679

of having onchocerciasis. All patients from onchocerca endemic areas complained of pruritis and had negative skin snips. Positive Mazzotti reactions were seen only in the four patients with eosinophilia and positive onchocerca serology.2,3 We feel that administration of DEC in a single-blind, placebocontrolled fashion is an objective method of determining a true Mazzotti reaction in patients with suspected onchocerciasis.

starting the drug. The mean daily dose is 22 g. The liver function abnormalities were mainly obstructive (mean times above upper limit of normal, bilirubin 11, y-glutamyltransferase 9-8, aspartate aminotransferase 4-3). Australia, Sweden, and, to a lesser degree, the UK appear affected. Sweden has reported 48 cases,’ the UK 21 (10 as the sole suspected drug), New Zealand 2, and Canada none. The World Health Organisation has received reports of 255 hepatitic adverse drug reactions to flucloxacillin, although this figure includes

patients suspected

Disease Unit, Toronto Hospital, Toronto, Ontario M5G 2C4, Canada

JAY S. KEYSTONE

Division of Infectious Diseases, Hospital for Sick Children, Toronto

DELE DAVIES

Tropical

abnormal liver-function tests alone. The incidence of this condition cannot be reliably calculated from reporting data; however, the incidence of results can be expressed in relation to the number of prescriptions written. Olsson et all in Sweden have received 1 report per 10 000 to 30 000 prescriptions written while Australia has received 1 report per 12 000 to 100 000 prescriptions. This is more than in the UK were 1 report has been received per 500 000 prescriptions written. This adverse reaction to flucloxacillin may be largely unrecognised in many countries, possibly because of its delayed onset after administration of the drug.

1. Mazzotti L. Posibilidad de utilizar como media de diagnostico auxiliar en la oncocercoiasis las reacciones allergicas consecutives a la administration de "Hetrazan". Rev Inst Salubr Enferm Trop 1948; 9: 235-37. 2. Lee SJ, Francis HL, Awadzi K, Ottesen EA, Nutman TB. Changes m antibody profile after treatment of human onchocerciasis. J Infect Dis 1990; 162: 529-33. 3 Weiss N, Karam M. Evaluation of a specific enzyme immunoassay for onchocerciasis using a low molecular weight antigen fraction of onchocerca volvulus. Am JTrop Med Hyg 1989; 40: 261-67.

Flucloxacillin

jaundice

SIR,-In the past two years Australia has observed a large increase in reports of cholestatic hepatitis in association with flucloxacillin. Despite worldwide use of this drug, only Sweden has seen a similar number of cases.’ Before the recent Swedish publication, only 12 cases had been published. This is a serious and probably largely unreported adverse drug reaction that often causes deep and prolonged jaundice with substantial morbidity.2,3 Flucloxacillin is a semisynthetic penicillin, similar to cloxacillin, dicloxacillin, and oxacillin, all of which have been reported as rare causes of cholestatic jaundice. It is available for intravenous and oral administration and has become widely used since its introduction in Australia in 1983. Since then the number of prescriptions written for flucloxacillin has risen from 12 136 in 1983 to 1000 000 in 1990 (figure). This increased has been paralleled by an increase in hepatitic adverse drug reactions received by the Australian Adverse Drug Reactions Advisory Committee (ADRAC). 131 reports (excluding those classified as ’unlikely", see below) were received to July, 1991. Adverse drug reactions are reported to ADRAC on a voluntary basis by doctors, dentists, and pharmacists. Each report is then classified, depending on the likelihood of causality, as certain,

probable, possible, or unlikely. Reports classified as unlikely are not used in further evaluation. When a patient has been taking one or more drugs concurrently, the committee may be unable to attribute responsibility for a suspected reaction to a single drug. On these occasions more than one suspected drug is entered in the registry. The clinical features of this condition are characteristic. We have

analysed 51 of the 131 reported cases where flucloxacillin was the sole suspected drug. Of these 51 reports, females predominate (34:17), and the mean age is 58 years. The mean duration of treatment is 14-9 days, with an onset latency of 22-6 days from

Year

Hepatic

adverse

Australia.

drug

reactions and

flucloxacillin

use

in

We thank the National Toxicology Group, University of Otago, Dunedin, New Zealand; the Product Related Disease Division, Health Protection Branch, Health and Welfare Canada, Ottawa, Ontario; the Committee on Safety of Medicines, London; and the WHO Collaborating Centre for International Drug Monitoring, Uppsala, Sweden for statistical information.

Department of Social and Preventive Medicine, Monash University, Alfred Hospital, Prahran, Victoria 3181, Australia, and Adverse Drug Reaction Section, Department of Drug Evaluation Branch, Therapeutic Goods Adminstration, Canberra, ACT

CHRISTOPHER K. FAIRLEY IAN BOYD PATRICK PURCELL JOHN MCNEIL

1. Olsson

R, Wiholm BE, Sand C, Zettergren L, Hultcrantz R, Myrhed M. Liver damage from flucloxacillin, cloxacillin and dicloxacillin. J Hepatol (in press). 2 Miros M, Kerlin P, Walker N, Harris O. Flucloxacillin induced delayed cholestatic hepatitis. Aust N Z J Med 1990; 20: 251-53. 3. Turner IB, Eckstem RP, Riley JW, Lunzer MR. Prolonged hepatic cholestasis after flucloxacillin therapy. Med J Aust 1989; 151: 701-05.

Follow-up of patients with

one

kidney

IR,—Ur Ladetoged (J 11, p 124) patient in whom renal failure developed 22 years after donation, and notes that continued long-term follow-up is necessary in living kidney donors. Another group of patients at risk of the same complications are adult survivors of childhood Wilms’ tumour. Several workers have investigated survivors of Wilms’ tumours at a mean of 15, 17, and 19 years postnephrectomy.1-3 Bhisitkul et all found no abnormalities in 12 survivors 9-23 years postnephrectomy; half had received no radiation therapy. Barrera et aF studied 16 patients 13-26 years postnephrectomy, and Makipernaa et aP 30 patients 11-28 years postnephrectomy; most patients in these two series received abdominal irradiation directed to the side of the tumour. Of these 46 patients, 7 had hypertension and 1 had raised urinary protein excretion. Inclusion of the vertebral column in the radiation field (to avoid radiation-induced scoliosis) would deliver radiation to the remaining kidney, which could produce some radiation nephritis, perhaps accounting for the few patients with an

describes

a

kidney

abnormalities at follow-up. Treatment of Wilms’ tumour has produced large numbers of survivors since the 1960s. Many patients are being followed up, either under the aegis of the National Wilms’ Tumour Study Group in the USA,4or within the late-effects follow-up clinics of individual institutions. Most of these patients, including those in the three series referred to here/-3 have been followed for an average of less than 20 years. These patients are almost certainly cured of their disease, but the risk of long-term complications is lifelong. The patient reported by Ladefoged reinforces the importance of continued vigilance; good results at 20 years from diagnosis cannot lead to complacency. All childhood survivors of malignant disease should have continued follow-up, and such follow-up should be maintained through the paediatric oncologist; only by seeing the

long-term effects of our treatment can we direct improvements

in

Flucloxacillin jaundice.

679 of having onchocerciasis. All patients from onchocerca endemic areas complained of pruritis and had negative skin snips. Positive Mazzotti reacti...
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