772 in patient B. Evolution into a histological malignant neoplastic process (immunoblastic sarcoma’) was not seen. These histological alterations in the skin are so characteristic for angioimmunoblastic lymphadenopathy that skin biopsy as an additional means of arriving at the correct diagnosis of this intriguing disease seems warranted. C. J. L. M. MEIJER Departments of Pathology, Dermatology, and Hæmatology, University Medical Centre, Leiden, Netherlands
E. SCHEFFER G. P. LAUW A. F. D. SMIT G. J. DEN OTTOLANDER
DERMATOMYOSITIS AFTER B.C.G. VACCINATION cause of dermatomyositis is unknown, but immechanisms are assumed to play a role. In adults, there can be a connection with malignancy, and resection of malignant tumours may result in improvement of the dermatomyositis. B.C.G. vaccination increases the immune response to a variety of antigens, so perhaps two cases of dermatomyositis concomitant with B.C.G. vaccination will be of interest. We would be interested to know if others have had similar experiences. If such associations are not fortuitous those affected might be able to claim compensation. A boy, who had been vaccinated with B.C.G. in the autumn of 1974 at the age of 14, remained Pirquet negative and was revaccinated in September, 1975, after which he became Pirquet positive. 5-6 weeks after revaccination he began to show signs of an exanthema which was typical of dermatomyositis, and pronounced muscular weakness developed. Muscle enzymes activities were greatly increased. Electromyography revealed a mixed myogenic and neurogenic lesion. Skin and muscle biopsy finding were typical of dermatomyositis. Rheumatoid factor or antinuclear antibodies have not been found. The patient’s HLA type was Al,9; B8,15; CW3; DRW3. No clinical or radiological signs of B.C.G. osteomyelitis or general infection have been found. He has been admitted to hospital several times, and, despite intensive treatment with prednisone and methotrexate, he is debilitated and there are signs of progression of the disease. The second patient, also a boy, was vaccinated with B.c.G. in 1975 at the age of 12. He became Pirquet positive, and began to show signs of myositis 2-3 weeks after vaccination, first in the vaccinated area, later in the other extremities, as well as on the chest, back and neck. Both liver and spleen were enlarged, and over the course of a few weeks a rash typical of dermatomyositis developed. Muscle-enzyme values were much increased. Skin and muscle biopsy showed dermatomyositis, and electromyography revealed a mixed neurogenic-myogenic lesion. Radiological examination showed considerable soft-tissue calcination. The patient’s HLA type was A9, W32; B7,15; CW3; DRW2. There was no sign of B.C.G. osteomyelitis or general infection. In the two years after vaccination the patient has been admitted to hospital several times, but despite prednisone and methotrexate therapy his condition is steadily
SIR,—The
mune
deteriorating. Oslo
Sanitetsforening Revmatismessykehus, University of Oslo, Oslo 1, Norway
E. KÅSS S. STRAUME E. MUNTHE
BUCOLOME AND ALBUMIN-BILIRUBIN BINDING CAPACITY IN INFANTS
SIR,-Semba et ai.,2 as a result of experiments in rats, warned of the danger of kernicterus if this drug is used to treat infants with hyperbilirubinaemia. We have studied newborn infants (thirteen females and seven males, birth-weight 2110-4070 g, gestational age 32-40 weeks) with non-haemolytic jaundice in the first 5 days of life. Albumin-bilirubin bind2.
Semba, R., Sato, H., Yamamura, H. Lancet, 1977, ii, 1134.
ing capacity
was
measured
by gel
filtration
(’Kernlute’
test,
Ames-Yissum, Jerusalem)3 before and after oral administration of a single dose of bucolome 15 mg/kg. Before and 8 h after bucolome administration the albumin-bilirubin binding capacity was greater than 5 mg/dl, and this is normal. We used bucolome prophylactically in three female and two male preterm babies (birth-weight 1880-2440 g, gestational age 33-36 weeks), 30 mg/kg in two doses’being given every day for 5 days after birth.4 Every day for 7 days the albuminbilirubin binding capacity was measured, and it was always above 5 mg/dl. These findings do not rule out a reduction in albumin-bilirubin binding capacity by bucolome, but if binding is reduced there do not seem to be any clinical consequences. In our experience a single dose of bucolome has no effect on serumtotal-bilirubin. However, when the drug is given prophylactically for 5 days the serum-total-bilirubin falls, beginning after 2 days of treatment and continuing after bucolome is withdrawn.’ Perhaps the mechanisms of the serum-bilirubin reduction induced by bucolome in man and Gunn rats2 are different: bucolome injected into Gunn rats rapidly reduces the serumbilirubin while bucolome given orally to newborn infants takes 48 h to have an effect. Our data accord with Baba’s,5 and conflict with the hypothesis that bucolome acts in man by displacing bilirubin from albumin. The mechanism of action of this drug needs further investigations. In the mean time bucolome should not be used to treat newborn infants ’with hyperbilirubinaemia because of the potential risk of reducing albumin-bilirubin binding capacity and because its effect is delayed. In prophylaxis bucolome should be used only when albumin-bilirubin binding capacity can be monitored. Department of Pædiatrics, Catholic University, 00168 Rome, Italy
COSTANTINO ROMAGNOLI GIANCARLO POLIDORI GIUSEPPE SEGNI
DIAGNOSIS OF ECTOPIC PREGNANCY BY RADIORECEPTOR ASSAY FOR CHORIONIC GONADOTROPHIN
SIR,-Professor Lindstedt and his colleagues (Jan. 14, p. stated that the highly sensitive quantitative radioligand assay for human chorionic gonadotrophin (H.C.G.) permits exclusion of the diagnosis of ectopic pregnancy. This has been made possible by the increased sensitivity of the assay (down to 6 mi.u./ml). We agree with this finding but not with the view that H.c.G. concentrations in extrauterine pregnancies are indistinguishable from those in normal pregnancies. In ectopic pregnancies which are 6 weeks or less from the last menstrual period the H.C.G. titres approximate to normal values, but in ectopic pregnancies of 7 or more weeks’ duration H.C.G. levels are significantly lower than in normal pregnancies of the same duration. More important than the initial values are the 2nd and 3rd determinations which may follow in 24-48 h. These subsequent assays usually show a plateau without the rapid increase in H.c.G. concentration found in normal pregnancies. Early ectopic gestations elaborate H.C.G. in normal amounts, but later, because of lack of normal growth and haemorrhage, H.C.G. output falls. To the clinican a reduced H.c.G. alone will not finalise the diagnosis of ectopic pregnancy. The H.c.G. results must be evaluated with the entire clinical picture. A threatened or missed abortion will demonstrate similar repeated low values. All the clinical observations including the presence of an adnexal mass, the lack of chorionic tissue in the endometrial cavity,
108)
3.
Kapitulnik, J., Valaes, T., Kaufmann, N. A., Blondheim, S. Childh 1974, 49, 886. 4. Segni, G., Polidori, G., Romagnoli, C. ibid. 1977, 52, 549. 5. Baba, K. Pædiatrician, 1972/73, 1, 109. 1. Saxena, B. B., Landesman, R. Fertil. Steril. 1975, 26, 397.
H. Archs Dis.
E. SCHEFFER G. P. LAUW A. F. D. SMIT G. J. DEN OTTOLANDER
DERMATOMYOSITIS AFTER B.C.G. VACCINATION cause of dermatomyositis is unknown, but immechanisms are assumed to play a role. In adults, there can be a connection with malignancy, and resection of malignant tumours may result in improvement of the dermatomyositis. B.C.G. vaccination increases the immune response to a variety of antigens, so perhaps two cases of dermatomyositis concomitant with B.C.G. vaccination will be of interest. We would be interested to know if others have had similar experiences. If such associations are not fortuitous those affected might be able to claim compensation. A boy, who had been vaccinated with B.C.G. in the autumn of 1974 at the age of 14, remained Pirquet negative and was revaccinated in September, 1975, after which he became Pirquet positive. 5-6 weeks after revaccination he began to show signs of an exanthema which was typical of dermatomyositis, and pronounced muscular weakness developed. Muscle enzymes activities were greatly increased. Electromyography revealed a mixed myogenic and neurogenic lesion. Skin and muscle biopsy finding were typical of dermatomyositis. Rheumatoid factor or antinuclear antibodies have not been found. The patient’s HLA type was Al,9; B8,15; CW3; DRW3. No clinical or radiological signs of B.C.G. osteomyelitis or general infection have been found. He has been admitted to hospital several times, and, despite intensive treatment with prednisone and methotrexate, he is debilitated and there are signs of progression of the disease. The second patient, also a boy, was vaccinated with B.c.G. in 1975 at the age of 12. He became Pirquet positive, and began to show signs of myositis 2-3 weeks after vaccination, first in the vaccinated area, later in the other extremities, as well as on the chest, back and neck. Both liver and spleen were enlarged, and over the course of a few weeks a rash typical of dermatomyositis developed. Muscle-enzyme values were much increased. Skin and muscle biopsy showed dermatomyositis, and electromyography revealed a mixed neurogenic-myogenic lesion. Radiological examination showed considerable soft-tissue calcination. The patient’s HLA type was A9, W32; B7,15; CW3; DRW2. There was no sign of B.C.G. osteomyelitis or general infection. In the two years after vaccination the patient has been admitted to hospital several times, but despite prednisone and methotrexate therapy his condition is steadily
SIR,—The
mune
deteriorating. Oslo
Sanitetsforening Revmatismessykehus, University of Oslo, Oslo 1, Norway
E. KÅSS S. STRAUME E. MUNTHE
BUCOLOME AND ALBUMIN-BILIRUBIN BINDING CAPACITY IN INFANTS
SIR,-Semba et ai.,2 as a result of experiments in rats, warned of the danger of kernicterus if this drug is used to treat infants with hyperbilirubinaemia. We have studied newborn infants (thirteen females and seven males, birth-weight 2110-4070 g, gestational age 32-40 weeks) with non-haemolytic jaundice in the first 5 days of life. Albumin-bilirubin bind2.
Semba, R., Sato, H., Yamamura, H. Lancet, 1977, ii, 1134.
ing capacity
was
measured
by gel
filtration
(’Kernlute’
test,
Ames-Yissum, Jerusalem)3 before and after oral administration of a single dose of bucolome 15 mg/kg. Before and 8 h after bucolome administration the albumin-bilirubin binding capacity was greater than 5 mg/dl, and this is normal. We used bucolome prophylactically in three female and two male preterm babies (birth-weight 1880-2440 g, gestational age 33-36 weeks), 30 mg/kg in two doses’being given every day for 5 days after birth.4 Every day for 7 days the albuminbilirubin binding capacity was measured, and it was always above 5 mg/dl. These findings do not rule out a reduction in albumin-bilirubin binding capacity by bucolome, but if binding is reduced there do not seem to be any clinical consequences. In our experience a single dose of bucolome has no effect on serumtotal-bilirubin. However, when the drug is given prophylactically for 5 days the serum-total-bilirubin falls, beginning after 2 days of treatment and continuing after bucolome is withdrawn.’ Perhaps the mechanisms of the serum-bilirubin reduction induced by bucolome in man and Gunn rats2 are different: bucolome injected into Gunn rats rapidly reduces the serumbilirubin while bucolome given orally to newborn infants takes 48 h to have an effect. Our data accord with Baba’s,5 and conflict with the hypothesis that bucolome acts in man by displacing bilirubin from albumin. The mechanism of action of this drug needs further investigations. In the mean time bucolome should not be used to treat newborn infants ’with hyperbilirubinaemia because of the potential risk of reducing albumin-bilirubin binding capacity and because its effect is delayed. In prophylaxis bucolome should be used only when albumin-bilirubin binding capacity can be monitored. Department of Pædiatrics, Catholic University, 00168 Rome, Italy
COSTANTINO ROMAGNOLI GIANCARLO POLIDORI GIUSEPPE SEGNI
DIAGNOSIS OF ECTOPIC PREGNANCY BY RADIORECEPTOR ASSAY FOR CHORIONIC GONADOTROPHIN
SIR,-Professor Lindstedt and his colleagues (Jan. 14, p. stated that the highly sensitive quantitative radioligand assay for human chorionic gonadotrophin (H.C.G.) permits exclusion of the diagnosis of ectopic pregnancy. This has been made possible by the increased sensitivity of the assay (down to 6 mi.u./ml). We agree with this finding but not with the view that H.c.G. concentrations in extrauterine pregnancies are indistinguishable from those in normal pregnancies. In ectopic pregnancies which are 6 weeks or less from the last menstrual period the H.C.G. titres approximate to normal values, but in ectopic pregnancies of 7 or more weeks’ duration H.C.G. levels are significantly lower than in normal pregnancies of the same duration. More important than the initial values are the 2nd and 3rd determinations which may follow in 24-48 h. These subsequent assays usually show a plateau without the rapid increase in H.c.G. concentration found in normal pregnancies. Early ectopic gestations elaborate H.C.G. in normal amounts, but later, because of lack of normal growth and haemorrhage, H.C.G. output falls. To the clinican a reduced H.c.G. alone will not finalise the diagnosis of ectopic pregnancy. The H.c.G. results must be evaluated with the entire clinical picture. A threatened or missed abortion will demonstrate similar repeated low values. All the clinical observations including the presence of an adnexal mass, the lack of chorionic tissue in the endometrial cavity,
108)
3.
Kapitulnik, J., Valaes, T., Kaufmann, N. A., Blondheim, S. Childh 1974, 49, 886. 4. Segni, G., Polidori, G., Romagnoli, C. ibid. 1977, 52, 549. 5. Baba, K. Pædiatrician, 1972/73, 1, 109. 1. Saxena, B. B., Landesman, R. Fertil. Steril. 1975, 26, 397.
H. Archs Dis.
