Both gout and pseudogout are forms of crystal-induced inflammatory arthritis caused by the deposition of mineral crystals within joint spaces, tendon sheaths, and surrounding soft tissues. Gout is caused by chronic hyperuricemia (serum uric acid > 6.8 mg/dL) which causes saturation and crystallization of Monosodium Urate (MSU) in peripheral joints. Pseudogout is caused by Calcium Pyrophosphate Dihydrate (CPPD) crystals in articular cartilage and synovial fluid.

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Causes

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Gout (Monosodium Urate)​

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• Under- or overexcretion of monosodium urate

  • Underexcretion (~90%): Renal insufficiency, diuretics (thiazides, loops), metabolic syndrome, alcohol.

  • Overproduction (~10%): Purine-rich diet (red meat, seafood, high-fructose corn syrup), tumor lysis syndrome, myeloproliferative disorders.
     

Pseudogout (Calcium Pyrophosphate Deposition - CPPD)

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• Often idiopathic and age-related (>60 years). Associated metabolic triggers include:

  • Hyperparathyroidism (elevated calcium)

  • Hemochromatosis (iron overload)

  • Hypomagnesemia

  • Hypophosphatasia
     

Presentation 
 

Gout (MSU Crystals)

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• Primary Joint Site: 1st MTP Joint (Podagra, over 50% of cases), Ankles, Instep, Knees.

• Onset & Course: Hyperacute (peaks in 12 to 24 hours); intense pain, erythema, and warmth.

• Key Features: Tophi (urate deposits in pinna, olecranon, Achilles tendon).

• Demographics: Predominantly males (30 to 50 years old) and postmenopausal females.

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Pseudogout (CPPD Crystals)

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• Primary Joint Site: Knees (over 50% of cases), Wrists, MCP joints, Shoulders.

• Onset & Course: Acute or subacute flares; can mimic rheumatoid arthritis or osteoarthritis.

• Key Features: Chondrocalcinosis (punctate or linear cartilage calcification on X-ray).

• Demographics: Equal gender distribution; typically older adults (over 60 years old).

Diagnostics

1.  Synovial Fluid Analysis (Arthrocentesis)

 

Arthrocentesis with compensated polarized light microscopy provides the definitive diagnosis and rules out septic arthritis (must order Gram stain, culture, cell count if considering; often affects large weight-bearing joints).

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2. Serum Uric Acid (Gout)

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• Target Diagnostic Level: Elevated above 6.8 mg/dL (the physiological saturation threshold where monosodium urate crystals precipitate).

• Target Treatment Level: Below 6.0 mg/dL (or < 5.0 in late-stage tophaceous gout) once urate-lowering therapy is started.

• Important Clinical Trap: Up to 30% of patients have normal or low serum uric acid during an acute gout flare. Uric acid is an acute-phase reactant excreted more rapidly by the kidneys during systemic inflammation, so a normal level does not rule out an acute gout attack. Recheck serum uric acid 2 to 4 weeks after the flare resolves for an accurate baseline.

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3. Inflammatory Markers (Both Conditions)

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• Erythrocyte Sedimentation Rate (ESR) & C-Reactive Protein (CRP): Elevated during acute flares in both gout and pseudogout due to systemic neutrophil activation.

• Clinical Utility: Useful for tracking the resolution of an acute flare, but non-specific—they cannot distinguish crystal arthritis from septic arthritis or rheumatoid arthritis.

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4. Complete Blood Count (CBC) (Both Conditions)

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• Leukocytosis (Elevated WBC Count) with a neutrophilic predominance is common during acute flares.

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5. Renal Function Panel (Both Conditions)

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• BUN & Serum Creatinine / eGFR:

  • In Gout: Impaired renal excretion is the cause of hyperuricemia in ~90% of patients. Knowing baseline kidney function is critical before prescribing NSAIDs, Colchicine (requires dose adjustment), or Allopurinol.

  • In Pseudogout: Evaluates baseline organ function for safe medication selection.

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6.  Metabolic Screening for Pseudogout (The "4 Hs")

Because Calcium Pyrophosphate Deposition (CPPD) is frequently driven by underlying metabolic disorders, an initial diagnostic workup for pseudogout should include:

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• Serum Calcium & Intact PTH: Screens for Hyperparathyroidism.

• Serum Ferritin & Transferrin Saturation: Screens for Hemochromatosis (iron overload).

• Serum Magnesium: Screens for Hypomagnesemia.

• Serum Alkaline Phosphatase (ALP): Low levels screen for Hypophosphatasia.

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Acute & Chronic Management
 

Gout Protocols
 

• Acute Attack (First 24 to 48 Hours):

  • First-line: NSAIDs (Indomethacin, Naproxen) OR Oral Colchicine (1.2 mg then 0.6 mg 1 hour later).

  • Systemic or intra-articular corticosteroids if NSAIDs or Colchicine are contraindicated (e.g., in CKD).

• Chronic / Prevention:

  • Urate-Lowering Therapy (ULT): Allopurinol (xanthine oxidase inhibitor) or Febuxostat.

  • Target Uric Acid: Less than 6.0 mg/dL.

  • Maintain prophylactic NSAID or Colchicine during ULT initiation.

Pseudogout Protocols
 

• Acute Attack (First 24 to 48 Hours):

  • First-line: Intra-articular corticosteroid injection OR NSAIDs.

  • Oral Colchicine for acute flares or prophylaxis.

  • Systemic steroids if polyarticular.

  • Note: No specific crystal-lowering therapy exists.

• Chronic / Prevention:

  • Treat underlying metabolic drivers (e.g., iron overload, hyperparathyroidism).

  • Low-dose oral Colchicine (0.6 mg daily) for frequent recurring flares.

  • Joint replacement for advanced destructive joint disease.

Patient Lifestyle Modifications for Gout
 

• Hydration: Maintain daily fluid intake above 2–3 liters to encourage renal uric acid clearance.

• Dietary Adjustments: Limit intake of red meats, organ meats, shellfish, and foods sweetened with high-fructose corn syrup.

• Alcohol Restriction: Avoid beer and spirits (beer is high in purines and inhibits renal urate excretion).

• Weight Management: Gradual weight loss reduces baseline hyperuricemia (avoid rapid crash dieting, which can trigger acute flares via transient hyperuricemia).