9.3 Inflammatory Arthritides (RA, Gout, SpA) & Systemic Autoimmune Diseases (SLE, Vasculitis)

Rheumatoid Arthritis (RA)

Rheumatoid arthritis is a chronic, systemic autoimmune disease characterized by persistent inflammatory synovitis leading to joint erosion, cartilage destruction, and progressive disability.

Clinical Presentation & Joint Involvement

• Pattern: Symmetric inflammatory polyarthritis predominantly affecting the small joints of the hands and feet: Metacarpophalangeal (MCP), Proximal Interphalangeal (PIP), and Metatarsophalangeal (MTP) joints, as well as wrists and ankles.
• Morning Stiffness: Joint stiffness lasting $>60\text{ minutes}$ in the morning or after prolonged inactivity, which improves with movement.
• Joint Sparing: Spares the Distal Interphalangeal (DIP) joints and the lumbar spine (though cervical spine involvement, specifically C1–C2 subluxation, can occur and causes compressive myelopathy).
• Extra-articular Manifestations: Rheumatoid nodules (extensor surfaces), interstitial lung disease, pericarditis, episcleritis, and Felty syndrome (triad of RA, splenomegaly, and neutropenia).

Diagnostic Serology & Imaging

• Anti-Cyclic Citrullinated Peptide (Anti-CCP / ACPA): High specificity ($>95%$) for RA; correlates with aggressive, erosive disease progression.
• Rheumatoid Factor (RF): IgM autoantibody targeting the Fc portion of IgG; present in 70-80% of RA patients (less specific than anti-CCP).
• Radiographic Features: Soft tissue swelling, periarticular osteopenia (demineralization), joint space narrowing, and marginal bony erosions.

Canadian Rheumatology Association (CRA) Management Guidelines

1. Early DMARD Initiation: Initiate Disease-Modifying Antirheumatic Drugs (DMARDs) as soon as diagnosis is established (target within 3 months of symptom onset).
2. First-Line csDMARD: Methotrexate (MTX) $10\text{--}25\text{ mg}$ once weekly, co-prescribed with Folic Acid $5\text{ mg}$ weekly (administered 24 hours after MTX) to minimize gastrointestinal, mucocutaneous, and hematologic toxicity.
3. Alternative / Combination csDMARDs: Leflunomide, Sulfasalazine, or Hydroxychloroquine ("triple therapy": MTX + SSZ + HCQ).
4. Biologic DMARDs (bDMARDs) & Targeted Synthetics: TNF inhibitors (Infliximab, Adalimumab, Etanercept), IL-6 inhibitors (Tocilizumab), or JAK inhibitors (Tofacitinib).
5. Mandatory Safety Screening Prior to Biologics: Screen for latent Tuberculosis using a Tuberculin Skin Test (TST) or Interferon-Gamma Release Assay (IGRA), check Hepatitis B (HBsAg, anti-HBc) and Hepatitis C serology, and update killed/inactivated vaccines.

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Crystal-Induced Arthropathies

Gout

Gout is a crystal arthropathy caused by monosodium urate (MSU) tissue deposition secondary to chronic hyperuricemia.

• Clinical Presentation: Monoarticular flare of sudden, excruciating joint pain, erythema, warmth, and swelling. First Metatarsophalangeal (MTP) joint is affected in >50% of initial presentation (podagra).
• Synovial Fluid Analysis (Gold Standard): Arthrocentesis demonstrates needle-shaped, strongly negatively birefringent crystals under polarized light microscopy (yellow when parallel to the red compensator axis).
• Acute Flare Management: First-line options include high-dose NSAIDs (Indomethacin, Naproxen), oral Colchicine ($1.2\text{ mg}$ loading dose followed by $0.6\text{ mg}$ 1 hour later; most effective within 36 hours of onset), or systemic/intra-articular corticosteroids.
• Chronic Urate-Lowering Therapy (ULT): Indicated for patients with $\ge 2$ flares/year, tophi, urate nephrolithiasis, or radiographic joint damage. Allopurinol (xanthine oxidase inhibitor) is first-line.
  • Screen for HLA-B*5801 allele prior to starting allopurinol in high-risk populations (Han Chinese, Thai, Korean with CKD) to prevent severe cutaneous adverse reactions (SJS/TEN).
  • Prophylaxis Mandate: When initiating or titrating ULT, co-prescribe low-dose colchicine ($0.6\text{ mg}$ daily) or an NSAID for 3 to 6 months to prevent mobilization flares triggered by rapid changes in serum urate levels.

Calcium Pyrophosphate Deposition (CPPD / Pseudogout)

• Synovial Fluid Analysis: Rhomboid-shaped, weakly positively birefringent crystals (blue when parallel to red compensator axis).
• Radiographs: Chondrocalcinosis (linear calcification of articular cartilage/menisci in the knees or TFCC of the wrist).

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Seronegative Spondyloarthropathies (SpA)

Seronegative spondyloarthropathies share common characteristics: Absence of Rheumatoid Factor (seronegative), strong association with HLA-B27, axial skeleton and sacroiliac joint inflammation, enthesitis (inflammation at tendon insertion sites), dactylitis ("sausage digits"), and extra-articular features (anterior uveitis).

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Systemic Lupus Erythematosus (SLE)

SLE is a multi-system autoimmune disease characterized by antinuclear autoantibody production and immune-complex deposition.

Clinical Spectrum (SOAP BRAIN MD)

• Serositis (pericarditis, pleuritis).
• Oral/nasopharyngeal ulcers (painless).
• Arthritis (non-erosive inflammatory polyarthritis affecting $\ge 2$ peripheral joints).
• Photosensitivity.
• Blood dyscrasias (autoimmune hemolytic anemia, leukopenia $<4.0 \times 10^9\text{/L}$, lymphopenia, or thrombocytopenia $<100 \times 10^9\text{/L}$).
• Renal disorder (Lupus Nephritis — proteinuria $>0.5\text{ g/day}$ or red cell casts; requires renal biopsy to classify Class I–VI).
• ANAs positive (highest sensitivity, $>95%$).
• Immunologic tests: Anti-dsDNA (high specificity; correlates with disease activity and renal flares), Anti-Smith (most specific autoantibody), Anti-Ro/SSA, Anti-La/SSB.
• Neurologic disorder (seizures, psychosis).
• Malar rash (fixed erythematous rash over cheekbones sparing nasolabial folds).
• Discoid rash.

Management Protocols

• Hydroxychloroquine (HCQ): Recommended for ALL SLE patients regardless of disease severity. It reduces flare rates, organ damage accumulation, and overall mortality. Requires baseline and annual ophthalmology screening after 5 years to monitor for retinal toxicity.
• Systemic Corticosteroids: Used for acute disease flares.
• Immunosuppressants: Mycophenolate Mofetil or Cyclophosphamide indicated for severe organ involvement (Class III/IV Lupus Nephritis).

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Systemic Sclerosis (Scleroderma) & Vasculitides

Systemic Sclerosis

Systemic sclerosis is characterized by vascular dysfunction, cutaneous fibrosis, and internal organ damage.

• Limited Cutaneous SSc (CREST Syndrome): Calcinosis, Raynaud's phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasias. Associated with Anti-Centromere antibodies. High risk of isolated Pulmonary Arterial Hypertension (PAH).
• Diffuse Cutaneous SSc: Rapid skin tightening extending proximal to elbows/knees and involving trunk. Associated with Anti-Scl-70 (anti-topoisomerase I) antibodies. High risk of Interstitial Lung Disease (ILD) and Scleroderma Renal Crisis.
• Scleroderma Renal Crisis: Abrupt onset of severe hypertension, acute renal failure, and microangiopathic hemolytic anemia.
  • Treatment: Immediate administration of ACE Inhibitors (e.g., Captopril).
  • Exam Trap: High-dose systemic corticosteroids are contraindicated in diffuse scleroderma as they can precipitate renal crisis.

ANCA-Associated Small Vessel Vasculitides

• Granulomatosis with Polyangiitis (GPA / Wegener's): Triad of upper respiratory tract (chronic sinusitis, saddle nose deformity), lower respiratory tract (pulmonary nodules, cavitary lesions, hemoptysis), and pauci-immune glomerulonephritis. Strongly associated with PR3-ANCA (c-ANCA).
• Microscopic Polyangiitis (MPA): Glomerulonephritis and pulmonary capillaritis without granulomatous inflammation. Associated with MPO-ANCA (p-ANCA).
• Treatment: Induction with high-dose pulse corticosteroids plus Cyclophosphamide or Rituximab.