Joint OB / Pediatrics M&M conference

PERINATAL CASE PRESENTATION AND DISCUSSION OF SEROLOGYCALLY POSITIVE MOTHER and INFANT FOR SYPHILIS

Christian Castillo, MD BK Rajegowda, MD

Congenital Syphilis
Syphilis is a Sexually transmitted disease Congenital Syphilis is a consequence of untreated or Inadequately treated maternal syphilis Rare but still occurs. A recent increase in cases is reported Prevention, early diagnosis and treatment will prevent fetal and neonatal infections

Presentation of cases Mothers profiles

Case #1 MR#2310021 Age Race Parity PNC 19 Hispanic G3P0020 Neighborhood Health Center ??? First time in LH RPR by Hx reactive and treated 2yrs ago at the health department. No documentation RPR 3/27/09 1:4 3/28/09 Penicillin B 2.4 IM 4/13/09 PNC #2 after Delivery at the clinic 4/1/09Patient DC AMA Case #2 MR#2310056 24 Black African American G6P3024 LH X 5 Late registrant at 34wk Case #3 MR#2310550 19 Caucasian G3P0020 LH X 10 late registrant at 19 wk 12/17/08 RPR 1:8 1st visit

Time / Date serology

2/23/09 RPR 1:32 first visit

Treatment

3/6/09 Pen G 2.4 mill second V 3/20/09 pen G 2.4 mill

1/26/09 Documented only prescription given for Pen B X 3 3/9/09 RPR 1:8 No Tx 3/23/09 RPR 1:8 no Tx Visit 4/7/09 refers to past Tx but not documentation 4/19/09 4/19/09 RPR 1:16 Mother tx after delivery

Follow up serology tx

No follow up titers before delivery

Day of Delivery Follow up Serology after Birth

3/28/09 No follow up serology. Post Natal visit 4/13/09

4/4/09 4/6/09 after delivery RPR 1:4 4/6/09 Pen G 2.4 mill

Case #1 Maternal tx undocumented, unknown PNC Delivery 3/28/09 FTAGA female born via C section at 40.3w by LMP Apgar 9 @ 1 min and 9 @ 5 min BWt: 3495 gms; L: 50.5 cms; HC: 34.5 cms; CC: 35 cms; Ag: 33 cms; SROM at 18:30hrs the day PTD, 13hr PTD; AF: clear Time of birth: 07:23hrs Normal VS and PE In view of unknown Labs and treatment prior to delivery, normal PE we decided to work up and treat this baby as unlikely syphilis

Patients profile

Cord RPR 3/28/09 1:2 TPPA reactive CBC: 30.9/19.3/59/212 N73 Band 3 L 15 Long bone X ray , WNL
CSF studies RBC 19519 WBC 5 Seg 70 Lymp 25 Mono 3 Eos 2 Glucose 46 protein 141 VDRL CSF no reactive 4/1/09 Tx Pen Benz 175000 Units IM 4/1/09 Discharge patient 5/7/09 Serum Patients RPR no reactive TPPA reactive IgG ab reactive

Patients profile
Case # 2 Maternal Late registrant, PNC X 5 LH RPR 1:32 no follow up titers Delivery 4/4/09 FT AGA, NSVD at 38.1 by LMP to 24 y/o G6P3024 APGAR 9@ 1 min and 9 @ 5 min B Wt: 3535 g, Length: 52.5 cm, HC: 35 cm, CC: 34 cm, AC: 35.5 cm ROM: 6 . AF: clear at the time of birth 10.07am normal VS and PE 4/4/09 Cord RPR 1:16 TPPA reactive 4/5/09 Patient Plasma RPR 1:16 TPPA reactive 4/6/09 CSF studies RBC 475 WBC 4 Glucose 38 protein 132 VDRL CSF no reactive 4/7/09 Long bones X- R WNL 4/7/09 , 4/8/09 / 4/9/09 Tx Pen Procaine until VDRL CSF no reactive 4/9/09 RPR 1:8 TPPA reactive 4/10/09 Pen G benz 4/10/09 Discharge

Patients profile
Case # 3 Maternal Late registrant, PNC X 10 LH incomplete Treatment Delivery 4/19/09 FTAGA, NSVD at 39.6 weeks by LMP to 19 y/o Caucasian, G3P0020 APGAR: 9 @ 1 min and 9 @ 5 min B Wt: 3085 g, Length: 49 cm, HC: 34. cm, CC: 31 cm, AC: 33.5 cm ROM: 12 hrs ptd. AF: clear Normal PE

4/19/09 Cord RPR 1:4 TPPA reactive 4/19/09 and 4/21/09 Patient Plasma RPR 1:4 TPPA reactive 4/21/09 CSF RPR: NR Cell count RBC 1 WBC 4 clear. Glucose 44 protein 84 4/21/09 4/22/09 4/23/09 Pen Procaine 50,000 Units/Kg 4/21/09 Long bones X ray . WNL 4/24/09 Pen G benz 50, 000 units / Kg 4/24/09 Discharge 5/6/09 RPR: no Reactive IgG reactive

Congenital Syphilis
The incidence of congenital syphilis corresponds to the incidence of disease in women.
Incidence increased dramatically during late 1980 and early 1990 but subsequently decreases.

In almost three quarter of cases the mother was not treated, or was inadequately treated.

Congenital Syphilis
Congenital Syphilis United States After 14 years of decline in the United States, the rate of congenital syphilis increased 15.4% between 2006 and 2007 (from 9.1 to 10.5 cases per 100,000 live births). In 2007, 430 cases were reported, an increase from 373 in 2006. This increase in the rate of congenital syphilis may relate to the increase in the rate of P&S syphilis among women that has occurred in recent years .

Congenital Syphilis by State In 2007, 29 states had rates of congenital syphilis that exceeded the 2010 target of one case per 100,000 live births . NYS reported 6.4 /100000 in 2007

CDC Congenital Syphilis Reported cases and rates in infants < 1 year 2003-2007
State/Area* 2003 2004
Cases 2005

2006

2007

Georgia Hawaii Idaho Illinois Louisiana Maine Maryland Massachusetts Michigan Nevada New Jersey New Mexico NEW YORK North Carolina Oklahoma Oregon Pennsylvania Texas Washington West Virginia Wisconsin Wyoming U.S. TOTAL

11 2 4 20 6 0 9 0 38 0 21 6 42 20 1 0 2 77 0 0 0 0 432

6 0 3 26 19 0 10 0 23 1 13 3 22 9 2 0 0 65 0 0 1 0 375

1 0 0 23 13 0 16 0 17 1 16 6 10 11 1 0 1 67 0 0 2 0 339

9 0 0 15 16 0 19 0 13 16 15 7 24 7 2 0 4 79 0 0 0 0 373

9 0 0 10 36 0 23 0 14 7 11 6 16 7 3 2 8 99 2 1 1 0 430

Congenital Syphilis
Clinical Presentation Congenital syphilis lack a primary stage: because it is disseminated through blood Fetal infections can occur at any time during pregnancy Hepatomegaly is present in almost 100% Necrotizing funisitis within the matrix of the umbilical cord is consider highly indicative 60% of patients are asymptomatic

Maternal Syphilis Dx and treatment

Test During Pregnancy : All women should be screened for syphilis with a non Treponemal test RPR / VRDL early in pregnancy and preferably again at delivery . In high risk areas testing at the beginning of 3rd Trimester is also recommended. All Positive tests should be confirmed with a Treponemal test FTS-ABS /TPPA. For women treated during pregnancy FU serology testing is necessary to assess efficacy of therapy. Treatment with penicillin is the gold standard.

Maternal Syphilis Dx and treatment

A single dose of Benzathine Penicillin therapy for early disease is only appropriate when is possible to document that there was a non reactive Syphilis test within the last Year. Some Give a second dose of Benzathine Penicillin 1 week after the first to improve the likelihood of a serology response in early disease.

In all other cases the disease should be consider Latent

syphilis of unknown duration for which 3 doses of Benzathine penicillin at weekly intervals are recommended. Follow up titers at 1,3,6,12 and 24 months decreases fourfold by 6 months and becomes negative by 12-24 months. Failure to decrease titers is likely to be failure to treat or reinfection.

Evaluation of Newborn with Congenital Syphilis

Mothers serological status for syphilis Blood cord testing is inadequate for screening (could be non-reactive even when the mother is +) Infants born from seropositive mothers require a careful examination and a quantitative non-treponemal test (same test should be performed to the mother) If maternal titers have increased to > 4 folds and/or infants titer is 4 fold greater than the mothers titers complete workup is warrant.

Evaluation of Newborn with Congenital Syphilis

Untreated, inadequately treated, or treatment not documented Treated with a non-penicillin regimen (i.e.,erythromycin)

Appropriately treated with PNC, but without the expected decrease in treponemal titers
Syphilis treated < 1 month prior to delivery Syphilis treated before pregnancy but with insufficient serologic f/u to assess response

Evaluation of Newborn with Congenital Syphilis -work upPhysical Examination Quantitative non-treponemal serologic test of serum from the infant for syphilis (not from cord blood) VDRL and cell count from CSF Long bone X-rays (unless Dx established otherwise) Complete blood cell and platelet count Other tests include: Chest X-ray LFT Pathological examination of placenta or umbilical cord using specific fluorescent antitreponemal antibody staining Vision and hearing test

Evaluation of Newborn with Congenital Syphilis

Transplacental transmission of nontreponemal and treponemal antibodies to the fetus can occur in a mother who has been treated appropriately for syphilis during pregnancy, resulting in + uninfected newborns, usually reverting by 4 to 6 months of age, whereas + FTA-ABS or TP-PA test result from passively acquired Ab and it may not become negative for 1 year or longer.

Congenital Syphilis

Hydrops fetalis Nasal discharge

Petechial rash Necrotizing funisitis

within the matrix of the umbilical cord

Hepatomegaly
Rash Ostitis , Metaphysitis, Periostitis Wimberger sign

Decreased mineralization of the metaphyses of long bones of the upper extremities bilateral lytic lesions of the talus, calcaneous, and proximal tibia (Wimberger sign) medially

Radiografic Abnormalities

A more specific finding is localized bony destruction of the medial portion of the proximal tibial metaphysis (Wimbergers sign). Other findings include metaphyseal serration (sawtooth metaphyses), and diaphyseal involvement with periosteal reaction.

Dermatology finding Congenital Syphilis

Dermatological findings are quite variable, although palmar/plantar, perioral, and anogenital regions are classically described as being involved. The images to the left demonstrate findings at birth in an affected infant, with a desquamating eruption that was widespread over the entire body. These lesions are extremely infectious. Because of the variable lesions and clinical symptoms seen with CS, it has frequently been termed "the great imitator", and it is important to consider alternative diagnoses or vesiculobullous diseases that involve the palms and soles.

CDC guideline 2006 Congenital Syphilis

Scenario 1. Infants with proven or highly probable disease and -an abnormal physical examination that is consistent with congenital syphilis, -a serum quantitative nontreponemal serologic titer that is fourfold higher than the mothers titer, or -a positive dark field or fluorescent antibody test of body fluid(s). Recommended Evaluation CSF analysis for VDRL, cell count, and protein CBC and PLT Other tests as clinically indicated (e.g., long-bone radiographs, chest radiograph, liver-function tests, cranial ultrasound, ophthalmologic examination, and auditory brainstem response) Recommended Regimens Aqueous crystalline penicillin G 100,000150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days

CDC guideline 2006 Congenital Syphilis

Scenario 2. Infants who have a normal physical examination and a serum quantitive nontreponemal serologic titer the same or less than fourfold the maternal titer and the -mother was not treated, inadequately treated, or has no documentation

of having received treatment; -mother was treated with erythromycin or other nonpenicillin regimen;** or -mother received treatment <4 weeks before delivery.
Recommended Evaluation

CSF analysis for VDRL, cell count, and protein -CBC and PLT Long bone RX
Recommended Regimens Aqueous crystalline penicillin G 100,000150,000 units/kg/day, administered as 50,000 units/kg/dose IV every 12 hours during the first 7 days of life and every 8 hours thereafter for a total of 10 days OR Procaine penicillin G 50,000 units/kg/dose IM in a single daily dose for 10 days

OR Benzathine penicillin G 50,000 units/kg/dose IM in a single dose

Some specialists prefer the 10 days of parenteral therapy if the mother has untreated early syphilis at delivery

CDC guideline 2006 Congenital Syphilis

Scenario 3. Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the mother was treated during pregnancy, treatment was appropriate for the stage of infection, and treatment was administered >4 weeks before delivery; and mother has no evidence of reinfection or relapse. Recommended Evaluation No evaluation is required. Recommended Regimen Benzathine penicillin G 50,000 units/kg/dose IM in a single dose

CDC guideline 2006 Congenital Syphilis

Scenario 4. Infants who have a normal physical examination and a serum quantitative nontreponemal serologic titer the same or less than fourfold the maternal titer and the -Mothers treatment was adequate before pregnancy, and -mothers nontreponemal serologic titer remained low and stable before and during pregnancy and at delivery (VDRL <1:2; RPR <1:4). Recommended Evaluation No evaluation is required. Recommended Regimen

No treatment is required; however, some specialists would treat with benzathine penicillin G 50,000 units/kg as a single IM injection, particularly if follow-up is uncertain.

Congenital Syphilis
Conclusions The incidence of congenital syphilis corresponds to the incidence of disease in women. All pregnant women should be tested 1st trimester and in the beginning of 3rd Trimester and at delivery. All positive test should be confirmed with a Treponemal Test , treat and follow up titers as per protocol. Documentation is an important aspect in the evaluation of treatment.

 Thank you !!