Transcript CONGENITAL SYPHILIS

CONGENITAL SYPHILIS
SINDHU E. PHILIP, MD.
DEPARTMENT OF PEDIATRICS
09/20/02
Introduction
Infant usually infected in utero by transplacental passage of
Treponema pallidum from infected mother at any time.
Infection may also occur from contact with an infectious
lesion during passage through the birth canal
It remains unclear what factors determine which mothers,
particularly those in the latent stage, will pass the disease to
the fetuses.
Also unclear why some infants, infected in utero, are born
asymptomatic, but develop overt dz. In first few wks./mo.
Epidemiology
 Worldwide, but more frequent in urban areas.
 Incidence of congenital syphilis has dramatically decreased
in the U.S. since 1991.
Infection can be transmitted to fetus at any
stage of disease.
Rate of infection 60% - 100% during second
stage.
Transmission rates slowly decreases with
increasing duration of the disease.
Women, untreated early syphilis: 40%
of pregnancies result in spontaneous abortion,
stillbirth, or perinatal death.
Pathogenesis
Infection before 4th month of pregnancy?
Possible that treponemes do in fact pass from mother
to fetus before 5th month of gestation, but classic
pathologic changes do not occur until after 5th month.
Infection involves the placenta, and spreads
hematogenously to the fetus, widespread involvement
is characteristic. Infected placenta is paler, thicker,
and larger than normal.
Clinical Manifestations
Damage to fetus depends on the stage of development
at which infection has taken place and time elapsed
before treatment.
Early infection, untreated: miscarriage, stillbirth, neonatal
death, IUGR, premature delivery.
Survivors:
Early congenital syphilis: clinical manifestations within first
2 years of life
Late congenital syphilis: clinical manifestations after 2yo.
Early Congenital Syphilis
Early manifestations are varied, with multi-system
Involvement
• Hepatosplenomegaly- diffuse
inflammation, scarring
• Jaundice – due to hepatitis
• Generalized lymphadenopathy –
epitrochclear nodes
• Coombs – hemolytic anemia,
thromobocytopenia, leukopenia, leukocytosis
• Hydrops fetalis
• Mucocutaneous: rhinitis (highly
infectious), “snuffles”, mucous
patches
• Macuolpapular rash
• Desquamation
• Pemphigus syphiliticus (vesicular
bullous eruptions of palms and soles)
• Petechial lesions
• Bony lesions, osteochondritis,
periostitis, pseudoparalysis
• Syphilitc leptomeningitis
• Chorioretinitis,salt and pepper
fundus, glaucoma
• Pancreatitis
Papulosquamous Plaques
Broken vesicles, desquamation
Condylomata around anus
Infiltration, desquamation and rhinitis
Rhinitis (snuffles), mucous
patches, damage to palate(late)
Bullae and vesicular rash on soles
Eroded papular lesions
Lone Bone Radiographs
Osteochondritis of distal radius and ulna
Osteochondritis of femur and tibia
metaphysis
Late Congenital Syphilis
Results primarily from chronic inflammation of bone, teeth,
and CNS.
• Interstitial keratitis (inflammatory)
• Nerve deafness
• Clutton’s Joints (synositis, restricted
movement)
• Hutchinson’s triad (teeth,
intersitial keratitis, 8th nerve
deafness)
• Mulberry molars
• Flaring scapulas
• Hydrocephalus
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Mental retardation
Frontal bossing
Saddle nose
Protruding mandible
High arched palate
Perioral fissures
Higouemenaki’s sign(periosteal rxn
of clavicle, sternocleidomastoid)
• Saber shins
• Rhagades (linear scars that become
fissured or ulcerated)
Hutchinson’s teeth – peg shaped upper incisors
Frontal Bossing
Saber shins:
Anterior bowing of tibias
Gumma:
Thin atrophic scar
Diagnosis
Definitive diagnosis can be made by dark-field microscopy
on specimen from skin lesions, placenta, umbilicus.
Serologic tests are the principal means for diagnosis:
1) Nontreponemal test: VDRL, RPR
2) Treponemal tests: TPI, FTA-ABS, MHA-TP
Diagnosis
Nontreponemal: VDRL, RPR
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Quantitative results correlate with disease activity,
therefore helpful in screening.
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Titers rise when disease is active, fall when
treatment is adequate
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In congenital infxn. These tests become non- reactive
within a few months of adequate treatment.
Non-treponemal testing
Detects antibodies against a cardiolipin- cholestrollecithin complex, not specific for syphilis.
False Positives:
Only in serum, not in CSF testing
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certain viral infxns: infectious mononucleosis,
hepatitis, varicella, measles
lymphoma, TB, malaria, endocarditis,
connective tissue disease
pregnancy (?)
abuse of injection drugs
Diagnosis
A sustained 4 fold decrease in titer of nontreponemal
test after treatment demonstrates adequate therapy.
A 4 fold increase titer increase after treatment suggests
reinfection or relapse.
Confirmatory Testing
Treponemal Tests: TPI, FTA-Abs,
MHA-TP
Treponemal antibody titers become
positive soon
After initial infection and usually
remain positive
For life, even with adequate
therapy.
Antibody titers do not correlate
with disease activity, and
are not quantified.
Not 100% specific for syphilis:
other spirochetal dz,
Infant Testing
Reactive serology in neonate could be due to IgG passively
transferred to newborn through placenta, and does not indicate
active infection.
If infant’s titer higher than mother’s  congenital infection
If decreasing titer in infant  passive transfer of antibodies,
should disappear by 3-4 months of age.
Persistently reactive VDRL, with rising titer  Active Infection
Recommended Interpretation
Non-treponemal Test
(VDRL, RPR, EIA,
ART)
Treponemal Test
(MHA-TP, FTAABS)
Mother
Infant
Mother
Infant
Interpretation
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No syphilis or incubating syphilis in the mother and infant.
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+
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No syphilis in mother (false-positive non-treponemal test with
passive transfer to infant).
+
+/-
+
+
Maternal syphilis with possible infant infection; or mother
treated for syphilis during pregnancy; or mother with latent
syphilis and possible infection of infant.
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Recent or previous syphilis in the mother; possible infection in
the infant.
+
Mother successfully treated for syphilis before or early in
pregnancy; or mother with Lyme disease, yaws, or pinta (ie,
false-positive serology).
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-
+
CSF Examination
CSF abnormalities may occur
in congenital syphilis
Even in absence of neurologic
involvement.
* Leukocytosis
* Elevated protein in CSF
* positive VDRL
(no false positives)
Evaluation
• Maternal hx, results of
serologic testing
• Thorough P.E.
• Long bone xrays
• Non-treponemal AB
titer
• Treponemal AB titer
• Head US
• Csf Analysis for
VDRL, cell count &
protein
• CBC with platlets
• LFT’s
• UA
• Chest xray
• HIV antibody test
• Opthalmologic exam
Treatment
Proven or highly probable:
Aqueous crystalline Penicillin G
100,000-150,000U/kg/day
(given q8-q12hrs) IV for
10 days
OR
Procaine Penicillin G
50,000 U/kg/day IM for
10days
If >1 day of therapy missed, entire course should be restarted!
Treatment
Asymptomatic, Normal CSF exam, CBC, platelets, and
Radiologic exam:
1. No maternal tx  aqueous PCN G IV for 10-14 days
2. Tx w/ Erythromycin  clinical, serologic follow-up,
and Benzathine Pcn G IM x 1
3. Tx < 1month before
Delivery, or <4 fold
Decrease in titers  clinical, serologic follow-up and
Benzathine Pcn G IM x 1
Treatment
 Treat all newborns w/ positive VDRL as if they have
congenital syphilis, even if mother thought to not have an
active infection.
1. Difficult to document that mother received adequate tx,
and has falling VDRL titer.
2. Low titer VDRL test may be compatible with latent
maternal syphilis.
3. Newborn may not have clinical manifestations at birth.
4. Compliance with follow-up visits may be problem.
Follow-up
 Should have careful follow-up examination at
1, 2, 4, 6, and 12 months of age.
Serologic non-treponemal tests: 3, 6, 12 months, and end of tx
(or until non-reactive)
Non-treponemal Ab titers decline by 3 months of age, and
Should be Non-reactive by 6 months, if infant was not infected.
(transplacentally aquired antibodies.)
If persistent, stable titers, consider retreatment.
Congenital neurosyphilis- CSF exam at 6 month intervals until
normal
Research Advances
UT Southwestern Medical Center at Dallas research team has
develop 2 blood test that quickly and reliably diagnose
Congenital syphilis in newborns. (June, 2002)
Detect neonatal antibodies to the syphilis bacterium or the
DNA of the syphilis organism itself, as predictors of CNS
Invasion. (one day vs. ten days of PCN)
1. IgM Immunoblotting test 2. PCR
In 1998 scientist at UTHSC in Houston, Institute for Genomic
Research in Maryland, mapped the 1.1 million base pairs of DNA that
make up the syphilis genome.Entire genomic pattern of Treponema
Pallidum now known. Difficult to study previously b/c of
dependence on mamalian host for viability. New breakthroughs?