Ethopropazine Hydrochloride in Treatment of Cerebral Palsy
Authors: R. G. Mitchell
Journal: BMJ (1953)

DICALITSORNAL 1313 was the cause of the bone-marrow aplasia in the patient under discussion.On the other hand, the patient was perfectly well (apart from arthritis) until treatment with phenylbutazone was begun; within one week she had developed epistaxis and a purpuric rash; and within two weeks a fulminating aplastic anaemia had led to death.It seems, on the whole, more reasonable to incriminate phenylbutazone, though it might be that in some way the patient had become sensitized to phenylbutazone by the previous course of gold.Two further possibilities should be mnentioned: that hypo- thyroidism or rheumatoid arthritis may have influenced the structure of the bone marrow in this patient.In hypo- thyroidism, hypoplasia of the bone marrow occurs, but the anaemia is not usually severe.As this patient had been adequately treated with thyroid extract for four years there is no reason to suppose that her myxoedema would affect the bone marrow.As regards rheumatoid arthritis, Leitner (1949) states that "in all our cases of rheumatoid arthritis we have observed plasma-cell proliferation" in the bone marrow.He cites Mester (1938), who " collected 75 cases and found an increase of plasma and reticulum cells in acute and chronic rheumatoid arthritis."Some relative proliferation of plasma cells is sometimes seen in idiopathic aplastic anaemia, but not to the same extent as in this patient.Infiltration of the bone marrow with plasma cells is, of course, a feature of multiple myelomatosis, of which there was no clinical or pathological evidence here.The relationship, if any, between plasma-cell proliferation and phenylbutazone remains to be determined.Are t.he toxic effects of phenylbutazone due mainly to overdosage or to idiosyncrasy ?With this question in mind, an attempt has been made to correlate the frequency of toxic reactions with the dosage of the drug administered.It seems, however, that no such broad correlation can be established, and this may indicate that idiosyncrasy to the drug is the predominant factor.Thus, on a dosage of 1 g.daily, Cudkowicz and Jacobs (1953) reported toxic effects in 26 out of 50 patients, whereas Currie (1952) reported no toxic effects in 81 patients.Loxton et al. gave doses varying from 0.4 to 0.8 g. daily, and reported toxic effects at each level: Of the patients with agranulocytosis, three had never received more than 0.8 g. daily, whereas two had received 1.2 g. daily.Of the present cases, Case 1 received 0.6 g. daily, a dosage normally regarded as safe, and Case 2 received 1.6 g. daily for the first week and 0.8 g. thereafter.It thus appears from these cases that the administration of small doses of phenylbutazone does not eliminate the possibility of developing serious blood dyscrasias.The possible dangers of phenylbutazone therapy are increased by its effectiveness, which encourages its employment in general practice.It would seem that its use should be closely controlled by frequent blood counts, and that it should be confined at present to patients in hospital.Summary Details of 356 toxic effects occurring in 1,526 patients