Rheumato

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

Irritable bowel syndrome (IBS) is common in ankylosing spondylitis (AS) and may be associated with the disease. We aimed to determine the prevalence of IBS in AS patients and its association with clinical and demographic patient characteristics and with macroscopic and microscopic gut lesions. Sixty consecutive AS patients were included in this study. Disease activity was assessed with the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and functional status with the BASFI (Bath Ankylosing Spondylitis Functional Index). The ROME III criteria were used to diagnose IBS. Macroscopic lesions were graded during colonoscopies. Biopsy specimens were taken from the terminal ileum, colon (ascending, transverse and descending) and rectum. Histological samples were scored with Cuvelier grading. The prevalence of IBS was 23.3% (14/60). The mean age of 14 IBS subjects (10 male) was 32 ± 8.50., with a higher BASDAI (p = 0.046). Macroscopic lesions were more frequent in IBS cases in the terminal ileum (46.2% vs. 34.9%), ascending colon (21.4% vs. 2.2%) and rectum (21.4% vs. 17.4%), with Grade 2 significantly more prevalent in the ascending colon (p = 0.03). Microscopic lesions did not differ among the IBS-present and -absent groups. In conclusion, the prevalence of IBS was high in AS patients and associated with higher disease activity. Grade 2 macroscopic lesions were more frequent in the ascending colon. Full article

Systemic lupus erythematosus (SLE) is a chronic, autoimmune, immune complex-mediated disease affecting mainly females at a young age. The disease etiology is still unknown, and different genetic and epigenetic factors related to disease onset and manifestations are being explored. The standard treatment regimen for SLE includes the long-term use of corticosteroids and non-specific immunosuppressive agents, often limited by co-morbidities or related side effects. However, recent advances in disease pathogenesis clarifying the role of inflammatory cytokines, chemokines, immune cells, and co-stimulation molecules have made a more practical, targeted approach possible, leading to personalized treatment strategies. This review summarizes current knowledge about SLE-targeted therapies in clinical practice. Full article

Lyme disease is a zoonotic infectious disease. Increased public interest in Lyme disease has caused increased efforts by researchers for its surveillance and control. The main concept for this paper is to determine the mammalian species composition of areas at high risk for Lyme disease utilizing GIS-based (Geographic Information Systems) techniques coupled with k-means clustering, random forest, and multinomial logistic regression. Cluster analysis results were similar to previous work involving maps that display areas where people are at high risk for developing Lyme disease. There were differences in which mammal species presence had associations with Lyme disease risk observed at the two different scales within this analysis, with some overlap observed between the national scale and the smaller regions, as well as some overlap between the Rocky Mountain and Southeast regions that was not found at the national scale. This is an investigative analysis to determine which species are needed for habitat suitability analyses in efforts to prioritize vaccine deployment locations. There has been limited research on vaccine deployment for Lyme disease. Increasing our understanding of not only the vaccine but also the interactions between the components of disease transmission is necessary to control this infectious disease successfully. Full article

The spectrum of disorders/phenomena encompassed in the practice of rheumatology is quite broad. In addition, our expertise is typically sought whenever other physicians encounter phenomena outside their knowledge base. While skin alterations typically prompt referrals to dermatology practices, alterations underlying the skin (e.g., subcutaneous) may well represent localization in “no man’s land” or an orphaned localization, with rheumatology thus referred as to the specialty of last resort—one of the roles that rheumatology has fulfilled for more than half a century. The current review addresses the cacophony of disorders producing or associated with variouslysized subcutaneous nodules. Their classifications, while necessarily artificial, encompass the full spectrum of pathologic processes. They are delineated in the current style to facilitate the consideration required to distinguish among them and to facilitate recognize the underlying processes for which we as rheumatologists are renowned. Full article