Rheumatoid arthritis (RA) is a chronic systemic autoimmune disorder characterized primarily by persistent inflammation of the synovial joints, leading to progressive joint damage, deformity, and functional disability.

This complex disease manifests through a multifaceted interplay of genetic predisposition and environmental triggers, with significant impact on quality of life and overall morbidity.

Pathogenesis and Etiology

Rheumatoid arthritis fundamentally arises when the immune system erroneously targets its own synovial tissues, specifically the lining of joints, initiating chronic inflammation.

This autoimmune reaction involves a cascade of cellular and molecular events including T-cell activation, B-cell autoantibody production (notably rheumatoid factor and anti-cyclic citrullinated peptide antibodies), and release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6).

Clinical Presentation and Diagnostic Features

RA characteristically presents insidiously with bilateral, symmetric involvement of small peripheral joints such as the metacarpophalangeal and proximal interphalangeal joints, often accompanied by morning stiffness lasting over an hour. Larger joints may become involved as the disease advances, including wrists, elbows, shoulders, knees, and cervical spine (notably C1-C2).

Besides articular symptoms, systemic manifestations like fatigue, low-grade fever, and rheumatoid nodules may appear.

Diagnosis hinges on clinical examination combined with laboratory findings. Elevated inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) reflect active inflammation. Serological tests detecting rheumatoid factor (RF) and anti-CCP antibodies support diagnosis and prognostication.

Imaging modalities including X-rays reveal characteristic joint space narrowing, marginal erosions, and periarticular osteopenia, with ultrasound and MRI providing earlier detection of synovitis and structural damage.

Therapeutic Approaches

Therapy for RA aims to achieve disease remission or low disease activity, prevent joint damage, preserve function, and improve quality of life. Early aggressive treatment within the first six months of symptom onset notably improves long-term outcomes.

Pharmacological management begins with disease-modifying anti-rheumatic drugs (DMARDs), which include conventional synthetic agents like methotrexate—the cornerstone of RA therapy—alongside leflunomide and sulfasalazine.

Biologic DMARDs targeting specific cytokines or immune cells, such as TNF inhibitors (etanercept, adalimumab), IL-6 receptor antagonists (tocilizumab), and B-cell depleting agents (rituximab), are employed in patients with inadequate response to conventional therapy. Janus kinase (JAK) inhibitors represent an emerging class of small molecules offering treatment alternatives.

Adjunctive medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids provide symptomatic relief but do not modify disease course. Non-pharmacological strategies including physical and occupational therapy play essential roles in maintaining joint mobility, muscle strength, and functional ability. Surgery may be indicated in advanced disease for joint replacement or corrective procedures.

Prognosis and Complications

RA remains a chronic, potentially disabling disease with variable clinical courses. Early and sustained control decreases risk of joint deformities and disability. Despite treatment advancements, many patients experience fluctuating disease activity and extra-articular complications affecting the lungs, heart, eyes, and vasculature.

Notably, RA is associated with increased cardiovascular morbidity driven by systemic inflammation. This necessitates comprehensive management encompassing disease control, cardiovascular risk reduction, and vigilant monitoring. Functional impairment substantially impacts patients’ quality of life, underscoring the importance of multidisciplinary care integrating medical, physical, and psychosocial support.

Dr. Joan Bathon, a world-renowned rheumatologist and a leading researcher in rheumatoid arthritis, states "The window of opportunity is early. We know that early, aggressive treatment of inflammatory arthritis is the best strategy to prevent long-term joint damage and disability."

Rheumatoid arthritis is a systemic autoimmune condition characterized by chronic synovial inflammation, resulting in progressive joint destruction and systemic involvement. It presents with symmetrical polyarthritis, morning stiffness, and systemic features.

Diagnosis integrates clinical evaluation, serology, and imaging, guided by standardized classification criteria. Treatment prioritizes early initiation of DMARDs and biologics alongside supportive therapies to control disease activity and prevent long-term disability.