Tertiary Syphilis: Symptoms, Diagnosis & Treatment

Marcela Lemos
Clinical review: Marcela Lemos Biomedical Scientist CRBM/PE #08598
Created by: Jillian Kinton-Vieira Registered Nurse

Tertiary syphilis is the final stage of syphilis. It occurs when the bacterium Treponema pallidum is not treated in the earlier stages.

The bacteria remain in the body, multiply in the blood, and spread to other organs. Tertiary syphilis can affect the heart, brain, and eyes.

Symptoms of tertiary syphilis can appear years after the first symptoms of syphilis. They mainly include skin and bone lesions, vision and hearing changes, and cardiovascular or neurological complications, such as aneurysm and stroke.

syphilis testing

Main symptoms

The main symptoms of tertiary syphilis are:

  • Skin, mouth, and nose lesions, which may also affect the bones

  • Severe headache

  • Muscle weakness

  • Seizures

  • Cardiovascular complications, such as arterial aneurysms

  • Hearing loss, dizziness, or vertigo

  • Vision changes, which may lead to blindness

  • Frequent nausea and vomiting

  • Confusion and memory loss

Neurosyphilis can also occur. This is a complication that happens when the bacteria invade the central nervous system, affecting the brain, meninges, and spinal cord, and may lead to meningitis or stroke.

Symptoms of tertiary syphilis can appear between 2 and 40 years after the first signs of primary syphilis. They usually progress gradually due to the persistent presence of the bacteria in the body.

If tertiary syphilis is not diagnosed and treated, it can affect multiple organs, including the heart and brain, and may be life-threatening.

Symptom quiz

If you are concerned you might have syphilis, please select the symptoms you are experiencing below:

  1. 1. Hard, painless lump or wound in the genital area
  2. 2. Have you had any unprotected sex in the last 3 months?
  3. 3. Red or brown patches on the skin, especially on the trunk, palms of the hands, or soles of the feet
  4. 4. Light-colored patches or lumps in the genital area, tongue, lips, or mouth
  5. 5. Hair loss or eyebrow loss
  6. 6. Low-grade fever
  7. 7. Feeling unwell
  8. 8. Swollen lymph nodes in one or more places on the body
  9. 9. Skin ulcers
  10. 10. Mental confusion or difficulty with reasoning/memory
  11. 11. Constant headache

This test is only a tool and does not replace a consultation with your primary care provider or an infectious disease specialist.

Confirming a diagnosis

The diagnosis of tertiary syphilis is usually made by an infectious disease specialist, gynecologist, or urologist. It involves reviewing the person’s medical history, symptoms, physical exam, and lab tests.

One test the doctor may order is the VDRL test, which detects antibodies in the blood against substances released by the bacteria that cause syphilis. This test helps assess the presence and activity of the infection.

In addition, when neurological symptoms are present, such as confusion, memory loss, or behavior changes, the doctor may order a cerebrospinal fluid (CSF) test. This test checks for the presence of the bacteria in the central nervous system and helps diagnose neurosyphilis.

Treatment options

Treatment for tertiary syphilis should be guided by a healthcare provider, often an infectious disease specialist.

According to the CDC, tertiary syphilis with a normal cerebrospinal fluid exam is treated with 3 weekly injections of benzathine penicillin G, given 7 days apart. The goal is to eliminate the bacteria that cause syphilis and prevent further complications.

In cases of neurosyphilis, treatment must be more intensive. According to the CDC, neurosyphilis is treated with intravenous aqueous crystalline penicillin G for 10 to 14 days. This treatment is typically given in a hospital, especially when there is a risk of permanent damage.

However, because tertiary syphilis can cause more serious symptoms, the doctor may recommend other treatments to manage complications and improve quality of life.

It is important to have regular VDRL testing to monitor the response to treatment. If the results are not satisfactory, the doctor may adjust the dose.

Update History
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References
  • Centers for Disease Control and Prevention. Tertiary Syphilis - STI Treatment Guidelines. CDC. Updated 22 Jul 2021. Accessed 28 Apr 2026 https://www.cdc.gov/std/treatment-guidelines/tertiary-syphilis.htm
  • Centers for Disease Control and Prevention. Neurosyphilis, Ocular Syphilis, and Otosyphilis. CDC. Accessed 28 Apr 2026 https://www.cdc.gov/std/treatment-guidelines/neurosyphilis.htm
  • Mahon, Connie R.; Lehman, Donald C. Textbook of Diagnostic Microbiology. 6 ed ed. St- Louis, Missouri: Elsevier; 2019.
  • Barer, Michael R Et Al. Medical Microbiology: A guide to microbial infections - pathogenesis, immunity, laboratory investigation and control. 19 ed ed. : Elsevier; 2018.
  • Ministério da Saúde. Sífilis. Ministério da Saúde. Accessed 30 Jun 2020 http://www.aids.gov.br/pt-br/publico-geral/o-que-sao-ist/sifilis
  • CDC. 2015 Sexually Transmitted Diseases Treatment Guidelines: Syphilis. CDC. Accessed 30 Jun 2020 https://www.cdc.gov/std/tg2015/syphilis.htm
  • Syphilis. Sexually Trans. Infec. Treat. Gudelines, 2021. 2024. Accessed 07 Jul 2025 https://www.cdc.gov/std/treatment-guidelines/syphilis.htm
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  • CHAUDHRY, Shahrukh et al. Secondary Syphilis: Pathophysiology, Clinical Manifestations, and Diagnostic Testing. Venereology. 2023;Vol.2(2.ed):65-75.
  • XIONG, Shun et al. Resurgence of syphilis: focusing on emerging clinical strategies and preclinical models. Journal of Translational Medicine volume. 2023;Vol.21():.