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- Herausgeber: Bentham Science Publishers
- Kategorie: Fachliteratur
- Serie: Frontiers in Arthritis
- Sprache: Englisch
Rheumatoid arthritis (RA) is the most common inflammatory complication and affects approximately 1 % of the global population. It affects three times more women than men. RA is an autoimmune disorder elicited by exposure of genetic factors from the host to unknown antigens causing arthritogenic complaints. It also includes the activation of lymphocytes as well as CD4+ helper T cells along with local release of chronic inflammatory mediators and cytokines like tumor necrosis factor (TNF‐α) and various cytokines like interleukins (IL) that enormously affect the joints. The available allopathic therapies for RA are not a cure for the complications, and antibody therapy and surgical procedures are expensive.
However, in the present era, researchers and healthcare professionals have moved toward natural medicines obtained from plants and other natural sources. Research based on developments in phytomedicine has progressed steadily. Evidence has been collected to show the massive therapeutic potential of medicinal plants used in various traditional systems against many pathological complications. Researchers have focused on the therapeutic potential of natural products used for treatment and counteracting various disorders along with their complications having negligible adverse effects.
Natural Products for the Management of Arthritic Disorders compiles current knowledge about the bioactive compounds and herbal formulations useful in the treatment of rheumatoid arthritis. 11 chapters explain the role of natural products in the management of rheumatoid arthritis. Topics have been contributed by experts in medicinal chemistry and rheumatology.
The book first introduces the reader to rheumatoid arthritis before delving into conventional and alternative therapies for the disease. The editors have also included special topics such as the biomarkers for RA, cytokines and anti-inflammatory mediators, preclinical and clinical studies. The range of topics should provide a comprehensive overview of natural remedies for arthritis and the role of natural products in anti-arthritic drug development.
The information will be useful for many readers including medical and pharmacology students, multidisciplinary research scholars, scientists, pharma / herbal / food industrialists, and policy makers.
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Seitenzahl: 486
Veröffentlichungsjahr: 2002
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PREFACE
Rheumatoid arthritis (RA) is the most common inflammatory complication that affects about 1 % of the population. It affects three times more women than men. RA is an autoimmune disorder elicited by exposure of genetic factors from the host to unknown antigens causing arthritogenic complaints. It also includes the activation of lymphocytes as well as CD4+ helper T cells along with local release of chronic inflammatory mediators and cytokines like tumor necrosis factor (TNF-α) and various cytokines like interleukins (IL) that enormously affect the joints. The available allopathic therapies for RA are not worthwhile to cure the complication and antibody therapy and surgical procedure are very expensive that cannot be afforded by middle class people.
However, in the present era, researchers and healthcare professionals have moved toward natural medicine obtained from plants and other natural sources. The research, based on development of phytomedicine, has globally increased. Evidence has been collected to show the massive therapeutic potential of medicinal plants used in various traditional systems against many pathological complications. In the present scenario, researchers have focused on the therapeutic potential of natural products used for treatment and counteracting various disorders along with their complications having negligible adverse effects. The main objective of this book is to collect the knowledge about the bioactive compounds/herbal formulations useful in the treatment of rheumatoid arthritis.
This book entitled ‘Natural Products for the Management of Arthritic Disorders’ contents the chapter related with role of various natural products, herbal formulations etc. in the treatment of RA. It covers various cytokines/mediators and biomarkers involved in RA. Clinical studies are also included.
We are very thankful and grateful to all the contributors who helped us to develop this fruitful book with a comprehensive literature review and compiled research work. All valuable facts are collected and brought together to form a good knowledgeable literature. We hope that this work will help to contribute a good content for future projects based on natural products in RA.
We extend our thanks to the Bentham Science Publishers for giving this opportunity.
List of Contributors
Rheumatoid Arthritis: Introduction
Diptendu Bhowmik1,Venu Kola1,Subba Rao Chamakuri2,Chiranjib Bhattacharjee1,*Abstract
Rheumatoid Arthritis elaborated as Rheumatoid Arthritis is a systemic chronic inflammatory condition that might affect numerous organs and tissues in a human body, but mainly it attacks the synovial joints. These methods result in the inflammatory synovitis (synovium) response. Factors that lead to an increase in the risk of rheumatoid arthritis are age, sex, family history, smoking, obesity, and exposure to pollutants. RA holds the ability to put a person at a higher risk of developing other medical conditions if it is not controlled timely. A syndrome named carpal tunnel is another common condition found in people suffering from rheumatoid arthritis. Trauma, infection, smoking cigarettes are some of the examples of external triggers which can trigger the reaction of the auto-immune system, which results in chronic joint inflammation and synovial hypertrophy in addition to a potential of other manifestations, which will be theorized for going on in people prone genetically. The pathological process of the disease usually results in destructing the articular cartilage as well as the joints ankylosis. Rheumatoid Arthritis could also result in diffusive lung inflammation, sclera, pleura, pericardium, as well as nodular lesions, which are also common in subcutaneous tissue. However, the causes of RA are still not known, the autoimmunity holds an important part in both the progression and chronicity. Rheumatoid Arthritis is a systemic disorder. RA can be prevented by using coldwater, living fish oil, from the herring, cod, mackerel, and salmon fish, which contains omega-3 fatty acids in high amounts, Vitamin-D supplements, and adopting the lifestyle modifications such as avoiding smokingand weight loss.
INTRODUCTION
Several statements can be found for rheumatoid arthritis (RA). RA is a polyar-
ticular chronic inflammatory form of arthritis that affects the smaller joints in the feet and hands as well as other large or medium joints. This is connected with exorbitant morbidity, mortality, along with disability. Rheumatoid arthritis is an intricate autoimmune inflammatory disorder along with symptoms [1]. RA is distinguished by chronic inflammation and swelling of synovium present in joints with successive erosion of articular structures that leads to progressive disease and provoked mortality [2, 3].
Types of Rheumatoid Arthritis [4, 5]
The secret remains in the periphery of the exact reasons behind RA creating inconvenience of categorizing this condition completely. Constantly, researchers are trying to find methods to align its types as well as sub-types of RA depending on the appropriate symptoms that people experience, along with many other aspects. Due to this dynamic nature of RA and the propensity to evolve, patients may have different types or subtypes of rheumatoid arthritis. As of now, two major types of rheumatoid arthritis are described along with other rheumatoid factors and associated conditions that are mentioned below.
Seropositive
Patients with rheumatoid arthritis are classified as seropositive if anti-cyclic citrullinated peptides (anti-CCPs) are present in their blood. Anti-CCP is a type of antibody known as anti-citrullinated protein antibodies (ACPAs), that attack the body, inflamed joints, and generate the symptoms of RA. Seropositive RA is the most common category, where, 60-80% of patient tests positive with the availability of Anti-CCPs. As soon as 5 to 10 years before the clinical symptoms of rheumatoid arthritis appear, the presence of such antibodies (Anti-CCPs) can be detected. Doctors can write a blood test to find out the presence of anti-CCPs, but having those antibodies doesn't always mean that somebody has RA.
Seronegative
Development of rheumatoid arthritis symptoms without the presence of ‘Anti-CCP’ antibodies in the blood is referred to as the seronegative category of rheumatoid arthritis. Patients are considered seronegative when they test negative for the anti-CCPs or another antibody named rheumatoid factor. Though anti-CCP antibodies are a helpful diagnostic marker for doctors to diagnose the condition and it shows negative in the case of seronegative patients, they can still make a diagnosis for rheumatoid arthritis in several other ways such as demonstrating clinical symptoms of rheumatoid arthritis, X-ray results that shows the mode of cartilage and bone deterioration. Unfortunately, several seronegative patients do not respond to conventional rheumatoid arthritis therapy, which also motivates the researchers in identifying the subtypes of rheumatoid arthritis to provide treatment for those patients. The difference between normal and Rheumatoid joints is shown in Fig. (1).
Fig. (1)) Diagrammatical representation of normal and rheumatoid arthritis joint.Miscellaneous Type
Juvenile RA [4, 6]
Juvenile Idiopathic Arthritis, also known as Juvenile Rheumatoid Arthritis affects only children and has an assorted group of problems which includes high fever, sore wrist, skin rashes, stiffness in the neck, hip, and other joints, lasts for a minimum of six weeks with an onset noted before the age of 16 years. For this age group, JIA is a common kind of arthritis and symptoms can be steady. The effect of juvenile arthritis may differ in adult and young or children patients because, in the case of children /youth, growth is an interfering factor. Inflammation of lymph nodes and the eye is also a matter of concern in juvenile rheumatoid arthritis.
Rheumatoid Arthritis Sub-types
The obscurity surrounding the symptoms that are developed in a patient as well as the severity and variations of signs, led the researchers to think of several subtypes of rheumatoid arthritis. It is very much difficult to diagnose a specific type of RA, especially when there is a combination of various autoimmune symptoms such as skin rashes or eye dryness [4].
The invention of subtypes of RA patients is a major area of research for the development of a response to treatment and personalized medicine strategies. A study that depends on the Chinese perspective categorized the RA patients into two groups as Cold RA and Heat RA. A cold reaction is distinguished by cold intolerance, pallor, clear profuse urine, loose stools, absence of thirst, and a slow pulse. A Heat RA is characterized by thirst, flushed face, fever, restlessness, irritability, deep-colored urine, constipation, reddened tongue, and rapid pulse [7].
Epidemiology
RA cases were estimated in around 0.5-1% population across the world, in which females are 2-3 times more prone/susceptible than men [8]. The ratio for developing the RA in women to a man is 3:1 [9]. In women aged less than 50 years, it is 4-5 times higher, but the ratio becomes nearly 2:1 after 60 years [10]. Across the world, the annual occurrence of RA is nearly three in every 10,000 people on an average that increases with age and apex between 35 and 50 years of age. Although rheumatoid arthritis affects almost every population, it is more comprehensive in some groups (E.g., in a few groups of Native America, it is 5-6%) and is not much prevalent among others (black persons residing in the Caribbean area). Rheumatoid arthritis patients' first-degree relatives have a 2-3-fold increased chance of developing the disease [11, 12]. RA affects 0.4% to 1% of the total population in North America and northern Europe, respectively and it holds 0.3% to 0.7% of the population in southern Europe [13, 14]. RA is another common reason for inflammatory arthritis which affects nearly 1% of the people in the country [15, 16].
Symptoms
The onset of Rheumatoid arthritis symptoms is very rapid in which a condition becomes worse in just a few weeks. Joints of the whole body including knees, fingers, hips, elbows, and hands can be affected by Rheumatoid arthritis. The onset of symptoms like muscle pain, low-grade fever, fatigue, malaise, weight loss, stiffness joint aches, and appetite loss are significant measures of disease development [17]. Rheumatoid Arthritis typically creates symmetrical synovitis in the small joints of hands and feet, though this effect may happen to any synovial joint. The 3 primary medical features of synovitis are:
Stiffness: Morning stiffness lasting over 1 hour [18].Swelling: Commonly near joint, not in the bones, giving a “marshy” palpation sensation.Pain: Generally worse while resting and during times of inactivity.Apart from the above symptoms, it also shows complications in doing simple daily tasks with hands, like rotating doorknobs and opening jars. RA can also lead to painful walking, especially in the morning after getting up from bed by involving the small joints of the feet [19].
Etiology
Unlike numerous autoimmune disorders, the etiology of Rheumatoid Arthritis is multi-factorial [20]. Although the definite causes of RA are not known, the beginning of this disease appears from an interaction between genotype and environmental triggers [21]. Hormonal, immunological, socioeconomic, and psychological factors may also play significant roles in the development and outcome of the disease [22].
Genetic
Genetic factors contribute to 50% of the chance of developing Rheumatoid Arthritis [23]. The MHC (Major histocompatibility complex) HLA regions are mire liable as compared to the 30% susceptibility to the genetic towards Rheumatoid Arthritis with higher significant HLA-DRB1 in the genes [24]. The MHC region of the human genome was also categorized among3 major classes that are MHC-I, MHC-II, and MHC-III. MHC-I contains 3 genes as HLA-A, HLA-B, and HLA-C, whereas MHC-II has HLA-DR, HLA-DQ, HLA-DP as its type of genes [25, 26]. MHC-III exists in MHC-I and MHC-II which contains A1F1 and NFKBIL1, those are relevant RAs susceptible genes [27]. The genetic factors associated with Rheumatoid Arthritis sensitivity are having variations in “Human Leukocyte Antigen-DRB1” (HLA-DRB1) alleles, particularly in people having positive results for ACPA (Anti-Citrullinated Protein Antibody) and RF (Rheumatoid factor) [28]. Availability of a common motif known as an amino acid motif (QKRAA, QRRAA, or RRRAA) in such alleles (HLA-DRB1) could be linked to a definite RA susceptibility and usually known as RA shared epitope [21, 29]. An evidence of gene-environment interactions is smoking. For example, cigarette smokers have reported an increased occurrence of HLA-DRB1 positive type of RA [30]. Chromosome 6 holds the genes for Human Leukocyte Antigen-DRB1, also contains genes that affect various immune processes, including tumor necrosis factor (TNF) modulation [31]. Genes apart from the major histocompatibility complex (MHC) are also engaged in RA. Genome-wide associations in their studies have marked out some more genetic impressions such as STAT4 gene and CD40 locus which increase the Rheumatoid Arthritis risk and other autoimmune disorders [32]. Evidence also reveals the link of CYP19 (estrogen synthase) [33], IFN-γ [34-36], corticotrophin-releasing hormone [37], other cytokines [38-40] to Rheumatoid Arthritis and TNF-receptors linked to TRAF1-C5 complement component to factor-1 [41], Protein tyrosin-phosphatase non-receptor 22(PTPN22) [42], Kinesin family member 5A (KIF5A) [43] engaged in the perpetuation of inflammation, autoimmunity, and progressive stiffness. The IL2RA/CD25 gene has a significant association with Juvenile Idiopathic Arthritis [44].
Hormonal
As females have an increased risk of Rheumatoid Arthritis, it leads to putting an effort to explore the role of pregnancy and hormonal factors in the occurrence of the disease. A study established that women who consumed oral contraceptives were at a decreased risk of developing Rheumatoid Arthritis [45]. RA ameliorates in pregnancy and could re-occur in an early period of postpartum [46]. Hyperprolactinemia may be a risk factor for RA [46]. In general, men with RA are lower in male sex hormones, especially testosterone [45]. It is observed that there is an increased concentration of estrogen (hydroxylated forms, especially 16a-hydroxyestrone and 4-hydroxyestradiol) in both males and females who have RA [47].
Immunologic Factors
RA is an autoimmune disease that involves the immune cells particularly macrophages, T-cells, or the B-cells, T-cells. B-cells physiologically release significant proteins like the ACPA, rheumatoid factors, and pro-inflammatory cytokines that support Rheumatoid Arthritis. By the expression of co-stimulatory molecules, B-cells also activate T-cells. In Rheumatoid Arthritis, the vital role of T-cells is the activation of fibroblasts and macrophages and also to convert them into cells that can destroy the tissues [48]. Activated macrophages generate various types of chemokines and cytokines which support the joint inflammation process [49]. The specific role of T-cells in RA is still not clear, but there exist some pieces of evidence that support the significant contribution of CD4+ T-cells in the autoimmune responses. During T-cell activation, an interaction happens between CD4+ T-cells with MHC-II: “Major Histocompatibility Class II” or HLA: “Human Leukocyte Antigen” or and also with co-stimulating molecules like CD28, leading to CD4+ cells the maturation [50], followed by naïve CD8+ T-cells activation that promotes inflammation [51]. Macrophages are continuously foundinsynovial tissue and inflamed joint, it helps in the release of damaging enzymes as well as the pro-inflammatory cytokines which produced inflammatory responses that destroy the joints. Macrophages also mediate many biological functions such as lymphocyte recruitment, joint erosion, cartilage damage, a proliferation of fibroblast, angiogenesis [52]. Other than the macrophages, B-cells, and T-cells the immune cells such asNK cells (Natural Killer), mast cell, and dendritic cells (DCs) also plays role in RA [53].
Environmental Influences
Non-genetic factors like smoking, air pollution, silica, and asbestos are prevalent environmental factors and they double the chance of developing RA [54]. Tobacco use not only affects different organs like the respiratory and cardiovascular systems but also influences the immune system [55]. Tobacco smoking has a selective association with an increased possibility of seropositive RA [56]. Tobacco along with increasing the risk of seropositive RA may also affect the phenotype and clinical expression of the disease [57]. Other potential environmental factors like alcohol consumption, coffee intake, Vitamin D status, contraceptive use also influence the initiation of rheumatoid arthritis [58].
Socioeconomic Factors
Socioeconomic status makes an impact on the way of the disease and may also decide an increased risk of developing RA [59]. The study reveals that living in a rural area increases the risk of developing rheumatoid arthritis when compared with an urban area and even lower-income earners are linked to the increased risk of RA [60].
Psychological Factors
According to Leventhal's research, certain psychological factors are related to an individual's conviction about their illness interpretation. It implies that illness perceptions and emotions have an impact on how an individual adapts and responds to illness [61]. According to the study by Cordingley et al. (2014) about psychological factors found that cognition, depression, and mood are highly associated with severe RA [62].
Risk Factors
Several issues are linked with rheumatoid arthritis and increase the chances of developing the disease. Followings are a list of risk factors:
Age and Sex [20, 63]
Anybody can develop rheumatoid arthritis, but according to the Centers for Disease Control and Prevention, the risk increases with age. Older age and females are prone to increased risk of rheumatoid arthritis, although in older patients the sex differential is less prominent.
Infections and the Microbiome
Evidence shows that infectious agents can cause the initiation of rheumatoid arthritis via different mechanisms like molecular mimicry, activation of toll-like receptors or directly attacking the synovium. Mycoplasma, Epstein-Barr virus Parvovirus B19, and Enteric bacteria are the commonly involved infectious agents [64]. It is observed that in the outbreaks of chikungunya fever with polyarthralgia, that is also raised as a risk factor for the future development of the disease [65]. The human microbiome is a consortium of microorganisms like bacteria and fungi living in the gut, airway, mouth, or somewhere else in the body can also influence the progression of rheumatoid arthritis by influencing the metabolism and immune system [66-69].
Periodontitis
Periodontitis, chronic inflammation of gingival has similar pathogenesis and risk factors like RA [70]. Rheumatoid arthritis patients with added periodontal symptoms have increased levels of RA. In RA patients, Periodontitis is a potential predictor of anti-citrullinated protein antibody (ACPA) [71]. The bacteria, namely Porphyromonasgingivalis, the causative organism for periodontitis, causes citrullination by using its own PADI enzyme [72].
Bodyweight
Overweight or obese peoples are at a greater risk of rheumatoid arthritis development [73, 74]. It is not well-known what RA pathogenesis entails. An external activator (e.g., consumption tobacco, illness, or trauma) inducing an auto-immune response that contributes to chronic joint inflammation and synovial hypertrophy along with possible extra-articular symptoms is potentially associated with genetically sensitive persons [75-77]. RA matches between 15 and 20 percent of identical twins indicate that non-genetic factors have a significant effect on the expression of disease. But HLA-DR is well known in conjunction with RA [78, 79]. The relative probability of RA in people with this allele is raised by about 4 to 5EU/ml. The Epstein - Barr virus (EBV) has been targeted for different purposes. The levels of B virus-infected cells and EBV antibody titers of the RA patients were higher than the general population. A virus has also been involved in RA, which is a possible triggering agent through its ability to activate B cells to generate RF. Parvovirus B19 and the retroviruses are also of concern. In nearly 70% of patients suffering from Rheumatoid Arthritis, the rheumatoid factor, an Ig M anti-Fc component of Ig G is found and evidence indicates its contribution to the pathogenesis of the disease. RF is attributed to extra-articular disease symptoms in RA and is usually related to milder disease absence. The pathways suggested include improved immuno-complex antigen presentation, cross-relation, and stabilization of IgG antibodies with low activity and essential cry precipitation. Despite its name and other conditions, inclusive of bacterial infections, lymphocytes, cancer, and other self-immune diseases, RF is not RA-specific. The immune complexes formed by lining cells and the inflamed blood vessels are prominent immunological abnormalities. Plasma cells develop antibodies (for example the autoantibody [RF], anti-cyclic peptide citrullinated [anti-CCP]) that contribute to these complexes and that, in the absence of those cells, may lead to damaging arthritis. CD4+T-cells are the most widely occurring lymphocytes that invade the synovial tissue. The pro-inflammatory chemokines and cytokine (like the TNF: Tumors Necrosis Factor-alpha, a colony-stimulating factor of the granulocytes-macrophages, various interleukin agents, gamma interferon) are produced by macrophages and lymphocytes in the synovium [80-82]. RA leads to systemic and joint effects, including cartilage and bone loss, which are caused by the release of inflammatory pharmaceutical agents and specific enzymes. Accumulative data shows that anti-CCP antibodies occur well before any inflammatory indications. In comparison, anti-carbamylated protein RA patients expect further radiological progression by the anti-carbamylated protein antibodies. In the preclinical study, the progress of RA is dependent on the distribution of autoantibody epitope, during which the release of self-antigens and the resultant inflammation is resistant. The usually thin synovium multiplies, thickens, and grows several vile folds in permanently affected articulations. Synovial-lined cells contain different components, including stromelysin and collagenase, which contribute to the degradation of cartilage and interleukin-1 (IL-1) and TNF-alpha, which promote cartilage destruction, prostaglandins, synovial inflammation, as well as osteoclast-mediated absorption in the bone. There is also deposition of fibrin, fibrosis, and necrosis. This inflammatory media, which erodes cartilage, subchondral bones, articular capsules, and ligaments, are released from hyperplastic synovial tissue [83, 84]. In the synovial fluid, polymorphonuclear leucocytes make up about 60% on average of white blood cells. In approximately 30% of RA patients, rheumatoid nodules form. They are granulomas composed of a core necrotic region and all of them are enveloped by lymphocytes, plasma cells, and fibroblasts. They are surrounded by histiocytic macrophages. In the visceral organ, modules and vasculitis may also grow [85, 86]. Pathophysiology of Rheumatoid Arthritis is explained in Fig. (2).
Fig. (2)) Pathogenesis of Rheumatoid Arthritis.Complications of Rheumatoid Arthritis
You may become more susceptible to rheumatoid arthritis, particularly if it is not properly managed. In patients suffering from RA, carpal tunnel syndrome is normal. It is caused by nervous compression that tracks sensation and motion (median nerve) in your hands and has signs including dolphin, stupor, wrist, fingertips, and part of the hand. It also affects the part of the hands. Carpal tunnel syndrome symptoms can also be managed by steroid injections or wrist splints but surgery can also be necessary in extreme cases to alleviate pressure on the median nerve [19].
Widespread Inflammation
RA is an inflammatory disease that may induce inflammation in other areas of the body, such as:
Lungs- Pulmonary fibroid or pleurisy, which may lead to chest pain and coughing, and shortness of breath, can lead to lung inflammation or lung lining.
Heart- Tissue inflammation can result in pericarditis, leading to chest pain in the heart.
Blood vessels- Inflammation in blood vessels, referred to as vasculitis, are the walls of blood vessels that are thickened, weakened, narrowed, and clotted. In extreme cases, it can impair blood supply to your organ and tissues and endanger your life.
Eyes- Eye inflammation may contribute to the disorder or syndrome of Sjögren. Scleritis can lead to red-eye and suffering, while Sjögren syndrome may lead to dry eyes.
Joint Damage
Increased inflammation in your joints can lead to substance and permanent damage if rheumatoid arthritis is not treated or not well managed early. Problems with the joints include:
Joint deformitiesDamaged tendons (flexible tissues that attach to the bones and muscles) can result in their rupture or breakage.Damage to cartilage or bones (flexible or tough material which covers the joint surface).Cardiovascular Disease
Cardiovascular disease is a generic term for cardiac or blood vessel disorders that involve life-threatening complications, including stroke and heart attack. There is no obvious cause for the rising risk of these complications in patients with RA. By ensuring that your arthritis is well managed and controlled, you will reduce your risk:
Regular exercise.Eating a balanced and healthy diet.Quitting smoking.Cervical Myelopathy
You are at an elevated risk of having a condition in the top of your spine called cervical myelopathy if you have had rheumatoid arthritis for some time. This dislocation of the joints on the rear of the back creates a strain on the spinal cord. It is a dangerous disorder that, while not widespread, may have a major effect on mobility and cause irreversible injury to the spinal cord if not rapidly treated with service. You can think about tense and sore joints when thinking about RA. But in other areas of the body, you do not know if any complications can occur. The same process that hurts your joints can cause problems for your eyes, lungs, skin, heart, blood vessels, as well as other organs. The RA prescriptions may have side effects. You should live with rheumatoid arthritis problems. Only take care of issues early and be treated accordingly [23].
Effects on Skin
You could get tissue lumps known as rheumatoid nodules. They also occur on your skin, especially on your fingertips, heels, forearms, or elbows. You may instantly pop up or slowly develop. Your rheumatoid arthritis may be a symptom of decline. In areas such as the lungs and heart, they can also develop.
Eye Complications
Rheumatoid arthritis may have multiple effects on the skin. Episcleral inflammation, a narrow membrane surrounding the eye, is normal. It is common. Typically, it's mild, but you may get a swollen and sore eye. Scleritis is more severe and can lead to a vision defect, an inflammation of the White area in the eye.
Sjogren's syndrome will also place you at risk of RA. This occurs as the immune system destroys the ripping glans. Your eyes can feel dry and gritty. It can also occur as dry coughing, vaginal dryness, or extremely dry skin. Eye lubricants may have to be used or medicines removed. The eye dryness will cause the conjunctive membrane which covers the eye and the cornea to become infected and scarred, without treatment.
Neck Pain
The joint pains of fingers and wrists are considered to cause rheumatoid arthritis. However, other regions of the body, such as spine may also be affected. If neck is tense and head twists discomfort, it can be RA. There may be some basic exercises. A doctor should be consulted for the right therapies to reduce the pain in your spine [19].
Blood Vessel and Heart Disease
The membrane around the heart normally forms during eruptions, pericarditis, or inflammation. Flares are when the RA is worse. Pericarditis will increase the thickening of the membrane if it occurs a lot. It will mess with the capacity of the heart to act as it should. Rheumatoid nodules could also grow and impact the way the heart functions. Inflammation of the heart muscle is a rare infection known as myocarditis. The patient may be more likely to develop cardiovascular disease with rheumatoid arthritis. It also increases the stroke chance. Heart disease is not necessarily pre-crisis in symptoms and practitioners can identify issues through an assessment and can prescribe improvements in diet or treatment. Another RA complication is thrombocytosis. This happens when inflammation results in higher platelet levels in the body. Platelets allow the blood to avoid swelling, but there can be so many conditions in the blood vessels such as heart failure, stroke, or clots. Rheumatoid arthritis with Felty's syndrome is a rare complication. This is because the spleen is elevated and the number of white blood cells is low. You may be more vulnerable to lymphoma, also called lymph glands cancer.
Lung Problems
Pleuritis, a disease that can make the respiratory tract uncomfortable, can cause inflammation within the lungs. In your lungs too, rheumatoid nodules will develop. It is normally harmless but can lead to a collapsing lung, blood cough, inflammation, or a pleural buildup of fluids between the lining of the pulmonary canal and the chest cavity. Interstitial lung conditions include lung tissue scarring and pulmonary hypertension, which are a form of hypertension, which may cause lung and heart damage to the lungs, owing to the complications of RA. Rarely many lung disorders can also be caused by the medication methotrexate, which many patients with RA take. You might not have signs, but your doctor may want to do more tests.
Osteoporosis
Osteoporosis results in delicate and thin bones, meaning that they are more likely to break. The chance of RA is greater for individuals. Bone deterioration may also result, so certain drugs, such as steroids, may be used. Also, you might be more likely to get osteoporosis if RA discomfort makes you less active. Osteoporosis Signs include back pain, bent upper back, stooped posture, and fractures. One could lose height as well.
Diabetes
Analysis reveals that RA increases diabetes risk by about 50%. And diabetes increases arthritis risk by about 20%, including RA and associated problems. Experts are not entirely positive about the link between these two diseases. There can be a variety of things:
Diabetes and RA both can lead to inflammation.Type-I diabetes and RA are both auto-immune disorders.Pain and stiffness from RA could keep a person from getting proper physical activities and risk of Type-II diabetes.Any RA-treated drugs also affect diabetes risk. Blood sugar can be boosted by steroids to statins and making the condition more likely. However, other RA prescriptions, including hydroxychloroquine, abatacept, or a group of medications known as TNF inhibitors, can protect against the disease.
Emotional Effects
It will take a toll to deal with chronic pain every day. In one study, almost 11% of people with rheumatoid arthritis reported depressive symptoms. The worse the RA, the more the participants felt depressed. The list of symptoms is:
Insomnia.Loss of interest in any hobbies or work.Trouble in making decisions or concentrating.Deep sadness, emptiness, anxiety, worthlessness, guilt, or hopelessness.Rheumatoid arthritis Diagnosis
Patients with RA typically have multi-joint pain and rigidity. Most commonly include the brackets, interphalangeal proximal joints, and metacarpophalangeal joints. Stiffness of more than an hour in the morning implies an inflammatory etiology. Synovitis can also cause boggy swelling, or synovial thickening, to be noticeable or subtle while the joints are inspected. Before clinically evident joint swelling starts, patients can also have more indolent arthralgia. Active disease may cause systemic symptoms of exhaustion, loss of weight, and low fever.
Diagnostic Criteria
In 2010, the American Rheumatology College and the European Rheumatism League partnered to define new standards for RA's designation. In patients that do not follow the “American College of Rheumatology classification” requirements of 1987, the current criteria were to aim to detect RA earlier. The standards of 2010, which are less typical in early RA, are not composed of erosive radiation or rheumatoid nodules changes.
Diagnostic Tests
Autoimmune disorders such as RA are typically differentiated by autoantibodies. Rheumatoid factor is not RA-specific and can exist in people with other disorders, such as hepatitis C and healthy elderly adults. The RA-specific anti-citrullinated protein antibody could be active in pathogenesis [89]. Nearly 50-80 percent of people who have RA have rheumatoid, anti-citrullines protein, or both [90]. RA patients may get a positive test outcome for their antinuclear antibody and the test is predictable in juvenile forms [91]. The sedimentation rate for erythrocytes is also elevated with active RA [92]. C-reactive amounts of protein and erythrocyte sedimentation can also be used to track disease development and drug response. A full blood count with differential and evaluation of renal and hepatic function is useful because the findings can affect treatment decisions, for example, NSID: “Nonsteroidal Anti-Inflammatory Drug” is not likely recommended for a patient with inadequate or severe thrombocytopenia). In 33 to 60 percent of all patients with RA, moderate chronic disease anemia occurs [93]. Gastrointestinal blood loss must also be taken into consideration in patients who take NSAIDs or corticosteroids. In hepatic diseases, such as hepatitis C, and patients with severe renal dysfunction, methotrexates are contraindicated [94]. The biologic therapy needs negative tuberculin testing, or latent tuberculosis treatment, such as a TNF inhibitor. The use of TNF inhibitors can also contribute to the reactivation of hepatitis B [95]. Hands and feet should be radiographed to determine the periarticular erosive shift feature that may suggest a more violent RA subtype.
Differential Diagnosis
Skin results show chronic erythematosus, systemic sclerosis, or arthritis psoriatic. In an elderly patient with symptoms, rheumatic Polymyalgia should mostly be considered in the shoulder and hip, and questions about the associated temporal arteritis should be addressed. Spondyloarthropathy can be found in people with symptoms of inflammatory back or a history of inflammatory disease. People with just six weeks of symptoms, such as parvoviruses, can have a viral phase. Recurrent autonomous episodes of intense articular swelling are characteristic of arthropathy, and calcium pyrophosphate dihydrate or mono-sodium uratemonohydrate crystals can be assessed by arthrocentesis. The involvement and somatic effects of multiple myofascial causes may lead to fibromyalgia that may coexist with RA. Patients suffering from inflammatory arthritis must be referred immediately to rheumatology subspecialists to help diagnose and define a treatment plan [96, 97]. The first step to treat RA successfully is to seek a correct diagnosis as quickly as possible. A specialist, specializing in arthritis care (rheumatologist), allows the most successful person with medical facts, a physical examination, and laboratory testing to make a valid diagnosis.
Medical History
A doctor would inquire about the symptoms related to the joints like difficulty in moving, stiffness, tenderness, or pain, when it started, if the symptoms are permanent or not, the actions which make them worse or better, and if any family members have Rheumatoid Arthritis or other autoimmune disorders.
Physical Examination
The doctor would check for joint swelling, tenderness, warmth, uncomfortable movements, low-grade fever, or skin bumps.
Blood Tests
Blood tests are available for the detection of antibodies (blood protein)and inflammation for RA.
CRP (C-Reactive Protein) and ESR, also called the “sed rate” (Erythrocyte Sedimentation Rate) levels, were the inflammation markers. A higher CRP or ESR combined with other RA clues helps in making a diagnosis.Eventually, the antibody was found, and the RF (Rheumatoid factor) in nearly 80% of people suffering from RA. CCP (Cyclic Citrullinated Peptide) antibodies were found in 60-70% of patients suffering from RA. Although, it can also be found in people with no RA.Imaging Tests
RA will make the bone ends and the joints will be worn down (erosions). Erosion can also be observed by an X-ray, MRI scan, or ultrasound. But if they do not occur during the initial testing, it may mean that RA has not yet weakened the bone and is in an early stage. The effects of the images will also demonstrate how well therapy performs.
Rheumatoid Arthritis Prevention
Follow-up or screening of patients who are at high risk of developing Rheumatoid Arthritis to develop more services to avoid the progress of the disease [98].Twins of patients suffering from RA or their first relatives, people with positive auto-antibodies, people with a higher prevalence rate of the disease are screened in different prospective researches. Although such researches proved to be expensive considering the outcomes showing a lower rate of prevalence of RA and auto-antibodies related to RA which can limit the statistical abilities of these researchers [99]. Screening done on a larger scale for spotting people at a higher risk of developing Rheumatoid Arthritis in the future (RA-related antibodies and genetic factors) would be costly. The lower prevalence of RA autoantibodies in RA needs screening on a larger scale to spot the individuals at higher risk. RA prevention by changing the environmental factors has proven to be an effective and cheap strategy for preventing Rheumatoid Arthritis. Patients with palindromic rheumatism usually respond to anti-malaria medications or other agents that can modify a disease [100, 101]. Numerous researches also show that people suffering from undifferentiated arthritis can also have some benefits from methotrexate [102]. It can also be said that experiments conducted on the role of steroids have not been much beneficial [103]. The combination of multiple DMARDs and DMARDs as well as corticosteroids, however has proven to be highly beneficial. Abatacept and other biological agents have proven to show better results [104]. Although, the trials are conducted in a randomized manner, with a long time of follow-ups are used to prove the kind of treatment that will provide better results or the ones that can change the course of the disease [105]. Numerous researches depict that treating Rheumatoid Arthritis appropriately in an early “window of opportunity” helps in improving both the long-term as well as the short-term results. As treating RA is costly, difficult, and not effective uniformly, it seems appealing to focus on individuals which are susceptible to some preclinical and recognizable stage, under which the interventions can abort the development of RA [106, 107].
CONCLUSION
Rheumatoid Arthritis is an autoimmune systemic chronic inflammatory condition that might affect numerous organs and tissues in a human body and mainly attacks the synovial joints. The ratio for developing RA in women to a man is 3:1. RA can be prevented by using cold water, living fish oil from the herring, cod, mackerel, and salmon fish which contains omega-3 fatty acids in high amounts, Vitamin-D supplements, and adopting the lifestyle modifications such as avoiding smoking, weight loss. Early diagnosis and initiation of Disease-Modifying Anti-rheumatic Drug (DMARD's) therapy are pivotal to prevent damage from occurring or becoming clinically significant. Therapeutic options for patients who remain unresponsive should ensure within the next 10 years that most patients will achieve the cessation of disease progression and disability and retention of high levels of quality of life.
ABBREVIATIONS
CCPCyclic Citrullinated PeptideCRPC-Reactive ProteinDMARDsDisease-modifying antirheumatic drugsESRErythrocyte Sedimentation RateRARheumatoid ArthritisRFRheumatoid factorCONSENT FOR PUBLICATION
Not applicable.
CONFLICT OF INTEREST
The authors declare no conflict of interest, financial or otherwise.
ACKNOWLEDGEMENTS
Authors are thankful to Prof. (Dr.) Amitsankar Dutta, Professor and Principal, The Eminent College of Pharmaceutical Technology, Moshpukur, Barbaria, Barasat 24 PGS(N) Kolkata– 700126 for his excellent guidance and constant encouragement.
