Syphilis is a bacterial infection usually spread by sexual contact. The disease starts as a painless sore — typically on your genitals, rectum or mouth. Syphilis spreads from person to person via skin or mucous membrane contact with these sores.
After the initial infection, the syphilis bacteria can lie dormant in your body for decades before becoming active again. Early syphilis can be cured, sometimes with a single injection of penicillin. Without treatment, syphilis can severely damage your heart, brain or other organs, and can be life-threatening.
Syphilis rates in the United States have been declining among women since 2010, but rising among men, particularly men who have sex with men. The genital sores associated with syphilis can make it easier to become infected with HIV, the virus that causes AIDS.
In addition to spread during sexual activity, syphilis can be spread from mother to baby during pregnancy, referred to as congenital syphilis.
Syphilis during pregnancy can result in a stillborn birth or a low birthweight baby, and if left untreated, a baby with syphilis can develop cataracts, deafness, or seizures. In some cases, infants can die from the disease.
Three genera of spirochetes cause human infection:
- Treponema, which causes syphilis, yaws, and pinta
- Borrelia, which causes Lyme disease and relapsing fever
- Leptospira, which causes leptospirosis
The particular spirochete responsible for syphilis is Treponemapallidum.
T pallidum is a fragile spiral bacterium 6-15 micrometers long by 0.25 micrometers in diameter. Its small size makes it invisible on light microscopy; therefore, it must be identified by its distinctive undulating movements on darkfield microscopy. It can survive only briefly outside of the body; thus, transmission almost always requires direct contact with the infectious lesion.
Syphilis is usually classified into 4 stages: primary, secondary, latent, and tertiary. It can be either acquired or congenital. That is, it can be transmitted either by intimate contact with infectious lesions (most common) or via blood transfusion (if blood has been collected during early syphilis), and it can also be transmitted transplacentally from an infected mother to her fetus.
In acquired syphilis, T pallidum rapidly penetrates intact mucous membranes or microscopic dermal abrasions and, within a few hours, enters the lymphatics and blood to produce systemic infection. Incubation time from exposure to development of primary lesions, which occur at the primary site of inoculation, averages 3 weeks but can range from 10-90 days. Studies in rabbits show that spirochetes can be found in the lymphatic system as early as 30 minutes after primary inoculation, suggesting that syphilis is a systemic disease from the outset.
The central nervous system (CNS) is invaded early in the infection; during the secondary stage, examinations demonstrate that more than 30% of patients have abnormal findings in the cerebrospinal fluid (CSF). During the first 5-10 years after the onset of untreated primary infection, the disease principally involves the meninges and blood vessels, resulting in meningovascularneurosyphilis. Later, the parenchyma of the brain and spinal cord are damaged, resulting in parenchymatousneurosyphilis. Go to Neurosyphilis for complete information on this topic.
Regardless of the stage of disease and location of lesions, histopathologic hallmarks of syphilis include endarteritis (which in some instances may be obliterative in nature) and a plasma cell–rich infiltrate. Endarteritis is caused by the binding of spirochetes to endothelial cells, mediated by host fibronectin molecules bound to the surface of the spirochetes. The resultant endarteritis can heal with scarring in some instances.
The syphilitic infiltrate reflects a delayed-type hypersensitivity response to T pallidum, and in certain individuals with tertiary syphilis, this response by sensitized T lymphocytes and macrophages results in gummatous ulcerations and necrosis. Antigens of T pallidum induce host production of treponemal antibodies and nonspecific reagin antibodies. Immunity to syphilis is incomplete.
For example, host humoral and cellular immune responses may prevent the formation of a primary lesion on subsequent infections with T pallidum, but they are insufficient to clear the organism. This may be because the outer sheath of the spirochete is lacking immunogenic molecules, or it may be because of down-regulation of helper T cells of the TH1 class.
Primary syphilis is characterized by the development of a painless chancre at the site of transmission after an incubation period of 3-6 weeks. The lesion has a punched-out base and rolled edges and is highly infectious.
Histologically, the chancre is characterized by mononuclear leukocytic infiltration, macrophages, and lymphocytes. The inflammatory reaction causes an obliterative endarteritis. In this stage, the spirochete can be isolated from the surface of the ulceration or the overlying exudate of the chancre. Whether treated or not, healing occurs within 3-12 weeks, with considerable residual fibrosis.
Secondary syphilis develops about 4-10 weeks after the appearance of the primary lesion. During this stage, the spirochetes multiply and spread throughout the body. Secondary syphilis lesions are quite variable in their manifestations. Systemic manifestations include malaise, fever, myalgias, arthralgias, lymphadenopathy, and rash.
Widespread mucocutaneous lesions are observed over the entire body and may involve the palms, soles, and oral mucosae. Most often, the lesions are macular, discrete, reddish brown, and 5 mm or smaller in diameter; however, they can be pustular, annular, or scaling. All such lesions contain treponemes. Of these, wet mucous patches are the most contagious. Histologically, the inflammatory reaction is similar to but less intense than that of the primary chancre.
Other skin findings of secondary syphilis are condylomatalata and patchy alopecia. Condylomatalata are painless, highly infectious gray-white lesions that develop in warm, moist sites. The alopecia is characterized by patchy hair loss of the scalp and facial hair, including the eyebrows. Patients with this finding have been referred to as having a “moth-eaten” appearance. During secondary infection, the immune reaction is at its peak and antibody titers are high.
Latent syphilis is a stage at which the features of secondary syphilis have resolved, though patients remain seroreactive. Some patients experience recurrence of the infectious skin lesions of secondary syphilis during this period. About one third of untreated latent syphilis patients go on to develop tertiary syphilis, whereas the rest remain asymptomatic.
Currently, tertiary syphilis disease is rare. When it does occur, it mainly affects the cardiovascular system (80-85%) and the CNS (5-10%), developing over months to years and involving slow inflammatory damage to tissues. The 3 general categories of tertiary syphilis are gummatous syphilis (also called late benign), cardiovascular syphilis, and neurosyphilis.
Gummatous syphilis is characterized by granulomatous lesions, called gummas, which are characterized by a center of necrotic tissue with a rubbery texture. Gummas principally form in the liver, bones, and testes but may affect any organ. Histological examination shows palisaded macrophages and fibroblasts, as well as plasma cells surrounding the margins. Gummas may break down and form ulcers, eventually becoming fibrotic. Treponemes are rarely visualized or recovered from these lesions.
Cardiovascular syphilis occurs at least 10 years after primary infection. The most common manifestation is aneurysm formation in the ascending aorta, caused by chronic inflammatory destruction of the vasa vasorum, the penetrating vessels that nourish the walls of large arteries. Aortic valve insufficiency may result.
Neurosyphilis has several forms. If the spirochete invades the CNS, syphilitic meningitis results. Syphilitic meningitis is an early manifestation, usually occurring within 6 months of the primary infection. CSF shows high protein, low glucose, high lymphocyte count, and positive syphilis serology.
Meningovascular syphilis occurs as a result of damage to the blood vessels of the meninges, brain, and spinal cord, leading to infarctions causing a wide spectrum of neurologic impairments.
Parenchymal neurosyphilis includes tabesdorsalis and general paresis. Tabesdorsalis develops as the posterior columns and dorsal roots of the spinal cord are damaged. Posterior column impairment results in impaired vibration and proprioceptive sensation, leading to a wide-based gait.
Disruption of the dorsal roots leads to loss of pain and temperature sensation and areflexia. Damage to the cortical regions of the brain leads to general paresis, formerly called “general paresis of the insane,” which mimics other forms of dementia. Impairment of memory and speech, personality changes, irritability, and psychotic symptoms develop and may advance to progressive dementia.
The Argyll-Robertson pupil, a pupil that does not react to light but does constrict during accommodation, may be seen in tabesdorsalis and general paresis. The precise location of the lesion causing this phenomenon is unknown.
Congenital syphilis, discussed briefly here, is a veritable potpourri of antiquated medical terminology. The treponemes readily cross the placental barrier and infect the fetus, causing a high rate of spontaneous abortion and stillbirth. Within the first 2 years of life, symptoms are similar to severe adult secondary syphilis with widespread condylomatalata and rash. “Snuffles” describes the mucopurulent rhinitis caused by involvement of the nasal mucosae.
Later manifestations of congenital syphilis include bone and teeth deformities, such as “saddle nose” (due to destruction of the nasal septum), “saber shins” (due to inflammation and bowing of the tibia), “Clutton’s joints” (due to inflammation of the knee joints), “Hutchinson’s teeth” (in which the upper incisors are widely spaced and notched), and “mulberry molars” (in which the molars have too many cusps).
Tabesdorsalis and general paresis may develop as in adults, with 8th cranial nerve deafness and optic nerve atrophy as well as a variety of other ophthalmologic involvement leading to blindness being additional features.
Syphilis develops in stages, and symptoms vary with each stage. But the stages may overlap, and symptoms don’t always occur in the same order. You may be infected with syphilis and not notice any symptoms for years.
The first sign of syphilis is a small sore, called a chancre (SHANG-kur). The sore appears at the spot where the bacteria entered your body. While most people infected with syphilis develop only one chancre, some people develop several of them. The chancre usually develops about three weeks after exposure. Many people who have syphilis don’t notice the chancre because it’s usually painless, and it may be hidden within the vagina or rectum. The chancre will heal on its own within six weeks.
Within a few weeks of the original chancre healing, you may experience a rash that begins on your trunk but eventually covers your entire body — even the palms of your hands and the soles of your feet. This rash is usually not itchy and may be accompanied by wart-like sores in the mouth or genital area. Some people also experience muscle aches, fever, sore throat and swollen lymph nodes. These signs and symptoms may disappear within a few weeks or repeatedly come and go for as long as a year.
If you aren’t treated for syphilis, the disease moves from the secondary to the latent (hidden) stage, when you have no symptoms. The latent stage can last for years. Signs and symptoms may never return, or the disease may progress to the tertiary (third) stage.
TERTIARY (LATE) SYPHILIS
About 15 to 30 percent of people infected with syphilis who don’t get treatment will develop complications known as tertiary (late) syphilis. In the late stages, the disease may damage your brain, nerves, eyes, heart, blood vessels, liver, bones and joints. These problems may occur many years after the original, untreated infection.
Babies born to women who have syphilis can become infected through the placenta or during birth. Most newborns with congenital syphilis have no symptoms, although some experience a rash on the palms of their hands and the soles of their feet. Later symptoms may include deafness, teeth deformities and saddle nose — where the bridge of the nose collapses.
Syphilis has several clinical manifestations, making laboratory testing a very important aspect of diagnosis. In North America, many unsuspected cases are discovered by laboratory testing. The etiological agent,Treponemapallidum, cannot be cultured, and there is no single optimal alternative test. Serological testing is the most frequently used approach in the laboratory diagnosis of syphilis. The present paper discusses the various serological and alternative tests currently available along with their limitations, and relates their results to the likely corresponding clinical stage of the disease. The need to use multiple tests is discussed, and the importance of quality control is noted. The complexity of syphilis serology means that the services of reference laboratories and clinical experts are often needed.
When diagnosed and treated in its early stages, syphilis is easy to cure. The preferred treatment at all stages is penicillin, an antibiotic medication that can kill the organism that causes syphilis. If you’re allergic to penicillin, your doctor will suggest another antibiotic.
A single injection of penicillin can stop the disease from progressing if you’ve been infected for less than a year. If you’ve had syphilis for longer than a year, you may need additional doses.
Penicillin is the only recommended treatment for pregnant women with syphilis. Women who are allergic to penicillin can undergo a desensitization process that may allow them to take penicillin. Even if you’re treated for syphilis during your pregnancy, your newborn child should also receive antibiotic treatment.
The first day you receive treatment you may experience what’s known as the Jarisch-Herxheimer reaction. Signs and symptoms include fever, chills, nausea, achy pain and headache. This reaction usually doesn’t last more than one day.
After you’re treated for syphilis, your doctor will ask you to:
- Have periodic blood tests and exams to make sure you’re responding to the usual dosage of penicillin
- Avoid sexual contact until the treatment is completed and blood tests indicate the infection has been cured
- Notify your sex partners so that they can be tested and get treatment if necessary
- Be tested for HIV infection