Merck Manual

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Sheldon R. Morris

, MD, MPH, University of California San Diego

Reviewed/Revised Feb 2023
Topic Resources

Syphilis is a sexually transmitted infection caused by the bacteria Treponema pallidum. It can occur in three stages of symptoms, separated by periods of apparent good health.

  • Syphilis begins with a painless sore at the infection site and, in the second stage, causes a rash, fever, fatigue, headache, and loss of appetite.

  • If untreated, the third stage of syphilis can damage the aorta, brain, spinal cord, and other organs.

  • Doctors usually do two types of blood tests to confirm that a person has syphilis.

  • Treatment is with penicillin, which can eliminate the infection.

  • Using condoms during genital sex can help prevent passing syphilis and other sexually transmitted infections (STIs) from one person to another.

In 2020, there were more than 130,000 reported cases of syphilis in the United States. The majority of cases of primary and secondary syphilis occurred in men (81%) and, among men, 53% of cases were in men who have sex with men. The incidence of syphilis has been increasing rapidly in the United States. From 2015 to 2020, the primary and secondary syphilis rate among women increased 147%, and the rate among men increased 34%.

Certain conditions and activities (risk factors) increase the risk of getting syphilis. They include the following:

People with syphilis often have other STIs.

Syphilis causes symptoms in three stages:

  • Primary syphilis

  • Secondary syphilis

  • Tertiary syphilis

The stages are separated by periods when no symptoms occur (latent stage).

Transmission of syphilis

Syphilis is highly contagious during the primary and secondary stages. It may be contagious early in the latent stage.

Infection is usually spread through sexual contact. A single sexual encounter with a person who has early-stage syphilis results in infection about one third of the time. The bacteria enter the body through mucous membranes, such as those of the vagina, penis, or mouth, or through the skin. Within hours, the bacteria reach nearby lymph nodes, then spread throughout the body through the bloodstream.

People can sometimes get syphilis by contact with infected skin sores. However, the bacteria cannot survive long outside the human body so syphilis is not spread through contact with objects (such as toilet seats, door handles) that have been touched by a person with syphilis.

Symptoms of Syphilis

Each stage of symptoms (primary, secondary, and tertiary) is progressively worse.

If not treated, syphilis can persist without symptoms for many years and may damage the aorta (the largest artery in the body) or brain, possibly leading to death. Neurosyphilis Tertiary (third, or late) syphilis Tertiary (third, or late) syphilis (which affects the brain and spinal cord) can develop during any stage of syphilis.

If detected and treated early, syphilis can be cured before there is permanent damage.

Primary syphilis

A painless sore (called a chancre) appears at the infection site—typically the penis, vulva, or vagina. A chancre may also appear on the anus, rectum, lips, tongue, throat, cervix, fingers, or other parts of the body. Usually only one chancre develops, but occasionally several develop. Symptoms usually start 3 to 4 weeks after infection but may start from 1 to 13 weeks later.

The chancre begins as a small red raised area, which soon turns into a relatively painless, raised, firm open sore. The chancre does not bleed and is hard to the touch. Nearby lymph nodes usually swell and are also painless. About half of infected women and one third of infected men are unaware of the chancre because it causes few symptoms. Chancres in the rectum or mouth, usually occurring in men, are often unnoticed.

Images of Primary Syphilis

The chancre usually heals in 3 to 12 weeks. Then, people appear to be completely healthy.

Secondary syphilis

The bacteria spread in the bloodstream, causing a widespread rash, swollen lymph nodes, and, less commonly, symptoms in other organs. The rash typically appears 6 to 12 weeks after infection. About one fourth of infected people still have a chancre at this time. Usually, the rash does not itch or hurt. It varies in appearance.

Unlike rashes caused by most other diseases, this rash commonly appears on the palms or soles. It may be short-lived or may last for months. Even without treatment, the rash eventually resolves, but it may recur weeks or months later. If a rash develops on the scalp, hair may fall out in patches, making it appear moth-eaten.

Raised flat, smooth growths called condylomata lata may develop in moist areas of the skin, such as the mouth, armpits, genital area, and anus. These painless growths contain many syphilis bacteria and are very infectious. They may break open and weep. As they resolve, they flatten and turn a dull pink or gray. Mouth sores develop in more than 20 to 30% of people.

Secondary-stage syphilis can cause fever, fatigue, loss of appetite, and weight loss.

About 50% of people with secondary-stage syphilis have enlarged lymph nodes throughout the body. In about 10% of people, other organs are affected. The eyes may become inflamed. Bones and joints may ache. In a few people, infection of the liver (hepatitis Overview of Hepatitis Hepatitis is inflammation of the liver. (See also Overview of Acute Viral Hepatitis and Overview of Chronic Hepatitis.) Hepatitis is common throughout the world. Hepatitis can be Acute (short-lived) read more ) causes abdominal pain and jaundice Jaundice in Adults In jaundice, the skin and whites of the eyes look yellow. Jaundice occurs when there is too much bilirubin (a yellow pigment) in the blood—a condition called hyperbilirubinemia. (See also Overview... read more Jaundice in Adults (the skin and whites of the eyes turn yellow), and urine become dark. Some have headaches or problems with hearing, balance, or vision because the brain, inner ears, or eyes are infected.

Images of Secondary Syphilis

Latent syphilis

After the secondary stage, people may have no symptoms for years to decades. During this time, the infection is inactive (latent). However, the bacteria are still present, and tests for syphilis are positive.

Syphilis may remain latent permanently, and generally, it is not contagious during this stage. But occasionally, sores may appear on the skin or mucous membranes early in the latent stage. Contact with these sores can spread the infection.

The latent stage is classified as early (if the initial infection occurred within the previous 12 months) or late (if the initial infection occurred more than 12 months previously).

Tertiary (third, or late) syphilis

Tertiary syphilis develops in about one third of untreated people years to decades after the initial infection. Symptoms range from mild to devastating.

Tertiary syphilis has three main forms:

  • Benign tertiary syphilis

  • Cardiovascular syphilis

  • Neurosyphilis

Benign tertiary syphilis usually develops 3 to 10 years after the initial infection. Soft, rubbery growths called gummas appear on the skin, most commonly on the scalp, face, upper trunk, and legs. They also often develop in the liver or bones, but they can develop in virtually any organ. They may break down, forming an open sore. If untreated, gummas destroy the tissue around them. In bone, they usually cause deep, penetrating pain, which is usually worse at night. Gummas grow slowly, heal gradually, and leave scars.

Cardiovascular syphilis usually appears 10 to 25 years after the initial infection. The bacteria infect the blood vessels connected to the heart, including the aorta. The following may result:

Neurosyphilis (which affects the brain and spinal cord) occurs in about 5% of all people with untreated syphilis. It occurs in the following forms:

  • Asymptomatic: This form is a mild infection of the tissues that cover the brain and spinal cord (meninges), causing mild meningitis Introduction to Meningitis Meningitis is inflammation of the layers of tissue that cover the brain and spinal cord (meninges) and of the fluid-filled space between the meninges (subarachnoid space). Meningitis can be... read more . Without treatment, in 5% of people it evolves to symptomatic neurosyphilis with symptoms including a headache, a stiff neck, and difficulty concentrating.

  • Meningovascular: The arteries of the brain or spinal cord become inflamed, causing a chronic form of meningitis. At first, people may have a headache and a stiff neck. They may feel dizzy, have difficulty concentrating and remembering things, and have insomnia. Vision may be blurred. Muscles in the arms, shoulders, and eventually legs may become weak or even paralyzed. People may have difficulty controlling urination and bowel movements (incontinence). This form can also cause strokes.

  • Paretic (parenchymatous): This form usually begins when people are in their 40s or 50s. The first symptoms are gradual changes in behavior. Symptoms may resemble those of a mental disorder or dementia. For example, people may become less careful about personal hygiene, and their moods may change frequently. They may become irritable and confused. They may have difficulty concentrating and remembering. They may have delusions of grandeur (that is, they believe that they are famous people or God or that they have magical powers). Tremors may occur in the mouth, tongue, outstretched hands, or whole body.

  • Tabetic (tabes dorsalis): The spinal cord progressively deteriorates. It typically develops 20 to 30 years after the initial infection. Symptoms begin gradually, typically with an intense, stabbing pain in the back and legs that comes and goes irregularly. Occasionally, people have similar bouts of pain in the stomach, bladder, rectum, or throat. Walking becomes unsteady. Sensation in the feet is decreased or feels abnormal. People usually lose weight and appear sad. Problems with vision may develop. Erectile dysfunction is common. Eventually, people have difficulty controlling urination (incontinence) and may become paralyzed.

Other symptoms

Syphilis can affect the eyes or ears at any stage of the disease.

Eye symptoms include watery eyes, blurred vision, eye pain, sensitivity to light, and loss of vision. If syphilis infects the eyes, the risk of developing neurosyphilis is increased.

Diagnosis of Syphilis

  • Tests on a sample of blood, fluid from a sore, or spinal fluid

Pregnant women should be screened for syphilis. Also, adolescents and adults who are not pregnant and do not have symptoms but who are at increased risk for syphilis infection should be screened for syphilis.

Health care practitioners suspect primary syphilis if people have a typical chancre. They suspect secondary syphilis if people have a typical rash on the palms and soles. Because syphilis can cause a wide range of symptoms during its various stages, doctors may check for syphilis when evaluating people with any of its possible symptoms, including problems with vision.

Laboratory tests are needed to confirm the diagnosis. Two types of blood tests are used:

  • A screening test, such as the Venereal Disease Research Laboratory (VDRL) or the rapid plasma reagin (RPR) test, is usually done first. These tests are called nontreponemal tests because they do not directly detect the bacteria that cause syphilis (treponema) or the antibodies produced in response to these bacteria. Screening tests are inexpensive and easy to do, but results can be negative for 3 to 6 weeks after the initial infection even though syphilis is present. Such results are called false-negative. If results of a screening test are negative but doctors think that primary syphilis is likely, the test may be repeated after 6 weeks. Screening test results are sometimes positive when syphilis is not present (false-positive) because another disorder has caused the test to be positive.

  • A confirmatory test must usually be done to confirm a positive screening test. These blood tests measure antibodies that are produced specifically in response to the bacteria that cause syphilis (sometimes called treponemal tests). Results of confirmatory tests may also be false-negative during the first few weeks after initial infections and thus may need to be repeated.

Traditionally, screening tests are done first, and positive results are confirmed by a confirmatory (treponemal) test. Sometimes doctors do the treponemal test first. If results are positive, the rapid plasma reagin test (a screening test) is then done.

If test results are positive, doctors may ask the person about former sex partners, previous laboratory test results, and previous treatments to help determine whether the person currently has syphilis or has had it in the past.

Screening tests results may slowly (over months to several years) become negative after successful treatment, but the confirmatory test results usually stay positive indefinitely.

In the primary or secondary stages, syphilis may also be diagnosed using darkfield microscopy. A sample of fluid is taken from a skin sore or lymph node and examined using a specially equipped light microscope. The bacteria appear bright against a dark background, making them easier to identify.

In the latent stage, the same blood tests (treponemal and nontreponemal) are used to diagnose syphilis. Doctors also try to determine whether the stage is early-latent syphilis or late-latent syphilis based on results of their evaluation, including a thorough physical examination and review of previous test results.

In the tertiary stage, the diagnosis is based on symptoms and antibody test results. Depending on which symptoms are present, other tests are done. For example, a chest x-ray may be taken or another imaging test may be done to check for an aneurysm in the aorta Overview of Aortic Aneurysms and Aortic Dissection The aorta, which is about 1 inch (2.5 centimeters) in diameter, is the largest artery of the body. It receives oxygen-rich blood from the left ventricle of the heart and distributes it to all... read more .

If neurosyphilis is suspected, regardless of the stage of syphilis, a spinal tap Spinal Tap Diagnostic procedures may be needed to confirm a diagnosis suggested by the medical history and neurologic examination. Imaging tests commonly used to diagnose nervous system (neurologic) disorders... read more Spinal Tap (lumbar puncture) is needed to obtain spinal fluid, which is tested for antibodies to the bacteria.

People with syphilis should also be tested for other STIs, including HIV infection.

Treatment of Syphilis

  • Penicillin given by injection

  • Another antibiotic for people who are allergic to penicillin

  • Simultaneous treatment of sex partners

Penicillin given by injection into a muscle is the best antibiotic for primary, secondary, and early latent syphilis.

  • For primary, secondary, and early-latent stages of syphilis, one dose of a long-acting penicillin is all that is needed.

  • For late-latent stage and some forms of the tertiary stage, three doses are given, separated by 1 week.

If syphilis affects the eyes, inner ears, or brain, penicillin may be given intravenously every 4 hours for 10 to 14 days. Then, another form of penicillin is given by injection into a muscle once a week for up to 3 weeks.

People who are allergic to penicillin may be given other antibiotics such as doxycycline (taken by mouth for 14 days or sometimes for 28 days). People who cannot take doxycycline may be given azithromycin (as a single dose by mouth). However, in some parts of the world, syphilis is becoming increasingly resistant to azithromycin. Pregnant women who are allergic to penicillin are hospitalized and desensitized to penicillin Allergen immunotherapy (desensitization) Allergic reactions (hypersensitivity reactions) are inappropriate responses of the immune system to a normally harmless substance. Usually, allergies cause sneezing, watery and itchy eyes, a... read more Allergen immunotherapy (desensitization) so that they can take penicillin.

Treatment of sex partners

Because people with primary, secondary, and even early-latent syphilis can pass the infection to others, they must avoid sexual contact until they and their sex partners have completed treatment.

If a person is diagnosed with syphilis, all of the person's sex partners are tested for syphilis. The sex partners are treated in the following circumstances:

  • They had sexual contact with the infected person during the 90 days before the diagnosis was made, even if their test results are negative.

  • They had sexual contact with the infected person more than 90 days before the diagnosis was made but only if their test results are not immediately available and their return for a follow-up visit is uncertain. If their test results are negative, no treatment is needed. If test results are positive, they are treated.

Jarisch-Herxheimer reaction

Many people with syphilis in an early stage, especially those with secondary syphilis, develop a reaction 6 to 12 hours after the first treatment. This reaction, called a Jarisch-Herxheimer reaction, causes fever, headache, sweating, shaking chills, and a temporary worsening of the sores caused by syphilis. Doctors sometimes mistake this reaction for an allergic reaction to penicillin.

Symptoms of this reaction usually subside within 24 hours and rarely cause permanent damage. However, rarely, people with neurosyphilis have seizures or a stroke.

After treatment

After treatment, examinations and blood tests are done periodically until no infection is detected.

If treatment of primary, secondary, or latent syphilis is successful, most people have no more symptoms. But treatment of tertiary syphilis cannot reverse damage done to organs, such as the brain or aorta. People with such damage usually do not improve after treatment.

People who have been cured of syphilis do not become immune to it and can be infected again.

Prevention of Syphilis

The following general measures can help prevent syphilis (and other STIs):

Did You Know...

  • A single sexual encounter with a person who has early-stage syphilis results in infection about one third of the time.

More Information

The following English-language resource may be useful. Please note that THE MANUAL is not responsible for the content of this resource.

Drugs Mentioned In This Article

Generic Name Select Brand Names
Acticlate, Adoxa, Adoxa Pak, Avidoxy, Doryx, Doxal, Doxy 100, LYMEPAK, Mondoxyne NL, Monodox, Morgidox 1x, Morgidox 2x , Okebo, Oracea, Oraxyl, Periostat, TARGADOX, Vibramycin, Vibra-Tabs
Azasite, Zithromax, Zithromax Powder, Zithromax Single-Dose , Zithromax Tri-Pak, Zithromax Z-Pak, Zmax, Zmax Pediatric
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