Congenital syphilis
From IDWiki
Background
Epidemiology
- Rare, with about 20 per 100,000 live births in the US
- Greatest risk to child is with untreated primary maternal syphilis, and almost exclusively to those mothers with an RPR titre of 1:8 or greater
Pathophysiology
- Transplacental transmission while bacteremic
- Can be transmitted during delivery, as well
Clinical Manifestations
- Mothers typically have had no prenatal care
- To the fetus, can cause spontaneous abortion (40% in untreated primary syphilis), preterm delivery, polyhydramnios, intra-uterine growth restriction, hydrops fetalis, or intra-uterine fetal demise
- At birth, two thirds of affected neonates are asymptomatic, with disease developing over the following 6 weeks
- Early disease, within the first two years, includes:
- At birth: necrotizing funisitis ("barbershop pole" umbilical cord)
- Shortly after birth:
- Rhinitis: called snuffles, often bloody and copious, which is often the first manifestation and present in about 40% of cases
- Musculoskeletal abnormalities start within a week of birth and develop over the child's lifetime
- Start as radiographic osteochondritis or perichondritis
- Later, pseudoparalysis, followed by the late findings described below
- At birth or delayed:
- Hematologic abnormalities, including anemia and thrombocytopenia
- Neurosyphilis in 50% of cases and usually asymptomatic
- Within the first eight weeks:
- Hepatomegaly and splenomegaly in 20%, and persists for years
- Rash in 50%, usually a diffuse maculopapular rash, but may be desquamating, vesicular, bullous, papulosquamous, or involve mucosal lesions
- Also: lymphadenopathy, condyloma lata, vesicular rash or bullous rash, periostitis, hydrops, hepatitis, jaundice, or glomerulonephritis
- Late disease, after the first two years, includes:
- Age 2-20 years: interstitial keratitis
- When permanent dentition appears: Hutchison teeth, with widely-spaced, screwdriver-shaped central and lateral incisors
- Age 10-40 years: sensorineural hearing loss
- Age 13-19 years: mulberry molars, where the first molars have dwarfing of the cusps and hypertrophy of the enamel surrounding the cusp
- Musculoskeletal abnormalities:
- Eventually frontal bossing, poorly-developed maxilae, saddle nose deformity, winged scapulae, and sabre shins, short stature
- Recurrent arthropathy and painless knee effusions (Clutton joints) as late disease
- Intellectual impairment
Hutchison Triad
- The classic triad of late congenital syphilis
- Includes:
- Sensorineural hearing loss from cranial nerve VIII
- Interstitial keratitis
- Abnormal dentition, including Hutchison teeth and mulberry molars
Diagnosis
- Darkfield microscopy and/or PCR on body fluids, including nasal discharge or CSF
- Serology
- RPR on infant blood (not cord blood), paired with maternal RPR
- May need CSF analysis
- Also check HIV serology, skeletal survey, chest x-ray, ophthalmology, audiology, and cranial ultrasound
Management
- Treat syphilis in pregnancy with penicillin to prevent congenital syphilis
- For infants that require treatment, the treatment of choice is crystalline penicillin G
- Age 1 to 7 days: 50,000 U/kg IV q12h
- Age 1-4 weeks: 50,000 U/kg q8h
- Age >4 weeks: 50,000 U/kg q6h
- Duration is typically 10 days
- Don't forget to dose adjust from q12h to q8h after the first 7 days
- Can treat lower-risk infants with benzathine penicillin G 50,000 U/kg IM once
Canadian Guidelines
- Treat infants at birth if:
- Symptomatic
- Infant's RPR at least four-fold higher than mother's
- Maternal treatment inadequate, did not contain penicillin, is unknown or occurred in the last month of pregnancy, or if the maternal serologic response is inadequate
- Adequate follow-up can't be ensured
- Specific scenarios are described in the table below
Maternal treatment | Neonatal assessment | Recommendations | |||||
---|---|---|---|---|---|---|---|
Type | Timing | Outcome | Monthly exam for 3 months | Serology | CBC/CSF/x-rays | Treatment | |
any | before pregnancy | adequate, with no RPR rise and no risk factors for reinfection | normal exam | no | no | no | none |
primary, secondary, or early latent | >4 weeks before delivery | adequate | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months | no | none |
≤4 weeks before delivery | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | usually | ||
not penicillin | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | usually | ||
before or during pregnancy | RPR not decline as expected | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | usually | |
before pregnancy | inadequate, or reinfection | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | consider | depends on risk and results of assessments | |
during pregnancy | unknown | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | consider | depends on risk and results of assessments | |
primary or secondary syphilis | during pregnancy | inadequate | normal exam, RPR < 4-fold maternal | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days |
late latent | during or after pregnancy | adequate | normal exam, RPR < 4-fold maternal | no | 0, 6, and 18 months | no | none |
any | during pregnancy | normal exam, RPR < 4-fold maternal | follow-up unlikely | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | consider | depends on risk and results of assessments |
any | any | treponemes on tissue examination | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |
infant's RPR four-fold or greater than the mother's at birth | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |||
four-fold rise in infant's titre | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |||
signs of congenital syphilis at any age | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |||
RPR & TT reactive at 6 months | — | — | yes | usually | |||
reactive RPR & TT at 12 months | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days | |||
reactive TT at 18 months | yes | 0, 3, 6, and 18 months; if not treated, also at 1, 2, and 12 months | yes | 10 days |
- Serology includes RPR and treponemal tests
- In the absence of congenital syphilis, RPR declines by about three months and is usually non-reactive by 6 months, and treponemal tests usually clear by 12 months and always by 18 months
- Investigations include long-bone x-rays, CBC, and CSF (for glucose, protein, and VDRL), ± ophthalmological and audiological tests
- Skin lesions, nasal discharge, placental lesions, and the umbilical cord can be sent for darkfield microscopy or DFA testing
US Guidelines
Initial neonatal assessment | Maternal treatment | Recommendations | |||
---|---|---|---|---|---|
RPR/VDRL | Evaluation | Timing | Type | Evaluation | Treatment |
any | physical exam suggests congenital syphilis | any | any | LP and CBC | 10 days |
spirochete in a clinical specimen | |||||
≥ fourfold maternal titre | any | any | any | LP and CBC | 10 days |
less than fourfold maternal titre | normal | before pregnancy | adequate | none | none (or one dose) |
reinfection or relapse (≥4-fold increase in titre) | LP and CBC | one dose (unless exam at all abnormal) | |||
during pregnancy | adequate | none | one dose (or none) | ||
inadequate or suboptimal | LP and CBC | one dose (unless exam at all abnormal) | |||
nonreactive | normal | during pregnancy | adequate | none | none (or one dose) |
inadequate or suboptimal | none | one dose |
- LP should be sent for VDRL, cell count, protein
- CBC with differential for platelet count
Further Reading
- Congenital syphilis: No longer just of historical interest. Canadian Paediatric Society Practice Point, reaffirmed 2018.