Rheumatoid Arthritis

Rheumatoid arthritis is an autoimmune disease that causes chronic inflammation of the joints and other areas of the body. In RA, the immune system attacks the synovium—the lining of the membranes that surround the joints. This results in inflammation that thickens the synovium, which can eventually destroy the cartilage and bone within the joint. The tendons and ligaments that hold the joint together weaken and stretch, causing the joint to lose its shape and alignment.

Unlike osteoarthritis, which typically affects one joint or joints on one side of the body, RA usually affects joints symmetrically—if one knee is affected, the other one usually is too. RA is a systemic disease, meaning it can affect the entire body. Beyond joints, RA can affect the skin, eyes, lungs, heart, blood vessels, and other organs.

The course of RA varies from person to person. Some people have mild symptoms that come and go, while others experience severe symptoms that never seem to improve. Most people fall somewhere in between, with periods of increased disease activity called flares alternating with periods of relative remission when symptoms fade or disappear. Early, aggressive treatment is key to slowing or stopping the progression of joint damage.

Joint Involvement Pattern

RA typically starts in smaller joints and progresses to larger ones:

• Early stage: Small joints of hands and feet
• Progression: Wrists, knees, ankles, elbows, hips, shoulders
• Symmetrical pattern: Both sides of body affected similarly
• Morning stiffness: Lasting more than 30 minutes

Extra-Articular Manifestations

About 40% of people with RA experience symptoms beyond the joints:

• Skin: Rheumatoid nodules, rashes
• Eyes: Dryness, inflammation, scleritis
• Lungs: Inflammation, scarring, nodules
• Heart: Pericarditis, increased cardiovascular risk
• Blood vessels: Vasculitis
• Blood: Anemia, Felty's syndrome
• Bones: Osteoporosis

What Causes RA?

The exact cause of rheumatoid arthritis remains unknown, but researchers believe it results from a combination of genetic and environmental factors that trigger an abnormal immune response.

Risk Factors

Non-Modifiable Risk Factors

• Gender: Women are 2-3 times more likely to develop RA
• Age: Can occur at any age but most common 40-60
• Genetics: Having relatives with RA increases risk
• HLA genes: Certain genetic markers increase susceptibility

Modifiable Risk Factors

• Smoking: Strongest environmental risk factor
• Obesity: Increases risk and severity
• Periodontal disease: Gum disease linked to RA
• Infections: Some viruses and bacteria may trigger RA
• Occupational exposures: Silica, asbestos

Protective Factors

• Breastfeeding (for women)
• Moderate alcohol consumption (controversial)
• Omega-3 fatty acids in diet
• Regular physical activity

The Autoimmune Process

In RA, the immune system malfunction involves:

1. T cells become activated and infiltrate joint tissue
2. B cells produce autoantibodies (RF and anti-CCP)
3. Inflammatory cytokines are released
4. Synovial membrane becomes inflamed and thickened
5. Pannus formation destroys cartilage and bone
6. Joint damage and deformity occur

Diagnosing RA can be challenging, especially in early stages. No single test confirms RA, so doctors use a combination of clinical findings, laboratory tests, and imaging studies.

Diagnostic Criteria

The 2010 ACR/EULAR classification criteria for RA considers:

• Joint involvement (number and size)
• Serology (RF and anti-CCP antibodies)
• Acute-phase reactants (ESR and CRP)
• Duration of symptoms

Laboratory Tests

Blood Tests

• Rheumatoid Factor (RF): Positive in 70-80% of RA patients
• Anti-CCP antibodies: More specific for RA, positive in 60-70%
• ESR and CRP: Indicate inflammation level
• Complete blood count: May show anemia
• ANA: To rule out other autoimmune diseases

Imaging Studies

• X-rays: Show joint damage and erosions
• Ultrasound: Detects early inflammation and erosions
• MRI: Most sensitive for early changes
• CT scan: Sometimes used for specific areas

Other Assessments

• Joint examination: Swelling, tenderness, range of motion
• Disease activity scores: DAS28, CDAI, SDAI
• Functional assessments: HAQ disability index
• Synovial fluid analysis: If needed to rule out infection

Differential Diagnosis

Conditions that can mimic RA include:

• Psoriatic arthritis
• Systemic lupus erythematosus
• Osteoarthritis
• Gout
• Fibromyalgia
• Viral arthritis
• Reactive arthritis

The goal of RA treatment is to stop inflammation, relieve symptoms, prevent joint and organ damage, improve function and overall well-being, and achieve remission. Treatment has evolved dramatically, with early, aggressive therapy now standard.

Medications

Disease-Modifying Antirheumatic Drugs (DMARDs)

These are the cornerstone of RA treatment:

• Methotrexate: First-line DMARD, "gold standard"
• Hydroxychloroquine: Often used in combination
• Sulfasalazine: Alternative or add-on therapy
• Leflunomide: Alternative to methotrexate

Biologic DMARDs

Target specific parts of immune system:

• TNF inhibitors: Adalimumab, etanercept, infliximab
• IL-6 inhibitors: Tocilizumab, sarilumab
• B-cell depletion: Rituximab
• T-cell costimulation blocker: Abatacept
• JAK inhibitors: Tofacitinib, baricitinib, upadacitinib

Symptom Relief Medications

• NSAIDs: For pain and inflammation
• Corticosteroids: Short-term for flares
• Pain medications: As needed

Non-Pharmacological Treatments

Physical and Occupational Therapy

• Exercise programs to maintain joint flexibility
• Muscle strengthening exercises
• Joint protection techniques
• Assistive devices and splints
• Energy conservation strategies

Lifestyle Modifications

• Regular exercise: Low-impact activities
• Weight management: Reduces joint stress
• Healthy diet: Anti-inflammatory foods
• Stress management: Can reduce flares
• Smoking cessation: Improves treatment response
• Adequate rest: Balance activity with rest

Surgical Options

When joint damage is severe:

• Synovectomy: Removal of inflamed synovium
• Tendon repair: Fix ruptured tendons
• Joint fusion: For stability
• Joint replacement: Hip, knee, shoulder

Treatment Strategy

Modern RA treatment follows these principles:

• Early intervention: Start DMARDs within 3 months
• Treat to target: Aim for remission or low disease activity
• Tight control: Frequent monitoring and adjustments
• Combination therapy: Often more effective
• Personalized approach: Based on disease severity and patient factors

Daily Management

• Medication adherence: Take as prescribed, even when feeling well
• Joint protection: Use proper body mechanics
• Activity pacing: Balance rest and activity
• Exercise routine: Regular, gentle exercise
• Heat and cold therapy: For symptom relief
• Assistive devices: Reduce joint stress

Diet and Nutrition

• Anti-inflammatory foods: Omega-3 fatty acids, fruits, vegetables
• Limit processed foods: Reduce inflammation
• Adequate calcium and vitamin D: For bone health
• Maintain healthy weight: Reduce joint stress
• Stay hydrated: Important for joint health
• Consider Mediterranean diet: May reduce inflammation

Exercise and Physical Activity

• Range of motion exercises: Daily stretching
• Strengthening exercises: Build muscle support
• Aerobic exercise: Swimming, walking, cycling
• Balance exercises: Prevent falls
• Tai chi or yoga: Gentle movement options
• Water therapy: Low-impact exercise

Work and Career

• Know your rights under ADA
• Request workplace accommodations
• Ergonomic workspace setup
• Flexible scheduling if needed
• Consider vocational rehabilitation
• Communicate with employer about needs

Emotional Well-being

• Acknowledge emotional impact
• Join support groups
• Consider counseling
• Practice stress reduction
• Maintain social connections
• Set realistic goals

Monitoring and Follow-up

• Regular rheumatologist visits (every 3-6 months)
• Laboratory monitoring for medications
• Annual eye exams (if on hydroxychloroquine)
• Bone density scans
• Cardiovascular risk assessment
• Vaccination updates

Joint-Related Complications

• Joint destruction: Erosions and deformity
• Tendon rupture: Especially in hands
• Carpal tunnel syndrome: Wrist inflammation
• Cervical spine instability: Can be serious
• Secondary osteoarthritis: From joint damage

Systemic Complications

• Cardiovascular disease: Leading cause of death in RA
• Lung disease: Interstitial lung disease, nodules
• Osteoporosis: From inflammation and medications
• Infections: Due to immune suppression
• Lymphoma: Slightly increased risk
• Amyloidosis: Rare but serious
• Felty's syndrome: RA with low white cell count

Medication Side Effects

• Methotrexate: Liver toxicity, lung problems
• Biologics: Increased infection risk
• Corticosteroids: Osteoporosis, diabetes, cataracts
• NSAIDs: Stomach ulcers, kidney problems

The prognosis for RA has improved dramatically with modern treatments. Early, aggressive treatment can prevent joint damage and disability in most patients.

Factors Affecting Prognosis

Good Prognostic Factors

• Early diagnosis and treatment
• Good response to initial therapy
• Male gender
• Younger age at onset
• Higher education and socioeconomic status
• Non-smoker

Poor Prognostic Factors

• High disease activity at diagnosis
• Positive RF and anti-CCP antibodies
• Early erosions on X-ray
• Extra-articular manifestations
• Smoking
• Delayed treatment

Long-term Outcomes

• With modern treatment, 40-50% achieve remission
• 70-80% have good functional outcomes
• Joint replacement less common than in past
• Work disability reduced by 30-50%
• Life expectancy approaching normal with good disease control

Current Research Areas

• New targeted therapies
• Precision medicine approaches
• Biomarkers for early diagnosis
• Predicting treatment response
• Regenerative medicine
• Microbiome research
• Gene therapy possibilities

Emerging Treatments

• New JAK inhibitors
• Novel biologic targets
• Combination therapy optimization
• Nanoparticle drug delivery
• Cell therapy approaches