Acute and Chronic Disease Reports
Open Access

Pathophysiology of Rheumatoid Arthritis: Impact on Health and in Therapy

Jefferson Reeves^{* *}Correspondence: Jefferson Reeves, Department of Rheumatology, Johns Hopkins Hospital, Maryland, USA, Email:

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Description

Rheumatoid Arthritis (RA) is a chronic autoimmune disease characterized by inflammation of the synovium, the tissue lining the joints. In RA, the immune system mistakenly attacks the synovium, leading to persistent inflammation, joint pain, swelling, stiffness and eventual damage to cartilage and bone within the affected joints. Unlike osteoarthritis, which primarily results from wear and tear on joints, RA is systemic and can affect multiple joints symmetrically throughout the body. It can also involve extra-articular manifestations, impacting organs such as the heart, lungs and skin.

Pathophysiology

The exact cause of RA remains elusive, but it is believed to result from a combination of genetic predisposition and environmental triggers. Immune cells, particularly T-cells and B-cells, play a central role in initiating and perpetuating inflammation within the joints. The production of autoantibodies, such as Rheumatoid Factor (RF) and anti-Cyclic Citrullinated Peptide (anti-CCP) antibodies, further contributes to the disease process by targeting self-proteins.

Clinical manifestations

RA typically presents with symmetric joint involvement, commonly affecting the small joints of the hands and feet initially. The characteristic symptoms include joint pain, stiffness (often worse in the morning), swelling and warmth. As the disease progresses, joints may become deformed, leading to impaired mobility and decreased quality of life. Extra-articular manifestations, such as rheumatoid nodules, lung involvement (e.g., pleuritis) and cardiovascular complications (due to systemic inflammation), can also occur.

Impact on health and quality of life

Beyond its physical manifestations, RA exerts a significant psychosocial impact on affected individuals. Chronic pain, fatigue and functional limitations can lead to depression, anxiety and social isolation. The unpredictable nature of disease flares and remissions adds to the emotional burden, requiring patients to adapt continually to varying levels of disease activity and its consequences.

Challenges in treatment

Managing RA poses substantial challenges due to its heterogeneity and variable disease course among individuals. Treatment goals aim to achieve disease remission or low disease activity, prevent joint damage and improve overall function and quality of life. Current therapeutic strategies include the following.

Disease-Modifying Anti-Rheumatic Drugs (DMARDs): Methotrexate inhibits immune cell proliferation and reduces inflammation. Other conventional DMARDs and biologic DMARDs (e.g., Tumor Necrosis Factor (TNF) inhibitors, Interleukin-6 (IL-6) inhibitors and Janus Kinase (JAK) inhibitors) target specific pathways involved in RA pathogenesis, offering varying degrees of efficacy and safety profiles.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs): Provide symptomatic relief by reducing pain and inflammation but do not alter the underlying disease process.

Corticosteroids: Used short-term to manage acute flares and as bridge therapy until DMARDs take effect.

Despite these treatment options, not all patients respond adequately to therapy and long-term use of some medications may be associated with significant side effects, including increased susceptibility to infections and potential organ toxicity.

Therapeutic approaches

Advances in understanding RA pathophysiology have prepared for novel therapeutic approaches aimed at more targeted and personalized treatment strategies. These include;

Targeted specific pathways: Biologic therapies targeting cytokines (e.g., IL-17, IL-23) and cellular receptors involved in inflammation offer new approaches for treatment, particularly in patients who are refractory to traditional therapies.

Precision medicine: Genetic profiling and biomarker identification enable clinicians to do treatment based on individual disease characteristics and predicted response to therapy, optimizing outcomes and minimizing adverse effects.

Regenerative medicine: Investigational therapies, such as mesenchymal stem cell transplantation and tissue engineering, repairing damaged joints and modulating immune responses in RA.