Syphilis

Introduction
• The rates of primary and secondary syphilis in women have been rising.
• It is more common among pregnant women who are poor, young (age
<29 yrs), African American and lack health insurance/prenatal care.
• Other risk factors include illicit druge use, STIs, residence in a high
syphilis prevalence area, being a sex worker, & having >1 sexual partner
in the past.
• However 50% of pregnant women w/ syphilis have no risk factors.
• The incubation period varies from 10-90 days (average is approximately
3 weeks).
• Candidates & timing of initial & repeat screening:
• 1. All pregnant women: screen at the first prenatal encounter
• 2. Women at high risk of infection: repeat screening at 28 to 32 weeks & at
delivery.
• 3. Women who have not been screened in pregnancy or who deliver a stillborn
after 20 weeks of gestation: screen at delivery.

• Serologic testing to diagnose syphilis should include both nontreponemal

& treponemal tests.
• Nontreponemal tests: Rapid Plasma Reagin (RPR), Venereal Disease Research
Laboratory (VDRL), & Toluidine Red Unheated Serum Test (TRUST)
• Treponemal tests: Fluorescent treponemal antibody absorption (FTA-ABS),
microhemagglutination test for Abs to Treponema pallidum (MHA-TP), T. pallidum
particle gglutination assay (TPPA), T. pallidum enzyme immunoassay (TP-EIA), &
chemiluminescence immunoassay (CIA).
• Traditional serologic testing algorithms for syphilis involve initial
screening w/ a nontreponemal test (e.g. RPR) and a reactive test is
then confirmed with treponemal test.
• CDC described treponemal test (e.g. TP-EIA) as screening followed by
a nontreponemal test for confirmation. This has a higher false
positive rate, but it can detect syphilis in some pts w/ very early
syphilis, those w/ prior treated syphilis, & those w/ late or late latent
syphilis whose nontreponemal test has become nonreactive over
time.
Interpretation of serologic testing
Positive nontreponemal/positive treponemal

• W/out hx of syphilis  new infection

• Hx of syphilis  requires nontreponemal titer & clinical presentation
• Treponemal tests usually remain positive after infection, but titers of
nontreponemal assays decline w/ treatment & usually revert to negative
over time.
• Titers should be compared w/ post-treatment titer (preferably same lab).
• New syphilis infection is diagnosed when quantitative testing using
nontreponemal test reveals a fourfold or greater increase in titer from
post-treatment test.
• Patient’s are considered serofast if they have persistently reactive
nontreponemal test s/p treatment at low titer (e.g., 1:8).
Positive nontreponemal/negative treponemal:

• Generally considered to have false positive syphilis.

• Biologic false-positive nontreponemal and treponemal results are
relatively common in pregnancy.
• 31% false positive rate w/ VDRL.
• 47-88% false positive rate w/ TP-EIAs or CIAs.
• A positive (reactive) low titer nontreponemal test can be considered a
transient biologic false-positive result due to pregnancy if the follow-up
treponemal test is negative & the pt is asymptomatic & at low risk of
acute syphilis. These abnormalities are transitory & last for 6 months or
less.
• All women w/ biologic false-positives attributed to pregnancy should
undergo follow-up testing at least 4-6 weeks after delivery.
Negative nontreponemal/positive
treponemal:
• Discordant results are often seen in pts w/ a hx of successfully treated
syphilis. No further evaluation or treatment is needed unless there is
concern for re-exposure.
• For pts w/out a hx of treated syphilis, a discordant result can occur in very
early syphilis or in late syphilis when nontreponemal tests have become
nonreactive over time.
• If chancre is present (suggesting early syphilis), a nontreponemal test should be
repeated to assess for seroconversion & presumptive treatment should be
administered.
• For pts w/ S&S of neurosyphilis, a LP may be indicated to assess for CNS involvement.
• If no S&S, counsel pts regarding a possible diagnosis of late latent syphilis.
Staging
• Each stage of syphilis has characteristic clinical findings that are not
altered by pregnancy.
• The stage of syphilis is clinical important b/c it impacts the treatment
regimen & the risk of vertical transmission.
Primary syphilis
• Painless papule at site of inoculation which
ulcerates to produce chancre (1-2 cm painless
ulcer w/ raised, indurated margin).
• The ulcer is associated w/ mild to moderate
regional lymphadenopathy that may be
bilateral.
• Chancres heal spontaneously w/in 3-6 weeks,
even in the absence of treatment.
Secondary syphilis
• Disseminated systemic process that
occurs in 25%$ of untreated patients,
usually beginning 6 weeks to 6 months
after appearance of the chancre.
• A generalized maculopapular skin rash
involving the palms, soles & mucous
membranes.
• The rash of secondary syphilis typically
resolves spontaneously within 2 to 6
weeks.
Latent syphilis
• “Early” latent when it is possible to document a nonreactive syphilis
serology w/in the past year or a hx of symptoms of early syphilis w/in
the past year.
• Otherwise considered “late” latent.
• Latent syphilis is by definition asymptomatic.
Tertiary (late) syphilis
• Characterized by slowly progressive
signs & symptoms.
• Clinical manifestations include gumma
formation & cardiovascular disease.
• The lesions of cardiovascular syphilis
include aortitis & aortic aneurysms,
aortic valvular insufficiency, &
narrowing of the coronary ostia.
• Usually develop 5 to 20 years after the
disease has been latent.
Neurosyphilis
• Early neurosyphilis can be asymptomatic or w/ signs of meningitis
(headache, confusion, nausea/vomiting stiff neck). Visual acuity can be
impaired w/ comcomitant uveitis, vitreitis, retinitis or optic neuropathy.
Can also include cranial neuropathies.
• Late neurosyphilis encompasses general paresis & tabes dorsalis.
• Tabes dorsalis is a disease of the posterior columns of the spinal cord & of the
dorsal roots. It has the longest latent period b/w primary infection & onset of
symptoms.
• The most frequent symptoms of tabes dorsalis is sensory ataxia, lancinating pains,
pupillary irregularities (Argyll-Robertson pupil – does not respond to light but
contracts normally to accommodation/convergence), absent lower extremity
reflexes, impaired vibratory & position sensation.
• Clinical suspicion & spinal fluid exam are keys to diagnosis of neurosyphilis.
Treatment
• Penicillin is the standard for the treatment of syphilis in both pregnant &
nonpregnant individuals.
• Penicillin therapy in pregnancy is effective for treating maternal disease,
preventing transmission to the fetus, & treating established fetal disease.
• The appropriate penicillin regimen depends on the stage of disease.
• If an asymptomatic patient w/ suspected latent syphilis was previously
treated for syphilis but receipt of an appropriate treatment regimen
cannot be verified, the full three-dose penicillin regimen recommended
for late latent syphilis should be administered.
• Women who are sexual contacts of partners w/ known or suspected
syphilis should be presumptively treated w/ a single dose of penicillin G
benzathine 2.4 million units IM.
Jarisch-Herxheimer Reaction
• Acute febrile reaction accompanied by headache, myalgia, rash &
hypotension.
• Thought to result from the release of large amts of treponemal
lipopolysaccharide from dying spirochetes & an increase in circulating
cytokine levels.
• Rxn begins w/in 1 – 2 hrs of treatment, peaks at 8 hrs, & typically
resolves w/in 24 – 48 hrs.
• Management is supportive care.
Penicillin allergies
• Patients with immediate type allergic rxns to penicillin should be
desensitized & then treated w/ penicillin.
• During pregnancy, nonpenicillin antibioitic regimens used for syphilis
treatment in nonpregnant women are either contraindicated (e.g.
tetracycline), lack sufficient data regarding efficacy (e.g. ceftriaxone), or
do not cross the placental barrier completely so the fetus is not treated
(e.g., erythromycin, azithromycin).
• Nonpenicillin regimens should only be considered when penicillin cannot
be obtained or for penicillin-allergic patients when penicillin
desensitization is not possible.
• Erythromycin 500 mg PO QID for 14 days (treatment of choice for late syphilis)
• Ceftriaxone 1 g IM QD for 10 – 14 days
• Azithromycin 2 g PO x1 dose
Post-treatment and monitoring
• Pts w/ early syphilis should be assessed clinically for resolution of symptoms.
• For individuals w/ symptomatic neurosyphilis, serial neuro exams should be
performed every 6 months.
• Once the nontreponemal titer has become nonreactive (seroreversion), add’l
testing is not needed.
• A nontreponemal titer should be obtained just before initiating therapy.
• Early syphilis: Serologic testing every 6-12 months & at any time clinical symptoms
recur. Pts should experience an adequate response by 12 months.
• Late syphilis: Serologic testing at 6, 12, & 24 months. Some pts may not have
adequate response for up to 2 yrs.
• Pts w/ HIV ate typically monitored more frequently.
Syphilis in the HIV-infected patient
• The HIV-infected pt w/ syphilis should be treated w/ the same
regimens as those recommended for HIV-seronegative patients.
• Pts w/ syphilis in the HIV-infected pt is greater than w/ HIV-uninfected
pts.
• Early syphilis: clinical & serologic eval at 3, 6, 9, 12 & 24 months after therapy.
Occurs 6-12 months after treatment.
• Late syphilis: clinical & serologic eval every 6 months for a 2 yr period.
• Occurs 12-24 months after treatment.
• Neurosyphilis: CSF exams every 6 months until the cell count is normal (in pts
w/ ocular or otic syphilis & a normal CSF exam do not need f/u LP). Are
expected to normalize w/in 2 yrs after treatment.
Treatment failure
• Treatment failure is suspected if nontreponemal titers do not decline
fourfold or greater.
• If pt has not had an adequate response to treatment, it is important
to determine if the individual has been reinfected, is experiencing a
slow response to treatment, or has failed treatment.
• Drug resistance to penicillin has not been described. Treatment failure is
likely due to poor adherence w/ the treatment regimen, treatment w/
alternative agent, immunocompromised status, or undiagnosed central
nervous system.
• For pts w/ neurosyphilis & evidence of treatment failure, retreatment usually
requires 14 days IV penicillin G.
Potential adverse pregnancy
outcomes
• Increased adverse outcomes from placental & fetal infection.
• Miscarriage, preterm birth, stillbirth, impaired fetal growth,
congenital infection, neonatal mortality.
Vertical transmission
• T. pallidum readily infects the placenta.
• Transplacental transmission to the fetus can occur from the 9th-10th week of
gestation & at any stage of maternal disease.
• Fetal abnormalities result from a robust inflammatory response to T.
pallidum; thus they are most pronounced after 20 weeks of gestation since
the fetal immunologic response is poorly developed in the first half of
pregnancy.
• After the placenta is infected, transplacental passage of spirochetes to the
fetal circulation leads to fetal hepatic infection/dysfunction, followed by
amniotic fluid infection, fetal hematologic abnormalities (anemia,
thrombocytopenia), ascites, hydrops, & fetal IgM production.
Factors influencing vertical
transmission
• The risk of congenital infection is high in the first 4 years after
maternal acquisition.
• The frequency of vertical transmission increases w/ increasing
gestational age at acquisition of maternal infection.
• Failure to appropriately identify & treat maternal infection.
Prenatal diagnosis
• Findings on ultrasound are nonspecific:
• Hepatomegaly (liver length >95th percentile for gestational age).
• Placentomegaly (placental thickness >2 SDs above mean for gestational age).
• Anemia (Doppler of MCA peak systolic velocity >1.5 MoM)
• Polyhydramnios
• Ascites or hydrops
• Hepatomegaly & placentomegaly are early findings.
• Maternal penicillin treatment is curative for fetal infection in most
cases.
Hepatomegaly

Fetal nonimmune hydrops

(ascites, skin edema & pleural
effusion)
Placentomegaly