(See also Syphilis.)
Congenital syphilis is a multisystem infection caused by Treponema pallidum and transmitted to the fetus via the placenta. Early signs are characteristic skin lesions, lymphadenopathy, hepatosplenomegaly, failure to thrive, blood-stained nasal discharge, perioral fissures, meningitis, choroiditis, hydrocephalus, seizures, intellectual disability, osteochondritis, and pseudoparalysis (Parrot atrophy of newborn). Later signs are gummatous ulcers, periosteal lesions, paresis, tabes, optic atrophy, interstitial keratitis, sensorineural deafness, and dental deformities. Diagnosis is clinical, confirmed by microscopy or serology. Treatment is penicillin.
Overall risk of transplacental infection of the fetus is about 60 to 80%, and likelihood is increased during the 2nd half of the pregnancy. Untreated primary or secondary syphilis in the mother usually is transmitted, but latent or tertiary syphilis is transmitted in only about 20% of cases. Untreated syphilis in pregnancy is also associated with a significant risk of stillbirth and neonatal death. In infected neonates, manifestations of syphilis are classified as early congenital (ie, birth through age 2 yr) and late congenital (ie, after age 2 yr).
Many patients are asymptomatic, and the infection may remain clinically silent throughout their life.
Early congenital syphilis commonly manifests during the first 3 mo of life. Manifestations include characteristic vesiculobullous eruptions or a macular, copper-colored rash on the palms and soles and papular lesions around the nose and mouth and in the diaper area, as well as petechial lesions. Generalized lymphadenopathy and hepatosplenomegaly often occur. The infant may fail to thrive and have a characteristic mucopurulent or blood-stained nasal discharge causing snuffles. A few infants develop meningitis, choroiditis, hydrocephalus, or seizures, and others may be intellectually disabled. Within the first 8 mo of life, osteochondritis (chondroepiphysitis), especially of the long bones and ribs, may cause pseudoparalysis of the limbs with characteristic radiologic changes in the bones.
Late congenital syphilis typically manifests after 2 yr of life and causes gummatous ulcers that tend to involve the nose, septum, and hard palate and periosteal lesions that result in saber shins and bossing of the frontal and parietal bones. Neurosyphilis is usually asymptomatic, but juvenile paresis and tabes may develop. Optic atrophy, sometimes leading to blindness, may occur. Interstitial keratitis, the most common eye lesion, frequently recurs, often resulting in corneal scarring. Sensorineural deafness, which is often progressive, may appear at any age. Hutchinson incisors, mulberry molars, perioral fissures (rhagades), and maldevelopment of the maxilla resulting in “bulldog” facies are characteristic, if infrequent, sequelae.
Diagnosis of early congenital syphilis is usually suspected based on maternal serologic testing, which is routinely done early in pregnancy, and often repeated in the 3rd trimester and at delivery. Neonates of mothers with serologic evidence of syphilis should have a thorough examination, darkfield microscopy or immunofluorescent staining of any skin or mucosal lesions, and a quantitative nontreponemal serum test (eg, rapid plasma reagin [RPR], Venereal Disease Research Laboratory [VDRL]); cord blood is not used for serum testing because results are less sensitive and specific. The placenta or umbilical cord should be analyzed using darkfield microscopy or fluorescent antibody staining if available.
Infants and young children with clinical signs of illness or suggestive serologic test results also should have a lumbar puncture with CSF analysis for cell count, VDRL, and protein; CBC with platelet count; liver function tests; long-bone x-rays; and other tests as clinically indicated (ophthalmologic evaluation, chest x-rays, neuroimaging, and auditory brain stem response).
Syphilis can cause many different abnormalities on long-bone x-rays, including
The osteitis is sometimes described as "diffuse moth-eaten changes of the shaft." Metaphysitis commonly appears as lucent or dense bands that can alternate to give a sandwich or celery stalk appearance. The Wimberger sign is symmetric erosions of the upper tibia but there can also be erosions in the metaphysis of other long bones. Excessive callus formation at the ends of long bones has been described. Many affected infants have more than one of these findings.
Diagnosis is confirmed by microscopic visualization of spirochetes in samples from the neonate or the placenta. Diagnosis based on neonatal serologic testing is complicated by the transplacental transfer of maternal IgG antibodies, which can cause a positive test in the absence of infection. However, a neonatal nontreponemal antibody titer > 4 times the maternal titer would not generally result from passive transfer, and diagnosis is considered confirmed or highly probable. Maternal disease acquired late in pregnancy may be transmitted before development of antibodies. Thus, in neonates with lower titers but typical clinical manifestations, syphilis is also considered highly probable. In neonates with no signs of illness and low or negative serologic titers, syphilis is considered possible; subsequent approach depends on various maternal and neonatal factors (see Congenital Syphilis : Follow up).
The utility of fluorescent assays for antitreponemal IgM, which is not transferred across the placenta, is controversial, but such assays have been used to detect neonatal infection. Any positive nontreponemal test should be confirmed with a specific treponemal test to exclude false-positive results, but confirmative testing should not delay treatment in a symptomatic infant or an infant at high risk of infection.
Diagnosis of late congenital syphilis is by clinical history, distinctive physical signs, and positive serologic tests (see also Syphilis : Diagnostic tests for syphilis). The Hutchinson triad of interstitial keratitis, Hutchinson incisors, and 8th cranial nerve deafness is diagnostic. Sometimes the standard nontreponemal serologic tests for syphilis are negative, but the fluorescent treponemal antibody absorption test (FTA-ABS) is positive. The diagnosis should be considered in cases of unexplained deafness, progressive intellectual deterioration, or keratitis.
All seropositive infants and those whose mothers were seropositive should have VDRL or RPR titers every 2 to 3 mo until the test is nonreactive or the titer has decreased 4-fold. In uninfected and successfully treated infants, nontreponemal antibody titers are usually nonreactive by 6 mo. Passively acquired treponemal antibodies may be present for longer, perhaps 15 mo. It is important to remember to use the same specific nontreponemal test to monitor titers in mothers, neonates, infants, and young children over time.
If VDRL or RPR remain reactive past 6 to 12 mo of age or titers increase, the infant should be reevaluated (including lumbar puncture for CSF analysis, and CBC with platelet count, long-bone x-rays, and other tests as clinically indicated).
Pregnant women in the early stages of syphilis receive benzathine penicillin G (2.4 million units IM in a single dose). For later stages of syphilis or neurosyphilis, the appropriate regimen for nonpregnant patients should be followed (see Syphilis : Late or tertiary syphilis). Occasionally, a severe Jarisch-Herxheimer reaction occurs after such therapy, leading to spontaneous abortion. Patients allergic to penicillin may be desensitized and then treated with penicillin.
After adequate treatment, RPR and VDRL test results decrease 4-fold by 6 to 12 mo in most patients and revert to negative by 2 yr in nearly all patients. Erythromycin therapy is inadequate for both the mother and fetus and is not recommended. Tetracycline is contraindicated.
In confirmed or highly probable cases, 2015 Centers for Disease Control and Prevention (CDC) guidelines for congenital syphilisrecommend aqueous crystalline penicillin G 50,000 units/kg IV q 12 h for the first 7 days of life and q 8 h thereafter for a total of 10 days or procaine penicillin G 50,000 units/kg IM once/day for 10 days (see Table: Recommended Dosages of Selected Parenteral Antibiotics for Neonates). If ≥ 1 day of therapy is missed, the entire course must be repeated. This regimen is also recommended for infants with possible syphilis if the mother fits any of the following criteria:
In infants with possible syphilis whose mothers were not adequately treated but who are clinically well and have a completely negative full evaluation, a single dose of benzathine penicillin 50,000 units/kg IM is an alternative treatment choice in selected circumstances, but only if follow-up is assured.
Infants with possible syphilis whose mothers were adequately treated and who are clinically well can also be given a single dose of benzathine penicillin 50,000 units/kg IM. Alternatively, if close follow-up is assured, some clinicians defer penicillin and do nontreponemal serologic testing monthly for 3 mo and then at 6 mo; antibiotics are given if titers rise or are positive at 6 mo.
CSF should be examined before treatment starts. The CDC recommends that any child with late congenital syphilis be treated with aqueous crystalline penicillin G 50,000 units/kg IV q 4 to 6 h for 10 days. A single dose of benzathine penicillin G 50,000 units/kg IM may also be given at the completion of the IV therapy. Alternatively, if a full evaluation is completely negative and the child is asymptomatic, benzathine penicillin G 50,000 units/kg IM once/wk for 3 doses may be used.
Many patients do not revert to seronegativity but do have a 4-fold decrease in titer of reagin (eg, VDRL) antibody. Patients should be reevaluated at regular intervals to ensure the appropriate serologic response to therapy has occurred and that there is no indication of relapse.
Interstitial keratitis is usually treated with corticosteroid and atropine drops in consultation with an ophthalmologist. Patients with sensorineural hearing loss may benefit from penicillin plus a corticosteroid such as prednisone 0.5 mg/kg po once/day for 1 wk, followed by 0.3 mg/kg once/day for 4 wk, after which the dose is gradually reduced over 2 to 3 mo. Corticosteroids have not been critically evaluated in these conditions.
Pregnant women should be routinely tested for syphilis in the 1st trimester and retested if they acquire other sexually transmitted diseases during pregnancy. In 99% of cases, adequate treatment during pregnancy cures both mother and fetus. However, in some cases, syphilis treatment late in pregnancy eliminates the infection but not some signs of syphilis that appear at birth. Treatment of the mother < 4 wk before delivery may not eradicate fetal infection.
When congenital syphilis is diagnosed, other family members should be examined for physical and serologic evidence of infection. Retreatment of the mother in subsequent pregnancies is necessary only if serologic titers suggest relapse or reinfection. Women who remain seropositive after adequate treatment may have been reinfected and should be reevaluated. A mother without lesions who is seronegative but who has had venereal exposure to a person known to have syphilis should be treated, because there is a 25 to 50% chance that she acquired syphilis.
Manifestations of syphilis are classified as early congenital (birth through age 2 yr) and late congenital (after age 2 yr).
Risk of transmission of maternal primary or secondary syphilis is 60 to 80%; risk of transmission of latent or tertiary syphilis is about 20%.
Diagnose clinically and by serologic testing of mother and child; darkfield examination of skin lesions and sometimes of placenta and umbilical cord samples may help diagnose early congenital syphilis.
Treat with parenteral penicillin.