to
be careful that children who
present with a Reye's-like illness are not misdiagnosed. Young children, in particular, may require biochemi¬
cal investigations for inborn errors of metabolism, and a liver biopsy may be indicated. In addition, review of the biopsy specimen by someone who is experienced in interpreting electron micrographs in patients with Reye's syndrome may help to avoid misdiagnoses. BRIAN W. FORSYTH, MB, CHB EUGENE D. SHAPIRO, MD Department of Pediatrics RALPH I. HORWITZ, MD Department of Medicine and
Epidemiology
CATHERINE M. VISCOLI, PHD DENISE ACAMPORA, MPH Department of Medicine Yale University School of Medicine Room IE-61 SHM PO Box 3333 New Haven, CT 06510 This research was supported in part by the American Home Products Corp, BristolMyers Co, and Sterling Drug Co, New York, NY; Miles Laboratories Ine, West Haven, Conn; and Procter and Gamble Co, Cincin¬
nati, Ohio. The authors have no ongoing affiliation or financial involvement with any of these
companies or with any other organization or entity with a direct financial interest in the subject matter or material of the research discussed in this letter.
Reprint requests to Yale University School of Medicine, Room IE-61 SHM, PO Box 3333, New Haven, CT 06510 (Dr Hor-
witz).
Members of
Expert Panel
DarrylC. De Vivo, MD, director, Pediatrie Neurology, Columbia-PresbyterianW.Medical
Center, New York, NY; Morey Haymond, MD, chief, Endocrine Research Unit, Department of Pediatrics and Medicine, Mayo Clinic, Rochester, Minn; and John C. Partin, MD, Department of Pediatrics, State
University of New York at Stony Brook. 1. Traumer DA. Reye's syndrome.
Curr Probl Pediatr. 1982;12:23-24. 2. Glasgow AM, Eng G, Engel AG. Systemic carnitine deficiency simulating recurrent
Reye syndrome. J Pediatr.
1980;96:889-891.
3. Bougneres PF, Rocchicciol F, Kolvraa S, et al. Median chain acyl CoA dehydrogenase deficiency in two siblings with a Reye-like syndrome. J Pedi-
atr. 1984;106:918-921. 4. Roe CR, Millington
DS, Maltby DA,
Kinneclerew P. Recognition of medium chain acyl-CoA dehydrogenase deficiency in asymptomatic siblings of chil-
dying of sudden infant death or Reye-like syndromes. J Pediatr. 1986;
dren
108:13-18. 5. Forsyth BW, Horwitz RI, Acampora D, et al. New epidemiologic evidence confirming that bias does not explain the aspirin/Reye's syndrome association.
JAMA. 1989;261:2517-2524. 6. Partin JC, Schubert WK, Partin JS.
Mitochondrial ultrastructure in Reye's syndrome. N Engl J Med. 1971;285:1339\x=req-\
1343. 7. Taubman
B, Hale DE, Kelley RI. Familial Reye-like syndrome: a presentation of medium-chain acyl-coenzyme A dehydrogenase deficiency. Pediatrics.
1987;79:382-385. 8. Bonnell HJ, Beckwith JB. Fatty liver in sudden childhood death: tions for Reye's syndrome.
implica-
AJDC. 1986;140:30-33. 9. Dodge PR, Brown SB, Ector WL, et al. Consensus conference: and treatment of Reye's
diagnosis syndrome.
JAMA. 1981;246:2441-2446. 10. Partin JS, Daugherty CC, McAdams AJ, Partin JC, Schubert WK. A com-
parison of index ultrastructure in salicylate intoxication and Reye's syndrome. Hepatology. 1984;4:687-690.
11. Fleiss JL. The measure of inter-rate In: Statistical Methods for Rates and Proportions. 2nd ed. New York, NY: John Wiley & Sons Inc; 1981; chap 13.
agreement.
Syringomas in Down Syndrome Sir. \p=m-\Syringomasare small, skin\x=req-\ colored or slightly yellow, firm papules that frequently appear in crops and are usually located in the periorbital area (Figure). They may also appear on the side of the neck, cheeks, thorax, abdomen, axilla, and pubic area. An association between Down syndrome (DS) and syringomas was first reported by Butterworth et al1 in 1964. They studied a residential population whose ages ranged from 10 to 52 years; the majority of the patients were adults. The incidence of syringomas in the population with DS was 18.5%, with 26% of the women and 13% of the men having syringomas. The comparison group, 1001 mentally retarded individuals without DS, had a 0.6% incidence of syringomas. Another study in 1976,2 also of institutionalized residents with DS, reported an incidence of syringomas in 26.6% of the male and 58.1% of the female subjects. There are no reports concern-
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/19/2015
Syringomas drome.
seen
in child with Down syn¬
ing the association of DS and syrin¬ gomas in a younger population. Patients and Methods. —In an attempt to confirm the results of previous studies, but in a younger population, 32 patients with DS between ages 14 and 25 years who were being seen for routine follow-up in our DS clinic were evaluated for facial syringomas. Because syringo¬ mas usually do not appear before pu¬ berty, only patients with DS aged 14 years or older were included in the study. These patients were followed up for an average of 13 years. A comparison group of 50 children without DS with and with¬ out mental retardation and matched for age was examined for the presence of sy¬ ringomas. The syringomas in both groups were restricted to the face.
Results. -Fifteen
(46.9%) of the 32
patients with DS examined had sy¬ ringomas. The majority of patients studied (62.5%)
were
in the 14- to
20-year age group and 21 (65.6%) of the 32 patients were men. Eight (38%) of the men and seven (63.6%) of the women had syringomas. Pa¬ tients with syringomas did not have
greater incidence of congenital heart disease, hypothyroidism, or other abnormalities associated with DS than the group with DS without syringomas, although one did have diabetes mellitus. One of the 50 pa¬ tients of the control group matched for age (a patient with Williams syn¬ drome) had facial syringomas. Comment. —The results of this study substantiate the findings of two prior reports concerning an association of syringomas with DS. The rate of oc¬ currence in our patients was higher than anticipated because of the pre¬ ponderance of men and younger indi¬ viduals in our study group (syringo¬ mas appear more coirimonly in women and older individuals). Howa
ever, this may be spuriously high due to the relatively small number of pa¬
tients in the
study group. Syringomas were first described by Kaposi in 1876. They are uncom¬ mon, appear usually during puberty, and have been reported to occur in families. They are usually 1 to 3 mm in diameter but can be larger. Syrin¬ gomas are benign, and there are no reports of them undergoing malig¬ nant degeneration. Histologie, histochemical, and electron microscopic findings show a close relationship between syringomas and intraepithelial eccrine sweat gland ducts. Brownstein3 described syringomas as adenomas of the intraepidermal portions of the eccrine duct. Small cystic ducts as well as solid epithelial strands embedded in fibrous stromas are seen on histologie examination of the upper and middle area of the dermis. Syringomas may be mistaken for xanthomas because of their location around the eyes. However, xantho¬ mas are somewhat larger and yellow¬ ish in color, while syringomas have a flesh-like or light yellow color. Treatment is usually not necessary except for cosmetic reasons. Isotretinoin has recently been used to treat syringomas, but it is not recom¬ mended for routine treatment be¬ cause of the benign nature of these skin lesions and the possible risks of the medication.4 The association of syringomas and DS has not previously been reported in the pediatrie literature. It is impor¬ tant for pediatricians to be aware of the significance of syringomas in pa¬ tients with DS so that they can in¬ form the patient and family of the benign nature of these lesions and not subject the patient to an unnec¬ essary evaluation. MURRAY FEINGOLD, MD National Birth Defect Center Franciscan Children's
Hospital
30 Warren St Boston, MA 02135 This study was supported by a grant from the Genesis Fund. 1. Butterworth T, Strean LP, Berman H, Wood MG. Syringoma and mongol-
ism. Arch Dermatol. 1964;90:483-487. 2. Carter DM, Jegasothy BV. Alopecia areata and Down syndrome. Arch Dermatol. 1976;112:1397-1399. 3. Brownstein MN. The sweat gland
adenomas. Int J Dermatol. 1975;14:397. 4. Maintitz M, Schmidt JB, Gebhardt W. Response of multiple syringomas to isotretinoin. Arch Dermatol Venereol.
1986;16:51-55.
Congenital Syphilis
Associated With Negative Results of Maternal Serologic
Tests at
Delivery
Sir. \p=m-\Theincidence of congenital syphilis has steadily increased in the last decade. In 1988, 691 cases of
early congenital syphilis were reported to the Centers for Disease Control.1 This is the largest number of cases reported to the centers since the early 1950s, when penicillin became widely used to treat syphilis in pregnant women.1 Because congenital syphilis generally can be prevented by detection and treatment of syphilis early in pregnancy, failure to obtain adequate prenatal care is believed to be the most important factor associated with congenital syph-
ilis.1,2 Current recommendations from the Centers for Disease Control require that all states perform serologic screening tests for detecting syphilis at the beginning of prenatal care. Additional screenings at the beginning of the third trimester (28 weeks) and at delivery also are recommended for mothers who live in arwith high incidences of eas syphilis.2-4 This approach will reveal almost all cases of antepartum infec¬ tion. However, it may not detect in¬ fection acquired immediately before delivery when results of serologie tests may be negative.3"10 We describe three infants born to mothers with peripartum syphilis that was not di¬
agnosed by routine serologie screen¬ ing at delivery. Two mothers were seronegative at delivery, but their
infants later developed evidence of congenital syphilis. The third infant was
with
born to
a
seronegative
mother
primary syphilis diagnosed
post partum; this infant was asymp¬
tomatic and received prophylactic antimicrobial therapy after delivery. These cases underscore the limita¬ tions of current prenatal screening methods.
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/19/2015
1.—A 2385-g Patient Reports.— male was delivered vaginally at 36 weeks' gestation to a 20-year-old black woman. The pregnancy was uncomplicated and the result of a maternal rapid plasma reagin (RPR) test did not show reactivity at delivery. No maternal genital lesions were noted. Results of physical examina¬ tion of the infant were normal, and he and his mother were discharged from the hospital. Two months after delivery, the mother was diagnosed with salpingitis due to Neisseria gonorrhoeae and received ceftriaxone sodium and doxycyclinehyclate. No genital lesions were noted; a serologie test to detect syphilis was not performed at that time. The infant was in good health until age 2 months, when he developed clear rhinorrhea and a generalized maculopapular rash with oval red lesions and su¬ perficial desquamation. On presentation at the emergency department, he¬ patosplenomegaly and axillary adenopathy were noted. Roentgenograms of the long bones revealed symmetric osteochondritis and periostitis. Laboratory evaluation revealed a hemoglobin level of 90 g/L, hematocrit of 0.27, and a platelet count of 422 x 107L. The alanine ami¬ notransferase, aspartate aminotrans¬ ferase, and "y-glutamyltransferase (GGT) levels were 65, 140, and 128 U/L, respec¬ tively. The total bilirubin level was 6 µ /L. The serum VDRL titer was 1:128, and the result of the microhemagglutination assay to detect Treponema pallidum (MHA-TP) antibody showed reac¬ tivity. Laboratory test results of the infant's cerebrospinal fluid showed no white blood cells and normal glucose and protein concentrations. The cerebrospi¬ nal fluid was nonreactive during VDRL testing. The IgM reactivity of whole se¬ rum with pallidum antigens was exam¬ ined using Western blotting11; an IgM resonse to pallidum antigens with ap¬ parent molecular masses of 47, 45, and 17 kd was observed. The infant was diag¬ nosed as having congenital syphilis and received 200 000 U/kg of intravenous pen¬ icillin G daily for 10 days. There was no history or physical signs of sexual abuse. The mother's VDRL titer was 1:8, and the result of an MHA-TP assay showed reactivity. Antibody to the human immu¬ nodeficiency virus (HIV) was not de¬ tected. She was diagnosed as having early latent syphilis and was treated with 2.4 million U of benzathine penicillin G
intramuscularly. Patient 2.—A 3550-g female was deliv¬ ered vaginally at 40 weeks' gestation to a 20-year-old black woman following an uncomplicated pregnancy. The result of a maternal RPR test at delivery did not show reactivity, and there were no signs of 1° or 2° syphilis. Results of physical ex¬ amination of the newborn
were
normal.
be careful that children who
present with a Reye's-like illness are not misdiagnosed. Young children, in particular, may require biochemi¬
cal investigations for inborn errors of metabolism, and a liver biopsy may be indicated. In addition, review of the biopsy specimen by someone who is experienced in interpreting electron micrographs in patients with Reye's syndrome may help to avoid misdiagnoses. BRIAN W. FORSYTH, MB, CHB EUGENE D. SHAPIRO, MD Department of Pediatrics RALPH I. HORWITZ, MD Department of Medicine and
Epidemiology
CATHERINE M. VISCOLI, PHD DENISE ACAMPORA, MPH Department of Medicine Yale University School of Medicine Room IE-61 SHM PO Box 3333 New Haven, CT 06510 This research was supported in part by the American Home Products Corp, BristolMyers Co, and Sterling Drug Co, New York, NY; Miles Laboratories Ine, West Haven, Conn; and Procter and Gamble Co, Cincin¬
nati, Ohio. The authors have no ongoing affiliation or financial involvement with any of these
companies or with any other organization or entity with a direct financial interest in the subject matter or material of the research discussed in this letter.
Reprint requests to Yale University School of Medicine, Room IE-61 SHM, PO Box 3333, New Haven, CT 06510 (Dr Hor-
witz).
Members of
Expert Panel
DarrylC. De Vivo, MD, director, Pediatrie Neurology, Columbia-PresbyterianW.Medical
Center, New York, NY; Morey Haymond, MD, chief, Endocrine Research Unit, Department of Pediatrics and Medicine, Mayo Clinic, Rochester, Minn; and John C. Partin, MD, Department of Pediatrics, State
University of New York at Stony Brook. 1. Traumer DA. Reye's syndrome.
Curr Probl Pediatr. 1982;12:23-24. 2. Glasgow AM, Eng G, Engel AG. Systemic carnitine deficiency simulating recurrent
Reye syndrome. J Pediatr.
1980;96:889-891.
3. Bougneres PF, Rocchicciol F, Kolvraa S, et al. Median chain acyl CoA dehydrogenase deficiency in two siblings with a Reye-like syndrome. J Pedi-
atr. 1984;106:918-921. 4. Roe CR, Millington
DS, Maltby DA,
Kinneclerew P. Recognition of medium chain acyl-CoA dehydrogenase deficiency in asymptomatic siblings of chil-
dying of sudden infant death or Reye-like syndromes. J Pediatr. 1986;
dren
108:13-18. 5. Forsyth BW, Horwitz RI, Acampora D, et al. New epidemiologic evidence confirming that bias does not explain the aspirin/Reye's syndrome association.
JAMA. 1989;261:2517-2524. 6. Partin JC, Schubert WK, Partin JS.
Mitochondrial ultrastructure in Reye's syndrome. N Engl J Med. 1971;285:1339\x=req-\
1343. 7. Taubman
B, Hale DE, Kelley RI. Familial Reye-like syndrome: a presentation of medium-chain acyl-coenzyme A dehydrogenase deficiency. Pediatrics.
1987;79:382-385. 8. Bonnell HJ, Beckwith JB. Fatty liver in sudden childhood death: tions for Reye's syndrome.
implica-
AJDC. 1986;140:30-33. 9. Dodge PR, Brown SB, Ector WL, et al. Consensus conference: and treatment of Reye's
diagnosis syndrome.
JAMA. 1981;246:2441-2446. 10. Partin JS, Daugherty CC, McAdams AJ, Partin JC, Schubert WK. A com-
parison of index ultrastructure in salicylate intoxication and Reye's syndrome. Hepatology. 1984;4:687-690.
11. Fleiss JL. The measure of inter-rate In: Statistical Methods for Rates and Proportions. 2nd ed. New York, NY: John Wiley & Sons Inc; 1981; chap 13.
agreement.
Syringomas in Down Syndrome Sir. \p=m-\Syringomasare small, skin\x=req-\ colored or slightly yellow, firm papules that frequently appear in crops and are usually located in the periorbital area (Figure). They may also appear on the side of the neck, cheeks, thorax, abdomen, axilla, and pubic area. An association between Down syndrome (DS) and syringomas was first reported by Butterworth et al1 in 1964. They studied a residential population whose ages ranged from 10 to 52 years; the majority of the patients were adults. The incidence of syringomas in the population with DS was 18.5%, with 26% of the women and 13% of the men having syringomas. The comparison group, 1001 mentally retarded individuals without DS, had a 0.6% incidence of syringomas. Another study in 1976,2 also of institutionalized residents with DS, reported an incidence of syringomas in 26.6% of the male and 58.1% of the female subjects. There are no reports concern-
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/19/2015
Syringomas drome.
seen
in child with Down syn¬
ing the association of DS and syrin¬ gomas in a younger population. Patients and Methods. —In an attempt to confirm the results of previous studies, but in a younger population, 32 patients with DS between ages 14 and 25 years who were being seen for routine follow-up in our DS clinic were evaluated for facial syringomas. Because syringo¬ mas usually do not appear before pu¬ berty, only patients with DS aged 14 years or older were included in the study. These patients were followed up for an average of 13 years. A comparison group of 50 children without DS with and with¬ out mental retardation and matched for age was examined for the presence of sy¬ ringomas. The syringomas in both groups were restricted to the face.
Results. -Fifteen
(46.9%) of the 32
patients with DS examined had sy¬ ringomas. The majority of patients studied (62.5%)
were
in the 14- to
20-year age group and 21 (65.6%) of the 32 patients were men. Eight (38%) of the men and seven (63.6%) of the women had syringomas. Pa¬ tients with syringomas did not have
greater incidence of congenital heart disease, hypothyroidism, or other abnormalities associated with DS than the group with DS without syringomas, although one did have diabetes mellitus. One of the 50 pa¬ tients of the control group matched for age (a patient with Williams syn¬ drome) had facial syringomas. Comment. —The results of this study substantiate the findings of two prior reports concerning an association of syringomas with DS. The rate of oc¬ currence in our patients was higher than anticipated because of the pre¬ ponderance of men and younger indi¬ viduals in our study group (syringo¬ mas appear more coirimonly in women and older individuals). Howa
ever, this may be spuriously high due to the relatively small number of pa¬
tients in the
study group. Syringomas were first described by Kaposi in 1876. They are uncom¬ mon, appear usually during puberty, and have been reported to occur in families. They are usually 1 to 3 mm in diameter but can be larger. Syrin¬ gomas are benign, and there are no reports of them undergoing malig¬ nant degeneration. Histologie, histochemical, and electron microscopic findings show a close relationship between syringomas and intraepithelial eccrine sweat gland ducts. Brownstein3 described syringomas as adenomas of the intraepidermal portions of the eccrine duct. Small cystic ducts as well as solid epithelial strands embedded in fibrous stromas are seen on histologie examination of the upper and middle area of the dermis. Syringomas may be mistaken for xanthomas because of their location around the eyes. However, xantho¬ mas are somewhat larger and yellow¬ ish in color, while syringomas have a flesh-like or light yellow color. Treatment is usually not necessary except for cosmetic reasons. Isotretinoin has recently been used to treat syringomas, but it is not recom¬ mended for routine treatment be¬ cause of the benign nature of these skin lesions and the possible risks of the medication.4 The association of syringomas and DS has not previously been reported in the pediatrie literature. It is impor¬ tant for pediatricians to be aware of the significance of syringomas in pa¬ tients with DS so that they can in¬ form the patient and family of the benign nature of these lesions and not subject the patient to an unnec¬ essary evaluation. MURRAY FEINGOLD, MD National Birth Defect Center Franciscan Children's
Hospital
30 Warren St Boston, MA 02135 This study was supported by a grant from the Genesis Fund. 1. Butterworth T, Strean LP, Berman H, Wood MG. Syringoma and mongol-
ism. Arch Dermatol. 1964;90:483-487. 2. Carter DM, Jegasothy BV. Alopecia areata and Down syndrome. Arch Dermatol. 1976;112:1397-1399. 3. Brownstein MN. The sweat gland
adenomas. Int J Dermatol. 1975;14:397. 4. Maintitz M, Schmidt JB, Gebhardt W. Response of multiple syringomas to isotretinoin. Arch Dermatol Venereol.
1986;16:51-55.
Congenital Syphilis
Associated With Negative Results of Maternal Serologic
Tests at
Delivery
Sir. \p=m-\Theincidence of congenital syphilis has steadily increased in the last decade. In 1988, 691 cases of
early congenital syphilis were reported to the Centers for Disease Control.1 This is the largest number of cases reported to the centers since the early 1950s, when penicillin became widely used to treat syphilis in pregnant women.1 Because congenital syphilis generally can be prevented by detection and treatment of syphilis early in pregnancy, failure to obtain adequate prenatal care is believed to be the most important factor associated with congenital syph-
ilis.1,2 Current recommendations from the Centers for Disease Control require that all states perform serologic screening tests for detecting syphilis at the beginning of prenatal care. Additional screenings at the beginning of the third trimester (28 weeks) and at delivery also are recommended for mothers who live in arwith high incidences of eas syphilis.2-4 This approach will reveal almost all cases of antepartum infec¬ tion. However, it may not detect in¬ fection acquired immediately before delivery when results of serologie tests may be negative.3"10 We describe three infants born to mothers with peripartum syphilis that was not di¬
agnosed by routine serologie screen¬ ing at delivery. Two mothers were seronegative at delivery, but their
infants later developed evidence of congenital syphilis. The third infant was
with
born to
a
seronegative
mother
primary syphilis diagnosed
post partum; this infant was asymp¬
tomatic and received prophylactic antimicrobial therapy after delivery. These cases underscore the limita¬ tions of current prenatal screening methods.
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Iowa User on 06/19/2015
1.—A 2385-g Patient Reports.— male was delivered vaginally at 36 weeks' gestation to a 20-year-old black woman. The pregnancy was uncomplicated and the result of a maternal rapid plasma reagin (RPR) test did not show reactivity at delivery. No maternal genital lesions were noted. Results of physical examina¬ tion of the infant were normal, and he and his mother were discharged from the hospital. Two months after delivery, the mother was diagnosed with salpingitis due to Neisseria gonorrhoeae and received ceftriaxone sodium and doxycyclinehyclate. No genital lesions were noted; a serologie test to detect syphilis was not performed at that time. The infant was in good health until age 2 months, when he developed clear rhinorrhea and a generalized maculopapular rash with oval red lesions and su¬ perficial desquamation. On presentation at the emergency department, he¬ patosplenomegaly and axillary adenopathy were noted. Roentgenograms of the long bones revealed symmetric osteochondritis and periostitis. Laboratory evaluation revealed a hemoglobin level of 90 g/L, hematocrit of 0.27, and a platelet count of 422 x 107L. The alanine ami¬ notransferase, aspartate aminotrans¬ ferase, and "y-glutamyltransferase (GGT) levels were 65, 140, and 128 U/L, respec¬ tively. The total bilirubin level was 6 µ /L. The serum VDRL titer was 1:128, and the result of the microhemagglutination assay to detect Treponema pallidum (MHA-TP) antibody showed reac¬ tivity. Laboratory test results of the infant's cerebrospinal fluid showed no white blood cells and normal glucose and protein concentrations. The cerebrospi¬ nal fluid was nonreactive during VDRL testing. The IgM reactivity of whole se¬ rum with pallidum antigens was exam¬ ined using Western blotting11; an IgM resonse to pallidum antigens with ap¬ parent molecular masses of 47, 45, and 17 kd was observed. The infant was diag¬ nosed as having congenital syphilis and received 200 000 U/kg of intravenous pen¬ icillin G daily for 10 days. There was no history or physical signs of sexual abuse. The mother's VDRL titer was 1:8, and the result of an MHA-TP assay showed reactivity. Antibody to the human immu¬ nodeficiency virus (HIV) was not de¬ tected. She was diagnosed as having early latent syphilis and was treated with 2.4 million U of benzathine penicillin G
intramuscularly. Patient 2.—A 3550-g female was deliv¬ ered vaginally at 40 weeks' gestation to a 20-year-old black woman following an uncomplicated pregnancy. The result of a maternal RPR test at delivery did not show reactivity, and there were no signs of 1° or 2° syphilis. Results of physical ex¬ amination of the newborn
were
normal.
