What is the next step when suspecting syphilis?

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Last updated: June 17, 2025View editorial policy

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From the Guidelines

When suspecting syphilis, the next step is to order serologic testing, which typically includes both non-treponemal tests (RPR or VDRL) and treponemal-specific tests (FTA-ABS, TP-PA, or treponemal EIA/CIA). This approach is supported by the guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, which recommend using both types of tests for diagnosis 1.

Importance of Serologic Testing

Serologic testing is crucial because syphilis is often asymptomatic or presents with non-specific symptoms that can mimic other conditions. The use of only one type of serologic test is insufficient for diagnosis, as false-positive nontreponemal test results may occur secondary to various medical conditions 1.

Treatment and Follow-Up

If serologic tests are positive, treatment should be initiated with benzathine penicillin G, with the dosage and duration depending on the stage of infection. For primary, secondary, or early latent syphilis (less than one year), a single intramuscular injection of 2.4 million units is recommended; for late latent syphilis or syphilis of unknown duration, three weekly injections of 2.4 million units are needed; and for neurosyphilis, aqueous crystalline penicillin G 3-4 million units IV every 4 hours for 10-14 days is required 1. For penicillin-allergic patients, doxycycline 100 mg orally twice daily for 14-28 days (depending on stage) is an alternative.

Partner Notification and Testing

It's essential to also test for other STIs, including HIV, as co-infections are common. Sexual partners from the past 90 days for primary syphilis, 6 months for secondary syphilis, or 1 year for early latent syphilis should be notified, evaluated, and treated 1.

Key Considerations

  • Serologic testing is the cornerstone of syphilis diagnosis.
  • Treatment should be stage-specific and consider penicillin allergy.
  • Partner notification and testing are critical for preventing further transmission.
  • Follow-up with quantitative nontreponemal serologic tests at 6,12, and 24 months is necessary to assess treatment response 1.

From the Research

Next Steps When Suspecting Syphilis

When suspecting syphilis, the next steps involve a combination of clinical evaluation, laboratory testing, and treatment. The key is to confirm the diagnosis through serologic tests and then proceed with appropriate treatment based on the stage of the disease.

  • Laboratory Testing: The diagnosis of syphilis can be challenging and requires the construction of a serologic profile based on the results of at least two types of antibody tests: treponemal and nontreponemal 2. A reverse algorithm, which involves screening with a treponemal assay first, followed by confirmation with a nontreponemal assay, can increase disease detection, especially in late latent and early primary stages of infection 2.
  • Interpretation of Test Results: All test results must be interpreted carefully, together with the patient's clinical history and symptoms, to arrive at a clinical diagnosis of syphilis 3. This is crucial because false-positive results can occur due to different medical conditions.
  • Treatment: The primary recommended treatment for early-stage syphilis is intramuscular (IM) benzathine penicillin G (BPG) 4, 5. However, due to potential shortages or patient allergies, alternatives such as doxycycline may be considered 4, 6. Doxycycline has been shown to be an effective agent for the treatment of early syphilis, with no statistically significant differences in serological responses compared to BPG at 6 and 12 months after treatment 6.
  • Considerations for Neurosyphilis: In cases of neurosyphilis, achieving treponemicidal levels of penicillin in the cerebrospinal fluid (CSF) is critical. This can be accomplished with specific regimens of procaine penicillin and probenecid, or intravenous benzyl penicillin 5.
  • HIV Co-infection: Patients co-infected with HIV may require special consideration, as syphilis can present atypically and treatment may need to be adjusted to achieve adequate CSF levels of antibiotics 5.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

A new reflex testing algorithm for syphilis screening.

MLO: medical laboratory observer, 2011

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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