Abstract in English:

Abstract Background Immunoglobulin A vasculitis (IgAV), also known as Henoch- Schönlein purpura (HSP), is the most common systemic vasculitis in childhood. Potential differences in demographic characteristics, clinical presentation, laboratory findings, and treatments approaches across age groups, remain poorly explored.To the best of our knowledge, no multicenter study in Latin America has systematically addressed these features. We aimed to assess demographic, clinical and laboratory features, and treatments in children versus adolescents with (IgAV)/ (HSP) in a large multicenter study. Methods A multicenter study involving four tertiary centers evaluated 687 children and adolescents (≤ 18 years-old) with IgAV/HSP (EULAR/PRINTO/PRES classification criteria) at first 3 months after diagnosis. The charts were retrospectively assessed for demographic data, initial clinical manifestations, laboratory tests and treatments. Data were compared between children (< 10 years-old) and adolescents (≥ 10 years-old), according to WHO definition. Results IgAV/HSP was diagnosed in 599/687(87%) children [5.33(0.88–9.91) years-old] and 88/687(13%) adolescents [11.33(10-17.5) years-old]. The median duration of purpura/petechiae was significantly lower in children compared to adolescents [14(1-120) vs. 15(2–90) days, p = 0.04]. The frequency of persistent purpura/petechiae (≥ 6 weeks of duration) was significantly reduced in the former group (7.2% vs. 19.5%, p = 0.002), likewise the frequency of gastrointestinal bleeding (17% vs. 34.1%, p = 0.01) and proteinuria (49.7% vs. 84%, p = 0.002). In contrast, the frequencies of arthritis/arthralgia (82.7% vs. 73%, p = 0.03) and orchitis(16.6% vs. 4.8%, p = 0.04) were significantly higher in children. Further analysis of laboratory tests showed that the median value of serum IgA was significantly lower in children than in adolescents [179.1(40-1002.0) vs. 279.0(104.0-488.0) mg/dL, p = 0.01], whereas thrombocytosis was higher (40.1% vs. 23%, p = 0.007). Logistic regression demonstrated that persistent purpura/petechiae after IgAV/HSP diagnosis (OR= 18.337; 95%CI 1.245-270.137; p = 0.034) was the only independently associated variable with dependent variable (adolescent). Conclusion In this large multicenter cohort, IgAV/HSP onset occurred rarely at adolescence, with a more prominent cutaneous involvement. Prolonged purpura/petechiae after IgAV/HSP diagnosis was associated with adolescent-onset IgAV/HSP, reinforcing the need for vigilant monitoring in this subgroup.

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Abstract Aim To determine the association of ultrasound (US) parameters with clinical features of patients with symptomatic hand osteoarthritis (HOA). Methods 72 patients (61.9 ± 10.3 years-old), 94 (92%) women with a diagnosis of painful HOA fulfilling ACR criteria seen between August 2019 and May 2023 were evaluated. Evaluations included pain (0–10 cm; VAS, visual analogue scale), grip (GrS) and pinch (PiS) strength (KgF), Cochin hand functional scale (CHFS), functional index for hand osteoarthritis (FIHOA), number of interphalangeal joints (IP) with pain/nodes, and serum C reactive protein (CRP). US was semi-quantitatively scored (0–3) in the most painful IP, assessing grey scale synovitis (GSS), synovial thickening (ST), effusion, and power Doppler signal (PD). Comparisons were made assuming the variables as independent and continuous, using Student's "t" test and multivariate analysis. Results GSS ≥ 2 synovitis was associated with lower GrS (p = 0.022) with a non-significant trend to be associated with higher FIHOA (p = 0.074) and Cochin (p = 0.093) scores. ST was also associated with lower GrS (0.003) and higher FIHOA (p = 0.045) with also a trend for higher Cochin score (p = 0.068). All but 4 joints had a negative PD, which precluded further evaluation. US parameters were neither associated with pain at rest/movement nor with number of IP nodes. Also, US features were similar regardless of serum CRP level and presence of OA in joints other than the hands. Conclusions GSS and ST are associated with worse physical function, meaning lower GrS, but not with pain level in symptomatic HOA patients.

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Abstract Background Sex differences in axial spondyloarthritis (axSpA) are increasingly recognized, with women often reporting higher disease burden despite similar objective inflammatory markers. This study aimed to compare clinical features, disease activity, function, quality of life, and treatment patterns between men and women with axSpA and identify sex-specific predictors of disease outcomes using data from the Brazilian Registry of Spondyloarthritis (RBE). Methods This was a cross-sectional, observational study based on data from the RBE, a nationwide multicenter cohort including 828 patients (568 men and 260 women) from 17 referral centers across Brazil. Standardized clinical and demographic data were collected using the REDCap platform. Disease activity (ASDAS-CRP, BASDAI), physical function (BASFI), spinal mobility (BASMI), and quality of life (ASQoL) were assessed with validated instruments. Sex-stratified multivariable linear regression models were constructed to identify independent predictors of each outcome. Results Women presented higher disease activity (median BASDAI 4.5 vs. 3.2; ASDAS-CRP 2.2 vs. 1.9), greater functional limitation (BASFI 5.0 vs. 4.0), and poorer quality of life (ASQoL 9.0 vs. 7.0) compared to men, despite similar CRP levels. Psychological distress was more frequent in women, while men had worse spinal mobility (BASMI 4.0 vs. 3.5) and higher HLA-B27 positivity. Regression models revealed that shoulder and hip pain were relevant predictors of disease activity in both sexes, but psychological factors and work activity more strongly influenced outcomes in women. Men's disease burden was more associated with structural damage and cardiometabolic comorbidities. Conclusions This study highlights distinct sex-related clinical patterns in axSpA. Women reported higher symptom burden, functional limitations, and reduced quality of life, largely influenced by subjective symptoms and comorbidities. Conversely, men presented greater structural impairment and different comorbidity profiles. These findings support the need for sex-informed clinical assessments and individualized management strategies in axSpA to tailor the care of these sex-specific disease trajectories, which may enhance equity and outcomes in real-world settings.

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Abstract Background Pain is a debilitating and persistent symptom of rheumatoid arthritis (RA), associated with impaired functional capacity and reduced quality of life. Despite targeted disease-modifying treatments, many RA patients experience persistent pain, suggesting mechanisms operating independently of classic inflammatory pathways. Psychological factors, such as depression and anxiety, can impact patterns of appraisal and behavioral coping strategies. Understanding how these associations underpin pain symptoms in RA is key for developing targeted symptom management interventions. Using data from the Patient-Reported Outcomes in patients with Persistent Rheumatoid Arthritis (PROsPer-RA) cohort, pain trends were assessed over 12 months following disease-modifying adjustment, mapping these against socioeconomic, psychological, and behavioral factors to identify associations and mechanisms. Methods This prospective study followed RA patients recruited to PROsPer-RA switching or escalating disease-modifying treatment. Clinical and patient-reported outcomes were collected at baseline, 3, and 12 months, including disease activity, joint pain (visual analog scale), widespread pain index (WPI), depression and anxiety symptoms, and cognitive and behavioral responses to symptoms. Latent growth curve models estimated associations between predictor variables and pain outcomes at baseline and over time. Mediation analyses examined whether cognitive and behavioral responses mediated the relationship between depression/anxiety symptoms and pain outcomes. Results Among 209 eligible patients, baseline joint pain was 49.8 ± 24.9 out of 100 (worst pain) and WPI was 4.9 ± 3.6 out of 17 areas, which persisted at similar levels at 3 and 12 months. Higher baseline pain was associated with male gender, financial stress, lower education, and unemployment. Higher levels in both pain outcomes associated with worse depression and anxiety symptoms at baseline and over time. Avoidance-based behavioral responses, particularly fear avoidance, were associated with worse pain and mediated the relationship between depression/ anxiety symptoms and both pain outcomes. Conclusions In this RA cohort, pain symptoms persisted at moderate-to-high levels over 12 months despite changing disease-modifying treatments. These symptoms were driven by psychological and behavioral factors alongside socioeconomic factors. Current RA therapies may be insufficient without considering the non-inflammatory processes driving persistent pain. Disease management should incorporate strategies that target mental health as well as cognitive and behavioral response patterns to symptoms.

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Abstract Background The myokines irisin and myostatin participate in bone and skeletal muscle homeostasis and may characterize the clinical status of these tissues. The study aimed to evaluate the association of myokines serum levels with one-year radiographic progression and lean mass in individuals with rheumatoid arthritis (RA). Methods Forty female individuals with RA, aged ≥ 18 years who met 2010 American College of Rheumatology criteria, and 30 individuals without RA and any chronical disease, matched by sex and body mass index (BMI) were included. Serum levels of irisin and myostatin were determined by immune assay. RA subjects had their radiographs of hands and feet evaluated by Sharp/van der Heijde score (SHS) at two timepoints, baseline and after one year. At baseline, disease activity was calculated by Disease Activity Score 28-C reactive protein (DAS28-CRP), body composition was evaluated using dual X-ray absorptiometry (DXA), muscle strength was assessed by handgrip test and chair rising test (CRT), and physical function was assessed by Health Assessment Questionnaire-Disability Index (HAQ-DI) and timed up and go (TUG) test. Results Mean age of individuals was 56 ± 7.8 years, mean DAS28-CRP was 3.3 ± 1.3, mean disease duration was 11.2 ± 9.2 years, and mean BMI was 28.1 ± 5.1 kg/m2. Rapid radiographic progression and low lean mass were present in 17.5% and 14.8% of the RA individuals, respectively, and showed no correlation with irisin and myostatin. Myostatin was significantly lower in RA than in controls (3021.7 ± 1217.2 vs. 4049.0 ± 1610.0 pg/ml; p = 0.011), and individuals treated with biologic disease-modifying antirheumatic drugs (bDMARDs) showed higher irisin levels than individuals non-treated with bDMARDs (31.7 ± 7.6 vs. 25.7 ± 6.8 ng/ml; p = 0.033). RA duration was correlated with baseline SHS (r = 0.563; p = 0.001) and appendicular lean mass index (ALMI; r= −0.451; p = 0.004), and irisin levels were positively correlated with TUG (r = 0.338; p = 0.35) in RA. Conclusions Long-term RA was related with higher SHS and lower ALMI, and the late disease stage of included individuals possibly masked the association of myokines with one-year radiographic progression or low lean mass. Otherwise, bDMARDs treatment influenced myokines circulating levels, specifically irisin.

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Abstract Objective Musculoskeletal complications represent a significant burden in diabetes, yet the distinct presentation between Type 1 (T1DM) and Type 2 Diabetes Mellitus (T2DM) remains under-characterized. This study aimed to evaluate and quantify the burden of rheumatic manifestations and subclinical enthesopathy in these two distinct clinical phenotypes. Methods We conducted a cross-sectional analysis of 65 patients (21 T1DM, 44 T2DM). A comprehensive rheumatological evaluation assessed adhesive capsulitis (defined as painful restriction of active and passive motion in ≥ 2 planes), knee osteoarthritis (per American College of Rheumatology clinical classification criteria), cheiroarthropathy, and soft tissue rheumatism. High-resolution musculoskeletal ultrasound evaluated five bilateral entheseal sites using the Glasgow Ultrasound Enthesitis Scoring System (GUESS). Effect sizes (Cohen's d) and 95% Confidence Intervals (CI) were calculated to assess the magnitude of intergroup differences. Results The T2DM phenotype was characterized by older age and higher BMI compared to T1DM. T2DM patients exhibited a markedly higher prevalence of adhesive capsulitis, knee osteoarthritis, and anserine bursitis. Ultrasound revealed a substantially higher enthesopathy burden in the T2DM group, with a mean GUESS score of 6.8 ± 2.1 compared to 1.1 ± 0.2 in T1DM. The effect size for the difference in enthesopathy scores (Cohen's d = 3.29) exceeded the effect size for the age difference (d = 2.79), suggesting that the observed structural burden may not be fully explained by age alone. Available HbA1c data showed similarly suboptimal glycemic control in both groups. Conclusion T2DM was associated with a higher burden of structural entheseal abnormalities and higher GUESS scores compared with T1DM. These findings may reflect the combined influence of obesity, metabolic factors, and age. Interpretation should consider baseline demographic differences between groups and the broad clinical definitions employed.

Abstract in English:

Abstract Background Although effectively controlling inflammation, up to 50% of patients with rheumatoid arthritis (RA) experience persistent pain, associated with central sensitization and neuroinflammation. Home-based transcranial direct current stimulation (tDCS) has shown efficacy in chronic pain. Objective To investigate whether anodal tDCS (a-tDCS) is more effective than sham stimulation in reducing pain. Methods Randomized, double-blind, sham-controlled trial with 34 women (18-70 years) with RA and VAS > 40 mm. Participants were randomized to receive a-tDCS (n = 17) or sham tDCS (n = 17). Home-based tDCS (2 mA, 20 min/day) or sham (2 mA, 90 s) for four weeks, using anodal-left M1 montage. Primary outcomes was pain (Visual Analogue Scale, VAS), Secondary outcomes included pressure pain threshold (PPT), central sensitization (CSI), physical function (HAQ-DI), fatigue (FACIT-F), CNS biomarkers, adherence, and safety. Results Mean VAS reduction from baseline was greater in the a-tDCS group (−33.5 mm) versus s-tDCS (−14.1 mm), with a between-group difference of −19.4 mm (95% CI, −29.3 to −9.5; p = 0.003). Linear mixed-effects models showed that a-tDCS reduced VAS pain by 27.7% versus 6.0% with sham, a between-group difference of 21.7% (Cohen’s d = 1.15). HAQ-DI improved by 38.0% versus 7.2% (ES = 1.10). a-tDCS reduced analgesic use by 62% (RR = 0.38; 95% CI, 0.18-0.79). Exploratory analyses suggested that neuroplasticity mechanisms might mediate these effects. Conclusion Home-based a-tDCS effectively reduced pain, disability, and analgesic use in RA patients with persistent pain without objective inflammation.

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Abstract Background Fibromyalgia is a stress-related disorder in which dorsal root ganglia (DRG) may play an important pathogenic role. DRG exhibit unique stress-induced, pro-algesic physio-anatomy, where each pain-sensing nerve fiber soma is encased and interacts with immune-competent satellite glial cells (SGCs). Patients suffering from fibromyalgia harbor anti-SGCs antibodies; however, the specific SGCs antigen(s) remain unidentified. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein serving as early SGCs activation marker. Different environmental stressors induce GFAP upregulation and structural modifications, including citrullination, potentially rendering it immunogenic. GFAP antibodies are implicated in autoimmune encephalomyelitis. We determine whether the serum of patients with fibromyalgia, collected before the COVID-19 pandemic, overexpresses GFAP and/or harbors antibodies against GFAP. Methods We studied 47 women with fibromyalgia and 31 healthy women. For GFAP antibody detection, a sensitive ELISA was developed using recombinant human GFAP. A commercial human GFAP ELISA Kit was used to measure GFAP serum levels. Results Significantly higher serum GFAP antibody optical density (OD) was detected in patients with fibromyalgia (median 0.04, 0.02–0.10 vs. 0.02, 0.01–0.05; p = 0.025). When the control group 99th percentile value (0.127 OD) was used as positive threshold, 9/47 (19%) patients tested positive for anti-GFAP antibodies. Patients with fibromyalgia showed numerically higher GFAP serum levels: (244.0 pg/ml ± 82.5 SD versus 211.4 ± 65.2. p = 0.057). Conclusion In this proof-of-concept study, patients suffering from fibromyalgia exhibit higher serum anti-GFAP antibodies and numerically augmented circulating GFAP levels. Future mechanistic studies will define GFAP role in the pathogenesis of FM.

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Abstract Background Sjögren disease (SjD) is an autoimmune disorder marked by exocrine gland dysfunction and systemic extraglandular manifestations (EGM). While nutritional status plays a key role in chronic diseases, its association with EGM in SjD remains underexplored. Aims This study aims to evaluate the nutritional status of patients with SjD using two validated tools the Controlling Nutritional Status (CONUT) score and the Prognostic Nutritional Index (PNI) and to examine their relationship with EGM. Methods A cross-sectional analysis was conducted on 113 patients diagnosed with SjD, categorized into two groups: those with EGM (n = 26) and those without (n = 87). Nutritional status was assessed using serum albumin, total lymphocyte count, and total cholesterol for CONUT, and serum albumin with lymphocyte count for PNI. Clinical, serological, and laboratory data were collected, including the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Results The mean age of participants was 56.2 ± 10.9 years, with 94.7% being female. The EGM group exhibited a significantly higher prevalence of anti-Ro and anti-Ro-52 antibodies. Compared to the non-EGM group, the EGM group had significantly lower levels of albumin, white blood cells, neutrophils, lymphocytes, and PNI scores, and higher ESSDAI and CONUT scores. Multivariate logistic regression identified ESSDAI, CONUT and PNI scores were independently associated with the presence of EGM at diagnosis. Conclusion This study underscores the importance of nutritional assessment in SjD, particularly in patients with systemic involvement. Malnutrition, as reflected by CONUT and PNI, is significantly associated with the presence of EGM. These findings highlight the need for routine nutritional screening in SjD management to support comprehensive care and improve patient outcomes. Key points SjD patients with extraglandular manifestation had significantly lower PNI scores and higher CONUT scores. CONUT and PNI scores were independently associated with the presence of EGM. Routine nutritional assessment is recommended in SjD management to support comprehensive care and improve outcomes.

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Abstract Background The clinical significance of IgM antiphospholipid antibodies (aPL) in antiphospholipid syndrome (APS) remains uncertain, while lupus anticoagulant is a well-established marker for thrombotic risk. Methods The objective of the study is to evaluate the impact of IgM aPL on the clinical phenotype of primary APS (PAPS). In this retrospective multicenter study, patients meeting updated Sapporo classification criteria were categorized into three aPL profiles: isolated lupus anticoagulant (isolated-LA), isolated IgM anticardiolipin and/or IgM anti-β2-glycoprotein I antibodies (isolated-IgM-aPL), and LA and IgM antibodies (LA + IgM-aPL). Clinical features were compared between isolated-LA vs. isolated-IgM-aPL and isolated-LA vs. LA + IgM-aPL groups. Results Among 202 patients, 17 (8.4%) had isolated-IgM-aPL, 145 (71.7%) isolated-LA, and 40 (19.8%) LA + IgM-aPL. Compared to isolated-LA, the isolated-IgM-aPL group had lower female prevalence (41.2% vs. 65.5%; p = 0.049), fewer venous thromboses (41.2% vs. 66%; p = 0.049), but more obstetric morbidity (58.8% vs. 26.2%; p = 0.005). There was a higher proportion of patients with livedo racemosa (47.1% vs. 20.7%; p = 0.015) and with white matter lesions (WML) (29.4% vs. 9.7%; p = 0.020) in the isolated-IgM-aPL group. In the multivariate analysis, WML remained independently associated (OR 3.7; p = 0.020). In the second comparison (isolated-LA vs. LA + IgM-aPL), a higher prevalence of livedoid vasculopathy (15.0% vs. 4.8%; p = 0.026) and WML (22.5% vs. 9.7%; p = 0.037) were observed in the LA + IgM-aPL group. Nonetheless, no independent associations were seen in the multivariate analysis. Conclusion IgM aPL may be associated with a distinct APS phenotype characterized by microvascular involvement, including livedo and WML. These findings support the need for further research into the clinical implications of IgM isotype positivity in APS.

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Abstract Background The increasing availability of biosimilars has raised important questions regarding their interchangeability with originator biologics in the treatment of immune-mediated rheumatic diseases. Addressing this issue is critical to ensuring patient safety, therapeutic efficacy, and informed clinical decision-making. Objective To present a position statement from the Biotechnology Committee of the Brazilian Society of Rheumatology on the interchangeability between originator and biosimilar biologic drugs in rheumatologic care. Methods A task force of 22 rheumatologists with expertise in immunobiological therapies followed a structured three-phase consensus process: (1) development of five key questions on biosimilar interchangeability; (2) comprehensive literature review using MEDLINE, EMBASE, and LILACS databases; and (3) final review and endorsement by relevant BSR committees. Expert opinion was used when evidence was limited or inconclusive. Results The position statement comprises five consensus-based recommendations, all unanimously supported by the task force, and supported by current scientific evidence and clinical experience. Conclusion The Biotechnology Committee of the Brazilian Society of Rheumatology endorses the safe and effective interchangeability of originator and biosimilar biologics when guided by principles that ensure patient safety, therapeutic continuity, and healthcare system sustainability. Clinical trial number Not applicable.

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Abstract Background Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk for infections due to both disease-related immune dysregulation and immunosuppressive therapy. Despite the benefits of vaccination, immunization rates in this population remain suboptimal, often due to concerns about safety, efficacy, and their potential for inducing disease flare. Regional-specific guidelines are necessary to address the particular epidemiological issues and aspects of the healthcare systems, especially in countries like Brazil. Objective To provide updated, evidence-based, and nationally relevant recommendations on vaccination in adult patients with IMRD in Brazil, focusing on immunogenicity, safety and disease activity outcomes. Methods A multidisciplinary task force from the Brazilian Society of Rheumatology conducted a systematic review and meta-analysis of studies addressing eleven clinical questions related to vaccine safety and efficacy in IMRD. Studies were selected using predefined PICO criteria. Risk of bias was assessed using JBI tools, and the certainty of evidence was evaluated with the GRADE approach. Statements were developed and submitted to a Delphi-based voting process; consensus was achieved if ≥80% of the panelists voted "agree" or "strongly agree" for all the statements. Results Eleven recommendations were developed based on a systematic review of the literature, with meta-analyses conducted when appropriate. Inactivated vaccines demonstrated a favorable safety profile, with low flare rates and no significant increase in disease activity, even under immunosuppression. Live attenuated vaccines, including yellow fever, were considered safe when administered according to timing protocols. Immunogenicity may be reduced in patients receiving methotrexate, mycophenolate, corticosteroids, rituximab, and JAK inhibitors, although this does not appear to compromise clinical protection in most cases. Temporary treatment interruption was associated with improved immunogenicity in selected contexts, but without consistent evidence of clinical benefit and with potential risks related to disease control. Specific guidance was provided for influenza and hepatitis B vaccination, as well as for prioritizing vaccination before initiating immunosuppression whenever feasible. Statements also addressed the approach to revaccination and post-vaccination serologic testing. Despite the overall very low to moderate certainty of evidence, most recommendations reached strong consensus (≥80% agreement). Shared decision-making and individualized strategies were emphasized across all scenarios. Conclusion These recommendations offer tailored guidance for improving vaccination strategies in IMRD patients in Brazil. Given the heterogeneity of evidence, clinical decisions should be individualized, considering disease activity, treatment regimen, vaccine availability, and patient preferences. Shared decision-making is essential in all scenarios to enhance vaccine uptake and align preventive care with patient-centered management.

Abstract in English:

Abstract We read with interest the study by Cirakoglu and Yuce on overactive bladder (OAB) and central sensitization (CS) in rheumatoid arthritis (RA) patients. While the study provides valuable hypothesis-generating insights, several methodological limitations warrant consideration. The OAB-V8 cut-off of 8 was validated in a primary care population, not in RA patients, and dichotomising this ordinal scale discards information and reduces statistical power. The regression model included correlated variables (HAQ-DI, VAS-pain, DAS-28) without testing for multicollinearity, which can inflate standard errors and produce unreliable p-values. Additionally, the authors did not verify key logistic regression assumptions, including linearity of continuous variables with the logit and absence of influential outliers. These limitations suggest that the findings should be interpreted as hypothesis-generating rather than definitive. Future studies should address these methodological issues to clarify the relationship between CS and OAB in RA.