Act Feb 2023 Congenital Syphilis Clinical Manifestations, Evaluation

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Official reprint from UpToDate®

www.uptodate.com © 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved.
Congenital syphilis: Clinical manifestations, evaluation,

and diagnosis
Author: Antonio C Arrieta, MD, FIDSA, FPIDS
Section Editor: Sheldon L Kaplan, 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: Feb 2023. | This topic last updated: Feb 14, 2023.
INTRODUCTION
Congenital syphilis occurs when the spirochete Treponema pallidum is transmitted from a
pregnant individual to the 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, evaluation, and diagnosis of congenital syphilis will be discussed here. The
management and prevention of congenital syphilis, syphilis in pregnancy, and acquired syphilis
are discussed separately:
● (See "Congenital syphilis: Management and outcome".)

● (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".)
EPIDEMIOLOGY
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● Incidence – Congenital syphilis is a significant public health problem, complicating an

estimated one million pregnancies per year throughout the world [2,3]. The incidence of
congenital syphilis reflects the rate of syphilis in women of childbearing age [4]. (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 1) [5-7]. Among women with
untreated early syphilis, 40 percent of pregnancies result in spontaneous abortion [8]. (See
"Syphilis in pregnancy", section on 'Prevalence'.)
Rates of congenital syphilis in the United States have risen steadily since 2012 [9,10]. In
2020, there were a total of 2152 reported cases of congenital syphilis in the United States,
including 122 syphilitic stillbirths and 29 infant deaths [10,11]. The 2020 case rate (57
cases per 100,000 live births) represents the highest reported rate since 1991. As is
expected, the increase in rates of congenital syphilis parallels increases in primary and
secondary syphilis among women during this period ( figure 1) [9,10,12].
Syphilis in pregnancy is commonly associated with adverse pregnancy outcomes (fetal

loss, stillbirth, neonatal death, prematurity, and low birth weight), as discussed separately.
(See "Syphilis in pregnancy", section on 'Potential adverse pregnancy outcomes'.)
● Risk factors – 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 (CDC) in 2014, nearly one-quarter were born to mothers who did
not receive prenatal care [9]. 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.
Social vulnerabilities including homelessness, substance abuse, and incarceration were

found to be barriers to timely diagnosis and treatment of syphilis in pregnant women in a
review of congenital cases in Indiana [13].
The rate of congenital syphilis is increased among infants born to mothers with human
immunodeficiency virus (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 2). Given the
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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'.)
● Missed opportunities – The most common missed opportunity for prevention of

congenital syphilis is lack of adequate maternal treatment despite a timely diagnosis,
which accounts for approximately 30 to 40 percent of cases [9,10]. Other missed
opportunities include lack of prenatal care (20 to 30 percent of cases), failure to perform
timely syphilis testing (10 to 15 percent of cases), and late identification of seroconversion
during pregnancy (approximately 10 percent of cases) [10,11,14]. In studies conducted in
New York, Florida, and Louisiana, repeat early testing during the third trimester is an
effective intervention for preventing congenital syphilis [15,16].
TRANSMISSION
Humans are the only natural host of T. pallidum [17]. Congenital syphilis generally is acquired
through transplacental transmission during maternal spirochetemia 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
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. Clinical
manifestations are the result of inflammation in the affected organs. Bones, liver, pancreas,
intestine, kidney, and spleen are most frequently and severely involved. The severity of illness is
variable and can range from isolated laboratory or radiographic abnormalities to fulminant
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involvement of multiple organ systems. Overt infection can manifest in the fetus, the newborn,
or later in childhood (if the newborn/infant is not treated appropriately and timely) [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".)
CLINICAL MANIFESTATIONS
Early congenital syphilis — Early congenital syphilis is arbitrarily defined by clinical

manifestations with onset before two years of age [25].
Clinical findings — Clinical manifestations in untreated infants usually appear by three

months of age, most often by five weeks [25,26].
Approximately 60 to 90 percent of live-born neonates with congenital syphilis are asymptomatic

at birth [9,27]. The presence of signs at birth depends upon the timing of intrauterine infection
and treatment [17]. Among symptomatic infants, the most common findings include [9,28]:
● Hepatomegaly
● Jaundice
● Nasal discharge ("snuffles")
● Rash
● Generalized lymphadenopathy
● Skeletal abnormalities
Clinical manifestations of early syphilis are varied and unpredictable ( table 3)

[1,17,23,25,29,30]. 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 abscess-like foci of necrosis within Wharton
jelly, centered around the umbilical vessels (necrotizing funisitis) [31,32]. (See "Care of the
umbilicus and management of umbilical disorders", section on 'Funisitis'.)
● Hepatomegaly – Hepatomegaly occurs in almost all infants with congenital syphilis [7,23].
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 [33]. Hepatomegaly is
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associated with jaundice and cholestasis. Spirochetes can be seen on liver biopsy (if one is
performed). (See 'Laboratory abnormalities' below.)
● Rhinitis – Syphilitic rhinitis ("snuffles") ( picture 1) may herald the onset of congenital
syphilis. It usually develops during the first week after birth 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 typical of most childhood viral upper respiratory infections. The nasal
discharge contains spirochetes, is contagious, and can transmit infection by direct contact.
● 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, palms, 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.
Other characteristic, but uncommon, cutaneous lesions of congenital syphilis include

fissures, mucous patches, and condylomata lata ( picture 3A-B). 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 ( picture 3A-B). 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 early congenital syphilis may include

[1,7,17,23,25,29,30]:
• 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
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• Failure to move an extremity secondary to painful periostitis ("pseudoparalysis of

Parrot")
• Sepsis due to other bacteria (eg, Escherichia coli, group B streptococci, Yersinia species)
(see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm
neonates")
• 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 (CNS) findings – CNS syphilis in children with congenital
infection may be asymptomatic or symptomatic.
Asymptomatic CNS syphilis is indicated by abnormalities in the cerebrospinal fluid (CSF)

(see 'Laboratory 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 in the neonatal period [17]. Symptomatic CNS syphilis in infants has two
overlapping presentations:
• 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 consistent with aseptic meningitis
(predominance of mononuclear cells, modest increase in protein, normal glucose)
[17,23]. Congenital syphilis should be considered in febrile infants with unexplained
aseptic meningitis. Acute syphilitic leptomeningitis generally responds to parenteral
penicillin therapy. (See "Congenital syphilis: Management and outcome", section on
'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
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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
● Bony abnormalities – Bony abnormalities are a common manifestation of early

congenital syphilis (occurring in 60 to 80 percent of cases) 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 after birth. 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 1A).
• 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
including nonaccidental trauma) ( image 1B).
• Irregular areas of increased density and rarefaction ("moth-eaten" appearance)

( image 1C and image 1D).
● Pulmonary findings – 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
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● Hematologic studies – Hematologic abnormalities of early congenital syphilis may

include [7,50,51]:
• Anemia – In the newborn period, the characteristic finding is direct antiglobulin test
(DAT; also called Coombs) negative hemolytic anemia. Hemolysis is often accompanied
by cryoglobulinemia, immune complex formation, and macroglobulinemia [23]. It may
last for weeks. Chronic DAT-negative anemia may persist beyond the neonatal period
and may be accentuated by the onset of physiologic anemia of infancy.
• Thrombocytopenia.
• Leukopenia or leukocytosis.
● Abnormal liver function tests (LFT) – This may include elevated aspartate
aminotransferase, alanine aminotransferase, alkaline phosphatase, and direct bilirubin.
Delayed prothrombin time may be seen if liver synthetic function is impaired. LFT
abnormalities may be exacerbated by penicillin therapy before improving [52].
Transaminitis generally resolves slowly, even after adequate therapy.
● CSF abnormalities – Findings that indicate CNS involvement include [1,7,53,54]:
• Reactive CSF VDRL – A reactive CSF Venereal Disease Research Laboratory (VDRL) test
supports the diagnosis of CNS syphilis. However, false positives can occur from
maternal nontreponemal antibodies crossing the placenta and diffusing into the fetal
CSF or through contamination of the CSF with blood from a traumatic lumbar puncture.
False negatives can also occur.
• CSF pleocytosis – The CSF white blood cell (WBC) count can be difficult to interpret
since normal values in newborns vary by gestational and postnatal age. Some experts
define CSF pleocytosis as >5 WBCs/microL [1,42]; others accept values as high as 20
WBCs/microL to be normal [55]. We generally consider a CSF WBC >15/microL in a term
newborn to be abnormal; a higher threshold is used in preterm neonates. After the age
of one month, CSF pleocytosis is defined as WBC >5 microL.
• Elevated CSF protein – As with WBCs, the definition of elevated CSF protein in
newborns is variably defined, ranging from >45 mg/dL to as high as 150 mg/dL (or 170
mg/dL in premature infants). After the age of one month, elevated CSF protein is
defined as ≥45 mg/dL.
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
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spirochetes in the CSF, the sensitivity and specificity of these findings 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
Examination of the CSF for T. pallidum deoxyribonucleic acid (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 'Other tests' below.)
Late congenital syphilis — Late congenital syphilis is arbitrarily defined by clinical

manifestations with onset after two years of age [25]. Manifestations of late congenital syphilis
are related to scarring or persistent inflammation from early infection and are characterized by
gumma formation in various tissues [56]. Late congenital syphilis develops in approximately 40
percent of infants born to women with untreated syphilis during pregnancy. Most
manifestations of late congenital syphilis are prevented by appropriate treatment of the mother
during pregnancy or by treatment of the infant within the first three months of life [57,58].
However, other manifestations (eg, keratitis, saber shins) may occur or progress despite
appropriate therapy [59].
Manifestations of late congenital syphilis include ( table 4) [1,23,58,60,61]:
● Facial features – Frontal bossing ( picture 4), saddle nose, short maxilla, protuberant
mandible.
● Ophthalmologic – Interstitial keratitis ( picture 5) (bilateral, usually occurs around

puberty but can occur anytime between 4 and 30 years), secondary glaucoma, corneal
scarring, optic atrophy.
● Hearing – 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 [62].
● Oropharynx – Hutchinson teeth (hypoplastic, notched, widely spaced permanent teeth

[upper central incisors most commonly affected] ( picture 6); before eruption,
Hutchinson teeth are visible on dental radiographs), mulberry molars (maldevelopment of
the cusps of the first molars) ( picture 7), and perforation of the hard palate (virtually
pathognomonic for congenital syphilis) ( picture 8).
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● Cutaneous – Rhagades (perioral fissures or a cluster of scars radiating around the mouth)
( picture 9), 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 10), enlargement of the
sternoclavicular portion of the clavicle (Higoumenakis sign), painless arthritis of the knees
("Clutton joints") ( picture 11), 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 [23,60].
EVALUATION AND DIAGNOSIS
The vagaries of the maternal history of syphilis 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 [10,63]. The United
States 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 [53,54]. Similar guidelines are provided by the World
Health Organization [64]. (See 'Society guideline links' below.)
The CDC and AAP guidelines continue to recommend that maternal samples be screened
according to the traditional algorithm (ie, a nontreponemal test followed when positive by a
confirmatory treponemal test) [53,54]. However, both organizations recognize that due to
practical and cost considerations, many antenatal care providers screen pregnant individuals in
reverse sequence (testing initially for syphilis antibodies, typically by enzyme immunoassay
[EIA] or chemiluminescence immunoassay [CIA], followed by nontreponemal test if EIA/CIA is
positive). The CDC has provided guidance for interpreting results, which is particularly
important when the initial EIA/CIA treponemal test is discordant with the subsequent
nontreponemal test [65]. Interpretation of maternal screening results with the traditional and
reverse sequence screening algorithms is discussed separately. (See "Syphilis in pregnancy",
section on 'Diagnosis' and "Syphilis: Screening and diagnostic testing", section on 'Serologic
testing algorithms'.)
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Clinical suspicion — The diagnosis of congenital syphilis may be suspected based upon any of
the following:
● Maternal syphilis during pregnancy – Evaluation for early congenital syphilis is

warranted in all newborns born to mothers who have reactive nontreponemal and
treponemal tests for syphilis during pregnancy. (See "Syphilis in pregnancy", section on
'Diagnosis'.)
● Maternal syphilis during first three months after delivery – This includes infants born
to women who are identified clinically or through contact tracing [25].
● Concerning clinical findings – The possibility of congenital syphilis should be considered

in all newborn infants with concerning clinical findings. This is particularly important when
there is prior history or risk factors for syphilis in the mother (eg, inadequate prenatal
care, other sexually transmitted diseases, homelessness or unstable housing, drug abuse,
incarceration, having sex in conjunction with drug use or transactional sex). Maternal risk
factors for syphilis are discussed separately. (See "Syphilis in pregnancy", section on
'Epidemiology'.)
Clinical findings that may raise concern for congenital syphilis in this setting include the
following; however, these are nonspecific findings:
• Unexplained prematurity (<37 weeks gestation)

• Unexplained hydrops fetalis
• Enlarged placenta
• Failure to move an extremity ("pseudoparalysis")
• Persistent rhinitis ( picture 1)
• Maculopapular or papulosquamous rash ( picture 2), particularly in the diaper area,
palms, and soles
• Jaundice, hepatomegaly
• Neonatal pneumonia
• Generalized lymphadenopathy
• Anemia (direct antiglobulin test negative)
• Thrombocytopenia
● Infants and children who are adopted internationally – This is discussed separately.
(See "International adoption: Infectious disease aspects", section on 'Syphilis'.)
Initial evaluation
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Neonates — Diagnostic testing for congenital syphilis is warranted in all newborn infants
whose mothers have reactive nontreponemal and treponemal tests for syphilis. For mothers
screened with the traditional approach, the treponemal test is necessary to exclude a false
positive nontreponemal result. When reverse sequencing is used, the nontreponemal test is still
necessary for comparison with the mother's result and for monitoring of treatment success
(two nontreponemal tests are needed when there is discordance between syphilis antibody and
nontreponemal test during reverse sequencing). (See "Syphilis in pregnancy", section on
'Diagnosis'.)
The initial evaluation of newborns born to mothers who tested positive for syphilis during
pregnancy should include all of the following ( algorithm 1) [53,54]:
● Quantitative nontreponemal test (Venereal Disease Research Laboratory [VDRL] test or

rapid plasma reagin [RPR]) on infant serum (umbilical cord blood should not be used for
testing since false positive results can occur if the sample is contaminated with maternal
blood). The nontreponemal test performed in the newborn should be the same as was
used for the mother so that the newborn's titers can be compared with the mother's. (See
'Nontreponemal tests' below.)
● Physical examination for evidence of congenital syphilis ( table 3). (See 'Clinical findings'
above.)
● Where available, testing for T. pallidum with direct fluorescent antibody (DFA) staining,
darkfield microscopic examination, and/or polymerase chain reaction (PCR) can be
performed on any concerning skin lesions or nasal discharge. However, these tests are not
available in many clinical settings. (See 'Other tests' below.)
● If possible, pathologic examination of the placenta or umbilical cord can be performed

using specific fluorescent antitreponemal antibody staining [20,32,66]. Characteristic
histopathologic features are described separately. (See "Care of the umbilicus and
management of umbilical disorders", section on 'Funisitis'.)
● Additional evaluation should be performed based upon the findings from the initial
evaluation, as discussed below. (See 'Evaluation for extent of organ involvement' below.)
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 [53,54]:
● Quantitative VDRL or RPR (see 'Nontreponemal tests' below)
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● Physical examination
● Darkfield microscopic examination or DFA staining of concerning skin lesions or nasal
discharge (if available) (see 'Other tests' below)
● Cerebrospinal fluid (CSF) analysis for VDRL, white blood cell (WBC) count, and protein
measurement (see 'Lumbar puncture' below)
● Complete blood count (CBC) with differential and platelet count
● Liver function tests
● Skeletal radiographs (see 'Skeletal survey' below)
● Hearing evaluation (see 'Hearing evaluation' below)
● Ophthalmologic examination (see 'Eye examination' below)
● Other tests as clinically indicated (eg, chest radiograph, abdominal ultrasonography, and
neuroimaging studies) (see 'Other assessments' below)
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].
In addition to the above testing, any child at risk for congenital syphilis should also undergo
testing for HIV [1]. (See "Diagnostic testing for HIV infection in infants and children younger
than 18 months" and "Screening and diagnostic testing for HIV infection".)
The distinction between congenital and acquired syphilis can be difficult and ultimately may
rest upon maternal history and clinical judgment [1]. CSF and CBC abnormalities may occur in
both congenital and acquired syphilis, but abnormalities on long-bone radiographs are strongly
supportive of congenital syphilis. (See 'Congenital versus acquired syphilis' below and
'Radiographic abnormalities' above.)
In a young child, the possibility of sexual abuse should be considered as a cause of acquired
syphilis [24]. (See "Evaluation of sexual abuse in children and adolescents", section on 'Sexually
transmitted infections'.)
Children who are diagnosed with syphilis after one month of age (including those with
previously untreated congenital syphilis) require parenteral penicillin therapy, as discussed
separately. (See "Congenital syphilis: Management and outcome", section on '>1 month of age'.)
Evaluation of siblings — Evaluation of the siblings of an index case of congenital syphilis may
be warranted if such an evaluation did not occur previously [56].
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Diagnostic tests — The diagnosis of syphilis is challenging because T. pallidum cannot be

cultured in the laboratory. The diagnosis of syphilis may be established by:
● Demonstration of serologic reactions typical of syphilis (see 'Interpretation' below)
● Detection of T. pallidum in infected body fluids, skin lesions, placenta, or umbilical cord by
any of the following (see 'Other tests' below):
• Direct visualization on darkfield microscopy ( picture 12)

• DFA, or
• PCR
● Demonstration of the T. pallidum by special stains ( picture 13) or histopathologic

examination [67,68]
Other tests that involve animal inoculation (eg, rabbit infectivity test [RIT]) are used mostly in
research settings.
These testing methods are briefly summarized here and are discussed in detail separately. (See
"Syphilis: Screening and diagnostic testing", section on 'Diagnostic tests'.)
Serologic tests — Serologic tests include:
● Nontreponemal tests – These include VDRL and RPR. (See 'Nontreponemal tests' below.)
● Treponemal tests – These include EIA and CIA, which are the two tests used for maternal
reverse sequencing, as discussed above (see 'Evaluation and diagnosis' above). Other
treponemal tests include fluorescent treponemal antibody absorption (FTA-ABS), T.
pallidum particle agglutination (TP-PA), and microhemagglutination test for T. pallidum
(MHA-TP). (See 'Treponemal tests' below.)
Nontreponemal tests — 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 semiquantitative results, which
can be compared with simultaneously obtained maternal results to categorize the likelihood of
neonatal infection ( table 5) [54]. Interpretation of the results is discussed below. (See
'Interpretation' below.)
Positive nontreponemal tests are reported as a titer of antibody (eg, 1:32, which represents the
detection of antibody in serum diluted 32-fold). The neonate's titer usually is one to two
dilutions less than mother's [69]. When the mother's titer is low, the neonate may have
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nonreactive serology but remains at risk for congenital syphilis. If testing is performed early
after maternal infection, both the mother and newborn may have negative nontreponemal
tests [70]. (See 'Congenital syphilis less likely' below.)
When congenital syphilis is suspected and the nontreponemal test is negative, evaluation for
prozone phenomenon (excess antibody) evaluation should be requested (test at dilution 1:512
and if that dilution is negative, test at 1:1024 dilution).
Nontreponemal titers are also useful for monitoring during treatment since successful
treatment is associated with a decline in the titer. (See "Congenital syphilis: Management and
outcome", section on 'Follow-up serology'.)
A disadvantage of serologic tests for syphilis is that they detect immunoglobulin G [IgG]
antibodies and do not differentiate between passively acquired maternal antibody and
endogenous antibody produced by the fetus/neonate. Thus, it is necessary to compare the
infant's titer with the mother's to determine the likelihood of congenital infection. It would be
more desirable if testing detected only immunoglobulin M [IgM] antibodies, which do not cross
the placenta, since this theoretically would be more accurate in confirming congenital infection.
Unfortunately, a sufficiently sensitive and specific IgM assay is not available for routine use in
the assessment of congenital syphilis [53]. The fluorescent antitreponemal IgM antibody test
(IgM FTA-ABS) was used in the past, but because of lack of sensitivity, the CDC suspended its
use for diagnostic testing of infants [71,72].
For maternal testing during pregnancy, rapid point-of-care serologic tests are available that can
be used as an alternative to laboratory testing, particularly in resource-limited settings. These
tests do not require the laboratory 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 (approximately 20 minutes). They have good
sensitivity and specificity, comparable to those of conventional treponemal and nontreponemal
tests [73,74]. However, they do not provide quantitative results and therefore are not
appropriate for testing the neonate. Rapid serologic tests are discussed in greater detail
separately. (See "Syphilis: Screening and diagnostic testing", section on 'Rapid serologic tests'.)
Treponemal tests — Treponemal tests (eg, FTA-ABS, TP-PA, EIA, CIA, MHA-TP) are not
used in the evaluation of newborns with suspected congenital syphilis when maternal
treponemal test results are available.
However, in instances when the diagnosis is uncertain, treponemal tests can be used later in
infancy or childhood to help establish the diagnosis of congenital syphilis. In infants known to
have had reactive nontreponemal serologic tests for syphilis as newborns or born to mothers
3/30/23, 1:58 PM 14428
who were seroreactive at delivery, a treponemal test can be performed after 12 to 15 months of
age [23,63]. If the treponemal test is reactive, it should be repeated at 18 and 24 months of age.
A positive treponemal test at ≥18 months of age (after the disappearance of passively acquired
maternal antibody) confirms the diagnosis of congenital syphilis [63,75]. Children who have a
positive treponemal test for syphilis at ≥18 months of age and did not previously receive
treatment should undergo full evaluation and treatment. (See "Congenital syphilis:
Management and outcome", section on 'Penicillin therapy'.)
Treponemal tests are discussed in greater detail separately. (See "Syphilis: Screening and
diagnostic testing", section on 'Treponemal tests'.)
Other tests
● Darkfield microscopy and DFA – Darkfield microscopy and DFA testing can be used to
detect the organism ( picture 12); however, these tests are not routinely available in
many clinical settings because they require special equipment to perform and
considerable experience and expertise to properly interpret the results. Thus, for most
clinicians, these tests are now viewed as alternative diagnostic tools.
Where available, darkfield microscopy can be performed on body fluids (eg, nasal
discharge) or moist skin lesions [76]. Darkfield microscopy enables demonstration of thin,
delicate, corkscrew-shaped organisms with rigid, tightly wound spirals ( picture 12). A
positive darkfield slide illustrates the characteristic motility associated with T. pallidum: a
forward and backward motion with rotation about the longitudinal axis [76]. 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.
● PCR – PCR has been used on neonatal blood and CSF for diagnosis of congenital syphilis,
but these tests are not widely available [18,40,41,77,78]. 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].
● Rabbit infectivity test – The RIT, which involves the inoculation of CSF or other body
fluids into rabbits to determine the presence of viable T. pallidum, is the reference
standard test for congenital syphilis [23,26,56]. However, routine use of RIT is not practical
because it involves animal testing and is not widely available.
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Interpretation — To maximize treatment of newborns potentially infected with T. pallidum, the

AAP categorizes congenital syphilis infection as "proven or highly probable," "possible," "less
likely," and "unlikely" ( table 5). The categories of "possible" and "less likely" include infants
with normal physical examination and serological results not meeting diagnostic criteria but
who nevertheless are still at risk of congenital syphilis. The inclusion of these at-risk infants
helps to ensure that all possible cases are treated; however, not all at-risk infants are truly
infected [53].
The following factors are considered when determining the likelihood of congenital infection:
● Whether the neonate has clinical findings that are consistent with congenital syphilis. (See
'Early congenital syphilis' above.)
● The neonate's syphilis serology, which must be compared with maternal titers. A titer that
is ≥4-fold (two dilutions) higher than the maternal titer is indicative of infection (for
example, a neonatal titer ≥1:32 when the maternal titer is 1:8). Lower titers in the newborn
do not exclude congenital syphilis. (See 'Nontreponemal tests' above.)
● The mother's syphilis serology (in relation to previous tests and/or treatment and in
relation to the neonate's titers).
● Maternal treatment for syphilis, including:
• Whether the mother received treatment.
• The timing of completion of treatment (before or during pregnancy; more or less than
four weeks before delivery).
• Whether treatment was adequate ( table 1).
• The likelihood of failure of maternal therapy to prevent congenital disease – Higher

maternal titers and unknown duration of maternal syphilis are associated with
increased risk of treatment failure [79].
Proven or highly probable congenital syphilis — For newborns born to women who tested
positive for syphilis during pregnancy, the diagnosis of congenital syphilis is proven or highly
probable if the neonate has any of the following findings [53]:
● Physical examination findings consistent with congenital syphilis.
● Serum VDRL or RPR 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]).
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● Positive darkfield microscopy ( picture 12), DFA or PCR of lesions, body fluid(s), placenta,
or umbilical cord (these tests are not be available in many clinical settings).
Neonates with proven or highly probable congenital syphilis should undergo further evaluation
to assess the extent of organ involvement, as summarized in the table ( table 5) and
discussed below. (See 'Evaluation for extent of organ involvement' below.)
Regardless of the results of additional evaluation, neonates in this category should receive a full
course of parenteral treatment, as summarized in the table and figure ( table 5 and
algorithm 1) and discussed in detail separately. (See "Congenital syphilis: Management and
outcome", section on '10-day regimen'.)
Possible congenital syphilis — Neonates who meet all of the following criteria are
considered to have possible congenital syphilis [53,54]:
● Mother was diagnosed with syphilis during pregnancy (reactive nontreponemal and
treponemal tests)
● Mother was not treated, received inadequate/suboptimal therapy, or had evidence of
relapse or reinfection ( table 1)
● Infant physical examination is normal
● Infant serum VDRL or RPR titer <4-fold maternal titer
Some experts would also consider a newborn to have possible congenital syphilis if the mother
had sexual contact with a person with primary or secondary syphilis within 90 days before
delivery and was not treated or was inadequately treated, even if the mother had nonreactive
serology [25,80].
For neonates in the "possible" congenital syphilis category, the need for additional evaluation
and choice of treatment regimen are as follows ( table 5 and algorithm 1):
● Neonates at higher risk – For neonates in the "possible" category who have a higher risk
of infection (ie, maternal risk of untreated syphilis is high or neonate's nontreponemal
titer is reactive), we suggest performing further evaluation to assess the extent of organ
involvement, as summarized in the table ( table 5) and discussed below. (See 'Evaluation
for extent of organ involvement' below.)
If any part of the additional evaluation is abnormal, not performed, or uninterpretable (eg,
traumatic lumbar puncture) or if follow-up is uncertain, the neonate should receive a full
course of parenteral treatment, as summarized in the table and figure ( table 5 and
3/30/23, 1:58 PM 14428
algorithm 1) and discussed in detail separately. (See "Congenital syphilis: Management

and outcome", section on '10-day regimen'.)
If the additional evaluation is performed and is completely normal and if follow-up is

assured, the neonate is treated with a single dose of intramuscular (IM) benzathine
penicillin. (See "Congenital syphilis: Management and outcome", section on 'Single-dose
regimen'.)
● Neonates at lower risk – For neonates in the "possible" category who have a lower risk of
infection (ie, maternal risk of untreated syphilis is low and neonate's nontreponemal titer
is nonreactive), no additional evaluation is required, and the neonate can be treated with a
single dose of IM benzathine penicillin. (See "Congenital syphilis: Management and
outcome", section on 'Single-dose regimen'.)
The CDC and AAP guidelines include a caveat that additional evaluation may not be necessary
for neonates in the "possible" category if a 10-day treatment course is planned [53,54].
Nevertheless, we suggest performing the evaluation in higher-risk neonates (as defined above)
since the evaluation may inform decisions regarding treatment and follow-up.
Congenital syphilis less likely — Infection is less likely if all of the following criteria are met
[53,54]:
● Mother was diagnosed with syphilis during pregnancy (reactive nontreponemal and
treponemal tests)
● Mother completed appropriate treatment ≥4 weeks before delivery
● Mother has no evidence of reinfection or relapse
● Newborn's physical examination is normal
● Newborn's serum VDRL or RPR titers are <4-fold the maternal titer
Neonates who meet these criteria do not require additional evaluation [53,54]. However, these
neonates are at risk and should receive treatment with a single dose of IM penicillin G
benzathine, as summarized in the table and algorithm ( table 5 and algorithm 1) and
discussed in detail separately. (See "Congenital syphilis: Management and outcome", section on
'Single-dose regimen'.)
Congenital syphilis unlikely — The diagnosis of congenital syphilis is unlikely if all of the
following criteria are met [53,54]:
● Mother had reactive nontreponemal and treponemal tests

● Mother completed appropriate treatment before pregnancy
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● Mother's nontreponemal titers remained low (VDRL <1:2; RPR <1:4) and stable before and
during pregnancy and at delivery (ie, serofast)
● Newborn's physical examination is normal
● Newborn's serum VDRL or RPR titers are <4-fold the maternal titer
These newborns generally do not require any additional evaluation or treatment (except in
instances when follow-up cannot be assured, in which case a single dose of IM benzathine
penicillin is sufficient). (See "Congenital syphilis: Management and outcome", section on
'Treatment according to diagnostic category'.)
Congenital versus acquired syphilis — In children who are found to have reactive serologic
tests for syphilis after infancy, 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.)
In a young child with reactive serologic tests for syphilis, the possibility of sexual abuse should
be considered. (See "Evaluation of sexual abuse in children and adolescents", section on
'Sexually transmitted infections'.)
CASE DEFINITION
The Centers for Disease Control and Prevention (CDC) case definition for congenital syphilis is
provided in the table ( table 6) [1]. Other case definitions may differ slightly from the CDC
definition [81].
In general, case definitions for congenital syphilis require only one of two criteria:
● The infant or child has physical, laboratory, or radiographic signs of congenital syphilis
(confirmed/highly probable congenital syphilis), or
● The infant or child was born to a mother with untreated, inadequately, or suboptimally
treated syphilis (presumed congenital syphilis) ( table 1)
EVALUATION FOR EXTENT OF ORGAN INVOLVEMENT
For neonates in the "proven or highly probably" category and those in the "possible" category
who have a higher risk of infection (ie, high risk of maternal untreated syphilis or neonate's
nontreponemal titer is reactive), we suggest performing all of the following additional tests to
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evaluate for the extent of organ involvement ( table 5) [53,54]. Details about these tests are
provided in the sections below.
● Lumbar puncture (LP) for cerebrospinal fluid (CSF) analysis. (See 'Lumbar puncture' below.)
● Complete blood count (CBC) with differential and platelet count. (See 'Blood tests' below.)
● Liver function tests (LFTs, including serum bilirubin and liver enzymes); if LFTs are grossly
abnormal, coagulation tests should also be obtained. (See 'Blood tests' below.)
● Skeletal survey. (See 'Skeletal survey' below.)
● Hearing evaluation and ophthalmologic examination – Our practice is to routinely perform

these evaluations in all newborns who are undergoing evaluation for extent of organ
involvement. This practice differs from the Centers for Disease Control and Prevention
(CDC) and American Academy of Pediatrics (AAP) guidelines, which do not recommend
routinely performing these assessments since retinitis and hearing loss are rare in
newborns with early congenital syphilis [53,54]. However, in affected infants, hearing and
vision problems may not be clinically apparent until later in childhood, and there can be
serious developmental consequences if these problems are not diagnosed and treated in
a timely manner. Thus, we suggest routinely performing these assessments in the
neonatal period. (See 'Hearing evaluation' below and 'Eye examination' below.)
● Other tests as clinically indicated (eg, neuroimaging if there are concerning neurologic
findings, chest radiograph if there are pulmonary findings). (See 'Other assessments'
below.)
The CDC and AAP guidelines include a caveat that the above evaluation is not necessary for
neonates in the "possible" category who will be treated with a 10-day course of parenteral
penicillin [53,54]. Nevertheless, we suggest performing the evaluation in neonates in this
category who are at higher risk for infection (as defined above) since the evaluation may inform
treatment and follow-up decisions.
No additional evaluation is necessary for neonates in the "possible" category who have a lower
risk of infection (ie, low risk of maternal untreated syphilis and neonate's nontreponemal titer is
nonreactive) and those in the "less likely" and "unlikely" categories.
Lumbar puncture — If LP is performed, CSF analysis should include [53,54]:
● Cell count with differential

● CSF protein and glucose
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● CSF Venereal Disease Research Laboratory (VDRL)
Ideally, the LP is nontraumatic since results of traumatic taps are not interpretable in this
setting.
CSF analysis may help to establish the diagnosis in some infants and it informs decisions about
the need for long-term CSF follow-up [42,45]. However, the diagnosis of congenital central
nervous system (CNS) syphilis 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. (See "Neurosyphilis".)
Blood tests — Routine blood tests performed in infants undergoing evaluation for congenital
syphilis include:
● CBC with differential and platelet count to assess for anemia and other hematologic
manifestations
● LFTs, including serum bilirubin and liver enzymes, to assess for liver involvement, which is
common in symptomatic newborns
● If LFTs are grossly abnormal, coagulation tests should also be obtained
Skeletal survey — Radiographic evaluation to detect bony abnormalities should be performed

in all neonates who warrant evaluation for extent of organ involvement. The CDC and AAP
guidelines suggest limiting the radiographic evaluation to the long bones (femur, tibia/fibular,
humerus, and radius/ulna) since these are the sites most frequently involved [53,54]. However,
we generally perform a full skeletal survey since bony abnormalities are occasionally noted in
other locations (eg, ribs, clavicles, hands, and feet) [82].
A skeletal survey (or long-bone radiographs) can also be helpful if there is uncertainty as to
whether the infant or child has congenital versus acquired syphilis. Bony abnormalities are
suggestive of congenital infection, as discussed above. (See 'Congenital versus acquired
syphilis' above.)
Radiographic abnormalities characteristically are bilateral, symmetric, and polyostotic

( image 1A-D); the femur, humerus, and tibia are most frequently involved, as described
above. (See 'Radiographic abnormalities' above.)
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Hearing evaluation — All infants and children with proven or highly probable congenital
syphilis should undergo formal hearing assessment, typically with auditory brainstem response
(ABR). This is best accomplished while the newborn is still in the hospital but can be done in the
outpatient setting if follow-up is assured. (See "Hearing loss in children: Screening and
evaluation", section on 'Formal audiology'.)
In many settings, all newborns routinely undergo hearing screening prior to discharge from the
birth hospitalization. Otoacoustic emissions (OAE) screening is often used for this purpose. OAE
is generally less sensitive compared with ABR (ie, higher false negative rate). Thus, in infants
with congenital syphilis, formal audiologic evaluation with ABR is generally warranted even if
the newborn passes the initial OAE screen. Newborns who pass a screening performed with
automated ABR do not require formal audiology. (See "Screening the newborn for hearing
loss".)
Eye examination — All infants and children with proven or highly probable congenital syphilis
should have formal vision assessment and dilated eye examination performed by a pediatric
eye care specialist. This is best accomplished while the newborn is still in the hospital but can be
done in the outpatient setting if follow-up is assured. (See "Vision screening and assessment in
infants and children".)
Other assessments — Additional testing is guided by the clinical findings and may include:
● Neuroimaging if there are concerning neurologic findings

● Chest radiograph if there are pulmonary findings
● Abdominal imaging if there is significant organomegaly or other concerning findings
DIFFERENTIAL DIAGNOSIS
The differential diagnosis for congenital syphilis includes:
● Other congenital and neonatal infections, including ( table 7):
• 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')
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• Herpes simplex virus infection (see "Neonatal herpes simplex virus infection: Clinical
features and diagnosis", section on 'Evaluation and diagnosis')
• Congenital lymphocytic choriomeningitis virus infection (see "Viral meningitis in

children: Epidemiology, pathogenesis, and etiology", section on 'Lymphocytic
choriomeningitis virus')
• Neonatal sepsis (see "Clinical features, evaluation, and diagnosis of sepsis in term and
late preterm neonates", section on 'Evaluation and initial management')
● Other causes of neonatal jaundice, hepatomegaly, and cholestasis, which are summarized
in the table ( table 8) and reviewed in detail separately. (See "Causes of cholestasis in
neonates and young infants".)
● Other causes of 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'.)
● Other causes of vesicular lesions in neonates, which are summarized in the table
( table 9), and reviewed in detail separately. (See "Vesicular, pustular, and bullous lesions
in the newborn and infant".)
Historical features, associated findings, and/or laboratory testing usually differentiate these
conditions from congenital syphilis.
REPORTING REQUIREMENTS
In the United States, congenital syphilis is a national notifiable disease [83]. 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].
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately.
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● (See "Society guideline links: TORCH infections".)

● (See "Society guideline links: Sexually transmitted infections".)
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
● Transmission and epidemiology – Congenital syphilis is acquired through transplacental

transmission of spirochetes. Pregnant individuals with untreated primary or secondary
syphilis are at highest risk of transmitting syphilis to the fetus. Treponema pallidum is not
transferred in breast milk. In the United States, reported cases of congenital syphilis have
increased dramatically since 2012 ( figure 1). (See 'Transmission' above and
'Epidemiology' above.)
● Clinical features
• Early congenital syphilis – Early congenital syphilis is arbitrarily defined by clinical

manifestations with onset before two years of age. Manifestations of early congenital
syphilis are varied and unpredictable, as summarized in the table ( table 3). (See
'Early congenital syphilis' above.)
• Late congenital syphilis – Late congenital syphilis is arbitrarily defined by clinical

manifestations with onset after two years of age. Manifestations of late congenital
3/30/23, 1:58 PM 14428
syphilis are summarized in the table ( table 4); most are related to scarring or
persistent inflammation from early infection.
● Clinical suspicion – The diagnosis of congenital syphilis should be suspected in all infants
born to mothers who have reactive nontreponemal and treponemal tests for syphilis
during pregnancy and infants/children with clinical findings compatible with congenital
syphilis ( table 3 and table 4). (See 'Clinical suspicion' above.)
● Evaluation – The initial evaluation for congenital syphilis includes the following (see 'Initial
evaluation' above):
• Venereal Disease Research Laboratory (VDRL) or rapid plasma reagin (RPR) titer; titers
should be measured in both the newborn and the mother using the same test. (See
'Nontreponemal tests' above.)
• Physical examination for evidence of congenital syphilis ( table 3). (See 'Clinical
findings' above.)
• Where available, testing for T. pallidum can be performed with direct fluorescent
antibody (DFA) staining, darkfield microscopy, and/or polymerase chain reaction (PCR)
of nasal discharge and/or swabs of skin lesions; however, these tests are not available
in many clinical settings. (See 'Other tests' above.)
• If possible, pathologic examination of the placenta and umbilical cord with specific
staining.
● Diagnosis – The diagnosis of congenital syphilis may be established by any of the

following ( table 6):
• Demonstration of serologic reactions typical of syphilis in relation to mother's serology

• Detection of T. pallidum by darkfield microscopy ( picture 12), DFA or PCR of infected
body fluids or lesions, placenta, or umbilical cord
• Demonstration of the T. pallidum by special stains ( picture 13) or histopathologic
examination
Based upon the physical examination, maternal and infant VDRL or RPR titers, maternal
treatment history, and other findings, the likelihood of congenital syphilis can be
categorized as "proven or highly probable," "possible," "less likely," and "unlikely"
( algorithm 1 and table 5). (See 'Interpretation' above.)
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● Further evaluation – For neonates in the "proven or highly probably" category and those
in the "possible" category who have a higher risk of infection (ie, high risk of maternal
untreated syphilis or neonate's nontreponemal titer is reactive), we suggest performing
all of the following additional tests to evaluate for the extent of organ involvement
( table 5) (see 'Evaluation for extent of organ involvement' above):
• Lumbar puncture for cerebrospinal fluid (CSF) analysis (see 'Lumbar puncture' above)
• Complete blood count (CBC) with differential and platelet count (see 'Blood tests'
above)
• Liver function tests (LFTs) (see 'Blood tests' above)
• Skeletal survey (see 'Skeletal survey' above)
• Hearing evaluation and ophthalmologic examination (see 'Hearing evaluation' above
and 'Eye examination' above)
• Other tests as clinically indicated (eg, neuroimaging if there are concerning neurologic
findings, chest radiograph if there are pulmonary findings) (see 'Other assessments'
above)
No additional evaluation is necessary for neonates in the "possible" category who have a
lower risk of infection (ie, low risk of maternal untreated syphilis and neonate's
nontreponemal titer is nonreactive) and those in the "less likely" and "unlikely" categories.
● Differential diagnosis – The differential diagnosis of congenital syphilis includes other

congenital infections ( table 7); neonatal sepsis; and other causes of neonatal hepatitis,
hydrops fetalis, long-bone abnormalities, and cutaneous lesions. Historical features,
associated clinical findings, and/or laboratory testing usually differentiate these conditions
from congenital syphilis. (See 'Differential diagnosis' above.)
ACKNOWLEDGMENT
The editorial staff at UpToDate would like to acknowledge Simon R Dobson, MD, FRCP(C), who
contributed to an earlier version of this topic review.
Use of UpToDate is subject to the Terms of Use.
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31. Fojaco RM, Hensley GT, Moskowitz L. Congenital syphilis and necrotizing funisitis. JAMA
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33. Hollier LM, Harstad TW, Sanchez PJ, et al. Fetal syphilis: clinical and laboratory
characteristics. Obstet Gynecol 2001; 97:947.
34. Braunstein GD, Lewis EJ, Galvanek EG, et al. The nephrotic syndrome associated with
secondary syphilis. An immune deposit disease. Am J Med 1970; 48:643.
35. Gamble CN, Reardan JB. Immunopathogenesis of syphilitic glomerulonephritis. Elution of
antitreponemal antibody from glomerular immune-complex deposits. N Engl J Med 1975;
292:449.
36. Kaplan BS, Wiglesworth FW, Marks MI, Drummond KN. The glomerulopathy of congenital
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38. Radcliffe M, Meyer M, Roditi D, Malan A. Single-dose benzathine penicillin in infants at risk
of congenital syphilis--results of a randomised study. S Afr Med J 1997; 87:62.
39. Paryani SG, Vaughn AJ, Crosby M, Lawrence S. Treatment of asymptomatic congenital
syphilis: benzathine versus procaine penicillin G therapy. J Pediatr 1994; 125:471.
40. Michelow IC, Wendel GD Jr, Norgard MV, et al. Central nervous system infection in
congenital syphilis. N Engl J Med 2002; 346:1792.
41. Sánchez PJ, Wendel GD Jr, Grimprel E, et al. Evaluation of molecular methodologies and
rabbit infectivity testing for the diagnosis of congenital syphilis and neonatal central
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42. Beeram MR, Chopde N, Dawood Y, et al. Lumbar puncture in the evaluation of possible
asymptomatic congenital syphilis in neonates. J Pediatr 1996; 128:125.
43. Daaboul JJ, Kartchner W, Jones KL. Neonatal hypoglycemia caused by hypopituitarism in
infants with congenital syphilis. J Pediatr 1993; 123:983.
44. Nolt D, Saad R, Kouatli A, et al. Survival with hypopituitarism from congenital syphilis.
Pediatrics 2002; 109:e63.
45. Moyer VA, Schneider V, Yetman R, et al. Contribution of long-bone radiographs to the
management of congenital syphilis in the newborn infant. Arch Pediatr Adolesc Med 1998;
152:353.
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46. Brion LP, Manuli M, Rai B, et al. Long-bone radiographic abnormalities as a sign of active
congenital syphilis in asymptomatic newborns. Pediatrics 1991; 88:1037.
47. Kocher MS, Caniza M. Parrot pseudoparalysis of the upper extremities. A case report. J
Bone Joint Surg Am 1996; 78:284.
48. Case of the week. Newborn infant with hepatomegaly. VCU Health System. http://www.ped
sradiology.com/Historyanswer.aspx?qid=144&fid=1 (Accessed on August 12, 2011).
49. Rasool MN, Govender S. The skeletal manifestations of congenital syphilis. A review of 197
cases. J Bone Joint Surg Br 1989; 71:752.
50. Lascari AD, Diamond J, Nolan BE. Anemia as the only presenting manifestation of
congenital syphilis. Clin Pediatr (Phila) 1976; 15:90.
51. Bulova SI, Schwartz E, Harrer WV. Hydrops fetalis and congenital syphilis. Pediatrics 1972;
49:285.
52. Shah MC, Barton LL. Congenital syphilitic hepatitis. Pediatr Infect Dis J 1989; 8:891.
53. Workowski KA, Bachmann LH, Chan PA, et al. Sexually Transmitted Infections Treatment
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54. American Academy of Pediatrics. Syphilis. In: Red Book: 2021-2024 Report of the Committe
e on Infectious Diseases, 32nd ed, Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH (Eds), A
merican Academy of Pediatrics, Itasca, IL 2021. p.729.
55. Cooper JM, Sánchez PJ. Congenital syphilis. Semin Perinatol 2018; 42:176.
56. Chakraborty R, Luck S. Syphilis is on the increase: the implications for child health. Arch Dis
Child 2008; 93:105.
57. PUTKONEN T. Does early treatment prevent dental changes in congenital syphilis? Acta
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59. OKSALA A. Interstitial keratitis after adequate penicillin therapy; a case report. Br J Vener
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62. Adams DA, Kerr AG, Smyth GD, Cinnamond MJ. Congenital syphilitic deafness--a further
review. J Laryngol Otol 1983; 97:399.
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sequence syphilis screening--five laboratories, United States, 2006-2010. MMWR Morb
Mortal Wkly Rep 2011; 60:133.
66. Genest DR, Choi-Hong SR, Tate JE, et al. Diagnosis of congenital syphilis from placental
examination: comparison of histopathology, Steiner stain, and polymerase chain reaction
for Treponema pallidum DNA. Hum Pathol 1996; 27:366.
67. Hardy JB, Hardy PH, Oppenheimer EH, et al. Failure of penicillin in a newborn with
congenital syphilis. JAMA 1970; 212:1345.
68. Rawstron SA, Vetrano J, Tannis G, Bromberg K. Congenital syphilis: detection of Treponema
pallidum in stillborns. Clin Infect Dis 1997; 24:24.
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syphilis. Am J Dis Child 1991; 145:1383.
70. Binnicker MJ, Jespersen DJ, Rollins LO. Treponema-specific tests for serodiagnosis of
syphilis: comparative evaluation of seven assays. J Clin Microbiol 2011; 49:1313.
71. Stoll BJ, Lee FK, Larsen S, et al. Clinical and serologic evaluation of neonates for congenital
syphilis: a continuing diagnostic dilemma. J Infect Dis 1993; 167:1093.
72. Lefevre JC, Bertrand MA, Bauriaud R. Evaluation of the Captia enzyme immunoassays for
detection of immunoglobulins G and M to Treponema pallidum in syphilis. J Clin Microbiol
1990; 28:1704.
73. Lago EG. Current Perspectives on Prevention of Mother-to-Child Transmission of Syphilis.
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74. Bonawitz RE, Duncan J, Hammond E, et al. Assessment of the impact of rapid syphilis tests
on syphilis screening and treatment of pregnant women in Zambia. Int J Gynaecol Obstet
2015; 130 Suppl 1:S58.
75. Rawstron SA, Mehta S, Marcellino L, et al. Congenital syphilis and fluorescent treponemal
antibody test reactivity after the age of 1 year. Sex Transm Dis 2001; 28:412.
76. Larsen SA. Syphilis. Clin Lab Med 1989; 9:545.
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77. Woznicová V, Smajs D, Wechsler D, et al. Detection of Treponema pallidum subsp. pallidum
from skin lesions, serum, and cerebrospinal fluid in an infant with congenital syphilis after
clindamycin treatment of the mother during pregnancy. J Clin Microbiol 2007; 45:659.
78. Garel B, Grange P, Benhaddou N, et al. Congenital syphilis: A prospective study of 22 cases
diagnosed by PCR. Ann Dermatol Venereol 2019; 146:696.
79. McFarlin BL, Bottoms SF, Dock BS, Isada NB. Epidemic syphilis: maternal factors associated
with congenital infection. Am J Obstet Gynecol 1994; 170:535.
80. Zenker PN, Berman SM. Congenital syphilis: trends and recommendations for evaluation
and management. Pediatr Infect Dis J 1991; 10:516.
81. Risser WL, Hwang LY. Problems in the current case definitions of congenital syphilis. J
Pediatr 1996; 129:499.
82. Sachdev M, Bery K, Chawla S. Osseous manifestations in congenital syphilis: a study of 55
cases. Clin Radiol 1982; 33:319.
83. Centers for Disease Control and Prevention. National Notifiable Diseases Surveillance Syste
m. http://www.cdc.gov/osels/ph_surveillance/nndss/phs/infdis.htm (Accessed on August 1
2, 2011).
Topic 14428 Version 36.0
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GRAPHICS
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.
Graphic 73418 Version 7.0
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Congenital syphilis: Reported cases among infants by year of birth and rates of
and secondary syphilis among women, United States, 2009 to 2020
CS: congenital syphilis; P&S: primary and secondary syphilis.
Adapted from: Centers for Disease Control and Prevention (CDC) Sexually Transmitted Disease Surveillance, 2020, available at:
https://www.cdc.gov/std/statistics/2020/tables.htm (Accessed on October 06, 2022).
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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.
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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)
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Condylomata lata Single or multiple, flat, wartlike, moist lesions around the
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
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Chronic meningovascular syphilis Onset toward the end of the first year; hydrocephalus;
cranial nerve palsies; intellectual/neurodevelopmental
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.
3/30/23, 1:58 PM 14428
Congenital syphilis: Snuffles
Reproduced from: the Public Health Image Library, Centers for Disease Control and
Prevention. Photo by Dr. Norman Cole.
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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.
3/30/23, 1:58 PM 14428
Condylomata lata
Perianal condylomata lata in an infant with early congenital syphilis.
Courtesy of Moise L Levy, MD, Baylor College of Medicine.
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Condylomata lata
Moist, gray papules that resemble condylomata acuminata are

present on the perianal skin.
Reproduced with permission from: www.visualdx.com. Copyright VisualDx. All rights

reserved.
3/30/23, 1:58 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.
3/30/23, 1:58 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.
3/30/23, 1:58 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.
3/30/23, 1:58 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.
3/30/23, 1:58 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.
3/30/23, 1:58 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.
3/30/23, 1:58 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.
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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.
3/30/23, 1:58 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
3/30/23, 1:58 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.
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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.
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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
3/30/23, 1:58 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.
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Approach to evaluation and management of newborns born to mothers who te

syphilis during pregnancy
This figure summarizes our suggested approach to evaluating and treating infants with suspected congenit
based upon maternal and infant serologies, adequacy of maternal treatment, clinical findings in the infant,
3/30/23, 1:58 PM 14428
Evaluation for congenital syphilis is warranted in all infants born to mothers who have reactive nontreponem
tests for syphilis during pregnancy. For mothers screened with the traditional approach, the treponemal tes
exclude a false-positive nontreponemal result. When reverse sequencing is used, the nontreponemal test is
comparison with the mother's result and for monitoring of treatment success (two nontreponemal tests are
there is discordance between syphilis antibody and nontreponemal test during reverse sequencing). Refer t
on syphilis during pregnancy and congenital syphilis for additional details.
VDRL: venereal disease research laboratory; RPR: rapid plasma regain; DFA: direct fluorescent antibody; PCR
reaction; LP: lumbar puncture; CBC: complete blood count; LFTs: liver function tests; ABR: auditory brainstem
Centers for Disease Control and Prevention; CSF: cerebrospinal fluid; IM: intramuscular; IV: intravascular.
* Findings of congenital syphilis may include hepatosplenomegaly, rash, condyloma lata, snuffles, jaundice
pseudoparalysis, pallor (anemia), or edema (nephrotic syndrome and/or malnutrition). Refer to UpToDate to
syphilis for additional details.
¶ A 4-fold titer is equivalent to two dilutions (eg, infant's titer 1:32 if maternal titer is 1:8).
Δ These tests are not available in most clinical settings.
◊ Additional testing may include neuroimaging if there are concerning neurologic findings, chest radiograp
pulmonary findings, or abdominal imaging if there is significant organomegaly.
§ Adequate treatment is defined as completion of a penicillin-based regimen, in accordance with CDC treatm
appropriate for stage of infection and initiated ≥4 weeks before delivery. Relapse or reinfection after treatm
a 4-fold increase maternal VDRL or RPR titers after treatment. Inadequate/suboptimal therapy includes any
Treatment given <4 weeks before delivery
Inadequate response to therapy (ie, maternal VDRL or RPR titers did not decline at least 4-fold after tr
¥ The CDC guidelines include a caveat that additional evaluation may not be necessary for neonates in the "
if a 10-day treatment course is planned. Nevertheless, we suggest performing the evaluation in higher-risk n
defined above) since the evaluation may inform decisions regarding treatment and follow-up.
‡ All neonates with reactive nontreponemal serologies should be monitored with follow-up examinations an
testing with VDRL or RPR (use same test as for initial testing) at 1, 2, 4, 6, and 12 months or until nonreactive
tests are still positive at 6-12 months, the infant should be re-evaluated (including LP) and treated with an ex
parenteral penicillin. Infants with nonreactive nontreponemal serologies at birth should be retested at 3 mo
that the infant remains seronegative.
† For infants in the "less likely" category, some specialists opt not to treat and instead provide close (ie, mon
follow-up. If this approach is chosen, treatment should be provided if the infant's titers do not decline as exp
few months after birth.
** If follow-up is uncertain, some specialists would provide a single dose of IM penicillin G benzathine to pro
the unlikely event that the mother was reinfected.
3/30/23, 1:58 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.
3/30/23, 1:58 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.
3/30/23, 1:58 PM 14428
Likelihood of congenital syphilis infection in newborn infants born to

mothers with reactive nontreponemal and treponemal tests during
pregnancy
Additional Follow-up tes

Category Definition evaluation to Treatment (applies to
perform categories
Proven or Mother diagnosed with LP for CSF cell 10 days of Monitor clinic
highly syphilis during count, protein, parenteral examination f
probable pregnancy (reactive and CSF VDRL penicillin development
nontreponemal and CBC with new concerni
treponemal tests), differential and findings
regardless of platelet count Perform follow
treatment received LFTs serologic test
Plus Long-bone For infant
radiographs with react
Newborn has ANY of
ABR nontrepon
the following:
serologies
Clinical findings Eye examination
Perform s
consistent with Other tests as
serologic
congenital syphilis* clinically
testing wi
Infant serum VDRL indicated:
VDRL or R
or RPR titer ≥4-fold Chest (use same
maternal titer ¶ radiograph if as for initi
Positive darkfield there are testing) at
microscopy, DFA, or pulmonary 4, 6, and 1
PCR of skin lesions, findings months o
body fluid(s), Neuroimaging nonreactiv
placenta, or if there are nontrepon
umbilical cord Δ concerning tests are s
neurologic positive at
findings months, t
Abdominal infant sho
imaging if be re-eval
there is (including
significant and treate
organomegaly with an
extended
Possible ALL of the following: We further classify newborns in the
course of
Mother diagnosed with "possible" category as higher or lower risk:
parentera
syphilis during Higher risk: Neonate's VDRL or RPR is
penicillin.
pregnancy (reactive reactive or maternal risk of untreated
For infant
nontreponemal and syphilis is high
with
treponemal tests)
3/30/23, 1:58 PM 14428
Mother did not receive Lower risk: Neonate's VDRL or RPR is nonreact
treatment, or received nonreactive and maternal risk of nontrepon
inadequate/suboptimal untreated syphilis is low serologies
treatment, or had Recheck V
Higher risk: Higher risk:
evidence of relapse or or RPR (us
Perform same If any part of
reinfection ◊ same test
evaluation as for the additional
Infant physical for initial
the "proven or evaluation is
examination is normal testing) at
highly probable" abnormal, not
Infant serum VDRL or 3 months
category (see performed, or
RPR titer <4-fold confirm in
above) § uninterpretable
maternal titer ¶ remains
(eg, traumatic
seronegat
LP) or if follow-
up is uncertain:
10 days of
parenteral
penicillin
If all tests in
the additional
evaluation are
performed and
are normal:
Single dose of
IM penicillin
benzathine
Lower risk: Lower risk:

Additional Single dose of
evaluation is not IM benzathine
necessary penicillin
Less likely ALL of the following: Not required Single dose of IM

Mother diagnosed with penicillin
syphilis during benzathine ¥
pregnancy (reactive
nontreponemal and
treponemal tests)
Mother received
appropriate treatment
during pregnancy (at
least 4 weeks before
delivery) ◊
Mother has no
evidence of reinfection
or relapse ◊
Infant physical
examination is normal
3/30/23, 1:58 PM 14428
Infant serum VDRL or

RPR titer <4-fold
maternal titer ¶
Unlikely ALL of the following: Not required Not required ‡

Mother had reactive
nontreponemal and
treponemal tests
during pregnancy
Mother received
appropriate treatment
before pregnancy ◊
Mother's titers
remained low (VDRL
<1:2; RPR <1:4) and
stable before and
during pregnancy and
at delivery
Infant physical
examination is normal
Infant serum VDRL or
RPR titer <4-fold
maternal titer ¶
This table summarizes the likelihood of congenital syphilis infection based upon maternal and
newborn serologies, adequacy of maternal treatment, clinical findings in the infant, and other
findings. Evaluation for congenital syphilis is warranted in all newborns born to mothers who have
reactive nontreponemal and treponemal tests for syphilis during pregnancy. For mothers screened
with the traditional approach, the treponemal test is necessary to exclude a false-positive
nontreponemal result. When reverse sequencing is used, the nontreponemal test is still necessary
for comparison with the mother's result and for monitoring of treatment success (two
nontreponemal tests are needed when there is discordance between syphilis antibody and
nontreponemal test during reverse sequencing). Refer to UpToDate's topics on syphilis during
pregnancy and congenital syphilis for additional details.
VDRL: venereal disease research laboratory; RPR: rapid plasma regain; DFA: direct fluorescent
antibody; PCR: polymerase chain reaction; LP: lumbar puncture; CBC: complete blood count; LFTs:
liver function tests; ABR: auditory brainstem response; CDC: Centers for Disease Control and
Prevention; CSF: cerebrospinal fluid; IM: intramuscular.
* Findings of congenital syphilis may include hepatosplenomegaly, rash, condyloma lata, snuffles,
jaundice (nonviral hepatitis), pseudoparalysis, pallor (anemia), or edema (nephrotic syndrome
and/or malnutrition). Refer to UpToDate topic on congenital syphilis for additional details.
¶ A 4-fold titer is equivalent to two dilutions (eg, newborn's titer 1:32 if maternal titer is 1:8).
Δ These tests are not available in many clinical settings.
3/30/23, 1:58 PM 14428
◊ Adequate treatment is defined as completion of a penicillin-based regimen, in accordance with

CDC treatment guidelines, appropriate for stage of infection and initiated ≥4 weeks before delivery.
Relapse or reinfection after treatment is suggested by a 4-fold increase of maternal VDRL or RPR
titers after treatment. Inadequate/suboptimal therapy includes any of the following:
Treatment given <4 weeks before delivery
Inadequate response to therapy (ie, maternal VDRL or RPR titers did not decline at least 4-fold
after treatment)
§ The CDC guidelines include a caveat that additional evaluation may not be necessary for neonates
in the "possible" category if a 10-day treatment course is planned. Nevertheless, we suggest
performing the evaluation in higher-risk neonates (as defined above) since the evaluation may
inform decisions regarding treatment and follow-up.
¥ Some specialists opt not to treat infants in this category and instead provide close (ie, monthly)
serologic follow-up. If this approach is chosen, treatment should be provided if the infant's titers do
not decline as expected over the first few months after birth.
‡ If follow-up is uncertain, some specialists would provide a single dose of IM benzathine penicillin
to protect the infant in the unlikely event that the mother was reinfected.
3/30/23, 1:58 PM 14428
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:

During the first 30 days after birth – CSF WBC count >15 WBC/mm 3 or CSF protein >120
mg/dL is abnormal
3/30/23, 1:58 PM 14428
For infants and children >30 days old – CSF WBC count >5 WBC/mm 3 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).
3/30/23, 1:58 PM 14428
Clinical manifestations that are suggestive of specific congenital infections

in the neonate
Congenital toxoplasmosis
Intracranial calcifications (diffuse)
Hydrocephalus
Chorioretinitis
Otherwise unexplained mononuclear CSF pleocytosis or elevated CSF protein
Congenital syphilis
Skeletal abnormalities (osteochondritis and periostitis)
Pseudoparalysis
Persistent rhinitis
Maculopapular rash (particularly on palms and soles or in diaper area)
Congenital rubella
Cataracts, congenital glaucoma, pigmentary retinopathy
Congenital heart disease (most commonly patent ductus arteriosus or peripheral pulmonary
artery stenosis)
Radiolucent bone disease
Sensorineural hearing loss
Congenital cytomegalovirus
Thrombocytopenia
Periventricular intracranial calcifications
Microcephaly
Hepatosplenomegaly
Herpes simplex virus
Perinatally acquired HSV infection
Mucocutaneous vesicles
CSF pleocytosis
3/30/23, 1:58 PM 14428
Thrombocytopenia
Elevated liver transaminases
Conjunctivitis or keratoconjunctivitis
Congenital (in utero) HSV infection (rare)
Skin vesicles, ulcerations, or scarring
Eye abnormalities (eg, micro-ophthalmia)
Brain abnormalities (eg, hydranencephaly, microcephaly)
Congenital varicella
Cicatricial or vesicular skin lesions
Microcephaly
Congenital Zika syndrome
Microcephaly
Intracranial calcifications
Arthrogryposis
Hypertonia/spasticity
Ocular abnormalities
CSF: cerebrospinal fluid; HSV: herpes simplex virus.
3/30/23, 1:58 PM 14428
Causes of neonatal cholestasis
Obstruction
Biliary atresia ¶
Biliary cysts
Inspissated bile/mucous plug
Cholelithiasis or biliary sludge
Tumors/masses (intrinsic and extrinsic to the bile duct)
Neonatal sclerosing cholangitis
Spontaneous perforation of the bile ducts
Infection ¶
Viral
Adenovirus, cytomegalovirus, echovirus, enterovirus, herpes simplex virus, HIV, parvovirus B19,
rubella
Bacterial
Urinary tract infection, sepsis, syphilis
Protozoal
Toxoplasma
Genetic/metabolic disorders
Inherited cholestatic disorders
Alagille syndrome ¶ Δ (MIM #118450)
Alpha-1 antitrypsin deficiency (PI*Z homozygotes or PI*SZ heterozygotes) ¶ (MIM #613490)
ARC syndrome (arthrogryposis-renal dysfunction-cholestasis) (MIM #208085)
Cystic fibrosis (MIM #219700)
Progressive familial intrahepatic cholestasis (types 1 to 5) ¶ ◊ (MIM #211600, MIM #601847,

MIM #602347, MIM #615878, MIM #617049)
MYO5B gene mutations (with or without congenital diarrhea due to microvillus inclusion
disease) [1] (MIM #251850, MIM #619868)
NISCH syndrome (neonatal ichthyosis sclerosing cholangitis) (MIM #607626)
Dubin-Johnson syndrome § (MIM #237500)
Rotor syndrome (MIM #237450)
Disorders of carbohydrate metabolism
3/30/23, 1:58 PM 14428
Galactosemia ¶ (MIM #230400)
Fructosemia (MIM #229600)
Glycogen storage disease type IV (MIM #232500)
Transaldolase deficiency (MIM #606003)
Disorders of amino acid metabolism
Tyrosinemia (type 1) ¶ (MIM #276700)
Disorders of lipid metabolism
Lysosomal acid lipase deficiency (Wolman disease) (MIM #278000), Niemann-Pick type C (MIM
#257220), Gaucher type 2 (MIM #230900)
Fatty acid oxidation defects (eg, MIM #201470, MIM #201475)
Disorders of bile acid synthesis
Bile acid synthesis defects (types 1 to 6) (MIM #607765, MIM #235555, MIM #613812, MIM
#214950, MIM #616278, MIM #617308)
Cerebrotendinous xanthomatosis (MIM #213700)
Amidation defects (BAAT or SLC27A5 gene mutations)
Zellweger spectrum disorders ◊ (MIM #214100 and others)
Smith-Lemli-Opitz syndrome ◊ (MIM #270400)
Mitochondrial disorders ¥
Urea cycle defect
Citrin deficiency (type II) (MIM #605814)
Congenital disorders of glycosylation
Phosphomannomutase 2 deficiency (MIM #212065)
Phosphoglucomutase 1 deficiency (MIM #614921)
Mannosephosphate isomerase deficiency (MIM #602579)
Alloimmune
Gestational alloimmune liver disease
Toxic
Intestinal failure-associated liver disease (parenteral nutrition) ¶
Drugs (ceftriaxone, erythromycin, sulfa-containing medications)
Miscellaneous
"Idiopathic" neonatal hepatitis
Nonsyndromic paucity of the interlobular bile ducts
3/30/23, 1:58 PM 14428
Hemophagocytic lymphohistiocytosis
Shock/hypoperfusion
Intestinal obstruction
Congenital portosystemic shunt
Hypothyroidism
Hypopituitarism (eg, in septo-optic dysplasia)
This table summarizes disorders in which cholestasis can be a prominent feature in the neonatal
period. For disorders that present with hepatic failure, refer to UpToDate content on acute hepatic
failure in infants and children.
HIV: human immunodeficiency virus.
¶ More common disorders causing neonatal cholestasis.
Δ Alagille syndrome is also known as syndromic paucity of the interlobular bile ducts or
arteriohepatic dysplasia.
◊ These disorders are classified as secondary bile acid metabolic defects.
§ Presentation of Dubin-Johnson syndrome in neonates and young infants is rare but has been
reported [2] .
¥ For mitochondrial hepatopathies, refer to UpToDate table and content on acute liver failure in
infants and children.
References:
1. Cockar I, Foskett P, Strautnieks S, et al. Mutations in Myosin 5B in Children With Early-onset Cholestasis. J Pediatr
Gastroenterol Nutr 2020; 71:184.
2. Towaga T, Mizuochi T, Sugiura T, et al. Clinical, Pathologic, and Genetic Features of Neonatal Dubin-Johnson
Syndrome: A Multicenter Study in Japan. J Pediatr 2018; 196:161.
3/30/23, 1:58 PM 14428
Vesiculopustular lesions in neonates and infants that require treatment

and/or monitoring
Condition Clinical features Significance
Infectious conditions
Congenital Grouped or single vesicles on Requires antiviral therapy; significant

herpes erythematous base in crops on skin morbidity and mortality if untreated
simplex virus and mucous membranes; lesions
(HSV) usually appear between 1 and 2 weeks
of age; may be associated with
nonspecific signs of serious illness:
temperature instability, respiratory
distress, poor feeding, lethargy
Neonatal Grouped or single vesicles on Requires antiviral therapy; associated

varicella erythematous base in crops on skin with significant morbidity and
zoster virus and mucous membranes mortality
Congenital Blisters, erosions that frequently Requires antibiotic therapy; late

syphilis involve the palms and soles; other manifestations in untreated infants
manifestations include rhinitis, may include central nervous system,
anemia, jaundice, hepatomegaly skeletal, and dental abnormalities;
hearing loss; and interstitial keratitis
Staphylococcal Erythematous papules, pustules, Requires antibiotic therapy; Gram stain

pustulosis honey-colored crusts often in areas of and culture of lesions should be
trauma obtained; may be associated with
systemic/invasive infection
Staphylococcal Fever, irritability, diffuse blanching Requires antibiotic therapy; cultures

scalded skin erythema, flaccid blisters; positive should be obtained from any
syndrome Nikolsky sign* suspected focus of infection (eg, blood,
(SSSS) urine, nasopharynx, umbilicus)
Streptococcal May mimic staphylococcal infections Same as for staphylococcal pustulosis

infections and SSSS
Listeria Pustules of the skin and mucus Requires antibiotic therapy; may be
membranes may be present in early associated with septicemia and/or
onset disease (<7 days of age) meningitis
Candidiasis Erythematous macules and papules Requires antifungal therapy; has the
evolving to pustules and vesicles potential to disseminate via the
bloodstream in susceptible hosts
Congenital disorders
3/30/23, 1:58 PM 14428
Epidermolysis Blister development with little or no Management involves prevention of

bullosa trauma trauma, careful wound care, and
treatment of infection
Epidermolytic Widespread blistering and erythema Increased susceptibility to cutaneous

hyperkeratosis and or hyperkeratosis; denuded areas infection
of skin
Aplasia cutis Erosions present at birth that re- May be associated with other disorders
congenita epithelialize to form hypertrophic or (eg, trisomy 13, 4p-)
atrophic scar; involves the epidermis
and dermis
Incontinentia Four stages that may occur Majority of cases associated with
pigmenti simultaneously: linear streaks of neurologic, ocular, dental, and
erythematous papules and vesicles; structural abnormalities
warty papules or plaques in linear or
swirling patterns; swirled;
hypopigmented patches or streaks
Miscellaneous
Scabies May be seen in infants as young as 3 to Requires treatment with scabicide and
4 weeks of age but never present at measures to prevent spread
birth; vesicles, pustules, and papules;
rare burrows on hands, feet, trunk,
genitalia
Cutaneous Bullous eruptions with hemorrhage; Requires symptomatic therapy and

mastocytosis positive Darier sign ¶ avoidance of triggers
* Nikolsky sign: Separation of the upper dermis and wrinkling of the skin with application of gentle
pressure.
¶ Darier sign: Urticaria and erythema with rubbing, scratching, or stroking.
3/30/23, 1:58 PM 14428
Contributor Disclosures
Antonio C Arrieta, MD, FIDSA, FPIDS 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. 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
conform to UpToDate standards of evidence.
Conflict of interest policy

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Congenital syphilis: Clinical manifestations, evaluation,

● (See "Congenital syphilis: Management and outcome".)

● Incidence – Congenital syphilis is a significant public health problem, complicating an

Syphilis in pregnancy is commonly associated with adverse pregnancy outcomes (fetal

Social vulnerabilities including homelessness, substance abuse, and incarceration were

difficulty in confirming adequate treatment/treatment response of the birth mother and

● Missed opportunities – The most common missed opportunity for prevention of

Early congenital syphilis — Early congenital syphilis is arbitrarily defined by clinical

Clinical findings — Clinical manifestations in untreated infants usually appear by three

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

Clinical manifestations of early syphilis are varied and unpredictable ( table 3)

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

● Generalized lymphadenopathy – Generalized, nontender lymphadenopathy is a

● Other manifestations – Other manifestations of early congenital syphilis may include

• Nonimmune fetal hydrops

• Failure to move an extremity secondary to painful periostitis ("pseudoparalysis of

Asymptomatic CNS syphilis is indicated by abnormalities in the cerebrospinal fluid (CSF)

palsies, papilledema, optic atrophy, neurodevelopmental regression, and seizures.

In addition, pituitary gland involvement may manifest with persistent hypoglycemia or

● Bony abnormalities – Bony abnormalities are a common manifestation of early

The radiographic abnormalities characteristically are bilateral, symmetric, and polyostotic;

• Symmetric localized demineralization and osseous destruction of the medial portion of

• Metaphyseal serration ("sawtooth metaphysis").

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

● Pulmonary findings – Complete opacification of both lung fields ("pneumonia alba") is

● Hematologic studies – Hematologic abnormalities of early congenital syphilis may

● CSF abnormalities – Findings that indicate CNS involvement include [1,7,53,54]:

However, none of these findings is highly sensitive or specific [40,42]. In an observational

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

Late congenital syphilis — Late congenital syphilis is arbitrarily defined by clinical

Manifestations of late congenital syphilis include ( table 4) [1,23,58,60,61]:

● Ophthalmologic – Interstitial keratitis ( picture 5) (bilateral, usually occurs around

● 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".)

EVALUATION AND DIAGNOSIS

● Maternal syphilis during pregnancy – Evaluation for early congenital syphilis is

● Concerning clinical findings – The possibility of congenital syphilis should be considered

• Unexplained prematurity (<37 weeks gestation)

● Quantitative nontreponemal test (Venereal Disease Research Laboratory [VDRL] test or

● If possible, pathologic examination of the placenta or umbilical cord can be performed

● Quantitative VDRL or RPR (see 'Nontreponemal tests' below)

Diagnostic tests — The diagnosis of syphilis is challenging because T. pallidum cannot be

● Demonstration of serologic reactions typical of syphilis (see 'Interpretation' below)

• Direct visualization on darkfield microscopy ( picture 12)

● Demonstration of the T. pallidum by special stains ( picture 13) or histopathologic

Serologic tests — Serologic tests include:

Nontreponemal tests — Nontreponemal tests are inexpensive and rapidly performed.

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

● Maternal treatment for syphilis, including:

• Whether the mother received treatment.

• Whether treatment was adequate ( table 1).

• The likelihood of failure of maternal therapy to prevent congenital disease – Higher

● Physical examination findings consistent with congenital syphilis.

algorithm 1) and discussed in detail separately. (See "Congenital syphilis: Management

If the additional evaluation is performed and is completely normal and if follow-up is

● Mother had reactive nontreponemal and treponemal tests

EVALUATION FOR EXTENT OF ORGAN INVOLVEMENT

● Skeletal survey. (See 'Skeletal survey' below.)

● Hearing evaluation and ophthalmologic examination – Our practice is to routinely perform

Lumbar puncture — If LP is performed, CSF analysis should include [53,54]: