A man, born 1932, has taken allopurinol for 10 years against gout. He has been suffering from myalg

Fråga: A man, born 1932, has taken allopurinol for 10 years against gout. He has been suffering from myalgic pain from the shoulder-region and the back for a long time. Could this be a side-effect of allopurinol-treatment?

Sammanfattning: Muscular pain has been stated as a side-effect of allopurinol treatment but the frequency seems to be low. Crystals of hypoxanthine, xanthine and oxipurinol occurred in the muscle tissue of allopurinol treated patients.

Svar: Muscular pain has been mentioned as a side-effect of allopurinol treatment (1). It was stated that fever, malaise and muscle aching may occur in 3 per cent of patients with normal renal function but is more frequent with renal impairment (2). However the frequency of muscle aching alone is not known. To the adverse drug reaction committee of National Board of Health, only one case of myalgia has been reported since 1967, and its cause-effect relationship was not established.

Myopathy associated with crystalline deposits in skeletal muscle has been described in the cases of xanthinuria which is caused by a congenital deficiency of xanthine oxidase. The presence of increased amounts of hypoxanthine and xanthine in the muscles of these patients was confirmed by mass spectrometry and therefore xanthinuria must be considered as a possible cause of muscle pain of undefined origin (3). Allopurinol is a competitive inhibitor of xanthine oxidase and is used to reduce uric acid production in patients with gout. Therefore, the occurrence of xanthine as well as hypoxanthine crystals may be explained on the basis of an alternative mechanism for the oxidation of hypoxanthine to xanthine to by xanthinuric patients. Consequent to the identification of crystalline deposits of xanthine and hypoxanthine in the muscle of xanthinuric patients, studies were also made on muscle from gout patients treated with allopurinol. It was found that uric acid and its monohydrated sodium salt occurred in the muscle tissue of untreated gout patients. Crystals in the muscles of gout patients treated with allopurinol were not only smaller but the number found was considerably smaller (average 15/section) than were observed in xanthinuria (more than 200/section) (3,4). The authors concluded that "small aggregates of xanthine, hypoxanthine and oxipurinol (a metabolite of allopurinol) are deposited in muscle tissue where they have not been harmful", "although the results suggested that the long-term use of allopurinol should be prescribed with some caution" (3,5).

We recommend that this case should be reported to the adverse drug reaction committee. 1 Meyler´s, Side effects of drugs. Ed by MNG Dukes, Elsevier, Amsterdam. 1988; 11th ed: 194-195 2 Goodman and Gilman, The pharmacological basis of therapeutics. 1985; 7th ed: 711-712 3 Chalmers RA: Crystals in skeletal muscle in xanthinuria and in allopurinol-treated gout patients. S African Med J 1975; 49: 2072 4 Watts RW, Scott JT, Chalmers RA, Bitensky L, Chayen J: Microscopic studies on skeletal muscle in gout patients treated with allopurinol. Q J Med 1971; 40: 1-14 5 Bowker CH, Turmer P: Myopathy after allopurinol. Lancet 1977; I: 365