Search Results (110)

Background: Systemic lupus erythematosus (SLE) may present with heterogeneous clinical manifestations in pediatric patients. Although infections are a major cause of morbidity and mortality in SLE, severe bacterial infections rarely represent the presenting clinical event leading to diagnosis. Case description: We report the case of a 13-year-old boy diagnosed with SLE with Sjögren’s syndrome overlap who presented with pneumococcal sepsis. The patient was admitted with high-grade fever and facial swelling, and blood cultures grew Streptococcus pneumoniae. Although an initial clinical response to antibiotic therapy was observed, fever subsequently recurred, accompanied by persistent systemic symptoms and progressive laboratory abnormalities. Further investigations revealed hematologic abnormalities, serosal involvement, renal disease, and a characteristic autoantibody profile. The patient fulfilled the 2019 ACR/EULAR classification criteria for SLE after comprehensive autoimmune evaluation. The overlap with Sjögren’s syndrome was supported by the autoantibody profile and imaging findings involving the parotid glands. Following treatment with intravenous methylprednisolone pulses, oral prednisone, hydroxychloroquine, and mycophenolate mofetil, the patient showed rapid clinical improvement and sustained remission. Conclusions: This case highlights that severe invasive bacterial infection may occasionally be the clinical circumstance that leads to the diagnosis of pediatric systemic lupus erythematosus. Persistent systemic inflammation or evolving multisystem involvement despite appropriate antimicrobial therapy should prompt consideration of an underlying autoimmune disease, even in patients without a prior history of immune dysfunction. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is frequently accompanied by psychological distress. Alexithymia, an impairment in identifying and describing emotions, has been reported in SLE, but its clinical and serological correlates remain insufficiently characterized. We aimed to estimate the prevalence of clinically significant alexithymia in SLE and to explore its clinical, laboratory, and coping-related correlates. Methods: In this cross-sectional observational study, adult outpatients fulfilling the 2019 ACR/EULAR SLE classification criteria were assessed at a tertiary referral centre (2024–2025). Alexithymia was measured using the Toronto Alexithymia Scale-20 (TAS-20), and clinically significant alexithymia was defined as a total score >60. Coping strategies were assessed with the 60-item COPE inventory (Italian version). Clinical indices (SLEDAI-2K, Lupus Low Disease Activity State (LLDAS), and SLICC/ACR Damage Index (SDI)), organ involvement, antiphospholipid syndrome (APS), selected autoantibodies, complement levels, and treatments were recorded. Group comparisons and exploratory logistic regression were performed. Results: Sixty-eight patients were included (94.1% female). Clinically significant alexithymia was present in 23.5%. In univariate analysis, alexithymia was more frequent among patients with APS. Alexithymic participants reported higher use of emotional venting and lower use of positive reinterpretation. In an exploratory multivariable logistic regression model, APS (adjusted OR 35.79, 95% CI 3.74–341.7), emotional venting (adjusted OR 1.684, 95% CI 1.162–2.44), and positive reinterpretation (adjusted OR 0.514, 95% CI 0.349–0.755) remained associated with alexithymia. Conclusions: Alexithymia was frequent in this SLE cohort and, in exploratory analyses, was associated with APS and specific coping patterns. These findings suggest that assessment of emotional processing and coping may provide complementary clinical information, particularly in patients with APS, but should be interpreted as associative and hypothesis-generating. Full article

Background: Interstitial lung disease (ILD) is the most frequent extra-muscular manifestation in patients with idiopathic inflammatory myopathies (IIMs). Although high-resolution chest tomography (HRCT) represents the gold standard for the evaluation of ILD, lung ultrasound (LUS) might be a useful tool for its assessment. The aim of our study was to evaluate the number and distribution of pleural irregularities (PIs) identified by lung US in a cohort of patients with IIMs and to find possible correlations with clinical, serological and HRCT data to verify the potential usefulness of lung US for the study of ILD in patients with IIM. Patients and methods: Fifty-three patients with IIM according to EULAR/ACR classification criteria were enrolled. All patients underwent a clinical evaluation with measurement of disease activity and myositis-specific autoantibodies, pulmonary function tests, HRCT evaluated with the Warrick score, and lung US for the measurement of PIs. Results: The number of PIs was higher in patients with myositis-specific autoantibodies, particularly those with anti-synthetase autoantibodies (p < 0.001) and in patients with high-grade dyspnea (p < 0.03). A negative correlation was identified between PIs and pulmonary function tests, particularly TLC (r = −0.74; p < 0.001) and DLCO (r = −0.56; p < 0.001). Interestingly, PI score was higher in patients with ILD identified with HRCT (p = 0.015) and a positive correlation between PIs and Warrick score (r = 0.542; p < 0.001) was also found. Conclusions: The study of PIs with lung US represents a promising diagnostic tool for the bedside evaluation of patients with IIMs. This can possibly allow for a reduction in unnecessary HRCTs, reducing the exposition of patients to ionizing radiations, optimizing resources and reducing the costs of patients’ management. Full article

Background/Objectives: Patients with rheumatoid arthritis (RA) have an increased risk of chronic kidney disease (CKD) and cardiovascular disease, largely driven by persistent systemic inflammation. This study aimed to assess the risk of CKD in RA patients and to evaluate its association with structural joint damage and cardiovascular risk (CVR). Methods: In this cross-sectional study, 70 patients fulfilling the 2010 ACR/EULAR criteria for RA were evaluated. Structural joint damage was assessed using the Sharp/van der Heijde score (SHS). Renal involvement was evaluated by estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR), and intrarenal resistive index (RRI). CVR was assessed using the SCORE system, adjusted according to EULAR recommendations, and carotid ultrasonography was performed to assess intima–media thickness (IMT) and atherosclerotic plaques. Results: SHS was significantly correlated with renal and vascular parameters, showing positive associations with ACR, RRI, and carotid IMT, and a negative correlation with eGFR (all p < 0.0001). CVR correlated positively with SHS, ACR, RRI, and IMT. Patients with elevated RRI (≥0.70) had longer disease duration, more severe joint damage, impaired renal function, and higher CVR. Conclusions: In RA patients, cumulative articular damage is closely associated with renal dysfunction and increased CVR, highlighting the central role of sustained inflammation in multiorgan involvement. Full article

Background/Objectives: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by fluctuating disease activity and multi-organ involvement. The identification of reliable biomarkers that accurately reflect disease activity remains a significant clinical challenge, particularly in predicting disease flares. Chemokines are key mediators of immune cell recruitment and inflammation, making them promising candidates for disease activity monitoring. Therefore, we evaluated serum concentrations of CCL2, CCL4, CCL5, CXCL8, and CXCL10 and examined their associations with disease activity and clinical manifestations in patients with SLE. Patients and Methods: A total of 52 patients with SLE were enrolled in the study, of whom 15 (28.8%) had active disease (SLE Disease Activity Index [SLEDAI] ≥ 5) and 37 (71.2%) were in remission (SLEDAI < 5). An additional group of 12 age- and sex-matched healthy individuals without a family history of autoimmune diseases served as controls. All SLE patients fulfilled the 2019 EULAR/ACR classification criteria. Serum levels of the selected chemokines were measured in all participants using the Luminex Human Premixed Multi-Analyte Discovery Assay. Results: Serum concentrations of CCL2 and CCL4 did not differ between SLE patients and healthy controls, nor between active and inactive disease subgroups (p > 0.05, for all). In contrast, CCL5 levels were 34.30% higher in patients with SLE compared with controls (p = 0.013), with the strongest increase observed in the inactive disease subgroup as compared to controls (by 40.29%, p = 0.021). CXCL8 levels were markedly elevated in patients with active SLE relative to those in remission (by 123.30%, p = 0.011) and to healthy individuals (by 183.96%, p = 0.049). CXCL10 levels were higher in both active and inactive SLE groups compared with controls (increase of 180.80%, p < 0.001 and increase of 100.80%, p = 0.018, respectively). No differences in chemokine levels were detected between patients with renal flares and those with non-renal flares, nor among patients in remission with and without a history of lupus nephritis (p > 0.05, for all). CXCL8 and CXCL10 correlated positively with disease activity scores, inflammatory markers, and several immune parameters, indicating their relevance to ongoing inflammatory processes (p < 0.05, for all). CCL5 was associated with complement components C3 (r_S = 0.36, p = 0.008) and C4 (r_S = 0.38, p = 0.006), while CXCL10 showed negative correlations with white blood cell (r_S = −0.34, p = 0.013), lymphocyte counts (r_S = −0.36, p = 0.008) and neutrophils (r_S = −0.32, p = 0.019). In the longitudinal follow-up of patients in remission (median follow-up time of 5.5 years), baseline chemokine levels did not predict subsequent disease flares among SLE patients who were inactive as the study baseline (p > 0.05, for all). Conclusions: In our study, serum levels of CXCL8 and CXCL10 reflect disease activity and systemic inflammation in SLE, supporting their potential value as biomarkers for monitoring ongoing immune activation. Baseline concentrations of the examined chemokines did not predict future disease flares, indicating their limited utility in this context. Full article

Background/Objectives: Systemic sclerosis (SSc) patients frequently develop osteoporosis; however, vertebral fracture risk factors remain poorly characterized. This study identifies general and SSc-specific predictors of vertebral fractures in SSc patients undergoing osteoporosis evaluation. Methods: This multicenter cross-sectional study enrolled consecutive SSc patients meeting ACR/EULAR 2013 criteria with suspected osteoporosis. Data included demographics, disease characteristics, bone density (DXA), and vertebral imaging. Stepwise logistic regression analyzed fracture associations (p ≤ 0.05 significant). Results: The majority of 103 enrolled patients were female and all were post-menopausal. The prevalence of osteoporosis was 52.4%, that of vertebral fractures was 38.8%, and that of osteopenia was 28.1%. General risk factor analysis identified family history of fragility fractures (OR 11.8, p = 0.008) and vertebral T-scores (OR 0.6, p = 0.049) as significant predictors. When adding SSc-specific factors, only family history (OR 13.8, p = 0.03) and gastrointestinal (GI) involvement (OR 4.8, p = 0.05) remained significant. Conclusions: Vertebral fractures in SSc patients are strongly linked to a family history of fractures. The suggestive association with GI involvement may imply a significant role for malabsorption-related metabolic impairment. Prioritizing bone density screening in SSc patients with GI symptoms may enable earlier intervention and reduce fracture risk. Full article

Antiphospholipid syndrome (APS), first described in 1983, is a systemic autoimmune disorder characterized by recurrent arterial and venous thrombosis, pregnancy complications, and persistent antiphospholipid antibodies (aPL). Over four decades, significant advancements have been made in understanding APS pathogenesis, diagnostics, and treatment. Key discoveries include the development of standardized anticardiolipin antibody (aCL) assays, the identification of β2-glycoprotein I (β2GPI) as a critical cofactor, and the elucidation of the “two-hit” hypothesis, which explains thrombotic events through a combination of aPL-induced prothrombotic priming and secondary external triggers. Recent research has highlighted the roles of complement activation, neutrophil extracellular traps (NETs), and genetic predispositions shared with systemic lupus erythematosus (SLE). Innovations like the antiphospholipid score (aPL-S) and updated classification criteria, including the 2023 ACR/EULAR guidelines, have improved diagnostic precision and risk stratification. Despite these advances, challenges remain in assay standardization and addressing seronegative APS. Future directions emphasize the integration of multimodal biomarkers, precision diagnostics, and targeted therapies aimed at complement and NET pathways. These efforts aim to achieve individualized care, improving outcomes for APS patients through harmonized diagnostics, mechanistic therapeutics, and data-driven approaches. This review underscores the evolving understanding of APS and its potential for personalized management strategies. Full article

In rheumatoid arthritis (RA), altered DNA methylation patterns could be associated with pro-inflammatory, immune, and metabolic risk profiles. Notably, DNA methylation is dynamically regulated by the interplay of multiple factors, including diet, cardiometabolic status, and aging. Therefore, this study aimed to assess the associations between global leukocyte DNA methylation, dietary methyl-donor intake, and cardiometabolic risk in RA and control subjects (CS). A cross-sectional study was conducted with 123 female RA patients classified by the 2010 ACR-EULAR criteria, and 130 female CS. Leukocyte DNA methylation status was assessed with the 5-mC DNA ELISA Kit. RA patients exhibited significantly lower global DNA methylation levels than those with CS. RA status was independently associated with lower DNA methylation levels after adjustment for age and body mass index. Similarly, in both study groups methionine intake showed an independent inverse association with global DNA methylation across adjusted models and lower methylation levels were consistently associated with an unfavorable cardiometabolic profile, characterized by increased adverse adiposity- and lipid-related indexes. In conclusion, RA patients exhibited lower global leukocyte DNA methylation levels compared with CS. In both study groups, lower DNA methylation levels were associated with low methionine intake and an unfavorable cardiometabolic profile. Full article

Introduction: Primary Sjögren’s (pSS) is an autoimmune disease that affects several organs, especially the heart, and raises cardiovascular risk. Investigating the associations of hemoglobin-to-red cell distribution width (RDW) ratio (HRR), vitamin D status, and cardiac function could provide valuable insights and biomarkers regarding early cardiovascular risk in patients with pSS. Method: This cross-sectional study involved 61 patients diagnosed with pSS based on ACR/EULAR criteria. Data on demographics, hematological (Hb, RDW), echocardiography, and serum vitamin D levels were collected. Echocardiograms were conducted by trained cardiologists following established guidelines, while vitamin D levels were measured using ELISA. Statistical analyses, including univariate linear regression, were performed with SPSS in order to identify whether HRR tertiles were related to cardiac function and vitamin D status. Results: A study of 61 pSS patients (mean age 59.8 years, 89% female) revealed that patients with a lower hemoglobin-to-RDW ratio (HRR ≤ 0.98) had significantly higher pulmonary artery pressures (PAPs) and lower values for the tricuspid annular plane systolic excursion (TAPSE)/PAPs ratio, contributing to poor right heart function. These associations were particularly strong in patients with insufficient levels of vitamin D (<30 ng/mL), while differences in other echocardiographic parameters remained nonsignificant between HRR groups. Conclusions: These findings underscore the clinical value of HRR as a composite biomarker that reflects the interplay between anemia, inflammation, and cardiovascular health in primary Sjögren’s disease. They also suggest that vitamin D status may be an important therapeutic consideration to mitigate cardiopulmonary risks in this population. Full article

Background/Objectives: SA001, a mofetil-ester prodrug of rebamipide, was developed to enhance gastrointestinal absorption and systemic exposure, which was confirmed in a prior Phase 1 study. Given the limited efficacy of current symptomatic therapies for primary Sjögren’s syndrome (pSS), this trial aimed to assess whether the improved bioavailability of SA001 could translate into clinical benefits. Methods: This multicenter, randomized, double-blind, placebo-controlled Phase 2a study enrolled adults who met the 2016 ACR–EULAR criteria for pSS. The participants were randomly assigned to one of four groups: SA001 at 360, 720, or 1080 mg/day (administered twice daily for 8 weeks) or placebo. Exploratory ocular assessments included tear break-up time, ocular surface staining, the Schirmer test, and the Standard Patient Evaluation of Eye Dryness. Oral endpoints included unstimulated whole salivary flow and the Xerostomia Inventory. Anti-SSA(Ro) antibodies were assessed both quantitatively and qualitatively. Safety evaluations comprised adverse events (AEs), ophthalmic examinations, laboratory tests, and vital signs. The efficacy outcomes were exploratory, and this study was not powered to formally test efficacy hypotheses. Results: Twenty-eight women (mean age 58.54 ± 9.29 years; range 41–75 years) were enrolled in this study and randomly assigned to one of the study groups. SA001 showed no statistically significant improvements versus placebo in ocular or oral endpoints, and no consistent dose–response relationship was observed. The anti-SSA(Ro) findings did not differ meaningfully across the groups. SA001 was generally well-tolerated, with infrequent, mostly mild-to-moderate AEs; however, one serious AE occurred in the placebo group. No clinically relevant ophthalmic or laboratory safety signals were detected. Conclusions: Despite the fact that markedly increased systemic exposure has been demonstrated previously, SA001 did not improve the dryness outcomes in pSS. These findings suggest that systemic exposure alone may be insufficient in established glandular disease and highlight the need for tissue-exposure-driven strategies and biomarker-informed patient selection in future studies. Predefined primary efficacy endpoints and objective, gland-proximal measures of target engagement (e.g., standardized salivary gland ultrasonography and salivary or tear fluid biomarker assessments) may help to better interpret local pharmacodynamic activity and the likelihood of a clinically meaningful benefit. Full article

Background and Objectives: Patients with Sjögren’s disease (SjD) do not experience any improvement in gastroesophageal reflux disease (GERD) symptoms after SjD treatment, and in some patients, reflux even worsens. It is important to note that GERD manifests itself through typical and atypical symptoms, the latter of which may include eye damage, as evidenced by a growing body of research. When SjD patients were prescribed medication to treat GERD, their condition improved at the same time. Therefore, we aim to investigate whether there is a link between ocular dryness and gastroesophageal reflux disease (GERD) in patients with Sjögren’s disease (SjD). Materials and Methods: Our study included 27 patients with SjD according to the 2016 American College of Rheumatology and the European League Against Rheumatism (ACR/EULAR) Sjögren’s syndrome Classification Criteria, and 28 patients with non-autoimmune sicca syndrome due to GERD (nonautoimmSicca). Results: The study involved 55 participants, 48 (87.3%) women and 7 (12.7%) men. The median age was 54 years (IQR 49–64). A total of 41 subjects (74.5%) had GERD, and 20 subjects (36.4%) tested positive for Helicobacter pylori: 13 (48.1%) and 1 (3.7%) in the SjD group, and 28 (100.0%) and 19 (67.9%) in the nonautoimmSicca group, respectively. A significant difference in asymmetric tear secretion (p < 0.001) was found between the nonautoimmSicca and SjD patients, with values of 5 (3–10) mm/5 min and 1 (0–2) mm/5 min, respectively. A low correlation was detected between sialometry results and tear secretion asymmetry (r = 0.48, p < 0.001). An increase of 1 mm/5 min in the tear secretion asymmetry between the eyes was associated with a 2.04-fold increase in the odds ratio for having GERD (95% CI 1.25–3.32, p = 0.004), and was associated with a 1.9-fold increase in the odds ratio for having GERD (95% CI 1.04–3.49, p = 0.038) in patients with SjD. The presence of Helicobacter pylori is associated with asymmetric tear secretion [95% CI 1.22 (1.05–1.41, p = 0.010)]. Conclusions: Asymmetric tear secretion between the eyes is associated with the odds of having GERD. Patients with non-autoimmune sicca syndrome due to GERD have significantly greater asymmetry in tear secretion compared to those diagnosed with Sjögren’s disease. Full article

Primary Sjögren’s syndrome (pSS) is an autoimmune disease characterized by inflammation and damage to salivary and lacrimal glands. Its etiology involves both genetic and environmental factors. Among susceptibility genes, IRF5 has been highlighted in European populations, but evidence in non-European groups remains limited. This study evaluated whether IRF5 variants rs2004640G/T, rs2070197T/C, rs10954213G/A, and rs59110799G/T are associated with pSS susceptibility, clinical manifestations, or the presence of autoantibodies in a Mexican population. The diagnosis was confirmed by rheumatologists using the 2016 ACR–EULAR classification criteria for pSS. Genotyping was performed using TaqMan probes in 231 controls and 132 pSS patients from central Mexico. Associations were analyzed through binary logistic regression under different genetic models, adjusting for age and geographic origin. Clinical correlations were examined with SNPStats, and haplotypes were constructed using Haploview. Results showed that all four IRF5 variants were significantly associated with pSS susceptibility. Moreover, rs2004640, rs2070197, and rs10954213 variants were associated with arthritis, a frequent clinical manifestation in pSS patients. This represents the first evidence in a Latin American population demonstrating that IRF5 variants contribute to increased risk of developing pSS. These findings suggest ethnicity-specific genetic influences and highlight the importance of expanding research beyond European cohorts. Replication in larger samples and functional analyses are needed to confirm these associations and clarify their biological relevance. Full article

Background: Seronegative rheumatoid arthritis (SNRA), defined by the absence of rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA), represents 20–30% of rheumatoid arthritis cases. Once considered a milder phenotype, SNRA is now recognised as a heterogeneous entity in which a substantial subset of patients develops structural progression comparable to seropositive RA. The binary RF/ACPA-based definition is increasingly viewed as insufficient, as the broader anti-modified protein antibody (AMPA) family—including antibodies against carbamylated, acetylated and malondialdehyde–acetaldehyde–modified proteins—indicates that many “seronegative” patients may harbour unconventional humoral autoimmunity undetected by standard assays. Objectives: To synthesise contemporary insights into the epidemiology, immunopathology, diagnostic challenges and therapeutic management of SNRA, with emphasis on erosive versus non-erosive phenotypes and the implications of the AMPA paradigm. Methods: A comprehensive literature search of PubMed, Cochrane Library and Google Scholar identified randomised trials, observational cohorts and systematic reviews, with focus on studies published within the past decade. Results: SNRA displays partially distinct immune features, including lower formation of tertiary lymphoid structures and variable activation of innate inflammatory circuits. However, the traditional adaptive–versus–innate dichotomy is overly reductionist. Growing evidence suggests that unconventional humoral responses directed against non-classical post-translational modifications may be present in a proportion of RF/ACPA-negative patients. Additional qualitative dimensions—such as IgA isotypes and fine-specificity profiles—represent further heterogeneity with potential prognostic significance. Although ACPA remains the strongest predictor of erosive progression, up to one-third of seronegative patients develop erosions within five years. The 2010 ACR/EULAR criteria may delay diagnosis in SNRA. Cytokine inhibitors and JAK inhibitors show largely serostatus-independent efficacy, whereas B-cell and T-cell–targeted therapies demonstrate attenuated responses in SNRA. Conclusions: SNRA is clinically and immunologically diverse. Integrating the AMPA framework is essential for refining classification and prognostication. Distinguishing erosive from non-erosive forms may guide treatment, while future work should prioritise biomarkers predicting progression and therapeutic response. Full article

Background and Objectives: Sjögren’s syndrome (SS) causes destructive salivary gland dysfunction with substantial oral morbidity. To synthesize practical, evidence-based approaches for early recognition, initial oral management, and timely referral to dental care. Materials and Methods: Narrative review of English-language literature from the Web of Science Core Collection and PubMed, prioritizing systematic reviews, randomized trials, and consensus guidelines. Results: Early oral signs include rapid multifocal root and cervical caries, burning sensations, and rising dental treatment needs. Unstimulated whole saliva ≤ 0.1 mL/min supports significant hypofunction and complements the 2016 ACR/EULAR criteria. Preventive care should combine dietary counseling, salivary stimulation, and topical remineralization. Adjuncts include high-fluoride toothpaste, biomimetic hydroxyapatite dentifrices, and casein phosphopeptide–amorphous calcium phosphate (CPP-ACP). However, evidence for fluoride varnish in SS remains mixed. Pharmacologic sialogogues require screening for contraindications. Conclusions: Embedding oral screening, simple salivary metrics, and a structured referral pathway into rheumatology visits can reduce preventable tooth loss and improve comfort, function, and treatment adherence. Full article

Calcium pyrophosphate deposition (CPPD) disease is a consequence of the immune response to the pathological accumulation of calcium pyrophosphate (CPP) crystals within joints. This clinically heterogeneous condition can cause significant disability, yet its management remains poorly defined. New discoveries are reshaping the therapeutic landscape beyond conventional anti-inflammatory agents—which remain the cornerstone of care—justifying this review on current standard of care and treatment advances in CPPD disease. We first address the two theoretical management goals, namely inflammation control and crystal dissolution—with attempts to address the latter having failed thus far. We then summarize the evidence supporting conventional anti-inflammatory treatments and review insights into the pathophysiology of CPPD disease, which are driving the development of novel therapeutic strategies. These include the current use of biologics (IL-1 and IL-6 inhibitors) to control inflammation and highlight the need to explore new pathways to inhibit crystal formation (e.g., selective NPP1 blockers). We present the treatments in the development pipeline for CPPD disease (including JAK inhibitors), and the therapies currently undergoing clinical trials in gout for which findings could be extended to CPPD disease given their shared pathophysiology (e.g., NLRP3 inhibitors). To support and improve research on CPPD disease treatments, clinical trial design needs to be standardized, incorporating the recent ACR/EULAR classification criteria for accurate diagnosis, careful phenotypic stratification to ensure homogeneous patient groups (although this point requires consensus), and validated core outcome domains currently being developed by the OMERACT. Full article