Open Access Rheumatology-Research and Reviews最新文献

Purpose: To describe the characteristics of patients with ankylosing spondylitis (AS) or psoriatic arthritis (PsA) treated with Acthar Gel, medication utilization, and physicians' assessments of the effects of Acthar Gel on patients' health status.

Patients and methods: A prospectively designed, cross-sectional, medical chart review study with a predefined protocol and analysis plan was conducted in November 2024, with data abstracted from patient records between April 2022 and November 2024. Eligible patients were aged ≥18 years, had AS or PsA, and had received Acthar Gel within ≤24 months.

Results: On average, patients with AS were 44 years, and those with PsA were 51 years; patients were primarily Caucasian/non-Hispanic. Most patients with AS were male (67%, 42/63), whereas PsA had a similar gender distribution (49% [38/77] each). Common comorbidities included arthritis/osteoarthritis, chronic joint disease, and hypertension. Before receiving Acthar Gel, physicians reported 41% (26/63) of patients with AS and 44% (34/77) with PsA had fair-to-poor health status. Frequent symptoms in AS were back pain, lower back/hip stiffness, and fatigue, and in PsA were joint swelling and pain, reduced range of motion, and fatigue. Based on physician assessment, 95% (60/63) with AS and 88% (68/77) with PsA had improved health after Acthar Gel treatment. Improvements included reduction in overall symptoms (AS: 70% [42/60]; PsA: 63% [43/68]), decreased pain (AS: 68% [41/60]; PsA: 62% [42/68]), improved physical function (AS: 53% [32/60]; PsA: 54% [37/68], improved fatigue (AS: 35% [21/60]; PsA: 32% [22/68]), and reduced corticosteroid use (AS: 30% [18/60]; PsA: 31% [21/68]).

Conclusion: Based on chart review, Acthar Gel may represent a potential treatment option for appropriate patients with AS or PsA. In this study, among patients with AS or PsA treated with Acthar Gel, physicians documented a reduction in overall symptoms, decreased pain, improved physical function, reduced corticosteroid use, improved strength, and improved fatigue using prespecified assessments.

Objective: To evaluate the efficacy of baricitinib in combination therapy for managing refractory, rapidly progressive systemic sclerosis (SSc) with severe cardiac conduction defects and interstitial lung disease (ILD).

Methods: A 48-year-old male patient with SSc complicated by significant cardiac enlargement, third-degree atrioventricular block, heart failure, progressive ILD, and partial intestinal obstruction was included in the study. Prior treatments with mycophenolate mofetil (MMF), tacrolimus, and cyclophosphamide (CTX) had shown limited efficacy. The patient subsequently received a combination regimen of glucocorticoids, intravenous immunoglobulins, CTX, and baricitinib (4 mg daily).

Results: The patient exhibited significant clinical improvements, including a reduction in cardiac size, restoration of sinus rhythm, and resolution of heart failure symptoms. ILD and skin sclerosis showed substantial regression. Pulmonary function tests indicated significant recovery in lung capacity and diffusion capacity. Additionally, gastrointestinal symptoms such as abdominal pain and bloating were completely resolved.

Conclusion: This case highlights the potential of baricitinib as an adjunctive therapy for refractory SSc with multiorgan involvement. The observed improvements in cardiac conduction defects, ILD, and skin fibrosis suggest that JAK inhibitors may offer a promising therapeutic avenue for severe SSc cases resistant to conventional treatments.

Antiphospholipid syndrome (APS) is a complex multisystem disorder traditionally classified into primary forms and those associated with autoimmune diseases. However, infection-induced APS is gaining attention as a distinct subset due to the increasing recognition of thrombotic complications occurring in the context of viral or bacterial infections. Despite its clinical relevance, this phenomenon remains poorly characterized. This narrative review synthesizes current knowledge on the pathogenesis, clinical manifestations, and diagnostic challenges of infection-induced APS. A literature search was conducted in the Medline and PubMed databases for English-language articles published between 2014 and May 2025. Of the identified publications, 35 were selected for detailed analysis. Evidence supports a multifaceted relationship between infections and APS, with proposed mechanisms including molecular mimicry, Toll-like receptor activation, generation of non-pathogenic antiphospholipid antibodies (aPL), impaired immune complex clearance, neutrophil extracellular trap formation, direct endothelial damage, and the "second hit" hypothesis. Clinical presentations are diverse, ranging from mild, transient symptoms to severe thrombotic events, and often complicate the distinction between true APS and transient aPL positivity secondary to infection. Diagnostic difficulties are compounded by the fluctuating presence of aPL and the overlap of infection-related symptoms with APS criteria. Currently, there are no standardised criteria for infection-induced APS, underscoring the need for definitions that reflect its temporal dynamics and immunological heterogeneity.

Objective: Osteoarthritis (OA) is a degenerative disorder associated with glycolysis. However, the precise mechanisms remain unclear. This study aimed to identify glycolysis-associated biomarkers and elucidate how glycolysis-related genes interact with the synovial immune microenvironment in OA progression.

Methods: Normal and OA synovial gene expression profile microarrays were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using limma package. Gene Ontology (GO) and KEGG enrichment analyses were conducted to explore biological functions. Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify OA-associated genes, which were intersected with glycolysis genes from The Molecular Signatures Database (MSigDB) and DEGs to obtain key genes. Lasso regression and random forest models were employed to establish a risk model, and its predictive performance was evaluated using nomogram, Receiver Operating Characteristic (ROC) analysis, and Decision Curve Analysis (DCA). Gene Set Enrichment Analysis (GSEA) and Cibersort analysis were conducted to explore pathways and immune infiltration correlations.

Results: A total of 239 OA-associated genes were identified through WGCNA. Six hub genes were obtained by intersecting with glycolysis genes and DEGs. Four key glycolytic genes were selected by Lasso regression and random forest models. The nomogram showed that three genes (DDIT4, SLC16A7, SLC2A3) could predict OA risk accurately. The ROC analysis demonstrated an area under the curve (AUC) of 0.85, indicating good predictive performance. Distinct immune cell distribution patterns were observed in OA groups. Interaction networks were constructed for the key genes with related miRNAs, transcription factors (TFs), and small molecule drugs.

Conclusion: This study identified three key glycolysis-related genes (DDIT4, SLC16A7, SLC2A3) in OA, revealing their potential roles in disease progression and immune infiltration. These findings may provide new insights into the pathogenesis and therapeutic targets for OA, based on the identified genes and their interactions with the immune microenvironment.

VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described adult autoinflammatory disease associated with somatic mutations in the gene encoding ubiquitin-activating enzyme 1 (UBA1) in hematopoietic progenitor cells. Loss of function mutation of UBA1 results in a broad range of inflammatory and hematological conditions. To date, there are no established targeted therapies for VEXAS syndrome, especially in patients who are refractory to conventional immunosuppressive treatments. We report the case of a 75-year-old Hispanic gentleman with hypertension, dyslipidemia, and type 2 diabetes mellitus who presented with a 2-year history of intermittent fever, weight loss, recurrent sore throat, recurrent soft tissue swelling (mimicking cellulitis), oligoarthritis, erythema nodosum, and venous thrombosis. Laboratory workup showed elevated inflammatory markers, macrocytic anemia, and leukopenia. Patient received several rounds of antibiotics and corticosteroids for presumed cellulitis and throat infections, with limited improvement. He subsequently underwent bone marrow biopsy, which showed characteristic vacuolization of myeloid precursors. Genetic testing revealed a missense mutation in UBA1, Exon 3 c.121A>G, pMet41Val. He was diagnosed with VEXAS syndrome. He was started on corticosteroids and Tocilizumab (anti-IL-6 receptor antibody). He had severe leukopenia with Tocilizumab and was switched to Ruxolitinib (Jak inhibitor). He had a significant clinical response to Ruxolitinib and was able to be tapered off prednisone. Our case report and review of the literature report Jak inhibition as a possible target for the management of inflammatory symptoms of VEXAS.

Background: Primary Sjögren's Syndrome (pSS) is a systemic autoimmune disease that predominantly impacts the exocrine glands. It is characterized by a diverse clinical manifestation and the existence of various autoantibodies. There is a lack of studies assessing the primary pSS phenome driven by anti-Sjögren syndrome autoantibodies in Africa, particularly in Egypt.

Objective: This study aims to evaluate the clinical implications of antinuclear antibodies (ANA) and anti-Ro/anti-La autoantibodies in an Egyptian national cohort of pSS patients.

Methods: We conducted a cross-sectional analysis of pSS patients, comparing clinical manifestations and disease severity based on serological profiles.

Results: A total of 301 pSS patients (mean age: 45.6±10.2 years; F:M ratio 7.4:1) were included. Patients with positive ANA (59.5%) had a higher prevalence of anti-Ro (p=0.001) and anti-La (p=0.0001) antibodies, along with lower rates of dry eyes (p=0.04) and enlarged parotid glands (p=0.001). Corticosteroid and azathioprine use was more frequent in ANA-positive patients (p=0.017, p=0.003). Double-positive anti-Ro/anti-La patients exhibited higher rates of dry mouth (p=0.045), articular manifestations (p<0.0001), fibromyalgia (p=0.001), RF positivity (p<0.001), and C4 consumption (p<0.001).

Conclusion: Patients with pSS exhibit distinct clinical and laboratory profiles based on their autoantibody status, emphasizing the importance of immunological assessment for disease management.

Giant cell arteritis (GCA) is the most common form of primary systemic vasculitis and primarily affects large- and medium-sized vessels. Diagnostic delay can occur from underrecognition of symptoms, and optimal treatment duration remains unclear. Patients with GCA can experience significant burdens related to adverse outcomes of GCA, including risk of vision impairment/loss and stroke, which can result in permanent disability. Glucocorticoids, which remain the first line of treatment, are often associated with adverse effects, and emerging glucocorticoid-sparing agents represent an important option for the treatment of this relapsing disease. Moreover, GCA is a costly illness in terms of both direct healthcare spending and healthcare resource utilization. This narrative review summarizes the clinical, psychosocial, and economic burdens of illness as well as the unmet needs of patients with GCA in terms of diagnosis, treatment, and healthcare resource utilization and spending. Reducing delays in diagnosis and making informed treatment decisions that optimize patient response, while minimizing exposure to potential adverse events, can lead to significant improvement in patient care and outcomes.

Objective: This study investigates the association between triglycerides and Rheumatoid arthritis (RA) risk through risk factor analysis and Mendelian randomization (MR).

Methods: Data from the Dryad database were used for a case-control study with 455 participants (224 with RA and 231 controls), with a median age of 54 years (IQR: 45-62) and 34% male participants. Logistic regression analyses identified risk factors, and correlation coefficient analysis assessed associations between triglycerides and RA. A two-sample MR analysis was conducted using genetic variants associated with triglyceride levels as instrumental variables.

Results: Logistic regression identified higher triglyceride levels, a history of non-smoking, lower levels of C-reactive protein, and apolipoprotein A as significant risk factors for RA (all P < 0.05). MR analysis showed no significant causal relationship, with odds ratios (IVW OR = 0.944, P = 0.154) close to 1. Heterogeneity tests showed no significant variation in causal estimates, supporting the absence of a causal link between triglycerides and RA.

Conclusion: While elevated triglyceride levels are associated with an increased risk of RA, MR suggests that triglycerides do not play a direct causal role in its development. These findings indicate that triglyceride management may not be a primary focus in RA treatment, but further research into the mechanisms underlying RA progression is needed.

Objective: To investigate the potential of quantitative ophthalmic posterior segment optical coherence tomography angiography (OCTA) imaging metrics to serve as biomarkers for systemic involvement in three rheumatologic diseases, systemic sclerosis (SSc), systemic lupus erythematosus (SLE), and Behçet disease (BD), by reviewing the reported correlations between such OCTA metrics and clinically relevant features of systemic involvement in these diseases.

Methods: This review is a correlational study conducted through a systematic review of the PubMed database for articles reporting OCTA metrics in any of SSc, SLE, and BD. Articles correlating ophthalmic posterior segment OCTA metrics to clinically relevant features of systemic involvement, specifically serum, cerebrospinal fluid (CSF), or other established biomarkers; systemic symptom and severity scores; stage; non-ocular organ involvement; non-ocular imaging findings; and medication use were included.

Results: OCTA parameters have been significantly correlated to autoantibody presence, digit and pulmonary involvement, disease stage, and medication use in SSc with significance values ranging from p = 0.008 to p = 0.048. OCTA parameters have been significantly correlated to serum markers, renal and cardiac involvement, damage indices, and medication use in SLE with significance values ranging from p < 0.0001 to p = 0.028. OCTA parameters have been correlated to systemic vascular involvement in BD with significance value p = 0.006.

Conclusion: Ophthalmic posterior segment OCTA metrics may provide value in prognosis, stratification, and treatment monitoring of the examined rheumatologic conditions. These results warrant further study.

Rheumatoid arthritis (RA) is a chronic inflammatory disease that causes joint damage, pain, and disability, leading to significant impairments in patients' physical, mental, and social well-being. While biological disease-modifying antirheumatic drugs (bDMARDs) such as tumor necrosis factor (TNF) inhibitors, interleukin-6 (IL-6) inhibitors, and Janus kinase (JAK) inhibitors have revolutionized the treatment of RA by effectively controlling disease activity, their influence on patients' quality of life (QoL) is crucial but not fully understood. The aim of this review is to evaluate the impact of bDMARDs on QoL in RA patients, particularly focusing on domains such as physical functioning, pain, fatigue, mental health, and social participation. A comprehensive literature search was conducted in databases such as PubMed and the Cochrane Library, including randomized controlled trials, cohort studies, and surveys assessing QoL outcomes in RA patients receiving bDMARD therapy. The review includes studies that utilized the Health Assessment Questionnaire (HAQ), EuroQol-5 Dimension (EQ-5D), and Short Form-36 (SF-36), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Fatigue Severity Scale (FSS), and Patient Global Assessment (PtGA) QoL questionnaires, among others, to assess patient-reported outcomes. The findings of the current review suggest that bDMARDs significantly improve QoL in RA patients by reducing pain, fatigue, and disability while enhancing physical function and mental well-being. However, variability in patient responses, side effects, and the long-term impact of these therapies remain key concerns. Future studies with standardized QoL assessments and longer follow-up periods are needed to provide a more comprehensive understanding of the sustained effects of bDMARD therapy on RA patients' overall well-being.