Some adverse reactions to allopurinol may be mediated by lymphocyte reactivity to oxypurinol

Emmerson, B. T.; Hazelton, R. A.; Frazer, Ian H.

doi:10.1002/art.1780310318

Cited by 50 publications

(39 citation statements)

References 12 publications

(4 reference statements)

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“…Some have attributed AHS to direct toxic effects of accumulation of oxypurinol and dose-dependent hypersensitivity to oxypurinol [10]. AHS is likely driven by cell-mediated immunity to allopurinol and oxypurinol [24]. For example, in immunologic studies on a patient with AHS, Braden et al [25] described T-cell infi ltration in the liver, an increased peripheral blood CD8/CD4 ratio, and an oxypurinol-induced T-cell proliferative and activation response substantially greater than that to allopurinol [25].…”

Section: Allopurinol Hypersensitivity Syndrome: Clinical Manifestatiomentioning

confidence: 97%

A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout

Chao¹,

Terkeltaub

2009

Curr Rheumatol Rep

109

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Allopurinol, the first-line drug for serum urate-lowering therapy in gout, is approved by the US Food and Drug Administration for a dose up to 800 mg/d and is available as a low-cost generic drug. However, the vast majority of allopurinol prescriptions are for doses < or = 300 mg/d, which often fails to adequately treat hyperuricemia in gout. This situation has been promoted by longstanding, non-evidence-based guidelines for allopurinol use calibrated to renal function (and oxypurinol levels) and designed, without proof of efficacy, to avoid allopurinol hypersensitivity syndrome. Severe allopurinol hypersensitivity reactions are not necessarily dose-dependent and do not always correlate with serum oxypurinol levels. Limiting allopurinol dosing to < or = 300 mg/d suboptimally controls hyperuricemia and fails to adequately prevent hypersensitivity reactions. However, the long-term safety of elevating allopurinol dosages in chronic kidney disease requires further study. The emergence of novel urate-lowering therapeutic options, such as febuxostat and uricase, makes timely this review of current allopurinol dosing guidelines, safety, and efficacy in gout hyperuricemia therapy, including patients with chronic kidney disease.

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Section: Allopurinol Hypersensitivity Syndrome: Clinical Manifestatiomentioning

confidence: 97%

A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout

Chao¹,

Terkeltaub

2009

Curr Rheumatol Rep

109

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“…1 We were unable to find any statements suggesting a relationship between ANCA-positive CGN and any of the other drugs, i.e., digoxin, tamocapril, or furosemide alone. However, diuretics, including thiazide, are known to decrease oxypurinol clearance, causing it to accumulate, 7,9,10 and drug interaction may have played a role.…”

Section: Discussionmentioning

confidence: 99%

Drug-induced MPO-ANCA-positive necrotizing crescentic glomerulonephritis preceded by granulomatous hepatitis

Nishimura

Shinoda

Suzuki

et al. 2002

Clinical and Experimental Nephrology

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A 67-year-old man being treated with allopurinol, furosemide, digoxin, and tamocapril for congestive heart failure and paroxysmal atrial fibrillation was admitted to our hospital because of intermittent fever, general fatigue, and liver dysfunction. On admission, myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) was positive, and the titer was high. Discontinuation of all four drugs led to improvement of the symptoms, but the patient's renal function deteriorated. Liver biopsy showed granulomatous hepatitis (GH), and renal biopsy findings led to a diagnosis of pauci-immune necrotizing crescentic glomerulonephritis (CGN). The patient's renal function spontaneously improved without immunosuppressive therapy, and the MPO-ANCA titer decreased. We speculate that some common pathway induced by the drugs, possibly allopurinol, led to the two different clinical diseases, GH and CGN.

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“…In view of the increased morbidity and mortality associated with allopurinol hypersensitivity reactions, there is a need to identify patients at risk for this syndrome. Recent data suggest that intradermal skin challenge and lymphocyte transformation with allopurinol or oxypurinol may detect those patients at risk for hypersensitivity reactions to these drugs [ 652 ] . Further, six of these nine patients had signi fi cant blastogenic responses when their mononuclear cells were exposed in vitro to oxypurinol but not allopurinol.…”

Section: Allopurinolmentioning

confidence: 99%

Management of Hyperuricemia and Gout

Newcombe¹

2012

Gout

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Some adverse reactions to allopurinol may be mediated by lymphocyte reactivity to oxypurinol

Cited by 50 publications

References 12 publications

A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout

A critical reappraisal of allopurinol dosing, safety, and efficacy for hyperuricemia in gout

Drug-induced MPO-ANCA-positive necrotizing crescentic glomerulonephritis preceded by granulomatous hepatitis

Management of Hyperuricemia and Gout

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