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Rheumatoid arthritis (RA) is characterized by chronic inflammation in joints. Obesity, stress, being women, and dietary pattern are important in pathogenesis. The joint damage in RA is accelerated by oxidative stress. The aim of this study was to examine the serum total antioxidant level, nutritional status, and Mediterranean diet adherence of adult women with RA. 35 adult women RA patients and 35 healthy control subjects participated in this study (45.4 ± 11.61 and 42.5 ± 8.50 years, respectively). Nutritional status, physical activity levels, and adherence to the Mediterranean diet were questioned. Physicians assessed the disease activity score of patients with RA. Serum total antioxidant (TAS) and oxidant status (TOS) were analysed. The serum TAS of the control group was higher, whereas the oxidative stress index (OSI) and TOS were lower than that of RA group. Dietary protein, fiber, eicosapentaenoic acid (EPA), retinol, iron, zinc, and total antioxidant intake in the RA group were lower than the control group (p < 0.05). Individuals with higher fiber intake showed a significantly lower risk for RA after adjusted for potential confounding factors (OR = 0.845, 95% CI = 0.773-0.923, p < 0.001). The mean physical activity level of the control group was higher than that of the RA group (1.59 ± 0.10 and 1.53 ± 0.13, respectively) (p = 0.01). In conclusion, serum antioxidant parameters and dietary antioxidant intake are decreased in patients with RA. Therefore, medical treatment for these patients should be supplemented with medical nutrition therapy to achieve optimal nutritional status.

Objective: To investigate the central sensitization (CS) in patients with autoimmune connective tissue diseases (ACTDs) and its relationship with disease activity, laboratory findings, medical treatments, organ involvements, and comorbidity., Methods: One hundred and eleven patients with ACTDs and 40 healthy individuals were included. All patients were divided into three groups in terms of their diseases: Sjögren's syndrome (SS), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). The CS was assessed using the central sensitization inventory (CSI-A and CSI-B scores). The disease activity, laboratory findings, medical treatments, organ involvements, and comorbidity of all patients were evaluated., Results: Overall, 41.4% patients with ACTDs had CS. SS group had the highest CS positivity (n = 21, 58.3%) compared to the RA (n = 14, 36.8%) and SLE (n = 11, 29.7%) groups. The SS group had a significantly higher CSI-A score (p < 0.016) than the RA and SLE group, which had similar scores. CSI-A (p = 0.008, r = -0.63) and CSI-B (p = 0.001, r = -0.76) scores were moderately to high correlated with vitamin D3 levels in SLE group. CSI-B score was moderately correlated with folic acid levels (p = 0.03, r = 0.50) and TSH (p = 0.005, r = 0.55) in SS group. The CSI-A score ≥ 40 subgroup had more female gender, frequency of COPD or asthma, more coexisting fibromyalgia, higher VAS score, more common exocrine gland involvement, and higher corticosteroid dose compared to the CSI score < 40 subgroup., Conclusions: CS is commonly seen in patients with ACTDs, especially in SS. CS is associated with vitamin D3, folic acid, and TSH levels in ACTD subgroups and the patients with clinical CS have a specific profile., (© 2025 The Author(s). International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Objectives: Defining predictors of damage would improve patient care. We applied damage indexes to patients with familial Mediterranean fever (FMF) and identified the predictors of damage., Methods: This is a cross-sectional analysis of 926 FMF patients, who fulfilled the Tel-Hashomer criteria and had at least six months of follow-up. Patients were stratified according to their damage status (damage vs. no damage) defined with autoinflammatory disease damage index (ADDI) and modified ADDI (excluding musculoskeletal pain). We used logistic regression analysis to investigate independent predictors of damage for both indexes., Results: Mean disease duration was 21.6±11.9 years. 527 patients (57%) had damage according to ADDI. Median ADDI score was 1 (0-11). Most common FMF-related damages were observed in musculoskeletal, reproductive and kidney domains. Female gender, inflammatory comorbidity, colchicine resistance, colchicine nonadherence, musculoskeletal attack dominance, diagnostic delay, follow-up time, and smoking history remained independent predictors of damage according to ADDI score. The rate of patients with damage defined by modified ADDI was only to 23%. M694V/M694V homozygosity, female gender, musculoskeletal attack dominance, colchicine resistance, persistent inflammation, follow up time and family history of amyloidosis were found to be predictors of damage according to modified ADDI score., Conclusions: Our study is the first to apply comprehensive damage indexes to FMF patients and identified predictors of damage. Factors linked to a severe FMF phenotype, including M694V homozygosity and persistent inflammation, were associated with only modified ADDI. Our findings justify the concerns about musculoskeletal pain and might point to the need for re-evaluation of ADDI for FMF patients.

Objectives: To characterise autoimmune congenital heart block (CHB) associated with a maternal diagnosis of primary Sjögren's syndrome (pSS) confirmed either before, concomitant or after the first pregnancy complicated with CHB., Methods: The following inclusion criteria were applied: (i) Mothers with positive Ro/La autoantibodies detected previously or at the time of diagnosis of the first case of CHB; (ii) diagnosis of CHB confirmed by fetal echocardiography; (iii) AV block diagnosed in uterus, at birth or within the neonatal period (0-27 days after birth) (8); (iv) absence of anatomical cardiac abnormalities which might be causal of AV block; and (v) maternal fulfillment of the 2002 SS criteria before, during or after having a pregnancy complicated with CHB., Results: We identified 49 cases of autoimmune CHB in children born from 44 mothers who had a mean age at the time of pregnancy of 30.3 years (range 18 to 41). At the time of diagnosis of autoimmune CHB, all mothers had positive anti-Ro antibodies and 28/44 (64%) were positive for anti-La antibodies. Only 10 (22%) mothers with affected pregnancies had a diagnosis of primary SS at the time of diagnosis of the first pregnancy complicated by CHB (a mean of 4 years before, ranging from 1 to 10 years). In 6 (14%) mothers, primary SS was diagnosed during pregnancy or less than 12 months after the delivery/termination. In the remaining 28 (64%) mothers, pSS was confirmed 1-5 years after CHB diagnosis (n=19, 68%), 6-10 years after (n=2, 7%), or more than 10 years after the first case of CHB was diagnosed (n=7, 25%). CHB was diagnosed in uterus in all cases but two. AV block was initially incomplete in 11 fetuses and complete in 36 (no available data in 2 cases). Among the 35 (71%) surviving children with CHB, 5 (14%) developed other features of neonatal lupus. After the index pregnancy, 12 women had 20 subsequent pregnancies: five were complicated by a CHB (recurrence rate of CHB of 25%). The 4 women who had recurrent CHB were double-positive for anti-Ro and anti-La antibodies, and all had a confirmed pSS before having the first index case of CHB., Conclusions: In pSS, autoimmune CHB could be one of the first "indirect" signs of the disease in women of childbearing-age, in whom the diagnosis is confirmed several years later. Some maternal characteristics could be related with recurrent CHB, such as having an already-confirmed diagnosis of pSS and carrying the two Ro/La autoantibodies.

Objectives: To evaluate the systemic phenotype associated with the presence of isolated anti-La/SSB antibodies in a large international registry of patients with primary Sjögren's syndrome (pSS) fulfilling the 2002 classification criteria., Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. Baseline clinical information from leading centres on clinical research in SS of the 5 continents was collected. Combination patterns of anti-Ro/SSA-La/SSB antibodies at the time of diagnosis defined the following four immunological phenotypes: double positive (combined Ro/SSA and La/SSB,) isolated anti-Ro/SSA, isolated anti-La/SSB, and immunonegative., Results: The cohort included 12,084 patients (11,293 females, mean 52.4 years) with recorded ESSDAI scores available. Among them, 279 (2.3%) had isolated anti-La/SSB antibodies. The mean total ESSDAI score at diagnosis of patients with pSS carrying isolated anti-La/SSB was 6.0, and 80.4% of patients had systemic activity (global ESSDAI score ≥1) at diagnosis. The domains with the highest frequency of active patients were the biological (42.8%), glandular (36.8%) and articular (31.2%) domains. Patients with isolated anti-La/SSB showed a higher frequency of active patients in all ESSDAI domains but two (articular and peripheral nerve) in comparison with immune-negative patients, and even a higher absolute frequency in six clinical ESSDAI domains in comparison with patients with isolated anti-Ro/SSA. In addition, patients with isolated anti-La/SSB showed a higher frequency of active patients in two ESSDAI domains (pulmonary and glandular) with respect to the most active immunological subset (double-positive antibodies). Meanwhile, systemic activity detected in patients with isolated anti-La/SSB was overwhelmingly low. Even in ESSDAI domains where patients with isolated anti-La/SSB had the highest frequencies of systemic activity (lymphadenopathy and muscular), the percentage of patients with moderate or high activity was lower in comparison with the combined Ro/SSA and La/SSB group., Conclusions: Patients carrying isolated La/SSB antibodies represent a very small subset of patients with a systemic SS phenotype characterised by a significant frequency of active patients in most clinical ESSDAI domains but with a relative low frequency of the highest severe organ-specific involvements. Primary SS still remains the best clinical diagnosis for this subset of patients.

Objectives: To analyse the frequency and characterise the systemic presentation of primary Sjögren's syndrome (SS) out of the ESSDAI classification in a large international, multi-ethnic cohort of patients., Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry based on world-wide data-sharing and cooperative merging of pre-existing clinical SS databases from leading centres in clinical research in SS from the five continents. A list of 26 organ-by-organ systemic features not currently included in the ESSDAI classification was defined according to previous studies; these features were retrospectively recorded., Results: Information about non-ESSDAI features was available in 6331 patients [5,917 female, mean age at diagnosis 52 years, mainly White (86.3%)]. A total of 1641 (26%) patients had at least one of the ESSDAI systemic features. Cardiovascular manifestations were the most frequent organ-specific group of non-ESSDAI features reported in our patients (17% of the total cohort), with Raynaud's phenomenon being reported in 15%. Patients with systemic disease due to non-ESSDAI features had a lower frequency of dry mouth (90.7% vs. 94.1%, p<0.001) and positive minor salivary gland biopsy (86.7% vs. 89%, p=0.033), a higher frequency of anti-Ro/SSA (74.7% vs. 68.7%, p<0.001), anti-La/SSB antibodies (44.5% vs. 40.4%, p=0.004), ANA (82.7% vs. 79.5%, p=0.006), low C3 levels (17.4% vs. 9.7%, p<0.001), low C4 levels (14.4% vs. 9.6%, p<0.001), and positive serum cryoglobulins (8.6% vs. 5.5%, p=0.001). Systemic activity measured by the ESSDAI, clinESSDAI and DAS was higher in patients with systemic disease out of the ESSDAI in comparison with those without these features (p<0.001 for all comparisons)., Conclusions: More than a quarter of patients with primary SS may have systemic manifestations not currently included in the ESSDAI classification, with a wide variety of cardiovascular, digestive, pulmonary, neurological, ocular, ENT (ear, nose, and throat), cutaneous and urological features that increase the scope of the systemic phenotype of the disease. However, the individual frequency of each of these non-ESSDAI features was very low, except for Raynaud's phenomenon.

Objectives: Colchicine is the main therapy for familial Mediterranean fever (FMF); however, 5-10% of patients are colchicine-resistant. There is no standard and validated definition for colchicine resistance. We aimed to compare the existing definitions for colchicine resistance in both adult and paediatric FMF patients to find out the best definition to determine colchicine-resistant patients., Methods: 385 FMF patients were evaluated and patients receiving anti-interleukin-1 treatment were included. The anti-IL-1 therapy had been initiated by the experts in the past based on their experience. Eleven different definitions (found out after PubMed search for colchicine resistance in FMF) were applied to all patients. Results were re-analysed after excluding the patients who had no clinical attacks but persistently high acute phase reactants (APRs) and/or amyloidosis., Results: Sixty patients (40 adults/20 children) who had been using anti-IL-1 therapy were included into this study as colchicine-resistant patients. The highest percentage of patients fulfilled definition 5 (93.3%). Definition 9 had the poorest performance (26%). Significantly, a higher percentage of adult patients met definitions 4 and 6 than paediatric patients (87.5% vs. 50%, p=0.002; 75% vs. 40%, p=0.008, respectively). After excluding patients without clinical attacks, the highest percentage of patients fulfilled definition 2 (94.4%). We combined the attack frequency (>1 typical episode/3 months) in definition 2 and presence of amyloidosis/APR increase (increase in ≥2/3 APRs) in definition 5 to create a new definition which was met by 59 (98.3%) colchicine-resistant FMF patients., Conclusions: Definition of colchicine resistance is still controversial. Definitions with both clinical and laboratory criteria were met by a higher percentage of resistant patients than those without laboratory criteria. However, the proper definitions for the attack-free period and persistence of APRs are still lacking.

Background/objective: In patients with systemic sclerosis (SSc) gastrointestinal (GI) involvement, nutritional status and medications may lead to cobalamin (Vit B12) deficiency. We aimed to determine the frequency and the potential causes of Vit B12 deficiency in SSc patients., Methods: We conducted a cross-sectional analysis of 62 SSc patients in a single center in 1 year period. Medical history and physical examination of patients were reevaluated. Data about organ involvements were obtained from hospital file records. The nutritional status of the patients was assessed with Malnutrition Universal Screening Tool (MUST). Vit B12, homocysteine (except in three patients) and Helicobacter Pylori Immunoglobulin G (H. Pylori IgG) levels were measured in all patients. Vit B12 deficiency was considered as serum Vit B12 level <200 pg/mL or being on Vit B12 replacement therapy. Serum Vit B12 levels of the patients were also grouped as low (<200 pg/mL), borderline (200-300 pg/mL) and normal (>300 pg/mL). Plasma homocysteine levels of the patients were classified as elevated (>9 μmol/L) and hyperhomocysteinemia (>15 μmol/L). Mann-Whitney U and Kruskal-Wallis tests were used to compare parameters among the groups. Correlation was tested by Spearman's correlation coefficient., Results: Forty-four (71.0%) patients were defined as Vit B12 deficient; 22 had Vit B12 level <200 pg/mL (four were on Vit B12 replacement therapy) and the remaining 22 had Vit B12 >200 pg/mL and were already on Vit B12 replacement therapy. The percentage of the patients with hyperhomocysteinemia was significantly higher in the group with Vit B12 <200 pg/mL as compared to other groups (P = 0.004) but only 33.3% (7/21) of the patients with Vit B12 <200 pg/mL had hyperhomocysteinemia. There were no statistically significant differences between patients with and without Vit B12 deficiency regarding age, mean disease duration, MUST scores, mean hemoglobin levels, H. Pylori IgG positivity and organ involvements (P > 0.05 for all)., Conclusions: Vit B12 deficiency is frequent in SSc and has multiple causes. All patients should be monitored for Vit B12 deficiency. The homocysteine levels seem unlikely to be helpful for confirmation of Vit B12 deficiency.

Objectives: To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjögren's syndrome (SjS)., Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays., Results: By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti- La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglo-bulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for cryoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESS- DAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains)., Conclusions: We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.

Objectives: The objective of this study was to report the experience with rituximab treatment in a case series of patients with long-standing systemic sclerosis-associated interstitial lung disease (SSc-ILD)., Methods: We reviewed the charts of 197 SSc patients. Fourteen patients who received rituximab for SSc-ILD participated in this analysis. Pulmonary function tests, high-resolution thorax computed tomography and modified Rodnan skin scores were evaluated at baseline and end of the follow-up., Results: Median age was 53.2 years (interquartile range, 46.8-55.5 years), and median disease duration was 9.1 years (interquartile range, 5.1-13.6 years). At the end of median follow-up (15 months), although the median forced vital capacity value increased compared with baseline, the change was not statistically significant (52.5 vs. 58.0, P = 0.065). Forced vital capacity was improved in 4 patients and stabilized in 10 patients. High-resolution computed tomography was stable in 7 patients and worsened in 3 patients. Modified Rodnan skin scores remained stable at the end of follow-up (8.0 vs. 6.0, P = 0.6)., Conclusions: The improvement or stabilization of pulmonary disease was observed in most SSc patients with longer disease duration and worse pulmonary function. Rituximab might be useful in this patient group who is resistant to conventional immunosuppressive treatments.