DESTIN, FLA. — Oral desensitization appears to be a safe and effective alternative for patients who are allergic to allopurinol and who cannot take other urate-lowering drugs for gout, Adel G. Fam, M.D., reported at a rheumatology meeting sponsored by Virginia Commonwealth University.
Although 1%–3% of patients experience a pruritic maculopapular rash in response to allopurinol, severe allopurinol hypersensitivity syndrome (AHS) occurs in only about 0.4% of patients, said Dr. Fam, a professor of rheumatology at the University of Toronto.
Dr. Fam suggested that allopurinol desensitization be considered in gout patients with any of the following circumstances:
▸ Renal impairment, which renders uricosuric drugs ineffective.
▸ Underexcretion hyperuricemia; and allergy, intolerance, or contraindications to both probenecid and sulfinpyrazone.
▸ Overproduction/overexcretion hyperuricemia, which—when coupled with uricosurics—can increase the risk of renal stones.
▸ History of transplantation, renal insufficiency, and severe and debilitating gout.
▸ The patient requires prevention of malignancy-associated hyperuricemia and tumor lysis syndrome due to cytolytic therapy for hematologic malignancies; the resulting massive uricosuria precludes the use of uricosuric drugs.
The standard allopurinol desensitization protocol starts patients at a 50-mcg dose of allopurinol in suspension. The dose is gradually increased at 3-day intervals up to a target dose of 50–100 mg/day (in tablet form). The dosage can be adjusted if a rash occurs, Dr. Fam said at the meeting, also sponsored by the International Society for Clinical Densitometry.
For high-risk patients, such as the elderly, who have multiple concomitant medical conditions, more severe rash, or eosinophilia, a modified protocol is recommended. This protocol begins with allopurinol, 10 mcg or 25 mcg, in suspension. The dosage is titrated every 5–10 days.
In a retrospective study of 32 patients, 78% were able to tolerate long-term allopurinol therapy following desensitization (Arthritis Rheum. 2001;44:231–8).
The diagnostic criteria for AHS includes a definite history of exposure to allopurinol, lack of exposure to another drug that may have caused similar symptoms, and the fulfillment of either two major criteria or one major and one minor criterion. Major criteria include worsening renal function, acute hepatocellular injury, and rash (toxic epidermal necrosis, erythema multiforme, diffuse maculopapular rash, or exfoliative dermatitis). Minor criteria include fever, eosinophilia, and leukocytosis.