CONGENITAL SYPHILIS

SINDHU E. PHILIP, MD.DEPARTMENT OF PEDIATRICS 09/20/02

Introduction

Infant usually infected in utero by transplacental passage ofTreponema 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 motherto fetus before 5th month of gestation, but classicpathologic changes do not occur until after 5th month.

Infection involves the placenta, and spreads hematogenously to the fetus, widespread involvementis characteristic. Infected placenta is paler, thicker,and larger than normal.

Clinical Manifestations

Damage to fetus depends on the stage of developmentat which infection has taken place and time elapsed before treatment. Early infection, untreated: miscarriage, stillbirth, neonataldeath, IUGR, premature delivery.

Survivors:Early congenital syphilis: clinical manifestations within first 2 years of lifeLate congenital syphilis: clinical manifestations after 2yo.

Early Congenital Syphilis

• 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

Early manifestations are varied, with multi-system Involvement

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 tibiametaphysis

Late Congenital Syphilis

• 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

• 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)

Results primarily from chronic inflammation of bone, teeth,and CNS.

Hutchinson’s teeth – peg shaped upper incisors

Frontal Bossing

Saber shins:Anterior bowing of tibias

Gumma:Thin atrophic scar

Diagnosis

Serologic tests are the principal means for diagnosis:

1) Nontreponemal test: VDRL, RPR

2) Treponemal tests: TPI, FTA-ABS, MHA-TP

Definitive diagnosis can be made by dark-field microscopy on specimen from skin lesions, placenta, umbilicus.

Diagnosis

Nontreponemal: VDRL, RPR

Quantitative results correlate with disease activity,therefore helpful in screening.

Titers rise when disease is active, fall when treatment is adequate

In congenital infxn. These tests become non- reactivewithin a few months of adequate treatment.

Non-treponemal testingDetects antibodies against a cardiolipin- cholestrol-

lecithin complex, not specific for syphilis.

False Positives: Only in serum, not in CSF testing

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 suggestsreinfection 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 passivelytransferred to newborn through placenta, and does not indicateactive 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

Non-treponemal Test(VDRL, RPR, EIA,

ART)

Treponemal Test(MHA-TP, FTA-

ABS)

Mother Infant Mother Infant Interpretation

- - - - No syphilis or incubating syphilis in the mother and infant.

+ + - - 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.

+ + + + 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).

Recommended Interpretation

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 G100,000-150,000U/kg/day(given q8-q12hrs) IV for10 days

ORProcaine 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 CNSInvasion. (one day vs. ten days of PCN)1. IgM Immunoblotting test 2. PCR

In 1998 scientist at UTHSC in Houston, Institute for GenomicResearch in Maryland, mapped the 1.1 million base pairs of DNA thatmake up the syphilis genome.Entire genomic pattern of TreponemaPallidum now known. Difficult to study previously b/c of dependence on mamalian host for viability. New breakthroughs?