Efficacy and safety of desensitization to allopurinol following cutaneous reactions

Abstract

Objective To evaluate the long‐term efficacy and safety of slow oral desensitization in the management of patients with hyperuricemia and allopurinol‐induced maculopapular eruptions. Methods A retrospective evaluation of an oral desensitization regimen using 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 μmoles/liter (range 495–750) (or, mean 10.4 mg/dl [range 8.3–12.6]), and a mean serum creatinine level of 249 μmoles/liter (range 75–753) (or, mean 2.8 mg/dl [range 0.8–8.5]) were studied. Desensitization failed in 4 patients because of unmanageable recurrent 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 dosage adjustments because of a recurrent rash over 53.8 days (range 40–189 days). Seven of these 28 patients developed late cutaneous reactions 1–20 months postdesensitization, 4 responding to dosage modification and 3 discontinuing the drug. Twenty‐five of the 32 patients (78%) continued to take allopurinol; their mean duration of followup was 32.6 months (range 3–92 months) and the mean postdesensitization serum urate level was 318 μmoles/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 oral desensitization to allopurinol in patients with maculopapular eruptions, particularly in those with gout, who cannot be treated with uricosurics or other urate‐lowering drugs. Although pruritic skin eruptions may recur both during and after desensitization, most of these cutaneous reactions can be managed by temporary withdrawal of allopurinol and dosage adjustment.

An effective strategy to prevent allopurinol-induced hypersensitivity by HLA typing

“…16 T-cell-mediated hypersensitivity is, however, a major mechanism in delayed hypersensitivity reaction, which requires dozens of days to increase the dose step by step for tolerance induction. 30 In the current study we used a 28-day slow tolerance induction protocol adapted from the desensitization protocol described by Fam et al, 21 which showed successful tolerance induction in 78% of hyperuricemic patients with allopurinol-induced maculopapular eruption, and borrowed the idea from the fact that allopurinol administration by a slow desensitization protocol could avoid activating already existing memory cells into effector cells. We speculated that slow, gradual escalation of the drug based on a tolerance induction protocol might help to skip the generation of effector and memory T cells, although the existence of those cells was not verified in the study.…”

“…Patients who were HLA-B*58:01-positive based on the HLA screening test were prescribed allopurinol following a 28-day schedule for the slow oral tolerance induction protocol 21 (Supplementary Table S1 online). The allopurinol tolerance induction protocol used in this study was originally made for patients who had allopurinol-induced maculopapular eruptions.…”

Treatment of hyperuricaemia and gout

“…Allopurinol is started at a very low dose and then escalated very slowly every few days, increasing up to 100 mg daily over a 1-month period. 16 Preventing ULT-induced acute attacksPrecipitation or worsening of an acute attack of gout can occur following initiation …”

Desensitization to Hydroxychloroquine: 4 Cases

“…Our experience confirms the validity of this procedure, which was managed on an outpatient basis, not involving hospitalization. A similar approach may be performed in cases of skin reactions after allopurinol administration 4 .…”