Rheumatoid Arthritis: Risk Factors and Symptoms

Risk Factors

• HLA-DRB1 genes associated with "shared epitope" increase risk for rheumatoid arthritis (RA)
• PTPN22 gene is another genetic risk factor
• Predominantly affects females, particularly those aged 25-55
• Smoking is identified as a significant lifestyle risk factor

Pathophysiology

• Characterized by pannus formation in synovial tissues, leading to destruction of bones and cartilage
• Insidious onset linked to breakdown of self-tolerance mechanisms

Symptoms

• General: fatigue, weight loss, low-grade fever
• Rheumatoid nodules appear on extensor surfaces
• Vasculitis may occur, along with morning stiffness lasting over 30 minutes, improving with activity and worsening with rest
• Symmetric joint swelling, tenderness, and pain primarily affecting:
  • Proximal interphalangeal (PIP) joints
  • Metacarpophalangeal (MCP) joints (notable ulnar deviation)
  • Metatarsophalangeal (MTP) joints, wrists, ankles, and knees
• Osteoarthritis (OA) differs: less involvement of wrists and feet, affecting only distal joints

Deformities

• Swan neck deformity: hyperextension of PIP joint and flexion of distal interphalangeal (DIP) joint
• Boutonnière deformity: flexion of PIP joint and extension of DIP joint

Systemic Symptoms

• Ocular complications, pulmonary issues, and cardiac involvement (e.g., pericarditis)

Laboratory Findings

• Elevated rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies
• Increased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP)
• Mild anemia and reactive thrombocytosis
• Synovial fluid analysis shows inflammatory effusion with predominant polymorphonuclear leukocytes (PMNs)

Radiographic Findings

• X-rays normal in early RA stages; soft tissue swelling and osteopenia observed initially
• Later stages show joint space narrowing and erosive changes

Diagnostic Criteria

• A score of at least 6 is required for RA diagnosis

Treatment (TX)

• Aim to control pain and inflammation; nonsteroidal anti-inflammatory drugs (NSAIDs) are not sufficient alone as they do not alter disease progression
• Preserve function and prevent deformity development
• Early diagnosis and initiation of disease-modifying anti-rheumatic drugs (DMARDs) are essential
• Corticosteroids used as a bridging treatment, taper as soon as possible, not for monotherapy or long-term use
• Methotrexate (MTX) initiated at 7.5 mg, effects observed in about a month, supplemented with daily folic acid; regular CBC and liver function tests (LFTs) are necessary
• Contraindications for MTX include pregnancy, liver disease, heavy alcohol use, and severe renal impairment, with side effects including GI upset and stomatitis
• Rheumatologist involvement is pivotal; patients may require combined DMARD therapies
• Common combination: MTX with TNF inhibitors

Biologics

• TNF inhibitors (e.g., Etanercept) are effective but come with high costs and risk of severe bacterial and granulomatous infections, including latent TB reactivation
• Screening for latent TB is mandatory prior to starting biologics

Pretreatment Screening

• Conduct comprehensive RA lab panel: RF, anti-CCP, ESR, CRP, CBC, and CMP
• Screen for Hepatitis B & C, perform baseline CBC, creatinine, LFTs, and assess for latent TB
• Conduct ophthalmic screening and rule out pregnancy
• Baseline radiographs to check for osteopenia and erosions

Follow-Up (F/U)

• Regular assessment of symptoms, functional status, lab work, and radiography every two years

Treatment Timeline

• Lifelong MTX therapy (with folic acid) begins with a notice of 4 weeks for noticeable effects
• Begin prednisone dosage of 5-20 mg/day with planned tapering

Felty's Syndrome

• Combination of symptoms including:
  • Splenomegaly
  • Anemia
  • Neutropenia
  • Thrombocytopenia
  • Arthritis rheumatoid