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Diagnosis and Management of Rheumatoid Arthritis

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Rheumatoid arthritis (RA) is a chronic inflammatory disease which affects up to 1 % of the population worldwide. It harms those joints of the body that are lined with synovia, a specialized tissue responsible for maintaining the nutrition and lubrication of the joint. The distribution of joints affected (synovial joints) is characteristic. It typically affects the small joints of the hands and the feet, and usually both sides equally in a symmetrical distribution, though any synovial joint can be affected. In patients with established and aggressive disease, most joints will be affected over time.

The initial trigger for RA is unknown. There is evidence to suggest abnormalities in components of the immune system that lead to the body developing abnormal immune and inflammatory reactions, particularly in joints. These changes may precede the symptomatic onset of RA by many years. Whatever sets the pathology in motion results in a large increase in blood flow to the joint (giving heat and sometimes redness), proliferation of the synovial membrane with an increase in synovial fluid (swelling), and pain (due to stretching of pain receptors in the soft tissues around, and the bone on either side, of the joint). These features result in rapid loss of muscle around an affected joint, and this, along with pain and swelling leads to loss of joint function. If the inflammation of the synovial membrane cannot be suppressed it will result in increasing damage to the joint, due to the release of protein-degrading enzymes from inflammatory and other cells, and a conversion of parts of the synovial membrane into an inflammatory tissue called «pannus» which can invade the bone and cartilage at the margins of the joint. The degree of progressive damage is related to the intensity and duration of the inflammation. Damage to joints results in progressive deformity, disability and handicap. Other structures have synovial linings, such as tendon sheaths, and inflammation of these can result in tendon rupture. Consequently, suppression of inflammation in the early stages of the disease can result in substantial improvements in long-term outcomes for joints and other components of the musculoskeletal system.

Compounding this widespread inflammatory arthritis is the fact that RA affects much more than the joints, and is a systemic disease. In all patients, the release of large concentrations of proteins that drive inflammatory processes (such as tumor necrosis factor-α (TNF-α)), resulting in symptoms of profound fatigue, with a feeling of ongoing influenza-like symptoms, and even fever, sweats, and weight loss. Furthermore, other body organ systems may be affected by the inflammatory process, with the dryness of the eyes and mouth (Sjögren’s syndrome), and nodules (hard lumps particularly over extensor surfaces like the backs of elbows) affecting up to a third of patients.

More significant inflammatory manifestations may lead to serious pathologies, such as fibrosis in the lungs, inflammation affecting the lining of the heart and lungs (pleural and pericardial effusions), or vasculitis. Vasculitis results in inflammation of the inner lining of the blood vessels and may lead to potentially devastating effects for whichever organ is supplied by the affected blood vessels. Examples of vasculitis are scleritis of the eye, a painful and potentially sight-threatening vasculitis, and peripheral neuropathy, where nerves are irreversibly damaged leading to weakness or sensory abnormalities. Inflammation of the joints can also be life-threatening when it affects the neck, causing potentially unstable articulations between the bones, and inflammatory pannus. This combination of bone deformity and swollen inflammatory tissue can press on the spinal cord, leading to ischemia and widespread neurological consequences affecting all four limbs, bowel and bladder function, or the respiratory muscles and centers in the brain stem that control respiration, potentially resulting in death.

Thankfully, these life-threatening inflammatory manifestations of the disease are uncommon and are possibly becoming rarer. However, it has become increasingly evident that the ongoing inflammation and loss of mobility can have other unforeseen circumstances for people with RA. Heart conditions such as ischemic heart disease and cardiac failure have been shown to be more common in RA, and result in premature death for many patients. Atherosclerosis (where the inner lining of arteries become progressively thickened and impair blood supply to whichever organ is being served) is driven in part by ongoing inflammation so that the people with the most active RA have the greatest risk of heart disease. Osteoporosis is also more common, due to reduced mobility, inflammation, and sometimes the drugs they are on (particularly steroids). People with RA are more prone to infections than the rest of the population, probably due to abnormalities in the immune system, and sometimes contributed to by medication (such as the immunosuppressant effects of steroids).

Clearly, RA has the potential for not only widespread joint and soft tissue damage, but also inflammatory processes that can directly or indirectly affect most organ systems in the body, and result in premature death. Appropriate management, therefore, needs to address not only the impact on joints, but also focus on the whole body, the person suffering from the disease, their families, and carers, and where appropriate their employers.

The field of biomarker research has expanded dramatically in the past 5-7 years coinciding with the advancement of high-throughput technologies such as genomic and proteomic arrays. A biomarker can be generally defined as a measurable indicator of either normal or pathogenic processes or pharmacological responses to therapeutic interventions. Clinically, biomarkers are commonly used for diagnostic (disease identification) and prognostic (predicted outcome or progression) purposes. However, the availability of biomarkers which support treatment choice (theranostic biomarkers) remains limited. A theranostic biomarker could identify the most appropriate treatment for an individual, indicate the correct dose, or predict response to treatment. This approach attempts to maximize drug efficacy, minimize toxicity and provides a more informed treatment choice.

The identification and adoption of diagnostic and prognostic biomarkers for rheumatoid arthritis have informed and improved the clinical management of this disease. With the advent of biologic treatments, achieving disease remission has become a realistic endpoint for clinicians. The life-changing efficacy of these therapies, however, is restricted to the 60-70% of patients who respond. The immune reaction to anti-inflammatory therapy is thought to be influenced by many genes which cumulatively contribute to a threshold for response. There is an inherent clinical need to provide theranostic biomarkers which could determine treatment outcome. The current study will focus on finding and verifying the predictive biomarkers of RA which can help in prognoses and diagnoses of the disease in its early stage far before then the serious damage caused by the disease.

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GradesFixer. (2019). Diagnosis and Management of Rheumatoid Arthritis. Retrived from https://gradesfixer.com/free-essay-examples/diagnosis-and-management-of-rheumatoid-arthritis/
GradesFixer. "Diagnosis and Management of Rheumatoid Arthritis." GradesFixer, 11 Feb. 2019, https://gradesfixer.com/free-essay-examples/diagnosis-and-management-of-rheumatoid-arthritis/
GradesFixer, 2019. Diagnosis and Management of Rheumatoid Arthritis. [online] Available at: <https://gradesfixer.com/free-essay-examples/diagnosis-and-management-of-rheumatoid-arthritis/> [Accessed 12 July 2020].
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