Hanan AlRayes,1,2 Ziyad Alakkas,3 Nashwa Nabil,4 Suzan Mansour Attar,5 Hassan Balubaid,5 Ali H Althagafi,6 Abdulrahman Alharthi,6 Rawan Waslallah Alsuwat,6 Wedad Abdullah Aldahasi,6 Khalid Bahamdein,5 Hamza Bukhari,5 Meshal Alharthi,2 Tariq Albalawi,2 Basant Elnady6,71Department of Medicine, College of Medicine, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia; 2Department of Rheumatology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia; 3Department of Medicine, King Faisal Medical Complex, Taif, Saudi Arabia; 4Community, Environmental and Occupational Medicine Department, Benha University, Benha, Egypt; 5Department of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 6Department of Medicine, Al Hada Armed Forces Hospital, Taif, Saudi Arabia; 7Department of Rheumatology, Benha University, Benha, EgyptCorrespondence: Basant Elnady, Department of Medicine, Al Hada Armed Forces Hospital, Taif, Saudi Arabia, Email basantelnady@gmail.comBackground: Difficult-to-treat rheumatoid arthritis (D2T RA) is a clinically challenging condition characterized by persistent disease activity despite appropriate disease-modifying antirheumatic drug (DMARD) therapy. Evidence regarding its frequency and contributing factors in Saudi Arabia remains limited.Objective: To determine the proportion of patients with D2T RA and identify the demographic, clinical, laboratory, and treatment-related factors associated with it in a multicentre Saudi cohort.Methods: This multicentre cross-sectional study used data from a registry of 928 patients with RA attending tertiary centres in Saudi Arabia. Patients were classified according to the EULAR definition as having D2T RA or controlled RA, defined as remission or low disease activity. Clinical, laboratory, and treatment-related characteristics were compared, and multivariable logistic regression identified factors independently associated with D2T RA.Results: Among 928 registry patients, 126 (13.6%) fulfilled the EULAR definition of D2T RA. For the comparative analysis, these patients were compared with 269 patients with controlled RA. D2T RA was associated with higher disease activity at the index visit, greater functional disability, elevated erythrocyte sedimentation rate, poorer patient global assessment, a longer interval between symptom onset and initial medical consultation, and lower treatment adherence. Joint deformities and swollen joint counts were more frequent, whereas C-reactive protein levels did not differ significantly. In multivariable analysis, age at diagnosis, longer disease duration, higher DAS28, greater Health Assessment Questionnaire disability, elevated erythrocyte sedimentation rate, poorer patient global assessment, treatment non-adherence, and methotrexate and glucocorticoid use were independently associated with D2T RA.Conclusion: Among patients with established RA and prolonged follow-up, 13.6% fulfilled the D2T RA criteria. D2T RA was associated with persistent inflammatory activity, accumulated disease burden, a longer interval before the first medical consultation, and potentially modifiable patient-related factors, particularly treatment adherence.Keywords: difficult-to-treat rheumatoid arthritis, rheumatoid arthritis, disease activity, treatment adherence, fibromyalgia, Saudi Arabia
Hani M Almoallim,1 Sami M Bahlas,2 Yasser Bawazir,3 Albadr H Hussein,4 Gamal Mahmoud Attia,5 Hanady Manasfi,6 Zain A Bafadhl,6 Raja Adib Bakhsh,7 Alhussain Mohammed Asiri,8 Ayda Rahma Ali,8 Mohammed M Alomair,8 Hanan Almalki,8 Mona Alsharaif,8 Muhammad Irfanullah Siddiqui,9 Aous S Alhazmi,10 Suzan M Attar31Department of Internal Medicine, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Medicine, International Medical Center, Jeddah, Saudi Arabia; 3Department of Medicine, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 4Department of Rheumatology, King Fahad Hospital, Madinah Munawara, Saudi Arabia; 5Department of Rheumatol-Ogy, Faculty of Medicine, Al-Azhar University, Cairo, Egypt; 6Department of Internal Medicine, SMC Healthcare Hospitals, Riyadh, Saudi Arabia; 7Internal Medicine Department, King Faisal Hospital, Makkah, Saudi Arabia; 8Department of Internal Medicine, Aseer Central Hospital, Abha, Saudi Arabia; 9Department of Preventive Medicine, Almualij Alamin Clinics Medical, Makkah, Saudi Arabia; 10Department of Academic and Training Affairs, Saudi German Hospital, Makkah, Saudi ArabiaCorrespondence: Hani M Almoallim, Department of Internal Medicine, Faculty of Medicine, Umm Al-Qura University, Makkah, 21955, Saudi Arabia, Email hmmoallim@uqu.edu.saPurpose: Rheumatoid arthritis (RA) affects women two–three times more frequently than men, and registries report sex-based differences in disease activity and remission. However, sex-stratified outcome data from Saudi Arabia are limited. We evaluated sex differences in disease activity, remission rates, and predictors of remission in the Rheumatoid Arthritis Saudi Database (RASD).Patients and Methods: We conducted a prospective cohort study of 647 patients with RA receiving biological or targeted synthetic DMARDs (574 female and 73 male) with at least 12 months of follow-up. Disease activity was assessed using DAS28-CRP, CDAI, FSS, and HAQ-DI across three visits. Remission was defined as DAS28-CRP < 2.6. Linear mixed-effects models examined disease activity trajectories by sex, and multivariable logistic regression identified predictors of remission at visit 3. Benjamini–Hochberg correction was applied across six Stage-4 chi-square tests and across three pairwise sex comparisons within each outcome.Results: Overall remission rates rose from 50.9% at visit 1 to 83.5% at visit 3, with no significant sex differences after correction for multiple comparisons. DAS28-CRP declined significantly over time in both sexes (p < 0.001). Males had higher adjusted CDAI at Visit 1 (13.43 vs 11.12; BH-adjusted p = 0.007), but not at visits 2 or 3; the visit-by-sex interaction was significant (unadjusted Type III p = 0.032). Fatigue and functional disability did not differ by sex. ACPA positivity was associated with higher odds of remission (OR 1.67, 95% CI 1.03– 2.68, p = 0.036), while RF positivity was associated with lower odds (OR 0.61, 95% CI 0.38– 0.96; p = 0.034). Sex was not an independent predictor.Conclusion: In this Saudi RA cohort, both sexes achieved high remission rates under treat-to-target management, and sex differences in disease activity did not persist after multiple-comparison correction. RF and ACPA, rather than sex, were the dominant predictors of remission.Keywords: rheumatoid arthritis, sex differences, remission, DAS28-CRP, ACPA, rheumatoid factor, Saudi Arabia
Purpose:To describe the clinical features of patients with idiopathic inflammatory myopathies (IIM) and report the prevalence of malignancy among them within a single-center cohort in southwestern Saudi Arabia. Patients and Methods:We conducted a retrospective study at Aseer Central Hospital, reviewing records of patients diagnosed with IIM according to the ACR/EULAR 2017 classification criteria over a five-year period (January 2021-December 2025). Demographic, clinical, laboratory, and treatment data were collected and analyzed using appropriate statistical tests. Results:Twenty-nine patients were included (75.9% female; mean age 41.9 years). Dermatomyositis (DM, 12/29, 41.4%) predominated, followed by polymyositis (PM, 10/29, 34.5%) and antisynthetase syndrome (ASA, 7/29, 24.1%). Skin manifestations were observed in all DM patients, with isolated involvement in one ASA patient (100% DM vs 0.0% PM vs 14.3% ASA; p < 0.001). Creatine phosphokinase (CPK) was significantly higher in PM and ASA versus DM (medians 4884 and 6334 vs 316 U/L; p = 0.005). Interstitial lung disease (ILD) was most prevalent in ASA (71.4% vs 20.0% PM vs 16.7% DM; p = 0.029). Two females with DM aged ≥40 years developed malignancy (ovarian and breast; 2/29, 6.9%). Anti-Jo1 antibodies were present in 7 of 27 tested patients (25.9%), and were significantly associated with ILD (71.4% vs 20.0%, p = 0.023). No malignancy occurred in patients with ILD or anti-Jo1 positivity. Full muscle strength recovery was achieved in 26 of 29 patients (89.7%), though 10 of 29 patients (34.5%) required escalation to intravenous immunoglobulin and/or rituximab for refractory disease. Conclusion:Malignancy prevalence (2/29 patients, 6.9%) aligns with recent Saudi data but is lower than that reported in East Asian and many Western reports. In this study, cancer occurred exclusively in DM patients aged ≥ 40 years, lacking ILD or anti-Jo1 antibodies, consistent with established risk patterns. These findings support a clinically guided approach to cancer screening, particularly in patients with DM.
Background:Endothelial and microvascular damage is a hallmark of systemic sclerosis (SSc), an autoimmune connective tissue disease characterized by progressive skin and organ fibrosis. Aminaphtone (3-Methyl-1,4-dioxo-1,4-dihydro-naphthalen-2-yl-amino-benzoate) is a synthetic molecule used to treat microvascular disorders. Nailfold videocapillaroscopy (NVC) is the most reliable non-invasive method for assessing microvascular status and disease progression in SSc patients. Aim:To evaluate long-term safety and potential beneficial effects of aminaphtone on microcirculation in SSc. Methods:Seventy-six SSc patients (68 females, 8 males; mean age 69 ± 15 years) fulfilling the 2013 ACR/EULAR criteria and presenting Raynaud's phenomenon received aminaphtone (75 mg twice daily) in addition to stable standard therapy (ST). Forty age- and sex-matched SSc patients treated with ST alone served as controls. Side effects were monitored every six months. NVC was performed at baseline and after 1 and 4 years, using the Cutolo classification ("Early", "Active", "Late" patterns) to evaluate microvascular damage progression. Results:Aminaphtone showed a high long-term retention rate (89.5%) over four years. Eight of 76 patients (10.5%) discontinued treatment due to mild transient intolerance or poor compliance; no serious adverse events were reported. NVC patterns remained stable in 91% of treated patients. Compared with controls, aminaphtone-treated patients showed a slower transition from "Active" to "Late" NVC pattern (120 ± 64 vs 50 ± 26 months, p = 0.05). Linear mixed-effects modelling showed a significantly slower capillary density decline in the aminaphtone group over 48 months (p < 0.05) in both "Early" and "Active" scleroderma pattern subgroups. On multivariate linear regression, this effect was independent of age, disease phenotype, and concomitant therapies. Conclusion:Aminaphtone appears safe and well tolerated during long-term treatment in SSc patients with secondary Raynaud's phenomenon. The stability of NVC scleroderma patterns and the independent protective effect on capillary loss suggest a potential adjunctive role of aminaphtone in limiting microvascular damage progression when added to ST in SSc.
Background:Autoantibody testing supports the diagnosis of systemic autoimmune diseases, but indiscriminate use in low pre-test probability settings can reduce test positivity and inflate direct laboratory costs. Hospital-wide audits of real-world ordering practices across specialties remain scarce and, to our knowledge, have not been reported in the Gulf region. Objectives:To describe the test positivity rate, direct laboratory cost, and departmental variation of hospital-wide autoantibody testing in a tertiary center in the Eastern Province of Saudi Arabia. Methods:We conducted a retrospective hospital-wide audit of all autoantibody tests ordered across 15 clinical departments at King Fahd University Hospital between 1 January and 30 April 2024. Test volumes, positivity rates, and direct laboratory costs were summarized at departmental and subspecialty levels. Rheumatology was compared with all non-rheumatology services as a pre-specified inferential contrast using chi-square or Fisher exact tests with 95% Wilson confidence intervals and Benjamini-Hochberg adjustment across per-marker comparisons; the unit of analysis was the test order. Results:A total of 5973 autoantibody tests were performed in 1059 patients, with an overall test positivity rate of 16.3% (95% CI 15.4-17.2). Total direct laboratory expenditure was USD 509,136, of which 87% was attributable to negative results. Test positivity ranged from 26% in Pediatrics to ≤7% in Neurology and Neurosurgery. Rheumatology had a higher positivity rate (24.4%, 95% CI 22.2-26.8) than non-rheumatology services combined (13.9%, 95% CI 12.9-14.9; p<0.001), with the largest absolute differences for antinuclear antibodies (88.7% vs 35.7%; p<0.001) and SSA antibodies (27.9% vs 5.9%; p<0.001). Direct cost per positive result was USD 364 in Rheumatology versus USD 606 in non-rheumatology services. Conclusions:In this single-center audit, autoantibody ordering practices clustered into two descriptive patterns: hypothesis-driven, higher-positivity testing within specialist care and broader, lower-positivity panel use in several non-specialist services. These differences were statistically significant and most plausibly reflect more disciplined application of pre-test probability by specialists, although referral filtering and case-mix differences contribute and cannot be fully separated from clinician-level reasoning in this dataset. These patterns suggest that targeted diagnostic stewardship-reflex-cascade algorithms, order-menu redesign, and indication-based gating-could concentrate autoantibody testing where pre-test probability is highest, improving positivity and reducing avoidable cost without restricting clinical access.
Purpose: Rheumatoid arthritis (RA) management emphasizes treat-to-target strategies with timely escalation from conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) to biologic (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) when remission or low disease activity is not achieved. Comparative real-world effectiveness evidence across advanced therapies remains limited in some settings. To compare 12-month outcomes and treatment persistence across biologic (bDMARD) and targeted synthetic DMARDs (tsDMARDs) in Saudi patients enrolled in the Rheumatoid Arthritis Saudi Database (RASD). Patients and Methods: We conducted a prospective multicenter cohort study of RASD patients receiving biologic or targeted synthetic DMARDs, with a minimum follow-up of 12 months and assessments at baseline, 3-6 months, and 12 months. Outcomes included longitudinal DAS28-CRP change, 12-month disease activity, function, fatigue, remission, and treatment persistence through 36 months. Analyses used mixed-effects, covariate-adjusted regression, ordinal regression, logistic regression, and Kaplan-Meier methods, as appropriate for each outcome. Results: We analyzed 647 treatment courses across nine advanced therapies. Disease activity improved significantly over time, with a strong overall DAS28-CRP time effect (p<0.0001), but no significant overall drug effect (p=0.327) or time-by-drug interaction (p=0.218). Model-estimated 12-month DAS28-CRP values were closely clustered across therapies, with overlapping confidence intervals and no significant pairwise differences. In adjusted 12-month analyses, DAS28-CRP, CDAI, fatigue severity, and remission were comparable across agents. Most adjusted between-drug comparisons were non-significant, except for worse HAQ category with certolizumab compared with tofacitinib (adjusted OR 2.45, 95% CI 1.12-5.37). Remission varied significantly across participating centers. Discontinuation rates were low, most commonly due to lack of efficacy, and treatment persistence did not differ significantly across therapies through 36 months (log-rank p=0.17). Conclusion: Advanced RA therapies were associated with significant disease activity improvement and minimal adjusted between-drug differences. Except for an isolated worse HAQ signal with certolizumab versus tofacitinib, outcomes were broadly comparable across agents. Center-level remission variation highlights the importance of standardized treat-to-target implementation. Trial Registration: ClinicalTrials.gov Identifier: NCT06417138.
Lupus enteritis is a recognized but uncommon and potentially life-threatening gastrointestinal manifestation of systemic lupus erythematosus. Its symptoms are often nonspecific and may mimic infectious enteritis, pseudomembranous colitis, intestinal obstruction, or a surgical acute abdomen. We report a 19-year-old woman with a prior diagnosis of SLE and irregular use of maintenance therapy who developed abdominal pain, watery diarrhea, nausea, vomiting, and progressive abdominal distension after ingestion of suspected contaminated food. During hospitalization, she passed large amounts of clear, gelatinous, pseudomembrane-like stool material. Laboratory evaluation showed anemia, thrombocytopenia, hypocomplementemia, positive antinuclear antibodies, positive anti-Ro52 antibodies, and negative microbiological studies, including stool culture and Clostridioides difficile toxin assays. Contrast-enhanced abdominal computed tomography demonstrated segmental small-bowel wall thickening with the target sign, mesenteric vascular engorgement with the comb sign, and ascites, supporting the diagnosis of lupus enteritis. After infection was considered unlikely, empirical antibiotics were discontinued. High-dose intravenous methylprednisolone, adjunctive intravenous immunoglobulin, and cyclophosphamide led to rapid clinical improvement within 48-72 hours, with subsequent radiological resolution. The novelty of this case lies not in lupus enteritis itself, but in its presentation with substantial clear gelatinous pseudomembrane-like stool material, a rarely emphasized manifestation that may mislead clinicians toward infectious or pseudomembranous colitis. Early recognition based on SLE activity, characteristic CT findings, exclusion of infection, and multidisciplinary assessment is essential to avoid diagnostic delay and prevent severe complications.
Lana Sbitan,1,2 Mu’ath Kanan,3 Hamzah A Hasan,2,4 Aya M Hassan4 1Department of General Surgery, Prince Hamza Hospital, Jordanian Ministry of Health, Amman, Jordan; 2Faculty of Medicine, The Hashemite University, Zarqa, Jordan; 3Department of Pediatric Hematology and Oncology, Sultan Qaboos University Hospital, Seeb, Oman; 4Department of Internal Medicine,Prince Hamza Hospital, Amman, JordanCorrespondence: Lana Sbitan, Email LanaY.Sbitan@gmail.com
Background:Behçet's syndrome (BS) is a chronic systemic inflammatory disorder with vascular involvement representing a severe complication. Despite its high prevalence along the Silk Route, data on vascular Behçet's in Middle Eastern populations remain limited. Purpose:This study evaluates the prevalence, clinical features, and treatment outcomes of vascular BS in Qatar's multinational cohort. Patients and Methods:A retrospective analysis was conducted on 82 BS patients (2016-2024) meeting the International Criteria for Behçet's Disease (ICBD). Vascular involvement was confirmed via imaging (Doppler, CTA/MRA). Demographics, clinical manifestations, and treatment responses were characterized using descriptive analyses, and intervariable associations were statistically examined. Results:Vascular involvement was identified in 20.7% (17/82) of patients, with a male predominance (76.5%) and earlier diagnosis among Arab patients (29.3 vs. 44.3 years, p=0.02). Multivascular involvement was the most common pattern (35.3%), followed by isolated venous thrombosis (29.4%) and isolated arterial involvement (11.8%). Overall, venous disease was the predominant vascular manifestation, occurring either as isolated venous thrombosis or as part of combined arterial-venous involvement. The favorable clinical outcomes observed with corticosteroid-immunosuppressant combination therapy strongly support the early initiation of aggressive immunomodulatory treatment in patients with vascular Behçet's disease. Conclusion:In Qatar, about 1 in 5 patients with Behçet's disease show signs of vascular involvement, with notable differences based on ethnicity and gender. Venous and multivascular involvement are more common, making comprehensive imaging essential. Immunosuppression, particularly steroid-biologic combinations, appears superior to anticoagulation alone. These findings highlight the need for region-specific management protocols in this high-risk population.
Purpose: Appropriate reporting of race and ethnicity in rheumatology research is critical to ensure equity and diversity of study participants and findings, as sociodemographic factors can affect outcomes, particularly for systemic lupus erythematosus (SLE). JAMA published guidance on reporting of race and ethnicity, highlighting the importance of reporting appropriately and building on emerging guidance. This study aimed to quantify reporting of race and ethnicity in high-impact rheumatology journals to assess adherence to accepted reporting recommendations. Patients and Methods: Studies investigating issues related to SLE published in three of the highest impact rheumatology journals between 1/1/2020-12/31/2023 were included. Manuscripts not involving human subjects were excluded. Two researchers (I.E. and H. B.) systematically abstracted sociodemographic variables to ensure consistent coding of data; conflicts were resolved by consensus. Descriptive statistics of each variable and reporting criteria were calculated. Results: In all, 117 articles met inclusion criteria. Among these, 114 (97%) included any demographic data, 87 (74%) reported race, 51 (44%) reported ethnicity. Of those that reported race, 65 (75%) were comprised of a majority White race and only 7 studies (8%) met the Office of Management and Budget (OMB) minimum reporting criteria for race. Only 20 studies (23%) mentioned that racial and ethnic categories were self-reported by patients. Additionally, 32 studies included any comorbidities, and 18 studies included various other socio-economic factors. Conclusion: Despite known racial and ethnic disparities in SLE care and outcomes, reporting of race and ethnicity is not standardized across SLE research in rheumatology journals. Most publications do not meet minimum suggested race and ethnicity reporting criteria.
Background: Gout is a common, treatable inflammatory arthritis, yet adherence to guideline-based care remains suboptimal worldwide. Data from Saudi Arabia evaluating real-world gout care processes are limited. Methods: We conducted a retrospective cohort study of adults with a a physician-documented diagnosis of gout who newly initiated allopurinol within a tertiary academic health system in Riyadh, Saudi Arabia, from January 2022 through December 2024. Pharmacy records were used to identify eligible patients, and electronic medical records were reviewed to extract demographic, clinical, and treatment data. Adherence to American College of Rheumatology (ACR) 2020 guideline-derived quality indicators was assessed, including guideline-concordant initiation of urate-lowering therapy (ULT), serum uric acid (SUA) monitoring, achievement of SUA < 6 mg/dL, and use of anti-inflammatory prophylaxis. Multivariable logistic regression was used to identify predictors of adherence. Results: Among 120 patients, 35.8% met ACR 2020 criteria for ULT initiation. SUA was measured within 6 months of initiation in 41.7% of patients, and at least annually in 61.7% of patients with at least 12 months of follow-up. Among 115 patients with at least 12 months of follow-up and at least one documented SUA measurement, 32.2% achieved SUA < 6 mg/dL. Anti-inflammatory prophylaxis was received at ULT initiation by 15 out of 107 eligible patients (14%). Primary care management was independently associated with lower odds of meeting initiation criteria (OR 0.05, 95% CI 0.01- 0.16) and of achieving the target SUA (OR 0.23, 95% CI 0.06- 0.89) compared with rheumatology. Older age (OR 0.97, 95% CI 0.92- 1.00) and male sex (OR 0.29, 95% CI 0.10- 0.83) were also associated with lower SUA target attainment. Conclusion: In this tertiary academic health system, guideline-recommended gout care processes were inconsistently executed across initiation, monitoring, target assessment, and prophylaxis domains. Primary care management was associated with lower odds of appropriate ULT initiation and target SUA attainment, and older age and male sex were also associated with lower target achievement. Standardized treat-to-target pathways supported by pharmacist- or nurse-led titration may improve performance.
Objective: Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders with diverse clinical and genetic backgrounds. Classical-like EDS (clEDS, OMIM 606408) is an extremely rare autosomal recessive subtype caused by biallelic variants in TNXB. Fewer than 100 cases have been described worldwide. This study aimed to identify and characterise TNXB-related variants in two Polish patients with clinical features suggestive of clEDS. Methods: Two male patients, aged 13 and 14 years, underwent comprehensive genetic testing, including next-generation sequencing (NGS) using a connective tissue gene panel, Multiplex Ligation-dependent Probe Amplification (MLPA), and Sanger sequencing. Family segregation analysis was performed to confirm compound heterozygosity. Results: NGS and confirmatory analyses identified compound heterozygous TNXB variants: c.[7222C>T];[8780T>C], p.[Pro2408Ser];[Ile2927Thr] in Patient 1, and c.[5947_5948delinsTT];[8300C>T], p.[Glu1983Leu];[Thr2767Ile] in Patient 2. Both variants were located in non-homologous TNXB exons, minimising the risk of misinterpretation due to pseudogene sequences. The clinical presentations of both patients were consistent with the major diagnostic criteria for classical-like EDS. Conclusion: This report presents the first genetically confirmed Polish patients with a classical-like form of Ehlers-Danlos syndrome, expanding the known clinical and molecular spectrum of TNXB-related EDS. Our findings reinforce the notion that heterozygous TNXB variants, particularly frameshift alterations, may occasionally contribute to mild connective tissue manifestations in carriers, underscoring the complexity of genotype-phenotype correlations in this rare disorder.
Objective:To evaluate the risk of immune-mediated rheumatic disease (IMRD) development among adult patients with temporomandibular disorders (TMDs) and to assess the risk factors for developing IMRD among patients with TMDs. Methods:A retrospective single-center cohort study that included patients between January 1, 2018 and June 30, 2024. Patients ≥ 18 years old with newly diagnosed TMDs according to the TMD diagnostic criteria, who had ≥ 3 follow-up visits at the center for maxillofacial surgery and dental medicine clinics, Galilee medical center, were included. Results:A total of 1,129 patients presented with TMDs, 130 patients met the inclusion criteria, of whom 114 (88%) were females. The most common temporomandibular joint (TMJ) symptoms were pain and click sounds in 128 (98.5%) and 24 (18.5%) of patients, respectively. Out of 130 patients with TMDs, 3 patients (2.3%) were diagnosed with IMRD (2 with rheumatoid arthritis (RA) (1.5%), and 1 with familial Mediterranean fever (0.8%)). The median follow-up was 39.9 months (IQR 29.1-51.6), and all patients contributed a total of 431.4 person-years at risk. The incidence rate for IMRD in patients with TMDs in our study was 695.4 per 100,000-person year, and for RA in particular was 463.6 per 100,000-person year None of the evaluated risk factors, including gender, TMJ pain, or other joints pain showed a significant association with the subsequent development of IMRD. Conclusion:In this small retrospective cohort, patients with TMDs have higher incidence of IMRD compared to estimated incidence in the general population, especially RA.
Objective:To report an unusual pediatric case of Guillain-Barré Syndrome (GBS) presented as the first manifestation of Systemic Lupus Erythematosus (SLE), highlighting diagnostic and clinical considerations. Methods:We document the clinical presentation, laboratory findings, diagnostic investigations, and management of a 4-year-old boy who presented with progressive weakness and sensory deficits. Initial Electrophysiology and cerebrospinal fluid analysis reveal GBS diagnosis while, autoimmune and renal workup revealed an underlying SLE. Results:We report a case of a 4-year-old boy who presented with progressive bilateral lower-limb weakness, absent deep tendon reflexes, sensory loss, and muscle weakness, confirmed as GBS through electrophysiological studies and cerebrospinal fluid analysis. Further investigations revealed thrombocytopenia, elevated antinuclear antibody titers, double-stranded DNA antibodies, proteinuria, and hematuria, leading to the diagnosis of SLE with GBS as the initial manifestation. The patient was referred for rheumatology and nephrology management and recovered from GBS but was diagnosed with SLE, complicated by membranous lupus nephritis (class V). Conclusion:GBS can rarely present as the first neurological manifestation of pediatric SLE. Early recognition and a multidisciplinary approach are critical for effective management and improved outcomes.
Objective: To investigate the potential toxicological effects of acetyl tributyl citrate (ATBC) on osteoarthritis (OA) and elucidate the underlying mechanisms using bioinformatics, machine learning, and network toxicology. Methods: ATBC targets were identified from multiple databases, and OA-associated differentially expressed genes (DEGs) were sourced from GSE51588. Intersection analysis identified common targets. Functional enrichment and protein-protein interaction (PPI) network analysis were performed. Machine learning algorithms (LASSO, Random Forest and SVM) validated core targets, with ROC curves assessing diagnostic potential. Immune infiltration differences were analyzed via Cibersort. Molecular docking confirmed ATBC binding to core targets, and an adverse outcome pathway (AOP) framework was developed to elucidate ATBC's role in exacerbating OA through key genes and pathways. Results: Intersection analysis identified 40 common targets related to both ATBC and OA. Functional enrichment analysis revealed that these targets were significantly involved in calcium signaling pathways and neuroactive ligand-receptor interactions, both of which are implicated in OA pathogenesis. The PPI network analysis identified TNF, MMP8, CXCR4, and SLC2A1 as core targets. Machine learning algorithms further validated these core targets. ROC curve analysis showed that these genes have diagnostic potential, with AUC values ranging from 0.762 to 0.970. Immune infiltration analysis using Cibersort revealed significant differences in immune cell infiltration between OA and control groups, with core targets showing distinct correlations with various immune cells. Molecular docking confirmed strong binding affinities between ATBC and the core targets, with binding energies less than -5 kcal/mol. A novel adverse outcome pathway (AOP) framework was established, suggesting that ATBC may influence the expression of TNF, CXCR4, MMP8, and SLC2A1, with the calcium signaling and neuroactive ligand-receptor interaction pathways potentially contributing to immune dysregulation and OA progression. Conclusion: The identification of key targets (TNF, MMP8, CXCR4, and SLC2A1) and molecular docking results elucidates potential mechanisms by which ATBC exposure may exacerbate OA progression. The AOP provides evidence for joint-health risk assessment of plasticizers and offers readily measurable biomarkers for regulatory toxicology and future therapeutic development.
Background:Curcuma longa L. (turmeric) is a widely used medicinal plant with potent antioxidant and anti-inflammatory properties. It has been traditionally employed to manage inflammatory diseases such as osteoarthritis. This study explored the therapeutic potential of turmeric fermentation liquid (TF) in reducing oxidative stress, inflammation, and cartilage degradation in a monosodium iodoacetate-induced rat model of knee osteoarthritis (KOA). Methods:Fresh turmeric was washed, sliced, and fermented using Lactobacillus strains under controlled conditions to enhance its bioavailability and produce TF. Male Wistar rats were divided into four groups: Control, MIA, MIA+glucosamine hydrochloride, and MIA+TF. TF was administered orally for four weeks, and its effects were assessed through ELISA, histological staining, and immunohistochemistry to measure oxidative stress markers, inflammatory cytokines, and cartilage integrity. Results:TF enhanced antioxidant capacity and significantly reduced lipid peroxidation. It suppressed pro-inflammatory cytokines (TNF-α, IL-1β) and increased anti-inflammatory IL-10 levels. Histological analysis revealed cartilage preservation, reduced proteoglycan loss, and decreased synovitis severity. Safranin O staining confirmed higher proteoglycan retention in TF-treated cartilage, while immunohistochemistry showed reduced IL-6 and IL-1β expression. Furthermore, TF improved synovial fluid quality and decreased chondrocyte apoptosis, resulting in better joint mobility and reduced pain behavior in KOA rats. Conclusion:Turmeric fermentation liquid exhibits potential as a natural therapy for KOA by addressing oxidative stress and inflammation. The fermentation process enhances bioavailability, providing a novel approach for preserving joint health and function. Further clinical studies are needed to confirm its efficacy and safety in humans.
Background:Fatigue is one of the most prevalent and disabling symptoms in patients with rheumatoid arthritis (RA), yet its relationship with disease activity remains complex and underexplored in many populations. Objective:To evaluate the association between disease activity and fatigue in RA patients at King Abdulaziz University Hospital using validated clinical measures. Methods:A cross-sectional study was conducted among 253 RA patients fulfilling the ACR/EULAR 2010 classification criteria. Disease activity was assessed using the Clinical Disease Activity Index (CDAI), and fatigue was measured with the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale. Relationships between fatigue (FACIT-F scores) and CDAI were examined using Pearson correlation with continuous CDAI scores. Descriptive statistics (mean ± SD) of FACIT-F scores across CDAI categories were provided for illustration. Multivariate linear regression adjusted for age, sex, disease duration, body mass index, employment status, serological markers, and treatment type. ANOVA was applied to assess differences in mean FACIT-F scores across disease activity categories. Statistical significance was set at p < 0.05. Results:Fatigue was reported by 80% of patients, with 10% experiencing severe fatigue (FACIT-F ≤13). Mean FACIT-F scores decreased as disease activity increased: remission 40.1 ± 8.2, low disease activity 35.7 ± 10.4, moderate disease activity 25.6 ± 9.8, and high disease activity 15.4 ± 7.3 (p < 0.001, ANOVA). Pearson correlation demonstrated a strong inverse relationship between CDAI and FACIT-F scores (r = -0.68, 95% CI: -0.83 to -0.45 in the high disease activity group). Multivariate analysis confirmed that disease activity remained a key determinant of fatigue after adjusting for potential confounders, with female sex, obesity, and longer disease duration also independently associated with lower FACIT-F scores. Conclusion:Fatigue in RA is strongly associated with disease activity but persists in patients with well-controlled inflammation, reflecting multifactorial origins. Routine fatigue assessment and holistic management strategies addressing both inflammatory and non-inflammatory contributors are essential to improve patient quality of life and treatment outcomes.
Purpose:Osteoporosis (OP), a common comorbidity in patients with rheumatoid arthritis (RA), is characterized by reduced bone mineral density (BMD) and an increased risk of fractures. The interplay between chronic inflammation, RA medications, and other contributing factors exacerbates bone loss. In this study, we sought to estimate the prevalence of OP and identify factors associated with OP in patients with RA. Patients and Methods:We conducted a retrospective cross-sectional study using medical record data from patients diagnosed with RA at rheumatology clinics. The collected data included demographic details, clinical history, disease activity scores, medication use, and BMD measurements. Statistical analyses were performed to assess the prevalence of and identify significant risk factors for OP in this cohort. Results:We included 173 Saudi patients with RA (mean age: 46.29 years; 154 women, 19 men) in the study. Mean age was significantly higher in the OP group than in the normal-BMD group. Disease duration was significantly associated with low BMD; 35.4% of patients in the normal-BMD group had disease duration <2 years, compared with only 4.3% in the OP group, whereas 50% of patients with OP had disease duration >10 years. Conclusion:OP affected 26.6% of patients with RA, indicating that bone fragility is common in this population. The discovery that advanced age and disease duration are major risk factors for high-risk groups emphasizes the importance of early screening and targeted preventive interventions.
