Rheumatoid arthritis (RA) is a chronic autoimmune systemic disease affecting mostly the small joints of the hands and feet. Extra-articular manifestations (EAMs) comprise the involvement of the skin, eyes, heart and lung. Among them, subcutaneous rheumatoid nodules (RN) are a common manifestation of systemic disease. However, disorders such as rheumatoid nodulosis, multicentric reticulohistocytosis (MRH) and others present subcutaneous nodules, similar to those seen in RA patients. A 41-year-old woman with a 10-year history of untreated RA, presented complaining of pain and tenderness in the small joints of the hands and feet. Past medical and family history were unremarkable. She presented swelling and tenderness on all metacarpophalangeal joints (MCPs) bilaterally and had multiple widespread subcutaneous RN affecting almost all the fingers of the hands, as well as, the Achille's tendons in a symmetrical manner. She had elevated levels of acute phase reactants and high titres of autoantibodies. Hand x-rays revealed severe erosive changes affecting all MCPs joints bilaterally. Thus, in this review we discuss the differential diagnosis of subcutaneous RN and their role in RA disease activity. This is an educational case of a patient with RA and extensive subcutaneous RN affecting the upper and lower extremities. To this end, physicians must be familiar and recognise early these signs which reflect RA disease activity and treat appropriately.
Introduction:Rheumatoid arthritis (RA) is a chronic inflammatory disease marked by bone loss, partly due to impaired Wnt signalling. The role of sclerostin, an endogenous Wnt inhibitor, in RA remains unclear. Methods:This 9-month cross-sectional case-control study included post-menopausal women recruited at a tertiary hospital in Athens, Greece. Participants underwent clinical assessment, DXA, radiographs, and blood tests. The aim was to assess serum sclerostin levels and their associations in RA. Results:A total of 97 RA patients and 45 controls were included. Mean age was 67 ± 7 years; median RA duration was 8 years; 40% were seropositive; 65% received bDMARDs. Median sclerostin levels did not differ significantly between groups (p=0.645). In RA patients, sclerostin levels were positively associated with ACPA (p=0.043). Notably, 27% of RA patients had extremely high sclerostin levels versus 11% of controls (p=0.035). Within this subgroup, high sclerostin was inversely associated with sarcopenia (p=0.020). Discussion:Although overall sclerostin levels were similar between groups, higher levels in seropositive RA suggest a possible link with ACPA.
Objective: Autoimmune cytopenias (AIC) may be associated with positive antinuclear antibodies (ANA) and can precede the onset of systemic lupus erythematosus (SLE). This study assessed ANA as a predictive factor for progression to SLE in adolescents with AIC. Methods: Medical records from a paediatric haematology referral centre were retrospectively reviewed. Presence of ANA (titer>1:80) was recorded in 90 adolescents and children with AIC. Possible progression to SLE was evaluated in the group. Results: A total of 90 patients with AIC were included, with a median age of 9 years and a predominance of ITP (67/90). ANA positivity was identified in 35/90 patients with AIC, most frequently in females (25/35). Among ANA-positive patients, 6/35 eventually developed SLE, whereas none of the ANA-negative patients progressed to SLE. Of the patients who developed SLE, the majority were female (5/6), with 5/6 initially diagnosed with autoimmune thrombocytopenia and 1 with Evans syndrome. The median age at AIC onset for those who later developed SLE was 10.4 years, and the median time interval between AIC diagnosis and SLE onset was 2.5 years. Additionally, 10/35 ANA-positive patients met high-risk criteria for future SLE according to Lambers et al. (2020), despite not fulfilling EULAR/ACR-2019 criteria for SLE at the time of review. Conclusions: Persistent ANA positivity in patients with AIC strongly predicts subsequent SLE, particularly in females older than 10 years with ITP. This finding warrants further investigation in larger, prospective studies, including follow-up of patients transitioning to adult care, as SLE may manifest later in adulthood.
Aim:The purpose of this study was to explore female patients' experiences regarding systematic exercise compared with low-intensity physical activity in relation to common symptoms and quality of life in RMDs. Methods:A qualitative study was conducted using semi-structured, face to face interviews. Fifteen women with RMDs were recruited; thirteen completed the interviews and were included in the analysis. Interviews lasted approximately 30 minutes and were audio-recorded. Data were analysed using Thematic Analysis following the six-phase approach of Braun and Clarke. Participants were categorised based on self-reported engagement in either systematic exercise or low-intensity physical activity (e.g. walking). NVIVO 15 software was used for data management and analysis. Results:Participants' mean age was 58.3 ±13.38 years. Five a priori thematic areas were explored (pain, fatigue, depression, quality of life and exercise/physical activity), while an additional theme regarding barriers to participation emerged inductively. Most participants reported limited awareness of the distinction between physical activity and exercise. Women engaged in systematic exercise described more favourable experiences regarding symptoms management and quality of life, whereas those performing low-intensity physical activity primarily emphasised psychological benefits. Barriers to participation included physical limitations, fatigue, and motivational factors. Conclusion:From patients' perspectives, systematic exercise and low-intensity physical activity are perceived differently in relation to symptom experiences and quality of life. These differences highlight the importance of individualised, patient-centred exercise counselling for women with RMDs.
Background:Takayasu arteritis (TAK) is a rare large-vessel vasculitis that predominantly affects young women. Familial cases are uncommon but suggest a possible genetic predisposition. Case Report:We describe five familial TAK cases from two families. In the first, two sisters had distinct disease patterns: one with severe supra-aortic involvement (Hata IIa), requiring intensive immunosuppression and vascular interventions; the other with isolated abdominal aortic disease (Hata IV), successfully managed with standard therapy. In the second family, three siblings presented with varying severity. One sister had mild disease responsive to therapy, whereas another developed rapidly progressive TAK with multivessel involvement, necessitating complex surgical management and ultimately succumbing to COVID-19 complications. Their brother presented with extensive Hata V involvement and achieved remission following brief medical therapy. Conclusion:Familial TAK demonstrates marked clinical and radiological heterogeneity, even among first-degree relatives. These findings underscore the importance of clinical vigilance and prompt evaluation for relatives who develop suggestive symptoms, to enable timely diagnosis and improve clinical outcomes.
Background:Ophthalmic involvement in systemic lupus erythematosus (SLE), particularly retinal vascular diseases, remains under-recognised despite its potential to cause severe visual impairment. This systematic review aims to evaluate the clinical presentation, pathophysiology, and treatment outcomes of retinal vascular diseases associated with SLE. Methods:A comprehensive literature search was conducted across PubMed/MEDLINE, ScienceDirect, Cochrane and Google Scholar using a combination of relevant MeSH terms. Data were extracted independently and quality assessment was conducted using the Joanna Briggs Institute Critical Appraisal Tool. Results:A total of 35 studies, corresponding to 39 patients, were included in quantitative synthesis. Mean age of patients was 27.8±12.9 years. Most patients were from India (n=10; 25%) and the USA (n=8; 20%), with a majority being female (n=31; 79.5%). Unilateral visual disturbances were reported in 25 (64%) cases while 14 (36%) patients showed bilateral symptoms. Disease was sudden in onset in 23 (59%) and followed a progressive course in 16 (41%) patients. Common findings included Central Retinal Artery Occlusion (CRAO) n 24 patients (61.5%) and Central Retinal Vein Occlusion (CRVO) in 22 patients (56.4%). 36 patients (92%) were treated with steroids but only 25% responded positively, necessitating the use of immunosuppressants in 24 (61.5%) and anticoagulants in 16 (41%) patients. Among the 38 patients where outcomes were reported, only 2 (5%) achieved complete recovery, 14 (37%) showed partial recovery, and 20 (52.6%) showed no improvement. Conclusion:Retinal vascular involvement in SLE is rare but associated with significant visual morbidity. Early diagnosis and combined immunosuppressive therapy may improve outcomes. Further research is required to stan-dardise treatment protocols.
Background: Scleroderma renal crisis (SRC) is a rare but severe complication of systemic sclerosis (SSc), often associated with high morbidity and mortality. Data from Indian population remains limited. Objectives: To describe the clinical features, predictors, and outcomes of SRC in a large, single-centre Indian SSc cohort over three decades. Methods: This retrospective cohort study included 880 SSc patients diagnosed between 1990 and 2019, classified by ARA 1980 or ACR/EULAR 2013 criteria. SRC was defined by new-onset hypertension and/or rapidly progressive renal failure, with supportive hematologic and urinary findings. Demographic, clinical, and serologic variables were analysed. Predictors of SRC were identified using multivariate logistic regression, and survival was assessed using Kaplan-Meier and Cox regression analyses. Results: SRC occurred in 27 patients (3.0%), with 85.2% developing SRC within one year of diagnosis. Steroid use preceded SRC in 66.6% of cases. SRC was associated with older age (OR 1.03, 95% CI 1.001-1.072), digital pitting scars (OR 6.16, 95% CI 1.60-23.65), and reduced by immunosuppressive therapy (OR 0.39, 95% CI 0.16-0.98). SRC patients had a significantly higher mortality risk (HR 3.66, 95% CI 1.94-6.89) and shorter survival (mean 7.2 vs. 23.8 years). Dialysis was required in 51.8% of SRC cases. Conclusions: SRC affected 3% of SSc patients and was associated with high mortality and dialysis dependence. Older age, steroid exposure, and digital pitting scars were key risk factors, while immunosuppression appeared protective. These findings highlight the importance of early identification and careful therapeutic strategies in high-risk patients.
Background:The understanding between Familial Mediterranean Fever (FMF) and cardiovascular diseases (CVDs) remains unclear. The study's objective was to investigate the association between FMF and CVD. Methods:Based on a survey targeting individuals with FMF, the patients diagnosed with coronary artery disease, cerebrovascular disease, and hypertension were considered patients with CVD. Results:Out of 522 patients, 201 had CVD. The mean ± standard deviation (SD) age was 53.00 ± 6.43 in patients without CVD and 57.60 ± 8.33 in patients with CVD. Hypertension was present in 188 patients (36%), coronary artery disease was observed in 51 patients (9.8%), and 10 patients (1.9%) had cerebrovascular disease. In patients with CVD, diabetes (30.3%) was the most common comorbidity. All patients consumed colchicine. Thirty-five patients with (17.2%) and 25 without CVD (7.8%) had colchicine resistance. 90% continued treatment with colchicine. 25 (12.4%) patients with CVD were using biological agents, as were 18 (5.7%) patients without CVD (p=0.006). The attack period average C-reactive protein (CRP) level was 61.3 (SD=53.1), while in remission, it had an average value of 3.39 (SD=4.28). CRP median was 3.00 (3.65) during attacks in the group with CVD, and 2.00 (2.5) in the group without CVD (p=0.011). CRP median was 2.8 (3.55) in patients with hypertension, and 2.00 (2.7) in patients without hypertension. Conclusion:FMF does not appear to increase the risk of CVD. Colchicine resistance was associated with the incidence of cardiovascular diseases. Colchicine and anti-interleukin-1 show promise in reducing the risk of cardiovascular diseases in patients with FMF.
Rheumatoid arthritis (RA) is a systemic autoimmune disorder characterised by chronic joint inflammation driven by both cellular and humoral immune mechanisms. Autoantibodies and autoreactive lymphocytes play central roles in disease onset and progression. Although therapeutic strategies targeting T lymphocytes (T cells) and B lymphocytes (B cells) have benefited many patients, the precise cell type driving RA pathogenesis remains debated. In genetically predisposed individuals, immune tolerance is disrupted by environmental triggers such as smoking, infections, and stress. Antigen-driven adaptive immune responses dominate RA, with B cells undergoing clonal expansion and somatic hypermutation to produce high-affinity autoantibodies, notably anti-citrullinated protein antibodies (ACPA) and rheumatoid factor (RF). Synovial inflammation exhibits diverse lymphocyte infiltration patterns, including diffuse inflammation (~50%), T-B cell aggregates with germinal centres (GC)~24%, and aggregates without GC ~20%. T cells within synovial tissue often display clonal restriction, enriched in memory and effector subsets such as CD4+ Th17, CD8+ resident memory, and innate-like T cells (γδ, MAIT, and NK cells), all contributing to persistent synovitis. Dysregulated cytokine signalling, particularly through the JAK/STAT pathway, characterises active disease. In ACPA-positive RA, autoantibodies enhance inflammation via innate immune activation, while B cells also function as antigen-presenting cells (APCs) that sustain T cell activation. However, in some patients, synovial autoimmunity may occur independently of GC formation or prominent B cell involvement, underscoring the disease's heterogeneity. This review highlights the evolving interplay between T and B cells from disease initiation to chronicity, which may help refine personalised immunotherapeutic approaches in RA.
The prognostic nutritional index (PNI), derived from serum albumin and lymphocyte count, reflects immunonutritional status and may be influenced by systemic inflammation. This study examined the association between PNI and disease activity in rheumatoid arthritis (RA). A total of 730 patients fulfilling the 2010 ACR/EULAR criteria were retrospectively analysed. Demographic, clinical, and laboratory data were collected; disease activity and disability were assessed using the DAS28-CRP and Health Assessment Questionnaire (HAQ). Correlation analyses, multivariable linear regression, ROC analyses, subgroup testing, and mediation analyses were performed. The mean age was 56.2±12.5 years and 76.3% were women. Median DAS28-CRP was 3.38, with 11.2% classified as having high disease activity. Mean PNI was 54.0±5.34. PNI was significantly lower in patients with high DAS28-CRP and in severe HAQ categories (p<0.01). PNI correlated negatively with DAS28-CRP, HAQ, CRP, ESR, and disease duration (all p<0.01). However, PNI was not independently associated with DAS28 or HAQ in adjusted regression models, whereas CRP and ESR remained significant predictors. ROC performance of PNI was modest (AUC 0.65-0.67). Associations were stronger in older adults and in men, and mediation analyses indicated that CRP and ESR largely explained the PNI-DAS28 relationship. Lower PNI was associated with greater RA burden, but this association appears to be largely driven by systemic inflammation.
This report describes a paediatric case of cold urticaria (ColdU) associated with markedly elevated cold agglutinin titres following Epstein-Barr virus (EBV) infection. An 11-year-old girl developed recurrent cold-induced urticaria and anaphylaxis after a recent EBV infection. Immunohaematologic testing revealed a cold-reactive IgM autoantibody with anti-i specificity. Despite the exceptionally high peak titres (>1:262,144 at 4°C), and the unusually broad thermal amplitude extending to 30°C, no clinical or laboratory evidence of haemolysis was observed, and the direct antiglobulin test remained persistently negative. Complement components and cryoprotein assays were consistently normal. Throughout an extended 52-month longitudinal follow-up, antibody titres gradually declined in parallel with the resolution of urticarial symptoms and withdrawal of antihistamines. This case demonstrates a non-haemolytic, post-infectious immune phenotype of ColdU, in which transient, high-titre cold agglutinins coexist with cutaneous hypersensitivity without haemolytic manifestations, and highlights the importance of comprehensive immunohaematologic evaluation and long-term monitoring in ColdU cases with atypical serologic findings.
Aim:Fibromyalgia syndrome (FMS) is a chronic rheumatic disorder characterised by body pain, decreased pain threshold and psychological distress. Our aim is to investigate the effects of breathing exercises on sexual function, sleep, and mood in FMS. Methods:This is a cross-sectional study comparing psychological assessments conducted prior to and following breathing exercises. Participants completed the Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS), and Jenkins Sleep Rating Scale (JSS) and Female Sexual Function Index (FSFI). Scores were analysed for comparison to controls. Results:A total of 56 women were enrolled to the study (30 intervention group, 26 controls). The mean age was 50.79 ± 9.06 years in intervention group. There were no statistical difference between groups occupational status (p > 0.05). The FIQ, HADS-depression, HADS anxiety, JSS and FSFI scores were similar between groups before breathing exercises (p > 0.05). FIQ, HADS depression- HADS anxiety, JSS scores after breathing exercises were better comparing to controls, p<0.001, p<0.001, p=0.002 and p=0.001, respectively. Although all symptoms were alleviated, the FSFI scores were not higher than FSD (Female sexual dysfunction) cut off value in intervention group after breathing exercises (p=0.033). The total FSFI score less than 26.55 was the cut-off for FSD. All of the participants had FSD. Conclusion:Breathing exercises can positively influence quality of sleep, anxiety, depression, and sexual life in patients with FMS. Incorporating breathing exercises into the curriculum may be considered to balance the quality of life for women with FMS.
Familial Mediterranean Fever is a well-known autoinflammatory disease resulting from mutations in the MEFV gene. A recent development has linked FMF pathogenesis and mode of expression to the gut micro-biota. There may be a change in the gut microbiota profile of FMF patients, characterised by low diversity and a depletion of beneficial bacteria. Dysbiosis tends to be linked to increased gut permeability, systemic inflammation, and low response to colchicine treatment. Probiotics and prebiotics, in this case, may help restore the previous idyllic state of the microbial balance, along with a reduction in inflammatory markers, thereby demonstrating therapeutic merit. Notably, however, it did argue in some instances that changes in the microbiota were secondary to the genetic and inflammatory nature of FMF itself. It is still important to carry out longitudinal studies of naïve patients that will integrate metagenomics with immune profiling to ascertain whether microbial changes arise from causes, contributions, or coincidence in the pathogenesis of FMF.
Objective:Behçet's disease (BD) is chronic multisystem inflammatory condition with wide spectrum of clinical manifestations, lacking specific laboratory biomarkers for diagnosis or monitoring. Follistatin-like protein 1 (FSTL1), having dual roles in inflammation, remains largely unexplored in BD. The present study aimed to evaluate FSTL1 levels in the serum of BD patients and investigate their association with disease activity and severity. Methods:This prospective, hospital-based case-control study included 40 BD patients, the control group consisted of 40 healthy individuals age and sex matched with the patients. FSTL1 concentrations were measured using a double-antibody sandwich ELISA. The disease activity and cumulative disease related damage were assessed using the Behçet's Disease Current Activity Form (BDCAF), and the Behçet's Syndrome Overall Damage Index (BODI). Results:The median serum FSTL1 concentrations were significantly elevated in BD patients in comparison to controls :4.05 (1.9 - 9.1), 3.55 (2.2 - 4.8) ng/ml; p = 0.024, r (rank-biserial correlation) = 0.036 represent very small effect size. FSTL1 levels also showed moderate positive correlations with both BDCAF (r = 0.397) and BODI (r = 0.391) scores, suggesting that higher FSTL1 levels reflect increased inflammatory activity and tissue involvement. Conclusion:Our study demonstrates an elevation in serum FSTL1 levels in BD and positively correlate with disease BD activity and cumulative damage. FSTL1 may reflect inflammatory burden in BD, but further validation is needed to establish causality.
Objective:To evaluate the real-world effectiveness of baricitinib (BARI) in rheumatoid arthritis (RA), compare outcomes in patients <65 years versus ≥65 years, and identify predictors of DAS28-ESR remission/low disease activity (LDA) at 6 and 12 months. Methods:Retrospective multicentre cohort (n=423). Baseline variables included age, sex, disease duration, and comorbidities. DAS28-ESR was recorded at baseline, 6 and 12 months; remission was defined as DAS28-ESR <2.6 and LDA as ≤3.2. Predictors of remission/LDA were assessed with multivariable logistic regression, reporting odds ratios (ORs), 95% confidence intervals (CIs), and p-values. Results:Median age was 60 years (IQR 50.5-69.5); 79% were female; median disease duration 76 months (IQR 31-157). Compared with patients <65, those ≥65 had longer disease duration (94 vs 65 months; p<0.05) and more diabetes (16% vs 5%), dyslipidaemia (47% vs 19%), and hypertension (62% vs 33%) (all p<0.05). Median DAS28-ESR fell from 5.42 (IQR 4.84-6.06) at baseline to 3.71 (2.83-4.59) at 6 months and 3.29 (2.42-4.19) at 12 months (global repeated-measures test significant). Remission+LDA was achieved by 135/421 (32.1%) at 6 months and 182/423 (43.0%) at 12 months; remission alone increased from 65/421 (15.4%) to 117/423 (27.7%). Age ≥65 was not associated with response (6 months: OR 0.71, 95% CI 0.44-1.14, p=0.16; 12 months: OR 0.83, 95% CI 0.55-1.24, p=0.37). ACPA positivity independently predicted remission/LDA (6 months: OR 2.32, 95% CI 1.43-3.77, p<0.05; 12 months: OR 1.71, 95% CI 1.12-2.59, p<0.05). Prior JAK inhibitor exposure was not associated with reduced response. Results were consistent in a per-protocol sensitivity analysis. Conclusion:In this large multicentre real-world cohort, BARI significantly reduced disease activity over 12 months, with comparable effectiveness across age groups. ACPA positivity emerged as an independent predictor of achieving remission/LDA, supporting its potential role in treatment stratification.
Background:Bromelain is a proteolytic enzyme that has been investigated as an adjuvant for treating autoimmune disorders. However, data regarding the role of bromelain in systemic lupus erythematosus is limited. In the present study, we examined the effect of bromelain on the mononuclear cells of SLE patients, precisely its anti-inflammatory properties. Materials and Methods:Peripheral blood mononuclear cells (PBMCs) from SLE patients and healthy controls were stimulated with bromelain (10μg/ml), lipopolysaccharide (10μg/ml), or without any stimulant and cultured for 12 hours. The supernatants were harvested and quantified for IL-1β, TNF-α, IL-6, and IL-17A levels. The mean cytokine levels were compared among different groups using ANOVA and Tukey's post hoc test. Results:Our study revealed that PBMCs of SLE patients (n=41) had significantly higher levels of IL-6 (P=0.0003) and IL-1β (P<0.0001) compared to healthy controls (n=36). When stimulated with lipopolysaccharide, PBMCs of SLE patients showed even higher cytokine levels than healthy controls (IL-6:P<0.0001, TNF-α:P=0.01; IL-1β:P<0.0001). However, the most significant finding was that PBMCs stimulated with bromelain exhibited reduced levels of IL-1β (P<0.0001) and TNF-α (P<0.0001) compared to unstimulated cells of SLE patients. Moreover, cells subjected to lipopolysaccharide and bromelain stimulation displayed lower levels of all cytokines than those stimulated with lipopolysaccharide alone (IL-6:P=0.005, TNF-α:P<0.0001, IL-1β:P<0.0001, IL-17A:P=0.02). Conclusions:The present study highlights the anti-inflammatory role of bromelain in SLE patients by reducing the production of pro-inflammatory cytokine levels in vitro cultured PBMCs derived from SLE patients. Bromelain may be an efficacious adjuvant in managing inflammation in SLE; however, further studies are required.
Aim:In Morocco, cannabinoid therapies have recently been legalised. This study aimed to explore the knowledge, attitudes, and perceptions of Moroccan rheumatologists toward these emerging treatments. Methods:A pretested online questionnaire was distributed via email to all members of the Moroccan Society of Rheumatology. The survey assessed participants' knowledge, prescribing confidence, perceived risks, safety precautions, and barriers to the use of cannabinoid therapies. Results:Of the 400 rheumatologists contacted, 126 responded (response rate: 32%). Among them, 59.5% reported confidence in their knowledge of cannabinoid therapies. A total of 80.6% of respondents believed that pharmacological cannabinoids may have a role in managing rheumatic diseases, while 9.7% declared that there is currently no therapeutic role for cannabinoids in rheumatology. Only 7.1% had recommended a therapeutic trial, and 52.8% expressed concern that the use of cannabinoids may cause patients to discontinue effective standard treatments. Fibromyalgia was the most frequently cited indication (85.7%). The main barriers to prescribing cannabinoid therapies were concerns about a history or risk of substance abuse (79.2%) and patient non-compliance with medical advice (79.2%). Conclusion:This finding highlights hesitation and caution toward these emerging treatments in Morocco. There is a clear need for evidence-based guidance to support rheumatologists in clinical decision-making concerning cannabinoids.
