Congenital syphilis

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.