- Email: [email protected]
NON-MOSAIC TRISOMY 16 CONFINED TO VILLI
915 this PG. These data would be of interest since even low doses of aspirin have been shown to inhibit human aortic PGI2 synthesis.4 Metabolic Unit,
Department of Chemical Pathology and Human Metabolism,
Royal Free Hospital and School of Medicine, London NW3 2PF
M. A. KHOKHER J. Y. JEREMY D. P. MIKHAILIDIS P. DANDONA
MA, Dandona P. The effect of indomethacin and aspirin on alkaline phosphatase secretion (3H)-thymidine incorporation by human osteoblasts. Br J
Plasma exchange had no beneficial effect on the disabling continuous muscle spasm in our patients. Immunosuppression also conferred no benefit over two months in patient 1. Longer term immunosuppressive treatment might be effective in SMS, and this needs to be studied. Theoretically, since there is evidence of intrathecal synthesis of anti-GAD antibodies in SMS,1 plasma exchange would not be expected to lead to improvement of SMS, as our experience shows.
1 Khokher
Rheumatol 1988; 27: 291-94. 2. Rashad S, Revell P, Hemingway A, Low F, Rainsford K, Walker F. Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989; ii: 519-21. 3. Jeremy JY, Mikhailidis DP, Dandona P. Vascular trauma and prostacyclin release. Microcirc Endothel Lymph 1984; 1: 629-44. 4. Tsang V, Jeremy JY, Mikhailidis DP, Walesby RK, Wright JC, Dandona P. Release of prostacyclin from human aorta. Cardiovasc Res 1988; 22: 489-93.
PLASMA EXCHANGE AND IMMUNOSUPPRESSION
We thank Dr F. Folli, Dr M. Solimena, and Prof P. de Camilli for measuring anti-GAD antibodies and other autoantibodies.
University Department of Clinical Neurology, and MRC Human Movement and Balance Unit, Institute of Neurology, London WC1N 3BG; National Hospital for Nervous Diseases,
London; and Department of Immunology, Royal Postgraduate Medical School, London
A. E. HARDING P. D. THOMPSON R. S. KOCEN
J. R. BATCHELOR N. DAVEY C. D. MARSDEN
IN THE STIFF MAN SYNDROME
SiR,—An autoimmune basis for the stiff man syndrome (SMS) is suggested by the finding of antibodies directed against glutamic acid decarboxylase (GAD) in the serum and cerebrospinal fluid (CSF) of patients with this disorder. In addition, there is an association between SMS and other autoimmune diseases.1,2 Striking improvement following plasma exchange has been reported in one patient with SMS;3 our experience of this approach to treatment has not been so rewarding. Patient 1.-A 50-year-old man; progressive painful stiffness of the back and abdominal muscles developed in 1985, leading to persistent lumbar extension and dyspnoea on exertion. The muscle spasm was partly relieved by diazepam 15 mg and baclofen 60 mg daily. He had been treated for pernicious anaemia since 1971, and insulin-dependent diabetes was diagnosed in 1985. On examination the abdominal and paraspinal muscles were continuously contracting, confirmed by surface and needle electromyography (EMG). Breathing was largely diaphragmatic and he had thoracolumbar scoliosis and lordosis. Antibodies against pancreatic islet cells and gastric parietal cells were present in serum; other autoantibodies were negative. HLA typing was A3, 32; B7, 8; Cw7; DR3,4; DQw2,3; DRW52,53. Plasma exchange was done daily for five days, with a total exchange of 121.Prednisolone 80 mg on alternate days and azathioprine (25 mg/kg) daily were begun. The patient’s diabetes became difficult to control and two months later, despite haematological monitoring, severe leucopoenia developed; azathioprine and prednisolone were withdrawn. The dose of baclofen and diazepam remained the same throughout. There was no evidence of clinical improvement, and neurophysiological assessments, done twelve days and two months after starting plasma exchange, showed no reduction in the amount of motor unit activity compared with that before treatment. Patient 2.-A 45-year-old man; he had a five-year history of progressive painful stiffness of his back and legs, and difficulty in walking. He had a severe lumbar lordosis with spasm of the paraspinal, abdominal, and thigh muscles. His gait was stiff and laborious. Autoantibodies against pancreatic islet cells and gastric parietal cells were present in serum. HLA typing was A2, 3; B40, 62; Cw3,4; DR3,4; DQw2,3; DRW52,53. A 15plasma exchange was done in five sessions over five days. No improvement was seen in a year of follow-up; surface EMG recordings before and seven days after plasma exchange showed no reduction in motor unit activity. The patient had some benefit from baclofen 50 mg, diazepam 25 I11g, and sodium valproate 600 mg daily throughout. In both patients, antibodies directed against GADl were present in serum and CSF; oligoclonal IgG was found in the CSF. These patients had the typical clinical features of SMS and clinical or investigative evidence of other autoimmune disease described in SMS.2 An association with HLA B44 has been suggested,2 but was not seen in either of these patients. However, both had the DR4 antigen, which is in linkage dysequilibrium with B44 in caucasian populations.2 It is also noteworthy that the DR3 and DR4 antigens (both seen in each patient) are strongly associated with insulin-dependent diabetes mellitus.4
M, Folli F, Denis-Donini S, et al. Autoantibodies to glutamic acid decarboxylase in a patient with stiff man syndrome, epilepsy and type 1 diabetes mellitus. N Engl J Med 1988; 318: 1012-20. 2. Williams AC, Nutt JG, Hare T. Autoimmunity in stiff man syndrome. Lancet 1988; ii: 1. Solimena
222.
AM, Folli F, Pozza G, et al. Plasmapheresis in the treatment of stiff man syndrome. N Engl J Med 1989; 320: 1499. 4. Todd JA, Acha-Orbea H, Bell JI, et al. Molecular basis for MHC class II-associated autoimmunity. Science 1988; 240: 1003-09. 3. Vicari
NON-MOSAIC TRISOMY 16 CONFINED TO VILLI
SIR,--4Chorionic villus sampling (CVS) is widely practised for the diagnosis of fetal genetic and chromosomal disorders in the first trimester of pregnancy. Few false-negative cytogenetic diagnoses have been reported. A more common finding is that of a chromosome abnormality confined to villus tissue--ie, not present in the fetus. In most such cases, either only direct preparations of villus chromosomes were analysed, or mosaicism (both normal and abnormal cell lines) were present in villi. We report here a case of non-mosaic chromosome abnormality in both direct preparations and cultured villus cells, with a phenotypically normal but borderline growth-retarded fetus. A 35-year-old woman, gravida 2, para 1, had CVS at ten weeks’ gestation. A previous pregnancy, in which CVS was also done, showed normal chromosome findings and resulted in the birth of a 3-66 kg male infant. In the current pregnancy, initial ultrasound examination at 8 weeks’ gestation showed no evidence of more than 1 fetus or of abnormality. 20 mg of villus tissue was obtained by transcervical aspiration. Both direct preparations and cultured villi were examined. All cells showed karyotype 47,XX, + 16. At fourteen weeks’ gestation ultrasound examination was normal. Amniocentesis showed normal chromosome and ot-fetoprotein results. The pregnancy continued and serial ultrasound examinations indicated fetal growth at the 10th percentile. At thirty-seven weeks’ gestation a phenotypically normal female infant weighing 2-315 kg was delivered. All growth indices were at the 10-25th centile. The placenta was grossly and microscopically normal with no evidence of a resorbed twin. Cord-blood lymphocytes showed normal chromosomes; samples from four placental sites were almost entirely 47,XX, + 16. We are aware of one other case of non-mosaic villus trisomy 16 in direct and culture preparations which resulted in a normal 2-724 kg (thirty-nine weeks’ gestation) livebom baby.’ Hashish et al2 have reported a pregnancy with mosaic villus trisomy 16 and a growth-retarded, phenotypically normal stillborn baby. The finding of a chromosome abnormality usually associated with non-viability, in the presence of a grossly normal fetus on ultrasound, should alert the physician to the likelihood that the chromosome abnormality is confined to the placenta. However, despite normal fetal chromosomes, a chromosomally abnormal placenta may have a deleterious effect on fetal growth.’ Previous surveys of aborted fetuses have shown a high frequency of trisomy 16. In some cases these findings may have represented an abnormality in chorionic villi only; nonetheless, the outcome was
916 pregnancy loss.
Perhaps
villus
trisomy
intrauterine growth, resulting in fetal loss in intrauterine growth in others. We thank Joan O’Brien, and Pat
16
disrupts normal
most cases
and poor
Schneider, for their help in following this
patient.
Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois 60637, USA
M. S. VERP B. ROSINSKY Z. SHEIKH A. P. AMAROSE
Tharapel AT, Elias S, Shulman LP, et al. Resorbed co-twin as an explanation for discrepant chorionic villus results: non-mosaic 47,XX,+16 in villi (direct and culture) with normal (46,XX) amniotic fluid and neonatal brain. Prenat Diagn 1989; 9: 467-72. 2. Hashish AF, Monk NA, Lovell-Smith MPF, et al. Trisomy 16 detected at chorionic villus sampling. Prenat Diagn 1989; 9: 427-32. 3. Kalousek DK, Dill FJ. Chromosomal mosaicism confined to the placenta in human conceptions. Science 1983; 221: 665-67. 4. Warburton D, Stein Z, Kline J, Susser M. Chromosome abnormalities in spontaneous abortion: data from the New York City study. In: Porter IH, Hook EB, eds. Human embryonic and fetal death. New York: Academic Press, 1980: 261-87. 1.
HYMENOPIERA STINGS AND BETA-BLOCKERS
SIR,-Dr Pedersen (Sept 9, p 619) usefully emphasises the dangers of anaphylaxis to patients taking beta-blockers following hymenoptera stings. Because of his personal experience, he now carries an intravenous dexamethasone shock-pack while playing golf. Although this practice is certainly of some value I think it important to emphasise that adrenaline (subcutaneous, intramuscular, or inhaled) is the emergency treatment of anaphylaxis, even in the presence of beta-blockers, because of its adrenergic effects. It is, unfortunately, common to see anaphylaxis treated in emergency departments with antihistamines and steroids only, despite the fact that they offer no immediate benefit.1 It is my practice to provide patients at risk of anaphylaxis with subcutaneous adrenaline and a metered-dose adrenaline aerosol, following clear instructions for their use.2 Department of Child Health, St George’s Hospital Medical School, London SW17 0RE
I. POLLOCK
1. Frankland AW.
Allergy to insects and arachnids. In: Lessof MH, ed. Allergy: immunological and clinical aspects. Chichester: Wiley, 1984: 425-45. 2. British National Formulary. No 17. 1989: 132-33.
Pedersen carries an intravenous dexamethasone shock pack in his golf bag. This is inappropriate not only because he will not be able to teach the wasps to visit him solely on the golf course but also because corticosteroids have a delayed onset of action of several hours. The therapy of first choice is adrenaline unless the patient is on a beta-blocker. It would be wise to carry an adrenaline autoinjector (eg, ’EpiPen’), provided that the beta-blocker has been stopped.4 Moreover, patients with a history of sting anaphylaxis and current evidence of venom-specific IgE should receive immunotherapy.s Department of General Practice, University of Leiden, 2301 CB Leiden, Netherlands
EM, Nowak RM, Lee TG, Tomlanovich MC. Epinephrine for treatment of anaphylactic shock. JAMA 1984; 251: 2118-22. Rubenstein HS. Bee-sting diseases: who is at risk? What is the treatment? Lancet 1982;
1. Barach 2.
i: 496-99. 3. Benitah E, Nataf P, Herman D. Accidents anaphylactiques chez des patients traites par
bêta-bloquants. Thérapie 1986; 41: 139-42. 4. Valentine MD, Lichtenstein LM. Anaphylaxis and stinging insect hypersensitivity. JAMA 1987; 258: 2881-85. 5. Reisman RE. Insect allergy. In: Middleton E, Reed CE, Ellis EF, Adkinson NF, Yunginger JW, ed. Allergy: principles and practice. 3rd ed. St Louis: CV Mosby, 1988.
INTRATHECAL BACLOFEN FOR CEREBRAL SPASTICITY
SIR,-Dr Saltuari and colleagues (Aug 26, p 503) report a lack of clinical improvement after application of up to 100 jig intrathecal baclofen in a patient with cerebral spasticity, although they found an apparently dose-related attenuation of stretch reflexes and a slight reduction of muscle tone. Should they have increased the dose further? We have used intrathecal baclofen in 11 children with cerebral spasticity, aged 3 to 18 years, most of whom required 100 J.ig or more for a successful response to a bolus test dose of intrathecal baclofen (table). The dose required was more dependent on severity of spasticity than on age. In 10 children who responded, implantation of a pump system enabled daily intrathecal delivery of 25-700 jlg baclofen. Spasticity was reduced in all patients, although increased doses have been necessary in several (1 has required an increase from 100 to 700 ug baclofen per day over 4 years of intrathecal therapy). A girl who had intractable seizures has not required anticonvulsants since intrathecal baclofen was started. DOSES OF INTRATHECAL BACLOFEN I
SIR,-Dr Pedersen draws attention to serious problems that may arise if beta-blocker users have an anaphylactic reaction to a wasp or bee sting, for example. He suggests that patients on beta-blockers should be warned, that they should avoid bees, wasps, yellowjackets, and hornets, and that if they are stung they will need urgent hospital attendance. Beta-blockers can enforce an IgE-mediated reaction to hymenoptera venom, if such a reaction occurs. Moreover, therapy with adrenaline can be dangerous in patients who use betablockers.1 However, beta-blockers do not cause such an allergic reaction. The risk of anaphylaxis after a sting is very small and is still very small in someone who takes a beta-blocker, without an allergic reaction in the past. The problem is that "those at risk have not been identified".2 This is much clearer in respect of anaphylaxis due to other antigens, such as food or medicines. We think that beta-blockers are contraindicated only in those with a known serious allergy or in those on immunotherapy (desensitisation). We agree with Rubenstein that "we must strive to liberate patients from unrealistic fears of highly improbable events".2 Pedersen mentions a "very disturbing" article, reporting that "all of 14 patients on beta-blockers had a severe anaphylactic shock after hymenoptera sting". From this, one might conclude that the use of a beta-blocker is by itself a serious risk factor for anaphylactic shock. The data cited, however, are from a retrospective study on 249 patients who were selected because they received immunotherapy with hymenoptera venom.
MARCEL J. J. S. CROBACH JAN D. MULDER DZN
I
1-
I
A word of caution. Two children were given ten times the intended bolus dose by mistake, because of misplacing of a decimal point, after 15 min they were hypnotic, and at around 10 hours they had vomiting, bradycardia, and respiratory arrest requiring ventilation. They both recovered without any obvious long-term deficit. Nevertheless, we would encourage Dr Saltuari to use a higher bolus dose of intrathecal baclofen (up to 200 pg) before this potentially valuable treatment for patients with cerebral spasticity is ruled out. Departments of Neuropaediatrics and Neurosurgery, Justus Liebig University, 6300 Giessen, West Germany
D. DRALLE G. NEUHAUSER J. C. TONN
Department of Chemical Pathology and Human Metabolism,
Royal Free Hospital and School of Medicine, London NW3 2PF
M. A. KHOKHER J. Y. JEREMY D. P. MIKHAILIDIS P. DANDONA
MA, Dandona P. The effect of indomethacin and aspirin on alkaline phosphatase secretion (3H)-thymidine incorporation by human osteoblasts. Br J
Plasma exchange had no beneficial effect on the disabling continuous muscle spasm in our patients. Immunosuppression also conferred no benefit over two months in patient 1. Longer term immunosuppressive treatment might be effective in SMS, and this needs to be studied. Theoretically, since there is evidence of intrathecal synthesis of anti-GAD antibodies in SMS,1 plasma exchange would not be expected to lead to improvement of SMS, as our experience shows.
1 Khokher
Rheumatol 1988; 27: 291-94. 2. Rashad S, Revell P, Hemingway A, Low F, Rainsford K, Walker F. Effect of non-steroidal anti-inflammatory drugs on the course of osteoarthritis. Lancet 1989; ii: 519-21. 3. Jeremy JY, Mikhailidis DP, Dandona P. Vascular trauma and prostacyclin release. Microcirc Endothel Lymph 1984; 1: 629-44. 4. Tsang V, Jeremy JY, Mikhailidis DP, Walesby RK, Wright JC, Dandona P. Release of prostacyclin from human aorta. Cardiovasc Res 1988; 22: 489-93.
PLASMA EXCHANGE AND IMMUNOSUPPRESSION
We thank Dr F. Folli, Dr M. Solimena, and Prof P. de Camilli for measuring anti-GAD antibodies and other autoantibodies.
University Department of Clinical Neurology, and MRC Human Movement and Balance Unit, Institute of Neurology, London WC1N 3BG; National Hospital for Nervous Diseases,
London; and Department of Immunology, Royal Postgraduate Medical School, London
A. E. HARDING P. D. THOMPSON R. S. KOCEN
J. R. BATCHELOR N. DAVEY C. D. MARSDEN
IN THE STIFF MAN SYNDROME
SiR,—An autoimmune basis for the stiff man syndrome (SMS) is suggested by the finding of antibodies directed against glutamic acid decarboxylase (GAD) in the serum and cerebrospinal fluid (CSF) of patients with this disorder. In addition, there is an association between SMS and other autoimmune diseases.1,2 Striking improvement following plasma exchange has been reported in one patient with SMS;3 our experience of this approach to treatment has not been so rewarding. Patient 1.-A 50-year-old man; progressive painful stiffness of the back and abdominal muscles developed in 1985, leading to persistent lumbar extension and dyspnoea on exertion. The muscle spasm was partly relieved by diazepam 15 mg and baclofen 60 mg daily. He had been treated for pernicious anaemia since 1971, and insulin-dependent diabetes was diagnosed in 1985. On examination the abdominal and paraspinal muscles were continuously contracting, confirmed by surface and needle electromyography (EMG). Breathing was largely diaphragmatic and he had thoracolumbar scoliosis and lordosis. Antibodies against pancreatic islet cells and gastric parietal cells were present in serum; other autoantibodies were negative. HLA typing was A3, 32; B7, 8; Cw7; DR3,4; DQw2,3; DRW52,53. Plasma exchange was done daily for five days, with a total exchange of 121.Prednisolone 80 mg on alternate days and azathioprine (25 mg/kg) daily were begun. The patient’s diabetes became difficult to control and two months later, despite haematological monitoring, severe leucopoenia developed; azathioprine and prednisolone were withdrawn. The dose of baclofen and diazepam remained the same throughout. There was no evidence of clinical improvement, and neurophysiological assessments, done twelve days and two months after starting plasma exchange, showed no reduction in the amount of motor unit activity compared with that before treatment. Patient 2.-A 45-year-old man; he had a five-year history of progressive painful stiffness of his back and legs, and difficulty in walking. He had a severe lumbar lordosis with spasm of the paraspinal, abdominal, and thigh muscles. His gait was stiff and laborious. Autoantibodies against pancreatic islet cells and gastric parietal cells were present in serum. HLA typing was A2, 3; B40, 62; Cw3,4; DR3,4; DQw2,3; DRW52,53. A 15plasma exchange was done in five sessions over five days. No improvement was seen in a year of follow-up; surface EMG recordings before and seven days after plasma exchange showed no reduction in motor unit activity. The patient had some benefit from baclofen 50 mg, diazepam 25 I11g, and sodium valproate 600 mg daily throughout. In both patients, antibodies directed against GADl were present in serum and CSF; oligoclonal IgG was found in the CSF. These patients had the typical clinical features of SMS and clinical or investigative evidence of other autoimmune disease described in SMS.2 An association with HLA B44 has been suggested,2 but was not seen in either of these patients. However, both had the DR4 antigen, which is in linkage dysequilibrium with B44 in caucasian populations.2 It is also noteworthy that the DR3 and DR4 antigens (both seen in each patient) are strongly associated with insulin-dependent diabetes mellitus.4
M, Folli F, Denis-Donini S, et al. Autoantibodies to glutamic acid decarboxylase in a patient with stiff man syndrome, epilepsy and type 1 diabetes mellitus. N Engl J Med 1988; 318: 1012-20. 2. Williams AC, Nutt JG, Hare T. Autoimmunity in stiff man syndrome. Lancet 1988; ii: 1. Solimena
222.
AM, Folli F, Pozza G, et al. Plasmapheresis in the treatment of stiff man syndrome. N Engl J Med 1989; 320: 1499. 4. Todd JA, Acha-Orbea H, Bell JI, et al. Molecular basis for MHC class II-associated autoimmunity. Science 1988; 240: 1003-09. 3. Vicari
NON-MOSAIC TRISOMY 16 CONFINED TO VILLI
SIR,--4Chorionic villus sampling (CVS) is widely practised for the diagnosis of fetal genetic and chromosomal disorders in the first trimester of pregnancy. Few false-negative cytogenetic diagnoses have been reported. A more common finding is that of a chromosome abnormality confined to villus tissue--ie, not present in the fetus. In most such cases, either only direct preparations of villus chromosomes were analysed, or mosaicism (both normal and abnormal cell lines) were present in villi. We report here a case of non-mosaic chromosome abnormality in both direct preparations and cultured villus cells, with a phenotypically normal but borderline growth-retarded fetus. A 35-year-old woman, gravida 2, para 1, had CVS at ten weeks’ gestation. A previous pregnancy, in which CVS was also done, showed normal chromosome findings and resulted in the birth of a 3-66 kg male infant. In the current pregnancy, initial ultrasound examination at 8 weeks’ gestation showed no evidence of more than 1 fetus or of abnormality. 20 mg of villus tissue was obtained by transcervical aspiration. Both direct preparations and cultured villi were examined. All cells showed karyotype 47,XX, + 16. At fourteen weeks’ gestation ultrasound examination was normal. Amniocentesis showed normal chromosome and ot-fetoprotein results. The pregnancy continued and serial ultrasound examinations indicated fetal growth at the 10th percentile. At thirty-seven weeks’ gestation a phenotypically normal female infant weighing 2-315 kg was delivered. All growth indices were at the 10-25th centile. The placenta was grossly and microscopically normal with no evidence of a resorbed twin. Cord-blood lymphocytes showed normal chromosomes; samples from four placental sites were almost entirely 47,XX, + 16. We are aware of one other case of non-mosaic villus trisomy 16 in direct and culture preparations which resulted in a normal 2-724 kg (thirty-nine weeks’ gestation) livebom baby.’ Hashish et al2 have reported a pregnancy with mosaic villus trisomy 16 and a growth-retarded, phenotypically normal stillborn baby. The finding of a chromosome abnormality usually associated with non-viability, in the presence of a grossly normal fetus on ultrasound, should alert the physician to the likelihood that the chromosome abnormality is confined to the placenta. However, despite normal fetal chromosomes, a chromosomally abnormal placenta may have a deleterious effect on fetal growth.’ Previous surveys of aborted fetuses have shown a high frequency of trisomy 16. In some cases these findings may have represented an abnormality in chorionic villi only; nonetheless, the outcome was
916 pregnancy loss.
Perhaps
villus
trisomy
intrauterine growth, resulting in fetal loss in intrauterine growth in others. We thank Joan O’Brien, and Pat
16
disrupts normal
most cases
and poor
Schneider, for their help in following this
patient.
Department of Obstetrics and Gynecology, University of Chicago, Chicago, Illinois 60637, USA
M. S. VERP B. ROSINSKY Z. SHEIKH A. P. AMAROSE
Tharapel AT, Elias S, Shulman LP, et al. Resorbed co-twin as an explanation for discrepant chorionic villus results: non-mosaic 47,XX,+16 in villi (direct and culture) with normal (46,XX) amniotic fluid and neonatal brain. Prenat Diagn 1989; 9: 467-72. 2. Hashish AF, Monk NA, Lovell-Smith MPF, et al. Trisomy 16 detected at chorionic villus sampling. Prenat Diagn 1989; 9: 427-32. 3. Kalousek DK, Dill FJ. Chromosomal mosaicism confined to the placenta in human conceptions. Science 1983; 221: 665-67. 4. Warburton D, Stein Z, Kline J, Susser M. Chromosome abnormalities in spontaneous abortion: data from the New York City study. In: Porter IH, Hook EB, eds. Human embryonic and fetal death. New York: Academic Press, 1980: 261-87. 1.
HYMENOPIERA STINGS AND BETA-BLOCKERS
SIR,-Dr Pedersen (Sept 9, p 619) usefully emphasises the dangers of anaphylaxis to patients taking beta-blockers following hymenoptera stings. Because of his personal experience, he now carries an intravenous dexamethasone shock-pack while playing golf. Although this practice is certainly of some value I think it important to emphasise that adrenaline (subcutaneous, intramuscular, or inhaled) is the emergency treatment of anaphylaxis, even in the presence of beta-blockers, because of its adrenergic effects. It is, unfortunately, common to see anaphylaxis treated in emergency departments with antihistamines and steroids only, despite the fact that they offer no immediate benefit.1 It is my practice to provide patients at risk of anaphylaxis with subcutaneous adrenaline and a metered-dose adrenaline aerosol, following clear instructions for their use.2 Department of Child Health, St George’s Hospital Medical School, London SW17 0RE
I. POLLOCK
1. Frankland AW.
Allergy to insects and arachnids. In: Lessof MH, ed. Allergy: immunological and clinical aspects. Chichester: Wiley, 1984: 425-45. 2. British National Formulary. No 17. 1989: 132-33.
Pedersen carries an intravenous dexamethasone shock pack in his golf bag. This is inappropriate not only because he will not be able to teach the wasps to visit him solely on the golf course but also because corticosteroids have a delayed onset of action of several hours. The therapy of first choice is adrenaline unless the patient is on a beta-blocker. It would be wise to carry an adrenaline autoinjector (eg, ’EpiPen’), provided that the beta-blocker has been stopped.4 Moreover, patients with a history of sting anaphylaxis and current evidence of venom-specific IgE should receive immunotherapy.s Department of General Practice, University of Leiden, 2301 CB Leiden, Netherlands
EM, Nowak RM, Lee TG, Tomlanovich MC. Epinephrine for treatment of anaphylactic shock. JAMA 1984; 251: 2118-22. Rubenstein HS. Bee-sting diseases: who is at risk? What is the treatment? Lancet 1982;
1. Barach 2.
i: 496-99. 3. Benitah E, Nataf P, Herman D. Accidents anaphylactiques chez des patients traites par
bêta-bloquants. Thérapie 1986; 41: 139-42. 4. Valentine MD, Lichtenstein LM. Anaphylaxis and stinging insect hypersensitivity. JAMA 1987; 258: 2881-85. 5. Reisman RE. Insect allergy. In: Middleton E, Reed CE, Ellis EF, Adkinson NF, Yunginger JW, ed. Allergy: principles and practice. 3rd ed. St Louis: CV Mosby, 1988.
INTRATHECAL BACLOFEN FOR CEREBRAL SPASTICITY
SIR,-Dr Saltuari and colleagues (Aug 26, p 503) report a lack of clinical improvement after application of up to 100 jig intrathecal baclofen in a patient with cerebral spasticity, although they found an apparently dose-related attenuation of stretch reflexes and a slight reduction of muscle tone. Should they have increased the dose further? We have used intrathecal baclofen in 11 children with cerebral spasticity, aged 3 to 18 years, most of whom required 100 J.ig or more for a successful response to a bolus test dose of intrathecal baclofen (table). The dose required was more dependent on severity of spasticity than on age. In 10 children who responded, implantation of a pump system enabled daily intrathecal delivery of 25-700 jlg baclofen. Spasticity was reduced in all patients, although increased doses have been necessary in several (1 has required an increase from 100 to 700 ug baclofen per day over 4 years of intrathecal therapy). A girl who had intractable seizures has not required anticonvulsants since intrathecal baclofen was started. DOSES OF INTRATHECAL BACLOFEN I
SIR,-Dr Pedersen draws attention to serious problems that may arise if beta-blocker users have an anaphylactic reaction to a wasp or bee sting, for example. He suggests that patients on beta-blockers should be warned, that they should avoid bees, wasps, yellowjackets, and hornets, and that if they are stung they will need urgent hospital attendance. Beta-blockers can enforce an IgE-mediated reaction to hymenoptera venom, if such a reaction occurs. Moreover, therapy with adrenaline can be dangerous in patients who use betablockers.1 However, beta-blockers do not cause such an allergic reaction. The risk of anaphylaxis after a sting is very small and is still very small in someone who takes a beta-blocker, without an allergic reaction in the past. The problem is that "those at risk have not been identified".2 This is much clearer in respect of anaphylaxis due to other antigens, such as food or medicines. We think that beta-blockers are contraindicated only in those with a known serious allergy or in those on immunotherapy (desensitisation). We agree with Rubenstein that "we must strive to liberate patients from unrealistic fears of highly improbable events".2 Pedersen mentions a "very disturbing" article, reporting that "all of 14 patients on beta-blockers had a severe anaphylactic shock after hymenoptera sting". From this, one might conclude that the use of a beta-blocker is by itself a serious risk factor for anaphylactic shock. The data cited, however, are from a retrospective study on 249 patients who were selected because they received immunotherapy with hymenoptera venom.
MARCEL J. J. S. CROBACH JAN D. MULDER DZN
I
1-
I
A word of caution. Two children were given ten times the intended bolus dose by mistake, because of misplacing of a decimal point, after 15 min they were hypnotic, and at around 10 hours they had vomiting, bradycardia, and respiratory arrest requiring ventilation. They both recovered without any obvious long-term deficit. Nevertheless, we would encourage Dr Saltuari to use a higher bolus dose of intrathecal baclofen (up to 200 pg) before this potentially valuable treatment for patients with cerebral spasticity is ruled out. Departments of Neuropaediatrics and Neurosurgery, Justus Liebig University, 6300 Giessen, West Germany
D. DRALLE G. NEUHAUSER J. C. TONN