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Tausche et al described a case of severe tophaceous gouty arthritis, which was treated with etanercept.1 They showed that anti-tumour necrosis factor α (TNFα) treatment can reduce the incidence of gouty attacks, which corresponds with the observation that TNFα is activated in patients with gouty arthritis.2 Clearly, this is a costly symptomatic approach that is only in addition to the main treatment, which is lowering the serum uric acid (SUA) level in order to deplete urate depots and prevent gouty attacks and joint damage in the long term.
In the case presented, uricosuric treatment could only lower SUA levels from 0.58 mmol/l to 0.56 mmol/l despite high doses of 2–3 g probenecid a day. This is in contrast with our experience. In our population of 95% undersecretors (defined as uric acid excretion in urine <6.0 mmol/day during normal diet) monotherapy with probenecid 500 mg twice daily lowers SUA levels by 35% (mean (SD) 0.17 (0.05) mmol/l), whereas probenecid 500 mg twice daily in combination with allopurinol 200 mg daily lowers SUA levels by 48% (0.27 (0.08) mmol/l) in patients with an adequate renal function (endogenous creatinine clearance >50 ml/min).
In the case presented by Tausche et al we would like to suggest another option for treating patients with severe tophaceous gout—that is, treatment with rasburicase. This recombinant form of urate oxidase very effectively metabolises uric acid in allantoin, which dissolves readily and is excreted by urine. So far one patient has been treated by applying rasburicase and urate depots were readily depleted (Moolenburgh JD et al, submitted paper)
In our opinion, for a case of severe tophaceous gout, when an expensive treatment is indicated, rasburicase should be considered as a potentially very effective treatment before using anti-TNFα.
Like Reinders et al, we have found that in the defined “normal” population of undersecretors, conventional treatment effectively lowers serum uric acid (SUA) levels to the norm.
In those critical cases of severe tophaceous gout, as presented by us, the multiple tophi in the tissue and joints contain around 50 g or more uric acid. Despite the escalation of antihyperuricaemic (uricosuric and uricostatic) drugs, the SUA levels cannot be lowered significantly because of uric acid mobilisation from these depots and secondary shift to the serum.
Therefore, measurement of SUA levels alone does not verify the efficiency of treatment.1 In view of our own experience (unpublished data), we agree with Reinders et al that the recombinant urate oxidase rasburicase should be introduced into the treatment of severe tophaceous gout if conventional uric acid lowering treatment is not effective or contraindicated. These cases are extremely rare and occur in under 0.01% of the population of undersecretors.
There are two principles in the treatment of gout: firstly, uric acid lowering treatment with uricostatic and uricolytic agents and, secondly, anti-inflammatory treatment of gouty attacks. Both of these treatment regimens should follow a “step scheme”.1
In the uric acid lowering treatment rasburicase might rank as the last step in treatment of patients with tophaceous gout. When gouty arthritis is refractory to treatment (with non-steroidal anti-inflammatory drugs, steroids, opioids) it is useful to introduce tumour necrosis factor α (TNFα) blockade, as we showed in the published case. Because two different principles of action can be followed there seems to be no need to answer the question of priority of one of these treatments. Rasburicase should not be considered before TNFα blockade but, rather, the two should be combined if conventional treatment is not sufficient.
The main dilemma of both treatments in the first instance is not the high cost but the missing approval by the FDA in severe tophaceous gout.2 Unfortunately, valid data are lacking, for instance, about the best way of application (dosage, application interval) owing to the absence of clinical studies. Shortly after infusion of rasburicase instant uric acid metabolisation with abrupt decrease of SUA is observed. The resultant shift of uric acid from tissues to blood may cause a higher intensity of gouty attacks, and as we observed in one patient with urate nephropathy the worsening of renal function.3 We are very interested to learn of the article proposed by Moolenburgh et al.
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