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HÆMATOLOGICAL EFFECTS OF ANTICONVULSANT TREATMENT
682 What is
worrying
is that he found it
so
easy
to
sign
on as
temporary resident with any general practitioner and, in almost every case, to obtain 100 capsules aftera brief interview, and to get 100-capsule repeat prescriptions without seethe doctor. It was, he observed, "Far too easy to con them". The addictive-properties of benzodiazepines may have been underrated and there may well have to be a campaign on their use and restriction-a point underlined by my local underworld contacts telling me that diazepam 10 mg tablets currently sell at no less than L1 each.
ing
macrocytosis, megaloblastic haemopoiesis, and low serum and red cell folate in non-anxmlc treated epileptics,2 that the drugs also play a role in the occasional anxmia. of
University Department of Neurology, Institute of Psychiatry,
E. H. REYNOLDS M. LAUNDY
RICHARD Fox
HÆMATOLOGICAL EFFECTS OF ANTICONVULSANT TREATMENT be surprised at their failure to detect macrocytosis in all but 1 of 96 mentally retarded patients on anticonvulsant therapy. Their findings are apparently at variance with at least nine studies in which macrocytosis was detected, by various techniques, in from 8% to 53% of epileptic patients.2 In the one previous report of the absence of macrocytosis, Jensen and Olesen3also failed to find any fall in red-cell folate, although Rose and Johnson agree with others that this is common. We have also examined mean cell volume (M.c.v.) with the Coulter S counter in 118 outpatient epileptics, all on a combination of phenytoin and primidone and compared the result with those of 18 untreated epileptic patients. All the untreated patients had an mt.c.v. within the normal control range of 80-90 fLm3, whereas 42% of the drug-treated patients had macrocytosis (see figure).2 Our findings accord with those of Eastham et al. who investigated an institutionalised retarded population, similar to that of Rose and Johnson, who do not refer to Eastham’s work. Rose and Johnson provide no details of the M.c.v. data for their patients, nor do they mention any control group. We are unaware of any evidence that "anticonvulsant therapy is often associated with megaloblastic anxmia". Indeed it
SIR,-Rose and Johnson1
3. 4.
may pregnancy. However, we agree with Dr Hawkins (Aug. 5, p. 317) that in many patients nutritional deficiency is not present, and there can be little doubt, in view of the high mcidence
London SE5 9RS
Severalls Hospital, Colchester C04 5HG
1. 2.
appears to be very uncommon, being seen in well under 1% of patients.2 It has long been recognised that additional nutrinonal deficiency may sometimes precipitate the anaemia,25 as
are
right
to
Rose, M. S., Johnson, I. Lancet, 1978, i, 1349.
Reynolds, E. H. in Clinics in Hæmatology vol. v, (edited by A. V. Hoffbrand); p. 661. London, 1976. Jensen, O. N., Olesen, O. V. Archs Neurol. 1969, 21, 208. Eastham, R. D, Jancar, J., Cameron, J. D. Br. J. Psychiat 1975, 126, 263.
MULTISYSTEM TOXICITY AFTER CO-TRIMOXAZOLE
SIR,-A report of fatal multisystem toxicity after co-trimoxazole’ prompts us to report a similar case, though with a hap-
pier outcome. This 84-year-old woman had a history of arthritis, diabetes controlled by diet, hypertension, cholecystectomy (1955), and a reaction to gold therapy. Previous medications included hydrochlorothiazide, chlorthalidone, clonidine (not tolerated), oestrogens, and porassium supplements. A previous urinaryinfection had been treated with co-trimoxazole. In 1974 intravenous pyelography and kidney function were normal (blood-urea-nitrogen 19 mg/dl). On May 19, 1978, she complained of dysuria and her doctor prescribed co-trimoxazole, which she started taking on May 20. She was admitted to hospital May 22 with an erythematous maculopapular eruption over the entire body, weakness, fever, low-back pain, cough, and decreased air entry to her right lower lobe. Other findings included: blood-urea-nitrogen 33 mg/dl, Hb 17.1g/dl, white blood-cells 18 100/µl, bloodsugar 169 mg/dl, and chloride 85, sodium 127, and potassium tract
2.9
mmol/l.
The second day after admission the patient had purpura on her back and under the E.c.G. suction cup sites and perioral pallor with cedema of eyes, neck, uvula, and lips. Other findings included Hb 18.7g/dl, white blood-cells 24 100/µl, tachycardia (115/min), prothrombin-time 54.0 s, and consolidation of right lower lobe on chest X-ray. On the third day the patient’s condition deteriorated, with oliguria (<20 ml/h despite fluid challenge) and loss of consciousness. Laboratory findings included blood-urea 52 mg/dl, serum creatinine 4-9 mg/dl, sodium 125 and potassium 4.1 mmol/1, prothrombin-time 18 s; and she had encephalopathy. Initial treatment consisted of fluids, antibiotics, hydrocortisone, hydroxyzme, diazepam, and paracetamol (acetaminophen). Digoxin, frusemide, and phytonadione were
added.
days were remarkable for a return of urine subsidence of skin lesions, and consciousness output, gradual fluctuating but returning to normal. Complications included a small gastrointestinal haemorrhage, treated with antacids and cimetidine; nausea and diarrhoea, treated with antihistamines and diphenoxylate; raised serum-uric-acid (10.9 mg/dl) treated with allopurinol; and some vaginal bleeding, treated with cestrogens. After continued but reducing steroid administration the patient was discharged from hospital 1 month after admission, taking prenisone, digoxin, allopurinol, propantheline, and antacid. On follow-up 1 month later the patient was mentally alert; she had a high systolic blood-pressure (220/80) as previously, a blood-urea-nitrogen of 20 mg/dl; and she complained of loss of hair at an "alarming rate" and loose fingernails. This case was diagnosed as an acute allergic reaction to cotrimoxazole with multisystem involvement, including skin, The
Mean cell volume
M.C.V. in untreated and
drug-treated epileptics.
next
5. Flexner,
few
J. M., Hartmann, R. C. Am. J. Med. 1960, 28, 386.
worrying
is that he found it
so
easy
to
sign
on as
temporary resident with any general practitioner and, in almost every case, to obtain 100 capsules aftera brief interview, and to get 100-capsule repeat prescriptions without seethe doctor. It was, he observed, "Far too easy to con them". The addictive-properties of benzodiazepines may have been underrated and there may well have to be a campaign on their use and restriction-a point underlined by my local underworld contacts telling me that diazepam 10 mg tablets currently sell at no less than L1 each.
ing
macrocytosis, megaloblastic haemopoiesis, and low serum and red cell folate in non-anxmlc treated epileptics,2 that the drugs also play a role in the occasional anxmia. of
University Department of Neurology, Institute of Psychiatry,
E. H. REYNOLDS M. LAUNDY
RICHARD Fox
HÆMATOLOGICAL EFFECTS OF ANTICONVULSANT TREATMENT be surprised at their failure to detect macrocytosis in all but 1 of 96 mentally retarded patients on anticonvulsant therapy. Their findings are apparently at variance with at least nine studies in which macrocytosis was detected, by various techniques, in from 8% to 53% of epileptic patients.2 In the one previous report of the absence of macrocytosis, Jensen and Olesen3also failed to find any fall in red-cell folate, although Rose and Johnson agree with others that this is common. We have also examined mean cell volume (M.c.v.) with the Coulter S counter in 118 outpatient epileptics, all on a combination of phenytoin and primidone and compared the result with those of 18 untreated epileptic patients. All the untreated patients had an mt.c.v. within the normal control range of 80-90 fLm3, whereas 42% of the drug-treated patients had macrocytosis (see figure).2 Our findings accord with those of Eastham et al. who investigated an institutionalised retarded population, similar to that of Rose and Johnson, who do not refer to Eastham’s work. Rose and Johnson provide no details of the M.c.v. data for their patients, nor do they mention any control group. We are unaware of any evidence that "anticonvulsant therapy is often associated with megaloblastic anxmia". Indeed it
SIR,-Rose and Johnson1
3. 4.
may pregnancy. However, we agree with Dr Hawkins (Aug. 5, p. 317) that in many patients nutritional deficiency is not present, and there can be little doubt, in view of the high mcidence
London SE5 9RS
Severalls Hospital, Colchester C04 5HG
1. 2.
appears to be very uncommon, being seen in well under 1% of patients.2 It has long been recognised that additional nutrinonal deficiency may sometimes precipitate the anaemia,25 as
are
right
to
Rose, M. S., Johnson, I. Lancet, 1978, i, 1349.
Reynolds, E. H. in Clinics in Hæmatology vol. v, (edited by A. V. Hoffbrand); p. 661. London, 1976. Jensen, O. N., Olesen, O. V. Archs Neurol. 1969, 21, 208. Eastham, R. D, Jancar, J., Cameron, J. D. Br. J. Psychiat 1975, 126, 263.
MULTISYSTEM TOXICITY AFTER CO-TRIMOXAZOLE
SIR,-A report of fatal multisystem toxicity after co-trimoxazole’ prompts us to report a similar case, though with a hap-
pier outcome. This 84-year-old woman had a history of arthritis, diabetes controlled by diet, hypertension, cholecystectomy (1955), and a reaction to gold therapy. Previous medications included hydrochlorothiazide, chlorthalidone, clonidine (not tolerated), oestrogens, and porassium supplements. A previous urinaryinfection had been treated with co-trimoxazole. In 1974 intravenous pyelography and kidney function were normal (blood-urea-nitrogen 19 mg/dl). On May 19, 1978, she complained of dysuria and her doctor prescribed co-trimoxazole, which she started taking on May 20. She was admitted to hospital May 22 with an erythematous maculopapular eruption over the entire body, weakness, fever, low-back pain, cough, and decreased air entry to her right lower lobe. Other findings included: blood-urea-nitrogen 33 mg/dl, Hb 17.1g/dl, white blood-cells 18 100/µl, bloodsugar 169 mg/dl, and chloride 85, sodium 127, and potassium tract
2.9
mmol/l.
The second day after admission the patient had purpura on her back and under the E.c.G. suction cup sites and perioral pallor with cedema of eyes, neck, uvula, and lips. Other findings included Hb 18.7g/dl, white blood-cells 24 100/µl, tachycardia (115/min), prothrombin-time 54.0 s, and consolidation of right lower lobe on chest X-ray. On the third day the patient’s condition deteriorated, with oliguria (<20 ml/h despite fluid challenge) and loss of consciousness. Laboratory findings included blood-urea 52 mg/dl, serum creatinine 4-9 mg/dl, sodium 125 and potassium 4.1 mmol/1, prothrombin-time 18 s; and she had encephalopathy. Initial treatment consisted of fluids, antibiotics, hydrocortisone, hydroxyzme, diazepam, and paracetamol (acetaminophen). Digoxin, frusemide, and phytonadione were
added.
days were remarkable for a return of urine subsidence of skin lesions, and consciousness output, gradual fluctuating but returning to normal. Complications included a small gastrointestinal haemorrhage, treated with antacids and cimetidine; nausea and diarrhoea, treated with antihistamines and diphenoxylate; raised serum-uric-acid (10.9 mg/dl) treated with allopurinol; and some vaginal bleeding, treated with cestrogens. After continued but reducing steroid administration the patient was discharged from hospital 1 month after admission, taking prenisone, digoxin, allopurinol, propantheline, and antacid. On follow-up 1 month later the patient was mentally alert; she had a high systolic blood-pressure (220/80) as previously, a blood-urea-nitrogen of 20 mg/dl; and she complained of loss of hair at an "alarming rate" and loose fingernails. This case was diagnosed as an acute allergic reaction to cotrimoxazole with multisystem involvement, including skin, The
Mean cell volume
M.C.V. in untreated and
drug-treated epileptics.
next
5. Flexner,
few
J. M., Hartmann, R. C. Am. J. Med. 1960, 28, 386.