What are the cause, risk factors, preventive measures, signs and symptoms, and treatment of Primary Syphilis (stage I)?

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Last updated: February 19, 2025View editorial policy

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From the Guidelines

Syphilis is a bacterial infection caused by Treponema pallidum. Stage I (Primary Syphilis) Cause and Risk Factors: The primary cause of syphilis is through sexual contact with an infected person, as noted in various studies on sexually transmitted diseases 1. Risk factors include unprotected sex, multiple sexual partners, and a history of other sexually transmitted infections (STIs).

Preventive Measures: Prevention of syphilis involves practicing safe sex, using condoms, and avoiding sexual contact with individuals who have untreated syphilis. Regular screening for STIs is also recommended for individuals at high risk.

Signs and Symptoms: The primary symptom of stage I syphilis is a painless sore or ulcer, known as a chancre, which appears at the site of infection, typically on the genitals, anus, or mouth. The chancre usually heals within 3-6 weeks without treatment.

Treatment: The recommended treatment for stage I syphilis is a single dose of intramuscular benzathine penicillin G (2.4 million units). For patients allergic to penicillin, doxycycline (100 mg orally twice daily for 14 days) is a recommended alternative treatment, as it has been used for many years and has better compliance compared to tetracycline due to fewer gastrointestinal side effects 1. Azithromycin (2 grams orally once) may also be used, but with caution, especially in areas with high resistance rates, and is not recommended for use in men who have sex with men (MSM) or pregnant women 1. It is essential to follow up with a healthcare provider after treatment to ensure the infection has been fully cleared. Pregnant women with syphilis should be treated with penicillin, as other antibiotics may not prevent transmission to the fetus. In cases where penicillin allergy is suspected, skin testing for penicillin allergy or desensitization may be necessary to ensure effective treatment 1.

From the FDA Drug Label

Syphilis–early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks. Patients being treated for gonococcal infection should have a serologic test for syphilis before receiving penicillin. All cases of penicillin treated syphilis should receive adequate follow-up including clinical and serological examinations.

The cause of Primary Syphilis (stage I) is not directly stated in the provided drug labels. The risk factors for Primary Syphilis (stage I) are not directly stated in the provided drug labels. Preventive measures for Primary Syphilis (stage I) are not directly stated in the provided drug labels. The signs and symptoms of Primary Syphilis (stage I) are not directly stated in the provided drug labels. The treatment for Primary Syphilis (stage I) includes doxycycline 100 mg, by mouth, twice a day for 2 weeks for patients allergic to penicillin 2. For patients not allergic to penicillin, the treatment is not directly stated in the provided drug labels.

From the Research

Cause of Primary Syphilis

  • Primary syphilis is caused by the spirochete Treponema pallidum subsp. pallidum, a sexually transmitted infection 3, 4, 5, 6
  • The bacteria are difficult to culture, and diagnosis is typically made through serologic testing 7

Risk Factors for Primary Syphilis

  • The risk factors for primary syphilis are similar to those for human immunodeficiency virus (HIV) infection, and patients with newly diagnosed syphilis should be tested for co-infection with HIV 3
  • Exposure to the bacteria through sexual contact is the primary risk factor for infection 4, 6

Preventive Measures for Primary Syphilis

  • Exposure prophylaxis is most important in the prevention of syphilis 4
  • The development of a syphilis vaccine would have a significant positive impact on global health, but it has not yet been achieved 5

Signs and Symptoms of Primary Syphilis

  • The primary stage of syphilis is characterized by the formation of an ulcer (primary affection) in the genitoanal region 4
  • Early syphilis lesions result from the host's immune response to the treponemes, and bacterial clearance and resolution of early lesions result from a delayed hypersensitivity response 5

Treatment of Primary Syphilis

  • The preferred treatment for all stages of syphilis, including primary syphilis, remains parenteral penicillin G 3
  • A single injection of 2.4 million units of benzathine penicillin G is effective in treating primary syphilis 7
  • Applying an adequate antibacterial treatment regime with benzylpenicillin derivatives can cure syphilis in most cases at any stage of the disease 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Ocular manifestations and treatment of syphilis.

Seminars in ophthalmology, 2005

Research

Syphilis – an update.

Medizinische Monatsschrift fur Pharmazeuten, 2017

Research

Biological basis for syphilis.

Clinical microbiology reviews, 2006

Research

Syphilis in the modern era: an update for physicians.

Infectious disease clinics of North America, 2013

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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