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by Michael Todd Sapko MD, PhD
Syphilis has earned the title “The Great Imitator” because it can cause a variety of different symptoms—many of which look like other diseases. While the treatment of syphilis is pretty straightforward in most cases, making the diagnosis is often the tricky part.
Syphilis is a sexually transmitted disease. It is transmitted from person to person through close contact, specifically from contact with infectious skin lesions. While it is possible for syphilis to be transmitted through a blood transfusion, modern blood screening makes this occurrence quite rare. The microorganism that causes syphilis is a spirochete called Treponema pallidum. What is a spirochete? A spirochete is simply an unusual looking bacterium that resembles a worm or corkscrew under a microscope.
Syphilis was a scourge for hundreds if not thousands of years. People afflicted with syphilis could expect various skin lesions, progressive neurological problems, and congenital abnormalities in their children. Before antibiotics were introduced in the 1940s and 50s, there was no effective treatment or cure for syphilis. When penicillin became widely available, however, the rates of syphilis decreased dramatically. While antibiotics have reduced the overall incidence of syphilis, it is still a major sexually transmitted disease affecting hundreds of thousands of people each year worldwide.
What Does Syphilis Look like?
Stages of acquired syphilis
Most cases of syphilis are acquired, meaning that a person contracts the disease from an infected sexual partner or intimate contact. The bacteria (spirochetes) that cause syphilis are transmitted from an infectious lesion to either the mucous membranes or a small skin tear of the recipient.
Acquired syphilis is grouped into three distinct stages: primary, secondary and latent syphilis. It is important to understand the differences between these three stages because syphilis causes different signs and symptoms in each of these stages. The life cycle of Treponema pallidum in the body helps explain the difference between these stages as does the body’s way of reacting to the bacterium.
Primary syphilis is the stage most people typically associate with the disease. The primary stage is characterized by the presence of a skin lesion known as a chancre. A chancre is an ulcer (crater; depression) in the skin, usually on the genitals, the anus, or (less often) the mouth. A chancre is usually painless, occurs by itself, and may leak a clear fluid. The lymph nodes around the ulcer may become swollen, firm, and tender though usually only if they are directly palpated (manually examined) by a doctor. Less frequently there can be many syphilitic lesions, they can be painful, and they can cause inflammation in the genital region.
The syphilitic chancre does not appear right after sexual contact with an infectious person but is usually delayed for 9 to 90 days. On average, though, a lesion will appear in about three weeks after contracting the disease. The chancre will go away on its own, even without treatment, in about four to sixteen weeks.
Secondary syphilis takes a bit longer to appear, but it is more serious for the patient. Secondary syphilis occurs within the first two years after initial infection, but will appear after about eight weeks on average. The rash in secondary syphilis looks different than a chancre. The rash is red and composed of small, raised bumps (rather than a depression/ulcer). Generally this rash is usually not itchy, but it can be, especially in people of color.
Instead of affecting a small region of skin as syphilis does in the primary stage, secondary syphilis affects many organs throughout the body. Secondary syphilis can lead to hair loss (alopecia) and an enlargement of the spleen (splenomegaly). The second stage of syphilis may lead to inflammation of:
Syphilis in the secondary stage can also paralyze cranial nerves of the face. The cranial nerves are responsible for virtually all of the actions and sensations of the face and head. When syphilis affects the cranial nerves, it can be mistaken for a stroke or other neurological problem, like multiple sclerosis.
If syphilis goes untreated past the primary and secondary stages, it enters the latent stage. Often in the latent stage of syphilis, especially early in the latent phase, there are no signs or symptoms of the disease—it is only detected by sampling and testing the blood. The early part of the latent phase would occur within two years of infection. After two years, the latent phase is considered “late stage” and may be associated with one or more severe diseases including neurosyphilis, cardiovascular syphilis and gummatous syphilis. This late stage syphilis is sometimes called tertiary syphilis although the nomenclature varies. Many authors consider neurosyphilis a completely separate entity from the other three phases.
Not all cases of syphilis are acquired through sexual contact; a mother can pass the infection to her unborn fetus. An infected mom can pass Treponema pallidum spirochetes across the placenta. In developed countries the rate of congenital syphilis is reasonably low because of prenatal screening campaigns. The disease is detected and treatment can be given before the disease can affect the fetus. Unfortunately the rate of congenital syphilis is still high in many underdeveloped countries around the world.
If syphilis is not detected in the mother and is passed to the unborn fetus, it can cause three characteristic features in the newborn (named after Dr. Hutchinson and called the Hutchinson triad). The Hutchinson triad is Hutchinson teeth, interstitial keratitis, and eighth nerve deafness. Hutchinson teeth are widely spaced incisors (a large space between the front teeth). Interstitial keratitis is an inflammation of the cornea of the eye, which can lead to vision loss. Eighth nerve deafness is deafness that is related to the eighth cranial nerve rather than a problem with the structures of the ear. Obviously congenital syphilis can have serious consequences for the unborn.
The first, most important part to diagnosing syphilis is for it to occur to the doctor as a possibility. If the physician does not consider the diagnosis, the proper tests will not be ordered and treatment will not proceed. Therefore it is important to be completely open and candid with your doctor about your sexual history. Remember that skin lesions may not appear right after the sexual encounter and may occur weeks later. Therefore it is important to disclose all sexual partners to your physician.
Once syphilis is considered as a possibility, there are two main ways to diagnose the disease. Either the lesion can be scraped onto a microscope slide and sent to a laboratory for further analysis or blood can be drawn and tested. The first test, the direct scraping, is very sensitive and is considered the gold standard for diagnosis of syphilis. The sample is viewed under a microscope by a pathologist using a “dark-field” technique. If the pathologist can see spirochetes on the sample, the diagnosis of syphilis is made.
The problem is that there are several ways that this scraping test can be falsely negative (that is, the patient has syphilis but the test is negative). The doctor may not catch spirochetes on the scraping. The spirochetes may die before they reach the lab. The pathologist may not see spirochetes on the slide because the dark field technique is quite technically challenging. One or more of these can erroneously lead to a negative test.
The second test for syphilis, a blood test, is much more commonly used. There are several blood tests that can detect syphilis, each one tests for the presence of a different antibody in the blood. In general, the first blood test that will be run is a screening test for syphilis, either RPR or VDRL. These antibodies are not specific to the Treponema spirochete, but they are fast, inexpensive, and good at ruling out the disease. If the RPR or VDRL test is positive, then a more specific blood test can be done to look for antibodies that recognize Treponema pallidum itself.
Why isn’t this specific test just done first? Well sometimes it is, but it is much more expensive than VDRL or RPR and it can lead to false negatives. The other problem is that the Treponema-specific test will return positive whether someone was exposed twenty days ago or twenty years ago, even if treatment was successful. VDRL and RPR go up with infection (or re-infection) and down with successful treatment.
At any rate, the diagnosis of syphilis can be rather complex, especially if there are no skin lesions present. Also, remember that syphilis is known as the Great Imitator. Its symptoms can be confused with several other diseases, which further complicates diagnosis. To compensate for this, most physicians will include an inexpensive syphilis screening test along with other blood work when the diagnosis is not straightforward.
The Great Imitator – Similar diseases that can be confused with syphilis
The following list shows a portion of skin diseases that may appear like or “imitate” syphilis.
Syphilis can affect almost every organ system in the body. When diagnosing a patient with most neurological symptoms, a blood test for syphilis is often sent. This is because the disease can cause virtually any neurological symptom, from meningitis to facial nerve paralysis.
Penicillin, the antibiotic that started it all over 60 years ago, has taken a back seat to newer generation antibiotics. Today, virtually all bacteria that cause human disease are unaffected by penicillin either by antibiotic resistance or mechanism of action. This is not true with syphilis. Penicillin is the first line treatment in all stages of syphilis and is considered the treatment of choice.
For primary, secondary, and early latent syphilis, a single injection of benzathine penicillin is usually enough to treat the disease. If secondary and early latent syphilis is unaffected by this treatment, procaine penicillin can be given over ten days. For late stage latent phase syphilis, benzathine penicillin is given once a week for three weeks or procaine penicillin is given once a day for 17 days. Neurosyphilis is treated with high, intravenous doses of penicillin drugs.
If patients have an allergy to penicillin, there are two options available. Since penicillin is so effective against Treponema pallidum, patients can go through desensitization treatment for the penicillin allergy. This is similar to allergy shots used to desensitize patients for troublesome allergies. Alternatively, other antibiotics can be tried, like doxycycline, azithromycin or ceftriaxone. Again, these antibiotics are generally less effective in treating syphilis than penicillin and are used only in patients with a severe penicillin allergy.
Doctors will usually determine if treatment was successful by comparing the RPR titer in the blood before and after treatment. If the RPR titer goes down by a factor of at least four, treatment was considered successful.
Since infection with Treponema pallidum spirochetes is the way in which syphilis is spread, avoiding contact with infectious lesions is an excellent way to prevent the disease. Condoms are somewhat effective in reducing transmission if the genital lesion is covered by the prophylactic. If not, condoms cannot prevent the spread of syphilis. The only true way to avoid contracting syphilis is to completely avoid sexual contact with an infected person.
Screening for syphilis is a routine part of prenatal screening assuming that prenatal screening is obtained. Successful treatment early in the pregnancy can avoid passing the disease to the fetus.
When a diagnosis of syphilis is made, many jurisdictions require the diagnosing physician or laboratory to report the infection to a local health department. Also, an effort is made to identify sexual partners of the patient that may have been infected or transmitted the infection initially. Efforts are made to treat all people infected with the disease to prevent greater transmission through the population.
In addition, the health department reporting is useful for keeping track of RPR titers. For example, if a patient is tested in present and the titer comes back positive at a certain concentration, the physician will not know if this is a new infection or not. After making a call to the health department, a record may show that in 1993 the patient’s RPR titer was highly concentrated then, after treatment, was less concentrated (by fourfold). The present titer is equal to the treated 1993 titer. This means that treatment was successful in 1993 and that the new titer is not a new case of syphilis.
Brown DL, Frank JE. Diagnosis and management of syphilis. Am Fam Physician 2003;68:283-290.
Domantay-Apostol GP, Handog EB, Gabriel MT. Syphilis: the international challenge of the great imitator. Dermatol Clin 2008;26:191-202, v.
Lee V, Kinghorn G. Syphilis: an update. Clin Med 2008;8:330-333.
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