TERATOGEN UPDATE
Congenital Syphilis JOHN GROSSMAN 111 Department of Obstetrics and Gynecology, George Washington University Medical Center, Washington, D.C. 20037
The damage due to fetal infection with Treponema pallidum, untreated during pregnancy, ranges from fulminent neonatal sepsis and death to asymptomatic infection persisting in childhood and culminating in tertiary syphilis in early adolescence. By convention, clinicians classify congenital syphilis as “early” and “late.” This terminology specifically refers to the time in the child‘s life when the diagnosis of syphilis is made.
Manifestations
neurologic and cardiovascular defects (figs. 24).
Epidemiology A t present, congenital syphilis occurs in approximately 0.05% of all live births in the United States. Approximately 1,900 cases were reported in 1973. Twenty percent of these were “early” and 80%“late” congenital syphilis. Fortunately, detection and treatment in the majority of cases makes clinical congenital syphilis uncommon. Dissemination of syphilis to the fetus is possible a t all stages of maternal infection, including the late latent stage, when asymptomatic patients remain persistently seropositive. Most frequently, however, dissemination is associated with a placentitis arising from hematogenous spread of the spirochetes between the first and second stage of infection in the mother. Contrary to previous thought, pregnancies are not impervious to treponemial invasion during the first half of gestation. Careful histologic examination has demonstrated spirochetes in products of conception in the first trimester. Dissolution of the cytotrophoblast was previously postulated as the cause of fetal susceptibility to infection after the eighteenth week, however electron microscopy has failed to demonstrate any loss of tissue integrity. Recently, immunologic immaturity in fetuses has been proposed to explain the absence of any apparent fetal inflammatory response to infection. Signs of congenital syphilis are uncommon before the infant is three weeks old; indeed if they are present a t birth, the prognosis is usually unfavorable.
Early congenital syphilis is an infectious, life threatening disease apparent in children under two years of age. The children are often small for gestational age or premature with hemolytic anemia, hepatosplenomegaly, and occasionally hydrops. The placenta is frequently large (fetoplacental ratios less than 5:1) with villitis and perivasculitis. Spirochetes may be demonstrable using special staining techniques. A maculopapular or vesiculobullous rash may be present. Fluid from skin lesions may be found to contain spirochetes when studied using darkfield microscopy. Over 50% of these infants have “snuffles,” a thick white or blood-tinged nasal discharge (fig. 1) teeming with treponemes. Periosteitis and long bone osteochondritis can cause Parrott’s pseudoparalysis, due to bone and joint pain. Meningitis and cerebrospinal fluid abnormalities are common. Late congenital syphilis appears in children over two years of age and is asymptomatic in two-thirds of all cases. Serology is invariably positive. Those with findings have the more classical “stigmata” of congenital syphilis. These include interstitial keratitis, VIII Diagnosis nerve deafness, dental and bony deformities (Hutchinson’s teeth, mulberry molars, sabre Demonstration of spirochetes in skin leshins, saddle nose, frontal bossing, palatal sions or nasal discharge is diagnostic as is a perforation, Clutton’s joints), cutaneous le- cord VDRL (Venereal Disease Research Labosions (rhagades and gummas) and rarely, ratory) antibody titre 4-fold greater than that TERAMLOGY.16: 217-224.
217
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JOHN GROSSMAN I11
of maternal serum. Unfortunately, many cases present more difficult diagnostic problems and often the only clue consists of a vague history of maternal venereal disease treated during pregnancy. Cord blood macroglobulin has been proposed as a general screening test for congenital infections and FTA-ABS-IgM (Fluorescent Treponeme Antibody Absorption-Immunoglobulin M) as a specific test for congenital syphilis. The latter assay is not generally available and recent work has suggested that false positives may arise from fetal IgM directed against maternal IgG. In such instances, maternal 7s globulins elaborated in response to infection are acquired passively by the fetus which then elaborates macroglobulin anti-antibody. Asymptomatic offspring of mothers treated in pregnancy with positive but non-diagnostically elevated cord VDRL’s present a problem in clinical management. More specific treponemal tests or macroglobulin assays can be employed if available. If the titer is due to passive maternal transfer of IgG, serial VDRL’s should show a quantitative decrease with time and revert to negative by three months of life. Examination of spinal fluid for pleocytosis, elevated protein, or positive serology is indicated in suspicious cases.
rosyphilis in their babies. Larger doses of penicillin may be used in such circumstances. Penicillin allergic pregnant women should not receive tetracycline due to potential adverse effects upon fetal dentition and bone. Oral erythromycin in doses of two grams per day for 15 to 20 days should be effective for the mother; however, congenital syphilis has been reported in infants after such therapy. Women treated for syphilis during pregnancy should be followed with monthly VDRL’s until delivery and their children examined and followed carefully after birth. Infants with congenital syphilis should be evaluated for evidence of neurosyphilis by lumbar puncture. Neonatal syphilis with neurologic involvement requires parenteral aqueous or procaine penicillin G 50,000 units per kilogram every day for ten days. Infants with normal cerebrospinal fluid should receive benzathine penicillin G 50,000 units per kilogram intramuscularly as a single dose.
Prevention Approximately 1,500-2,000 cases of congenital syphilis are reported each year of which one half have received no serological screening for syphilis during pregnancy. A proportion of such cases have received no prenatal care. Others are missed because of failure to screen both in the first and third Treatment trimester of pregnancy, the latter being espeEarly in vitro studies have shown 0.03 mcg/ cially appropriate in “high risk” patient popuml of penicillin to be treponemicidal, however lations. All patients with positive serologies the long replication time of the spirochete in pregnancy require follow-upconsisting of a necessitates maintaining these levels for pe- history for recent or past syphilis exposure, a riods of one to two weeks for adequate thorough re-examination for mucocutaneous therapy. Benzathine penicillin is well suited lesions, a treponemal test for syphilis, and for maternal therapy and the CDC recom- evaluation for neurosyphilis with appropriate mends 2.4 million units given IM in one dose chemotherapy as indicated. Serological testfor early adult syphilis. The same dose given ing must be repeated monthly for the reweekly for three doses is adequate therapy for mainder of pregnancy and the importance of late syphilis. In the latter instance, neuro- tracing contacts and the possibility of re-insyphilis must be specifically excluded by lum- fection should be remembered. Infants of such bar puncture. Positive cerebrospinal fluid mothers require careful scrutiny and should findings require parenteral penicillin-G be treated if there is any question concerning (aqueous or procaine since benzathine crosses the adequacy of previous therapy in utero. the blood/brain barrier poorly) in doses rang- Finally, even in the absence of positive matering from twelve to 24 million units per day for nal serology, congenital syphilis should be a t least ten days. Some authorities have ex- part of the differential diagnosis of any pressed concern about the adequacy of single seriously infected child and appropriate steps dose benzathine penicillin therapy of women should be instituted to establish the diagwith primary syphilis for intrauterine neu- nosis.
CONGENITAL SYPHILIS LITERATURE CITED Harter, C. A. and K. Benirschke 1976 Fetal Syphilis in the First Trimester. American Journal of Obstetrics and Gynecology, 124: 705-711. Henderson, R, H,, and J, H. ill^^ et al. 1976 Syphilis-CDC Recommended Treatment Schedules 1976. Journal of Infectious Diseases, 134: 97-99. July, 1976.
219
Reimer, C. B., e t al. 1975 The specificity of fetal IGM; antibody or anti-antibody? Annals of the New York Academy of science, volume, 254,. 77-93, Taber, L. H., and T. W.H u k r 1975 Congenital syphilis. In: Infections of the Fetus and Newborn Infant. S. Krugman and A. Gershon, eds. A. Liss Incorporated, New York.
The Editors welcome contributwns to “Teratcgen Update. ” Manuscripts should be sent to Dr. John L. Sewer, Teratology Update Editor, Building 36,Room 50-04,National Institutes of Health, Bethesda, Maryland 20014. Articles should concisely summarize the clinical manifestations, etiology, pathogenesis, treatment, and prevention of the phenomena; and be accompanied by high-quality photographs of affected indiwiduals. Color illustrations will be at the author’s expense. Please address reprint requests to the author.
PLATE 1 EXPLANATION OF FIGURES
1 Nasopharyngeal discharge of early congenital syphilis 2 Interstitial keratitis of late congenital syphilis.
220
CONGENITAL SYPHILIS John Grossman I l l
PLATE 1
221
PLATE
2
EXPLANATION OF FIGURES
3 Notched incisors (Hutchinson’s teeth) of late congenital syphilis. 4 Sabre shins of late congenital syphilis.
222
CONGENITAL SYPHILIS John Grossman 111
PLATE 2
223
Congenital Syphilis JOHN GROSSMAN 111 Department of Obstetrics and Gynecology, George Washington University Medical Center, Washington, D.C. 20037
The damage due to fetal infection with Treponema pallidum, untreated during pregnancy, ranges from fulminent neonatal sepsis and death to asymptomatic infection persisting in childhood and culminating in tertiary syphilis in early adolescence. By convention, clinicians classify congenital syphilis as “early” and “late.” This terminology specifically refers to the time in the child‘s life when the diagnosis of syphilis is made.
Manifestations
neurologic and cardiovascular defects (figs. 24).
Epidemiology A t present, congenital syphilis occurs in approximately 0.05% of all live births in the United States. Approximately 1,900 cases were reported in 1973. Twenty percent of these were “early” and 80%“late” congenital syphilis. Fortunately, detection and treatment in the majority of cases makes clinical congenital syphilis uncommon. Dissemination of syphilis to the fetus is possible a t all stages of maternal infection, including the late latent stage, when asymptomatic patients remain persistently seropositive. Most frequently, however, dissemination is associated with a placentitis arising from hematogenous spread of the spirochetes between the first and second stage of infection in the mother. Contrary to previous thought, pregnancies are not impervious to treponemial invasion during the first half of gestation. Careful histologic examination has demonstrated spirochetes in products of conception in the first trimester. Dissolution of the cytotrophoblast was previously postulated as the cause of fetal susceptibility to infection after the eighteenth week, however electron microscopy has failed to demonstrate any loss of tissue integrity. Recently, immunologic immaturity in fetuses has been proposed to explain the absence of any apparent fetal inflammatory response to infection. Signs of congenital syphilis are uncommon before the infant is three weeks old; indeed if they are present a t birth, the prognosis is usually unfavorable.
Early congenital syphilis is an infectious, life threatening disease apparent in children under two years of age. The children are often small for gestational age or premature with hemolytic anemia, hepatosplenomegaly, and occasionally hydrops. The placenta is frequently large (fetoplacental ratios less than 5:1) with villitis and perivasculitis. Spirochetes may be demonstrable using special staining techniques. A maculopapular or vesiculobullous rash may be present. Fluid from skin lesions may be found to contain spirochetes when studied using darkfield microscopy. Over 50% of these infants have “snuffles,” a thick white or blood-tinged nasal discharge (fig. 1) teeming with treponemes. Periosteitis and long bone osteochondritis can cause Parrott’s pseudoparalysis, due to bone and joint pain. Meningitis and cerebrospinal fluid abnormalities are common. Late congenital syphilis appears in children over two years of age and is asymptomatic in two-thirds of all cases. Serology is invariably positive. Those with findings have the more classical “stigmata” of congenital syphilis. These include interstitial keratitis, VIII Diagnosis nerve deafness, dental and bony deformities (Hutchinson’s teeth, mulberry molars, sabre Demonstration of spirochetes in skin leshins, saddle nose, frontal bossing, palatal sions or nasal discharge is diagnostic as is a perforation, Clutton’s joints), cutaneous le- cord VDRL (Venereal Disease Research Labosions (rhagades and gummas) and rarely, ratory) antibody titre 4-fold greater than that TERAMLOGY.16: 217-224.
217
218
JOHN GROSSMAN I11
of maternal serum. Unfortunately, many cases present more difficult diagnostic problems and often the only clue consists of a vague history of maternal venereal disease treated during pregnancy. Cord blood macroglobulin has been proposed as a general screening test for congenital infections and FTA-ABS-IgM (Fluorescent Treponeme Antibody Absorption-Immunoglobulin M) as a specific test for congenital syphilis. The latter assay is not generally available and recent work has suggested that false positives may arise from fetal IgM directed against maternal IgG. In such instances, maternal 7s globulins elaborated in response to infection are acquired passively by the fetus which then elaborates macroglobulin anti-antibody. Asymptomatic offspring of mothers treated in pregnancy with positive but non-diagnostically elevated cord VDRL’s present a problem in clinical management. More specific treponemal tests or macroglobulin assays can be employed if available. If the titer is due to passive maternal transfer of IgG, serial VDRL’s should show a quantitative decrease with time and revert to negative by three months of life. Examination of spinal fluid for pleocytosis, elevated protein, or positive serology is indicated in suspicious cases.
rosyphilis in their babies. Larger doses of penicillin may be used in such circumstances. Penicillin allergic pregnant women should not receive tetracycline due to potential adverse effects upon fetal dentition and bone. Oral erythromycin in doses of two grams per day for 15 to 20 days should be effective for the mother; however, congenital syphilis has been reported in infants after such therapy. Women treated for syphilis during pregnancy should be followed with monthly VDRL’s until delivery and their children examined and followed carefully after birth. Infants with congenital syphilis should be evaluated for evidence of neurosyphilis by lumbar puncture. Neonatal syphilis with neurologic involvement requires parenteral aqueous or procaine penicillin G 50,000 units per kilogram every day for ten days. Infants with normal cerebrospinal fluid should receive benzathine penicillin G 50,000 units per kilogram intramuscularly as a single dose.
Prevention Approximately 1,500-2,000 cases of congenital syphilis are reported each year of which one half have received no serological screening for syphilis during pregnancy. A proportion of such cases have received no prenatal care. Others are missed because of failure to screen both in the first and third Treatment trimester of pregnancy, the latter being espeEarly in vitro studies have shown 0.03 mcg/ cially appropriate in “high risk” patient popuml of penicillin to be treponemicidal, however lations. All patients with positive serologies the long replication time of the spirochete in pregnancy require follow-upconsisting of a necessitates maintaining these levels for pe- history for recent or past syphilis exposure, a riods of one to two weeks for adequate thorough re-examination for mucocutaneous therapy. Benzathine penicillin is well suited lesions, a treponemal test for syphilis, and for maternal therapy and the CDC recom- evaluation for neurosyphilis with appropriate mends 2.4 million units given IM in one dose chemotherapy as indicated. Serological testfor early adult syphilis. The same dose given ing must be repeated monthly for the reweekly for three doses is adequate therapy for mainder of pregnancy and the importance of late syphilis. In the latter instance, neuro- tracing contacts and the possibility of re-insyphilis must be specifically excluded by lum- fection should be remembered. Infants of such bar puncture. Positive cerebrospinal fluid mothers require careful scrutiny and should findings require parenteral penicillin-G be treated if there is any question concerning (aqueous or procaine since benzathine crosses the adequacy of previous therapy in utero. the blood/brain barrier poorly) in doses rang- Finally, even in the absence of positive matering from twelve to 24 million units per day for nal serology, congenital syphilis should be a t least ten days. Some authorities have ex- part of the differential diagnosis of any pressed concern about the adequacy of single seriously infected child and appropriate steps dose benzathine penicillin therapy of women should be instituted to establish the diagwith primary syphilis for intrauterine neu- nosis.
CONGENITAL SYPHILIS LITERATURE CITED Harter, C. A. and K. Benirschke 1976 Fetal Syphilis in the First Trimester. American Journal of Obstetrics and Gynecology, 124: 705-711. Henderson, R, H,, and J, H. ill^^ et al. 1976 Syphilis-CDC Recommended Treatment Schedules 1976. Journal of Infectious Diseases, 134: 97-99. July, 1976.
219
Reimer, C. B., e t al. 1975 The specificity of fetal IGM; antibody or anti-antibody? Annals of the New York Academy of science, volume, 254,. 77-93, Taber, L. H., and T. W.H u k r 1975 Congenital syphilis. In: Infections of the Fetus and Newborn Infant. S. Krugman and A. Gershon, eds. A. Liss Incorporated, New York.
The Editors welcome contributwns to “Teratcgen Update. ” Manuscripts should be sent to Dr. John L. Sewer, Teratology Update Editor, Building 36,Room 50-04,National Institutes of Health, Bethesda, Maryland 20014. Articles should concisely summarize the clinical manifestations, etiology, pathogenesis, treatment, and prevention of the phenomena; and be accompanied by high-quality photographs of affected indiwiduals. Color illustrations will be at the author’s expense. Please address reprint requests to the author.
PLATE 1 EXPLANATION OF FIGURES
1 Nasopharyngeal discharge of early congenital syphilis 2 Interstitial keratitis of late congenital syphilis.
220
CONGENITAL SYPHILIS John Grossman I l l
PLATE 1
221
PLATE
2
EXPLANATION OF FIGURES
3 Notched incisors (Hutchinson’s teeth) of late congenital syphilis. 4 Sabre shins of late congenital syphilis.
222
CONGENITAL SYPHILIS John Grossman 111
PLATE 2
223
