What alternatives are available for gout patients who have skin rashes due to allopurinol?

Most patients do very well with allopurinol. Therefore, when a patient on allopurinol develops a skin rash, the first question is whether the rash is actually due to this medication. Most commonly, rash due to allopurinol is a pruritic and maculopapular, although on occasion it can have an element of angioedema, and in rarer cases can be a true vasculitis. Since the implications of this rash in the long-term care of the patient may be quite significant, dermatology evaluation is often indicated.

Second, the accuracy of the diagnosis of gout should be carefully considered. Several diseases can involve the first metatarso-phalangeal joint and masquerade as gout, including psoriatic arthritis, Reiter's syndrome, pseudogout, and rheumatoid arthritis.

Third, the question of whether this patient absolutely needs allopurinol should be evaluated. The indications for allopurinol are:

• recurrent gout despite colchicine prophylaxis
• gout with kidney stones
• gout with presence of tophi
• gout with very high 24 hour urine for uric acid
• patient who was a good candidate for uricosuric therapy but could not tolerate the uricosuric
• recurrent gout and renal insufficiency
• gout prophylaxis before chemotherapy.

If the patient simply had hyperuricemia, or had gout attacks but never had a trial of colchicine prophylaxis, perhaps the allopurinol is not needed. If the 24 hour urine uric acid excretion is < 300 mg, and the creatinine is less than 1.3, probenecid might be substituted.

If it is apparent after the above considerations that allopurinol is the drug of choice and the dosing is correct, several options are available.

First, an oral desensitization regimen can be tried in which the drug is discontinued and then reintroduced with gradually increased doses. This has been well-described[1]  and allows a number of patients to get back on allopurinol. The first dose should be given under close observation. However, a number will eventually have another allergic reaction to allopurinol. For these, another option is an intravenous desensitization regimen[2], although this requires hospitalization, ideally in an ICU, in view of the potential for more serious reactions. Unfortunately, even intravenous desensitization regimens are far from universally successful.

If oral desensitization is unsuccessful, an alternative to trying the intravenous route is oxypurinol. This is the main metabolic breakdown product of allopurinol and has been reported to have about a 50% cross-reactivity with allopurinol[3]. This drug can be obtained with a compassionate use ""N of 1"" study protocol from Cardiome Pharma Corp[4]. (The company now has the drug in Phase I/II trials for congestive heart failure.)

If both desensitization and oxypurinol fail, options are very limited. While uricase has recently been approved for use in chemotherapy prophylaxis in children, it can only be used intravenously and has had significant adverse effects. In its present formulation, it is clearly not relevant for the usual patient with gout or kidney stones.

One last alternative is benzbromarone, which is available in Europe but not in the United States. This uricosuric is effective at higher creatinine levels than probenecid. For those patients who do not have 24 hour urinary urate >300mg, this drug may be an option, even if their creatinine is in the 2.0-2.5 range.

In patients who have had the more rare and severe skin rash to allopurinol which present as a true vasculitis, all forms of allopurinol desensitization and the use of oxypurinol are likely inappropriate. Thus, the options not related to allopurinol or its breakdown products would be much preferred.