Key Facts

Crystal arthropathies are inflammatory joint diseases caused by crystal deposition. The two main types are gout (monosodium urate) and calcium pyrophosphate deposition disease (CPPD/pseudogout).

Epidemiology

• Gout: prevalence ~2.5–3.9% in the UK; most common inflammatory arthritis in men; M:F 3.5:1
• CPPD: increases with age; ~50% of >85 year olds have chondrocalcinosis on X-ray (most asymptomatic)

Aetiology

Gout:

• Hyperuricaemia → urate crystal deposition
• Under-excretion of urate (~90%): CKD, diuretics (thiazides, loop), low-dose aspirin
• Over-production (~10%): myeloproliferative disorders, tumour lysis syndrome
• Diet: red meat, shellfish, alcohol (especially beer), fructose-sweetened drinks

CPPD:

• Idiopathic (most common; age-related)
• Secondary: haemochromatosis, hyperparathyroidism, hypomagnesaemia, hypothyroidism

Pathophysiology

• Crystal deposition in synovium → phagocytosis by macrophages → NLRP3 inflammasome activation → IL-1β release → intense neutrophilic inflammation
• Gout: supersaturation of urate → crystal nucleation in avascular tissues (cartilage, tendons, bursae)
• CPPD: CPP crystals form in hyaline and fibrocartilage → shed into joint space during 'crystal shedding' → acute inflammation

Gout

• Acute monoarthritis (>80%): 1st MTP (podagra ~70% first presentation), ankle, knee, wrist
• Exquisitely painful, red, hot, swollen joint
• Rapid onset (peaks within 12–24 hours)
• Triggers: dietary excess, alcohol, dehydration, surgery, acute illness, starting/stopping ULT
• Chronic tophaceous gout: tophi (chalky white deposits in soft tissue — ears, elbows, fingers, Achilles)

Pseudogout (CPPD)

• Acute pseudogout: monoarthritis (knee most common, then wrist) — clinically identical to gout or septic arthritis
• Often triggered by acute illness, surgery, or metabolic disturbance
• Chronic CPPD: may mimic OA or RA

Red Flags

• Cannot exclude septic arthritis without aspiration (clinical overlap)
• Fever and systemically unwell (septic arthritis coexisting)
• Polyarticular crystal arthritis mimicking sepsis

Bedside

• Joint aspiration (ESSENTIAL): appearance (turbid), WCC, Gram stain, culture, polarised light microscopy
  • Gout: negatively birefringent needle-shaped crystals
  • CPPD: weakly positively birefringent rhomboid crystals

Bloods

• Serum urate: may be normal/low during acute gout flare (unhelpful acutely; measure 2–4 weeks after)
• FBC, CRP/ESR: inflammatory markers elevated
• U&Es: CKD (risk factor)
• LFTs: before starting allopurinol

Imaging

• X-ray:
  • Gout: soft tissue swelling (acute); punched-out erosions with overhanging edges, tophi (chronic)
  • CPPD: chondrocalcinosis (linear calcification in cartilage — knee menisci, triangular fibrocartilage of wrist, pubic symphysis)
• Dual-energy CT (DECT): highly specific for gout (identifies urate deposits); emerging role
• USS: double contour sign on joint cartilage surface (gout)

Gout — Acute Flare

• NSAID: naproxen 750mg stat then 500mg BD (first-line) + PPI
• Colchicine 500mcg BD–TDS: if NSAID contraindicated (renally adjust; avoid if eGFR <10)
• Prednisolone 30mg OD × 5 days: if NSAIDs and colchicine contraindicated
• Intra-articular corticosteroid: if single joint accessible
• IL-1 inhibition (anakinra/canakinumab): refractory or contraindications to above

Gout — Prophylaxis (Urate-Lowering Therapy)

• Allopurinol (first-line): start 100mg OD, titrate by 100mg/month to target urate <360 µmol/L (<300 if tophi)
  • Start low, go slow (especially CKD: start 50mg)
  • Cover with colchicine 500mcg OD for 6 months when starting ULT
  • Do NOT start during acute flare (wait 2–4 weeks)
• Febuxostat 80–120mg OD: if allopurinol intolerant/contraindicated (NICE TA164)
• Uricosuric agents (probenecid, lesinurad): add-on if target not met

Pseudogout — Acute

• NSAIDs, colchicine, or corticosteroids: same as gout acute management
• Joint aspiration itself is therapeutic
• No effective prophylactic therapy (no equivalent of ULT)
• Treat underlying cause if secondary (iron studies for haemochromatosis, calcium/PTH, Mg, TFTs)

Referral Criteria

• Rheumatology: refractory gout, tophaceous gout, diagnostic uncertainty, young CPPD (screen for secondary cause)

• Gout with ULT: excellent — target urate achievable in ~80%; flare frequency reduces significantly
• Without ULT: progressive joint damage, tophaceous gout, CKD, cardiovascular risk
• CPPD: no disease-modifying treatment; generally good prognosis for acute episodes
• Chronic CPPD: may cause progressive joint damage resembling OA
• Gout mortality: associated with increased cardiovascular mortality (urate is a cardiovascular risk factor)

Crystal Comparison