), RAMRIS bone edema (OR 1.65, 95%CI 1.14 a 2.37, p=0.007) and total inflammation at baseline (OR 1.14, 95%CI 1.0 a 1.30, p=0.045) and a trend toward an association with baseline RAMRIS synovitis (OR 1.29, 95%CI 0.98 a 1.69, p=0.065). In the multivariate analysis, bone edema was the only significant independent predictor associated with h-MRI progression of erosions (OR 1.65 95%CI 1.14 a 2.37, p=0.007). ROC analysis identify a cut-off point of 2 for RAMRIS bone edema (AUC of 0.75, 95%CI 0.55 to 0.95, p=0.002) and 5 for RAMRIS synovitis (AUC 0.68 95%CI 0.46 to 0.89, p=0.007) as a “acceptable inflammatory activity in h-MRI” and suggest that these cutoffs were the best for to discriminate patients with or without risk of h-MRI progression at one year with a value of sensitivity >0.60 and and specificity >90%. Conclusions In RA remission patients, baseline bone edema on h-MRI was the most important independent predictor associated with h-MRI progression of erosions at one year.The discriminative ability of inflammatory h-MRI cut-offs (2 for RAMRIS-bone edema and 5 for RAMRIS-synovitis) between patients with or without risk of h-MRI progression were acceptable. *REMAR study: Investigator Initiated Research funded by Pfizer Disclosure of Interest None declared

THU0015 IL2RA Locus is Associated with Joint Damage in a Specific Rheumatoid Arthritis Phenotype

Background Joint damage is a key pathological feature of Rheumatoid Arthritis (RA) and is characterized by a high level of heterogeneity. There is recent evidence suggesting an association of IL2RA and C5orf3 loci with the degree of joint destruction in RA. Objectives Using a large cohort of RA patients we have performed the validation of this two candidate genes for joint destruction and analyzed in relation to the main disease phenotypes. Methods A total of 857 RA patients were recruited and their level of joint destruction was measured. The previously reported single nucleotide polymorphisms at IL2RA (rs2104286) and C5orf30 (rs26232) loci were genotyped in the patient cohort using Taqman RealTime-PCR. The two loci were tested for association with the level of joint destruction using linear regression. Clinically relevant variables were analyzed independently with the level of joint damage and in relation to the genetic polymorphisms using linear regression analysis. Results We found a highly significant association between IL2RA locus SNP rs2104286 with the level of joint destruction in RA (P=0.0017). In our cohort, variation at C5orf30 locus did not show any evidence of association. Years of disease duration (P=2.6e-54), number of previous biological therapies (P=4.3e-9), body-mass index (BMI, P=6.9e-5), Anti-Citrullinated Peptide Antibodies (ACPA) status (P =0.0001) and Rheumatoid Factor (RF) status (P=0.009) were also found to be significantly associated with the level of joint damage in RA. The genetic association between IL2RA locus and bone erosions was found to be restricted to autoantibody-positive (74% ACPA-positive, P=0.001; 74% RF-positive, P=0.004) and female (77%, P =0.01) patients. Conclusions The results of this study confirm the association of IL2RA with joint destruction in RA and suggest that this genetic variation is relevant to a specific patient phenotype. Acknowledgements This work was supported by the Spanish Ministry of Economy and Competitiveness Strategic Project grants [PSE-010000-2006-6, IPT-010000-2010-36] and the Fondo de Investigaciόn Sanitaria grant [11/0551]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Disclosure of Interest None declared