N. Inanc

Anti-CCP antibodies in rheumatoid arthritis and psoriatic arthritis

Our aim is to assess the prevalence and associated clinical features of anti-CCP (cyclic citrullinated peptide) antibodies for RF (rheumatoid factor)-positive and RF-negative rheumatoid arthritis (RA) and psoriatic arthritis (PsA). In a prospective, cross-sectional, multi-centre study, we determined the titres of anti-CCP antibodies in 208 RA patients (129 RF-positive, 79 RF-negative), 56 PsA patients and 39 healthy controls (HC). Clinical parameters including disease activity (disease activity score 28—DAS28), physical disability (health assessment questionnaire—HAQ), functional capacity (functional class) and radiological erosions were investigated in patients with RA. In PsA patients, clinical and radiological features were determined. Anti-CCP2 antibodies were measured using a second-generation anti-CCP enzyme-linked immunosorbent assay (Euro-Diagnostica, Netherlands). One-hundred four of 129 RF-positive RA (81%), 16 of 79 RF-negative RA (20%), seven of 56 PsA patients (12.5%) and none of the HC had anti-CCP antibodies. RA patients with anti-CCP antibodies had significantly higher disease activity, greater loss of function and more frequent erosive disease than anti-CCP antibody-negative group. In subgroup analysis, anti-CCP antibodies in RF-negative patients were also associated with erosive disease. All PsA patients with anti-CCP antibodies had symmetric arthritis with higher number of swollen joints. The prevalence of anti-CCP antibodies in RF-positive RA patients was significantly higher than in RF-negative RA and PsA patients. Anti-CCP antibodies were also associated with erosive disease in RF-negative RA patients. Both anti-CCP and RF tests were negative in 30% of the patients. Anti-CCP positivity was a frequent finding in PsA and associated with symmetrical polyarthritis.

Patient's global assessment of disease activity and patient's assessment of general health for rheumatoid arthritis activity assessment: are they equivalent?

Objectives To assess (A) determinants of patients global assessment of disease activity (PTGL) and patients assessment of general health (GH) scores of rheumatoid arthritis (RA) patients; (B) whether they are equivalent as individual variables; and (C) whether they may be used interchangeably in calculating common RA activity assessment composite indices. Methods Data of 7023 patients from 30 countries in the Quantitative Standard Monitoring of Patients with RA (QUEST-RA) was analysed. PTGL and GH determinants were assessed by mixed-effects analyses of covariance models. PTGL and GH equivalence was determined by Bland-Altman 95% limits of agreement (BALOA) and Lins coefficient of concordance (LCC). Concordance between PTGL and GH based Disease Activity Score 28 (DAS28), Clinical Disease Activity Index (CDAI) and Routine Assessment of Patient Index Data 3 (RAPID3) indices were calculated using LCC, and the level of agreement in classifying RA activity in four states (remission, low, moderate, high) using κ statistics. Results Significant differences in relative and absolute contribution of RA and non-RA related variables in PTGL and GH ratings were noted. LCC of 0.64 and BALOA of −4.41 to 4.54 showed that PTGL and GH are not equivalent. There was excellent concordance (LCC 0.95–0.99) for PTGL and GH based DAS28, CDAI and RAPID3 indices, and >80% absolute agreement (κ statistics 0.75–0.84) in RA activity state classification for all three indices. Conclusions PTGL and GH ratings differ in their determinants. Although they are individually not equivalent, they may be used interchangeably for calculating composite indices for RA activity assessment.

Agreement Between Quantiferon-TB Gold Test and Tuberculin Skin Test in the Identification of Latent Tuberculosis Infection in Patients with Rheumatoid Arthritis and Ankylosing Spondylitis

Objective. To compare the Quantiferon-TB Gold test (QTF-G) with the tuberculin skin test (TST) for the detection of latent tuberculosis infection (LTBI) among patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS), with reevaluation of the patients treated with tumor necrosis factor-α (TNF-α) antagonists in the followup. Methods. The study involved 140 consecutive patients, 82 with RA and 58 with AS. Thirty patients were evaluated with QTF-G for detection of LTBI before and after 6 months of TNF-α antagonist treatment. QTF-G was also performed on 49 healthy controls. QTF-G results were recorded as positive, negative, or indeterminate. A positive TST was defined as ≥ 5 mm for RA and AS. Results. The percentages of positive QTF-G were comparable in RA and AS (37% vs 32%). The rate of positive QTF-G in healthy controls (29%) was also similar to RA and AS. In contrast to QTF-G results, a high rate of TST positivity was observed in AS compared to RA (82% vs 55%; p = 0.02). The total agreement between QTF-G and TST was observed to be 61% (κ = 0.29) in the whole group, 70% (κ = 0.42) in RA, and 49% (κ = 0.14) in AS. After 6 months of treatment with TNF-α antagonists, a high rate of QTF-G change was observed in patients with indeterminate results (23% vs 3%; p = 0.03). Conclusion. The comparable prevalence of LTBI among the study groups according to QTF-G supports the view that QTF-G is less susceptible to external factors than TST. Sequential testing for QTF-G in patients with indeterminate or negative results may also be helpful in discriminating LTBI better.

The Role of Depression, Anxiety, Fatigue, and Fibromyalgia on the Evaluation of the Remission Status in Patients with Rheumatoid Arthritis

Objective. To investigate the effect of depression, anxiety, fatigue, and fibromyalgia (FM) on the remission status in patients with rheumatoid arthritis (RA), defined according to the 28-joint count Disease Activity Score (DAS28)-erythrocyte sedimentation rate (ESR) and the Boolean-based new American College of Rheumatology/European League Against Rheumatism remission criteria. Methods. The subjects were patients with RA who participated in a hospital-based observational cohort. Patients who met the DAS28-ESR remission criteria at their latest visit were invited to participate in our study. The patient groups fulfilling or not fulfilling the Boolean remission criteria were identified and compared with each other with regard to the presence of depression, anxiety, fatigue (0–50), and FM. The relationship between psychosocial factors and Simplified Disease Activity Index (SDAI) remission, which is the index-based definition of remission in RA, was also investigated. Results. A total of 87 out of 428 patients (20%) with RA met the DAS28-ESR remission criteria and 32 (37%) of these also met the Boolean remission criteria, while 55 (63%) did not. Forty patients were also in SDAI remission. In the Boolean remission group, 2 patients had depression and 2 had anxiety (p = 0.004). In the Boolean nonremission group, 19 patients had depression and 13 had anxiety (p = 0.04). Continuous scales of anxiety (3.34 ± 3.76 vs 5.83 ± 4.70, p = 0.012) and depression (2.18 ± 2.75 vs 4.63 ± 4.10, p = 0.001) were also lower in the Boolean remission group in comparison with the nonremission group. Though FM syndrome was detected in only 1 patient of the Boolean remission group and in 7 patients of the Boolean nonremission group (p = 0.249), patients’ polysymptomatic distress scores of FM in the Boolean remission group were significantly lower than those of the nonremission group (3.12 ± 3.25 vs 6.27 ± 5.19, p = 0.001). The mean fatigue scores were 9.5 ± 10.6 in the Boolean remission group and 16.8 ± 12.8 in the Boolean nonremission group (p = 0.006). In multivariate analysis, patient’s global assessment (PtGA) and depression were found as the independent discriminators of Boolean-based definition. Similar relationships were also observed between psychosocial factors and SDAI remission. Conclusion. In patients with RA who do not fulfill the Boolean remission criteria, to avoid overtreatment, assessment of anxiety, fatigue, FM, and especially depression must be considered if PtGA scores and disease activity variables are significantly different.

Skin manifestations of rheumatoid arthritis: a study of 215 Turkish patients.

Objective  To investigate the frequency and clinicopathological features of skin involvement in rheumatoid arthritis (RA), to find out whether early and aggressive disease‐modifying treatment is changing the spectrum towards a milder disease pattern.

Salivary levels of antimicrobial peptides Hnp 1-3, Ll-37 and S100 in Behcet's disease

BACKGROUND Oral ulcer is the cardinal clinical sign and increased neutrophilic activity is a part of the pathogenesis in Behcets disease (BD). Saliva, as a part of the innate immune response, contains antimicrobial peptides (AMPs) that are derived from both oral epithelial cells and neutrophils. The aim of this study was to investigate the associations between salivary levels of AMPs HNP 1-3, LL-37 and S100 and disease course in patients with Behcets disease (BD). METHODS Fifty-three patients with BD and 44 healthy controls (HC) were included in the study. Disease severity score reflecting organ involvement was calculated. Salivary HNP 1-3, LL-37 and S100 levels were measured in unstimulated saliva samples by ELISA. RESULTS Salivary HNP 1-3 and S100 levels in BD patients (2715.2 ± 1333.4 μg/ml and 430.6 ± 203.9 ng/ml) were significantly higher compared to HC (1780.6 ± 933.2 μg/ml and 365.3 ± 84.7 ng/ml) (p = 0.000 and p = 0.004, respectively). Although LL-37 levels were also higher in BD than HC (190.9 ± 189.1 vs 143.1 ± 128.9 ng/ml), no significant difference was observed (p = 0.53). Salivary HNP 1-3 and LL-37 levels were associated with the severity of BD (mild disease: 1975.1 ± 1174.2 μg/ml and 115.9 ± 109.4 ng/ml vs severe disease: 2955.7 ± 1305.6 μg/ml and 215.3 ± 203.8 ng/ml, p=0.020 and p=0.031, respectively). Salivary LL-37 levels also correlated with the number of monthly oral ulcers (r = 0.5 p = 0.000). CONCLUSION An increase in salivary HNP 1-3 and S100 levels might be associated with enhanced local and systemic innate responses in BD.

Comparison of QuantiFERON-TB Gold test and tuberculin skin test for the identification of latent Mycobacterium tuberculosis infection in lupus patients

The tuberculin skin test (TST) has low sensitivity for the diagnosis of tuberculosis (TB). QuantiFERON-TB Gold (QFT-G) is an IFN-gamma-release assay that measures the release of interferon-gamma after stimulation in vitro by Mycobacterium tuberculosis antigens using ELISA. The main advantage of this assay compared with TST is the lack of cross-reaction with Bacillus Calmette-Guérin (BCG) as well as most of non-tuberculous mycobacteria. The aim of our study is to compare QFT-G with TST for the detection of latent tuberculosis infection (LTBI) among patients with systemic lupus erythematosus (SLE). Methods: Seventy-eight patients with SLE and 49 healthy subjects (HCs) participated in the study. All patients and controls were interviewed for a history of TB then BCG vaccinations were recorded and chest X-rays were examined for a sign of TB infection. QTF-G and TST were performed on both patients and controls. QTF-G results were recorded as positive, negative or indeterminate. A positive TST for SLE was defined as ≥5 mm. Results: Seventy-six SLE patients (97.4%) had been BCG vaccinated. Similar to the HC (28.5%), 19 of 78 (24.3%) SLE patients had positive QTF-G. Two patients had an indeterminate result. The agreement between QTF-G and TST was 49/76 (64.4%) (κ = 0.33). There were fewer positive QFT-G test results than positive TST results (24.3% vs. 50%; p < 0.01). Twenty-two (28.9%) patients were TST(+)/QTF-G(−) while only 3(3.9%) patients were TST(−)/QTF-G(+). When the positive TST was defined as ≥10 mm indurations, which is the cut-off in screening for LTBI in Turkey, the agreement between two tests increased up to 58/76 (76.3%) with a κ value of 0.47. The mean TST measurements was higher in QTF-G positive patients (13.4 ± 8.8 mm) than the QTF-G negative patients (4 ± 5.3 mm) (p < 0.001). Discussion: In a TB-endemic and BCG vaccinated population, the QuantiFERON-TB Gold assay seemed to be a more accurate test for the detection of LTBI in SLE patients. Although 5 mm is usually accepted to be the standard cut-off for TST in immunocompromised patients such as SLE, the level of agreement between QTF-G and TST was better with a 10 mm cut-off in our population.

Assessment of the New 2012 EULAR/ACR Clinical Classification Criteria for Polymyalgia Rheumatica: A Prospective Multicenter Study

Objective. To assess the performance of the new 2012 provisional European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) polymyalgia rheumatica (PMR) clinical classification criteria in discriminating PMR from other mimicking conditions compared with the previous 5 diagnostic criteria in a multicenter prospective study. Methods. Patients older than 50 years, presenting with new-onset bilateral shoulder pain with elevated acute-phase reactants (APR), were assessed for the fulfillment of the new and old classification/diagnostic criteria sets for PMR. At the end of the 1-year followup, 133 patients were diagnosed with PMR (expert opinion) and 142 with non-PMR conditions [69 rheumatoid arthritis (RA)]. Discriminating capacity, sensitivity, and specificity of the criteria sets were estimated. Results. Discriminating capacity of the new clinical criteria for PMR from non-PMR conditions and RA as estimated by area under the curve (AUC) were good with AUC of 0.736 and 0.781, respectively. The new criteria had a sensitivity of 89.5% and a specificity of 57.7% when tested against all non-PMR cases. When tested against all RA, seropositive RA, seronegative RA, and non-RA control patients, specificity changed to 66.7%, 100%, 20.7%, and 49.3%, respectively. Except for the Bird criteria, the 4 previous criteria had lower sensitivity and higher specificity (ranging from 83%–93%) compared with the new clinical criteria in discriminating PMR from all other controls. Conclusion. The new 2012 EULAR/ACR clinical classification criteria for PMR is highly sensitive; however, its ability to discriminate PMR from other inflammatory/noninflammatory shoulder conditions, especially from seronegative RA, is not adequate. Imaging and other modifications such as cutoff values for APR might increase the specificity of the criteria.

The 2013 ACC/AHA 10-year atherosclerotic cardiovascular disease risk index is better than SCORE and QRisk II in rheumatoid arthritis: is it enough?

OBJECTIVE To determine the ability of the new American College of Cardiology and American Heart Association (ACC/AHA) 10-year atherosclerotic cardiovascular disease (ASCVD) risk algorithm in detecting high cardiovascular (CV) risk, RA patients identified by carotid ultrasonography (US) were compared with Systematic Coronary Risk Evaluation (SCORE) and QRisk II algorithms. METHODS SCORE, QRisk II, 2013 ACC/AHA 10-year ASCVD risk and EULAR recommended modified versions were calculated in 216 RA patients. In sonographic evaluation, carotid intima-media thickness >0.90 mm and/or carotid plaques were used as the gold standard test for subclinical atherosclerosis and high CV risk (US+). RESULTS Eleven (5.1%), 15 (6.9%) and 44 (20.4%) patients were defined as having high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. Fifty-two (24.1%) patients were US + and of those, 8 (15.4%), 7 (13.5%) and 23 (44.2%) patients were classified as high CV risk according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. The ACC/AHA 10-year ASCVD risk index better identified US + patients than SCORE and QRisk II (P < 0.0001). With EULAR modification, reclassification from moderate to high risk occurred only in two, five and seven patients according to SCORE, QRisk II and ACC/AHA 10-year ASCVD risk, respectively. CONCLUSION The 2013 ACC/AHA 10-year ASCVD risk estimator was better than the SCORE and QRisk II indices in RA, but still failed to identify 55% of high risk patients. Furthermore adjustment of threshold and EULAR modification did not work well.

Response rate of initial conventional treatments, disease course, and related factors of patients with adult-onset Still's disease: Data from a large multicenter cohort.

BACKGROUND Adult-onset Stills disease (AOSD) is a rare condition, and treatment choices are frequently dependent on expert opinions. The objectives of the present study were to assess treatment modalities, disease course, and the factors influencing the outcome of patients with AOSD. METHODS A multicenter study was used to reach sufficient patient numbers. The diagnosis of AOSD was based on the Yamaguchi criteria. The data collected included patient age, gender, age at the time of diagnosis, delay time for the diagnosis, typical AOSD rash, arthralgia, arthritis, myalgia, sore throat, lymphadenopathy, hepatomegaly, splenomegaly, pleuritis, pericarditis, and other rare findings. The laboratory findings of the patients were also recorded. The drugs initiated after the establishment of a diagnosis and the induction of remission with the first treatment was recorded. Disease patterns and related factors were also investigated. A multivariate analysis was performed to assess the factors related to remission. RESULTS The initial data of 356 patients (210 females; 59%) from 19 centers were evaluated. The median age at onset was 32 (16-88) years, and the median follow-up time was 22 months (0-180). Fever (95.8%), arthralgia (94.9%), typical AOSD rash (66.9%), arthritis (64.6%), sore throat (63.5%), and myalgia (52.8%) were the most frequent clinical features. It was found that 254 of the 306 patients (83.0%) displayed remission with the initial treatment, including corticosteroids plus methotrexate with or without other disease-modifying antirheumatic drugs. The multivariate analysis revealed that the male sex, delayed diagnosis of more than 6 months, failure to achieve remission with initial treatment, and arthritis involving wrist/elbow joints were related to the chronic disease course. CONCLUSION Induction of remission with initial treatment was achieved in the majority of AOSD patients. Failure to achieve remission with initial treatment as well as a delayed diagnosis implicated a chronic disease course in AOSD.