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Gout /hyperuricaemia.
Cardinal features of gout
Increase in serum uric acid concentration (>7.0 mg/dL in males and >6.0 mg/dL in females).
Recurrent attacks of a characteristic acute arthritis, in which crystals of monosodium urate monohydrate are demonstrable in leucocytes of synovial fluid.
Aggregated deposits of monosodium urate monohydrate (tophi) in and around the joints.
Renal disease involving interstitial tissue and blood vessels.
Uric acid nephrolithiasis.
Aetiology of gout and hyperuricaemia
Increased production of uric acid Decreased renal excretion of uric acid
Increased purine synthesis de novo Renal failure
Hypoxanthine-guanine-phosphoribosyl Lead poisoning
transferase (HGPRT) deficiency Alcohol
Phosphoribosyl pyrophosphate (PRPP)
Drugs—diuretics, low dose aspirin, pyrazinamide, cyclosporin levodopa
synthetase overactivity
Lactic acidosis
Glucose-6-phosphatase deficiency
Hyperparathyroidism
Idiopathic
Myxoedema
Increased turnover of purine,s
Down's syndrome
Myeloproliferative disorders
Unidentified inherited defects
Lymphoproliferative disorders
Cancer chemotherapy
Haemolysis
Clinical features
The full natural history of gout comprises four stages:
1.Asymptomatic hyperuricaemia.
2.Acute gouty arthritis.
3.Intercritical period.
4.Chronic tophaceous gout (tophi and chronic gouty arthritis).
The onset may be insidious or explosively sudden.
The metatarsophalangeal joint of the great toe is the site of the first attack of acute gouty arthritis (podagra) in 70% of patients.
Other joints which can get affected include tarsal joints, ankles, knees and wrists. Central joints such as hips, shoulders and spine are seldom affected, possibly because higher temperatures in these joints are not conducive to crystallisation.
The affected joint is hot, red and swollen, with shiny overlying skin and dilated veins. The joint is excruciatingly painful and tender. These joint manifestations may be associated with anorexia, nausea, fever, leucocytosis and raised ESR.
The joint manifestations may last only a day or two, or up to several weeks, but characteristically subside spontaneously. 0 Gout can also cause bursitis and tenosynovitis.
This is followed by an asymptomatic phase (intercritical period) which is diagnostically important.
In chronic tophaceous gouty arthritis, crystal deposits appear in cartilage, synovial membranes, tendons and .soft tissues. The classic location of a tophus is the helix and antihelix of the ear.
Nephropathy
Nephropathy is seen in 90% of subjects with gouty arthritis. Two types of parenchymal renal damage have been described:
Urate nephropathy results from deposition of urate crystals in the interstitial tissue, leading to albuminuria, isosthenuria or renal failure.
Obstructive uropathy (nephrolithiasis) results from the formation of uric acid crystals in the collecting tubules, renal pelvis or ureter with blockage of urine flow. The formation of urate calculi is favoured by hyperuricosuria, purine overproduction, excessive purine ingestion, uricosuric drugs and acidic urine.
Other features
Gout may be associated with increased incidence of hypertension and cardiovascular disorders. 0 On the other hand, hypertension is also a risk factor for development of gout.
Diagnosis
Serum uric acid levels are elevated. However, during an acute attack, serum uric acid may be normal in 50% cases. 0 Synovial fluid examination by compensated polarised microscopy can demonstrate urate crystals. They are seen as slender, needle-shaped, negatively birefringent structures.
Plain radiographs are helpful to differentiate chronic tophaceous gout from rheumatoid arthritis.
Erosions in gout are characteristically punched out with overhanging sclerotic margins and are situated away from joint margins, sometimes outside the joint capsule.
Rheumatoid arthritis causes marginal erosions, always within the limits of the joint capsule.
Periarticular osteopaenia is absent and joint space is preserved in gout,
Management
Treatment of acute attack
NSAIDs are the agents of choice. All NSAIDs are equally effective. Commonly used NSAIDs. are indomethacin (50 mg 6 hourly), naproxen, fenoprofen and phenylbutazone.
Colchicine is the second choice of drug. It is highly effective at a dose of 1.0 mg stat followed by 0.5 mg hourly till symptoms subside or GI side effects (vomiting and diarrhoea) occur or a total of 4 mg of colchicine has been given.
If patient does not tolerate NSAIDs or colchicine, intra-articular corticosteroids may be tried if a medium or large joint is involved.
In patients with polyarticular involvement not responding to NSAIDs or colchicine, prednisolone 20-30 mg/day with tapering over 7-10 days is effective.
Prophylaxis
Avoidance of alcohol.
Avoidance of meat and seafood. However, consumption of oatmeal and purine-rich vegetables (for example, peas, beans, lentils, spinach, mushrooms and cauliflower) does not produce increased risk of gout.
Controlled weight reduction in obese patients.
Drugs for prophylaxis
62% of patients 'experience a second episode within 1 year, 78% within 2 years, while 7% have no further episode for 10 years even without anti-hyperuricaemic drugs.
Anti-hyperuricaemic drugs are therefore appropriate under following circumstances:
Frequent episodes.
Chronic tophaceous gout.
Radiological erosions.
Urate calculi.
Asymptomatic patients with urinary urate excretion >1100 mg/24 hours (there is a 50% chance of developing renal calculi in these patients).
Persistently raised serum urate (>13 mg/dL in males and >10 mg/dL in females) as there is high risk of urate nephropathy.
Allopurinol reduces uric acid production through competitive inhibition of xanthine. oxidase, which converts xanthine and hypoxanthine to uric acid. Its dose is 300-900 mg daily.
Uricosuric agents like probenecid and sulphinpyrazone are indicated in selected cases (when uric acid excretion in the urine is below 600 mg/day). Uricosuric drugs are risky if urinary urate excretion is already >800 mg/24 hours. These are contraindicated in those with urate calculi. Uricosurics are ineffective in renal impairment (creatinine clearance <50 mL/minute).
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