Introduction: Rheumatoid arthritis (RA) is associated with profound alterations in iron metabolism, contributing to chronic inflammation, immune dysfunction, and, in some cases, the development of anemia. This systematic review and meta-analysis evaluated serum biomarkers of iron metabolism in RA patients compared to healthy controls and assessed differences between anemic and non-anemic RA subgroups. Methods: PubMed, Embase, Scopus, and Web of Science were systematically searched up to December 2024. Nineteen studies (n = 1,640) were included for the RA versus healthy control analysis, and six studies (n = 325) for the anemia subgroup comparison. Random-effects meta-analyses were performed to calculate standardized mean differences (SMDs) with 95% confidence intervals (CI). Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS), and meta-regression was used to explore sources of heterogeneity. Results: RA patients had significantly elevated ferritin (SMD = 1.14, p < 0.01), IL-6 (SMD = 3.94, p < 0.01), hepcidin, sTFR, and TNF-α levels, and reduced serum iron (SMD = -1.30, p < 0.01) and transferrin saturation. Hepcidin and transferrin levels were not significantly different. In anemic RA patients, lower iron and higher hepcidin and TIBC levels were observed. Meta-regression analyses did not identify significant moderators of heterogeneity. Discussion: This meta-analysis indicates that RA is linked to inflammation-induced iron dysregulation, characterized by elevated ferritin levels, diminished serum iron, and functional iron deficiency. These modifications occur independently of anemia; however, anemic individuals exhibit additional alterations, such as elevated hepcidin and TIBC levels. Iron metabolism biomarkers may possess diagnostic and therapeutic significance in rheumatoid arthritis, especially for inflammation-mediated pathways. Conclusion: RA is characterized by systemic iron dysregulation, including ferritin upregulation and functional iron deficiency, independent of anemia. These findings highlight potential targets for future therapeutic strategies and improved disease monitoring.
Introduction: Given the ongoing debate surrounding the validity of Autoimmune/ Inflammatory Syndrome Induced by Adjuvants (ASIA), this study aimed to evaluate the clinical evidence related to this syndrome, with particular emphasis on its major diagnostic criteria and methodological quality. Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. Extracted data included demographic characteristics, exposure types, fibromyalgia-related symptoms, latency, histopathological findings, and autoantibody profiles. The risk of bias was assessed using validated tools appropriate to the study design. Results: Between 1983 and 2024, 51 studies were identified: 27 case series, 18 case reports, 4 cohort studies, 1 case-control study, and 1 cross-sectional study. Silicone was the most frequent exposure. Only 61% of case reports fulfilled ASIA criteria, while 59% of case series described fibromyalgia-compatible features. Complete improvement after removal was reported in 67% of case reports and 33% of case series. Comparative studies yielded inconsistent findings, and substantial outcome heterogeneity precluded meta-analysis. Discussion: The predominance of descriptive studies, heterogeneity in exposures, clinical manifestations, and study populations, as well as methodological limitations, restrict causal interpretation. Although symptomatic improvement following prosthesis removal was commonly reported, responses were variable and frequently incomplete. This uncertainty does not preclude the possibility that specific materials may trigger immune-mediated responses in susceptible individuals. Potential circularity may arise if clinically derived criteria identify cases that are subsequently used as evidence for the syndrome. Conclusion: Current evidence is insufficient to establish that manifestations grouped under ASIA constitute a distinct clinical entity with a common causal mechanism. Robust analytical, population-based studies with clearly defined exposures and appropriate comparison groups are warranted.
Introduction: Diagnosing amyloid arthropathy remains challenging because its manifestations often mimic those of other inflammatory musculoskeletal diseases. This review aimed to describe the clinical, biological, and imaging characteristics of musculoskeletal involvement in light-chain (AL) Amyloidosis. Methods: We conducted a review in accordance with the PRISMA guidelines. We searched SCOPUS and MEDLINE for case reports and series published between January 2000 and December 2023 that detailed musculoskeletal manifestations of AL amyloidosis. To minimize the risk of omitting relevant articles, we also manually searched the reference lists of the articles identified in the initial search. Reports describing isolated cardiac amyloidosis or patients under active chemotherapy were excluded. Results: We identified 140 patients, all of whom presented with musculoskeletal manifestations as the initial manifestation of systemic AL amyloidosis. The mean age was 62.6 ± 11.6 years. Musculoskeletal findings included joint involvement in 33.6% of cases, muscular symptoms in 10.7%, carpal tunnel syndrome in 30%, and bone lesions in 12.1%. Among patients with joint disease, 42 (30%) had a rheumatoid arthritis-like presentation, and five (3.6%) exhibited features resembling giant cell arteritis. Diagnosis was confirmed by positive immunostaining for lambda light chains in all cases. Multiple myeloma was identified in 37.5% of patients. Of the 46 patients with available treatment data and a median follow-up of 11.5 months (range: 6–23 months), 25 (17.8%) achieved hematologic remission after chemotherapy, whereas 21 (15%) died during follow- up. Discussion: Our review offers a more comprehensive picture of the diverse musculoskeletal manifestations of AL amyloidosis. It showed that amyloid arthropathy can mimic common rheumatologic disorders, especially rheumatoid arthritis. Publication bias was identified as the main study limitation. Conclusions: Our findings suggest that the diagnosis of AL amyloidosis should be considered when joint involvement is associated with macroglossia, nephrotic syndrome, polyneuropathy, periorbital purpura, cutaneous lesions, or heart failure.
Introduction: Several genetic association studies have investigated Inflammatory Arthropathy (IA), a term used in this study to refer specifically to rheumatoid arthritis classified according to the 1987 American College of Rheumatology (ACR) criteria and the 2010 ACR/EULAR classification criteria. However, limited data are available regarding the role of the Angiotensin‑Converting Enzyme (ACE) Insertion/Deletion (I/D) polymorphism across different populations. The present study aimed to evaluate the association between the ACE I/D polymorphism and IA susceptibility in the Western Algerian population Materials and Methods: A total of 101 patients diagnosed with IA and 140 healthy unrelated controls were enrolled. Genotyping of the ACE I/D polymorphism (rs4340) was performed using multiplex Polymerase Chain Reaction (PCR). Genotype and allele frequencies were compared between groups, and Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were calculated using SPSS software. Results: Our findings indicated a strong risk of IA associated with genotypic distributions of ACE I/D, DD ((OR) = 4(1,02-15.72), p-value = 0.04, as well as the dominant model (ID+DD) (OR) =16,01(1-29), p-value = 0.01, in the development of IA. However, no significant association was observed between ACE I/D genotypes and age in our study. Discussion: These findings suggest that the ACE I/D polymorphism, particularly the D allele, may contribute to IA susceptibility, possibly through inflammatory pathways involving the renin-angiotensin system. Conclusion: This is the first study in the Algerian population to demonstrate a potential association between the ACE I/D polymorphism and rheumatoid arthritis.
Introduction: Rheumatoid Arthritis (RA) is an autoimmune disease that has heterogeneous clinical manifestations. The A3 Adenosine Receptor (A3AR), a protein implicated in numerous inflammatory pathways, is overexpressed in patients with RA. Methods: The available preclinical and clinical literature about A3AR signaling in RA was reviewed, and published data on its molecular pathways, immunomodulatory functions, and role in synovial fibroblasts were searched. Studies exploring A3AR agonists and their mechanistic interactions with NF-κB and p53 pathways were also reviewed. Results: The mechanisms in which the A3AR is involved in alleviating inflammatory status resulting from alterations in transcriptional activity of the nuclear factor kappa B-light- chain-enhancer of activated inflammatory cells (NF-κB) in RA and the clinical and preclinical studies working on A3AR agonists alongside the apoptosis process by interacting with the p53 expression level. In contrast, we explained that the canonical and non-canonical pathways for A3AR, which may lead to worsening inflammation, were detailed. Discussion: The implication of A3AR in the worsening of destructive effects on RA synovium in cases of hypoxia, as well as the consequences of low oxygen levels on FLSs, was detailed. Conclusion: In conclusion, we hypothesized that the overexpressed A3AR could provide the activation of Ras, leading to the inflammatory and senescent phenotype of FLSs during the pathological processes in RA.
