This document describes the case of a 0-day-old female infant admitted for respiratory distress. She was born at 37 weeks gestation to a mother who tested positive for syphilis during the third trimester. On examination, the infant had hepatomegaly, jaundice, and laboratory findings consistent with congenital syphilis. She received IV penicillin treatment and improved. However, she later developed projectile vomiting and was found to have hypertrophic pyloric stenosis requiring surgery. Her growth remained poor and she continued to have liver dysfunction, consistent with sequelae of congenital syphilis.

1. Congenital syphilis
高雄榮總新生兒科
張振宗

2. Patient profiles
• Name：沈X爰
• Age：0-day-old
• Sex：Female
• Date of Admission：2023/06/17

3. Chief complaint
Respiratory distress with tachypnea, subcostal
retraction and desaturation after birth.

4. Birth history
• Gestational age: 37 weeks
• Birth weight: 2764 gm
• Apgar score: 5(1st min)-＞8(5th min)
• via NSD at 2023/06/17 17:00

5. Maternal history
• 22-year-old woman, G1P1, HBsAg/HBeAg(-/-), HIV(-), Rubella IgG(+), GBS(-), GDM(-),
PIH(-), Pre-eclampsia(-)
• Amniocentesis: no abnormalities
• 1st RPR test on 2022/11/28: negative

6. Maternal history
• Fetal ultrasound in May: ascites(+)
• 2nd RPR test on 2023/6/9: positive (RPR 1:128, TPPA 1:5120)
• s/p Benzathine penicillin G 2.4MU IM x1 dose on 6/14.
• Follow-up fetal ultrasound on 6/14: No more ascites, but hepatomegaly(+)
• Uterine contractions and premature rupture of membrane on 6/16.
• Cefazolin was given regularly since 6/17 early morning and the baby was delivered at
17:00 on 6/17.

7. Physical examination
• BW: 2764 gm (15th percentile), HC: 32 cm (3-15th
percentile), BL: 51 cm? (85th percentile)
• BP: 61/41 mmHg, HR: 144 /min, RR: 47 /min,
BT: 36.7 ℃
• Acute ill-looking, fair activity
• HEENT: grunting(-), nasal flaring(-), conjunctival
congestion(-), icteric sclera(-).
• Ant. fontanelle: soft and flat, 1.5 fb in width
• Neck: supple, no LAP
• Chest: tachypnea(+), bilateral coarse breath
sound(+), subcostal retraction(+)
• Heart: regular heart beats, no murmur
• Abdomen: soft and mild distension,
normoactive bowel sounds, hepatomegaly(+)
• Extremities: freely movable
• Skin: no skin rash, no cyanosis
• Genitalia: female
• Umbilical cord: 2A1V

8. 2023/6/17
1st Hospital Course
• No delay of initial crying
• Bradycardia at birth s/p ambu-bagging twice
before her heart rate and activity improved.
• Respiratory distress with tachypnea and
subcostal retraction
• Saturation was 70-80% under room-air
ambience
6/17

9. Approach to evaluation and management of newborns born
to mothers who tested positive for syphilis during pregnancy
• Hepatosplenomegaly,
• rash,
• condyloma lata,
• snuffles,
• jaundice (nonviral hepatitis),
• pseudoparalysis,
• pallor (anemia), or
• edema (nephrotic syndrome
and/or malnutrition)

11. 2023/6/17
1st Hospital Course
• WBC:37.28 K/uL, HGB:15.6 g/dL, PLT:67 K/uL, BAND:5.9%,
SEG:39.5%, LYM:44.9%, MONO:2.9%, ATY LYM:0.5%, META:1.9%,
MYELO:1.5%, PROMYELO:1.0% (I/T ratio: 20.6%)
• CRP:5.89 mg/dL;
• GPT/GOT:89/283 U/L;
• D/T.BIL:2.0/3.5 mg/dL;
• IgM:613.3 mg/dL;
• RPR test (blood): REACTIVE 1:≥1024 (Mother: RPR 1:128)
(report on 6/19)

12. 2023/6/17
1st Hospital Course
• Lumbar puncture:
Nucleated cells:600 cells/mm3, (>15/mm3 in a term newborn; >5/mm3 after 1 m/o)
NEUTRO:21%, LYM:75%, MONO:4%;
RBC:102600 /cumm;
Sug:31 (65 in serum) mg/dL;
Protein:255.0 mg/dL; (>150 mg/dL in a term newborn; ≥45 mg/dL after 1 m/o)
Lactate:1.36 mmol/L;
Bacteria Ag: negative;
VDRL: REACTIVE 1:≥1024 (report on 6/19)

13. 2023/6/17
1st Hospital Course
• Tentative diagnosis:
1. Neonatal respiratory distress, cause?
2. R/O congenital syphilis
• Management:
1. NPO first
2. Nasal CPAP with FiO2:30%, Flow: 5 L/min, PEEP: 5 cmH2O
3. Penicillin 140000 U, q12h (50000 U/kg/dose) and Cefotaxime 140
mg, q8h (150 mg/kg/day)

15. 1st Hospital Course
• Nasal CPAP was off at 6 am on 6/21.
• Direct type neonatal jaundice, and light yellowish
stool noted since 6/25.
->Try Ursolic treatment since 6/28, but in vain.
• Abdominal sonogram: hepatomegaly (+), no
splenomagaly
• Echocardiogram: Mild PS and trivial PDA
• OPH: no ophthalmologic manifestations of syphilis
• aABR test: “PASS”
2023/6/18
-
2023/7/5

16. 1st Hospital Course
2023/6/18
-
2023/7/5
I/T ratio 20.6%
I/T ratio 4%

17. 2023/6/18
-
2023/7/5
1st Hospital Course

18. 1st Hospital Course
• 2nd lumbar puncture on 6/27:
-> VDRL: REACTIVE 1:≥1024
• Completed a 10-day antibiotic treatment course with
Penicillin 50000 U/kg/dose, q12h x7 days and then
50000 U/kg/dose, q8h x3 days.
• Transferred to SBR on 6/30.
• Intermittent tachypnea and feeding difficulty.
• MBD on 7/5.
2023/6/18
-
2023/7/5

19. Hepatomegaly (+);
No obvious
periostitis or other
bony abnormality
2023/6/18
-
2023/7/5
6/27

20. Final diagnosis
1. Congenital syphilis s/p 10 days of IV aqueous crystalline penicillin G treatment
⚫ The diagnosis could be made by laboratory results:
✓ Her RPR titer was at least fourfold higher than her mother’s. (1:≥1024 of the patient vs.
1:128 of the mother)
⚫ Other clinical manifestations that resulted from congenital syphilis:
✓ Leukocytosis and thrombocytopenia.
✓ Hepatomegaly, liver function impairment and direct type neonatal jaundice.
✓ Congenital pneumonia with respiratory distress s/p nasal CPAP.
✓ R/O CNS syphilis (positive VDRL titer, 1:≥1024 , in CSF).

21. 2023/7/21
2nd Hospital Course
• Easy milk regurgitation or even non-bilious
projectile vomiting since 7/18.
• As frequently as 4-5 times in 2 hours.
• Under breast milk feeding, 95->70 cc/q4h
• Abdominal sonogram: c/w idiopathic
hypertrophic pyloric stenosis (IHPS)
- The muscle thickness:3.3 mm. (>3)
- The length of pyloric canal: 20.7 mm. (>16)
- The diameter of pylorus: 13.7 mm. (>3)
7/21

22. Physical examination
• BW: 2912 gm (<3rd percentile), HC: 33.5 cm (<3rd
percentile), BL: 48 cm (<3rd percentile)
• BP: 91/63 mmHg, HR: 150 /min, RR: 56 /min,
BT: 36.5 ℃
• Acute ill-looking, fair activity
• HEENT: injected throat(-), conjunctival
congestion(-), icteric sclera(+)
• Ant. fontanelle: soft and flat, 1.5 fb in width
• Chest: clear breath sound, no retraction
• Heart: regular heart beats, no murmur
• Abdomen: soft and distension, normoactive
bowel sounds, hepatomegaly(+)
• Extremities: freely movable
• Skin: grey-yellowish skin color(+); some
petechiae over nasal bridge and the areas
below both eyes(+)
• Genitalia: female

24. 2023/7/21
2nd Hospital Course
• CRP:0.72 mg/dL; WBC:20.48 K/uL, HGB:15.7 g/dL, PLT:230 K/uL,
SEG:15.5%, LYM:76%, MONO:5.5%, ATY LYM:1.5%
• GPT/GOT:89/343 U/L, D/T.BIL:7.2/15.4 mg/dL
• PT:14.8 (INR:1.32); APTT:43.0 (control:33.4)
• RPR test: REACTIVE 1:256, more than 4 folds of decline while
compared to 1:≥1024 at birth (6/17).
• Laparoscopic pyloromyotomy and wedge liver biopsy
✓ Negative immunostains for treponema, CMV and HSV.
2023/7/24

25. 2nd Hospital Course
• Fair oral feeding condition after the surgery.
• Transferred to SBR on 7/28 and MBD on 8/2 .
• Note:
Cytomegalovirus (CMV) from throat isolation;
Adenovirus from rectal isolation.
-> Clinical significance?
2023/7/24
-
2023/8/2

26. Final diagnosis
1. Idiopathic hypertrophic pyloric stenosis (IHPS) s/p laparoscopic pyloromyotomy
2. Congenital syphilis with hepatomegaly, liver function impairment and
cholestasis
⚫ The latest RPR titer was 1:256 on 7/21, more than 4 folds of decline (1:≥1024 at birth on
6/17).
3. Failure to thrive

27. 2023/8/17
at 2 m/o
The latest OPD follow-up
• BW: 3300 gm (<3rd percentile), HC: 35.5 cm (<3rd percentile),
BL: 52 cm (<3rd percentile)
• Easy-looking, no cardio-pulmonary distress
• Under formula-fed with Alfare, 0.8 kcal/cc, 85 cc/q4-5h
-> Change milk strength to 0.9 kcal/cc.
• Yellow-greenish stools now.
• CRP:0.18 mg/dL; WBC:19.46 K/uL, HGB:13.6 g/dL, PLT:301 K/uL,
SEG:28%, LYM:62%, MONO:6%, ATY LYM:1%
• GPT/GOT:92/145 U/L, D/T.BIL:4.2/7.6 mg/Dl, GGT:68 U/L

28. Discussion
Congenital syphilis

29. Epidemiology
• Incidence – reflects the rate of syphilis in women of childbearing age;
complicating an estimated one million pregnancies per year throughout the
world.
• USA, 2020: 2152 reported cases rate (57 cases per 100,000 live births)
including 122 syphilitic stillbirths and 29 infant deaths

32. Risk factors
• Poor access to prenatal care
✓Near one-quarter were born to mothers who did not receive prenatal care.
✓Among those who received prenatal care, 43% received no treatment for syphilis during
the pregnancy and 30% received inadequate treatment.
• Social vulnerabilities including homelessness, substance abuse, and
incarceration were found to be barriers to timely diagnosis and treatment.
• The rate of congenital syphilis increases in mothers with HIV infections.

33. Transmission
• Humans are the only natural host of Treponema pallidum.
• Transplacental transmission during maternal spirochetemia; occurs with
increasing frequency as gestation advances.
• Direct contact with an infectious lesion during birth.
• Not transferred in breast milk, but transmission may occur if the mother has
an infectious lesion (eg, chancre) on her breast.

34. Pathogenesis
• T. pallidum directly into the circulation of the fetus.
-> Spirochetemia with widespread dissemination to almost all organs.
-> Clinical manifestations are the results of inflammation in the affected
organs.
• The severity of illness is variable: from isolated laboratory or radiographic
abnormalities to fulminant involvement of multiple organ systems.

35. Clinical manifestations
• Early congenital syphilis — onset before 2 y/o
• Clinical findings — in untreated infants usually appear by 3 months of age, most
often by 5 weeks
• Approximately 60-90% asymptomatic at birth.
• Among symptomatic infants, the most common findings are hepatomegaly,
jaundice, nasal discharge ("snuffles"), rash, generalized lymphadenopathy and
skeletal abnormalities.

38. 具傳染性，須做好防護措施!!!

39. https://www.cdc.gov/ncbddd/birthdefects/surveillancemanual/
quick-reference-handbook/congenital-syphilis.html

41. https://radiopaedia.org/articles/wimberger-sign-1
在沒治療的early congenital syphilis病人中，大約60-80%會有骨頭方面的異常，而且可能是
唯一症狀
大多是雙側、對稱、多處
大多是單側、發生於上肢、很少一出生
就出現、跟X光的異常發現不見得吻合

43. 大約40%的CNS syphilis只是實驗室數據異常而沒有臨床上的症狀
A fluffy, diffuse infiltrate involving all lung areas is
more common in the era of penicillin therapy.

44. Clinical manifestations
• Late congenital syphilis — onset after 2 y/o
• Scarring or persistent inflammation from early infection→ “gumma” formation in various
tissues
• Develop in approximately 40% infants born to women with untreated syphilis during
pregnancy.
• Most are prevented by appropriate treatment of the mother during pregnancy or by
treatment of the infant within the first 3 months.
• Other manifestations (eg, keratitis, saber shins) may occur or progress despite appropriate
therapy.

45. 雙側、通常在青春期左右發生
突然在8-10歲發生、常伴隨interstitial keratitis
Hutchinson triad
Relatively specific for congenital syphilis

46. Gummas
https://www.merckmanuals.com/en-
ca/professional/multimedia/image/syphilis-gumma
https://doi.org/10.5070/D35gs4q6wz

48. Higoumenakis sign
https://slideplayer.com/slide/9719222/
doi:10.1001/archderm.1940.01490120062008
https://www.slideshare.net/priya2486/syphilis-65695419

49. Clinical suspicion
✓ Unexplained prematurity
✓ Unexplained hydrops fetalis
✓ Enlarged placenta
✓ Failure to move an extremity (“pseudoparalysis)
✓ Persistent rhinitis
✓ Maculopapular or papulosquamous rash, particularly
in the diaper area, palms, and soles
✓ Jaundice, hepatomegaly
✓ Neonatal pneumonia
✓ Generalized lymphadenopathy
✓ Anemia (direct Coombs test negative)
✓ Thrombocytopenia
• Maternal syphilis during pregnancy
• Maternal syphilis during the first 3 months after delivery
• Concerning clinical findings (but nonspecific):

50. Diagnosis
• The diagnosis of syphilis is challenging because T. pallidum cannot be cultured in the lab.
• May be established by:
➢Demonstration of serologic reactions typical of syphilis.
✓ Serology tests include nontreponemal tests (eg, VDRL and RPR) and treponemal tests (eg, TPPA).
✓ Serology tests detect IgG antibodies and do not differentiate between passively acquired maternal antibody and
endogenous antibody produced by the fetus/neonate.
✓ A sufficiently sensitive and specific IgM assay is not available for routine use in the assessment of congenital
syphilis.
➢Detection of T. pallidum in infected body fluids, skin lesions, placenta, or umbilical cord by
direct visualization on darkfield microscopy, DFA, or PCR.
➢Detection of the T. pallidum by special stains or histopathologic examination.

51. Nontreponemal tests
• VDRL (Venereal Disease Research Laboratory) and RPR (Rapid Plasma Reagin)
✓Sensitive, but not specific.
✓The neonate’s titer usually is one to two dilutions less than mother’s.
✓Lower titers or even nonreactive serology in the newborn do not exclude congenital
syphilis.
✓Nontreponemal titers are also useful for monitoring during treatment.

52. Treponemal tests
• Include FTA-ABS (fluorescent treponemal antibody absorption), TP-PA (T. pallidum particle
agglutination), MHA-TP (microhemagglutination test for T. pallidum), EIA and CIA.
• Not used in the evaluation of newborns with suspected congenital syphilis when maternal
treponemal test results are available.
• Not used in the follow-up evaluations because it remains positive despite effective
treatment.
• A positive treponemal test at ≥18 months of age (after the disappearance of passively
acquired maternal antibody) confirms the diagnosis of congenital syphilis.

53. Other tests
• Darkfield microscopy
• DFA (direct flourescent antibody) testing
• PCR
• Immunohistochemistry or special staining
(eg, silver staining)
• Can be used to detect the organism
directly.
• Not routinely available in many clinical
settings -> being viewed as alternative
diagnostic tools.

54. Approach to evaluation and management of newborns born
to mothers who tested positive for syphilis during pregnancy

57. Follow-up evaluations
• Examination: should carefully assess for manifestations of congenital syphilis.
• Developmental surveillance and sensory screening
✓ Yearly hearing evaluation
✓ Yearly vision screening and eye examination
✓ Serial developmental assessments throughout infancy and childhood
• Follow-up serologic testing
✓ All infants born to mothers with syphilis require follow-up serologic monitoring, regardless
of whether seropositive or seronegative at birth and whether the infant was treated with
penicillin.

58. Follow-up evaluations
• Timing of testing – Follow-up serologic testing every 2-3 months, until the test becomes
nonreactive or the titer has decreased fourfold.
• Tests to perform
- Nontreponemal tests (ie, VDRL or RPR titers)
- Ideally with the same test as was used in the newborn
- Treponemal tests should not be used to evaluate treatment response -> remain
positive despite effective treatment.

59. Follow-up evaluations
• Expected response: successfully treated or not infected
-> VDRL or RPR titers should decline by 3 m/o and be nonreactive by 6 m/o.
• Treatment failure:
-> Failure of the VDRL or RPR titers to decline, or
-> Increase in the VDRL or RPR after 6 to 12 m/o
-> Should undergo a lumbar puncture for VDRL, cell count, and protein, and be treated with
an extended course of parenteral penicillin, even if the infant/child was treated previously.

60. Follow-up evaluations
• Repeat CSF evaluations are generally not necessary unless the infant has persistently
positive nontreponemal titers at 6 to12 m/o.
• If repeat LP abnormal (ie, reactive CSF VDRL or abnormal CSF WBC or protein that
cannot be attributed to other ongoing illnesses) -> should be treated with an extended
course of parenteral penicillin therapy.
• Neuroimaging studies may be warranted in children with persistently reactive CSF VDRL,
elevated CSF cell count, and/or elevated CSF protein.

61. Outcome
• In USA, fatality rate for congenital syphilis: 6-8%, approximately 90% with lack of or inadequate
prenatal care.
• Syphilis infection may persist for life.
- History of syphilis -> relatively unreliable protection against subsequent infection.
- Active disease after reinfection is common, regardless of nontreponemal antibody reactivity.
• Interstitial keratitis and “saber shins” may occur or progress despite appropriate therapy.
• Appropriate treatment of early congenital syphilis within the first 3 months after birth
prevents most late manifestations.

62. Thanks!

64. United States Centers for Disease Control and Prevention
surveillance case definition for congenital syphilis