Congenital syphilis laboratory findings: Difference between revisions

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== Laboratory Findings ==
== Laboratory Findings ==
===Prenatal Diagnosis===
*Detection of [[IgM]] [[antibodies]] aganist [[T.pallidum]] in the blood collected by [[chordocentesis]].<ref name="pmid1923218">{{cite journal |vauthors=Wendel GD, Sánchez PJ, Peters MT, Harstad TW, Potter LL, Norgard MV |title=Identification of Treponema pallidum in amniotic fluid and fetal blood from pregnancies complicated by congenital syphilis |journal=Obstet Gynecol |volume=78 |issue=5 Pt 2 |pages=890–5 |year=1991 |pmid=1923218 |doi= |url=}}</ref><ref name="pmid26753496">{{cite journal| author=Park JY, Han GH, Kwon DY, Hong HR, Seol HJ| title=Prenatal diagnosis of congenital syphilis presenting with transient pleural effusion in the fetus: a case report and rising incidence of congenital syphilis in South Korea. | journal=Clin Exp Obstet Gynecol | year= 2015 | volume= 42 | issue= 6 | pages= 822-4 | pmid=26753496 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26753496  }} </ref>
*[[PCR]] of the [[amniotic fluid]] to detect [[T. pallidum]] [[DNA]].<ref name="MullerEwert2006">{{cite journal|last1=Muller|first1=M|last2=Ewert|first2=I|last3=Hansmann|first3=F|last4=Tiemann|first4=C|last5=Hagedorn|first5=H J|last6=Solbach|first6=W|last7=Roider|first7=J|last8=Nolle|first8=B|last9=Laqua|first9=H|last10=Hoerauf|first10=H|title=Detection of Treponema pallidum in the vitreous by PCR|journal=British Journal of Ophthalmology|volume=91|issue=5|year=2006|pages=592–595|issn=0007-1161|doi=10.1136/bjo.2006.110288}}</ref>
*[[Antenatal]] [[ultrasound]] is commonly done and the findings suggestive of [[congenital syphilis]] include: [[hydrops fetalis]] characterised by scalp oedema, [[placental thickening]], serous cavity effusion, and [[polyhydramnios]]. Other additional findings inlcude [[hepatosplenomegaly]], [[placentomegaly]], non-continuous [[gastrointestinal obstruction]] and dilatation of the [[small bowel]].<ref name="pmid9565220">{{cite journal |vauthors=Levine Z, Sherer DM, Jacobs A, Rotenberg O |title=Nonimmune hydrops fetalis due to congenital syphilis associated with negative intrapartum maternal serology screening |journal=Am J Perinatol |volume=15 |issue=4 |pages=233–6 |year=1998 |pmid=9565220 |doi=10.1055/s-2007-993933 |url=}}</ref><ref name="Russell1974">{{cite journal|last1=Russell|first1=Peter|title=Placental Abnormalities of Congenital Syphilis|journal=American Journal of Diseases of Children|volume=128|issue=2|year=1974|pages=160|issn=0002-922X|doi=10.1001/archpedi.1974.02110270034007}}</ref><ref name="pmid7927729">{{cite journal |vauthors=Riley BS, Oppenheimer-Marks N, Radolf JD, Norgard MV |title=Virulent Treponema pallidum promotes adhesion of leukocytes to human vascular endothelial cells |journal=Infect. Immun. |volume=62 |issue=10 |pages=4622–5 |year=1994 |pmid=7927729 |pmc=303152 |doi= |url=}}</ref>


* Blood tests
====Postnatal Diagnosis====
** [[Complete blood count]]
*Examination of the [[placenta]] or [[umbilical cord]] using a [[silver  stain]] demonstrates [[spirochetes]] or a [[T. pallidum]] [[PCR]] test can be done.
** Differential count
*The use of [[serological tests]] to identify the infection in infants less than 15 months of age born to infected mothers is not performed as passive transfer of [[IgG]] [[antibodies]] to the [[fetus]] occurs during the [[pregnancy]].
** [[Platelet count]]
*Other laboratory findings in the [[new born]] include:<ref name="pmid11384701">{{cite journal |vauthors=Hollier LM, Harstad TW, Sanchez PJ, Twickler DM, Wendel GD |title=Fetal syphilis: clinical and laboratory characteristics |journal=Obstet Gynecol |volume=97 |issue=6 |pages=947–53 |year=2001 |pmid=11384701 |doi= |url=}}</ref>
* CSF analysis
*Elevated [[liver enzymes]]
*[[Leucocytosis]]
*[[Coombs]] negative [[hemolytic anaemia]]
*[[Thrombocytopenia]]
*[[Hypoalbuminemia]]
*[[Hyperbilirubinemia]]


Infants delivered of women with a reactive STS should have a cerebrospinal fluid (CSF) evaluation in any of the following circumstances:
===Imaging Studies===
====X-Ray====
*Skeletal survey in a [[still born]], typical [[osseous lesions]] are demonstrated in [[congenital syphilis]].


:* The infant shows any signs compatible with congenital syphilis OR
====Long Bone Radiographs====
:* Maternal therapy was inadequate, unknown, or it occurred late (greater than or equal to 20 weeks) in pregnancy OR
*Radiographs typically demonstrate bilateral, symmetric, and [[polyostotic]] lesions in [[femur]], [[humerus]], and [[tibia]].<ref name="pmid2584243">{{cite journal| author=Rasool MN, Govender S| title=The skeletal manifestations of congenital syphilis. A review of 197 cases. | journal=J Bone Joint Surg Br | year= 1989 | volume= 71 | issue= 5 | pages= 752-5 | pmid=2584243 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2584243  }} </ref><ref name="pmid8609122">{{cite journal| author=Kocher MS, Caniza M| title=Parrot pseudoparalysis of the upper extremities. A case report. | journal=J Bone Joint Surg Am | year= 1996 | volume= 78 | issue= 2 | pages= 284-7 | pmid=8609122 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8609122  }} </ref>
:* Maternal therapy did not include [[penicillin]] OR
*Common findings on [[radiographs]] include:
:* Adequate follow-up cannot be ensured
**[[Metaphyseal]] lucent bands
**Symmetric localized demineralization and [[osseous]] destruction of proximal [[tibial]] [[metaphysis]]
**[[Metaphyseal]] serration


Other living infants with a diagnosis of confirmed or compatible congenital syphilis should have a CSF examination before treatment to provide a baseline for follow-up examination. Although the importance of the CSF examination is debated, a quantitative VDRL CSF test can be meaningful if it is done in conjunction with tests for elevated total protein and [[lymphocyte]] count. The RPR card test should not be used for CSF evaluation.
====Ultrasound====
Antenatal sonographic features include:<ref name="radiop2"> https://radiopaedia.org/articles/in-utero-syphilis-infection. Accessed on September 28th, 2016. </ref><ref name="pmid21844732">{{cite journal| author=Reyna-Figueroa J, Esparza-Aguilar M, Hernández-Hernández Ldel C, Fernández-Canton S, Richardson-Lopez Collada VL| title=Congenital syphilis, a reemergent disease in Mexico: its epidemiology during the last 2 decades. | journal=Sex Transm Dis | year= 2011 | volume= 38 | issue= 9 | pages= 798-801 | pmid=21844732 | doi=10.1097/OLQ.0b013e31821898ca | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21844732  }} </ref>
*Fetal [[hepatosplenomegaly]]
* Placentomegaly
* Fetal [[ascites]]<br>
In severe cases findings include:
*Fetal [[hydrops]]
*Bent fetal long bones


Regardless of CSF results, however, all children with a diagnosis of confirmed or compatible congenital syphilis should be treated with a regimen effective for [[neurosyphilis]].
====Doppler Studies====
[[Doppler ultrasound]] of the [[uterine]] and [[umbilical]] [[arteries]] show increase in the mean [[systolic]] to [[diastolic]] ratios in mothers infected with [[syphilis]] indicating an increased resistance to [[perfusion]] of the [[placenta]] secondary to [[vasculitis]], placental villitis and obliterative arteritis caused by [[syphilis]].<ref name="Genc2000">{{cite journal|last1=Genc|first1=M.|title=Syphilis in pregnancy|journal=Sexually Transmitted Infections|volume=76|issue=2|year=2000|pages=73–79|issn=13684973|doi=10.1136/sti.76.2.73}}</ref>


=== Evaluation in the First Month of Life ===
===Other Diagnostic Studies===
All infants born to mothers who have reactive nontreponemal and treponemal test results should be evaluated with a quantitative nontreponemal serologic test (RPR or VDRL) performed on infant serum, because umbilical cord blood can become contaminated with maternal blood and yield a false-positive result. Conducting a treponemal test (i.e., TP-PA, [[FTA-ABS]], [[EIA]], or chemiluminescence assay) on a newborn’s serum is not necessary.
====CSF Analysis====
 
'''Indications : ''' [[Lumbar puncture]] is indicated in the following situations.<ref name="Phiske2014">{{cite journal|last1=Phiske|first1=MeghanaMadhukar|title=Current trends in congenital syphilis|journal=Indian Journal of Sexually Transmitted Diseases and AIDS|volume=35|issue=1|year=2014|pages=12|issn=0253-7184|doi=10.4103/0253-7184.132404}}</ref>
=== Serology ===
*If the [[infant]] or [[child]] has [[signs]] and [[symptoms]] of [[congenital Syphilis]].
 
*If there is no documentation of treatment for [[maternal]] infection during the period of [[gestation]].
The diagnosis of congenital syphilis is complicated by the transplacental transfer of maternal nontreponemal and tre-ponemal IgG antibodies to the fetus. This transfer of antibodies makes the interpretation of reactive serologic tests for syphilis in infants difficult.
*If the mother was treated within 4 weeks of [[delivery]].
 
*If the mother was inadequately treated or documentation of the treatment is incomplete.
All infants born to mothers who have reactive nontreponemal and treponemal test results should be evaluated with a quantitative nontreponemal serologic test ([[RPR]] or [[VDRL]]) performed on infant serum because [[umbilical cord blood]] can become contaminated with maternal blood and could yield a false-positive result. Conducting a treponemal test (i.e., TP-PA or FTA-ABS) on a newborn’s serum is not necessary. No commercially available immunoglobulin ([[IgM]]) test can be recommended.
*A four-fold decline in [[titer]] following therapy in the mother is not documented.
 
'''CSF Findings:'''
=== Dark Microscopic Examination ===
*Reactive [[CSF]] [[VDRL]]. <ref name="pmid26042815">{{cite journal| author=Workowski KA, Bolan GA, Centers for Disease Control and Prevention| title=Sexually transmitted diseases treatment guidelines, 2015. | journal=MMWR Recomm Rep | year= 2015 | volume= 64 | issue= RR-03 | pages= 1-137 | pmid=26042815 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26042815  }} </ref>
 
*[[CSF pleocytosis]](>25 white blood cells [WBC]/microL for infants <1 month)
[[Darkfield microscope|Darkfield microscopic]] examination or DFA staining of suspicious lesions or body fluids (e.g., nasal discharge) also should be performed.
*Elevated [[CSF]] [[protein]] (>150 mg/dL in term infants <1 month of age and >170 mg/dL in preterm infants <1 month of age)
 
=== Standard Tests ===
 
* Antibody Screening Tests (nontreponemal)
** [[Rapid plasma reagin]] (RPR)
** [[Venereal Disease Research Laboratory]] (VDRL)
** Unheated serum reagin (USR)
** Reagin screen test (RST)
 
* Antibody Confirmatory Tests (treponemal)
** Fluorescent treponemal antibody absorption (FTA-ABS)
** Fluorescent treponemal antibody absorption double staining (FTA-ABS DS)
** Microhemagglutination assay for antibody to T. pallidum (MHA-TP)
** Hemagglutination treponemal test for syphilis (HATTS)
** Bio-enzaBead Test (ELISA)
 
* Direct Examination of Lesion or Tissue
** [[Darkfield microscope|Darkfield microscopy]]
** Direct fluorescent antibody test for T. pallidum (DFA-TP)
** [[Silver stain]]s (modified Steiner)
** Hematoxylin and eosin (H & E) stains
 
=== Non Standard Tests ===
 
* FTA-ABS immunoglobulin (IgM)
* FTA-ABS 19S IgM
* IgM capture [[ELISA]]


== References ==
== References ==

Revision as of 18:23, 15 February 2017


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[2]; Aditya Govindavarjhulla, M.B.B.S. [3]

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Laboratory Findings

Prenatal Diagnosis

Postnatal Diagnosis

Imaging Studies

X-Ray

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Ultrasound

Antenatal sonographic features include:[10][11]

In severe cases findings include:

  • Fetal hydrops
  • Bent fetal long bones

Doppler Studies

Doppler ultrasound of the uterine and umbilical arteries show increase in the mean systolic to diastolic ratios in mothers infected with syphilis indicating an increased resistance to perfusion of the placenta secondary to vasculitis, placental villitis and obliterative arteritis caused by syphilis.[12]

Other Diagnostic Studies

CSF Analysis

Indications : Lumbar puncture is indicated in the following situations.[13]

  • If the infant or child has signs and symptoms of congenital Syphilis.
  • If there is no documentation of treatment for maternal infection during the period of gestation.
  • If the mother was treated within 4 weeks of delivery.
  • If the mother was inadequately treated or documentation of the treatment is incomplete.
  • A four-fold decline in titer following therapy in the mother is not documented.

CSF Findings:

  • Reactive CSF VDRL. [14]
  • CSF pleocytosis(>25 white blood cells [WBC]/microL for infants <1 month)
  • Elevated CSF protein (>150 mg/dL in term infants <1 month of age and >170 mg/dL in preterm infants <1 month of age)

References

  1. Wendel GD, Sánchez PJ, Peters MT, Harstad TW, Potter LL, Norgard MV (1991). "Identification of Treponema pallidum in amniotic fluid and fetal blood from pregnancies complicated by congenital syphilis". Obstet Gynecol. 78 (5 Pt 2): 890–5. PMID 1923218.
  2. Park JY, Han GH, Kwon DY, Hong HR, Seol HJ (2015). "Prenatal diagnosis of congenital syphilis presenting with transient pleural effusion in the fetus: a case report and rising incidence of congenital syphilis in South Korea". Clin Exp Obstet Gynecol. 42 (6): 822–4. PMID 26753496.
  3. Muller, M; Ewert, I; Hansmann, F; Tiemann, C; Hagedorn, H J; Solbach, W; Roider, J; Nolle, B; Laqua, H; Hoerauf, H (2006). "Detection of Treponema pallidum in the vitreous by PCR". British Journal of Ophthalmology. 91 (5): 592–595. doi:10.1136/bjo.2006.110288. ISSN 0007-1161.
  4. Levine Z, Sherer DM, Jacobs A, Rotenberg O (1998). "Nonimmune hydrops fetalis due to congenital syphilis associated with negative intrapartum maternal serology screening". Am J Perinatol. 15 (4): 233–6. doi:10.1055/s-2007-993933. PMID 9565220.
  5. Russell, Peter (1974). "Placental Abnormalities of Congenital Syphilis". American Journal of Diseases of Children. 128 (2): 160. doi:10.1001/archpedi.1974.02110270034007. ISSN 0002-922X.
  6. Riley BS, Oppenheimer-Marks N, Radolf JD, Norgard MV (1994). "Virulent Treponema pallidum promotes adhesion of leukocytes to human vascular endothelial cells". Infect. Immun. 62 (10): 4622–5. PMC 303152. PMID 7927729.
  7. Hollier LM, Harstad TW, Sanchez PJ, Twickler DM, Wendel GD (2001). "Fetal syphilis: clinical and laboratory characteristics". Obstet Gynecol. 97 (6): 947–53. PMID 11384701.
  8. Rasool MN, Govender S (1989). "The skeletal manifestations of congenital syphilis. A review of 197 cases". J Bone Joint Surg Br. 71 (5): 752–5. PMID 2584243.
  9. Kocher MS, Caniza M (1996). "Parrot pseudoparalysis of the upper extremities. A case report". J Bone Joint Surg Am. 78 (2): 284–7. PMID 8609122.
  10. https://radiopaedia.org/articles/in-utero-syphilis-infection. Accessed on September 28th, 2016.
  11. Reyna-Figueroa J, Esparza-Aguilar M, Hernández-Hernández Ldel C, Fernández-Canton S, Richardson-Lopez Collada VL (2011). "Congenital syphilis, a reemergent disease in Mexico: its epidemiology during the last 2 decades". Sex Transm Dis. 38 (9): 798–801. doi:10.1097/OLQ.0b013e31821898ca. PMID 21844732.
  12. Genc, M. (2000). "Syphilis in pregnancy". Sexually Transmitted Infections. 76 (2): 73–79. doi:10.1136/sti.76.2.73. ISSN 1368-4973.
  13. Phiske, MeghanaMadhukar (2014). "Current trends in congenital syphilis". Indian Journal of Sexually Transmitted Diseases and AIDS. 35 (1): 12. doi:10.4103/0253-7184.132404. ISSN 0253-7184.
  14. Workowski KA, Bolan GA, Centers for Disease Control and Prevention (2015). "Sexually transmitted diseases treatment guidelines, 2015". MMWR Recomm Rep. 64 (RR-03): 1–137. PMID 26042815.


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