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Syphilis !si-f(u-)lus

by J. Allen McCutchan, MD, MSc

Syphilis is a sexually transmitted disease caused by the bacteria Treponema pallidum.

  • Syphilis can occur in three stages of symptoms, separated by periods of apparent good health.

  • It 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 heart, brain, spinal cord, and other organs.

  • Doctors usually do two types of blood tests—one to screen for and one to confirm the infection.

  • Penicillin can eliminate the infection, but people can be reinfected.

In the United States, about 6,000 cases of syphilis were reported in 2000, but the number increased to over 15,000 in 2012. Most people with syphilis are men, often men who have sex with men and who live in cities. In the United States, the percentage of blacks infected is about 3 times that of other ethnic or racial groups.

Syphilis causes symptoms in three stages (primary, secondary, and tertiary), separated by periods when no symptoms occur (latent stages).

Syphilis is highly contagious during the primary and secondary stages. 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 in the vagina or mouth, or through the skin. Within hours, the bacteria reach nearby lymph nodes, then spread throughout the body through the bloodstream.

Syphilis can also be spread in other ways. It can infect a fetus during pregnancy (see Table: Some Infections of Newborns), causing birth defects and other problems. It can also be spread through contact with skin. However, the bacteria cannot survive long outside the human body.

People with syphilis often have other infections, including other sexually transmitted diseases (STDs).

Symptoms

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 heart or brain, possibly leading to death. If detected and treated early, syphilis can be cured, and there is no permanent damage.

Primary stage

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 painless open, deep sore. The chancre does not bleed and is hard to the touch. Lymph nodes in the groin 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.

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

Secondary stage

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.

Did You Know...

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

  • About half of the women and one third of the men who have the initial sore of syphilis (chancre) do not notice it.

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 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 have enlarged lymph nodes throughout the body. In about 10% of people, other organs are affect. The eyes may become inflamed. Bones and joints may ache. In a few people, infection of the liver (hepatitis) causes abdominal pain and jaundice (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.

Latent stage

After the secondary stage, people may have no symptoms for years to decades. During this time, the infection is inactive (latent) and is not contagious. However, the bacteria are still present, and tests for syphilis are positive. 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) stage

Late 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. It is rare today. 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 heart and the blood vessels connected to it, including the aorta (the largest artery in the body). The following may result:

  • The wall of the aorta may weaken, forming a bulge (aneurysm). The aneurysm may press on the windpipe or other structures in the chest, causing difficulty breathing, a cough, and hoarseness.

  • The valve leading from the heart to the aorta (aortic valve) may leak.

  • The arteries that carry blood to the heart (coronary arteries) may narrow.

These problems can cause chest pain, heart failure, and death.

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

  • 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. For example, people may become less careful about personal hygiene, and their moods may change frequently. They may become irritable, confused, and eventually demented (see Dementia). 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 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.

Diagnosis

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

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.

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 done first. 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. Results of confirmatory tests may also be false-negative during the first few weeks after initial infections and thus may need to be repeated.

Screening tests results may slowly (over months to several years) become negative after successful treatment, but the confirmatory test results 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 or mouth sore 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, antibody tests of blood and spinal fluid are used to diagnose syphilis.

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. If neurosyphilis is suspected, a spinal tap (lumbar puncture—see Tests for Brain, Spinal Cord, and Nerve Disorders : Spinal Tap) is needed to obtain spinal fluid, which is tested for antibodies to the bacteria.

Treatment

  • 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 and secondary 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.

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 (see Allergen immunotherapy (desensitization)) so that they can take penicillin.

Because people with primary or secondary syphilis can pass the infection to others, they must avoid sexual contact until they and their sex partners have completed treatment. If people have primary-stage syphilis, all their sex partners of the previous 3 months are at risk of being infected. If they have secondary-stage syphilis, all sex partners of the previous year are at risk. Such sex partners require a blood test for antibodies to the bacteria. If test results are positive, the sex partners need to be treated. Some doctors simply treat all sex partners without waiting for test results.

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

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 heart. 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.

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  • ZITHROMAX
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