826 AGENESIS OF APPENDIX: A FURTHER THALIDOMIDE ANOMALY
CRANIAL SYNOSTOSIS IN JOB’S SYNDROME et al.’ described two girls with recur"cold" staphylococcal abscesses, chronic purulent sinusitis and otitis media, eczematoid skin lesions, and chronic pulmonary disease. No defect in neutrophil phagocytic or bactericidal function was indentified, thus distinguishing these patients from children with chronic granulomatous disease. This entity was named "Job’s syndrome". Pabst et al.2 noted extreme hyperimmunoglobulinaemia E in a girl with Job’s syndrome as well as defective in-vivo neutrophil chemotaxis. These findings were extended by Buckley et al. when they described two adolescent boys with the clinical aspects of Job’s syndrome as well as coarse facies, eosinophilia, and very high serum-IgE concentrations. These boys also had depressed invivo cellular immunity and antibody formation. Later reports4-6 suggested that a defect in neutrophil chemotaxis might br related to the undue susceptibility to bacterial infection. Since these initial reports, other children have been described with recurrent infections, most often due to Staphylococcus aureus but also occasionally with Candida albicans, hyperimmunoglobulinsemia E, and defective neutrophil chemotaxis .1,8
SIR,-In 1966, Davis
SIR,-A "thalidomide" child with agenesis of the appendix,
rent
We report three boys who have recurrent infections and serum-IgE levels who also have a striking physical
raised
finding not previously reported-namely, cranial synostosis. This abnormality was clinically obvious in a child seen in New York City in January, 1977. This boy had had corrective cranial surgery when he was 4 years old and had been extensively investigated in Sao Paulo in 1975. A child with a similar cranial defect who also had surgical correction at age 4 years has been followed up at Emory University in Atlanta since 1964. A third boy was seen in New York in March, 1977. His cranial defect had not been noted before; it was concealed by his thick, long hair. A prominent sagittal suture was easily palpated, and premature fusion was confirmed on X-ray. We will describe these three cases in detail later, but we believe that cranial abnormalities should be looked for in other children with Job’s syndrome. These abnormalities may provide a clue to the basic mechanism underlying the recurrent infections and the most consistent immunological aberration, the impaited regulation of immunoglobulin E. Skeletal abnormalities have been associated with other immune-deficiency diseases (e.g., short-limbed dwarfism, cartilage-hair hypoplasia, and adenosine-deaminase deficiency). This seems unlikely to be due to chance. Patieni investigation CA19267.
supported Dy U.S.
Memorial Sloan-Kettering Cancer Centre, New York, N.Y. 10021, U.S.A.
Public Health Service grant
E. M. SMITHWICK M. FINELT S. PAHWA R. A. GOOD
Escola Paulista de Medicina, São Paulo, Brasil
C. K. NASPITZ N. F. MENDES S. KOPERSZTYCK
Center for Disease Control, Atlanta
T.
J. SPIRA
Emory University Medical School, Atlanta
A.
J. NAHMIAS
Davis, S. D., Schaller, J., Wedgwood, R. J. Lancet, 1966, i, 1013. Pabst, H. F., Holmes, B., Quie, P. G., Gewurz, H., Rodey, G., Good, R. A. Soc. pediat. Res. 1971, 5, 380. 3. Buckley, R. H., Wray, B. B., Belmaker, E. Z. Pediatrics, 1972, 49, 59. 4. Clark, R. A., Root, R. K., Kimball, H. R., Kirkpatrick, C. H. Ann. intern. Med. 1973, 78, 515. 5. Hill, H. R., Quie, P. G. Lancet, 1974, i, 183. 6. Hill, H. R., Quie, P. G., Pabst, H. F., Ochs, H. D., Clark, R. A., Klebanoff, S. J., Wedgwood, R. J. ibid. 1974, ii, 617. 7. Buckley, R. H., Fiscus, S. A. J. clin. Invest. 1975, 55, 157. 8. Snyderman, R., Buckley, R. H. Clin. Res. 1975, 23, 25A. 1. 2.
due to maternal ingestion of the drug, has lately been described.’ We have come across the case-record of another child who, at operation, had agenesis of the appendix while also having physical defects which could be related to thalidomide ingestion by her mother. A 6-year-old female (born February, 1962) was admitted with central abdominal pain of 24 h duration which later shifted to the right iliac fossa. At operation no appendix could be found despite a careful search of the ileocmcal region, and enlarged mesenteric lymph-nodes were noted. The caecum was normal so the appendicular agenesis was Collins’ type in (the commonest).2 She made an uneventful recovery. On scrutiny of her medical records recently we noted that she had been treated for severe anorectal stenosis by operation and repeated dilation before she was 2 and that she had small pits in both ears with some deformity. Since her mother had taken ’Distaval’ while pregnant the child’s physical anomalies are most likely to be thalidomide-induced and can be graded C2D3 with disability group 9/10.3 Surgeons seeing patients with thalidomide-related anomalies should bear in mind the possibility of agenesis of the appendix when dealing with the acute abdomen.
presumably
D. N. BREMNER GRANT MOONEY
Kelso
Cottage Hospital, Kelso, Roxburghshire
EXCESSIVE SWEATING AND REDUCTION DEFORMITIES
SIR,-The mother of 7-year-old identical twin girls, one of whom has reduction deformities of both forearms and hands, the other being anatomically normal, states that the deformed child sweats excessively. The excessive sweating is particularly prominent about the head and neck. Sweat-measurement tests with starch and iodine powder confirm that the child with reduction deformities does sweat more than her sister. Questioning a group of parents of other children with reduction deformities confirms this mother’s observation. The parents also state that the deformed limb appears to be hypersensitive to pressure, and I have confirmed this. The increase in sweating seems out of proportion to the reduction of total body-surface area caused by the deformities. It would be interesting to know if synhidrosis occurs in all children with reduction deformities. If synhidrosis is confirmed as a feature of children with congenital reduction deformities it will be likely that they also have dysautonomia. Foundation 41, Women’s Hospital, Sydney, New South Wales 2010, Australia
W. G. MCBRIDE
IS FETAL RADIOGRAPHY REALLY NECESSARY?
SIR,-Dr Fletcher (March 18, p. 600) suggests that ultrasonic scanning of all pregnant women is desirable to reduce the number of X-rays necessary in pregnancy but that this is not possible on economic grounds. I agree that all pregnant women should be ultrasonically scanned, not only on the grounds stated but also because such a policy will give early information on placental site, dates, and possible intrauterine growth retardation. Real-time scanning also provides a quick method of screening for neural-tube defects, though the accuracy of this method of screening has not been determined. If the 1. 2. 3.
Shand, J. E. G., Bremner, D. N. Br. J. Surg. 1977, 64, 203. Collins, D. C. Am. J. Surg. 1951, 82, 689. Smithells, R. W. Br. med. J. 1973, i, 269.
CRANIAL SYNOSTOSIS IN JOB’S SYNDROME et al.’ described two girls with recur"cold" staphylococcal abscesses, chronic purulent sinusitis and otitis media, eczematoid skin lesions, and chronic pulmonary disease. No defect in neutrophil phagocytic or bactericidal function was indentified, thus distinguishing these patients from children with chronic granulomatous disease. This entity was named "Job’s syndrome". Pabst et al.2 noted extreme hyperimmunoglobulinaemia E in a girl with Job’s syndrome as well as defective in-vivo neutrophil chemotaxis. These findings were extended by Buckley et al. when they described two adolescent boys with the clinical aspects of Job’s syndrome as well as coarse facies, eosinophilia, and very high serum-IgE concentrations. These boys also had depressed invivo cellular immunity and antibody formation. Later reports4-6 suggested that a defect in neutrophil chemotaxis might br related to the undue susceptibility to bacterial infection. Since these initial reports, other children have been described with recurrent infections, most often due to Staphylococcus aureus but also occasionally with Candida albicans, hyperimmunoglobulinsemia E, and defective neutrophil chemotaxis .1,8
SIR,-In 1966, Davis
SIR,-A "thalidomide" child with agenesis of the appendix,
rent
We report three boys who have recurrent infections and serum-IgE levels who also have a striking physical
raised
finding not previously reported-namely, cranial synostosis. This abnormality was clinically obvious in a child seen in New York City in January, 1977. This boy had had corrective cranial surgery when he was 4 years old and had been extensively investigated in Sao Paulo in 1975. A child with a similar cranial defect who also had surgical correction at age 4 years has been followed up at Emory University in Atlanta since 1964. A third boy was seen in New York in March, 1977. His cranial defect had not been noted before; it was concealed by his thick, long hair. A prominent sagittal suture was easily palpated, and premature fusion was confirmed on X-ray. We will describe these three cases in detail later, but we believe that cranial abnormalities should be looked for in other children with Job’s syndrome. These abnormalities may provide a clue to the basic mechanism underlying the recurrent infections and the most consistent immunological aberration, the impaited regulation of immunoglobulin E. Skeletal abnormalities have been associated with other immune-deficiency diseases (e.g., short-limbed dwarfism, cartilage-hair hypoplasia, and adenosine-deaminase deficiency). This seems unlikely to be due to chance. Patieni investigation CA19267.
supported Dy U.S.
Memorial Sloan-Kettering Cancer Centre, New York, N.Y. 10021, U.S.A.
Public Health Service grant
E. M. SMITHWICK M. FINELT S. PAHWA R. A. GOOD
Escola Paulista de Medicina, São Paulo, Brasil
C. K. NASPITZ N. F. MENDES S. KOPERSZTYCK
Center for Disease Control, Atlanta
T.
J. SPIRA
Emory University Medical School, Atlanta
A.
J. NAHMIAS
Davis, S. D., Schaller, J., Wedgwood, R. J. Lancet, 1966, i, 1013. Pabst, H. F., Holmes, B., Quie, P. G., Gewurz, H., Rodey, G., Good, R. A. Soc. pediat. Res. 1971, 5, 380. 3. Buckley, R. H., Wray, B. B., Belmaker, E. Z. Pediatrics, 1972, 49, 59. 4. Clark, R. A., Root, R. K., Kimball, H. R., Kirkpatrick, C. H. Ann. intern. Med. 1973, 78, 515. 5. Hill, H. R., Quie, P. G. Lancet, 1974, i, 183. 6. Hill, H. R., Quie, P. G., Pabst, H. F., Ochs, H. D., Clark, R. A., Klebanoff, S. J., Wedgwood, R. J. ibid. 1974, ii, 617. 7. Buckley, R. H., Fiscus, S. A. J. clin. Invest. 1975, 55, 157. 8. Snyderman, R., Buckley, R. H. Clin. Res. 1975, 23, 25A. 1. 2.
due to maternal ingestion of the drug, has lately been described.’ We have come across the case-record of another child who, at operation, had agenesis of the appendix while also having physical defects which could be related to thalidomide ingestion by her mother. A 6-year-old female (born February, 1962) was admitted with central abdominal pain of 24 h duration which later shifted to the right iliac fossa. At operation no appendix could be found despite a careful search of the ileocmcal region, and enlarged mesenteric lymph-nodes were noted. The caecum was normal so the appendicular agenesis was Collins’ type in (the commonest).2 She made an uneventful recovery. On scrutiny of her medical records recently we noted that she had been treated for severe anorectal stenosis by operation and repeated dilation before she was 2 and that she had small pits in both ears with some deformity. Since her mother had taken ’Distaval’ while pregnant the child’s physical anomalies are most likely to be thalidomide-induced and can be graded C2D3 with disability group 9/10.3 Surgeons seeing patients with thalidomide-related anomalies should bear in mind the possibility of agenesis of the appendix when dealing with the acute abdomen.
presumably
D. N. BREMNER GRANT MOONEY
Kelso
Cottage Hospital, Kelso, Roxburghshire
EXCESSIVE SWEATING AND REDUCTION DEFORMITIES
SIR,-The mother of 7-year-old identical twin girls, one of whom has reduction deformities of both forearms and hands, the other being anatomically normal, states that the deformed child sweats excessively. The excessive sweating is particularly prominent about the head and neck. Sweat-measurement tests with starch and iodine powder confirm that the child with reduction deformities does sweat more than her sister. Questioning a group of parents of other children with reduction deformities confirms this mother’s observation. The parents also state that the deformed limb appears to be hypersensitive to pressure, and I have confirmed this. The increase in sweating seems out of proportion to the reduction of total body-surface area caused by the deformities. It would be interesting to know if synhidrosis occurs in all children with reduction deformities. If synhidrosis is confirmed as a feature of children with congenital reduction deformities it will be likely that they also have dysautonomia. Foundation 41, Women’s Hospital, Sydney, New South Wales 2010, Australia
W. G. MCBRIDE
IS FETAL RADIOGRAPHY REALLY NECESSARY?
SIR,-Dr Fletcher (March 18, p. 600) suggests that ultrasonic scanning of all pregnant women is desirable to reduce the number of X-rays necessary in pregnancy but that this is not possible on economic grounds. I agree that all pregnant women should be ultrasonically scanned, not only on the grounds stated but also because such a policy will give early information on placental site, dates, and possible intrauterine growth retardation. Real-time scanning also provides a quick method of screening for neural-tube defects, though the accuracy of this method of screening has not been determined. If the 1. 2. 3.
Shand, J. E. G., Bremner, D. N. Br. J. Surg. 1977, 64, 203. Collins, D. C. Am. J. Surg. 1951, 82, 689. Smithells, R. W. Br. med. J. 1973, i, 269.
