Juvenile Idiopathic Arthritis (JIA) is a heterogeneous group of inflammatory arthritides encompassing at least six different categories, each with distinct clinical and biological characteristics. Despite significant advancements in the treatment of JIA, many cases of arthritis and/ or associated comorbidities such as chronic uveitis and interstitial lung disease (ILD) are refractory to current therapies. Janus kinase (JAK) inhibitors (JAKi) are small molecules or target–specific Disease Modifying Anti Rheumatic Drugs (tsDMARDs) that selectively inhibit janus kinases (JAKs) and block the JAK – Signal Transducers and Activators (STAT) pathway and the down steam proinflammatory effects associated with its activation. Herein, we review JAKi approved for the treatment of JIA and comment on JAKi currently with off- label use, with special considerations for their use in JIA-associated extraarticular manifestations and complications.
Obesity is common in psoriatic arthritis (PsA) and is associated with higher disease activity, poorer treatment response, and increased cardiometabolic risk. Digital lifestyle interventions may offer significant support for weight management, but their role in PsA care remains insufficiently explored. To evaluate the impact of a PsA-tailored version of the Gro Health app and digital tier 2 weight management program on patient body weight and disease activity. A secondary objective was to assess patient engagement with this platform as part of a service innovation in routine rheumatology care. This longitudinal observational study recruited 200 adults with PsA and BMI ≥ 25 kg/m² from routine NHS rheumatology clinics at University Hospitals Coventry and Warwickshire NHS Trust, UK. Of these, 100 patients were offered access to the Gro Health app alongside usual care, and 100 were BMI-matched controls receiving standard care alone. Patients were followed for six months. App engagement, body weight, Composite Psoriatic Disease Activity Index (CPDAI), domain-specific disease activity, and patient-reported outcomes were analyzed. Outcomes were compared between app engagers, non-engagers, and BMI-matched controls. Forty-six patients engaged with the app at least weekly. App engagers achieved significantly greater weight loss compared with non-engagers and controls (− 1.55 kg vs. − 0.18 kg vs. + 1.7 kg; p < 0.001). CPDAI improved in engagers (− 0.58) but worsened in non-engagers and controls (p < 0.001). Improvements were most pronounced in arthritis (p = 0.017) and enthesitis (p = 0.034) domains. Weight loss correlated significantly with improvements in disease activity (ρ = 0.372, p < 0.001). In multivariable analysis, changes in body weight and baseline disease activity remained independent predictors of CPDAI. A multidimensional lifestyle app incorporating tier 2 weight management content, health coaching, and structured digital guidance was associated with modest weight loss and improvements in PsA disease activity, particularly in the arthritis and enthesitis domains. These findings support integrating coached digital weight management strategies into PsA care; however, larger controlled studies are required to confirm efficacy and optimize patient engagement.
To characterise the clinical and genetic profile of adult familial Mediterranean fever (FMF) patients at a German tertiary referral centre and examine genotype–phenotype associations. In this prospective single-centre registry study (October 2019–March 2021), 95 adult FMF patients at University Hospital Tübingen were evaluated using structured questionnaires and medical record review. All patients had a pre-existing clinical diagnosis of FMF based on the Tel Hashomer and/or Eurofever/PRINTO criteria. Demographic data, clinical manifestations, treatment, and MEFV mutations were analysed. Patients were stratified by mutation status (homozygous M694V, heterozygous/compound-heterozygous M694V, other mutations). Statistical analyses included the Fisher–Freeman–Halton exact test and ANOVA. Variants were classified according to the INSAID consensus classification; R202Q was treated as a benign polymorphism. All subgroup comparisons were exploratory and were not corrected for multiple testing. Median age was 36 years, with median symptom onset at 10 years. Most patients were of Turkish origin (74.7
Juvenile idiopathic arthritis (JIA) frequently leads to musculoskeletal complications that persist into adulthood. This study aimed to comprehensively assess bone mineral density (BMD), body composition, and muscle strength in young adults with JIA compared with healthy controls. In this cross-sectional case-control study, 147 participants (81 JIA patients, 66 healthy controls) were evaluated. BMD and body composition were assessed via dual-energy X-ray absorptiometry; muscle strength was measured by handgrip strength (HGS) dynamometry. Sarcopenia was defined according to the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. Data were analyzed using analysis of covariance (ANCOVA) adjusted for age, sex, and height. Adjusted odds ratios (OR) for sarcopenia and low BMD (Z-score ≤ − 2.0) were calculated using Firth’s penalized logistic regression to account for age and sex. Patients with JIA had significantly lower BMD at all sites (p < 0.01), with the largest deficit in total forearm BMD (0.524 ± 0.094 vs. 0.691 ± 0.100 g/cm², p < 0.001). JIA patients also showed a significantly lower skeletal muscle index (SMI) (6.05 ± 1.52 vs. 6.89 ± 1.19 kg/m², p < 0.001) and markedly reduced HGS (18.0 [14.0; 25.0] vs. 25.5 [22.0; 37.5] kg, p < 0.001). Sarcopenia was present in 54
Interdisciplinary team-based rheumatology care models are a promising solution for improving access to high quality, equitable care for people with rheumatic and musculoskeletal disorders. There is limited understanding on health professionals’ perspectives on their needs to deliver care under this model. We explored rheumatology team members’ perceptions on individual and practice features required for optimal team-based care. We conducted a qualitative descriptive study using secondary analysis of semi-structured interviews with rheumatologists (n = 3), interdisciplinary health professionals (IHPs) (n = 7), and administrators (n = 5) in an interdisciplinary rheumatology team in Ontario, Canada. Interviews explored team members’ experience working within the team and the health professional and clinic characteristics they perceived as necessary for optimal team-based care. We coded interview transcripts inductively and constructed themes using thematic analysis. We identified three themes: (1) Key health professional qualities; (2) Synergy of complementary skillsets; and (3) Supportive operational structures. Participants felt that health professionals must acquire rheumatology-specific training in addition to bringing discipline-specific skillsets to work collaboratively to meet patients’ needs. They perceived that their complementary skillsets benefited patients (e.g., better clinical outcomes) and was also professionally rewarding. Participants emphasised the importance of operational structures necessary for optimal team-based rheumatology care, including shared workspaces and electronic medical records, competitive compensation, and stable funding. Rheumatology team members highlighted key considerations for health professionals and practices when developing optimal team-based rheumatology practices. This study offers insights to support policy, practice, and health system-level efforts to spread and scale team-based rheumatology care models.
To describe real-world clinical outcomes of belimumab (BEL) treatment in patients with systemic lupus erythematosus (SLE), with a particular focus on longitudinal glucocorticoid tapering and exploratory renal analyses. This single-center retrospective observational study included 46 patients with SLE who initiated BEL treatment between 2018 and 2025. Clinical and laboratory data, including prednisolone (PSL) dose, disease activity indices, serological markers, urine protein-to-creatinine ratio (UPCR), and estimated glomerular filtration rate (eGFR), were collected at baseline and during follow-up, when available. Longitudinal changes in concomitant background therapies were summarized descriptively. Exploratory renal analyses were performed in patients with lupus nephritis (LN) using changes in the UPCR and eGFR. Drug retention was evaluated using the Kaplan–Meier method. Renal histopathological analyses were performed in a subset with available biopsy data and were considered exploratory because of the heterogeneous clinical backgrounds and variable biopsy timing. The median PSL dose decreased from 10 mg/day at baseline to 8 mg/day at 24 weeks and 6 mg/day at 52 weeks after BEL initiation, with significant within-patient decreases at both time points (p < 0.001). Overall disease activity remained controlled, while complement levels improved during the follow-up. Among patients with LN (n = 12), UPCR showed a numerical decrease at 24 weeks (p = 0.055) and decreased at 52 weeks (p = 0.016) among patients with paired data, whereas the eGFR showed no significant change at either time point. Exploratory analyses did not identify significant associations between the available renal histopathological indices and changes in proteinuria. BEL treatment was continued in many patients during follow-up, although adverse events, including severe infections and death, were observed. In this real-world cohort, PSL doses decreased during follow-up after the initiation of BEL, while the overall disease activity remained controlled. In the small LN subgroup, the UPCR decreased at 52 weeks, and the eGFR remained stable. Because this study lacked a comparator group and the renal analyses were exploratory and limited by the small sample size, heterogeneous treatment backgrounds, and variable biopsy timing, these findings should be interpreted as within-patient observational data and require validation in future studies. What is already known about this subject? • Belimumab is effective in reducing disease activity in patients with systemic lupus erythematosus. • Its role in glucocorticoid tapering and renal outcomes in real-world clinical settings remains insufficiently characterized. What does this study add? • In this single-center real-world cohort, prednisolone doses decreased during follow-up after belimumab initiation, while overall disease activity remained controlled. • In the small lupus nephritis subgroup, the UPCR decreased at 52 weeks and the eGFR remained stable; however, these renal findings were exploratory and should not be interpreted as evidence of causal effects of treatment.
The concept of the gut-joint axis is often mentioned when exploring the pathogenesis of Ankylosing spondylitis (AS). This study aims to explore whether there is a causal association between Celiac disease (CeD) and AS. Two-sample Mendelian randomization (MR) analysis was conducted using the CeD dataset (the largest pure CeD phenotype dataset in the IEU OpenGWAS database at the time of data retrieval, n = 24,269) and the AS dataset (strictly defined, from the IEU OpenGWAS database, n = 218,030). Inverse Variance Weighting (IVW) was adopted as the primary MR analysis method, supplemented by Weighted Median Estimator, MR-Egger regression, Simple Mode, and Weighted Mode to comprehensively evaluate the causal association between CeD and AS. Additionally, horizontal pleiotropy, heterogeneity, and leave-one-out analysis were performed to further evaluate the robustness and reliability of the results. IVW analysis showed a positive causal effect of genetically predicted CeD on AS (OR: 1.435, 95
Patients with giant cell arteritis (GCA) are considered to be at increased risk of infections. The objectives of this study were to investigate the risk of severe infections in different time intervals after the diagnosis of GCA, compared to the general population, and to explore potential predictors for severe infections including large vessel involvement (LVI). Patients with biopsy-proven GCA, diagnosed between 2002 and 2010 in Region Skåne, Sweden, were identified and each case compared with 4 age-, sex- and residence area-matched reference subjects. Aortic involvement and other LVI was identified by case record review. Data on severe infections (requiring hospitalization) were obtained from linkage to the Skåne Healthcare Register through 2011. Prevalent comorbidities at GCA diagnosis were identified using ICD-10 codes. Predictors of severe infection in patients with GCA were evaluated using Cox regression. In 516 patients with GCA (100 with LVI), 22.9
To analyze the available scientific evidence on differences in inflammatory biomarker levels between patients with fibromyalgia and healthy controls. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. Methodological quality was assessed using the Newcastle–Ottawa Scale. Inflammatory, neuroendocrine, and oxidative stress biomarkers were analyzed, along with their association with clinical symptoms. Eighteen observational studies (case–control and cross-sectional) involving a total of 1,605 participants were included. Of these 18 studies, quantitative data suitable for meta-analysis could be extracted from only 10 studies. The fibromyalgia group showed elevated levels of p =high sensitive C-reactive protein (hsCRP) levels confirmed by meta-analysis too (SMD = 0.34; 95
Sjögren’s disease is an autoimmune condition that may have neurological involvement. Rituximab is a monoclonal antibody against CD20 that has shown potential in the management of central and peripheral neuropathy in lymphomas and some autoimmune disease. There is limited data on the efficacy of rituximab on central nervous system (CNS) involvement in Sjögren’s disease. The aim of this systematic review was to assess the effects of rituximab on CNS involvement among adults with Sjögren’s disease. The PubMed, Scopus, and Web of Science medical databases were searched and the related articles were included in the review based on the inclusion and exclusion criteria. All articles published in English language that reported the effect of rituximab in the management of CNS involvement in Sjögren’s disease were included and reviewed. Of the primary retrieved 173 articles, three (N = 62) were included in the review. All the studies were cohort studies and reported the effects of rituximab on CNS involvement as secondary analysis. Rituximab was administered in combination of other medications. Data synthesis revealed that rituximab, especially in combination with other medications, might have beneficial effects in severe and refractory CNS involvement in Sjögren’s disease. Rituximab administration should be limited to severe and refractory CNS involvements in Sjögren’s disease. However, due to the scarcity of articles and low level of confidence, further studies should be conducted to reach a definite conclusion.
Abstract Background Systemic lupus erythematosus (SLE) is a systemic autoimmune disease targeting multiple organ systems, including the nervous system. The cerebellum may be involved in prevalent neuropsychiatric manifestations, such as depression and cognitive dysfunction, alongside other prevalent SLE manifestations such as pain and fatigue. We aim to compare cerebellar volumes in SLE patients and healthy individuals (HI) and assess the correlation between cerebellar volumes and cognitive impairment, fatigue, pain, and depression in SLE. Methods 72 female SLE patients and 25 age- and sex-matched HI underwent 3 tesla magnetic resonance imaging (MRI), clinical evaluations, and cognitive testing. T1-weighted MRI scans were segmented using CEREbellum Segmentation (CERES) volBrain automatic segmentation. Extracted cerebellar lobule volumes (normalized to total cerebellar volume) were compared between SLE and HI using analyses of covariance (ANCOVA). In regions showing significant volume changes between SLE and HI, the relationship between volume and clinical scores for cognitive impairment, fatigue, pain, and depression was analyzed using either ANCOVAs or partial correlation analyses. Results Lobular analysis of the cerebellum revealed significant (p < 0.05) region-specific volume alterations in SLE compared with HI. Bilateral and left lobule IV volumes were larger, while bilateral, right, and left lobule VIIB volumes were smaller in SLE compared to HI. Smaller white matter volumes in right lobule VIIIA, and right lobule X and larger white matter volumes in lobule crus I were observed in SLE compared to HI. In SLE, smaller VIIB volumes were significantly correlated with poorer cognitive performance (both complex attention and cognitive flexibility), and with higher fatigue scores. Conclusion The findings suggest that the cerebellum, and particularly lobule VIIB, is involved in SLE and may contribute to both cognitive dysfunction and fatigue in patients with systemic lupus erythematosus. Trial registration Not applicable.
Abstract Background Autoimmune connective tissue diseases (ACTD), including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), Sjögren’s disease (SD), and idiopathic inflammatory myopathies (IIM), are associated with markedly increased cardiovascular risk (CVR) that is insufficiently captured by conventional risk scores. Reliable biomarkers for CVR stratification in ACTD are lacking. This exploratory, hypothesis-generatig study aimed to investigate whether metabolomic alterations reflect CVR across ACTD subtypes. Methods In this cross-sectional, exploratory study, patients with SLE (n = 33), SSc (n = 18), SD (n = 16), and IIM (n = 9) were recruited from a tertiary rheumatology center. Serum metabolomic profiling was performed using ¹H-NMR spectroscopy. Associations between 113 quantified metabolites and clinical CVR parameters (including age, sex, body mass index, glucocorticoid use, Framingham score, hypertension, diabetes, lipid parameters, and lifestyle factors) were analyzed using non-parametric statistics with false discovery rate correction. Correlation analyses were conducted using Spearman coefficients. Results Metabolomic alterations varied substantially across ACTD subtypes and CVR factors. Lipid metabolites showed the strongest and most consistent associations with CVR parameters. The Framingham score correlated with 11 metabolites in SLE, 1 in SSc, 2 in SD, and 93 in IIM, predominantly involving lipid components. Diabetes mellitus was associated with extensive metabolomic changes, particularly in SSc (n = 62 metabolites), followed by SD (n = 20) and SLE (n = 5). In contrast, arterial hypertension showed minimal metabolomic differentiation across most ACTD, except in IIM. Body mass index correlated mainly with lipid metabolites in SSc, but not in SLE. Glucocorticoid therapy and dosage were strongly associated with alterations in lipid metabolism, especially in SLE and SSc. Across all entities, correlations with total cholesterol, LDL, and HDL were dominated by lipid metabolites. Associations with renal markers (UACR) were limited. Conclusions ACTD are characterized by heterogeneous metabolomic signatures associated with cardiovascular risk factors. Larger, longitudinal studies are required to validate these findings and to determine their clinical utility in cardiovascular risk stratification in ACTD.
Systemic lupus erythematosus (SLE) has a significant female bias; however, it remains unclear whether X-chromosomal dysregulation increases the risk in females. Furthermore, while the role of X-linked genes in SLE pathogenesis is recognised, the analysis of genetic risks in SLE has largely focussed on autosomal genes. Here, we analysed a public single-cell RNA sequencing (scRNA-seq) dataset of peripheral blood mononuclear cells using machine learning to test whether X-linked gene expression classifies female SLE in a cell type-specific manner. Using pseudobulked expression profiles from 1.1 million cells across 228 female donors, we trained an ensemble of classifiers on all X-chromosomal genes or a literature-derived set of SLE-associated genes. In CD4+ and CD8+ T cells, models based on X-chromosomal genes achieved classification performance comparable to SLE gene models and were significantly enriched for XCI escape genes, with IL2RG, CD40LG, and TKTL1 emerging as key features. When applied to an independent paediatric–adult SLE cohort, CD8+ T-cell models retained a consistent performance, indicating a stable and reproducible X-linked signature in this subset. Flow cytometry revealed a modest increase in IL2RG protein expression in SLE T cells, consistent with partial escape from XCI in these cells. These findings demonstrate that X-linked transcriptional programs, enriched for known XCI escape genes and concentrated in activated T cells, encode a reproducible transcriptional signal of female SLE and provide a framework for dissecting the contributions of sex chromosomes to autoimmunity.
Systemic Lupus Erythematosus (SLE) is a severe autoimmune disorder that impacts multiple organ systems, with African American (AA) adults having worse outcomes and poor prognoses compared to other ethnic groups. Ineffective patient–provider communication and inadequate screening for modifiable risk factors contribute to poorer SLE outcomes and ongoing health disparities. This scoping review evaluated the influence of patient–provider communication among adults with SLE, with particular attention to implications for African American populations, to inform the development of strategies to mitigate SLE health disparities. An electronic search was conducted using PubMed, CINAHL, Embase and PsycINFO databases to systematically identify published literature between 2012 and mid-2025. Studies were eligible (1) if participants included African American adults (over 18 years old) with a diagnosis of SLE or included a sample with ≥ 50
Clinicians often recognise broader deterioration in a patient’s overall condition that is not fully captured by conventional disease-specific measures. Ageing is associated with reduced physiological reserve and altered body fluid distribution. However, objective markers that capture these changes remain limited. Because the extracellular water-to-total body water ratio (ECW/TBW) reflects fluid distribution, we hypothesised that its prognostic relevance is age-dependent rather than uniform. In this retrospective cohort study, 186 adults with rheumatoid arthritis underwent bioelectrical impedance analysis in 2017 and were followed until December 2025. The primary outcome was a composite of all-cause death or transition to do-not-attempt-resuscitation/best supportive care (DNAR/BSC) status. Cox proportional hazards models including an age × ECW/TBW interaction term were used. Age-stratified analyses used the cohort median age (68 years). During a median follow-up of 95.2 months, 17 participants experienced death or transition to DNAR/BSC status. Age was strongly associated with risk (HR per 10-year increase 2.53, 95
Rheumatoid arthritis (RA) is a chronic inflammatory disease that impacts patients’ quality of life. Evidence regarding the effectiveness of metformin use as an adjunct therapy in RA is limited and fragmented. This systematic review and meta-analysis aimed to evaluate the effectiveness of metformin as an adjunct therapy in RA and to quantitatively synthesize available evidence. This systematic review and meta-analysis were conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, focusing on randomised controlled trials (RCTs) that assessed the effect of metformin as an adjunct therapy for patients with RA receiving conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). C-reactive protein (CRP), Disease Activity Score in 28 joints (DAS-2)8, and Health Assessment Questionnaire Disability Index (HAQ-DI) were included as an outcome. A search was conducted across four databases up to 31 December 2025, including PubMed, Embase, Cochrane Central, and Scopus. The methodological quality of the included RCTs was evaluated using risk of bias 2 (RoB 2) tool. Statistical analysis was conducted with StataNow version 19.5. For each outcome, pooled mean differences (MDs) with 95
Interstitial lung disease (ILD) is a serious extra-articular complication of rheumatoid arthritis (RA) and a leading cause of mortality. This meta-analysis aims to comprehensively evaluate the diagnostic utility and clinical relevance of tumor-associated biomarkers in patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD). A systematic literature search was conducted in PubMed, EMBASE, Web of Science, CBM, Wan-Fang, and CNKI databases from inception to April 1, 2025. We included case-control and cohort studies that compared tumor marker levels between RA-ILD and RA-non-ILD patients, following the PICOS framework. Study quality was assessed using the Newcastle-Ottawa Scale (NOS). Pooled effect sizes were calculated as standardized mean differences (SMD) with 95
Abstract Background Gout is among the most prevalent arthritides worldwide and is associated with high morbidity, cardiovascular risk, and substantial healthcare burden. Despite effective urate-lowering therapies (ULT), many patients remain undertreated, particularly those with severe or complex disease. Nurse-led gout management has improved outcomes in primary care, but data in multimorbid tertiary center populations are lacking. We aimed to evaluate the effectiveness of a supervised nurse-led gout clinic in achieving and maintaining serum urate (SU) targets in a tertiary hospital cohort. Methods In this observational study at the University Hospital (Inselspital) Bern we report on the performance during May 2023 and Jan 2026 in 69 patients with confirmed gout per a restricted panel of EULAR/ACR 2015 classification criteria. Patients were assigned to SU targets of ≤ 300 µmol/L (group 1: severe gout) or ≤ 360 µmol/L (group 2: non-severe gout). An Advanced Practice Nurse (APN) provided education, a rheumatologist provided pharmacological management per 2016 EULAR/ACR guidelines. SU levels, flare frequency, prophylaxis, and treatment adjustments were monitored, with follow-up at six and twelve months. Results Group 1 required higher allopurinol doses than group 2 ( p ≤ 0.01). SU targets were achieved in 80% of group 1 regimens and 68% of Group 2. Flare rates and prophylaxis use were comparable. At six/twelve months follow-up, 62/67% of group 1 and 85/88% of group 2 maintained SU targets. Failures were often due to external treatment modifications. No major ULT-related adverse events were observed. Conclusion Supervised nurse-led gout management effectively achieves SU targets in this difficult-to-manage cohort. Maintaining SU targets may benefit from shorter follow-up intervals and enhanced education for patients and healthcare providers.
Abstract Background It is known that pregnancy affects disease activity in Rheumatoid arthritis (RA), but earlier studies have shown conflicting results regarding the degree of change and the role of antibodies. Few studies have been conducted on patients with use of Tumor Necrosis Factor-α Inhibitors (TNFi) throughout pregnancy. The aims of this study were to investigate disease activity in women with RA from preconception to 12 months postpartum and assess the influence of anti-cyclic citrullinated protein antibodies (ACPA), rheumatoid factor (RF), erosive disease, and time trends. Methods This prospective multicenter cohort study used data from the Norwegian RevNatus registry (2007–2024). Women with RA were followed before pregnancy, each trimester, and until 12 months postpartum. We assessed disease activity using Disease Activity Score in 28 joints with C-Reactive Protein (DAS28(3)CRP). Linear mixed models were used to evaluate changes over time and interactions with ACPA, RF and erosions, and we divided pregnancies into three groups by year of delivery. Flares were defined as a change of DAS28(3)CRP > 1.2. Results A total of 598 pregnancies in 475 women were included. The estimated mean DAS28(3)CRP decreased from 2.39 in 2 nd to 2.27 in 3 rd trimester ( p = 0.003) and increased significantly to 2.52 ( p < 0.001) at 6 weeks postpartum with 16% experiencing flares. The proportion improving during pregnancy was 11%, but 49% in those with DAS28(3)CRP > 3.2 in 1 st trimester. Seropositive women had more fluctuations during pregnancy and higher postpartum activity; seronegative women showed minimal variation. Erosive disease did not have a significant effect. Disease activity before, during and after pregnancy decreased in later years of delivery, corresponding to increased use of TNFi. Conclusion Most women with RA maintained remission during pregnancy, but postpartum flares still occurred. Improvement was seen in pregnancies with initial high disease activity, but not in women with well managed disease. Seropositive women experienced higher disease activity and larger increase in DAS28(3)CRP postpartum. Women with pregnancies after 2020 had consistently lower disease activity compared to those who were pregnant in 2007–2019, coinciding with broader TNFi use during pregnancy.
Juvenile idiopathic arthritis (JIA) is a chronic autoimmune disorder, characterized by chronic idiopathic joint inflammation in children under sixteen years of age. Emerging evidence suggests that food allergens- particularly cow’s milk proteins may modulate inflammatory pathways, and that their elimination could potentially ameliorate disease activity. This study aimed to evaluate through a randomized controlled clinical trial whether eliminating cow’s milk protein from the diet influences disease activity and symptom severity in children with JIA. In this randomized controlled trial, 120 children with controlled juvenile idiopathic arthritis (JIA) receiving stable standard therapy were randomly allocated to either a cow’s milk protein–free diet (intervention group, n = 60) or an unrestricted diet (control group, n = 60) for one month. Disease activity was assessed at baseline and post-intervention using subjective measures (patient- and physician-reported Visual Analog Scale [VAS]) and objective parameters, including erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), active joint count, morning stiffness duration, fever. Compared with baseline, the intervention group demonstrated statistically significant improvements in multiple outcomes, including patient VAS (2.9 ± 1.9 to 1.7 ± 1.4; P < 0.001), physician VAS (2.5 ± 1.8 to 1.6 ± 1.3; P < 0.001), ESR (14.6 ± 13.7 to 9.4 ± 7.3 mm/hr; P < 0.001), CRP (7.3 ± 13.7 to 2.5 ± 3.6 mg/dL; P = 0.011), morning stiffness duration (6.1 to 0.6 min; P = 0.002), active joint count (0.55 to 0.11; P < 0.001), and Disease Activity Score (5.53 ± 4.44 to 3.0 ± 2.6; P < 0.001). In contrast, the control group exhibited only minor or non-significant changes. In children with well-controlled JIA, a cow’s milk protein–free diet was associated with modest short-term improvements in pain and disease activity. These findings suggest a potential adjunctive benefit alongside standard therapy, but the short duration, low baseline disease activity, and reliance on parental self-report warrant cautious interpretation. The protocol of this clinical trial has been registered in the Iranian Clinical Trial Registration Center (registration code: IRCT20241230064216N1). Registered 28 April 2025, available from https://irct.behdasht.gov.ir/search/result?query=IRCT20241230064216N1, and ethical approval was obtained from the Ethics Committee of Shahid Beheshti University of Medical Sciences, registered 10 November 2024 (Ethics Code: IR.SBMU.MAP.REC.1403.531).
