Syphilis laboratory findings

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Aysha Anwar, M.B.B.S[2]; Nate Michalak, B.A. Muhammad Saad, M.B.B.S.[3]

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## Overview

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Laboratory tests which may help diagnose syphilis include darkfield examinations and tests to detect T. pallidum in lesion exudate or tissue, PCR, nontreponemal (e.g., venereal disease research laboratory (VDRL) and rapid plasma reagent test) and treponemal tests (e.g., fluorescent treponemal antibody absorbed (FTA-ABS) tests, the T. pallidum passive particle agglutination (TP-PA) assay, various enzyme immunoassays, and chemiluminescence immunoassays).[1][2][3][4][5]

## Laboratory Findings

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Laboratory tests which may help diagnose syphilis include the following:[1][2][4][3][4][5]

* Darkfield examinations and tests to detect T. pallidum in lesion exudate or tissue are the definitive methods for diagnosing early syphilis.

* Although no T. pallidum detection tests are commercially available, some laboratories provide locally developed PCR tests for the detection of T. pallidum.

* A presumptive diagnosis of syphilis is possible with the use of two types of serologic tests:

* Nontreponemal tests (e.g., venereal disease research laboratory (VDRL) and rapid plasma reagent test) and
* Treponemal tests (e.g., fluorescent treponemal antibody absorbed (FTA-ABS) tests, the T. pallidum passive particle agglutination (TP-PA) assay, various enzyme immunoassays, and chemiluminescence immunoassays).

* The use of only one type of serologic test is insufficient for diagnosis because each type of test has limitations, including the possibility of false-positive test results in persons without syphilis.

* False-positive nontreponemal test results can be associated with various medical conditions unrelated to syphilis, including autoimmune conditions, older age, and injection-drug use.[6][7] Therefore, persons with a reactive nontreponemal test should receive a treponemal test to confirm the diagnosis of syphilis.

### Nontreponemal test

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* Includes VDRL and RPR tests
* Antibody titers may correlate with disease activity
* May reverse following treatment
* Used to follow treatment response
* A fourfold change in titer is necessary to demonstrate significant difference between two nontreponemal tests
* Results from two tests cannot be compared directly with each other
* The sensitivity of NTTs reaches 100% during secondary and early latent stage syphilis, and declines in late latent and tertiary syphilis. [8][9] [10][11][12][13] [14] [15]

### Trepenomal tests

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* Include fluorescent treponemal antibody absorbed (FTA-ABS) tests, T. pallidum passive particle agglutination (TP-PA) assay, enzyme immunoassays, and chemiluminescence immunoassays
* Antibody titers, once positive, remain positive for the rest of the patient's life, regardless of treatment or disease activity
* Cannot be used for monitoring treatment response
* Screening using trepenomal tests may help identify individuals previously treated for syphilis, those with untreated or incompletely treated syphilis, and persons with false-positive results
* The sensitivity and specificity of TTs is 95% to 100% across all stages.[16][12][17]

## References

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1. ↑ 1.0 1.1 http://www.cdc.gov/std/tg2015/syphilis.htm Accessed on September 28th, 2016
2. ↑ 2.0 2.1 Ratnam S (2005). "The laboratory diagnosis of syphilis". Can J Infect Dis Med Microbiol. 16 (1): 45–51. PMC 2095002. PMID 18159528.
3. ↑ 3.0 3.1 Tsang RS, Radons SM, Morshed M (2011). "Laboratory diagnosis of syphilis: A survey to examine the range of tests used in Canada". Can J Infect Dis Med Microbiol. 22 (3): 83–7. PMC 3200370. PMID 22942884.CS1 maint: Multiple names: authors list (link)
4. ↑ 4.0 4.1 4.2 Morshed MG, Singh AE (2015). "Recent trends in the serologic diagnosis of syphilis". Clin Vaccine Immunol. 22 (2): 137–47. doi:10.1128/CVI.00681-14. PMC 4308867. PMID 25428245.
5. ↑ 5.0 5.1 Pastuszczak M, Wojas-Pelc A (2013). "Current standards for diagnosis and treatment of syphilis: selection of some practical issues, based on the European (IUSTI) and U.S. (CDC) guidelines". Postepy Dermatol Alergol. 30 (4): 203–10. doi:10.5114/pdia.2013.37029. PMC 3834708. PMID 24278076.
6. ↑ Nandwani R, Evans DT (1995). "Are you sure it's syphilis? A review of false positive serology". International Journal of STD & AIDS. 6 (4): 241–8. PMID 7548285. `|access-date=` requires `|url=` (help)
7. ↑ "www.aphl.org" (PDF). Retrieved 2012-12-19.
8. ↑ Tuddenham S, Katz SS, Ghanem KG (June 2020). "Syphilis Laboratory Guidelines: Performance Characteristics of Nontreponemal Antibody Tests". Clin Infect Dis. 71 (Suppl 1): S21–S42. doi:10.1093/cid/ciaa306. PMC 7312285 Check `|pmc=` value (help). PMID 32578862 Check `|pmid=` value (help).
9. ↑ "Treponema pallidum Nucleic Acid Amplification Testing To Augment Syphilis Screening among Men Who Have Sex with Men | Journal of Clinical Microbiology".
10. ↑ "Sensitivity, specificity and likelihood ratios of PCR in the diagnosis of syphilis: a systematic review and meta-analysis | Sexually Transmitted Infections".
11. ↑ "Use of Treponema pallidum PCR in Testing of Ulcers for Diagnosis of Primary Syphilis - Volume 21, Number 1—January 2015 - Emerging Infectious Diseases journal - CDC".
12. ↑ 12.0 12.1 "CDC Laboratory Recommendations for Syphilis Testing, United States, 2024 | MMWR".
13. ↑ "Characterization of the Western blotting IgG reactivity patterns in the clinical phases of acquired syphilis - ScienceDirect".
14. ↑ "www.semanticscholar.org".
15. ↑ "Qualitative and quantitative aspects of the serological diagnosis of early syphilis - A Mcmillan, H Young, 2008".
16. ↑ "Sexually Transmitted Diseases".
17. ↑ "The Laboratory Diagnosis of Syphilis | Journal of Clinical Microbiology".

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