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Topic Review
Copper Toxicosis
Copper, manganese, and iron are vital elements required for the appropriate development and the general preservation of good health. Additionally, these essential metals play key roles in ensuring proper brain development and function.
  • 674
  • 11 Aug 2021
Topic Review
Comorbidities in Rheumatoid Arthritis
Comorbidities in patients with rheumatoid arthritis (RA) are often associated with poor health outcomes and increased mortality. Treatment decisions should consider these comorbidities due to known or suspected associations with certain drug classes. In clinical practice, it is critical to balance potential treatment benefit against the possible risks for comorbidities as well as the articular manifestations of RA. This entry summarises the current literature relating to prevalence and risk factors for the important comorbidities of cardiovascular disease, infections, lymphomas and nonmelanoma skin cancers in patients with RA. The impact on patient outcomes and the interplay between these comorbidities and the therapeutic options currently available, including tumour necrosis factor inhibitors and newer biological therapies, are also explored. As newer RA therapies are developed, and patients gain wider and earlier access to advanced therapies, in part due to the emergence of biosimilars, it is important to consider the prevention or treatment of comorbidities as part of the overall management of RA.
  • 673
  • 25 Apr 2021
Topic Review
Post-Translational Modifications in Rheumatic Diseases
Post-translational modifications (PTMs) are reversible or irreversible chemical reactions that occur in specific amino acids (aas) of some proteins after their translation. In fact, more than 140 different aa-based structures can constitute the proteins when considering the PTMs that could modify the 20 natural aas. Several factors, such as the location of the aa within the protein’s primary sequence, will determine whether PTMs occur as well as their type and frequency. PTMs are not encoded by the cellular genome and can significantly modify protein structure and modulate functions such as folding, degradation, signaling, localization, stability, enzymatic activity and protein-protein interactions. More than 400 different types of PTMs have been described in humans occurring in several cellular organelles (nucleus, cytoplasm, endoplasmic reticulum and Golgi apparatus). They are involved in a large number of cellular events and are considered a key mechanism for the regulation of the biological activity of proteins. The latest findings about the role of PTMs in the generation of autoimmunity is discussed. Meanwhile, the most relevant PTMs in rheumatic diseases that occur in synovial tissue are discussed.
  • 672
  • 22 Dec 2022
Topic Review
Extracellular Vesicles in Osteoarthritis
Along with cytokines, extracellular vesicles (EVs) released by immune cells in the joint contribute to osteoarthritis (OA) pathogenesis. By high-resolution flow cytometry, we characterized 18 surface markers and 4 proinflammatory cytokines carried by EVs of various sizes in plasma and synovial fluid (SF) from individuals with knee OA, with a primary focus on immune cells that play a major role in OA pathogenesis.
  • 668
  • 09 Sep 2021
Topic Review
Medicinal and Aromatic Plants against Obesity and Arthritis
Obesity is a significant health concern, as it causes a massive cascade of chronic inflammations and multiple morbidities. Rheumatoid arthritis and osteoarthritis are chronic inflammatory conditions and often manifest as comorbidities of obesity. Adipose tissues serve as a reservoir of energy as well as releasing several inflammatory cytokines (including IL-6, IFN-γ, and TNF-α) that stimulate low-grade chronic inflammatory conditions such as rheumatoid arthritis, osteoarthritis, diabetes, hypertension, cardiovascular disorders, fatty liver disease, oxidative stress, and chronic kidney diseases. Dietary intake, low physical activity, unhealthy lifestyle, smoking, alcohol consumption, and genetic and environmental factors can influence obesity and arthritis. Current arthritis management using modern medicines produces various adverse reactions. Medicinal plants have been a significant part of traditional medicine, and various plants and phytochemicals have shown effectiveness against arthritis and obesity; however, scientifically, this traditional plant-based treatment option needs validation through proper clinical trials and toxicity tests. In addition, essential oils obtained from aromatic plants are being widely used for complementary therapy (e.g., aromatherapy, smelling, spicing, and consumption with food) against arthritis and obesity; scientific evidence is necessary to support their effectiveness.
  • 645
  • 08 Mar 2022
Topic Review
Treatment of Cardiovascular Disease in Rheumatoid Arthritis
Rheumatoid arthritis (RA) carries significant risk for atherosclerotic cardiovascular disease (ASCVD). Traditional ASCVD risk factors fail to account for this accelerated atherosclerosis. Shared inflammatory pathways are fundamental in the pathogenesis of both diseases. Considering the impact of RA in increasing cardiovascular morbidity and mortality, the characterization of therapies encompassing both RA and ASCVD management merit high priority. Despite little progress, several drugs discussed here promote remission and or lower rheumatoid disease activity while simultaneously conferring some level of atheroprotection. Methotrexate, a widely used disease-modifying drug used in RA, is associated with significant reduction in cardiovascular adverse events. MTX promotes cholesterol efflux from macrophages, upregulates free radical scavenging and improves endothelial function. Likewise, the sulfonamide drug sulfasalazine positively impacts the lipid profile by increasing HDL-C, and its use in RA has been correlated with reduced risk of myocardial infraction.
  • 643
  • 20 Jan 2022
Topic Review
Strategies for Achieving Drug-Free Remission in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a chronic immune-mediated systemic disease, which affects approximately 1% of the population and is characterized by a symmetrical inflammatory polyarthropathy.  It has been demonstrated that drug-free remission (DFR) is possible in a proportion of RA patients achieving clinically defined remission (both on cs and b-DMARDS). Immunological, imaging and clinical associations with/predictors of DFR have all been identified, including the presence of autoantibodies, absence of Power Doppler (PD) signal on ultrasound (US), lower disease activity according to composite scores of disease activity and lower patient-reported outcome scores (PROs) at treatment cessation. 
  • 630
  • 16 Jun 2022
Topic Review
Dietary Intervention in Connective Tissue Diseases
Dietary intervention and nutritional counseling might have an important role as adjuvant therapy in patients with connective tissue diseases, particularly in the light of the comorbidities which characterize these conditions. 
  • 622
  • 15 Dec 2021
Topic Review
Adult-Onset Still’s Disease
Adult-onset Still’s disease (AoSD) is a rare systemic autoinflammatory disease characterized by arthritis, spiking fever, skin rash and elevated ferritin levels. 
  • 621
  • 12 Jul 2021
Topic Review
SARS-CoV-2 Infection in Systemic Juvenile Idiopathic Arthritis
Systemic juvenile idiopathic arthritis (sJIA) is a serious multifactorial autoinflammatory disease with a significant mortality rate due to macrophage activation syndrome (MAS). Recent research has deepened the knowledge about the pathophysiological mechanisms of sJIA-MAS, facilitating new targeted treatments, and biological disease-modifying antirheumatic drugs (bDMARDs), which significantly changed the course of the disease and prognosis. From the data analyzed so far, there have been no exacerbations of both COVID-19 and sJIA under bDMARDs treatment, but multicenter international studies are still needed to highlight all risk factors for a possible severe course of COVID-19 among sJIA patients. Children with sJIA and COVID-19 should be monitored to identify eventual long-run exacerbations after infection.
  • 619
  • 24 Apr 2022
Topic Review
Mitochondrial Dysfunction in Rheumatoid Arthritis
Rheumatoid arthritis, a chronic autoimmune disease with complex etiology, is characterized by excessive proliferation of synovial cells, massive production of inflammatory cells and cartilage destruction. Studies have shown that mitochondrial dysfunction plays an important role in promoting the occurrence of RA. Mitochondria with normal structure and function are essential for the normal survival of chondrocytes and synovial cells. Once mitochondrial function is destroyed, it will affect the survival, activation and differentiation of immune cells and non-immune cells involved in the pathogenesis of RA, thus leading to the occurrence of RA.
  • 618
  • 16 Sep 2022
Topic Review
Effects of Vitamin D on the Immune System
Vitamin D intervenes in calcium and phosphate metabolism and bone homeostasis. Experimental studies have shown that 1,25-dihydroxyvitamin D (calcitriol) generates immunologic activities on the innate and adaptive immune system and endothelial membrane stability. Low levels of serum 25-hydroxyvitamin D (25(OH)D) are associated with an increased risk of developing immune-related diseases such as psoriasis, type 1 diabetes, multiple sclerosis, and autoimmune diseases.
  • 613
  • 13 Sep 2022
Topic Review
Vitamin D and Infectious Diseases
It is now 2 years since we have seen the impact of the CoronaVirus Disease-19 (COVID-19) caused by Syndrome-Coronavirus-2 worldwide, affecting millions of people and rates of mortality close to 6 million. Although we are beginning to see the real benefit of vaccines, in terms of reduced mortality rates, many individuals still remain to be vaccinated or do not respond to them leaving a large number of patients still experiencing severe respiratory symptoms associated with COVID-19. In recent months, we have seen another surge in individuals infected with COVID-19 and mortality rates are also increasing. In the absence of effective therapies or vaccines, the medical and scientific community have extensively explored a range of current available therapeutic agents, mainly focused on targeting viral replication as well as managing severe respiratory symptoms associated with COVID-19.  Vitamin D has emerged as one such candidate due to its recognized immunomodulatory effects. In this regard, the activation of the vitamin D receptor (VDR) signaling pathway may generate beneficial effects in acute respiratory distress syndrome by decreasing the cytokine/chemokine storm, thus having an important immunomodulatory and anti-inflammatory role.
  • 597
  • 07 Feb 2022
Topic Review
Adipose Tissue in Rheumatoid Arthritis
Rheumatoid arthritis (RA) is a systemic autoimmune disease that primarily affects the joints. Organokines can produce beneficial or harmful effects in this condition. Among RA patients, organokines have been associated with increased inflammation and cartilage degradation due to augmented cytokines and metalloproteinases production, respectively. The adipose tissue (AT) is involved in the endocrine regulation of the body’s homeostasis and not only in the energetic homeostasis. Adipocytes drive the production and secretion of endocrine molecules (adipokines), which can control lipid metabolism and insulin sensitivity, inflammation, fibrogenesis, immunological responses, liver fat deposition, and fibrogenesis. Adipokines were the first organokines related to the pathophysiology of RA, collaborating in the inflammatory response on the affected joints. Adipokines also play a relevant role in developing extra-articular inflammation-dependent manifestations of RA. In musculoskeletal disorders such as RA, adipokines were described as modulators of bones, synovial membranes, and cartilages activities. Additionally, higher levels of adipokines are encountered in both serum and synovial fluid in patients with RA than in those who are healthy.
  • 597
  • 10 Jun 2022
Topic Review
The Neuropathic Pain
A consensus definition of neuropathic pain is ‘pain resulting from a lesion of the somatosensory system, which results in faulty pain signaling’
  • 593
  • 12 Jul 2022
Topic Review
Risk Factors for Systemic Sclerosis–Associated Interstitial Lung Disease
Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by immune dysregulation and progressive fibrosis, typically affecting the skin, with variable internal organ involvement. Interstitial lung disease (ILD), with a prevalence between 35 and 75%, is the leading cause of death in patients with SSc, indicating that all newly diagnosed patients should be screened for this complication. Some patients with SSc-ILD experience a progressive phenotype, which is characterized by worsening fibrosis on high-resolution computed tomography (HRCT), a decline in lung function, and premature mortality. To assess progression and guide therapeutic decisions, regular monitoring is essential and should include pulmonary function testing (PFT), symptom assessment, and repeat HRCT imaging when indicated. Multidisciplinary discussion allows a comprehensive evaluation of the available information and its consequences for management. There has been a shift in the approach to managing SSc-ILD, which includes the addition of targeted biologic and antifibrotic therapies to standard immunosuppressive therapy (particularly mycophenolate mofetil or cyclophosphamide), with autologous hematopoietic stem-cell transplantation and lung transplantation reserved for refractory cases.
  • 587
  • 06 Nov 2023
Topic Review
Vitamin D on Immune System
Vitamin D deficiency, which causes an imbalance in bone remodeling, is a global public health problem and its frequency is increasing.
  • 580
  • 06 Dec 2021
Topic Review
Autoantibodies as Biomarker in Systemic Sclerosis
Systemic sclerosis (SSc) is a rare connective tissue disorder characterized by immune dysregulation evoking the pathophysiological triad of inflammation, fibrosis and vasculopathy. In SSc, several alterations in the B-cell compartment have been described, leading to polyclonal B-cell hyperreactivity, hypergammaglobulinemia and autoantibody production. Autoreactive B cells and autoantibodies promote and maintain pathologic mechanisms. In addition, autoantibodies in SSc are important biomarkers for predicting clinical phenotype and disease progression. Autoreactive B cells and autoantibodies represent potentially promising targets for therapeutic approaches including B-cell-targeting therapies, as well as strategies for unselective and selective removal of autoantibodies.
  • 556
  • 14 Nov 2022
Topic Review
Obesity-Associated Low-Grade Chronic Inflammation
Current lifestyle and environmental factors contribute to obesity development, leading to low grade chronic inflammation (LGCI). Apart from obesity, LGCI is also related to rheumatic diseases like osteoporosis (OP) and osteoarthritis (OA). In these, an excessive accumulation of adipose tissue has been linked to an excessive production proinflammatory factors as adipokines. Obesity is a risk factor to develop OA, where a systemic LGCI state has been founded. Concretely, obesity associated LGCI has been described as an OA instauration and progression promoter. To avoid this, several therapeutical approaches (as diet control, physical exercise, or nutraceuticals) have been tested. OP is another major rheumatic disease where a basal LGCI has been described, being worsened by obesity. As in OA, diet management and supplementation with vitamin D or probiotics have been proposed as approaches to treat obesity-associated LGCI in this pathology. The augment of rheumatic diseases prevalence is unstoppable. Nonetheless, obesity is a risk factor that can be controlled. Thus, the study of new interventions to control obesity-associated LGCI impact is a challenge for patients with rheumatic diseases management.
  • 552
  • 23 Dec 2022
Topic Review
Systemic Sclerosis Treatment
Systemic sclerosis (SSc) is a connective tissue disease caused by abnormal activation of the immune system. Characterized by vascular damage and fibrosis in various organs, the disease has a high frequency of complications, a poor prognosis, and high unmet medical needs.
  • 534
  • 15 Aug 2022
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