Gout and pseudogout (crystal arthropathies)

Gout and pseudogout pathophysiology

Gout and pseudogout are crystal arthropathies
Crystals of urate (in gout) and calcium pyrophosphate (in pseudogout) are precipitated in joints
Neutrophils phagocytose the crystals whilst releasing pro-inflammatory cytokines which trigger attacks
Asymptomatic deposition of crystals between attacks is normal; what triggers an attack is unknown

Alcohol
Chronic renal disease
Hypertension, hyperlipidaemia, diabetes i.e. cardiovascular risk factors (majority of cases)
Medications
- Diuretics, aspirin
Malignancy (high cell turnover)
- Lymphoproliferative and myeloproliferative disorders
Certain genetic disorders e.g. G6PD

Acute urate synovitis (acute attack of gout – what is mainly covered here).
- Classically, acute gout affects the first MTP (podagra): initial presentation in 50%.
- Other joints include ankles, wrists, fingers & knees.
- Clinical features are sudden onset exquisite tenderness, swelling, redness.
Polyarticular gout
- Initial presentation in 10%, particularly elderly women
Rheumatoid-like (usually when becomes chronic)
- May have gouty tophi: smooth, white deposits of uric acid in the skin and around joints
Urate renal stone formation
- Can precede gout in 15%

Often similar to gout with acute presentation, but can also be a chronic inflammatory arthritis
Typically knees, wrists, ankles, elbows i.e. large joints

Always exclude septic arthritis in acutely painful joint
- Increased risk in, and may co-exist with, crystal arthropathy
Joint fluid microscopy
- Usually need to specifically request crystals (as well as MC&S)
- Gout: needle-shaped, negatively-birefringent crystals (when viewed under plain polarised light)
  - Positive in about 85% cases
- Pseudogout: rhomboid, positively-birefringent crystals (when viewed under plain polarised light)
Bloods
- Serum urate
  - May be elevated during an attack, but may also be suppressed (15%)
  - Therefore a normal urate does not exclude gout
- U&Es:
  - Look for underlying renal impairment
- Lipids & glucose
Plain XR
- Gout: punched-out lesions, sclerosis and tophi in chronic gout (with preservation of joint space)
- Pseudogout: chondrocalcinosis (calcification of cartilage)
Ultrasound
- ‘Double contour’ sign in gout: hyperechoic, irregular band over the superficial margin of the articular cartilage (present in over 90%)

NSAID
- E.g. Naproxen 500mg BD for 2-5 days, then reduce dose
Colchicine
- E.g. Colchicine 5mg BD
- Higher levels can cause GI upset so start slowly to avoid this
In patients who are intolerant of NSAIDs and colchicine (e.g. renal impairment), a short course of oral steroids may be used
- 40mg od for three days, then taper over 2 weeks
Intra-articular steroids may be used in mono-articular attacks

Lifestyle advice
- Reduce alcohol, healthy diet, optimise weight, increase activity
Treat modifiable risk factors
- Change diuretics, optimise renal function, treat hyperlipidaemia
Allopurinol (xanthine oxidase inhibitor)
- Indicated in:
  - Recurrent attacks, gouty tophi, urate nephropathy, radiographic changes of gout
- Do not start during an acute attack as will worsen it
- Titrate up to maximum tolerated dose (max 900mg/day)
  - Target urate is <300µmol/L
- Contraindicated in renal failure
- Small risk of severe allopurinol hypersensitivity reaction
Febuxostat (another xanthine oxidase inhibitor)
- Can be used in patients with renal impairment
- Indicated in those intolerant to allopurinol/ineffective in maximum tolerated dose