Features and Diagnosis Sifilis

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Official reprint from UpToDate®

www.uptodate.com © 2022 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Congenital syphilis: Clinical features and diagnosis

Author: Simon R Dobson, MD, FRCP(C)
Section Editors: Sheldon L Kaplan, MD, Leonard E Weisman, MD
Deputy Editor: Carrie Armsby, MD, MPH
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: May 2022. | This topic last updated: Mar 26, 2021.
INTRODUCTION
Congenital syphilis occurs when the spirochete Treponema pallidum is transmitted from a
pregnant woman to her fetus. Infection can result in stillbirth, prematurity, or a wide spectrum
of clinical manifestations; only severe cases are clinically apparent at birth [1].
The clinical features and diagnosis of congenital syphilis will be discussed here. The evaluation,
management, and prevention of congenital syphilis are discussed separately. (See "Congenital
syphilis: Evaluation, management, and prevention".)
Syphilis in pregnancy and acquired syphilis also are discussed separately:
● (See "Syphilis in pregnancy".)

● (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients
without HIV".)
● (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients
without HIV", section on 'Clinical manifestations'.)
● (See "Syphilis: Treatment and monitoring".)
● (See "Neurosyphilis".)
● (See "Syphilis: Screening and diagnostic testing".)
CASE DEFINITION
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The Centers for Disease Control and Prevention (CDC) case definition for congenital syphilis is
provided in the table ( table 1) [1]. Other case definitions may differ slightly from the CDC
definition [2]. In general, case definitions for congenital syphilis require only one of two criteria:
● The child has physical, laboratory, or radiographic signs of congenital syphilis

(confirmed/highly probable congenital syphilis), or
● The child was born to a mother with untreated, inadequately, or suboptimally treated
syphilis (presumed congenital syphilis) ( table 2)
Some experts would also presume infants to have congenital syphilis if their mothers had
contact with a person with primary or secondary syphilis within 90 days before delivery and
were not treated or were inadequately treated [3,4].
EPIDEMIOLOGY
Congenital syphilis is a significant public health problem, complicating an estimated one million
pregnancies per year throughout the world [5]. The incidence of congenital syphilis reflects the
rate of syphilis in women of childbearing age [6]. (See "Syphilis: Epidemiology, pathophysiology,
and clinical manifestations in patients without HIV", section on 'Epidemiology'.)
Most cases develop because the mother received no prenatal care or insufficient treatment for
syphilis before or during pregnancy ( table 2) [7-10]. Among women with untreated early
syphilis, 40 percent of pregnancies result in spontaneous abortion [11]. (See "Syphilis in
pregnancy", section on 'Prevalence'.)
In the United States, the rate of congenital syphilis among infants <1 year of age peaked at
approximately 100 cases per 100,000 live births in 1991 (in part because of a change in the case
definition to include infants born to women with untreated or inadequately treated syphilis in
1988), then declined steadily in the 1990s and early 2000s [8]. Since 2012, there has been a
steady year-on-year increase in reported cases [12,13]. In 2018, there were a total of 1306
reported cases of congenital syphilis in the United States, including 78 syphilitic stillbirths and
16 infant deaths [13,14]. This represents the highest reported rate since 1991. The 2018 case
rate (33 cases per 100,000 live births) represents a 40 percent increase relative to 2017 and a
nearly 400 percent increase relative to 2012. As is expected, the increase in rates of congenital
syphilis parallels increases in primary and secondary syphilis among all women and
reproductive-aged women during this period ( figure 1) [12-15].
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Poor access to prenatal care is an important risk factor for congenital syphilis. Among the 458
cases of congenital syphilis reported to the Centers for Disease Control and Prevention in 2014,
nearly one-quarter were born to mothers who did not receive prenatal care [12]. Among the
314 cases in which the mother received prenatal care, 135 (43 percent) received no treatment
for syphilis during the pregnancy and 94 (30 percent) received inadequate treatment. Similarly,
in a report by the New York City Department of Health and Mental Hygiene of 578 syphilis
infections reported in pregnant women during 2010 to 2016, >85 percent did not result in
congenital infection, presumably because of early screening and treatment [16]. Of the 68 cases
of congenital syphilis that occurred, 31 percent were born to women who received no prenatal
care or did not have a syphilis test ≥45 days before delivery. In addition, of the women who had
appropriate testing during pregnancy, 15 percent received no or inadequate treatment.
Obstacles to accessing health care identified in this report included substance use, mental
health disorders, recent arrival in the United States, unstable housing, and lack of health care
coverage.
The rate of congenital syphilis is increased among infants born to mothers with HIV infection.
However, the contribution of maternal coinfection with syphilis and HIV to vertical transmission
of either syphilis or HIV is not completely understood. (See "Syphilis in patients with HIV",
section on 'Effect of syphilis on HIV'.)
The rate of congenital syphilis is generally low among children adopted internationally; however
it is relatively increased among those adopted from Africa ( table 3). Given the difficulty in
confirming adequate treatment/treatment response of the birth mother and the risk of long-
term sequelae in untreated children, we recommend screening international adoptees for
congenital syphilis (regardless of the country of origin). (See "International adoption: Infectious
disease aspects", section on 'Syphilis'.)
TRANSMISSION
Humans are the only natural host of T. pallidum [17]. Congenital syphilis generally is acquired
through transplacental transmission of spirochetes in the maternal bloodstream or,
occasionally, through direct contact with an infectious lesion during birth [18-20]. (See "Syphilis
in pregnancy", section on 'Vertical transmission'.)
Transplacental transmission of T. pallidum can occur at any time during gestation but occurs
with increasing frequency as gestation advances. Women with untreated primary or secondary
syphilis are more likely to transmit syphilis to their fetuses than women with latent disease (60
to 90 versus 40 percent in early latent and <10 percent in late latent syphilis) [21,22]. The risk of
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transmission decreases with increasing time since primary or secondary infection and is only 2
percent after four years.
T. pallidum is not transferred in breast milk, but transmission may occur if the mother has an
infectious lesion (eg, chancre) on her breast [23].
PATHOGENESIS
At the onset of congenital syphilis, T. pallidum is liberated directly into the circulation of the
fetus, resulting in spirochetemia with widespread dissemination to almost all organs. The
clinical manifestations result from the inflammatory response. The bones, liver, pancreas,
intestine, kidney, and spleen are the most frequently and severely involved. The severity of the
manifestations is variable and can range from isolated laboratory or radiographic abnormalities
to fulminant involvement of multiple organ systems. Overt infection can manifest in the fetus,
the newborn, or later in childhood (if the infant is not treated) [24].
The pathophysiology of and immune response to acquired syphilis infection are discussed
separately. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients
without HIV".)
EARLY CONGENITAL SYPHILIS
Clinical findings — Early congenital syphilis is arbitrarily defined by clinical manifestations with
onset before two years of age [4]. Clinical manifestations in untreated infants usually appear by
three months of age, most often by five weeks [4,25].
Approximately 60 to 90 percent of live-born neonates with congenital syphilis are asymptomatic

at birth [12,26]. The presence of signs at birth depends upon the timing of intrauterine infection
and treatment [17]. Among symptomatic infants, the most common findings include [12,27]:
● Hepatomegaly
● Jaundice
● Nasal discharge ("snuffles")
● Rash
● Generalized lymphadenopathy
● Skeletal abnormalities
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Manifestations of early clinical syphilis are varied and unpredictable ( table 4)

[1,4,17,23,28,29]. Common clinical findings are reviewed here:
● Placenta and umbilical cord – The placenta of neonates with congenital syphilis is often
large, thick, and pale. The umbilical cord is edematous and may resemble a "barber's pole"
with spiral stripes of red and light blue discoloration alternating with streaks of chalky
white. It may be significantly inflamed with an abscess-like foci of necrosis within Wharton
jelly, centered around the umbilical vessels (necrotizing funisitis) [30,31]. (See "Care of the
umbilicus and management of umbilical disorders", section on 'Funisitis'.)
● Hepatomegaly – Hepatomegaly occurs in almost all infants with congenital syphilis

[10,23]. Hepatomegaly may or may not be associated with splenomegaly, but isolated
splenomegaly does not occur. When noted on fetal ultrasonography, hepatomegaly may
indicate failure of maternal treatment to prevent fetal infection [32]. Hepatomegaly is
associated with jaundice and cholestasis. Laboratory findings may include elevated
aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and direct
bilirubin; delayed prothrombin time; and visible spirochetes on liver biopsy (if one is
performed) (see 'Laboratory abnormalities' below). Abnormalities of liver function may be
exacerbated by penicillin therapy before improving [33]. Liver dysfunction generally
resolves slowly, even after adequate therapy.
● Rhinitis – Syphilitic rhinitis ("snuffles") ( picture 1) may herald the onset of congenital
syphilis. It usually develops during the first week of life and seldom after the third month.
The nasal discharge is white and may be bloody (secondary to mucosal erosion) or
purulent if there is secondary bacterial infection. It is more severe and persistent than the
nasal discharge of the common cold (see "The common cold in children: Clinical features
and diagnosis", section on 'Clinical features'). The nasal discharge contains spirochetes, is
contagious, and can transmit infection by direct contact. It should be examined by
darkfield microscopy to confirm the diagnosis. (See 'Younger than one month' below.)
● Rash – The rash of congenital syphilis usually appears one to two weeks after the rhinitis.
It is maculopapular and consists of small, initially red or pink spots. The lesions may occur
anywhere, but are more prominent on the back, buttocks, posterior thighs, and soles (
picture 2). The rash generally progresses over one to three weeks, followed by
desquamation and crusting. As it fades, the lesions become dusky red or copper-colored,
and the pigmentation may persist. If present at birth, the rash may be widely
disseminated and bullous (pemphigus syphiliticus). Ulcerative lesions and bullous fluid
contain spirochetes, are contagious, and can transmit infection by direct contact; samples
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of such lesions should be examined by darkfield microscopy to confirm the diagnosis. (See
'Younger than one month' below.)
Other characteristic, but uncommon, cutaneous lesions of congenital syphilis include

fissures, mucous patches, and condylomata lata. The fissures occur around the lips, nares,
and anus. They bleed easily and heal with scarring. The mucous patches may occur on any
mucous membrane, particularly those in the mouth and genitalia. Condylomata lata are
flat, wart-like, moist lesions around the mouth, nares, anus, and other areas of the skin
where there is moisture or friction. They contain spirochetes and can transmit infection.
● Generalized lymphadenopathy – Generalized, nontender lymphadenopathy is a

common manifestation. Palpable epitrochlear lymphadenopathy in an infant is highly
suggestive of congenital syphilis [23].
● Other manifestations – Other manifestations of congenital syphilis may include

[1,4,10,17,23,28,29]:
• Nonimmune fetal hydrops

• Fever (may be more prominent in infants born to mothers who are affected late in
pregnancy and whose serology is negative at delivery)
• Myocarditis
• Pneumonia
• Failure to move an extremity secondary to pain ("pseudoparalysis of Parrot")
• Sepsis due to other bacteria (eg, Escherichia coli, group B streptococci, Yersinia species)
• Ophthalmologic manifestations – Loss of eyebrows, chorioretinitis, uveitis, cataract,
glaucoma, and chancre of the eyelid
• Gastrointestinal manifestations – Rectal bleeding (from ileitis), necrotizing enterocolitis,
malabsorption
• Nephrotic syndrome (immune complex mediated; responsive to penicillin) [34-37] (see
"Congenital and infantile nephrotic syndrome", section on 'Infectious causes')
Central nervous system syphilis — Central nervous system (CNS) syphilis in children with
congenital infection may be asymptomatic or symptomatic. Asymptomatic CNS syphilis is
indicated by abnormalities in the cerebrospinal fluid (see 'Cerebrospinal fluid abnormalities'
below). Asymptomatic CNS syphilis occurs in approximately 40 percent of infants who have
clinical, laboratory, or radiographic abnormalities of congenital syphilis, but is infrequent in
infants without such manifestations [17,38-42].
Symptomatic CNS involvement is rare among infants with congenital syphilis in the era of
penicillin therapy but may develop from ongoing dissemination in infants who are not treated
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in the neonatal period [17]. Symptomatic CNS syphilis in infants has two overlapping
presentations: acute syphilitic leptomeningitis and chronic meningovascular syphilis.
● Acute syphilitic leptomeningitis typically manifests during the first year of life, usually
between three and six months. The clinical findings are suggestive of bacterial meningitis
(eg, vomiting, bulging fontanelle, increased head circumference, splitting of the cranial
sutures), but the CSF findings are more suggestive of aseptic meningitis (predominance of
mononuclear cells, modest increase in protein, normal glucose) [17,23]. Acute syphilitic
leptomeningitis generally responds to penicillin therapy.
● Chronic meningovascular syphilis typically manifests toward the end of the first year [17].
The clinical findings include signs of progressive hydrocephalus, cranial nerve palsies,
papilledema, optic atrophy, neurodevelopmental regression, and seizures. Syphilitic
endarteritis may cause cerebral infarction in the second year of life.
In addition, pituitary gland involvement may manifest with persistent hypoglycemia or diabetes
insipidus [43,44].
Radiographic abnormalities
Long-bone radiographs — Abnormal long-bone radiographs are a common manifestation of

early congenital syphilis (occurring in 60 to 80 percent) and may be the sole manifestation in
infants born to mothers with untreated syphilis [45,46]. The changes usually are present at birth
but may appear in the first few weeks of life. Long-bone abnormalities may be associated with
pathologic fractures or pain, which may limit movement of the involved extremity, giving the
appearance of paralysis ("pseudoparalysis of Parrot") [47].
The radiographic abnormalities characteristically are bilateral, symmetric, and polyostotic; the
femur, humerus, and tibia are most frequently involved. Findings may include [47-49]:
● Metaphyseal lucent bands (this finding may occur in response to other systemic illnesses) (
image 1).
● Symmetric localized demineralization and osseous destruction of the medial portion of the
proximal tibial metaphysis (Wimberger sign), which also may occur in neonatal
hyperparathyroidism and osteomyelitis.
● Metaphyseal serration ("sawtooth metaphysis").
● Diaphyseal periostitis with new bone formation (may occur in other conditions) (
image 2).
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● Irregular areas of increased density and rarefaction ("moth-eaten" appearance) (

image 3 and image 4).
Long-bone abnormalities may be helpful in the diagnosis of congenital syphilis and may be
warranted in [50-52]:
● Neonates who have Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin
(RPR) titers less than fourfold the maternal titer, normal physical examination, and whose
mothers were not treated or were inadequately treated ( table 2); were treated ≤4 weeks
before delivery; or have evidence of relapse or reinfection (fourfold or greater increase in
titers). (See "Congenital syphilis: Evaluation, management, and prevention", section on
'Possible congenital syphilis'.)
● Infants and children with reactive VDRL or RPR and with abnormal skeletal findings on
physical examination (eg, extremity pain, lack of movement of one or more extremities).
(See "Congenital syphilis: Evaluation, management, and prevention", section on 'Proven or
highly probable disease' and "Congenital syphilis: Evaluation, management, and
prevention", section on 'Evaluation and management of children >1 month of age'.)
Chest radiographs — Complete opacification of both lung fields ("pneumonia alba") is the
classic radiographic appearance of pneumonia in infants with congenital syphilis. However, a
fluffy, diffuse infiltrate involving all lung areas is more common in the era of penicillin therapy.
Laboratory abnormalities
Hematologic studies — Hematologic abnormalities of early congenital syphilis may include

[10,53,54]:
● Anemia – Direct Coomb test (also known as direct antiglobulin test) negative hemolytic
anemia in the neonatal period; nonhemolytic anemia after the neonatal period
● Thrombocytopenia
● Leukopenia or leukocytosis
Hemolysis is often accompanied by cryoglobulinemia, immune complex formation, and

macroglobulinemia. It does not respond to therapy and may last for weeks.
Cerebrospinal fluid abnormalities — Laboratory evidence of CNS involvement may include

[10,51,52]:
● Reactive CSF VDRL.
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● CSF pleocytosis (defined by consensus as >25 white blood cells [WBC]/microL for infants <1
month, although some experts use a threshold of >5 WBC/microL).
● Elevated CSF protein (defined by consensus as >150 mg/dL in term infants <1 month of
age and >170 mg/dL in preterm infants <1 month of age, although some experts use a
threshold of >40 mg).
However, none of these findings is highly sensitive or specific [40,42]. In an observational study
that used the rabbit infectivity test as the reference standard for identification of spirochetes in
the CSF, the sensitivity and specificity of reactive CSF VDRL, elevated CSF WBC, and elevated CSF
protein were as follows [40]:
● Reactive CSF VDRL – Sensitivity 54 percent, specificity 90 percent

● Elevated CSF WBC count – Sensitivity 38 percent, specificity 88 percent
● Elevated CSF protein – Sensitivity 56 percent, specificity 78 percent
The significance of a reactive CSF VDRL in a neonate is not clear, since there may be false
positives (related to maternal nontreponemal immunoglobulin G [IgG] antibodies that cross the
placenta and diffuse into the fetal CSF or contamination of the CSF with blood from a traumatic
lumbar puncture) and false negatives (neonates with initial nonreactive CSF VDRL may
subsequently develop signs of neurosyphilis). (See 'Congenital neurosyphilis' below.)
Examination of the CSF for T. pallidum DNA by polymerase chain reaction (PCR) may prove more
useful for definitive diagnosis of congenital neurosyphilis [18,40,41], but this test is not widely
available. (See 'Diagnostic tests' below.)
LATE CONGENITAL SYPHILIS
Late congenital syphilis is arbitrarily defined by clinical manifestations with onset after two
years of age [4]. Manifestations of late congenital syphilis are related to scarring or persistent
inflammation from early infection and are characterized by gumma formation in various tissues
[55]. Late congenital syphilis develops in approximately 40 percent of infants born to women
with untreated syphilis during pregnancy. Some manifestations of late congenital syphilis can
be prevented by treatment of the mother during pregnancy or treatment of the infant within
the first three months of life [56,57]. However, other manifestations (eg, keratitis, saber shins)
may occur or progress despite appropriate therapy [58].
Manifestations of late congenital syphilis include ( table 5) [1,23,57,59,60]:
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● Facial features – Frontal bossing ( picture 3), saddle nose, short maxilla, protuberant
mandible.
● Eyes – Interstitial keratitis ( picture 4) (bilateral, usually occurs around puberty but can
occur anytime between 4 and 30 years), secondary glaucoma, corneal scarring, optic
atrophy.
● Ears – Sensorineural hearing loss associated with late congenital syphilis typically develops
suddenly at 8 to 10 years of age and often accompanies interstitial keratitis. The higher
frequencies are affected first; normal conversational tones are affected later. Syphilis-
associated hearing loss may respond to long-term glucocorticoid therapy [61].
● Oropharynx – Hutchinson teeth (hypoplastic, notched, widely spaced permanent teeth

[upper central incisors most commonly affected] ( picture 5); before eruption,
Hutchinson teeth are visible on dental radiographs), mulberry molars (maldevelopment of
the cusps of the first molars) ( picture 6), and perforation of the hard palate ( picture 7
) (virtually pathognomonic for congenital syphilis).
● Cutaneous – Rhagades (perioral fissures or a cluster of scars radiating around the mouth) (
picture 8), gummas (granulomatous inflammatory response to spirochetes) in the skin
or mucous membranes.
● Neurologic – Intellectual disability, arrested hydrocephalus, cranial nerve palsies
● Skeletal – Anterior bowing of the shins ("saber shins") ( picture 9), enlargement of the
sternoclavicular portion of the clavicle (Higoumenakis sign), painless arthritis of the knees
("Clutton joints") ( picture 10), and, rarely, other joints.
● Hematologic – Paroxysmal cold hemoglobinuria. (See "Paroxysmal cold hemoglobinuria".)
Among these manifestations, Hutchinson triad (Hutchinson teeth, interstitial keratitis, and
sensorineural hearing loss), mulberry molars, and Clutton joints are relatively specific for
congenital syphilis [23,59].
DIFFERENTIAL DIAGNOSIS
The manifestations of congenital syphilis in neonates may be similar to those of other neonatal
infections or newborn conditions, including:
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● Toxoplasmosis infection (see "Toxoplasmosis and pregnancy", section on 'Fetal infection'

and "Congenital toxoplasmosis: Clinical features and diagnosis", section on 'Clinical
features')
● Rubella virus infection (see "Congenital rubella", section on 'Evaluation')
● Cytomegalovirus infection (see "Congenital cytomegalovirus infection: Clinical features

and diagnosis", section on 'Clinical manifestations')
● Herpes simplex virus infection (see "Neonatal herpes simplex virus infection: Clinical
features and diagnosis", section on 'Evaluation and diagnosis')
● Neonatal sepsis (see "Clinical features, evaluation, and diagnosis of sepsis in term and late
preterm infants", section on 'Evaluation and initial management')
● Neonatal hepatitis (see "Causes of cholestasis in neonates and young infants")
● Hydrops fetalis (see "Nonimmune hydrops fetalis", section on 'Etiology and prenatal
management of disorders associated with hydrops' and "Postnatal diagnosis and
management of hemolytic disease of the fetus and newborn", section on 'Diagnosis')
● Long-bone abnormalities (eg, osteomyelitis, rickets, physical abuse) or failure to move an

extremity (see "Differential diagnosis of the orthopedic manifestations of child abuse" and
"Brachial plexus syndromes", section on 'Neonatal brachial plexus palsy')
● Vesicular lesions (see "Vesicular, pustular, and bullous lesions in the newborn and infant")
Historical features, additional findings, and/or laboratory testing usually differentiate these
conditions from congenital syphilis.
DIAGNOSTIC TESTS
The diagnosis of syphilis is complicated by the absence of a method to culture T. pallidum on

laboratory media. In clinical settings, the diagnosis of syphilis may be established by:
● Direct visualization of T. pallidum by darkfield microscopy ( picture 11) or fluorescent

antibody staining of infected body fluids or lesions, placenta, or umbilical cord
● Demonstration of the T. pallidum by special stains ( picture 12) or histopathologic

examination [62,63]
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● Demonstration of serologic reactions typical of syphilis
Tests that may be used to establish the diagnosis of congenital syphilis in research settings
include:
● Animal inoculation (ie, rabbit infectivity test)
● Detection of T. pallidum DNA in a clinical specimen (eg, polymerase chain reaction [PCR])
[18,40,41,64]
These testing methods are discussed in detail separately. (See "Syphilis: Screening and
diagnostic testing", section on 'Diagnostic tests'.)
Darkfield microscopy can be performed on body fluids (eg, nasal discharge) or moist skin
lesions [65]. Darkfield microscopy enables demonstration of thin, delicate, corkscrew-shaped
organisms with rigid, tightly wound spirals ( picture 11). A positive darkfield slide illustrates
the characteristic motility associated with T. pallidum: a forward and backward motion with
rotation about the longitudinal axis [65]. Soft side-to-side bending and twisting may also be
seen. Failure to identify spirochetes with darkfield microscopy does not exclude the diagnosis of
syphilis. Darkfield microscopy depends upon the direct visualization of live, active spirochetes,
characteristics that are rapidly destroyed by the previous use of antibiotics.
Serologic testing can establish a diagnosis of proven/highly probable, at-risk, or unlikely

congenital syphilis infection (see 'Interpretation' below). Serologic tests include nontreponemal
tests (eg, Venereal Disease Research Laboratory or rapid plasma reagin [RPR]) and treponemal
tests (eg, fluorescent treponemal antibody absorption [FTA-ABS], T. pallidum particle
agglutination, enzyme immunoassay, chemiluminescence immunoassay,
microhemagglutination test for T. pallidum [MHA-TP]) [1].
Nontreponemal tests are inexpensive and rapidly performed. They are sensitive, but not
specific. Nontreponemal tests generally are used in the evaluation of neonates with possible
congenital syphilis because they provide quantitative results, which can be compared with
simultaneously obtained maternal results to categorize neonatal infection [52]. The neonate's
nontreponemal titer usually is one to two dilutions less than that of the mother [66]. When the
mother's titer is low, the neonate may have nonreactive serology but remains at risk for
congenital syphilis. (See 'Congenital syphilis less likely' below.)
Serologic tests for immunoglobulin G [IgG] antibodies are problematic because it is not possible
to differentiate between passively acquired maternal antibody and endogenous antibody
produced by the fetus/neonate. The ability to detect immunoglobulin M [IgM] antibodies, which
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do not cross the placenta, would confirm fetal infection. Unfortunately, a sufficiently sensitive
and specific IgM assay is not available for routine use in the assessment of congenital syphilis
[51]. The fluorescent anti-treponemal IgM antibody test IgM FTA-ABS was used in the past, but
because of lack of sensitivity [67,68], the Centers for Disease Control and Prevention suspended
its use for diagnostic testing of infants.
The rabbit infectivity test (RIT), which involves the inoculation of cerebrospinal fluid [CSF] or
other body fluids into rabbits to determine the presence of viable T. pallidum, is the reference
standard test for congenital syphilis [23,25,55]. However, routine use of RIT is not practical
because it involves animal testing and is not widely available.
PCR has been used on neonatal blood and CSF for diagnosis of congenital syphilis, but these
tests are not widely available [18,40,41,69]. Compared with isolation of the spirochetes by rabbit
infectivity testing, the sensitivity and specificity of PCR on cerebrospinal fluid was 65 to 71
percent and 97 to 100 percent, respectively [40,41]. Among 17 infants who had spirochetes
detected in CSF by rabbit inoculation, blood PCR was the best predictor of central nervous
system infection with T. pallidum [40].
APPROACH TO DIAGNOSIS
The vagaries of the maternal history and signs or lack of signs in the newborn in combination
with the potential consequences of delayed or missed diagnosis of congenital syphilis demand
a "safety first" approach to both diagnosis and treatment [4]. The Centers for Disease Control
and Prevention (CDC) and the American Academy of Pediatrics (AAP) Committee on Infectious
Diseases provide guidelines for the evaluation and management of congenital syphilis (
algorithm 1 and table 6) [51,52]. Maternal nontreponemal test results are required for
entry into the algorithm.
The CDC and AAP guidelines recommend that maternal samples be screened according to the
traditional algorithm (ie, a nontreponemal test followed by a treponemal test if the
nontreponemal test is positive). However, some laboratories screen samples in reverse (ie, a
treponemal test before the nontreponemal test) [70]. Interpretation of results with reverse
sequence screening is discussed separately. (See "Syphilis: Screening and diagnostic testing",
section on 'Serologic testing algorithms'.)
Point-of-care testing (usually linked with HIV testing) using immunochromatographic strips
provides an alternative to laboratory testing that is particularly useful in resource-limited
settings. These tests can be done during antenatal visits, do not require the laboratory
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infrastructure necessary for conventional tests, and can be performed on finger-stick blood
samples. They are easy to perform, it is easy to interpret their results, and they have a quick
turnaround time of 20 minutes or so. They have good sensitivity and specificity, comparable to
those of conventional treponemal and nontreponemal tests [70,71].
Clinical suspicion — The diagnosis of congenital syphilis should be suspected in all infants
born to women who have reactive nontreponemal and treponemal tests for syphilis; the
treponemal test is necessary to exclude a false-positive nontreponemal test (see "Syphilis in
pregnancy"). The diagnosis of congenital syphilis also should be suspected in infants born to
women who are identified clinically or through contact tracing as having early syphilis during
the three months after delivery [4].
In addition, the possibility of congenital syphilis should be considered in infants and children
with the following nonspecific clinical findings, particularly in infants born to women with a
history of syphilis or risk factors for syphilis (see "Syphilis in pregnancy", section on
'Prevalence'):
● Unexplained prematurity (<37 weeks gestation)

● Unexplained hydrops fetalis
● Enlarged placenta
● Failure to move an extremity ("pseudoparalysis")
● Persistent rhinitis ( picture 1)
● Persistent maculopapular or papulosquamous rash ( picture 2), particularly in the
diaper area
● Jaundice, hepatomegaly
● Neonatal pneumonia
● Generalized lymphadenopathy
● Anemia (Coomb [direct antiglobulin] test negative)
● Thrombocytopenia
● Sensorineural hearing loss
● Interstitial keratitis
Finally, the possibility of congenital syphilis should be suspected in children who are adopted
internationally. (See "International adoption: Infectious disease aspects", section on 'Syphilis'.)
Initial evaluation
Younger than one month — The initial evaluation of infants younger than one month of age
who were born to women with reactive nontreponemal and treponemal test results should
include ( algorithm 1 and table 6) [51,52]:
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● A quantitative nontreponemal test (rapid plasma reagin [RPR] or Venereal Disease

Research Laboratory [VDRL]) on infant serum; testing umbilical cord blood could yield a
false positive result if the cord blood is contaminated with maternal blood. The
nontreponemal test that is performed on the infant should be the same that was done on
the mother so that the infant's titers can be compared with those of the mother.
● Physical examination for evidence of congenital syphilis and darkfield microscopic

examination or direct fluorescent antibody staining of suspicious lesions or body fluids
(eg, nasal discharge). (See 'Early congenital syphilis' above and 'Diagnostic tests' above.)
● Pathologic examination of the placenta or umbilical cord with specific fluorescent

antitreponemal antibody staining (if possible) [20,31,72]. Characteristic histopathologic
features are described separately. (See "Care of the umbilicus and management of
umbilical disorders", section on 'Funisitis'.)
Additional evaluation depends upon the findings from the initial evaluation and is discussed
separately. (See "Congenital syphilis: Evaluation, management, and prevention", section on
'Subsequent evaluation and management'.)
Older than one month — The initial evaluation of infants and children older than one month
of age with clinical, radiographic, or laboratory manifestations compatible with congenital
syphilis should include a quantitative VDRL or RPR, physical examination, and darkfield
microscopic examination (if it is available) or direct fluorescent antibody staining of suspicious
body fluids [51,52].
Infants and children who are found to have reactive serologic tests for syphilis when they are
older than one month of age should have maternal serology and records reviewed to assess
whether the child has congenital or acquired syphilis, although this distinction may be difficult
[1,24]. Additional evaluation of such children may include [51,52]:
● Cerebrospinal fluid (CSF) analysis for VDRL, cell count, and protein
● Complete blood count with differential and platelet count
● Evaluation and testing for HIV infection
● Other tests as clinically indicated (eg, chest radiograph, long-bone radiographs, liver
function tests, abdominal ultrasonography, ophthalmologic examination, and auditory
brainstem response, and neuroimaging studies)
CSF and complete blood count abnormalities may occur in both congenital and acquired
syphilis, but radiographic abnormalities are more suggestive of congenital than acquired
syphilis. (See 'Radiographic abnormalities' above.)
6/19/22, 10:55 PM 14428
Interpretation — To maximize treatment of children potentially infected with T. pallidum, the

CDC provides categories of congenital syphilis infection that encompass infants with proven or
highly probable disease, as well as those who are at risk of congenital syphilis without any
clinical evidence of infection. The inclusion of infants at risk for congenital syphilis helps to
ensure that possible cases are treated, although not all treated infants will be infected [51].
Proven or highly probable congenital syphilis — Congenital syphilis is proven or highly

probable if the neonate (<1 month of age) has any of the following [51]:
● An abnormal physical examination that is consistent with congenital syphilis
● A serum quantitative nontreponemal serologic titer that is ≥4-fold the corresponding

maternal titer (which is equivalent to two dilutions [eg, neonate's titer 1:32 and maternal
titer 1:8])
● A positive darkfield ( picture 11) or fluorescent antibody test of lesions, body fluid(s),
placenta, or umbilical cord (these procedures may not be available in all centers)
Neonates with proven or highly probable congenital syphilis should undergo further evaluation
and treatment. (See "Congenital syphilis: Evaluation, management, and prevention", section on
'Subsequent evaluation and management'.)
Possible congenital syphilis — Neonates with normal physical examination and serum VDRL
or RPR titers less than fourfold the maternal titer, but whose mothers were not treated or
received inadequate/suboptimal therapy ( table 2) are considered to have possible congenital
syphilis [51,52].
Some experts would also consider infants to have possible congenital syphilis if their mothers
had contact with a person with primary or secondary syphilis within 90 days before delivery and
were not treated or were inadequately treated, even if the mother had nonreactive serology
[3,4].
Additional evaluation and management of infants with possible congenital syphilis are
discussed separately. (See "Congenital syphilis: Evaluation, management, and prevention",
section on 'Possible congenital syphilis'.)
Congenital syphilis less likely — Infection is less likely if a neonate has a normal physical
examination, serum VDRL or RPR titers are <fourfold the maternal titer, mother received
appropriate treatment >4 weeks before delivery, and mother has no evidence of reinfection or
relapse. However, these neonates are at risk and should receive treatment with a single dose of
intramuscular penicillin G benzathine [51,52,73]. No additional evaluation is needed [51].
6/19/22, 10:55 PM 14428
Management of infants in whom congenital syphilis is less likely is discussed separately. (See
"Congenital syphilis: Evaluation, management, and prevention", section on 'Congenital syphilis
less likely'.)
Congenital syphilis unlikely — A diagnosis of congenital syphilis is unlikely if the neonate has
a normal physical examination, serum VDRL or RPR titers are <fourfold the maternal titer,
mother was adequately treated before pregnancy, and mother's titers remained low (VDRL <1:2;
RPR <1:4) and stable before and during pregnancy and at delivery [51]. These infants generally
do not require any additional evaluation or treatment. (See "Congenital syphilis: Evaluation,
management, and prevention", section on 'Congenital syphilis unlikely'.)
Congenital neurosyphilis — A lumbar puncture to evaluate central nervous system (CNS)

syphilis should be performed in infants <1 month with proven or highly probable congenital
syphilis; infants <1 month of age whose mothers were not adequately treated (possible
congenital syphilis); and in infants and children who were identified as having reactive serologic
tests for syphilis at older than one month of age ( algorithm 1 and table 6) [51,52]. (See
"Congenital syphilis: Evaluation, management, and prevention", section on 'Subsequent
evaluation and management'.)
The diagnosis of congenital neurosyphilis can be difficult to establish. Given the lack of a widely
available laboratory test with high sensitivity and specificity for CNS syphilis and the potential
consequences of untreated CNS syphilis, the diagnosis of CNS syphilis usually is presumed in
children with clinical, radiographic, and laboratory abnormalities compatible with congenital
syphilis. Children with presumed congenital neurosyphilis should be treated with 10 days of
parenteral penicillin [40]. (See 'Central nervous system syphilis' above and "Congenital syphilis:
Evaluation, management, and prevention", section on 'Penicillin therapy'.)
Congenital versus acquired syphilis — In children who are found to have reactive serologic
tests for syphilis when they are older than one month of age, the distinction between
congenital and acquired syphilis can be difficult [1]. The ultimate diagnosis may rest upon
maternal history and clinical judgment [1]. Radiographic abnormalities of the long bones are
more suggestive of congenital than acquired syphilis. (See 'Radiographic abnormalities' above.)
The possibility of sexual abuse must be considered in children who are determined to have
acquired syphilis. (See "Evaluation of sexual abuse in children and adolescents", section on
'Sexually transmitted infections'.)
REPORTING REQUIREMENTS
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In the United States, congenital syphilis is a national notifiable disease [74]. However, reporting
requirements vary by state. Reporting to the Centers for Disease Control and Prevention by the
states is voluntary. For reporting purposes, congenital syphilis includes stillbirths due to
syphilis, cases of congenital syphilis detected in newborns, and cases of congenitally acquired
syphilis in infants and children [1].
INFORMATION FOR PATIENTS
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the
Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade
reading level, and they answer the four or five key questions a patient might have about a given
condition. These articles are best for patients who want a general overview and who prefer
short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more
sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading
level and are best for patients who want in-depth information and are comfortable with some
medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print
or email these topics to your patients. (You can also locate patient education articles on a
variety of subjects by searching on "patient education" and the keyword[s] of interest.)
● Basics topic (see "Patient education: Congenital syphilis (The Basics)")
SUMMARY AND RECOMMENDATIONS
● Congenital syphilis is acquired through transplacental transmission of spirochetes.

Women with untreated primary or secondary syphilis are more likely to transmit syphilis
to their fetuses than women with latent disease. Treponema pallidum is not transferred in
breast milk. In the United States, the reported cases of congenital syphilis have increased
dramatically since 2012 ( figure 1). (See 'Transmission' above and 'Epidemiology' above.)
● Early congenital syphilis is arbitrarily defined by clinical manifestations with onset before
two years of age. Manifestations of early clinical syphilis are varied and unpredictable (
table 4). (See 'Early congenital syphilis' above.)
● Late congenital syphilis is arbitrarily defined by clinical manifestations with onset after two
years of age. Manifestations of late congenital syphilis are related to scarring or persistent
inflammation from early infection ( table 5). (See 'Late congenital syphilis' above.)
6/19/22, 10:55 PM 14428
● The differential diagnosis of congenital syphilis in neonates includes other congenital

infections (toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, neonatal sepsis)
and other causes of neonatal hepatitis, hydrops fetalis, long-bone abnormalities, and
cutaneous lesions. Historical features, additional clinical findings, and/or laboratory
testing usually differentiate these conditions from congenital syphilis. (See 'Differential
diagnosis' above.)
● The Centers for Disease Control and Prevention (CDC) and the American Academy of
Pediatrics (AAP) Committee on Infectious Diseases provide guidelines for the evaluation
and management of congenital syphilis ( algorithm 1 and table 6). (See 'Approach to
diagnosis' above.)
● The diagnosis of congenital syphilis should be suspected in all infants born to women who
have reactive nontreponemal and treponemal tests for syphilis and infants/children with
clinical findings compatible with congenital syphilis ( table 4 and table 5). (See
'Clinical suspicion' above.)
● The initial evaluation for congenital syphilis in infants and children should include a
quantitative Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR)
titer (for infants <1 month of age, the test should be the same as that which was
performed on the mother); physical examination for evidence of congenital syphilis;
darkfield microscopic examination or direct fluorescent antibody staining of suspicious
lesions or body fluids (eg, nasal discharge); and, for newborns, pathologic examination of
the placenta and umbilical cord with specific fluorescent antitreponemal antibody staining
(if possible). (See 'Initial evaluation' above.)
● The diagnosis of syphilis may be established by direct visualization of T. pallidum in clinical

specimens ( picture 11 and picture 12) or serologic reactions typical of syphilis. To
prevent long-term morbidity, it is also important to identify (and treat) infants at risk for
clinical syphilis. (See 'Interpretation' above.)
Use of UpToDate is subject to the Terms of Use.
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2, 2011).
Topic 14428 Version 34.0
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GRAPHICS
United States Centers for Disease Control and Prevention surveillance case
definition for congenital syphilis
Laboratory criteria for diagnosis

Demonstration of Treponema pallidum by any of the following:
Darkfield microscopy of lesions, body fluids, or neonatal nasal discharge, or
PCR or other equivalent direct molecular methods of lesions, neonatal nasal discharge,
umbilical cord, or autopsy material, or
Immunohistochemistry or special staining (eg, silver staining) of lesions, neonatal nasal
discharge, umbilical cord, or autopsy material
Case classification
Probable
An infant whose mother had untreated or inadequately treated* syphilis at delivery, regardless of
signs in the infant, or
An infant or child who has a reactive non-treponemal test for syphilis (VDRL, RPR, or equivalent
methods) and any of the following:
Evidence of congenital syphilis on physical examination¶
Evidence of congenital syphilis on radiographs of long bones
Reactive CSF VDRL
Elevated CSF WBC count or CSF protein (in a nontraumatic LP and without any other cause)Δ
Confirmed
Any case that is laboratory confirmed according to the laboratory criteria above
PCR: polymerase chain reaction; VDRL: venereal disease research laboratory; RPR: rapid plasma
reagin; CSF: cerebrospinal fluid; WBC: white blood cell; LP: lumbar puncture; CDC: United States
Centers for Disease Control and Prevention.
* Adequate treatment is defined as completion of a penicillin-based regimen, in accordance with

CDC treatment guidelines, appropriate for stage of infection and initiated 30 or more days before
delivery.
¶ Physical examination findings of congenital syphilis in an infant or child <2 years old may include
hepatosplenomegaly, rash, condyloma lata, snuffles, jaundice (nonviral hepatitis), pseudoparalysis,
pallor (anemia), or edema (nephrotic syndrome and/or malnutrition). Findings in older children may
include interstitial keratitis, hearing loss, anterior bowing of shins, frontal bossing, mulberry molars,
Hutchinson teeth, saddle nose, rhagades, or Clutton joints. Refer to UpToDate topic on congenital
syphilis for additional details.
Δ Suggested parameters for abnormal CSF WBC and protein values:
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During the first 30 days after birth – CSF WBC count >15 WBC/mm3 or CSF protein >120
mg/dL is abnormal
For infants and children >30 days old – CSF WBC count >5 WBC/mm3 or CSF protein >40
mg/dL is abnormal
Adapted from: Centers for Disease Control and Prevention. Syphilis (Treponema pallidum) 2018 Case Definition.
https://ndc.services.cdc.gov/case-definitions/syphilis-2018/ (Accessed on June 17, 2021).
Graphic 60607 Version 9.0
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Inadequate or suboptimal treatment of maternal syphilis
Inadequate therapy
Treatment with a nonpenicillin antibiotic
Treatment less than four weeks before delivery (including treatment with penicillin)
Inappropriate dose for stage of disease
Inadequate documentation of maternal treatment

Lack of performance of serial non-treponemal* antibody titers after maternal treatment
Maternal therapy was not documented
Inadequate response to therapy
Maternal non-treponemal antibody titers did not decline at least fourfold (two dilutions) after
treatment
Maternal non-treponemal antibody titers suggest reinfection or relapse (ie, fourfold increase)
* Non-treponemal test: Rapid plasma reagin (RPR) test or Venereal Disease Research Laboratory
(VDRL) test.
References:
1. Centers for Disease Control and Prevention. Syphilis (Treponema pallidum) 2018 Case Definition.
https://ndc.services.cdc.gov/case-definitions/syphilis-2018/ (Accessed on June 17, 2021).
2. American Academy of Pediatrics. Syphilis. In: Red Book: 2021-2024 Report of the Committee on Infectious Diseases,
32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), American Academy of Pediatrics, Itasca, IL 2021.
p.729.
3. Workowski KA, Bolan GA. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
6/19/22, 10:55 PM 14428
Congenital syphilis: Reported cases among infants by year of birth and rates
of primary and secondary syphilis among women, United States, 2009 to
2018
CS: congenital syphilis; P&S: primary and secondary syphilis.
Reproduced from: Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2018: Syphilis.
Available at: https://www.cdc.gov/std/stats18/Syphilis.htm (Accessed on March 25, 2021).
6/19/22, 10:55 PM 14428
Prevalence of infectious diseases in newly arrived internationally adopted

children
Country or region
Condition
Russia China Guatemala Korea Africa
Hepatitis A
- Acute <1 percent 0 percent 0 percent 0 percent 2 percent
- Past 18 percent 9 percent 32 percent 0 percent 68 percent
Hepatitis B
- Chronic <1 percent 2 percent 0 percent 0 percent 3 percent
- Past recovered 2 percent 6 percent 2 percent 6 percent 9 percent
Hepatitis C <1 percent 0 percent 0 percent 0 percent 0 percent
Syphilis <1 percent <1 percent <1 percent 0 percent 5 percent
HIV 0 percent 0 percent 0 percent 0 percent 2 percent
Latent tuberculosis 22 percent 18 percent 32 percent 6 percent 27 percent
Intestinal parasites 44 percent 14 percent 10 percent 0 percent 49 percent

(pathogen)
- Giardia intestinalis 30 percent 11 percent 6 percent 0 percent 32 percent
- Helminths <1 percent <1 percent <1 percent <1 percent 15 percent
HIV: human immunodeficiency virus.
Data from:
1. Abdulla RY, Rice MA, Donauer S, et al. Hepatitis A in internationally adopted children: Screening for acute and
previous infection. Pediatrics 2010; 126:e1039.
2. Stadler LP, Mezoff AG, Staat MA. Hepatitis B virus screening for internationally adopted children. Pediatrics 2008;
122:1223.
3. Trehan I, Meinzen-Derr JK, Jamison L, Staat MA. Tuberculosis screening in internationally adopted children: the need
for initial and repeat testing. Pediatrics 2008; 122:e7.
4. Staat MA, Rice M, Donauer S, et al. Intestinal parasite screening in internationally adopted children: Importance of
testing multiple stool specimens. Pediatrics 2011; 128:e613.
5. Staat MA, Rice M, Leach K, Rawlings A. Medical Conditions in Internationally Adopted Children from Africa [abstract].
Pediatric Academy Societies Annual Meeting: Boston Massachusetts, 2012.
6/19/22, 10:55 PM 14428
Clinical manifestations of early congenital syphilis*
Gestational/perinatal
Stillbirth
Prematurity
Birth weight <2500 g
Nonimmune hydrops fetalis
Placenta Large, thick, pale (send for pathologic/histologic

evaluation)
Umbilical cord Inflamed with abscess-like foci of necrosis within Wharton's

jelly, centered around the umbilical vessels (necrotizing
funisitis); barber-pole appearance (send for
pathologic/histologic evaluation)
Systemic
Fever May be more prominent in infants born to mothers who

are affected late in pregnancy and whose serology is
negative at delivery
Hepatomegaly Splenomegaly occurs in approximately one-half of patients

with hepatomegaly—isolated splenomegaly does not occur
Generalized lymphadenopathy May be as large as 1 cm; generally nontender and firm
Failure to thrive
Edema Due to anemia/hydrops fetalis, nephrotic syndrome,

malnutrition
Mucocutaneous
Syphilitic rhinitis ("snuffles") Can be an early feature, developing after the first week of
life; contains spirochetes and is infectious (use contact
precautions)
Maculopapular rash Usually appears one to two weeks after rhinitis. Oval
lesions, initially red or pink and then coppery brown; may
be associated with superficial desquamation or scaling,
particularly on the palms or soles; more common on the
buttocks, back, posterior thighs, and soles; contains
spirochetes and is infectious (use contact precautions).
Vesicular rash (pemphigus May be present at birth, most often develops in first four
syphiliticus) weeks; widely disseminated; vesicular fluid contains
spirochetes and is infectious (use contact precautions)
Condylomata lata Single or multiple, flat, wartlike, moist lesions around the
6/19/22, 10:55 PM 14428
mouth, nares, and anus and other areas of the skin where
there is moisture or friction; lesions contain spirochetes
and are infectious (use contact precautions); frequently
present without other signs of infection
Jaundice Hyperbilirubinemia secondary to syphilitic hepatitis and/or

hemolysis
Hematologic
Anemia Newborn period: Hemolytic (Coomb's test [direct

antiglobulin test] negative); may persist after effective
treatment
After one month of age: May be chronic and nonhemolytic
Thrombocytopenia May be associated with bleeding or petechiae; can be the

only manifestation of congenital infection
Leukopenia
Leukocytosis
Musculoskeletal
Pseudoparalysis of Parrot Lack of movement of an extremity because of pain
associated with bone lesion; affects upper extremities
more often than lower; usually unilateral; rarely present at
birth; poorly correlated with radiographic abnormalities
Radiographic abnormalities: Most frequent abnormality in untreated early congenital

syphilis; not usually clinically discernible; typically multiple
and symmetric
Periostitis Irregular periosteal thickening; usually present at birth,

but may appear in the first few weeks of life
Wegner sign Metaphyseal serration or "sawtooth metaphysis"
Wimberger sign Demineralization and osseous destruction of the upper

medial tibial
Neurologic
CSF abnormalities Reactive CSF VDRL; elevated CSF white blood cell count;
elevated CSF protein
Acute syphilitic leptomeningitis Onset during the first year of life, usually between 3 and 6
months; presentation similar to bacterial meningitis but
CSF findings more consistent with aseptic meningitis
(mononuclear predominance); responds to penicillin
therapy
Chronic meningovascular syphilis Onset toward the end of the first year; hydrocephalus;
cranial nerve palsies; intellectual/neurodevelopmental
6/19/22, 10:55 PM 14428
deterioration; cerebral infarction; protracted course
Miscellaneous
Pneumonia/pneumonitis/respiratory Complete opacification of both lung fields on chest
distress radiograph
Nephrotic syndrome Usually occurs at two to three months of age and

manifests with generalized edema and ascites
CSF: cerebrospinal fluid; VDRL: Venereal Disease Research Laboratory test.
* All of these findings may occur in other congenital infections; none is specific for congenital
syphilis.
Data from:
1. Ingall D, Sanchez PJ, Baker CH. Syphilis. In: Infectious Diseases of the Fetus and Newborn infant, 6th edition,
Remington JS, Klein JO, Wilson CB, Baker CJ (Eds), Elsevier Saunders, Philadelphia 2006. p.545.
2. Dobson SR, Sanchez PJ. Syphilis. In: Feigin and Cherry's Textbook of Pediatric Infectious Diseases, 7th, Cherry JD,
Harrison GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.1761.
3. Woods CR. Syphilis in children: congenital and acquired. Semin Pediatr Infect Dis 2005; 16:245.
4. Saloojee H, Velaphi S, Goga Y, et al. The prevention and management of congenital syphilis: an overview and
recommendations. Bull World Health Organ 2004; 82:424.
5. Chakraborty R, Luck S. Syphilis is on the increase: the implications for child health. Arch Dis Child 2008; 93:105.
6. Rawstron SA. Treponema pallidum (Syphilis). In: Principles and Practice of Pediatric Infectious Diseases, 3rd edition,
Long SS, Pickering LK, Prober CG (Eds), Churchill Livingstone Elsevier, Philadelphia 2008. p.930.
6/19/22, 10:55 PM 14428
Congenital syphilis: Snuffles
Reproduced from: the Public Health Image Library, Centers for Disease Control and
Prevention. Photo by Dr. Norman Cole.
6/19/22, 10:55 PM 14428
Congenital syphilis: Rash on soles
Pigmented lesions on the soles of an infant with congenital syphilis.
Reproduced with permission from: Fleisher GR, Ludwig W, Baskin MN. Atlas of
Pediatric Emergency Medicine. Lippincott Williams & Wilkins, Philadelphia 2004.
Copyright © 2004 Lippincott Williams & Wilkins.
6/19/22, 10:55 PM 14428
Congenital syphilis: Transverse metaphyseal bands

and diaphyseal destruction
Transverse bands of increased density across the metaphyses (small

arrows) associated with patchy areas of bone destruction in the
diaphyses. There is solid periosteal new bone formation (large
arrow), which is best seen about the distal humerus.
Reproduced with permission from: Eisenberg RL. An Atlas of Differential Diagnosis,

4th ed. Lippincott Williams & Wilkins, Philadelphia 2003. Copyright © 2003
Lippincott Williams & Wilkins.
6/19/22, 10:55 PM 14428
Congenital syphilis: Periostitis
Solid periosteal reaction (arrows) in a patient with congenital

syphilis.
Reproduced with permission from: Daffner RH. Clinical Radiology: The Essentials, 3rd
Edition. Lippincott Williams & Wilkins, Philadelphia 2007. Copyright © 2007
Lippincott Williams & Wilkins.
6/19/22, 10:55 PM 14428
Congenital syphilis: Osteitis
Note the extensive destruction, with metaphyseal (arrows) and

diaphyseal radiolucencies throughout the humerus, radius, and
ulna. Observe the exuberant periosteal overgrowth, with expansile
deformity of the bones of the upper extremity. Syphilitic granulation
tissue may extend from the metaphysis to the diaphysis, creating an
extension of the infectious focus. Reactive sclerosis often surrounds
the osteolytic lesions, with associated periostitis of the long tubular
bones.
Reproduced with permission from: Yochum TR, Rowe LJ. Yochum And Rowe's
Essentials of Skeletal Radiology, 3rd ed. Lippincott Williams & Wilkins, Philadelphia
2004. Copyright © 2004 Lippincott Williams & Wilkins.
6/19/22, 10:55 PM 14428
Congenital syphilis: Sclerosis
Diffuse sclerosis with transverse bands of lucency (arrows) in the diaphyses

of the femurs and tibias.
Reproduced with permission from: Eisenberg RL. An Atlas of Differential Diagnosis, 4th ed.
Lippincott Williams & Wilkins, Philadelphia 2003. Copyright © 2003 Lippincott Williams &
Wilkins.
6/19/22, 10:55 PM 14428
Stigmata of late congenital syphilis
Facial features Frontal bossing, saddle nose, short maxilla, protuberant mandible
Ophthalmologic Interstitial keratitis, chorioretinitis, secondary glaucoma, corneal scarring, optic

atrophy
Ears Sensorineural hearing loss
Oropharynx Hutchinson teeth, mulberry molars, perforation of hard palate
Cutaneous Rhagades, gummas
Central nervous Intellectual disability, arrested hydrocephalus, seizures, optic atrophy, juvenile
system general paresis
Skeletal Saber shins (anterior bowing of the tibia), Higoumenakis sign (enlargement of the
sternoclavicular portion of the clavicle), Clutton joints (painless arthritis), scaphoid
scapula
Data from:
1. Ingall D, Sanchez PJ, Baker CH. Syphilis. In: Infectious Diseases of the Fetus and Newborn infant, 6th edition,
Remington JS, Klein JO, Wilson CB, Baker CJ (Eds), Elsevier Saunders, Philadelphia 2006. p.545.
2. Dobson SR, Sanchez PJ. Syphilis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 7th, Cherry JD,
Harrison GJ, Kaplan SL, et al. (Eds), Elsevier Saunders, Philadelphia 2014. p.1761.
3. Woods CR. Syphilis in children: congenital and acquired. Semin Pediatr Infect Dis 2005; 16:245.
4. Chakraborty R, Luck S. Syphilis is on the increase: the implications for child health. Arch Dis Child 2008; 93:105.
6/19/22, 10:55 PM 14428
Congenital syphilis: Facial stigmata
Facial stigmata of congenital syphilis depicted above include bulging

of the frontal bones and depression of the nasal bridge ("saddle
nose"), both due to periostitis; rhinitis from weeping nasal mucosal
lesions ("snuffles"); and a circumoral rash.
Reproduced with permission from: Bickley LS, Szilagyi P. Bates' Guide to Physical
Examination and History Taking, 8th ed, Lippincott Williams & Wilkins, Philadelphia
2003. Copyright © 2003 Lippincott Williams & Wilkins.
6/19/22, 10:55 PM 14428
Congenital syphilis: Interstitial keratitis
This photograph shows a stromal haze in both eyes of this child due
to interstitial keratitis, a manifestation of late congenital syphilis.
Interstitial keratitis is an inflammation of the connective tissue
structure of the cornea. It usually is bilateral.
Prevention. Photo by Susan Lindsley.
6/19/22, 10:55 PM 14428
Congenital syphilis: Hutchinson teeth
Hutchinson teeth are smaller and more widely spaced than normal
and are notched on their biting surfaces. The sides of the teeth
taper toward the biting edges. The upper central incisors of the
permanent (not the deciduous) teeth are most often affected.
Reproduced with permission from: Robinson HBG, Miller AS. Colby, Kerr, and
Robinson's Color Atlas of Oral Pathology. JB Lippincott, Philadelphia 1990. Copyright
© 1990 Lippincott Williams & Wilkins.
6/19/22, 10:55 PM 14428
Congenital syphilis: Mulberry molar
Reproduced with permission from: Sweet RL, Gibbs RS. Atlas of Infectious Diseases of
the Female Genital Tract. Lippincott Williams & Wilkins, Philadelphia 2005. Copyright
6/19/22, 10:55 PM 14428
Congenital syphilis: Perforated hard palate
This patient with congenital syphilis has developed a perforation of

hard palate due to gummatous destruction. These destructive
tumors can also attack the skin, long bones, eyes, mucous
membranes, throat, liver, or stomach lining.
6/19/22, 10:55 PM 14428
Congenital syphilis: Rhagades
This photograph demonstrates rhagades, which are cracks or

fissures in the skin around the mouth, in a patient with late
congenital syphilis.
6/19/22, 10:55 PM 14428
Congenital syphilis: Saber shins
Reproduced with permission from: Sweet RL, Gibbs RS. Atlas of Infectious Diseases of
the Female Genital Tract. Lippincott Williams & Wilkins, Philadelphia 2005. Copyright
6/19/22, 10:55 PM 14428
Congenital syphilis: Clutton joints
This patient with congenital syphilis shows "Clutton joints," or

symmetrical hydrarthrosis of the knee joint. This is a painless
condition that often occurs during the late stages of congenital
syphilis.
6/19/22, 10:55 PM 14428
Treponema pallidum spirochetes depicted with

darkfield microscopy
Using a darkfield microscopy technique, this photomicrograph

revealed the presence of Treponema pallidum spirochetes, which are
the bacterial agents that cause syphilis.
Courtesy of the Centers for Disease Control and Prevention/Schwartz WF.
6/19/22, 10:55 PM 14428
Congenital syphilis: Treponema pallidum, silver

stain
Spirochetes of Treponema pallidum, visualized by silver

impregnation, in the eye of a child with congenital syphilis.
Reproduced with permission from: Rubin E, Farber JL. Pathology, 3rd ed. Lippincott
Williams & Wilkins, Philadelphia 1999. Copyright © 1999 Lippincott Williams &
Wilkins.
6/19/22, 10:55 PM 14428
Congenital syphilis: Evaluation and management
RPR: rapid plasma reagin; VDRL: Venereal Disease Research Laboratory; TP-PA: Treponema pallidum particle a
antibody absorption; TP-EIA: T. pallidum enzyme immunoassay; MHA-TP: microhemagglutination test for ant
* This algorithm does not apply if maternal samples are screened in reverse order (ie, treponemal test is pe
of interpretation of reverse sequence testing, please refer to the UpToDate topic on diagnosis of syphilis.
¶ TP-PA, FTA-ABS, TP-EIA, or MHA-TP.
Δ Test for HIV antibody. Infants of HIV-infected mothers do not require different evaluation or treatment.
◊ A fourfold change in titer is the same as a change of 2 dilutions. For example, a titer of 1:64 is fourfold gre
fourfold lower than a titer of 1:16.
§ Women who maintain a VDRL titer 1:2 or less or an RPR 1:4 or less beyond 1 year after successful treatmen
6/19/22, 10:55 PM 14428
¥ Complete blood cell and platelet count; CSF examination for cell count, protein, and quantitative VDRL; oth
radiographs, long-bone radiographs, eye examination, liver function tests, neuroimaging, and auditory brai
‡ Some experts would consider a single intramuscular injection of benzathine penicillin (treatment option 2)
† Treatment (option 1 or option 2, above) with many experts recommending treatment option 1. If a single d
infant must be fully evaluated, full evaluation must be normal, and follow-up must be certain. If any part of t
performed, or if the CSF analysis is rendered uninterpretable, then a 10-day course of penicillin is required.
From: American Academy of Pediatrics. Syphilis. In: Red Book: 2012 Report of the Committee on Infectious Diseases, 29th ed, Pickering
Village, IL 2012. Copyright © 2012 American Academy of Pediatrics. Used with permission. The contents of this figure remain unchang
Infectious Diseases, 31st ed.
6/19/22, 10:55 PM 14428
Evaluation and management of neonates (<1 month) born to women with

syphilis or history of syphilis*
Initial neonatal
Maternal treatment Subsequent
evaluation Treatment
neonatal
of neonate
Neonate Neonate evaluation
Timing Type
VDRL/RPR evaluation
Any result Examination Any Any or none CSF VDRL, 10 days of

compatible cell count, parenteral
with protein penicillin◊
congenital CBC with
syphilis or differential
visualization and platelet
of spirochete count
in clinical Additional
specimen¶ tests as
clinically
indicatedΔ
≥ Fourfold Any Any Any CSF VDRL, 10 days of

maternal cell count, parenteral
titer protein penicillin◊
CBC with
differential
and platelet
count
Additional
tests as
clinically
indicatedΔ
< Fourfold Normal During None, CSF VDRL, If the entire

maternal titer physical pregnancy inadequate, cell count, evaluation is
examination suboptimal‡ protein performed
CBC with and normal† :
differential Single dose
and platelet IM benzathine
count penicillin¥ ;
some experts
Additional
would treat
tests as
with 10 days
clinically
of parenteral
indicatedΔ
penicillin◊
6/19/22, 10:55 PM 14428
If any portion
of the
evaluation is
abnormal, not
performed, or
not
interpretable:
10 days of
parenteral
penicillin◊
< Fourfold Normal Before Evidence of CSF VDRL, If the entire

maternal titer physical pregnancy reinfection or cell count, evaluation is
examination relapse (≥ protein performed
fourfold CBC with and normal:
increase in differential Single dose
post- and platelet IM benzathine
treatment count penicillin¥
titer) Additional If any portion
tests as of the
clinically evaluation is
indicatedΔ abnormal, not
performed, or
not
interpretable:
10 days of
parenteral
penicillin◊
< Fourfold Normal During Adequate§ None Single dose

maternal titer physical pregnancy IM benzathine
examination penicillin¥ ;
some experts
would not
treat but
provide close
serologic
follow-up
< Fourfold Normal Before Adequate§ None None; some

maternal titer physical pregnancy experts would
examination treat with a
single dose of
IM benzathine
penicillin¥
Nonreactive Normal During None, None Single dose

physical pregnancy inadequate, IM benzathine
6/19/22, 10:55 PM 14428
examination suboptimal‡ penicillin¥
Nonreactive Normal During Adequate§ None None; some

physical pregnancy experts would
examination treat with a
single dose of
IM benzathine
penicillin¥
Neonate characteristics in bold text indicate proven or highly probable congenital syphilis disease in
the infant.
VDRL: Venereal Disease Research Laboratory serologic test for syphilis; RPR: rapid plasma reagin
serologic test for syphilis; CSF: cerebrospinal fluid; CBC: complete blood count; IM: intramuscular; IV:
intravenous.
* Mother with reactive nontreponemal (VDRL or RPR) and treponemal (microhemagglutination test
for T. pallidum [MHA-TP] or fluorescent treponemal antibody absorption [FTA-ABS]) serologic tests
for syphilis. All such infants require clinical and serologic follow-up (see text for details).
¶ Examination findings compatible with early congenital syphilis may include (but are not limited to)
hepatomegaly/hepatosplenomegaly; rash; condyloma lata; snuffles; jaundice; pseudoparalysis;
anemia; and edema.
Δ Additional tests may include: Long-bone radiographs, chest radiograph, liver function tests, cranial
ultrasonography, ophthalmologic examination, and auditory brainstem response.
◊ There are two alternate regimens: Aqueous penicillin G (50,000 units/kg IV every 12 hours [for
infants ≤7 days of age] and every 8 hours [>7 days of age] for a total of 10 days); or procaine
penicillin G 50,000 units/kg IM as a single daily dose for 10 days.
§ Adequate therapy encompasses treatment with penicillin more than four weeks before delivery;
appropriate dose for the stage of disease; documentation of treatment response (fourfold decline in
titer for early syphilis and titer remained stable or low [VDRL ≤1:2; RPR ≤1:4] for late syphilis); no
evidence of reinfection or relapse (fourfold increase in titer after treatment).
¥ Benzathine penicillin G (50,000 units/kg intramuscularly as a single dose).
‡ Inadequate or suboptimal maternal therapy encompasses: Treatment with a nonpenicillin

antibiotic; treatment less than four weeks before delivery; inappropriate dose for the stage of
disease; no documentation of maternal therapy; maternal titers did not decline at least fourfold
after treatment for early syphilis or did not remain stable and low [VDRL ≤1:2; RPR ≤1:4] for late
syphilis; or maternal titers increased by fourfold after treatment (suggesting reinfection or relapse).
† Normal CSF is generally defined by nonreactive VDRL, CSF WBC <25 cells/microL, and CSF protein
<150 mg/dL for term infants and <170 mg/dL for preterm infants; however, some experts define
normal CSF WBC as <5 cells/microL and normal CSF protein as <40 mg/dL.
References:
1. Workowski KA, Bolan GA. Sexually Transmitted Diseases Treatment Guidelines, 2015. MMWR Recomm Rep 2015; 64:1.
6/19/22, 10:55 PM 14428
2. American Academy of Pediatrics. Syphilis. In: Red Book: 2018 Report of the Committee on Infectious Diseases, 31st ed,
Kimberlin DW, Brady MT, Jackson MA, Long SS (Eds), American Academy of Pediatrics, Itasca, IL 2018. p.773.
3. Dobson SR, Sanchez PJ. Syphilis. In: Feigin and Cherry’s Textbook of Pediatric Infectious Diseases, 8th ed, Cherry JD,
Harrison GJ, Kaplan SL, et al (Eds), Elsevier Saunders, Philadelphia 2019. p.1268.
4. Kollmann TR, Dobson SD. Syphilis. In: Infectious Diseases of the Fetus and Newborn infant, 7th edition, Remington JS,
Klein JO, Wilson CB, et al (Eds), Elsevier Saunders, Philadelphia 2011. p.524.
6/19/22, 10:55 PM 14428
Contributor Disclosures
Simon R Dobson, MD, FRCP(C) No relevant financial relationship(s) with ineligible companies to
disclose. Sheldon L Kaplan, MD Grant/Research/Clinical Trial Support: MeMed Diagnostics [Bacterial and
viral infections];Merck [Staphylococcus aureus];Pfizer [Streptococcus pneumoniae]. Consultant/Advisory
Boards: MeMed Advisory Board [Diagnostics bacterial and viral infections]. Other Financial Interest:
Elsevier [Pediatric infectious diseases];Pfizer [PCV13]. All of the relevant financial relationships listed have
been mitigated. Leonard E Weisman, MD Equity Ownership/Stock Options: Vax-Immune [Ureaplasma
diagnosis, vaccines, antibodies, other medical diagnostics and pre-analytical devices]. Patent Holder:
Baylor College of Medicine [Ureaplasma diagnosis, vaccines, antibodies, process for preparing biological
samples]. All of the relevant financial relationships listed have been mitigated. Carrie Armsby, MD,
MPH No relevant financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
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Features and Diagnosis Sifilis

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Congenital syphilis: Clinical features and diagnosis

Syphilis in pregnancy and acquired syphilis also are discussed separately:

● (See "Syphilis in pregnancy".)

● The child has physical, laboratory, or radiographic signs of congenital syphilis

EARLY CONGENITAL SYPHILIS

Approximately 60 to 90 percent of live-born neonates with congenital syphilis are asymptomatic

Manifestations of early clinical syphilis are varied and unpredictable ( table 4)

● Hepatomegaly – Hepatomegaly occurs in almost all infants with congenital syphilis

Other characteristic, but uncommon, cutaneous lesions of congenital syphilis include

● Generalized lymphadenopathy – Generalized, nontender lymphadenopathy is a

● Other manifestations – Other manifestations of congenital syphilis may include

• Nonimmune fetal hydrops

Long-bone radiographs — Abnormal long-bone radiographs are a common manifestation of

● Metaphyseal serration ("sawtooth metaphysis").

● Irregular areas of increased density and rarefaction ("moth-eaten" appearance) (

Hematologic studies — Hematologic abnormalities of early congenital syphilis may include

Hemolysis is often accompanied by cryoglobulinemia, immune complex formation, and

Cerebrospinal fluid abnormalities — Laboratory evidence of CNS involvement may include

● Reactive CSF VDRL.

● Reactive CSF VDRL – Sensitivity 54 percent, specificity 90 percent

LATE CONGENITAL SYPHILIS

Manifestations of late congenital syphilis include ( table 5) [1,23,57,59,60]:

● Oropharynx – Hutchinson teeth (hypoplastic, notched, widely spaced permanent teeth

● Neurologic – Intellectual disability, arrested hydrocephalus, cranial nerve palsies

● Hematologic – Paroxysmal cold hemoglobinuria. (See "Paroxysmal cold hemoglobinuria".)

● Toxoplasmosis infection (see "Toxoplasmosis and pregnancy", section on 'Fetal infection'

● Rubella virus infection (see "Congenital rubella", section on 'Evaluation')

● Cytomegalovirus infection (see "Congenital cytomegalovirus infection: Clinical features

● Neonatal hepatitis (see "Causes of cholestasis in neonates and young infants")

● Long-bone abnormalities (eg, osteomyelitis, rickets, physical abuse) or failure to move an

The diagnosis of syphilis is complicated by the absence of a method to culture T. pallidum on

● Direct visualization of T. pallidum by darkfield microscopy ( picture 11) or fluorescent

● Demonstration of the T. pallidum by special stains ( picture 12) or histopathologic

● Demonstration of serologic reactions typical of syphilis

● Animal inoculation (ie, rabbit infectivity test)

Serologic testing can establish a diagnosis of proven/highly probable, at-risk, or unlikely

● Unexplained prematurity (<37 weeks gestation)

● A quantitative nontreponemal test (rapid plasma reagin [RPR] or Venereal Disease

● Physical examination for evidence of congenital syphilis and darkfield microscopic

● Pathologic examination of the placenta or umbilical cord with specific fluorescent

Interpretation — To maximize treatment of children potentially infected with T. pallidum, the

Proven or highly probable congenital syphilis — Congenital syphilis is proven or highly

● An abnormal physical examination that is consistent with congenital syphilis

● A serum quantitative nontreponemal serologic titer that is ≥4-fold the corresponding

Congenital neurosyphilis — A lumbar puncture to evaluate central nervous system (CNS)

INFORMATION FOR PATIENTS

● Basics topic (see "Patient education: Congenital syphilis (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Congenital syphilis is acquired through transplacental transmission of spirochetes.

● The differential diagnosis of congenital syphilis in neonates includes other congenital

● The diagnosis of syphilis may be established by direct visualization of T. pallidum in clinical

Use of UpToDate is subject to the Terms of Use.

70. Lago EG. Current Perspectives on Prevention of Mother-to-Child Transmission of Syphilis.

Laboratory criteria for diagnosis

* Adequate treatment is defined as completion of a penicillin-based regimen, in accordance with

Δ Suggested parameters for abnormal CSF WBC and protein values:

Graphic 60607 Version 9.0

Inadequate or suboptimal treatment of maternal syphilis

Inappropriate dose for stage of disease

Inadequate documentation of maternal treatment