991
1102 g) and of these, 9 (41 %) babies had mechanical ventilation for days and only 3 (14%) were ventilated for more than 28 days, despite no prenatal TRH or betamethasone. We wonder whether the good results Ballard et al achieve-a 30% reduction in babies ventilated at 7 days and almost 50% at 28 days-can be applied to the UK, where it is our impression that fewer babies neeed such prolonged respiratory support.
more than 7
We thank Dr D. Thistlethwaite, Dr I. L. Swann, and Dr I. H. Brown for
permission to report results for their patients. Paediatric Department,
A. SHRIVASTAVA P. EHRHARDT
Burnley General Hospital, Burnley BB10 2PQ, UK
Pertussis in infants SIR,-Your Feb 29 editorial, "Pertussis: adults, infants, and herds", neglects the most important component of its title-the infants. Pertussis is an unusual childhood infection in that it can affect babies only days old, often with devastating results. Indeed the highest mortality rates for pertussis are among infants too young to receive the vaccine. You suggest that babies will not get pertussis if their siblings are immune, but Nelson, in an 18-year review of pertussis in infancy in the USA,’ concluded that the principal source of infection shifted during that time from older siblings to adults; this was especially true for neonatal infections. Other workers have emphasised the importance of mothers as the source of such infections Z3 As the adult population comes to rely increasingly on vaccination during infancy for its immunity to pertussis, so will the pool of susceptible young adults increase. It is this pool that provides the source for infections in very young infants. Few vaccines afford protection that is as lasting as that given by exposure to the disease in question. In countries that enjoy high vaccination rates many future adults will not be immune to diseases such as measles and pertussis. International travel to countries where the diseases are still common could provide index cases for outbreaks among non-immune adults. The ultimate goal of vaccination programmes should be global disease eradication. Where this is not possible programmes should aim to provide lifelong immunity for vaccinees. With current vaccines this will not be achieved if vaccination is confined to early childhood. MRC Laboratories, PO Box 273, Banjul, Gambia
KIM MULHOLLAND
1 Nelson JD. The changing epidemiology of pertussis in young infants.
Am J Dis Child
1978, 132: 371-73. 2 Trollfors B, Rabo E. Whooping cough in adults. Br Med J 1981; 283: 696-97. 3. Williams WO. Whooping cough m adults. Br Med J 1981; 283: 1122.
Possible association of erythema multiforme with acamprosate SiR,-Acamprosate is on the market in France for the prevention of alcoholic relapsed Severe skin reactions have not hitherto been reported. We describe a case of erythema multiforme developing shortly after the introduction of acamprosate in a patient with cirrhosis of the liver. A 40-year-old woman with alcoholic cirrhosis was admitted for ascites in August, 1991. Vulvar herpes was diagnosed on Sept 4, lasting a few days, with no sign of skin extension. She was discharged on Sept 12 on spironolactone and acamprosate 1-3 g daily. She was readmitted on Sept 24 for an eruption that had appeared 2 days earlier, consisting of many pruriginous erythematous target plaques with a purpuric centre, on the trunk and limbs, but not affecting the face or mucosae (mouth, eyes, or vulva). Laboratory tests confirmed liver disease and revealed mild eosinophilia. Antibodies against viral and bacterial agents implicated in erythema multiforme were sought before and after the episode but there was no evidence of viral infection (hepatitis A, B, and C, influenza A and B, paramyxovirus A, B, and C, adenovirus,
Epstein-Barr virus, cytomegalovirus, picomavirus, mumps, herpes zoster) or infection with Mycoplasma pneumoniae or chlamydiae. Her IgG titre against herpes was consistently high (2560 before and
after both the genital ulceration and the erythema multiforme). Skin biopsy revealed endothelial swelling, mixed lymphohistiocytic infiltrates, lymphohistiocytic exocytosis, and prenecrosis of keratinocytes, characteristic of erythema multiforme. The drugs were stopped and the rash resolved in 2 weeks. Erythema multiforme is usually either infective or drug-related.2 There are arguments against herpes being the culprit in this case: the woman had chronic herpes (as shown by stable high titres of IgG antibodies) but had not had erythema multiforme before; the interval between the onset of herpes and that of erythema (at least 21 days) is long, and the timing more favours acamprosate (10 days); and during the episode she had no sign of herpes recurrence or mucous lesions. Other arguments pointing to acamprosate as the culprit are severe itching, eosinophilia, and absence of subsequent recurrence. A rechallenge might have been hazardous and was not attempted. There was no evidence for any other infective cause; spironolactone was reintroduced uneventfully. We suggest that acamprosate caused this adverse skin reaction, even though herpes cannot be completely excluded. This drug is new, and physicians and patients should be on guard for such a reaction, at least until the frequency has been proven to be low. Department of Internal Medicine, Hôpital de Boisguillaume, 76233 Boisguillaume, France, Department of Pharmacology, Hôpital de Boisguillaume, and Department of Pathology, Hôpital Charles-Nicolle, Rouen
MARC FORTIER-BEAULIEU CATHERINE NOBLET FLORENCE CARDOT ELIZABETH THOMINE NICHOLAS MOORE JACQUES HEMET JACQUES BOURREILLE
1. Lhuintre JP, Moore N, Tran
G, et al. Acamprosate appears to decrease alcohol intake in weaned alcoholics. Alcohol Alcoholism 1990; 25: 613-22. 2. Chan H, Stem R, Amdt K, et al. The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Arch Dermatol 1990; 126: 43-47.
Angiogenesis and regressing cutaneous malignant melanoma SIR,-Cutaneous malignant melanomas (CMM) less than 1 mm in thickness are associated with 5-year survival rates of about 95 to 100%.1 However, a small subset of these thin CMM metastasise and show regression on histological examinationAlthough some workers believe that regression has no effect on prognosis of CMM,3 two studies have shown an independent adverse effect of regression on survival.4,s Despite these findings, little is known about the mechanisms of CMM regression and metastasis. We report a patient with metastatic melanoma associated with a
completely regressed primary tumour. A 74-year-old man underwent biopsy for a mass on the spinal cord near the sixth cervical vertebra. Histological examination disclosed metastatic malignant melanoma. The patient had a lifelong pigmented lesion on the right second toe which had begun 1 year earlier. He also had right inguinal to change lymphadenopathy suspect for metastatic melanoma. The toe lesion was clinically suspect for primary CMM, and histological examination revealed
a
dense nodular accumulation of melanin-
containing macrophages in the papillary dermis. There was no evidence of residual CMM or a melanocytic naevus. The pathological features were typical of complete spontaneous regression of primary CMM. Striking vascular proliferation was also noted in and near the zones of regression. Microvessels (capillaries and venules) were identified microscopically by indirect immunoperoxidase studies with an antibody directed against Ulex Europaeus agglutinin-I (a marker for endothelium) (Barnhill RL, Fandrey K, Levy MA, Mihm MC, Hyman B, unpublished). The number of microvessels was quantified by counting all vessels within an ocular grid (area 7’84xl0"2mm2 at x 400 magnification). The mean vessel count for five microscopic fields was 63-0. We have quantified tumour vascularity in 38 primary CMM and recorded a mean vessel count of 24-9 (unpublished). Thus the density of vascularity at the site of regression in this man was about three times the vascularity found in the 38 tumours. Weidner and associates have reported that tumour vascularity is a risk factor for metastasis in breast carcinoma.6 These investigators
1102 g) and of these, 9 (41 %) babies had mechanical ventilation for days and only 3 (14%) were ventilated for more than 28 days, despite no prenatal TRH or betamethasone. We wonder whether the good results Ballard et al achieve-a 30% reduction in babies ventilated at 7 days and almost 50% at 28 days-can be applied to the UK, where it is our impression that fewer babies neeed such prolonged respiratory support.
more than 7
We thank Dr D. Thistlethwaite, Dr I. L. Swann, and Dr I. H. Brown for
permission to report results for their patients. Paediatric Department,
A. SHRIVASTAVA P. EHRHARDT
Burnley General Hospital, Burnley BB10 2PQ, UK
Pertussis in infants SIR,-Your Feb 29 editorial, "Pertussis: adults, infants, and herds", neglects the most important component of its title-the infants. Pertussis is an unusual childhood infection in that it can affect babies only days old, often with devastating results. Indeed the highest mortality rates for pertussis are among infants too young to receive the vaccine. You suggest that babies will not get pertussis if their siblings are immune, but Nelson, in an 18-year review of pertussis in infancy in the USA,’ concluded that the principal source of infection shifted during that time from older siblings to adults; this was especially true for neonatal infections. Other workers have emphasised the importance of mothers as the source of such infections Z3 As the adult population comes to rely increasingly on vaccination during infancy for its immunity to pertussis, so will the pool of susceptible young adults increase. It is this pool that provides the source for infections in very young infants. Few vaccines afford protection that is as lasting as that given by exposure to the disease in question. In countries that enjoy high vaccination rates many future adults will not be immune to diseases such as measles and pertussis. International travel to countries where the diseases are still common could provide index cases for outbreaks among non-immune adults. The ultimate goal of vaccination programmes should be global disease eradication. Where this is not possible programmes should aim to provide lifelong immunity for vaccinees. With current vaccines this will not be achieved if vaccination is confined to early childhood. MRC Laboratories, PO Box 273, Banjul, Gambia
KIM MULHOLLAND
1 Nelson JD. The changing epidemiology of pertussis in young infants.
Am J Dis Child
1978, 132: 371-73. 2 Trollfors B, Rabo E. Whooping cough in adults. Br Med J 1981; 283: 696-97. 3. Williams WO. Whooping cough m adults. Br Med J 1981; 283: 1122.
Possible association of erythema multiforme with acamprosate SiR,-Acamprosate is on the market in France for the prevention of alcoholic relapsed Severe skin reactions have not hitherto been reported. We describe a case of erythema multiforme developing shortly after the introduction of acamprosate in a patient with cirrhosis of the liver. A 40-year-old woman with alcoholic cirrhosis was admitted for ascites in August, 1991. Vulvar herpes was diagnosed on Sept 4, lasting a few days, with no sign of skin extension. She was discharged on Sept 12 on spironolactone and acamprosate 1-3 g daily. She was readmitted on Sept 24 for an eruption that had appeared 2 days earlier, consisting of many pruriginous erythematous target plaques with a purpuric centre, on the trunk and limbs, but not affecting the face or mucosae (mouth, eyes, or vulva). Laboratory tests confirmed liver disease and revealed mild eosinophilia. Antibodies against viral and bacterial agents implicated in erythema multiforme were sought before and after the episode but there was no evidence of viral infection (hepatitis A, B, and C, influenza A and B, paramyxovirus A, B, and C, adenovirus,
Epstein-Barr virus, cytomegalovirus, picomavirus, mumps, herpes zoster) or infection with Mycoplasma pneumoniae or chlamydiae. Her IgG titre against herpes was consistently high (2560 before and
after both the genital ulceration and the erythema multiforme). Skin biopsy revealed endothelial swelling, mixed lymphohistiocytic infiltrates, lymphohistiocytic exocytosis, and prenecrosis of keratinocytes, characteristic of erythema multiforme. The drugs were stopped and the rash resolved in 2 weeks. Erythema multiforme is usually either infective or drug-related.2 There are arguments against herpes being the culprit in this case: the woman had chronic herpes (as shown by stable high titres of IgG antibodies) but had not had erythema multiforme before; the interval between the onset of herpes and that of erythema (at least 21 days) is long, and the timing more favours acamprosate (10 days); and during the episode she had no sign of herpes recurrence or mucous lesions. Other arguments pointing to acamprosate as the culprit are severe itching, eosinophilia, and absence of subsequent recurrence. A rechallenge might have been hazardous and was not attempted. There was no evidence for any other infective cause; spironolactone was reintroduced uneventfully. We suggest that acamprosate caused this adverse skin reaction, even though herpes cannot be completely excluded. This drug is new, and physicians and patients should be on guard for such a reaction, at least until the frequency has been proven to be low. Department of Internal Medicine, Hôpital de Boisguillaume, 76233 Boisguillaume, France, Department of Pharmacology, Hôpital de Boisguillaume, and Department of Pathology, Hôpital Charles-Nicolle, Rouen
MARC FORTIER-BEAULIEU CATHERINE NOBLET FLORENCE CARDOT ELIZABETH THOMINE NICHOLAS MOORE JACQUES HEMET JACQUES BOURREILLE
1. Lhuintre JP, Moore N, Tran
G, et al. Acamprosate appears to decrease alcohol intake in weaned alcoholics. Alcohol Alcoholism 1990; 25: 613-22. 2. Chan H, Stem R, Amdt K, et al. The incidence of erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Arch Dermatol 1990; 126: 43-47.
Angiogenesis and regressing cutaneous malignant melanoma SIR,-Cutaneous malignant melanomas (CMM) less than 1 mm in thickness are associated with 5-year survival rates of about 95 to 100%.1 However, a small subset of these thin CMM metastasise and show regression on histological examinationAlthough some workers believe that regression has no effect on prognosis of CMM,3 two studies have shown an independent adverse effect of regression on survival.4,s Despite these findings, little is known about the mechanisms of CMM regression and metastasis. We report a patient with metastatic melanoma associated with a
completely regressed primary tumour. A 74-year-old man underwent biopsy for a mass on the spinal cord near the sixth cervical vertebra. Histological examination disclosed metastatic malignant melanoma. The patient had a lifelong pigmented lesion on the right second toe which had begun 1 year earlier. He also had right inguinal to change lymphadenopathy suspect for metastatic melanoma. The toe lesion was clinically suspect for primary CMM, and histological examination revealed
a
dense nodular accumulation of melanin-
containing macrophages in the papillary dermis. There was no evidence of residual CMM or a melanocytic naevus. The pathological features were typical of complete spontaneous regression of primary CMM. Striking vascular proliferation was also noted in and near the zones of regression. Microvessels (capillaries and venules) were identified microscopically by indirect immunoperoxidase studies with an antibody directed against Ulex Europaeus agglutinin-I (a marker for endothelium) (Barnhill RL, Fandrey K, Levy MA, Mihm MC, Hyman B, unpublished). The number of microvessels was quantified by counting all vessels within an ocular grid (area 7’84xl0"2mm2 at x 400 magnification). The mean vessel count for five microscopic fields was 63-0. We have quantified tumour vascularity in 38 primary CMM and recorded a mean vessel count of 24-9 (unpublished). Thus the density of vascularity at the site of regression in this man was about three times the vascularity found in the 38 tumours. Weidner and associates have reported that tumour vascularity is a risk factor for metastasis in breast carcinoma.6 These investigators
