Efficacy and safety of desensitization to allopurinol following cutaneous reactions

Objective. To evaluate the long-term efficacy and safety of slow oral desen sitization in the management of patients with hyperuricemia and allopurinol -induced maculopapular eruptions. Methods, A retrospective evaluation of an oral desensitization regimen usin g gradual dosage-escalation of allopurinol in 32 patients (30 with gout and 2 with chronic lymphocytic leukemia) whose therapy was interrupted because of a pruritic cutaneous reaction to the drug. Results. Twenty-one men and 11 women with a mean age of 63 years (range 17- 83 years), a mean serum urate level of 618 mu moles/liter (range 495-750) ( or, mean 10.4 mg/dl [range 8.3-12.6]), and a mean serum creatinine level of 249 mu moles/liter (range 75-753) (or, mean 2.8 mg/dl [range 0.8-8.5]) wer e studied. Desensitization failed in 4 patients because of unmanageable rec urrent rash. Twenty-eight patients completed the desensitization procedure to a target allopurinol dosage of 50-100 mg/day, 21 without deviation from the protocol for a mean of 30.5 days (range 21-56 days) and 7 requiring dos age adjustments because of a recurrent rash over 53.8 days (range 40-189 da ys). Seven of these 28 patients developed late cutaneous reactions 1-20 mon ths postdesensitization, 4 responding to dosage modification and 3 disconti nuing the drug. Twenty-five of the 32 patients (78%) continued to take allo purinol; their mean duration of followup was 32.6 months (range 3-92 months ) and the mean postdesensitization serum urate level was 318 mu moles/liter (range 187-452) (or, mean 5.3 mg/dl [range 3.0-7.5]). Conclusion. The study confirms the long-term efficacy and safety of slow or al desensitization to allopurinol in patients,vith maculopapular eruptions, particularly in those with gout, who cannot be treated with uricosurics or other urate-lowering drugs. Although pruritic skin eruptions may recur bot h during and after desensitization, most of these cutaneous reactions can b e managed by temporary withdrawal of allopurinol and dosage adjustment.