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The histories of 269 patients whose death certificates did not mention a drug as the cause of aplastic anaemia or agranulocytosis were investigated. Eighty-three deaths were probably caused by drugs, the most common cause of aplastic anaemia being treatment with phenylbutazone (28 deaths) and oxyphenbutazone (11 deaths). Thirteen out of 17 deaths from agranulocytosis were attributed to co-trimoxazole treatment. A separate survey of general practitioners' prescriptions enabled the mortality to be estimated. With the addition of one death due to oxyphenbutazone and four deaths due to phenylbutazone that were reported independently to the committee, the mortality from oxyphenbutazone was 3-8 per 100 000 and from phenylbutazone 2-2 per 100 000. With phenylbutazone the rates varied from under 1 death per 100 000 for men aged under 65 years to 6 per 100 000 for women aged 65 and over. Small numbers precluded estimates for oxyphenbutazone in these subgroups, although a similar trend was suggested. No particular indication for treatment seems to carry a higher risk, the main concern being the use of these two drugs in elderly patients.

Fifty-nine patients on long-term treatment with phenylbutazone or oxyphenbutazone for chronic rheumatic conditions were switched to treatment with naproxen and followed-up for 6 months in a compliance study. All patients were started on 500 mg naproxen twice daily but adjustment of the dosage was permitted. During the 6 months of the study only 3 patients returned to treatment with phenylbutazone. Of the remaining 56 patients, 45 were still taking naproxen after 6 months, 9 were changed to other non-steroidal, anti-inflammatory drugs and 2 were lost to follow-up. The study demonstrates that in routine general practice, phenylbutazone and oxyphenbutazone can be successfully replaced by less toxic drugs.

A combined cholestatic-hepatocellular injury and noncaseating granulomas occurred in two patients 1 and 4 weeks after phenylbutazone therapy. Both patients were jaundiced, one had a macular rash, and both had peripheral blood eosinophilia. Symptoms and signs subsided, and abnormal findings from tests of hepatic function rapidly returned to normal following withdrawal of the drug. Sections of liver biopsy specimens 6 months later showed no granulomas or other pathologic changes. Previously reported cases are reviewed.

We describe two patients who developed generalized pustular psoriasis after taking phenylbutazone and oxyphenbutazone respectively, and discuss the possible pharmacological mechanism of this effect.

A case history is presented of the occurrence of a high binding capacity for native DNA in the serum of a patient on phenylbutazone. This reverted to normal on stopping the drug. The patient also had a reversible neutropenia and leucopenia, and it is suggested that the high anti-DNA binding capacity was a feature of a drug-induced lupus-like phenomenon.