Rheumatoid Arthritis: Symptoms, Causes & Treatments

Rheumatoid arthritis is a chronic inflammatory disease characterized by hyperplasia of synovial lining cells, angiogenesis, and infiltration of the mononuclear cells that results in pannus formation (hallmark), cartilage erosion, & ultimately ending in joint destruction. 1% of the adult population suffers from rheumatoid arthritis (RA). 75% are women. 25% are male.

• F
  ratio - 3:1
• The peak age of incidence is 40 to 50 years.
• It is the most common inflammatory joint disorder.

1. Etiology

• 15 to 20% of monozygotic twins exhibit concordance.
• HLA-DR4 is found to be a major risk factor.
• HLA DW16 is a major risk factor in Asian Indians.
• Infectious Causes
  • Bacteria: Mycoplasma, Mycobacteria, E. coli
  • Virus: EBV, CMV, Parvo, Rubella
• HLA DRB1 individuals who smoke are at high risk.

2. Pathogenesis

Increased cellularity includes synovial infiltration by B cells, macrophages, and fibroblasts. B cells develop into plasma cells and produce RA factor, leading to complement activation. This leads to the migration and proliferation of fibroblasts, vascular infiltration, and granulation tissue development. This granulation tissue is called a pannus. The bone and cartilage destruction appears to be caused by the activation of collagenases and other degrading enzymes released from the inflammatory pannus by the cytokines.

3. Symptoms of Rheumatoid Arthritis

Joint Symptoms

• Swelling is present due to inflammation in joints.
• Pain: Often in multiple joints, typically symmetrical (affecting both sides of the body).
• Stiffness is present, especially in the morning or after periods of inactivity.
• Tenderness in joints.

Systemic Symptoms

• Fatigue: Persistent lack of energy and tiredness.
• Fever: Low-grade fever may occur during flare-ups.
• Weight Loss: Unexplained weight loss can happen due to chronic inflammation.

Other Symptoms:

• Joint deformities occur due to chronic inflammation.
• Rheumatoid nodules may develop, typically under the skin near affected joints.
• Some patients may experience symptoms like dry eyes and mouth.

Complications

• There is risk of heart disease.
• There are chances of anemia due to low RBCs.

Clinical Features

• Symmetrical involvement of small joints of hands and feet.
• Joints involved (decreasing frequency):
  • MCP (metacarpophalangeal) >> wrist >> PIP (proximal interphalangeal) >> Knee >> MTP (metatarsophalangeal) >> shoulder >> ankle >> CS (cervical spine) >> hip >> elbow >> TMJ (temporomandibular joint).
• In the whole spine, only the cervical spine is involved.
• Back pain is not a feature of RA.

Rheumatoid Nodules

• Present only in 25% of cases.
• Commonly seen:
  • Olecranon aspect of:
    • Elbow
    • Achilles tendon
  • Extensor aspect of:
    • Hand
    • Foot
• Methotrexate may cause nodulosis (↑ size).

4. Typical Deformities of RA

Upper Limb

• Swan Neck deformity (Distal Phalanx): Swan Neck deformity is characterized by hyperextension of the proximal interphalangeal (PIP) joint and flexion of the distal interphalangeal (DIP) joint. This results in a claw-like appearance of the fingers, presenting the following diagram.

• Boutonniere/Buttonhole deformity (proximal interphalangeal): Boutonniere/Buttonhole Deformity involves flexion of the proximal interphalangeal joint and hyperextension of the distal interphalangeal joint. This deformity occurs due to the rupture of the central slip of the extensor tendon present in the following diagram.

• Hitch-Hikers deformity (thumb is involved).
• Z-deformity (Hand).
  • MCP goes to Ulnar.
  • PIP comes to the opposite (radial deviation).

• Main-En-Lorgnette deformity (Telescoping Fingers)
  • Subluxation of PIP
  • The finger will go down and up like a telescope.

Lower Limb

• Wind-swept deformity:

• One side knee joint will go to the genu valgum.
• Other side knee joints will go to the genu varum.

• Torch-light deformity (all fingers are fanned out).
• Sudden onset flat foot:
  • Due to tibialis posterior insufficiency.
  • Usually after 40 years.
• Protrusio Acetabuli.
• Bakers' cyst.

5. Diagnosis of Rheumatoid Arthritis

1987 American College of Rheumatology Revised Criteria

• Morning stiffness of more than one hour.
• Arthritis of three or more areas.
• Arthritis of hand joints.
• Symmetrical arthritis.
• Rheumatoid nodules.
• Positive rheumatoid factor.
• Positive radiological features.
• Note: 4/7 for six weeks is considered positive for rheumatoid arthritis (RA).

6. Lab Investigations

• Anti-CCP
  • Cyclic citrullinated phosphate
  • Can be positive in the early stages.
  • Has prognostic importance.
  • Best investigation.
• Rheumatoid Factor
  • Good investigation.
  • Positive only in 60% of cases.
  • Maybe give false positive results in:
    • Cryoglobulinemia
    • Parvo 19 infection
    • Hepatitis C
    • Sjogren's Syndrome
    • SLE
    • 5% of normal individuals
    • Malaria
• Positive ANA occurs in 40%.
• Elevated ESR and CRP (active disease).

7. Treatment

Acute Stage

• Active disease
• +ve classical signs
• Corticosteroids are used temporarily for 1 to 2 weeks.

DMARDs

• HCQ (200 mg BD)
  • Complication: Bull's eye-like maculopathy/hemeralopia.
• Sulfasalazine
• Methotrexate (Gold standard)
  • 7.5 mg once a week.
  • Better to give on an empty stomach.
  • The WBC count is to be monitored every month (to check bone marrow suppression).
• Leflunomide (Upcoming drug)
• Biological DMARDs (Usually Monoclonal Antibodies)
  • Infliximab
  • Etanercept
  • Adalimumab
  • Golimumab
  • Anakinra
  • Tocilizumab (Currently very effective)

8. Surgical Treatments for Rheumatoid Arthritis

Synovectomy:

• Description: Removal of the inflamed synovial tissue (lining of the joint) to reduce pain and swelling.
• Indication: It is often used in early-stage RA or in specific joints.

(Arthroplasty) Joint Replacement:

• Total Joint Replacement:
  • Description: Total joint replacement surgery commonly performed on the hip, knee, and shoulder. Under total joint replacement surgery, there is replacement of the damaged joints with artificial components.
  • Indication: Recommended for severely damaged joints causing significant pain and disability.
• Partial Joint Replacement:
  • Under partial joint replacement, only the damaged portion of the joint is replaced.
• Arthrodesis (Joint Fusion):
  • Description: Fusion of bones in a joint to eliminate motion and relieve pain.
  • Indication: Arthrodesis is typically used for smaller joints (like the fingers or wrists) when joint replacement is not feasible.
• Tendon Repair or Reconstruction:
  • Description: Addresses issues with tendons that may be affected by RA, such as tendon ruptures or deformities.
  • Indication: Tendon repair surgery is necessary when tendon function is compromised; due to this, it affects joint stability and function.
• Osteotomy:
  • Description: Realignment of bones in a joint to improve function and relieve pressure on the joint.
  • Indication: Sometimes considered for joint deformities or misalignment.

Considerations for Surgery

• Timing: Surgery is generally considered when there is significant joint damage, loss of function, or persistent pain despite other treatments.
• Rehabilitation: Post-surgery rehabilitation is crucial for recovery and restoring function.
• Risks: There are risks involved, including infection, blood clots, and complications from anesthesia.

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