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Friday, November 12, 2010

Gout

Definition

Disorder of purine metabolism characterised by hyperuricaemia and recurrent attacks of acute synovitis due to urate crystal deposition
Associated with accumulation of articular, osseous, cartilaginous and soft tissue crystalline deposits (tophi)


Aetiology

Hyperuricaemia is the common denominator of the syndrome (all patients with gout have hyperuricaemia)
If levels increase above its solubility® crystal deposition
Hyperuricaemia is present in 2 - 18% of the population but only 5% of patients with hyperuricaemia® gout

Primary Hyperuricaemia

(Secondary to disordered uric acid metabolism)
Accounts for 95%
Inherited disorder with over production (20%) or under excretion (80%)
Classification based on 24 hour urine collection and urate excretion

Secondary Hyperuricaemia

Gout is a secondary feature of a number of genetic, or acquired processes and accounts for 5% of cases

Over-production:
Myelo-proliferative and lympho-proliferative disorders
(polycythemia, thrombocytopenia, myeloid metaplasia, leukaemias, lymphomas, paraprotinaemias, haemolytic anaemias, pernicious anaemia, infectious mononucleosis)
Cytotoxic and radiation therapy for malignancy
Psoriasis

Under excretion:
Renal disease
Drugs (thiazide diuretics and low dose salicylates)
Hyper and hypoparathyroidism
Myxoedema

Contributing Factors:
Diabetes
Hypertension and coronary heart disease
Excessive alcohol intake
High purine diets
Obesity
Low urine volume with normal renal function

90% of patients with gout have a disorder of uric acid excretion and drugs that alter renal tubular function can contribute to the occurrence of gout (eg diuretics, aspirin, ethanol)

Diuretics are the most common cause of secondary hyperuricaemia due to volume depletion and enhanced tubular resorption of urate
Increased risk of developing the disease with increasing age and serum urate concentration
Genetic studies suggest multi factorial inheritance


Incidence

20 - 30 / 100,000
Prevalence 0.13 - 0.37 % of population
Male : Female 20:1 (5% of cases are female)
Males usually more than 35 years, women usually more than 55 years
Gout is the most common form of inflammatory disease in men over 30 years of age
Rarely seen before the menopause in women


Clinically

Stages of Disease

Asymptomatic hyperuricaemia
Acute gouty arthritis
Inter-critical gout
Chronic tophacious gout

Acute Attack

Sudden attack of joint pain lasting several days
May follow trauma, surgery, drugs, exercise or alcohol
Commonly affects MTP joint of great toe (at least 50% of initial attack and 90% at some stage), also ankle and finger joints and the olecranon bursa
Joints feel hot and extremely tender
Hyperuricaemia is present at some stage
7% never have a second attack
60%® recurrent attack within one year
Negative birefringent crystals are seen in synovial fluid® diagnosis
X-Rays: Soft tissue swelling

Chronic Gout

Recurrent attacks® poly-articular gout, usually more severe, more prolonged and associated with fever
May be difficult to differentiate from other inflammatory arthropathies or infection

Joint erosions® chronic pain, stiffness and deformity
Tophi may appear around joints, olecranon and pinna of the ear
May ulcerate through the skin® discharge chalky material
Only a minority of patients develop visible tophi, permanent joint changes or chronic symptoms
Renal calculi may form and parenchymal renal disease occur secondary to crystal deposition with some renal dysfunction occurring in 90% of patients with gouty arthritis
In 10% gout is preceded by nephrolithiasis
Typically the first attack occurs during the night and tends to subside after 3 - 10 days
Tophi generally noted an average of 10 years after the first attack

X-Rays:
Symmetrical punched out cysts in extra-articular bone
Bony erosions either extra-articular or articular
Joint space is preserved until late in the disease


Pathology

Histopathology

Tophi® chronic foreign body granulation tissue surrounding urate crystals
Uric acid crystals deposited in synovium, tendons and tendon sheaths and articular cartilage
Results in activation of acute inflammation® cartilage degeneration and peri-articular cysts formation secondary to deposition of mono-sodium urate
Large cartilage and soft tissue tophi appear


Investigations

If excretion of uric acid is greater than 750mg per 24 hours suggests over production of urate
Measure 24 hour urate excretion after 1 week of a purine free diet® over production if more than 600mg and under excreter if less than 350mg per 24 hours
Synovial fluid® high cell count more than 90% neutrophils
Urate crystals usually remain in the synovium after the acute attack has settled

Compensated polarised light microscopy

With polarising filters and a first order red compensator monosodium urate crystals are 3-20mm in length needle shaped and strongly negatively birefringent (yellow in colour when the crystal axis is parallel to the compensator)
Calcium pyrophosphate crystals are short, rhomboidal and weakly positively birefringent (blue when the crystal axis is parallel to the compensator)


Differential Diagnosis

Infection
Reiters disease
Pseudo-gout (tends to affect large rather than small joints)
Rheumatoid arthritis
Arthritis mutilans


Treatment

Aim of therapy

Terminate the acute at

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