A/Professor David Bossingham, James Cook University
Gout is common, crippling, capable of causing a premature death, poorly diagnosed, misunderstood and mismanaged which is tragic for sufferers when it is potentially manageable. It is an erosive arthritis which may be acute, recurrent or chronic, the result of crystals of uric acid provoking a profound inflammatory reaction in the synovial fluid.
Gout affects up to 5% of the Australian population with the greatest prevalence in males and post-menopausal women, it is very uncommon before puberty and can be associated with overindulgence in protein containing foods and alcohol but also has a strong familial basis.
Uric acid is the endpoint of protein metabolism, it is excreted through the kidney and liver at a ratio of 4:1. Normal blood levels are 0.25 – 0.48 mmol/l in men and 0.21 – 0.43 mmol/l in women over the age of 60, as a general rule menstruating women have much lower levels and these rise slowly with age. Greater than 0.36mmol/l uric acid is in a supersaturated solution; it is selectively reabsorbed in the kidney and genetically driven abnormalities of this pathway are the cause of familial gout and hyperuricemia seen in the Polynesian and Maori people. Hyperuricemia can also occur when there is increased protein turnover in inherited conditions, neoplastic, some inflammatory conditions and as a result of some medications most particularly thiazide diuretics.
Acute gout usually becomes apparent in the evening reaching its peak in the early hours, a monarthritis is more common affecting the first metatarsophalangeal joint, in later and more chronic cases it may involve almost any other joint. Severe pain may last up to five days but is commonly less, inflammation may be so profound that the overlying skin can exfoliate and it can be sufficient to prevent weight bearing. Peripheral joints are affected preferentially because the crystals most readily form in conditions of relative anoxia, acidemia and cold.
Tophi, accumulations of uric acid in the skin most commonly over the olecranon process, are unlikely to be seen before the first attack of arthritis, aspiration or expression of a tophus will produce yellow material in which the crystals are easily recognised. In older, postmenopausal women the arthritis can be more indolent and the distal interphalangeal joints of the fingers are commonly affected especially those affected by osteoarthritis with Heberden’s nodes.
Diagnosis is by examination of joint fluid under polarised light microscopy. Joint puncture should be performed as a matter of urgency, the principle differential is joint sepsis and failure to treat either will result in permanent joint damage within hours. Dual energy CT or DECT can suggest the presence of uric acid crystals in the synovium but is not yet an accepted diagnostic test.
Investigation should include renal and hepatic function, renal disease is a common finding especially diabetic nephropathy, abnormalities of the blood count can indicate a developing haematological disease. Hepatic abnormalities may be an indication of problems, ethanol induced disease is common. Measurement of uric acid is NOT indicated in the acute situation as normuricemia is common, check this a few days after the acute attack has passed.
Treatment of the acute attack is with NSAID’s classically Indomethacin 50mg TDS pc or Naproxen 500mg BD pc. If these drugs are contraindicated then colchicine 1mg stat and 500ug tds prn is recommended. Colchicine acts by inhibiting neutrophil chemotaxis and can cause abnormalities of neutrophil function as well as diarrhoea. Corticosteroids can be used a parenteral form, methyl prednisone 40mg by S/C injection is preferable. Whilst the pharmacological approach is very effective, a RICE regime should also be a part of management.
The consequences of chronic gout are apart from a severe destructive arthritis; hypertension, accelerated arterial disease, coronary artery insufficiency and premature death. The maxim that “Young men with recurrent gout rarely become old men” still holds. The association with alcohol is complex, gout in an alcoholic is difficult to treat without abstention, conversely many gout sufferers are lifelong teetotallers.
The treatment of hyperuricemia is central, dietary treatment has little to offer, those who grossly overindulge need to correct their behaviour but for the majority there is little benefit.
Increased renal excretion of uric acid with Probenecid is poorly tolerated and beset with side effects and poor tolerance, it is best used in specialist cases.
Allopurinol, a xanthine hydroxylase inhibitor is the basis of treatment and can be invaluable. It must be introduced gradually; tablet strengths are 100 and 300mg and most authorities recommend 50mg daily for at least two weeks gradually increasing by 50 mg increments at two or three weekly intervals. When the dose reaches 300mg daily the uric acid level must be assessed and the dose altered to achieve a level < 0.35mmol/l unless there are tophi when a level < 0.30mmole/l is recommended. Doses of 450mg daily are common some will need more, it was believed that allopurinol should not be used in full doses in renal disease, there is no basis for this as allopurinol is excreted hepatically. The drug must be continued lifelong, levels should be checked occasionally, missing a dose or two can result in severe often polyarticular gout. Historically allopurinol was only started in an intercritical period and stopped during an acute attack, both practices have no justification.
Allopurinol will change uric acid balance often precipitating an acute attack, patients must be warned and treated prophylactically with NSAID or colchicine for the first 6 weeks of therapy, gastrointestinal problems and allergic rashes are common and can be overcome by lower starting and incremental doses. Patients with renal insufficiency are particularly susceptible to the rash which can be fatal “Allopurinol Hypersensitivity Syndrome, certain Chinese populations are at particular risk.
Occasionally a rash occurring some months into treatment can be a sign of a syndrome identical to granulomatosis with polyangiitis with ANCA, the drug must be stopped immediately and an alternative found.
Recently Febuxostat has been introduced, this is also a xanthine hydroxylase inhibitor and has fewer rash and intolerance problems though there is a shadow concerning cardiac disease which needs clarification.
Whilst new agents are becoming available those we have are effective, our knowledge and approach need to be fine-tuned if we are to be effective in our management.