• Differential diagnosis of joint diseases
• Diagnostic workup (CBC, anti-CCP, RA, ANA, DNA, autoimmunity tests)
• Arthrocentesis indications
• Plain radiographs of joints
• Treatment of rheumatologic diseases
• Crystalline arthropathies (gout, pseudogout)

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Rheumatology Learning Objectives: GM 7.10 - GM 7.17

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GM 7.10 - Differential Diagnosis of Joint Diseases (Prioritized by Clinical Features)

• Monoarthritis (1 joint): gout, septic arthritis, pseudogout, trauma, reactive arthritis (early)
• Oligoarthritis (2-4 joints): reactive arthritis (Reiter's), psoriatic arthritis, enteropathic arthritis
• Polyarthritis (>4 joints): RA, SLE, viral arthritis, osteoarthritis (OA)

• Acute (hours): septic arthritis, gout, pseudogout, hemarthrosis
• Subacute/chronic: RA, SLE, OA, psoriatic arthritis

• Skin rash (malar rash): SLE
• Psoriatic plaques: psoriatic arthritis
• Urethritis + conjunctivitis + arthritis: reactive arthritis (Reiter's triad)
• Subcutaneous nodules: RA
• Tophi: gout
• Iritis, oral ulcers: ankylosing spondylitis, Behcet's

• Diabetes (septic arthritis risk, Charcot joint)
• Hypothyroidism (can cause non-inflammatory arthralgia)
• Hemochromatosis (calcium pyrophosphate deposition)
• Hyperparathyroidism

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GM 7.11 - Diagnostic Workup Based on Presumed Aetiology

Indications and Interpretation of Tests

• Leukocytosis: suggests septic arthritis or systemic infection
• Anaemia of chronic disease: common in RA (normocytic normochromic)
• Thrombocytosis: seen in active RA, reactive arthritis
• Thrombocytopenia + lymphopenia: SLE (lupus)

• Both elevated in inflammatory arthritis
• CRP is a more sensitive acute-phase reactant
• Useful to monitor disease activity and treatment response

• Autoantibody to IgG Fc fragment
• Positive in ~70-80% of RA patients
• NOT specific for RA - also positive in: SLE, Sjogren's, hepatitis, TB, infective endocarditis, normal elderly
• RF-positive RA has more severe, erosive, extraarticular disease

• More specific than RF for RA (specificity ~97%)
• Positive earlier in disease course (can precede symptoms by years)
• Predicts erosive/destructive joint disease
• Anti-CCP + RF positivity = high likelihood of RA

• Screening test for SLE and other connective tissue diseases
• Positive ANA alone is not diagnostic (positive in 5% of normal population)
• ANA titre >1:160 is clinically significant
• Patterns and their associations:
  • Homogeneous/diffuse: SLE, drug-induced lupus
  • Speckled: SLE, Sjogren's, MCTD, SSc
  • Nucleolar: systemic sclerosis (diffuse)
  • Centromere: limited systemic sclerosis (CREST)

• Highly specific for SLE (~95% specific)
• Titre correlates with disease activity, especially lupus nephritis
• Used to monitor SLE flares

• Elevated (>7 mg/dL men, >6 mg/dL women) in gout
• Note: may be normal during acute attack; not diagnostic alone

• Low in active SLE (consumed by immune complex deposition)
• Normal/elevated in RA

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GM 7.12 - Indications for Arthrocentesis

Specific Indications:

1. Suspected septic (infectious) arthritis - most urgent indication; must rule out joint infection
2. Crystal analysis - to diagnose gout or pseudogout
3. Drain large hemarthrosis - secondary to trauma or injury
4. Intra-articular medication injection - corticosteroids, local anaesthetic
5. Evaluate laceration for possible extension into the joint

Contraindications:

• Absolute: Needle must pass through cellulitis or infected overlying skin
• Relative: Coagulopathy (but can be performed with INR in therapeutic range with <0.5% complication rate); prosthetic joints (discuss with orthopedic surgeon first)
• If septic arthritis is strongly suspected, perform arthrocentesis even in anticoagulated patients

Complications:

• Inoculation of infection into the joint
• Bleeding (intra-articular or external)
• Pain, allergic reaction to injected medication
• Adverse effects of intra-articular corticosteroids

Algorithm for Arthrocentesis in Suspected Septic Joint:

Synovial Fluid Analysis - Key Findings:

• Gout: Monosodium urate crystals - needle-shaped, negatively birefringent (yellow under parallel polarized light)
• Pseudogout (CPPD): Calcium pyrophosphate crystals - rhomboid-shaped, positively birefringent (blue under parallel polarized light)
• Note: Presence of crystals does NOT rule out co-existing infection

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GM 7.13 - Plain Radiographs of Joints

When to Request X-rays:

• Suspected fracture or infection
• History of malignancy
• Physical examination fails to localize source of pain
• Pain persists despite conservative treatment
• Baseline before starting disease-modifying therapy

Radiographic Findings by Disease:

• Early: Periarticular soft tissue swelling, periarticular osteoporosis (juxta-articular)
• Late: Marginal bony erosions (at "bare areas" where synovium contacts bone), joint space narrowing, subluxation
• Distribution: Hands and feet - MCP, PIP, wrist joints; symmetric

• Joint space narrowing (non-uniform/asymmetric)
• Subchondral sclerosis (increased bone density under cartilage)
• Osteophytes (bone spurs at joint margins)
• Subchondral cysts
• No periarticular osteoporosis

• Acute: Soft tissue swelling only
• Chronic tophaceous gout: "Punched-out" erosions with overhanging edges (rat-bite erosions), NO periarticular osteoporosis (bone density preserved), tophi (soft tissue calcifications), asymmetric

• Chondrocalcinosis: calcification in fibrocartilage (menisci of knee, triangular fibrocartilage of wrist, symphysis pubis) - pathognomonic
• Joint space narrowing

• Sacroiliitis: joint space widening then sclerosis then fusion
• Bamboo spine: squaring of vertebrae + syndesmophytes (vertical)
• Classic sign: "shiny corner" (Romanus lesion)

• "Pencil-in-cup" deformity (destruction of base of phalanx, erosion of distal phalanx head)
• DIP joint involvement
• Periosteal reaction ("ivory" phalanx)

• Early: soft tissue swelling, joint effusion, periarticular osteoporosis
• Late (if untreated): rapid joint space narrowing, bone destruction

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GM 7.15 / GM 7.17 - Treatment Plan for Rheumatologic Diseases

Rheumatoid Arthritis Treatment:

• Early, aggressive treatment is essential to prevent joint destruction

• 70% of RF-positive polyarticular RA develops joint damage/erosion within 2 years without treatment

• Almost all patients should start a DMARD as soon as diagnosis is confirmed

• Ibuprofen, naproxen, diclofenac
• Used for pain and inflammation while DMARDs take effect (weeks to months)

• Methotrexate (MTX): most commonly used; weekly dosing; requires folic acid supplementation; monitor LFTs, CBC
• Hydroxychloroquine (HCQ): for mild disease; monitor for retinopathy
• Sulfasalazine: for mild-moderate disease
• Leflunomide: alternative to MTX

• Anti-TNF agents: Etanercept, Infliximab, Adalimumab, Certolizumab, Golimumab
• Abatacept (T-cell co-stimulation blocker)
• Rituximab (anti-CD20, B-cell depleting)
• Tocilizumab (anti-IL-6 receptor)

• JAK inhibitors: Tofacitinib, Baricitinib, Upadacitinib

• Short-term "bridge" therapy while DMARDs take effect
• Low-dose prednisolone (<10 mg/day) for disease control
• Intra-articular injections for localized flares

• Patient education, joint protection
• Physical and occupational therapy
• Exercise to improve ROM and function
• Surgery (joint replacement) for severe destruction

SLE Treatment:

• Mild (skin, joints): NSAIDs + hydroxychloroquine (all SLE patients)
• Moderate: Low-dose corticosteroids + hydroxychloroquine
• Severe (nephritis, CNS, haematologic): High-dose corticosteroids + cyclophosphamide or mycophenolate mofetil
• Maintenance: Azathioprine, mycophenolate mofetil
• Biologics: Belimumab (anti-BLyS), Anifrolumab (anti-type I IFN)
• Sun protection, avoid triggers (UV, infections, certain drugs)

Ankylosing Spondylitis Treatment:

• NSAIDs (first-line, continuous use)
• Physiotherapy (essential - extension exercises, posture)
• Anti-TNF biologics (for NSAID-refractory disease)
• IL-17 inhibitors: Secukinumab, Ixekizumab
• No benefit from DMARDs for axial disease

Osteoarthritis Treatment:

• Non-pharmacological: Weight reduction, exercise, physiotherapy, assistive devices
• Topical NSAIDs (first-line for hand and knee OA)
• Oral NSAIDs / COX-2 inhibitors
• Intra-articular corticosteroids (for acute flares)
• Intra-articular hyaluronic acid (for knee OA)
• Surgery: Joint replacement for severe/refractory disease

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GM 7.16 - Crystalline Arthropathies: Medications for Joint Pain and Preventive Therapy

GOUT

1. Asymptomatic hyperuricemia
2. Acute intermittent gout
3. Intercritical gout (symptom-free between attacks)
4. Chronic tophaceous gout

A. Treatment of Acute Gout Attack:

• Indomethacin 50 mg TDS for 2 days then taper, OR
• Naproxen, ibuprofen at maximum doses
• Taper over 1-2 weeks
• Contraindicated in renal impairment, peptic ulcer disease

• Mechanism: Inhibits microtubule polymerization; decreases neutrophil migration and phagocytosis of urate crystals
• Dose: 1 mg initially, then 0.5 mg 1 hour later (modern low-dose protocol)
• Side effects: Nausea, vomiting, diarrhoea (dose-limiting GI toxicity)
• Best when started within 12-24 hours of attack onset
• IV route now avoided (bone marrow suppression, renal/hepatic toxicity)

• Oral: Prednisolone 0.5 mg/kg/day, taper by 5 mg/day
• Intra-articular: Triamcinolone hexacetonide 10-40 mg (large joints), 5-20 mg (small joints) - preferred for monoarticular attack
• IM/IV ACTH: 40-80 mg every 8-12 hours (last resort)

B. Preventive / Urate-Lowering Therapy (ULT):

• Recurrent attacks (≥2/year)
• Presence of tophi
• Uric acid nephrolithiasis
• Uric acid level >12 mg/dL
• Patients undergoing cancer chemotherapy
• Renal damage from gout

• Mechanism: Inhibits xanthine oxidase, reducing uric acid production
• Effective regardless of cause (overproduction or underexcretion)
• Start at 100 mg/day with food, increase by 100 mg/day at weekly intervals
• Target: Serum uric acid <6 mg/dL
• Usual dose: 200-300 mg/day (up to 600 mg/day)
• Adjust dose in renal impairment
• Side effects: Rash (can cause severe hypersensitivity - allopurinol hypersensitivity syndrome, especially in HLA-B*58:01 carriers), hepatotoxicity, bone marrow suppression

• Alternative to allopurinol
• Useful in allopurinol intolerance or renal impairment
• Monitor cardiovascular events

• Mechanism: Blocks renal tubular reabsorption of urate, increases excretion
• Only effective if normal/good renal function
• Contraindicated with nephrolithiasis
• Adequate hydration required (>2 L/day urine output)
• Drug interactions: reduces excretion of penicillin, methotrexate

• 0.5 mg twice daily for 3-6 months while initiating ULT
• Prevents precipitation of acute attacks when uric acid levels are fluctuating

• Avoid alcohol (especially beer - high in purines)
• Reduce high-purine foods (red meat, organ meats, shellfish)
• Avoid aspirin, diuretics if possible
• Maintain hydration
• Weight reduction

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PSEUDOGOUT (Calcium Pyrophosphate Deposition Disease - CPPD)

• NSAIDs (same as gout)
• Colchicine
• Intra-articular or oral corticosteroids
• NOTE: No equivalent of allopurinol/ULT for CPPD (no drug reliably prevents CPPD crystal formation)
• Treat any underlying metabolic cause (hyperparathyroidism, haemochromatosis)

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Summary Table: Key Differentiating Features

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• Harrison's Principles of Internal Medicine, 22nd Edition (2025)
• Textbook of Family Medicine (Rakel, 9th Edition), Chapters 32-33
• Rosen's Emergency Medicine: Concepts and Clinical Practice, 9th Edition, pp. 2331-2335
• *Grainger & Allison's Diagnostic Radiology, p. 1125 (Crystal Arthropathies)*All 7 learning objectives are now covered. Here's a quick orientation to the full answer above:

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What Was Covered

• Anti-CCP is more specific than RF for RA; anti-dsDNA is specific for SLE and tracks disease activity
• Gout crystal = negatively birefringent, needle-shaped; pseudogout = positively birefringent, rhomboid
• Never start allopurinol during an acute gout attack; cover with colchicine for 3-6 months
• Synovial WBC >50,000 = presumptive septic arthritis until proven otherwise
• Chondrocalcinosis on X-ray = pseudogout (CPPD); punched-out erosions = chronic gout