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Objective: To investigate and compare trends in incidence rates (IRs) of seropositive and seronegative rheumatoid arthritis (RA) in Denmark using various data sources for serostatus definition. Method: This nationwide population-based cohort study was based on data from Danish healthcare and clinical quality registries between 2000 and 2018. Information on anti-cyclic citrullinated peptide and immunoglobulin M rheumatoid factor was obtained, and definitions of seropositivity according to the number of applied data sources were prespecified. Annual age- and sex-standardized IRs were calculated as the number of incident seropositive and seronegative cases, divided by the number of person-years (PY) in the general population in that given year. Results: An increasing temporal trend in IR of seropositive RA and a decreasing trend in seronegative RA were observed. The IRs were higher for seropositive RA than for seronegative RA from 2009 onwards, with a widening of the IR gap between 2009 and 2016 regardless of the definition of seropositivity. When combining laboratory- and physician-reported autoantibody information and ICD-10 codes, the IR of seropositive RA in 2018 was approximately twice that of seronegative RA, at 19.0 and 9.0 per 100 000 PY, respectively. The level of antibody testing increased significantly during the study period. Conclusions: The IR of seropositive RA increased over time, whereas the IR of seronegative RA decreased. Temporal IR changes may be caused by a real change in the RA serology subtypes, an increase in autoantibody testing and availability, changes in registration practice over time, or a combination of these factors. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate an individually tailored smoking-cessation intervention delivered in rheumatology care and compare the characteristics of patients who quit smoking with those who did not. This was an open single-group prospective intervention study over 24 months, with assessments at baseline and at 6, 12, 18, and 24 months. Current smokers with rheumatoid arthritis (RA) were invited to a smoking-cessation programme including behavioural change support, with or without pharmacotherapy. Data on disease activity, medical treatment, and patient-reported outcomes were retrieved from the Swedish Rheumatology Quality Register. The primary outcome was the proportion of patients at month 24 who reported having quit smoking with self-reported 7 day smoking abstinence. In total, 99 patients participated in the study. Median age was 58 years (interquartile range 50–64); 69% were female and 88% rheumatoid factor and/or anti-cyclic citrullinated peptide positive. At 24 months, 21% of the patients had quit smoking. At 6, 12, and 18 months, 12%, 12%, and 14% of patients, respectively, had quit smoking. For patients still smoking at 24 months, the median number of cigarettes per day was significantly reduced from 12 to 6 (p ≤ 0.001). Among patients who had quit smoking at 24 months, a smaller proportion reported anxiety at baseline compared to those still smoking (28% vs 58%, p = 0.02). A smoking-cessation intervention including behavioural change support with or without pharmacotherapy can be helpful for a substantial number of RA patients. Anxiety is associated with lower smoking-cessation success rates. [ABSTRACT FROM AUTHOR]

Smoking and periodontitis are risk factors for developing rheumatoid arthritis (RA), suggesting a break of tolerance on mucosal surfaces. Immunoglobulin A (IgA) antibodies are part of the mucosal immune system. The dominant autoantibodies in RA are anti-cyclic citrullinated protein antibodies (ACPAs), and IgG and IgA subclasses exist simultaneously. This study aimed to investigate the association of ACPA IgA subtypes with disease activity and long-term radiographic outcomes in RA, compared with ACPA IgG. Total ACPA IgG, IgA, IgA1, and IgA2 were quantified in serum from patients with early RA (n = 97). Patient characteristics, IgM rheumatoid factor (IgM-RF) status, clinical and biochemical disease activity scores, and radiographic status evaluated by total Sharp score (TSS), were assessed at baseline and after 2 and 11 years of treatment. All patients with ACPA IgA also had ACPA IgG. ACPA IgA positivity was associated with IgM-RF and male gender. Both ACPA IgA and IgG levels at baseline were weakly associated with disease activity markers. Baseline ACPA IgA and IgG did not show a linear correlation with radiographic status after 10 years, but could predict radiographic progression (ΔTSS ≥ 5 from 0 to 11 years), with positive likelihood ratios of 3.7 and 4.0, respectively. ACPA IgA and IgG were weakly associated with disease activity in early RA. RA patients with a ΔTSS ≥ 5 after 11 years of treatment had higher ACPA IgG and ACPA IgA levels at baseline; however, none of the ACPA subtypes was superior in predicting long-term radiographic progression. [ABSTRACT FROM AUTHOR]

There is a need to better define symptom characteristics associated with arthritis development in individuals at risk of rheumatoid arthritis (RA). We investigated whether reported symptoms in at-risk individuals could predict arthritis development and whether predictive symptoms differed between seropositive and seronegative at-risk individuals. At-risk individuals from four cohorts (Netherlands, UK, Sweden, and Switzerland) completed the Symptoms in Persons At Risk of Rheumatoid Arthritis (SPARRA) questionnaire. Participants had either (i) anti-citrullinated protein antibodies and/or rheumatoid factor, or (ii) relevant symptoms with or without RA antibodies. Follow up was ≥ 24 months or until clinical arthritis development. Stepwise forward selection created SPARRA prediction models for the combined group and for a seropositive subgroup. Of 214 participants, the mean age was 50 years, 67% were female, and 27% (n = 58) developed clinical arthritis after a median time of 7 months. Four symptoms predicted arthritis development: self-reported joint swelling, joint pain moving from side to side (combined group only), feeling pins and needles in the joints, and often feeling fatigued (predicting non-arthritis). Specific symptoms can provide useful information to estimate a person's RA risk. Differences in predictive symptoms between seropositive and seronegative at-risk individuals need to be further investigated. Future research is needed to determine whether changes in symptoms over time improve prediction and to determine the value of SPARRA in optimizing the selection of individuals who need to consult a rheumatologist. [ABSTRACT FROM AUTHOR]

: Knowledge of the correspondence between clinical ICD diagnoses and classification criteria fulfilment is crucial to interpret studies identifying cases via ICD codes. We assessed the degree to which patients registered with ICD-10 diagnoses of psoriatic arthritis (PsA) in the Swedish National Patient Register (NPR) fulfil established PsA classification criteria. Four hundred patients with at least one outpatient visit to one of five rheumatology or internal medicine departments (three university/two county departments across Sweden) in 2013–2015, with a main ICD-10 diagnosis of PsA (L40.5, M07.0–M07.3), were randomly selected (80 cases/site). Through a structured medical record review, positive predictive values (PPVs) for fulfilment of the following classification criteria were assessed: CASPAR, Moll and Wright, Vasey and Espinoza, and modified ESSG criteria for PsA. A subset analysis regarding CASPAR fulfilment was also performed among cases with available rheumatoid factor and peripheral X-ray status (central CASPAR items; n = 227). Of the 400 patients with a main ICD-10 diagnosis of PsA, 343 (86%) fulfilled at least one of the four PsA classification criteria. PPVs for the different criteria were: CASPAR 69% (82% in the subset analysis), Moll and Wright 51%, Vasey and Espinoza 76%, and modified ESSG 64%. Overall, only 6.5% of the 400 PsA diagnoses were judged as clearly incorrect by the medical record reviewers. The validity of rheumatologist-made, clinical ICD-10 diagnoses for PsA in the Swedish NPR is good, with PPVs of 69–82% for CASPAR fulfilment and 86% for meeting any established PsA classification criteria. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown aetiology that affects approximately 1% of the population. The disease presents a temporal variability in different geographic areas. We investigated RA incidence over a 40-year-period in a defined area of north-west Greece, with a total population of about 400 000 inhabitants. This incidence study was based on retrospective review of clinical records among adults with RA newly diagnosed from 1980 to 2019 at the referral university hospital of Ioannina. An incident case was defined as any patient diagnosed with RA based on the 1987 American College of Rheumatology criteria, over 16-years-old, and resident in the study area for at least 1 year before diagnosis. Out of 1411 cases diagnosed, women constituted a 2.65-fold higher number than men, with a lower mean age at diagnosis. The overall age-adjusted annual incidence rate (95% confidence interval) was 9.5 (8.5–10.5) for the total observation period, 11.7 (10.7–13.0) in 1980–1989, 10.4 (9.4–10.8) in 1990–1999, 9.8 (8.9–10.8) in 2000–2009, and 6.1 (5.3–6.9) in 2010–2019, presenting a statistically significant decline over time, along with a constant decrease in rheumatoid factor (RF)-positive incidence for both sexes. Our findings suggest a decrease in the incidence of RA over 40 years in a geographically defined Greek population. Also, the progressive decrease in the incidence of RF-positive disease may relate to less severe expression of RA in Greek patients. These trends could be explained by different clinical, serological, and genetic factors reported in Greece compared to northern European countries. [ABSTRACT FROM AUTHOR]

The objective of this medical record review study is to define the association between smoking and Sjӧgren's syndrome (SS) in a large rheumatoid arthritis (RA) cohort. Electronic health records from a population-based cohort were screened for RA eligibility between 2005 and 2018. Inclusion criteria were age ≥ 18 years, two or more RA diagnoses, including two diagnoses by a rheumatologist, or positive rheumatoid factor or anti-cyclic citrullinated peptide (anti-CCP) antibody. The independent variable, smoking status, was defined as never, current, or past. The outcome, SS, was defined by two or more ICD-9 codes. Multivariable logistic regression was performed to determine odds ratios (ORs) of SS adjusted for age, sex, and race. Among 1861 patients with RA identified for cohort inclusion, 1296 had a reported smoking status. Current smokers were younger and less likely to be female than never smokers. The adjusted OR of current compared to never smokers was negatively associated with SS [OR 0.20, 95% confidence interval (CI) 0.06–0.65]. Female sex and age were associated with SS (OR 2.70, 95% CI 1.18–6.14; OR 3.75, 95% CI 1.23–11.4). We report that RA patients who currently smoke had 80% lower odds of SS. Age had a 3.7-fold association and female sex a 2.7-fold association with SS among RA patients. Our data suggest a negative correlation between current smoking and prevalent SS among RA patients. Prospective studies examining pack-year relationships or smoking cessation could further examine risk reduction and causality to follow-up our cross-sectional observational study. [ABSTRACT FROM AUTHOR]

Objective: Predictors of arthritis development in patients with anti-citrullinated protein antibodies (ACPAs) and musculoskeletal symptoms are needed for risk stratification and to improve clinical outcomes. The aim of this study was to assess the relationship between serum protein electrophoresis (SPE) constituents and the development of clinical arthritis in ACPA-positive patients with musculoskeletal pain., Method: We prospectively followed 82 ACPA-positive patients with musculoskeletal pain but no baseline arthritis during a median of 72 months (interquartile range 57-81 months). The primary outcome was arthritis development, as judged by clinical examination. SPE constituents were evaluated in baseline sera by immunoturbidimetric methods. Serum levels of the analysed proteins (albumin, orosomucoid, α 1 -anti-trypsin, haptoglobin, and immunoglobulins IgA, IgG, and IgM) were related to arthritis development by Cox regression analyses., Results: During the follow-up period, 39/82 patients (48%) progressed to arthritis. Median baseline levels of orosomucoid and α 1 -anti-trypsin were higher in patients who developed arthritis than in those who did not (p = 0.04), while median albumin levels were significantly lower (p = 0.03). Immunoglobulin levels did not differ between the groups. Univariable analysis demonstrated a significantly increased risk of arthritis with elevated baseline haptoglobin [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.32-4.85, p = 0.005] and orosomucoid levels (HR 2.63, 95% CI 1.09-6.31, p = 0.03). However, neither remained significant in multivariable analysis adjusting for elevated C-reactive protein (CRP) levels., Conclusion: SPE does not add prognostic value for arthritis development in ACPA-positive patients with musculoskeletal pain.

Objectives: Peptidylarginine deiminases (PADs) are a family of calcium-dependent enzymes catalysing the conversion of arginine residues to citrulline, which may constitute a risk factor in rheumatoid arthritis (RA) pathogenesis. We investigated PAD activation by serum (PADAct) in early RA, and the associations between PAD activation and disease characteristics, treatment response, and progression of radiographic damage.Method: Sera from disease-modifying anti-rheumatic drug (DMARD)-naïve early RA patients (n = 225), classified according to the 2010 American College of Rheumatology/European League Against Rheumatism criteria, and healthy controls (n = 63) were analysed for PAD4 activating capacity at 0, 3, 12, and 24 months using a high-performance liquid chromatography fluorometric method. Associations for PADAct were evaluated by Mann-Whitney U and chi-squared tests. Changes in PADAct levels were compared using the Wilcoxon signed-rank test.Results: PADAct positivity occurred in 42% (n = 95) of the patients and was more prevalent in anti-citrullinated protein antibody (ACPA)-positive vs ACPA-negative patients (47% vs 20%, p = 0.002), but not in rheumatoid factor (RF)-positive vs RF-negative patients (44% vs 38%, p = 0.49). PADAct-positive were younger than PADAct-negative patients [mean ± sd 48.7 ± 13.5 vs 53.2 ± 13.7 years, p = 0.011]. Median [25th, 75th percentile] PADAct levels were higher in patients than in controls (8768 [7491, 11 393] vs 7046 [6347, 7906], p < 0.0001) and decreased after initiation of DMARD treatment, but were not associated with treatment response or progression of radiographic damage after 2 years of follow-up.Conclusion: Serum capacity to activate PAD4 was associated with ACPA and RF positivity and earlier disease onset in early RA patients, and decreased after initiation of DMARD treatment, indicating that anti-PAD treatment could potentially be beneficial in RA. [ABSTRACT FROM AUTHOR]

Objective: Successful rheumatoid arthritis (RA) outcome depends on treatment efficacy in the early stages of the disease and its sustainability. It is thus critical to identify factors predicting treatment persistence with biological agents, such as abatacept. We compared clinical profiles, including early changes in autoantibody titres at 3 months, between patients with RA demonstrating sustained persistence and those discontinuing abatacept treatment.Method: We prospectively enrolled 71 and 78 active RA patients treated with abatacept and tumour necrosis factor inhibitors (TNF-Is), respectively, who had previous disease-modifying anti-rheumatic drug) failure. Clinical characteristics were compared between non-continuation and continuation groups stratified according to abatacept or TNF-I persistence for at least 12 months from treatment initiation.Results: Significantly larger decreases in rheumatoid factor titre and anti-citrullinated protein autoantibody (ACPA) titre were observed in the continuation group of abatacept therapy at 3 months, and early reduction in ACPA titre remained a significant and independent predictor of sustained persistence with abatacept in multivariate analysis. In addition, we obtained the area under the receiver operator characteristics curve of 0.904 from a model including baseline ACPA titre and reduction of ACPA titre at 3 months. Sustained reduction of RA disease activity score at 12 months was significantly and independently associated with reduced ACPA titre at 3 months.Conclusions: Persistence with abatacept and sustained therapeutic response are associated with an early reduction in ACPA titre. Prediction of abatacept continuation and efficacy will facilitate the optimal design of therapy in the early stages of RA. [ABSTRACT FROM AUTHOR]

Objective: Infliximab-treated patients with rheumatoid arthritis (RA) may respond insufficiently due to low serum infliximab (sIFX) levels, caused by anti-drug antibodies (ADAs). However, monitoring of sIFX and ADAs is not routinely implemented, and levels for optimal outcome have not been validated. We searched for predictors for sIFX < 0.2 μg/mL and ADA development in a randomized setting. Methods: In the SWEFOT trial, of 128 patients randomized to methotrexate + IFX therapy, 101 had serum samples at 3, 9, and 21 months that were analysed for sIFX [enzyme-linked immunosorbent assay (ELISA)] and ADAs [ELISA, and precipitation and acid dissociation (PandA) when sIFX > 0.2 μg/mL]. The primary and secondary outcome measures were low disease activity [LDA = 28-joint Disease Activity Score (DAS28) ≤ 3.2] and remission (DAS28 < 2.6). Baseline characteristics were assessed as potential predictors of sIFX < 0.2 μg/mL or ADA positivity, using logistic regression. Results: Categorization of sIFX levels into < 0.2, 0.2-2.9, 3.0-7.0, and > 7.0 μg/mL showed a dose-response association with LDA (30%, 64%, 67%, and 79%, respectively, p = 0.008) and remission (10%, 45%, 39%, and 66%, p = 0.004) at trial cessation (21 months). Female patients had sIFX < 0.2 μg/mL more often than males (35% vs 7%, p = 0.006), with a similar trend for rheumatoid factor (RF)-positive vs RF-negative patients (34% vs 16%, p = 0.059). ADA positivity showed similar patterns, also after adjustment for potential confounders (female sex: p = 0.050; RF positivity: p = 0.067). PandA captured four highly ADA-reactive patients with sIFX > 0.2 μg/mL, of whom three were ADA positive at other time-points, all with high DAS28 at follow-up. Conclusion: In early RA patients receiving IFX as a second-line agent, sIFX < 0.2 μg/mL and ADA development were associated with treatment failure and were more common in females, with a similar trend for RF positivity. Our findings support the use of therapeutic drug monitoring, and PandA in ADA-negative non-responders. Trial registration: SWEFOT NCT00764725 ( https://clinicaltrials.gov/ct2/show/NCT00764725 ). [ABSTRACT FROM AUTHOR]

Objective: The aim was to investigate prevalence and degree of ocular and oral involvement in patients with primary Sjögren's syndrome (PSS).Method: We analysed 134 participants from the Korean Initiative of PSS cohort who completed a 2 year follow-up oral and ocular sign test. The severity of keratoconjunctivitis sicca (KCS) was determined with the Schirmer I test value (STV) [abnormal (AB) ≤ 5 mm/5 min; normal (N) > 5 mm/5 min]. Salivary gland dysfunction (SGD) was determined by unstimulated whole salivary (UWS) flow rate [moderate to severe (MS) < 0.1 mL/min; mild (Mi) ≥ 0.1 mL/min]. Subgroups were divided into three groups according to STV and severity of SGD: AB-STV/MS-SGD, AB-STV/Mi-SGD, and N-STV/MS-SGD groups. We analysed the changes in STV and SGD during the follow-up period.Results: Among the 134 participants enrolled in this study, 105 (78%) were placed in the AB-STV/MS-SGD group, 16 (12%) in the AB-STV/Mi-SGD, and 13 (10%) in the N-STV/MS-SGD at the 2 year follow-up. The AB-STV/Mi-SGD group was younger than the other two groups, and had a lower Xerostomia Inventory score and lower level of β2-microglobulin. Participants in the N-STV/MS-SGD group had less hyperimmunoglobulinaemia, rheumatoid factor (RF), and antinuclear antibodies (ANAs). Patients and those with positive RF or ANA ≥ 1:320 at baseline were more likely to have abnormal STV at the 2 year follow-up.Conclusions: Patients with PSS and positive RF or ANA ≥ 1:320 at baseline may benefit from regular ophthalmology examinations, even if they do not have KCS at baseline or dry eye symptoms. [ABSTRACT FROM AUTHOR]

Objective: In this retrospective population-based register study, we wanted to determine the positive predictive values (PPVs) of immunoglobulin M rheumatoid factor (IgM RF) and anti-citrullinated protein antibodies (ACPAs) at 3 × upper normal limit (UNL), since they are weighted equally in the American College of Rheumatology (ACR)/ European League Against Rheumatism (EULAR) 2010 criteria for rheumatoid arthritis (RA).Methods: Test results, ordering unit, test date, and patient social security number were collected from the Department of Clinical Immunology at Odense University Hospital from 2007 to 2016 and merged with patient diagnosis from the Danish National Patient Registry.Results: The PPV of IgM RF at 3 × UNL was 14%, compared to a PPV of 43% for ACPAs at 3 × UNL.Conclusion: The PPV of ACPAs is higher than the PPV of IgM RF at 3 × UNL. These findings are not reflected in the ACR/EULAR 2010 classification criteria for RA. [ABSTRACT FROM AUTHOR]

Objectives: Heterophilic antibodies, such as rheumatoid factor (RF), are known to interfere with enzyme-linked immunosorbent assays (ELISAs). Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF)-α blockers is well established. The aims of this study were to develop a protocol for blocking the interaction of present heterophilic antibodies and to validate this procedure by evaluating the effect on correlations of cytokine levels to clinical response in RA patients treated with adalimumab.Method: Fourteen patients with active RA were evaluated at baseline and 3 months after starting adalimumab treatment. Cytokines were analysed with a commercial 12-plex bead ELISA. To block interference by RF, a commercial blocker (HeteroBlock) was used. To determine the optimal concentration of HeteroBlock, patient sera were analysed with different concentrations of HeteroBlock. Subsequently, baseline and follow-up sera from the 14 patients were analysed and correlated with clinical outcome.Results: Measured cytokine levels were reduced in the majority of samples when adding the blocker. The optimal concentration of HeteroBlock was 1600 μg/mL of serum. Sera with high RF levels were more prone to produce false positive values, although some RF-negative sera also demonstrated evidence of interference. HeteroBlock did not interfere with the analysis. In RA patients treated with adalimumab, changes in interleukin (IL)-6 levels between baseline and follow-up correlated with changes in erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in sera with added HeteroBlock.Conclusions: When analysing sera from patients with RA with multiplex bead ELISA, the assay should be evaluated for interference by heterophilic antibodies, and if present corrected with, for example, HeteroBlock. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the validity of rheumatoid arthritis (RA) diagnoses in patients participating in Finnish biobanks., Method: We reviewed the electronic medical records of 500 Finnish biobank participants: 125 patients with at least one visit with a diagnosis of seropositive RA, 125 patients with at least one visit with a diagnosis of seronegative RA, and 250 age- and gender-matched controls. The patients were chosen from five different biobank hospitals in Finland. A rheumatologist reviewed the medical records to assess whether each patients' diagnosis was correct. The diagnosis was compared with the diagnostic codes in the Finnish Care Register for Health Care (CRHC) and special reimbursement data of the Social Insurance Institution of Finland., Results: The positive predictive value (PPV) of CRHC diagnosis of RA (for seropositive and seronegative RA combined) was 0.82. For patients with a special reimbursement for anti-rheumatic medications for RA, the PPV was 0.89. The PPV was higher in patients with more than one visit. For one, two, five, and 10 visits, the PPV was 0.82, 0.85, 0.89, and 0.90, respectively, and for patients who also had the special reimbursement, the PPV was 0.89, 0.91, 0.93, and 0.94 for one, two, five, and 10 visits, respectively. In patients positive for anti-citrullinated protein antibodies, the PPV was 0.98., Conclusion: These results demonstrate that the validity of RA diagnoses in Finnish biobanks was good and can be further improved by including data on special reimbursement for medication, number of visits, and serological data.

Objectives: To compare baseline sociodemographic characteristics in two rheumatoid arthritis (RA) cohorts enrolled 10 years apart, and to examine differences with respect to the general population. Method: Clinical and sociodemographic data were collected in 320 early RA patients during 1996-98 (TIRA-1) and 467 patients in 2006-09 (TIRA-2). Multivariate logistic regression tests were performed and intercohort comparisons were related to general population data, obtained from official databases. Results: TIRA-2 patients were older than TIRA-1 (58 vs. 56 years). Women (both cohorts, 67%) were younger than men in TIRA-1 (55 vs. 59 years) and in TIRA-2 (57 vs. 61 years). Disease activity was similar but TIRA-2 women scored worse pain and worse on the HAQ. Approximately 73% were cohabiting, in both cohorts and in the general population. Education was higher in TIRA-2 than in TIRA-2 but still lower than in the general population. Women had consistently higher education than men. Education was associated with age, younger patients having higher education. In both cohorts, lower education was associated with increased disability pension and increased sick leave. Sick leave was lower in TIRA-2 than in TIRA-1 (37% vs. 50%) but disability pension was higher (16% vs. 10%). In TIRA-1, 9% of women had disability pension compared with 17% in TIRA-2. A similar decrease in sick leave and an increase in disability pension were also seen in the general population. Older age and a higher HAQ score were associated with increased sick leave and being in the TIRA-2 cohort was associated with decreased sick leave. Conclusions: TIRA-2 patients were slightly older, better educated, had lower sick leave and higher disability pension than those in TIRA-1. Similar changes were seen simultaneously in the general population. Belonging to the TIRA-2 cohort was associated with decreased sick leave, indicating that societal changes are of importance. [ABSTRACT FROM AUTHOR]

Objectives: Signal transducer and activator of transcription 4 ( STAT4) transmits signals induced by the cytokines interleukin (IL)-12, IL-23, and interferon (IFN)-γ, which play an important role in the development of rheumatoid arthritis (RA). Studies have shown conflicting results concerning the association between the rs7574865 G/T polymorphism in the STAT4 gene and RA in an Asian population. We have performed a meta-analysis to examine this relationship. Method: We searched PubMed and WanFang databases for all papers published up to 5 October 2013. Eight case-control studies with 6029 cases and 4685 controls were retrieved based on the search criteria for RA susceptibility related to the STAT4 rs7574865 G/T polymorphism. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed using Begg's test. Results: A significant association was found between the STAT4 rs7574865 G/T polymorphism and RA risk (e.g. GG+GT vs. TT: RR 0.96, 95% CI 0.95-0.97; GG+TT vs. GT: RR 0.94, 95% CI 0.91-0.97). Subgroup analysis of rheumatoid factor (RF) status revealed a protective relationship between the STAT4 rs7574865 G/T polymorphism and RF+/RF− RA risk. A similar relationship was detected in the anti-cyclic citrullinated peptide (CCP) status subgroup. No clear evidence of publication bias was detected in the overall analysis. Conclusions: Our study indicates that the STAT4 rs7574865 G/T polymorphism was significantly associated with a decreased RA risk in an Asian population. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the clinical implications of serum levels of R-spondin 1 (RSPO1), a natural antagonist for Dickkopf-1 (DKK1), and of DKK1/RSPO1 ratios in rheumatoid arthritis (RA) patients. Method: Serum DKK1 and RSPO1 levels were measured in 102 RA patients and 39 age- and gender-matched healthy controls. In addition, DKK1 and RSPO1 levels were determined prior to and 3 months after anti-tumour necrosis factor alpha (anti-TNF-α) therapy in 15 RA patients. Clinical and laboratory data and baseline radiographs of the hands and feet were obtained. Serial radiographs were evaluated in 83 RA patients. Radiographic joint damage was assessed by the modified Sharp/van der Heijde score (SHS). Results: Serum RSPO1 levels were significantly reduced whereas serum DKK1 levels and DKK1/RSPO1 ratios were significantly increased in RA patients compared with controls (all p < 0.0001). Anti-TNF-α treatment significantly suppressed DKK1/RSPO1 ratios (p < 0.01). In contrast to DKK1 or RSPO1 levels, the ratios were significantly associated with erosive disease, elevated acute phase reactants, Disease Activity Score in 28 joints (DAS28) > 3.2, and radiographic progression rate (all p < 0.05). Although the RA patients with radiographic progression exhibited significantly increased DKK1 and reduced RSPO1 levels (p < 0.05), only the DKK1/RSPO1 ratio (log-transformed) was found to be a significant predictor of subsequent radiographic progression [odds ratio (OR) 2.07, p < 0.01]. Conclusions: In this study, the presence of RSPO1 in the circulation was shown for the first time. Our results suggest that the serum DKK1/RSPO1 ratio represents a better predictor of structural progression than either DKK1 or RSPO1 levels alone in RA patients. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate work status and associated factors in patients with early rheumatoid arthritis (RA), with the emphasis on shoulder function, work-related mechanical exposure, and activity limitations related to the shoulder-arm-hand. Method: Patients with early RA were provided with self-report questionnaires quantifying work-related mechanical exposure and activity limitations. Shoulder function (i.e. isometric muscle strength, shoulder-arm movement, and shoulder pain), hand-grip force, and number of tender and swollen joints were assessed. Results: The study comprised 135 patients (103 women and 32 men), with a mean age of 48 (SD 9.6) years, a mean disease duration of 21 (SD 9.6) months, and a mean Disease Activity Score using 28 joint counts (DAS28) of 3.7 (SD 1.4). The majority (75.6%) were working full- or part-time. Work hours correlated with work-related mechanical exposure (rs = −0.34, p < 0.001) and with physical work load (rs = 0.26, p = 0.0036). Work hours also correlated with shoulder function, that is shoulder-arm movement (rs = 0.34, p < 0.0001), shoulder strength (rs = 0.25, p = 0.0032), and activity-induced shoulder pain (rs = −0.45, p < 0.0001). Significant correlations were found between work hours and hand-grip force (rs = 0.45, p < 0.0001), activity limitations related to the shoulder-arm-hand (using the Disabilities of the Arm, Shoulder and Hand Questionnaire, DASH) (rs = −0.61, p < 0.0001), and DAS28 (rs = −0.43, p < 0.0001). DASH was found to be the only significant (p < 0.001) variable to independently explain the ability of working full-time [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.29-0.55 per 10 increments, area under the receiver operating characteristic (ROC) curve (AUC) 0.81, 95% CI 0.74-0.89]. Conclusions: Work status in early RA is associated with shoulder function and activity limitations related to the shoulder-arm-hand accentuated by work-related mechanical exposure. [ABSTRACT FROM AUTHOR]

Objectives: Published studies have shown conflicting results concerning the association between the -169T/C promoter polymorphism in the Fc receptor-like 3 (FCRL3) gene and rheumatoid arthritis (RA). In this study we conducted an up-to-date meta-analysis to examine the relationship. Method: We searched the PubMed database for all papers published up to 20 April 2012. Overall, 18 case-control studies with 12 620 cases and 12 613 controls were retrieved based on the search criteria for RA susceptibility related to the FCRL3 -169T/C polymorphism. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of this association. Publication bias was assessed using the Egger test. Results: We found that the FCRL3 -169T/C polymorphism increased the risk for RA overall in genetic models (allelic contrast: OR 1.09, 95% CI 1.03-1.14, p = 0.001; homozygote comparison: OR 1.20, 95% CI 1.08-1.34, p = 0.001; dominant genetic model: OR 1.03, 95% CI 1.01-1.05, p = 0.001). Stratified analysis by race also showed a significant positive association with Asians and Caucasians. Subgroup analysis of rheumatoid factor (RF) revealed a slightly positive relationship between the FCRL3 -169T/C polymorphism and RF-positive RA risk. No obvious evidence of publication bias was detected in the overall analysis. Conclusion: Our study indicates that the FCRL3 -169T/C polymorphism is significantly associated with increased RA risk. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the prevalence of metabolic syndrome (MetS) in patients with rheumatoid arthritis (RA) vs. controls, and to verify possible associations of MetS with specific disease-related factors. Methods: The subjects were 283 RA patients and 226 healthy controls, frequency matched by age and sex. MetS was defined according to National Cholesterol Education Program (NCEP) criteria. Disease activity was evaluated with the Disease Activity Score using 28 joints (DAS28). A standardized clinical evaluation was performed and cardiovascular risk factors were assessed. Results: The criteria for MetS were met by 39.2% RA patients vs. 19.5% in the control group (p < 0.001). Increased waist circumference, elevated blood pressure (BP), and fasting glucose were more frequent in RA patients than controls (p < 0.001 for all associations). By multiple logistic regression analysis (adjusted for age, sex, and years at school), the risk of having MetS was significantly higher for RA patients than for controls [odds ratio (OR) 1.87, 95% confidence interval (CI) 1.17-3.00, p = 0.009]. The DAS28 was significantly higher in RA patients with MetS than in those without MetS (3.59 ± 1.27 vs. 3.14 ± 1.53; p = 0.01). Disease duration, the presence of rheumatoid factor, and extra-articular manifestations were similar for patients with and without MetS. Conclusions: MetS frequency was higher in RA patients than in controls. Among RA patients, MetS was associated with disease activity. The higher prevalence of cardiovascular risk factors in RA suggests that inflammatory processes play a notable role in the development of cardiovascular disease (CVD), and indicates that tight control of systemic inflammatory activity and CVD modifiable risk factors should be recommended. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine how many patients with undifferentiated arthritis (UA) are classified as patients with rheumatoid arthritis (RA) by the 2010 American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria for RA. Methods: The 2010 ACR/EULAR criteria for RA were applied to 102 patients with UA. UA is defined as an inflammatory arthritis that does not meet any criteria for a definitive diagnosis. We analysed discrepancy in the classification between previous criteria and the 2010 criteria by identifying patients who were categorized as those with RA. Results: The mean age of the patients was 46.8 ± 14.3 years. Rheumatoid factor (RF) was positive in 36 patients (35.2%), and 30 patients (29.5%) were positive for anti-cyclic citrullinated peptide antibody (anti-CCP). The 2010 ACR/EULAR criteria classified 33 patients (32.4%) as having RA, and 31 of them (93.9%) had the involvement of 1-3 small joints. All patients were seropositive, and 25 of them (75.8%) had high positive RF or anti-CCP. Seropositivity and small joint involvement was significantly different between patients who were classified with RA and those who were not (p < 0.001). Conclusion: Using the 2010 ACR/EULAR criteria, 32.4% of patients with UA were classified as having RA, and all were seropositive. Most of the UA patients with high positive RF or anti-CCP could be classified as having RA when we applied the 2010 ACR/EULAR criteria. [ABSTRACT FROM AUTHOR]

Objectives: Rheumatoid arthritis (RA) is a complex autoimmune disease with a strong genetic contribution in its pathogenesis. There is compelling evidence that autoimmunity is under genetic control and that oestrogens and their receptors (ESRs) can play a role in the high prevalence of RA in females. Methods: A total of 318 female patients with RA and 250 controls were examined. Common single nucleotide polymorphisms (SNPs) in the ESR1 (rs9340799:A>G, rs2234693:T>C) and ESR2 (rs4986938:G>A, rs1256049:G>A) genes encoding oestrogen receptors, previously associated with altered receptor expression, were selected for the purpose of this study. Results: There were no significant differences in the distributions of studied genotypes and alleles between RA patients and a control group. The age at disease diagnosis was lower in carriers of the ESR1 rs9340799 A allele compared with GG homozygotes as well as in patients with ESR1 rs2234693 TT and CT genotypes compared with CC homozygotes. There was no significant association of the genotypes with rheumatoid factor (RF), erosive disease, extra-articular manifestations, or anti-cyclic citrullinated peptide (anti-CCP) antibodies. Conclusions: The results of the study suggest that polymorphisms in the ESR1 gene may be associated with the age of onset of RA. [ABSTRACT FROM AUTHOR]

Objective: Radiographic damage is an important outcome in rheumatoid arthritis (RA). The disease course varies considerably, and there is a need for simple and reliable prognostic markers. The aim of the study was to determine the utility of early signs of extra-articular disease, manifested as rheumatoid nodules (RN), in predicting radiographic outcome. Methods: In a cohort (n == 1589) of consecutive, newly diagnosed patients with RA, 112 cases with RN at inclusion (7%%) were identified. Each case was compared to two age- and sex-matched controls without nodules from the same cohort. Radiographs of the hands and feet were performed at inclusion, after 1, 2, and 5 years and scored according to the modified Sharp van der Heijde Score (SHS; range 0--448). Results: Fifty-two cases with RN and 139 controls without RN had available radiographs at baseline and after 5 years. Cases were more often rheumatoid factor (RF) positive and anti-cyclic citrullinated peptide (anti-CCP) positive, and had higher disease activity and radiographic damage scores at baseline (7.9 vs. 2.5). After 5 years, there was more extensive radiographic damage among the cases (mean SHS progression 21.7 vs. 13.5). In bivariate analysis, positive RF, positive anti-CCP, SHS, and RN were strong baseline predictors for radiographic progression up to 5 years. In multivariate analysis, positive anti-CCP and SHS at baseline were independently associated with radiographic progression. Conclusion: The presence of RN at baseline is a marker of extra-articular involvement and severe disease, and a predictor of subsequent joint damage. [ABSTRACT FROM AUTHOR]

Objective: To describe a family with 13 members in four generations affected by early-onset isolated painful arthritis limited to the first metatarsophalangeal (MTP) joint but without evidence of generalized joint disease at follow-up. Methods: A complete family pedigree was constructed and radiographs from the affected family members and their offspring were taken. Laboratory tests including serum measurements of C-reactive protein (CRP), urate, and rheumatoid factor (RF) were performed to exclude gout and rheumatoid arthritis from the diagnosis. Results: The age at onset of first MTP joint symptoms varied from 12 to 51 years. Both females and males were affected in the four successive generations, including male-to-male transmission as well as maternal inheritance. The affected patients were often treated surgically with good pain-relieving results. Conclusion: To our knowledge, this is the first report of early-onset isolated foot metatarsal arthritis with apparent autosomal dominant inheritance. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate possible predictors of remission, normalized physical function, and work change in rheumatoid arthritis (RA). Methods: We determined in our early RA cohort the proportion of patients in remission [Disease Activity Score (DAS28)<2.6], with normalized function [Health Assessment Questionnaire (HAQ) = 0], and with changed working situation since disease onset. Candidate predictors of remission, normalized function, and work change were studied by subgroup comparison and logistic regression analysis, including demographics, education, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, treatment, and DAS28, HAQ, pain and fatigue scores (on the visual analogue scale, VAS). Results: Median (interquartile range, IQR) disease duration was 18 (29) months. Of 89 patients included, 69% were in remission. DAS28, HAQ, pain and fatigue scores of these patients were lower throughout year 1, although similar at baseline, compared to patients not in remission. At month 4, more of these patients were already good responders. Remission at month 4 independently predicted remission at follow-up. Thirty-eight per cent had no functional limitations; compared to patients with limitations, they had a lower baseline HAQ and lower DAS28, HAQ, pain and fatigue scores during year 1. At month 4, more achieved remission or HAQ = 0. Male sex, baseline HAQ, and month 4 good European League Against Rheumatism (EULAR) response predicted long-term HAQ = 0, but month 4 HAQ = 0 was the strongest independent predictor. Of the 40% with a paid job at baseline, 43.8% reported changes in their work situation; they had higher DAS28, HAQ, pain and fatigue scores during year 1. Failing a month 4 good EULAR response independently predicted work change. Conclusion: Month 4 disease response predicts later remission, normalized physical function, and work change in RA. [ABSTRACT FROM AUTHOR]

Objective: To determine whether the Simplified Disease Activity Index (SDAI) and the Clinical Disease Activity Index (CDAI) are equally applicable for the total population with rheumatoid arthritis (RA). Methods: Five hundred and fifty-seven outpatients with RA [432 females, 125 males; median age 64 years (range 18-85); median disease duration 48 months (range 2-548)] were enrolled consecutively in this cross-sectional study. SDAI, CDAI, patient's assessment of pain on the visual analogue scale (VAS) 0-100, rheumatoid factor (RF), and disease duration were recorded. Linear regression analysis was performed for each confounding factor. Results: The median SDAI for all 557 patients was 11.6 (range 0.07-46.60) and the median CDAI was 10.7 (0.00-42.10). The median SDAI was 12.2 (0.07-46.60) in females and 8.0 (0.10-35.20) in males. The respective medians for the CDAI were 11.3 (0.00-42.10) and 7.1 (0.00-32.00). These differences were highly statistically significant (p<0.001). Patient's assessment of pain on the VAS 0-100 scale had a median value of 32 mm. Regression analysis revealed a highly significant relationship between SDAI/CDAI levels and patient's pain rating (SDAI: r = 0.660, p<0.001; CDAI: r = 0.671, p<0.001). On multiple regression analysis, pain exerted a highly significant influence on SDAI and CDAI levels (p<0.001), whereas age, disease duration, and RF were not correlated with either level. Conclusion: SDAI and CDAI values are highly dependent on the patient's pain perception and gender. The effects of patient's age, disease duration, and RF were inconclusive with respect to the values of the respective disease activity indexes. [ABSTRACT FROM AUTHOR]

Objectives: To examine the diagnostic utility of the second generation of anti-cyclic citrullinated peptide (anti-CCP2) antibodies versus rheumatoid factor (RF) in rheumatoid arthritis (RA), and to study the association between anti-CCP2 and RA disease parameters. Methods: Fifty consecutive Egyptian patients with RA, 37 patients with other rheumatic diseases, and 10 healthy controls were recruited for testing for anti-CCP2 and immunoglobulin M (IgM) rheumatoid factor (RF). Assessment measures included the Disease Activity Score (DAS28) for disease activity, the Health Assessment Questionnaire - Disability Index (HAQ-DI) for disability and the Short Erosion Narrowing Score (SENS) for radiological damage. Results: The sensitivities of anti-CCP2 and IgM-RF in RA patients were 70% and 52%, with specificities of 91.5% and 89.4%, respectively. There was 73.2% agreement between anti-CCP2 and RF for all groups tested (κ = 0.42, p<0.001) but agreement was only 66% for RA patients (κ = 0.31, p<0.05). Anti-CCP2 had superior diagnostic properties [sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)] than RF, but using both RF and anti-CCP2 enhanced the sensitivity to 78%, when either test was positive, and the specificity to 100%, with a PPV of 1, when both tests were positive. Anti-CCP2 titre was significantly correlated with disease severity [rheumatoid nodules, rheumatoid factor (RF), and radiological damage] and HAQ-DI (p<0.05) but not with parameters of disease activity. Conclusion: Anti-CCP2 has superior diagnostic and prognostic properties in RA compared with RF. It should not replace RF as a serological test; however, since using both tests modestly increases sensitivity and markedly enhances specificity, so that diagnosis of RA is highly probable when both tests are positive. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to determine the prevalence of primary Sjögren's syndrome (pSS) according to European criteria (1993) and to the US–European Consensus Group (US‐EU) criteria (2002) in adult women in Bornova, Izmir, Turkey.Materials and method: The study was designed as a two‐phase cross‐sectional survey consisting of a baseline questionnaire and collection of blood samples and clinical examination. In the initial phase, positivity for autoantibodies Ro(SS‐A), La(SS‐B), rheumatoid factor (RF), and anti‐nuclear antibodies (ANA) was determined, and in the clinical phase, clinical examination, salivary and ocular tests were performed. Minor salivary gland biopsy was performed for those who had at least three of these five criteria positive.Results: In our sample the prevalence of SS was 1.56% [95% confidence interval (CI) 0.92–2.66] according to the European criteria and 0.72% (95% CI 0.33–1.57) according to the US‐EU criteria.Conclusion: To prevent the loss in diagnosis of pSS, the addition of ANA, RF, and tear break‐up time (BUT) tests to US‐EU criteria would be appropriate. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the prognostic value of rheumatoid factor (RF), detected in the Waaler–Rose agglutination assay and by nephelometry, in patients with recent‐onset rheumatoid arthritis (RA). Methods: Consecutive patients with new‐onset RA between 1993 and 1997 were followed for a median period of 4.7 years. Clinical data at baseline and drug use during the disease course were recorded. Outcome parameters studied were disease process, damage (erosions, joint surgery, extra‐articular manifestations, and new co‐morbidity), and death. Cut‐off levels for RF were >40 IU/mL (nephelometry) and titres &geqslant;1:160 (Waaler–Rose haemagglutination). Results: RF tests were negative by both methods in 22% of RA patients (RF- group), while 33% were RF positive by nephelometry only (RF+ group) and 45% were positive by Waaler–Rose and nephelometry (RF++ group). Baseline clinical and laboratory findings as well as the number of subsequently used disease‐modifying anti‐rheumatic drugs (DMARDs), the number of patients starting and the time spent on steroid therapy were similar in the three RF groups. Odd ratios for death (n = 23), erosions (n = 62), and serious extra‐articular disease manifestations (EAMs) (n = 13) as well as patient survival, erosion‐free or surgery‐free survival rates did not differ between the RF groups. Only rheumatoid nodules were more frequent in RF++ patients. Conclusion: The baseline presence of RF by either Waaler–Rose or nephelometry was not associated with differences in drug therapy, morbidity other than rheumatoid nodules, or mortality in RA patients in the first 5 years of disease. Being immunoglobulin M (IgM) RF positive thus had little impact on RA patient outcome. [ABSTRACT FROM AUTHOR]

We describe the case of a 30-year-old man with a severe autoimmune disease characterized by cryoglobulinaemia, pulmonary hypertension, Raynaud's phenomenon, lymphadenopathy, and glomerulonephritis. Despite initial remission following autologous stem cell transplantation, his disease relapsed and he died from pulmonary hypertension. At presentation the patient had hypergammaglobulinaemia and a number of autoantibodies, including rheumatoid factor (1:10240). The most striking feature was the extremely high level of cryoglobulins. The cryoprecipitate consisted of polyclonal IgM, IgG and albumin. Interestingly, the albumin in the cryoprecipitate was exclusively present in SS-bonded oligomeric forms, and contained an abnormal acidic component as judged by 2D gel electrophoresis. Oxidized albumin was also present in serum, and represented a small but significant fraction. None of the many known albumin variants have so far been associated with a particular disease; thus our results may represent the first description of an altered albumin associated with severe disease. [ABSTRACT FROM AUTHOR]

Objective: We investigated the rheumatoid arthritis (RA) diagnostic performances of anti-cyclic citrullinated peptide antibody (anti-CCP) and antifilaggrin antibody (AFA) in comparison with RF and matrix metalloproteinase-3 (MMP-3).Methods: We used a second generation enzyme-linked immunosorbent assay (ELISA) kit for the detection of anti-CCP. We constructed recombinant human filaggrin, which was citrullinated in vitro by human peptidylarginine deiminase, and subsequently used it as the coating antigen for AFA-ELISA. A total of 549 RA patients and 208 other rheumatic disease patients were included in the study.Results: The specificities of anti-CCP (88.9%) and AFA (94.7%) were superior to those of RF (81.7%) and MMP-3 (49.5%). The sensitivity of anti-CCP (87.6%) was superior to all others. However, the sensitivity of AFA (68.7%) was inferior to those of RF (69.8%) and MMP-3 (75.7%). Furthermore, receiver operating characteristic curves of anti-CCP and AFA passed closer to the upper left corner than those of RF and MMP-3, and the areas under the curves (AUC) of AFA and anti-CCP were significantly larger. In addition, the AUC of anti-CCP was significantly larger than that of AFA.Conclusion: ELISA detection of antibodies to citrullinated antigens, especially a second generation anti-CCP, showed higher discriminative ability than other assays, including RF, and would be useful to aid the diagnosis of RA in clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To investigate and compare the accuracy and usefulness of diagnostic tests for rheumatoid factor (RF).Methods: In a cross-sectional study sera derived from patients admitted to the Section of Rheumatology were tested for presence of RF using either nephelometry or the Waaler test. Diagnostic sensitivity and predictive values of the tests were calculated and compared. The accuracy of the tests was compared using receiver-operating characteristics (ROC) methodology.Results: Good agreement was found between the tests (kappa approximately 0.7). At cut-off 19 IU/mL nephelometry showed the highest sensitivity (82.4%) and specificity (95.9%) for rheumatoid arthritis (RA). In comparison, the Waaler test had a sensitivity of 60.3% and specificity of 95.9% at cut-off titer 128. The tests showed nearly equal performance characteristics when predicting SS.Conclusion: Although both tests exhibit good performance characteristics, nephelometry has a higher accuracy when predicting RA and SS. The common practice of using both tests for detection of RF is not recommended. [ABSTRACT FROM AUTHOR]

Not all extraocular photoreceptors in the human brain have been identified or their functions determined. The efferent and afferent fibres between the orbital frontal cortex and the hypothalamus cannot be overlooked in the context of the neuro-endocrine-immune feedback loop. It is suggested here that there are extraocular photoreceptors in the orbital frontal cortex, conceivably crucial for immunoregulation. The orbital frontal cortex of 7 volunteers with rheumatoid arthritis (RA) was photostimulated through the roof of the orbits with filtered visible light in sessions of 12, 14 and 16 minutes for a period of 6 weeks. Within 5 weeks, a significant decrease in the rheumatoid factor titres of 6 subjects was observed together with marked clinical improvement in 4 cases. [ABSTRACT FROM AUTHOR]

In the present study, the IgA rheumatoid factor (IgA RF) was assayed by ELISA in 114 sera of patients with active RA. IgA RF was found in the sera of 38 (33.3%) patients. A total of 56 disease variables were studied, differences in variables between IgA RF positive and negative patients were analyzed. The presence of IgA RF was found to be associated with a rapid progressive course, RA activity, onset of extra-articular manifestations (especially systemic rheumatoid vasculitis), high IgM RF titres, circulating immune complexes, cryoglobulins, and C-reactive protein levels. There was no statistically significant difference in serum IgA levels between IgA RF seropositive and seronegative patients. The presence of IgA RF showed a positive correlation with the level of IgM RF. The results of this study showed that the determination of IgA RF has a practical use in the establishment of the severe course of RA with systemic damages. [ABSTRACT FROM AUTHOR]

The aim of the study was to assess the prevalence of rheumatoid factor (RF) in a community-based rheumatoid arthritis (RA) series. The subjects of the series represented prevalent RA cases in the Kuusamo community in Northern Finland with 13,000 adult inhabitants. The patients were selected from the official Finnish data registers and from among the subjects who had consulted the local general practitioners due to rheumatic complaints in the recent years, using the American Rheumatism Association (ARA) 1987 classification criteria for inclusion. For this study, ninety-five out of the 103 RA patients so found were RF-tested by immunoturbidimetry. At the time of the study. 71 (75%) of the 95 cases were RF positive, 83 (87%) being 'ever' positive (in one case the early RF status was unclear). Our result contrasts with the much lower prevalence figures (25-60%) obtained from the earlier cross-sectional population-based RA studies, which have used the ARA 1958 definite RA as the inclusion criterion of the subjects. All the eleven patients with RF-negative RA had erosive joint disease. The RF-negative RA patients had a significantly lower frequency of HLA-DR4 (18%) than the RF-positive ones (58%), p < 0.05. We found a high frequency of RF among prevalent community-based RA cases meeting the ARA criteria. According to our results, RF-negative non-erosive RA is very rare among cases selected with the above methods. [ABSTRACT FROM AUTHOR]

The article presents several case studies of interstitial lung disease (ILD) after leflunomide (LEF) was combined with methotrexate (MTX) treatment in patients who had no pre-existing lung disease. Topics discussed include case of a 74 year old man with history of rheumatoid factor-positive (RF+) and used MTX for 85 months, case of a 49 year old woman with a history of ankylosing spondylitis and used MTX for 41 months and case study of a 59 year old man with RF+ RA and used MTX for 20 months.