Rheumatoid Arthritis (RA)
Also known as: RA (rheumatoid arthritis), Rheumatoid arthritis, Rheumatoid disease, Chronic rheumatoid arthritis, Seropositive rheumatoid arthritis, Seronegative rheumatoid arthritis, Inflammatory polyarthritis, Autoimmune arthritis
Last updated: December 18, 2024
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disorder that mainly affects the lining of joints, especially the small joints of the hands and feet in a symmetric pattern. It can cause swelling, warmth, tenderness, prolonged morning stiffness, and pain that may worsen after rest and improve with gentle activity, with symptoms often fluctuating in flares. It may also involve organs such as the lungs, eyes, skin, and heart.
Key Facts
- •Rheumatoid arthritis (RA) be described as a chronic systemic autoimmune inflammatory disorder that targets synovial joints and extend beyond the musculoskeletal system
- •Inflammatory joint pain that worsens after rest and improve with gentle activity, with flares that vary over time
- •Diagnosed through history, physical exam, and imaging
- •First-line treatment includes exercise, weight management, and activity modification
What It Is
Rheumatoid arthritis (RA) may be described as a chronic systemic autoimmune inflammatory disorder that typically targets synovial joints and can extend beyond the musculoskeletal system. Immune-mediated synovitis can lead to synovial hyperplasia (pannus), cartilage degradation, and progressive bone erosions that may contribute to joint deformity and functional limitation. Inflammation often presents in a symmetric pattern in small joints of the hands and feet, although larger joints can also be involved. Extra-articular inflammation can occur and may affect organs such as the lungs, eyes, skin, and cardiovascular system.
Affected Anatomy
This condition affects several structures in and around the joint:
- •Synovial membrane (synovium) of diarthrodial joints, including synovial lining cells and sublining tissue
- •Articular cartilage of the metacarpophalangeal (MCP) joints
- •Articular cartilage of the proximal interphalangeal (PIP) joints
- •Subchondral bone and marginal bone at joint edges where erosions can develop
- •Joint capsule and periarticular ligaments of the wrist (radiocarpal and midcarpal joints)
- •Flexor and extensor tendon sheaths of the hand and wrist (tenosynovium), which can become inflamed
- •Atlantoaxial (C1–C2) articulation and supporting ligaments, which can be involved in some cases
- •Pleura and pulmonary interstitium, which can be affected in extra-articular disease
Common Symptoms
Symptoms can vary in intensity and may change over time. Common experiences include:
- •Inflammatory joint pain that may worsen after rest and can improve with gentle activity, with flares that often vary over time
- •Morning stiffness that can last for prolonged periods and may correlate with inflammatory activity
- •Joint swelling, warmth, and tenderness that often involve wrists, MCP, and PIP joints in a symmetric distribution
- •Reduced range of motion and grip strength that can reflect synovitis, pain inhibition, and tendon involvement
- •Fatigue and low energy that can accompany systemic inflammation and may fluctuate with disease activity
- •Low-grade fever and malaise that can occur during active inflammatory phases
- •Rheumatoid nodules that can develop over pressure points (such as the olecranon) in some seropositive cases
- •Dry eyes or eye irritation that can reflect associated inflammatory eye disease or secondary sicca symptoms
Causes and Risk Factors
Multiple factors can contribute to the development of this condition:
Causes
- •Autoimmune dysregulation in which the immune system can target synovial tissues, often involving inflammatory cytokine pathways and autoantibody formation
- •Genetic susceptibility that may include HLA-DRB1 shared epitope variants, which can increase the likelihood of immune activation against self-antigens
- •Environmental exposures that can promote mucosal and systemic immune activation, with cigarette smoking often cited as a contributor in susceptible individuals
- •Post-translational protein modification (such as citrullination) that can generate neoantigens and may contribute to anti-citrullinated protein antibody (ACPA) development
- •Microbiome and mucosal immune interactions (oral, lung, and gut) that can influence immune priming and inflammatory signaling
- •Hormonal and immunologic factors that can modulate immune responses and may help explain differences in prevalence by sex
Risk Factors
- •Female sex, which can be associated with higher prevalence and may relate to hormonal and immune differences
- •Family history of RA or related autoimmune disease, which can reflect inherited susceptibility
- •Cigarette smoking, which can increase risk and is often associated with seropositive RA
- •Older age, as incidence can increase with age even though onset can occur across adulthood
- •Obesity, which can be associated with systemic inflammation and may relate to higher disease activity in some populations
- •Periodontal disease, which can correlate with immune activation and may be linked to citrullination pathways
- •Occupational or environmental inhalational exposures (such as silica), which can be associated with increased risk in some studies
- •Presence of autoantibodies (such as rheumatoid factor or ACPA) prior to symptoms, which can indicate higher likelihood of developing clinical RA
How It's Diagnosed
Diagnosis typically involves a combination of clinical assessment and imaging studies:
- •Clinical history and symptom pattern assessment that can include duration of inflammatory joint symptoms, morning stiffness, functional impact, and flare behavior
- •Physical examination that typically includes tender and swollen joint counts, assessment of range of motion, evaluation for synovitis, and screening for extra-articular findings (such as nodules or lung findings)
- •Serologic testing that can include rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA/anti-CCP), which may support diagnosis and can correlate with erosive risk
- •Inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), which can reflect systemic inflammation and may help monitor activity
- •Plain radiography (X-ray) of hands, wrists, and feet to evaluate for joint space narrowing and erosions, which can appear with established disease
- •Musculoskeletal ultrasound to detect synovial hypertrophy, effusions, and power Doppler signal that can indicate active synovitis and can identify subclinical inflammation
- •Magnetic resonance imaging (MRI) to evaluate early erosions, bone marrow edema (osteitis), and synovitis when X-rays can appear normal in early disease
Treatment Options
Treatment approaches range from conservative measures to surgical interventions, often starting with the least invasive options:
Self-Care and Activity Modification
- •Patient education and shared decision-making frameworks that can support understanding of chronic inflammatory disease patterns and monitoring needs
- •Activity modification and joint protection strategies that can reduce mechanical stress during flares and may support function
- •Conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) such as methotrexate, sulfasalazine, hydroxychloroquine, or leflunomide, which can reduce inflammatory activity and may slow joint damage
- •Biologic DMARDs (for example, TNF inhibitors, IL-6 receptor inhibitors, T-cell costimulation modulators, or B-cell–directed therapies) that can target specific immune pathways and may be used when disease activity remains elevated
- •Targeted synthetic DMARDs (JAK inhibitors) that can modulate intracellular signaling and may be considered in selected patients based on risk-benefit assessment
Physical Therapy and Exercise
- •Physical therapy and occupational therapy interventions that can include range-of-motion work, strengthening, splinting, and adaptive equipment to support daily activities
Medications
- •Nonsteroidal anti-inflammatory drugs (NSAIDs) that can reduce pain and inflammation symptoms, although they typically do not prevent structural progression
Injections and Office-Based Procedures
- •Glucocorticoids (systemic or intra-articular) that can provide short-term anti-inflammatory effects and may be used as bridging therapy in some care plans
Surgery
- •Surgical options for advanced joint damage that can include synovectomy, tendon repair, joint fusion (arthrodesis), or joint replacement (arthroplasty) to address pain and deformity when conservative measures provide limited benefit
Prognosis and Recovery
The course of this condition varies between individuals:
- •Disease course can vary widely, with periods of increased activity (flares) and relative improvement, and some individuals can experience persistent inflammation without sustained remission.
- •Earlier control of inflammatory activity can be associated with less radiographic progression and better functional outcomes, although response can differ by individual biology and comorbidities.
- •Seropositive disease (RF and/or ACPA) can be associated with higher likelihood of erosive changes and extra-articular manifestations, though severity can still vary.
- •Extra-articular involvement (such as interstitial lung disease or vasculitis) can increase overall disease burden and may influence long-term health outcomes.
- •Functional limitations can develop from joint damage, tendon dysfunction, and pain sensitization, and disability risk can increase when inflammation remains active over time.