Dapsone-mediated agranulocytosis: risks, possible mechanisms and prevention

Toxicology
M D Coleman

Abstract

Agranulocytosis is a rare, severe and unpredictable idiosyncratic reaction associated with drug therapy that can lead to life-threatening illness. Typically, the patient presents with a fever and evidence of infection 1-3 months after initiation of drug administration with a neutrophil count below 0.5x10(9) l. Of the drugs linked with this disease, aminopyrine, dipyrone, clozapine, anti-thyroid agents, sulphonamides and dapsone are the best documented. Generally, agranulocytosis is associated with older individuals (>60 years) and those of non-Caucasian descent. The incidence of agranulocytosis in subjects taking oral dapsone in combination with maloprim for malaria is 1 -- 10-20,000 while leprosy patients treated with dapsone exhibit virtually zero risk of agranulocytosis. However, dapsone is unusual in that during the rare but severe inflammatory disease, dermatitis herpetiformis (DH), the risk of agranulocytosis is multiplied between 25 and 33 fold compared with normal patients. It is conceivable that dapsone might exhibit a similar risk in coeliac disease, a condition related to DH. As dapsone plasma levels in DH subjects can be high (2-10 microg/ml) the increased risk of agranulocytosis could be related to drug dosage, or ...Continue Reading

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Citations

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