Rheumato

Living with inflammatory arthritis can have a significant impact; early identification, diagnosis and treatment has been shown to improve outcomes. The clinician working in settings where people with undiagnosed inflammatory arthritis may present for assessment has a crucial role in early identification and onwards referral. Inflammatory arthritis varies in its presentation with respect to gender. Rheumatoid arthritis tends to affect females more than males; historically, Axial Spondyloarthropathy was felt to predominately affect males but the distribution is now known to be equal between men and women. Psoriatic arthritis also affects males and females without obvious sex prevalence. Objectives: To investigate, through a narrative literature review, the early clinical manifestations of inflammatory arthritis, focusing on sex differences and key signs which primary care clinicians should recognise. Methods: A narrative literature review was undertaken with regards to presentation of three commonly seen inflammatory arthritis conditions: Rheumatoid Arthritis, Psoriatic Arthritis and Axial Spondyloarthritis. Studies describing differences in presentation of these conditions between the sexes were selected for this descriptive analysis. Results: Overall, when compared to males, females endure a longer time to diagnosis, and experience increased disease activity, elevated levels of pain and poorer response to medication. Conclusions: Understanding the difference in presentation of inflammatory arthritis between sexes can accelerate diagnosis and improve treatment. Full article

Background/Objectives: Chronic medical conditions are comorbid with psychological disorders, often attributed to the weight of managing persistent demands associated with debilitating illness. Lifestyle adjustments, physical pain, and costs of health care can impose impairment of functioning, exacerbated by the onset of a chronic disease. While cause-and-effect directionality is difficult to ascertain, it is widely assumed that psychological stress can exacerbate the ability of patients to manage chronic medical conditions. Methods: The current study examined a novel model comprising five psychological factors which might explain variations in patients’ level of adherence, satisfaction, and quality of life. The sample consisted primarily of 124 low-income, female Hispanic patients, who were patients diagnosed with rheumatic and endocrine medical diagnoses. Results: Psychological distress and the lingering psychological effects of the COVID-19 pandemic were negatively associated with patient adherence, satisfaction, and quality of life, and that patients’ reports of the working alliances with their doctors moderated (i.e., significantly lessened) the negative association between the lingering impact of the COVID-19 pandemic and their satisfaction with care. Patients’ self-efficacy, resilience, and working alliance were all positively and significantly associated with adherence, satisfaction, and QOL. The association between working alliance and satisfaction represents a very large effect (r = 0.77, p < 0.001). Path analysis found a direct effect between psychological distress (stand. est. = 0.28, p = 0.05) and treatment adherence and a direct effect between COVID-19 impact and adherence (stand. est. = −0.19, p = 0.05). Conclusions: This study provides evidence of the role that both psychological stress and psychological strengths play in the experience of receiving medical care for low-income patients with rheumatic and endocrine conditions. Psychological stress inhibits adherence, and the physician–patient working alliance moderates the negative correlation between COVID impact and treatment satisfaction. Full article

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder with significant racial and ethnic disparities in prevalence, disease severity, and outcomes. Cardiovascular complications, including pericarditis, myocarditis, valvular disease, and conduction abnormalities, contribute to increased morbidity and mortality in SLE patients. This study examines racial and ethnic disparities in cardiovascular outcomes among hospitalized SLE patients in the United States. Methods: This retrospective study utilized the National Inpatient Sample (NIS) database from 2016 to 2021 to analyze hospitalizations of adult patients (≥18 years) with a primary or secondary diagnosis of SLE. Patients were stratified into racial/ethnic groups: White, Black, Hispanic, Asian, Native American, and Other. Primary outcomes include major adverse cardiovascular events (MACEs), which are a composite of in-hospital mortality, myocardial infarction (MI), sudden cardiac death, and other SLE-related outcomes including cardiac, pulmonary, and renal involvement. Statistical analyses included multivariable logistic regression models adjusted for demographic, socioeconomic, and hospital-related factors to assess racial disparities. Results: The study included 514,750 White, 321,395 Black, and 146,600 Hispanic patients, with smaller proportions of Asian, Native American, and Other racial groups. Black patients had significantly higher odds of in-hospital mortality (OR = 1.17, 95% CI = 1.08–1.26, p < 0.001) and sudden cardiac death (OR = 1.64, 95% CI = 1.46–1.85, p < 0.001) compared to White patients. Asian patients also exhibited increased mortality risk (OR = 1.37, 95% CI = 1.14–1.63, p = 0.001) as compared to Whites. Conversely, Black (OR = 0.90, 95% CI = 0.85–0.96, p = 0.01) and Hispanic (OR = 0.87, 95% CI = 0.80–0.96, p = 0.03) patients had lower odds of MI. Racial disparities in access to care, socioeconomic status, and comorbidity burden may contribute to these differences. Conclusion: Significant racial and ethnic disparities exist in cardiovascular outcomes among hospitalized SLE patients. Black and Asian individuals face higher in-hospital all-causes mortality and sudden cardiac death risks, while Black and Hispanic patients exhibit lower MI rates. Addressing social determinants of health, improving access to specialized care, and implementing targeted interventions may reduce disparities and improve outcomes in minority populations with SLE. Full article

Obesity, characterized by excessive or abnormal accumulation of body fat, is associated with a range of metabolic and inflammatory diseases, including osteoarthritis (OA). In obese individuals, adipose tissue expansion—via adipocyte hypertrophy or hyperplasia—is accompanied by altered secretion of adipokines such as leptin and adiponectin, which play significant roles in immune modulation, metabolism, and skeletal homeostasis. Leptin, acting through the hypothalamus, regulates the sympathetic nervous system and modulates hormonal axes, influencing bone metabolism and cartilage integrity. Elevated leptin concentrations in the synovial fluid, and the presence of its receptors on cartilage surfaces, suggest its direct role in cartilage degradation and OA progression. Conversely, adiponectin exerts anti-inflammatory effects, modulates osteoblast and macrophage activity, and appears to have a protective function in joint metabolism. These findings underscore the complex interplay between the adipose tissue, adipokines, and the osteochondral unit, highlighting the importance of their balance in maintaining joint health. Full article

Background/Objectives: This review analyzes the effects of invasive and non-invasive methods of knee joint unloading on knee loading, employing a biomechanical model to evaluate their impact. Methods: PubMed, Web of Science, Cochrane, and Scopus were searched up to 15 May 2024 to identify eligible clinical studies evaluating Joint Space Width, Cartilage Thickness, the Western Ontario and McMaster Universities Osteoarthritis Index, the Knee Injury and Osteoarthritis Outcome Score system, Gait velocity, Peak Knee Adduction Moment, time to return to sports and to work, ground reaction force, and the visual analogue scale pain score. A second search was conducted to select a biomechanical model that could be parametrized, including the modifications that each treatment would impose on the knee joint and was capable of estimate joint loading to compare the effectiveness of each method. Results: Analyzing 28 studies (1652 participants), including 16 randomized clinical trials, revealed significant improvements mainly when performing knee joint distraction surgery, increasing Joint Space Width even after removal, and high tibial osteotomy, which realigns the knee but does not reduce loading. Implantable shock absorbers are also an attractive option as they partially unload the knee but require further investigation. Non-invasive methods improve biomechanical indicators of knee joint loading; however, they lack quantitative analysis of cartilage volume or Joint Space Width. Conclusions: Current evidence indicates a clear advantage in knee joint unloading methods, emphasizing the importance of adapted therapy. However, more extensive research, particularly using non-invasive approaches, is required to further understand the underlying knee joint loading mechanisms and advance the state of the art. Full article

Statins are effective drugs for lowering cholesterol and reducing cardiovascular risk. Rarely, they can trigger autoimmune myopathies like immune-mediated necrotizing myopathy (IMNM), associated with anti-HMGCR antibodies. This condition may persist after statin discontinuation and requires immunosuppressive treatment. Despite these rare side effects, the benefits of statins outweigh the risks for most patients. Full article

Objectives: This study aimed to compare hip abductor muscle composition and its age-related alterations between female patients with unilateral and bilateral osteoarthritis (OA) of the hip. Methods: This study enrolled 57 and 43 female patients with unilateral and bilateral advanced OA, respectively. Muscle composition of the glutei medius and minimus and the upper portion of the gluteus maximus was evaluated by computed tomography for planning unilateral total hip arthroplasty. The cross-sectional area ratio of the individual composition to the total muscle was calculated. Correlation coefficients were calculated to determine associations between age and muscle composition variables. Results: Comparison of hip abductor muscle composition between the affected and the contralateral sides in unilateral OA patients showed increased fatty infiltration in the muscles around the affected joint. Comparison of the composition around bilateral OA between the joint scheduled for operation and the contralateral joint demonstrated enhanced fatty infiltration in the glutei medius and minimus but no increase in the gluteus maximus around the operation-scheduled joint. Comparison of muscle composition between unilateral and bilateral OA demonstrated similar fatty infiltration around the operation-scheduled joint whereas there was increased fatty infiltration around the contralateral joint of bilateral OA. Significant association was found between age and hip abductor muscle composition around both sides of unilateral OA. However, there was no association between age and hip abductor muscle composition around both sides of bilateral OA. Conclusions: There were significant differences in hip abductor muscle composition and its age-related alterations between female patients with unilateral and bilateral OA. Full article

Hemophilia is an X-linked genetic disorder that predominantly affects males, with females typically serving as asymptomatic carriers. Hemophilia A results from a deficiency or dysfunction of coagulation factor VIII, while a deficiency in factor IX causes hemophilia B. A less common condition, factor XI deficiency (formerly hemophilia C), is categorized as a rare bleeding disorder. The severity of hemophilia is classified based on the activity concentration of factors VIII and IX: severe (<1 IU/dL), moderate (1–5 IU/dL), and mild (6–<40 IU/dL). One of the most prevalent complications of hemophilia is hemarthrosis, bleeding into joint cavities, which, if unrecognized or untreated, can lead to hemophilic arthropathy. The pathophysiology of hemophilic arthropathy involves two key mechanisms: the accumulation of iron from blood in synovial joints, which cannot be cleared due to repeated bleeding, and the inflammatory response, resulting in synovial hyperplasia and the progressive destruction of cartilage and bone. Hemophilic arthropathy significantly impairs quality of life, causing chronic pain, joint deformities, and sometimes requiring surgical intervention. This thesis will examine the pathophysiology and management strategies for hemophilic arthropathy. Full article

Background: Although the Profile of Mood States has been proposed by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) to measure emotional functioning in chronic pain patients, it has not yet been validated in these patients. Objective: To confirm the factor structure and internal consistency of the Shortened Version of the Profile of Mood States (37 items) in patients with chronic pain. Methods: A confirmatory factor analysis (CFA) was conducted to test the theoretical structure of six factors that result in a Total Mood Disturbance episode: Tension–Anxiety (six items), Depression–Dejection (eight items), Anger–Hostility (seven items), Vigor–Activity (six items), Fatigue–Inertia (five items), and Confusion–Bewilderment (five items). Participants: A total of 588 patients with chronic pain from Spanish primary care health and community centers completed the questionnaire. Results: The factors presented adequate reliability coefficients, McDonald’s Omega (ω) between 0.77 and 0.91, and appropriate average discrimination indexes (D), ranging from 0.35 to 0.67. The Total Mood Disturbance yielded excellent results, ω = 0.95, D = 0.61. The original structure was confirmed, ECVI = 4.361 (saturated ECVI = 2.395; independent ECVI = 21.855); RMSEA = 0.070, 90% CI [0.067, 0.072]; GFI = 0.974; AGFI = 0.971; CFI = 0.853; NFI = 0.812; and NNFI = 0.843. Conclusions: The Shortened Version of the Profile of Mood States has been proven to be a valid and reliable measure of emotional functioning in chronic pain patients. Full article

Rheumatoid arthritis (RA) is an immune-mediated chronic and long-term condition that can lead to severe joint damage and disability. It has been shown that doctor–patient interaction and communication can have a significant impact on faster patient diagnosis and treatment outcomes. Primary care (PC) is the first level of patient contact with doctors and the health system. Communication between them is often ineffective, leading to delays in diagnosis, care, and the use of disease-modifying antirheumatic drugs (DMARDs). The protocols and standards for the treatment of RA are well established by all rheumatology organizations. All of them recommend early initiation of DMARDs, which leads to better long-term outcomes. There are some recommendations that would lead to better optimization of recognition, management, and referral practices. Early diagnosis, effective communication between general practitioners and specialists, and patient education about possible targeted therapies and biological products, as well as subsequent monitoring of therapies and screening for risk factors and comorbidities, will improve patient health and optimize costs. We aimed to offer strategies and possibilities for integrating and optimizing primary care and specialized therapies in RA because proper management will reduce the severity of the disease and even reduce mortality from chronic diseases such as RA. Full article

Muscle function and pathology are complex subjects; the medical fields involved in their diagnosis and treatment represent rheumatology, physiatry and metabolic disease, among others. While we, rheumatologists, concentrate our efforts predominantly on inflammatory varieties and those associated with medications (e.g., corticosteroid and statin use), we are often the “turn to” gatekeepers for the identification of the diagnostic category represented by a patient’s symptomatology. The broad base of rheumatologic training prepares us for the recognition of endocrinologically derived myopathy. This subject and fundamentally biochemically derived myopathies form the basis for this review. Full article

The SARS-CoV-2 virus can cause hyperstimulation of the immune system, sometimes leading to the production of various autoantibodies and increased levels of interferons and interleukins in blood plasma. Background/Objectives: Only a few studies are currently focusing on the dynamics of immunological indices after any transferred infectious disease encountered by an organism for the first time. The attention of researchers and clinicians is captured by the dynamics of antibody titers and immunologic markers (interferons and interleukins), as well as the correlation of immunologic indices with changes in the symptomatology of long COVID. This paper discusses the association of antibodies against various autoantigens with rheumatological and neurological manifestations of COVID-19. Our study patient was a 36-year-old man diagnosed with polyneuropathy, which developed after COVID-19. We conducted a dynamic follow-up of the patient for two years. Methods: The blood plasma samples collected were analyzed by ELISA for different autoantigens, IFN-γ, and a variety of interleukins. Results: An association between rheumatologic and neurologic markers in patients with long COVID symptoms was considered. Antibody titers for myelin basic protein (MBP), double-stranded DNA (dsDNA), single-stranded DNA (dsDNA), and IFN-γ, IL-1, IL-6, and IL-10 levels significantly increased during the posthospital period when the patient reported persistent symptoms of long COVID, with complaints decreasing after the symptoms were resolved. Conclusions: The findings of this study shed light on the dynamic alterations of immunological factors, and elucidate the mechanism by which SARS-CoV-2 infection disrupts immunotolerance and eventually restores equilibrium, leading to the rheumatological pathology. Significantly, the notable rise in antibody titers for various autoantigens was transient and did not lead to the progression of autoimmune pathology. Full article

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease with a complex pathogenesis, primarily affecting women. SLE is associated with the presence of autoantibodies, chronic inflammation, and multi-organ dysfunction. Increasing evidence suggests that SLE is linked to a higher risk of malignancies, compared to the general population, though the mechanism behind this phenomenon remains unclear. Malignant tumors are the fourth most common cause of death in SLE patients. SLE is associated with an elevated risk of hematological cancers, as well as cancers of the lungs, thyroid, liver, and bile ducts. The aim of this paper is to review the latest literature on the pathogenesis, epidemiology, and risk factors for malignancies in SLE patients. The mechanisms of oncogenesis in SLE are still not fully understood, and the pathophysiology includes such risk factors as chronic inflammation, immune disorders, therapies used, overlap syndromes of connective tissue diseases, viral infections, and traditional cancer risk factors. Evaluating these factors and understanding the process of oncogenesis are crucial for prevention. Systemic lupus erythematosus may be an independent risk factor for the development of malignancies. It is important to raise awareness among SLE patients about the increased risk of malignancies. Further research is needed to establish guidelines for prevention, including screening recommendations. Full article

Early diagnosis and therapy in axial spondyloarthritis, axSpA, is known to reduce long-term morbidity. However, the time from symptom onset to diagnosis is typically delayed by several years, and this situation has not improved in recent years despite greater clinical awareness and better imaging. This narrative review discusses the underlying causes for axSpA diagnostic delay. It is proposed that to reduce axSpA diagnostic delay, a better understanding of the axSpA subclinical inflammatory process is required, together with machine learning-enabled inflammation/repair biomarkers such as lipocalin 2 and lipocalin 2-matrix metalloprotease 9, developed through extensive clinical domain knowledge. Full article

Background: Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy characterized by a variety of clinical manifestations, mainly affecting joints and entheses, but also skin, nails, the eye, and the intestine. Objectives: In this review, we describe the essential characteristics of both synovial membranes and synovial fluid (SF) in PsA. Similarly to other inflammatory arthritis, the histological peculiarities in PsA synovitis are lining hyperplasia, neoangiogenesis, and sublining infiltration by immune cells and inflammatory mediators. Synovial effusions are frequent in PsA patients and SF analysis allows us to determine the pathological process occurring in the joint. Routine examinations help clinicians in defining the inflammatory status and possibly the detection of specific cell subsets. In addition, pathogenic crystals including monosodium urate and calcium pyrophosphate may be found in PsA SF. Conclusions: SF represents a potential substrate to identify the biomarkers that are useful to predict disease progression and response to medications in PsA patients, thus guiding the choice of appropriate and tailored pharmacological treatment. Full article

Background/Objectives: Accurate detection and classification of nodules in medical images, particularly rheumatoid nodules, are critical due to the varying nature of these nodules, where their specific type is often unknown before analysis. This study addresses the challenges of multi-class prediction in nodule detection, with a specific focus on rheumatoid nodules, by employing a comprehensive approach to feature extraction and classification. We utilized a diverse dataset of nodules, including rheumatoid nodules sourced from the DermNet dataset and local rheumatologists. Method: This study integrates 62 features, combining traditional image characteristics with advanced graph-based features derived from a superpixel graph constructed through Delaunay triangulation. The key steps include image preprocessing with anisotropic diffusion and Retinex enhancement, superpixel segmentation using SLIC, and graph-based feature extraction. Texture analysis was performed using Gray-Level Co-occurrence Matrix (GLCM) metrics, while shape analysis was conducted with Fourier descriptors. Vascular pattern recognition, crucial for identifying rheumatoid nodules, was enhanced using the Frangi filter. A Hybrid CNN–Transformer model was employed for feature fusion, and feature selection and hyperparameter tuning were optimized using Gray Wolf Optimization (GWO) and Particle Swarm Optimization (PSO). Feature importance was assessed using SHAP values. Results: The proposed methodology achieved an accuracy of 85%, with a precision of 0.85, a recall of 0.89, and an F1 measure of 0.87, demonstrating the effectiveness of the approach in detecting and classifying rheumatoid nodules in both binary and multi-class classification scenarios. Conclusions: This study presents a robust tool for the detection and classification of nodules, particularly rheumatoid nodules, in medical imaging, offering significant potential for improving diagnostic accuracy and aiding in the early identification of rheumatoid conditions. Full article

Background: Interleukin-11 (IL-11) is increased in patients with systemic sclerosis (SSc) and is thought to play a role in fibrosis. Many studies have reported decreased fibrosis when IL-11 is blocked, but few have examined factors that induce IL-11 expression. Because fibrosis has been linked to activated inflammasomes driving caspase-1 maturation and the secretion of IL-1β, we set out to determine if IL-11 expression was dependent on caspase-1 activity. Methods: Primary lung fibroblast cell lines derived from patients with SSc, IPF (fibrotic control), and healthy individuals were cultured at low passage. Gene expression for IL-11 and the IL-11 receptor (IL-11Rα1) was analyzed using qPCR and normalized to the control, and collagen production was measured using Sirius Red. Results: SSc and IPF fibroblasts expressed significantly more IL-11 transcripts than normal cells (3.35-fold and 9.97-fold more, p = 0.0396 and p = 0.0023, respectively). IL-11Rα1 was expressed 2.32-fold and 2.27-fold more in SSc and IPF (p = 0.0004 and p = 0.0032, respectively) than in normal cells. In SSc fibroblasts, inhibition of caspase-1 with YVAD decreased IL-11 expression by 49.59% (p = 0.0016) but did not affect IL-11Rα1 expression (p > 0.05). IL-11 expression was increased 2.97-fold with TGF-β1 (p = 0.0030) and 22.24-fold with IL-1β (p < 0.0001), while the expression of IL-11Rα1 was not induced with these two cytokines. LPS increased IL-11 expression in normal fibroblasts 1.52-fold (p = 0.0042), which was abolished with YVAD (p < 0.0001). IL-11Rα1 gene transcripts were also increased with LPS 1.50-fold (p = 0.0132), but YVAD did not inhibit this expression. In these studies, we were unable to detect IL-11 protein nor were we able to induce COL1A1 expression or increase the total amount of collagen secreted by fibroblasts with human recombinant IL-11. Conclusions: IL-11 and its receptor, IL-11Rα1, are both elevated in fibrosis. IL-11 expression is dependent on inflammasome activation of caspase-1 and the downstream cytokines TGF-β1 and IL-1β, while IL-11Rα1 was only dependent on NF-kB. Full article

Sjogren’s Disease (SjD) is associated with an increased risk of lymphoma. We investigated the prevalence of lymphoma in a retrospective case series of patients with SjD and reported on the clinical presentation, treatment, response, and outcome. A retrospective review of 132 patients diagnosed with Sjogren’s Disease was conducted at our institution from June 2000 to November 2023, and 10 cases of malignant lymphoma were identified. Clinical and biological markers known to be predictors of lymphoma, as well as lymphoma characteristics, were examined. The most common predictive lab findings were hypergammaglobulinemia, the rheumatoid factor, and lymphopenia. Persistent parotid gland enlargement was also found in greater than 50% of patients. The majority of patients were Caucasian females, and the average time between the diagnosis of SjD and lymphoma was 14.3 years. The median age at lymphoma diagnosis was 59.5 years, with 9 out of 10 lymphomas identified as non-Hodgkin lymphoma, the majority of cases being mucosa-associated lymphoid tissue (MALT) lymphoma. We identified similarities in our series, such as laboratory markers and clinical symptoms, to those previously identified as possible predictors of lymphoma development. These factors may be useful in determining the risk of malignancy development and justify the need for long-term monitoring, as well as provider education and awareness. Full article