605
disease.5 One cannot preclude an idiopathic myocarditis, but the temporal relation between administration of mesalazine and symptoms suggests a drug-related myocarditis; the absence of hypersensitivity symptoms and eosinophil infiltrations rules out a classic hypersensitivity myocarditis.6 We suggest that mesalazine or sulphasalazine are replaced by glucocorticoids if cardiac symptoms arise during treatment. Departments of Internal Medicine, Pathology, and Surgery, County Central Hospital,
Portable infusor.
Naestved, Denmark
49 inpatients received intravenous infusion2 with this apparatus. 12 had 500 ml of isotonic sodium chloride solution3in about 10 min. 1 patient who needed fast infusion received the same volume of solution in 3 min. In the other 36 patients the same volume was given in about 60 min. In every case the apparatus was efficient and no adverse effect was noted. This infusor would be useful in emergency perfusion of victims of catastrophes. Service for Emergencies, Hôpital de Brabois, 54500 Vandoeuvre-Les-Nancy, France
1.
GILBERT THIBAUT
KJELD S. KRISTENSEN ASBJØRN HØEGHOLM LENE BOHR SØREN FRIIS
1. Agnholt J, Sørensen HT, Rasmussen SN, Gøtzsche C-O, Halkier P. Cardiac hypersensitivity to 5-aminosalicylic acid. Lancet 1989; i: 1135. 2. Deboever G, Devogelaere R, Holvoet G. Sulphasalazine-induced lupus-like syndrome with cardiac tamponade in a patient with ulcerative colitis. Am J Gastroenterol 1989; 84: 85-86. 3. Weber P, Becker W, Jenss H. Pericardial effusion during treatment on Crohn’s disease with 5-aminosalicylic acid. Dtsch Med Wochenschr 1988; 113: 1806-07. 4. Thuesen L, Sørensen J. Ulcerative colitis complicated by myopericarditis and complete atrio-ventricular block. Ugeskr Laeger 1979; 141: 2760-61. 5. Frid C, Bjarke B, Eriksson M. Myocarditis in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1986; 5: 964-65. 6. Fenoglio JJ, McAllister HA, Mullick FG. Drug related myocarditis, I: hypersensitivity myocarditis. Hum Pathol 1981; 12: 900-07.
Viljoen JF. The ubiquitous (and extravagant) intravenous infusion. JAMA 1977; 237:
1927-28. 2. Hirlekar G, Hauksson H, Jonsson B, Gariglia N, Arnthorsson G. Haemodilution in elective surgery. Bibl Haematol 1981; 47: 279-86. 3. Lundsgaard-Hansen P. Emploi clinique des solutions d’albumine, de colloides artificiels et d’électrolytes. Méd Hyg Genève 1972; 30: 638-40.
Fatal myocarditis associated with mesalazine SIR,-Dr Agnholt and colleagues1 showed that mesalazine could induce myocardial injury. We report a case of fatal myocarditis in which mesalazine is also incriminated. A 20-year-old woman with a 6-month history of bloody diarrhoea was admitted. For 3 years she had had a benign exostosis on the iliac crest that was not growing, light arthralgia, and psoriatic lesions mainly on the palms and soles. No infectious cause of the diarrhoea was established. Double-contrast barium enema showed ulcerations throughout the colon, and a rectal biopsy showed acute mucosal inflammation. Chest radiography and electrocardiogram (ECG) were normal. Treatment with mesalazine 1-5 g daily was started, and stool frequency decreased. Thirteen days later the patient had sudden severe chest pain and dizziness; ECG showed left anterior hemiblock followed by ventricular fibrillation, which was successfully treated by DC cardioversion. Echocardiography showed fluctuating dyskinesia septally and laterally. She had anteroseptal ST-elevations and Q-waves on ECG. Plasma lactic dehydrogenase isoenzyme 1 was six times over the upper reference level. Despite inotropic support and artificial ventilation the patient died 22 hours later in cardiogenic shock. At necropsy a pancolitis was seen which had been healing. Heart size and coronary arteries were normal, no pericarditis or endocarditis was present. The myocardium was speckled throughout; microscopically there were confluent necrotic areas with intense infiltration by neutrophils. The lesions were of the same age and without Aschoff bodies, eosinophils, or perivascular predilection. The unaffected myocardium appeared normal. Viral cultures from myocardium and intestines as well as tests for antinuclear antibodies were negative. Sulphasalazine can induce a lupus-like syndrome with pericarditis2 whereas its metabolite mesalazine has been suspected to induce pericardial effusion3 and myocarditis.l Perimyocarditis is also a rare but recognised extra-intestinal manifestation of inflammatory bowel diseases Our patient had a very severe myocarditis without pericarditis. The latter in conjunction with the lack of association between severity of intestinal and cardiac involvement argues against the carditis being an extra-intestinal manifestation of the bowel
Vigabatrin and
behaviour disturbances
SIR,-Dr Sander and Dr Hart (Jan 6, p 57) draw attention to some side-effects of the new effective antiepileptic drug vigabatrin. I have been using vigabatrin since 1981 and have conducted a single-blind trial,’ a double-blind tria1,2 and long-term studies on this drug.3 In all we have treated 117 patients, many of whom have been on vigabatrin for up to eight years. Although the side-effects Sander and Hart mention are not unknown, I have not seen them with the same severity. Nor has the drug had to be withdrawn in about 20% of patients as they suggest. I have seen only 2 patients with frank psychotic symptoms; one required withdrawal but the other is still on vigabatrin and has responded well. Other behavioural disturbances such as irritability, confusion, and aggression were seen in 8 patients, usually mentally retarded patients with severe brain lesions, and in only 7 of these were they significant enough to necessitate withdrawal of
vigabatrin. Confusion was observed in the early studies in 2 elderly patients, and was probably related to decreased renal clearance. We now find that this effect is easily prevented by the use of a lower dose. Patient selection may account for my different experience with vigabatrin, since my patients may not be as severely affected as those referred to the Chalfont Centre for Epilepsy. I agree that treatment with vigabatrin in severely retarded patients should be monitored closely in the early stages. Elderly patients with reduced renal clearance should be treated with lower doses. In all our patients the behavioural disturbances have reversed on either lowering the dose or stopping the drug. University Clinic of Neurology, Hvidovre Hospital, DK-2650 Hvidovre, Denmark
M. DAM
1. Gram L, Blatt
Lyon B, Dam M. Gamma-vinyl-GABA: a single-blind trial in patients with epilepsy. Acta Neurol Scand 1983; 68: 34. 2. Gram L, Klosterskov P, Dam M. Gamma-vinyl-GABA: a double-blind placebocontrolled trial in partial epilepsy. Ann Neurol 1985; 17: 262. 3. Dam M. Long-term evaluation of vigabatrin (Gamma Vinyl GABA) in epilepsy. Epilepsia 1989; 30 (suppl 3): S26-S30.
SIR,-Dr Sander and Dr Hart warn of adverse behavioural disturbances, including psychosis, in patients taking vigabatrin as an anticonvulsant. 31 patients out of 145 had side-effects sufficiently severe to warrant withdrawal from the drug. Most of these adverse responses were behavioural disturbances, including 7 patients who had psychotic reactions (4 of whom had had complete cessation of seizures).
disease.5 One cannot preclude an idiopathic myocarditis, but the temporal relation between administration of mesalazine and symptoms suggests a drug-related myocarditis; the absence of hypersensitivity symptoms and eosinophil infiltrations rules out a classic hypersensitivity myocarditis.6 We suggest that mesalazine or sulphasalazine are replaced by glucocorticoids if cardiac symptoms arise during treatment. Departments of Internal Medicine, Pathology, and Surgery, County Central Hospital,
Portable infusor.
Naestved, Denmark
49 inpatients received intravenous infusion2 with this apparatus. 12 had 500 ml of isotonic sodium chloride solution3in about 10 min. 1 patient who needed fast infusion received the same volume of solution in 3 min. In the other 36 patients the same volume was given in about 60 min. In every case the apparatus was efficient and no adverse effect was noted. This infusor would be useful in emergency perfusion of victims of catastrophes. Service for Emergencies, Hôpital de Brabois, 54500 Vandoeuvre-Les-Nancy, France
1.
GILBERT THIBAUT
KJELD S. KRISTENSEN ASBJØRN HØEGHOLM LENE BOHR SØREN FRIIS
1. Agnholt J, Sørensen HT, Rasmussen SN, Gøtzsche C-O, Halkier P. Cardiac hypersensitivity to 5-aminosalicylic acid. Lancet 1989; i: 1135. 2. Deboever G, Devogelaere R, Holvoet G. Sulphasalazine-induced lupus-like syndrome with cardiac tamponade in a patient with ulcerative colitis. Am J Gastroenterol 1989; 84: 85-86. 3. Weber P, Becker W, Jenss H. Pericardial effusion during treatment on Crohn’s disease with 5-aminosalicylic acid. Dtsch Med Wochenschr 1988; 113: 1806-07. 4. Thuesen L, Sørensen J. Ulcerative colitis complicated by myopericarditis and complete atrio-ventricular block. Ugeskr Laeger 1979; 141: 2760-61. 5. Frid C, Bjarke B, Eriksson M. Myocarditis in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1986; 5: 964-65. 6. Fenoglio JJ, McAllister HA, Mullick FG. Drug related myocarditis, I: hypersensitivity myocarditis. Hum Pathol 1981; 12: 900-07.
Viljoen JF. The ubiquitous (and extravagant) intravenous infusion. JAMA 1977; 237:
1927-28. 2. Hirlekar G, Hauksson H, Jonsson B, Gariglia N, Arnthorsson G. Haemodilution in elective surgery. Bibl Haematol 1981; 47: 279-86. 3. Lundsgaard-Hansen P. Emploi clinique des solutions d’albumine, de colloides artificiels et d’électrolytes. Méd Hyg Genève 1972; 30: 638-40.
Fatal myocarditis associated with mesalazine SIR,-Dr Agnholt and colleagues1 showed that mesalazine could induce myocardial injury. We report a case of fatal myocarditis in which mesalazine is also incriminated. A 20-year-old woman with a 6-month history of bloody diarrhoea was admitted. For 3 years she had had a benign exostosis on the iliac crest that was not growing, light arthralgia, and psoriatic lesions mainly on the palms and soles. No infectious cause of the diarrhoea was established. Double-contrast barium enema showed ulcerations throughout the colon, and a rectal biopsy showed acute mucosal inflammation. Chest radiography and electrocardiogram (ECG) were normal. Treatment with mesalazine 1-5 g daily was started, and stool frequency decreased. Thirteen days later the patient had sudden severe chest pain and dizziness; ECG showed left anterior hemiblock followed by ventricular fibrillation, which was successfully treated by DC cardioversion. Echocardiography showed fluctuating dyskinesia septally and laterally. She had anteroseptal ST-elevations and Q-waves on ECG. Plasma lactic dehydrogenase isoenzyme 1 was six times over the upper reference level. Despite inotropic support and artificial ventilation the patient died 22 hours later in cardiogenic shock. At necropsy a pancolitis was seen which had been healing. Heart size and coronary arteries were normal, no pericarditis or endocarditis was present. The myocardium was speckled throughout; microscopically there were confluent necrotic areas with intense infiltration by neutrophils. The lesions were of the same age and without Aschoff bodies, eosinophils, or perivascular predilection. The unaffected myocardium appeared normal. Viral cultures from myocardium and intestines as well as tests for antinuclear antibodies were negative. Sulphasalazine can induce a lupus-like syndrome with pericarditis2 whereas its metabolite mesalazine has been suspected to induce pericardial effusion3 and myocarditis.l Perimyocarditis is also a rare but recognised extra-intestinal manifestation of inflammatory bowel diseases Our patient had a very severe myocarditis without pericarditis. The latter in conjunction with the lack of association between severity of intestinal and cardiac involvement argues against the carditis being an extra-intestinal manifestation of the bowel
Vigabatrin and
behaviour disturbances
SIR,-Dr Sander and Dr Hart (Jan 6, p 57) draw attention to some side-effects of the new effective antiepileptic drug vigabatrin. I have been using vigabatrin since 1981 and have conducted a single-blind trial,’ a double-blind tria1,2 and long-term studies on this drug.3 In all we have treated 117 patients, many of whom have been on vigabatrin for up to eight years. Although the side-effects Sander and Hart mention are not unknown, I have not seen them with the same severity. Nor has the drug had to be withdrawn in about 20% of patients as they suggest. I have seen only 2 patients with frank psychotic symptoms; one required withdrawal but the other is still on vigabatrin and has responded well. Other behavioural disturbances such as irritability, confusion, and aggression were seen in 8 patients, usually mentally retarded patients with severe brain lesions, and in only 7 of these were they significant enough to necessitate withdrawal of
vigabatrin. Confusion was observed in the early studies in 2 elderly patients, and was probably related to decreased renal clearance. We now find that this effect is easily prevented by the use of a lower dose. Patient selection may account for my different experience with vigabatrin, since my patients may not be as severely affected as those referred to the Chalfont Centre for Epilepsy. I agree that treatment with vigabatrin in severely retarded patients should be monitored closely in the early stages. Elderly patients with reduced renal clearance should be treated with lower doses. In all our patients the behavioural disturbances have reversed on either lowering the dose or stopping the drug. University Clinic of Neurology, Hvidovre Hospital, DK-2650 Hvidovre, Denmark
M. DAM
1. Gram L, Blatt
Lyon B, Dam M. Gamma-vinyl-GABA: a single-blind trial in patients with epilepsy. Acta Neurol Scand 1983; 68: 34. 2. Gram L, Klosterskov P, Dam M. Gamma-vinyl-GABA: a double-blind placebocontrolled trial in partial epilepsy. Ann Neurol 1985; 17: 262. 3. Dam M. Long-term evaluation of vigabatrin (Gamma Vinyl GABA) in epilepsy. Epilepsia 1989; 30 (suppl 3): S26-S30.
SIR,-Dr Sander and Dr Hart warn of adverse behavioural disturbances, including psychosis, in patients taking vigabatrin as an anticonvulsant. 31 patients out of 145 had side-effects sufficiently severe to warrant withdrawal from the drug. Most of these adverse responses were behavioural disturbances, including 7 patients who had psychotic reactions (4 of whom had had complete cessation of seizures).
