Harvey's Garden

Rheumatoid arthritis

4 min read

Epidemiology

Etiology

  • Idiopathic inflammatory autoimmune disorder of unknown etiology
  • Risk factors include:
    • Genetic disposition: associated with HLA-DR4 and HLA-DR1
    • Environmental factors (e.g., smoking)
    • Hormonal factors (premenopausal women are at the highest risk, suggesting a predisposing role of female sex hormones)

Pathophysiology

  • Core Concept: A systemic autoimmune disease triggered by an environmental factor in a genetically susceptible host, leading to chronic synovial inflammation and joint destruction.
  • Initiation
    • Genetics: HLA-DR4 is the key association.
    • Triggers: Smoking is the most significant environmental risk factor.
    • Mechanism: Triggers cause citrullination of self-antigens, creating neoantigens targeted by the immune system.
  • Key Immune Components
    • TH cells (CD4+): The central drivers. They activate B-cells and macrophages.
    • B-cells: Produce autoantibodies:
      • Rheumatoid Factor (RF): IgM antibody against the Fc portion of IgG. Low specificity.
      • Anti-CCP: Highly specific antibody targeting citrullinated peptides.
    • Macrophages: Release key pro-inflammatory cytokines.
  • The “Big 3” Cytokines
    • TNF-α, IL-1, and IL-6 are the primary mediators of inflammation and joint destruction. (High-yield for pharmacology).
  • Joint Destruction Cascade
    1. Synovitis: Synovial lining becomes inflamed and hypertrophied.
    2. Pannus Formation: The inflamed synovium transforms into an aggressive a pannus (a mass of synovium, inflammatory cells, and granulation tissue).
    3. Erosion: The pannus invades and destroys adjacent cartilage (via MMPs) and bone (via RANKL-mediated osteoclast activation).

Clinical features

  • Articular (Joints):
    • Symmetric polyarthritis: Hallmark feature.
    • Joints involved: Typically affects small joints of the hands and feet, such as the metacarpophalangeal (MCP), proximal interphalangeal (PIP), and metatarsophalangeal (MTP) joints, as well as the wrists.
    • Morning stiffness: Lasts >1 hour and improves with activity (unlike osteoarthritis).
    • Spared joints: The distal interphalangeal (DIP) joints are typically spared.
    • Deformities (late-stage): Ulnar deviation of fingers, swan-neck deformity (PIP hyperextension, DIP flexion), and Boutonnière deformity (PIP flexion, DIP hyperextension).
  • Extra-articular Manifestations:
    • Constitutional: Fever, fatigue, weight loss, and malaise are common.
    • Rheumatoid Nodules: Most common extra-articular finding; firm, subcutaneous nodules over extensor surfaces or pressure points.
    • Pulmonary: Interstitial lung disease, pleuritis, and pulmonary nodules.
    • Cardiovascular: Increased risk of premature atherosclerosis and coronary artery disease; pericarditis.
    • Hematologic: Anemia of chronic disease, thrombocytosis.
    • Ocular: Scleritis, episcleritis, and secondary Sjögren’s syndrome.

Subtypes and variants

Atlantoaxial subluxation (Vertebral subluxation)

  • Definition: a potentially life-threatening complication caused by the inflammatory destruction of the ligaments affecting the atlantoaxial joint and the intervertebral joints
  • Clinical features
    • Pain and stiffness of the neck (typically early-morning neck pain at rest)
    • Head tilt
    • Neurological deficits
      • Cervical radiculopathy with peripheral paresthesias of the upper limb
      • In some cases, symptoms of high spinal cord compression
        • Slowly progressive spastic quadriparesis
        • Hyperreflexia or positive Babinski reflex
        • Respiratory insufficiency
  • Diagnostics
    • Extension and flexion x-rays of the cervical spine
    • MRI

Warning

Endotracheal intubation can acutely worsen the subluxation and cause compression of the spinal cord and/or vertebral arteries.

Diagnostics

  • Anticitrullinated peptide antibodies (ACPA), e.g., anticyclic citrullinated peptide (anti-CCP)
    • Tissue inflammation causes arginine residues in proteins such as vimentin to be enzymatically converted into citrulline through a process called citrullination. This alters the shape of the proteins, which can then serve as neoantigens that generate an immune response.
  • Rheumatoid factor (RF): IgM autoantibodies against the Fc region of IgG antibodies t

Differential diagnostics

Osteoarthritis (OA) vs Rheumatoid Arthritis (RA)

FeatureOsteoarthritis (OA)Rheumatoid Arthritis (RA)
MechanismMechanical “Wear & Tear”Autoimmune (Pannus)
Stiffness< 30 min (Worse w/ use)> 1 hr (Better w/ use)
SymmetryAsymmetricSymmetric
Key JointsDIP (Heberden), PIP, KneesMCP, PIP, Wrist (Spares DIP)
LabsNormal+Anti-CCP (Specific), +RF, ↑ ESR
X-rayOsteophytes, SclerosisMarginal Erosions, Osteopenia
TreatmentNSAIDs, AcetaminophenDMARDs (Methotrexate)

1. Stiffness

  • OA (<30m): “Gelling.” Synovial fluid gets thick at rest. Movement quickly warms and lubricates it.
  • RA (>1h): Edema. Inflammatory fluid pools during sleep. Takes time to mechanically pump/drain the boggy joint.

2. Pain

  • OA (Worse w/ use): Mechanical. Bone-on-bone friction compresses exposed nerve endings.
  • RA (Better w/ use): Washout. Movement flushes out stagnant inflammatory cytokines and fluid, relieving pressure.

3. Pathology

  • OA (Osteophytes): Construction. Bone grows spurs to widen surface area and stabilize the failing joint.
  • RA (Erosions): Destruction. Pannus (granulation tissue) releases enzymes/RANKL that eat into the bone.
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Treatment

Acute anti-inflammatory treatment

  • Glucocorticoids
    • Systemic prednisone
      • Longer-term therapy: Only use in patients with highly active RA
  • NSAIDs and selective COX-2 inhibitors: relieve symptoms, but do not improve the prognosis

Long-term pharmacological treatment

Disease-modifying antirheumatic drugs (DMARDs)

  • Methotrexate (MTX): first-line treatment in patients with moderate to high disease activity
    • To minimize adverse effects, administer folic acid.
  • Hydroxychloroquine: Consider in patients with low disease activity.
    • Decreases complement-dependent antigen-antibody reactions

Biologic DMARDs

  • Indication: persistent moderate or severe disease activity after 3 months of conventional DMARD therapy
  • Agents
    • TNF-α inhibitors: e.g., adalimumab, infliximab, etanercept

Complications

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