St Luke's Hospital, Little Horton Lane, Bradford BD5 0NA, UK
SIR, I read with interest the article referring to allopurinol hypersensitivity in renal disease with subsequent reintroduction of allopurinol in an oral desensitization regime [1]. The possibility of a familial tendency to allopurinol hypersensitivity is raised by the following case.
In 1991, a 57-yr-old man was admitted with a 6-week exacerbation of a painful, swollen knee. He gave a history of some years of classical gout for which he had been treated with NSAIDs. Similarly, his brother had gout which had been treated with allopurinol, but this had to be discontinued when he developed a rash. The rash disappeared after the drug was discontinued. Subsequently, his brother had been successfully densitized to allopurinol and continues to take this medication.
On examination, the patient was febrile and had obvious tophi in both hands and an inflamed olecranon bursa at the right elbow. His swollen left knee was aspirated and the purulent-looking fluid grew Group C haemolytic streptococci and also contained profuse uric acid crystals. Similarly, uric acid crystals were seen in the exudate from a lateral malleolar ulcer. Abnormal investigations included a haemoglobin of 7.2 g/dl, urea of 29.3 mmol/l and creatinine of 421 µmol/l. His creatinine clearance was 16 ml/min and his ESR 129 mm/1 h.
He was taking lisinopril for hypertension and had recently had an NSAID introduced for treatment of his gout. This and infection had presumably precipitated renal failure.
He was treated with i.v. benzylpenicillin, and the lisinopril and NSAID were discontinued. He was transfused with 2 units of blood. On this treatment, his pyrexia settled. However, over the next 2 weeks the inflammation in the left knee increased. The knee was arthroscoped and lavaged. His serum creatinine fell to the normal range and the repeat creatinine clearance had risen to 44 ml/min. Allopurinol 100 mg/day and colchicine 500 µg b.d. were introduced. Two months later, he developed a generalized florid rash which disappeared after allopurinol was discontinued. However, the patient was desensitized to allopurinol and has remained on this medication for the last 8 yr, initially taking 100 mg a day and subsequently 200 mg daily. His blood pressure remains controlled on nifedipine sustained release 20 mg b.d. On admission, his uric acid had been 480 mmol/l, but had gradually risen over the next months to 564 mmol/l. After restarting allopurinol, the serum uric acid has now fallen to normal. He has had no attacks of gout for several years and his tophi have disappeared.
It seems likely that a family history of allopurinol hypersensitivity is a risk factor for this complication. This letter describes two brothers who developed allopurinol hypersensitivity and were successfully desensitized to allopurinol.
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