Syphilis is a bacterial infection caused by the organism Treponema pallidum and is typically diagnosed through blood tests that look for specific antibodies. A false positive result occurs when a test indicates the presence of an infection when the patient is not actually infected. Because the body’s immune response can sometimes lead to an inaccurate finding, a positive result on the initial screening test does not automatically mean a person has syphilis. For this reason, a two-step testing approach is standard practice to ensure an accurate diagnosis, acknowledging the limitations of initial screening methods.
The Two Types of Syphilis Tests
Syphilis testing relies on serology, the detection of antibodies in the blood, and tests are divided into two categories. Non-treponemal tests (e.g., RPR or VDRL) are used for initial screening because they are inexpensive and easy to perform. They detect antibodies the body produces in response to damaged cells and lipids that occur during infection, rather than antibodies specific to the Treponema pallidum bacterium.
The antigens used in non-treponemal tests are composed of substances like cardiolipin. Because the test reacts to these general anti-lipid antibodies, it can sometimes react to similar antibodies produced during other non-syphilis conditions. This lack of specificity is why false positive results almost exclusively occur with this type of initial screening test.
The second category is treponemal tests (e.g., TP-PA or various immunoassays), which are highly specific and used to confirm a diagnosis. These tests detect antibodies directly aimed at the Treponema pallidum organism. Unlike screening tests, these antibodies usually remain present in the blood for life, even after successful treatment. A positive treponemal test therefore indicates either a current or a successfully treated past infection, distinguishing a true syphilis infection from a biological false positive.
Medical Conditions That Cause False Positives
A false positive result on a non-treponemal syphilis test is known as a “biological false positive.” This occurs because various medical conditions cause the body to produce the same non-specific antibodies the test detects. The test reagents cross-react, incorrectly signaling syphilis. This reaction is an inherent limitation of the screening methodology, not a lab error.
Autoimmune disorders, such as systemic lupus erythematosus (SLE) or rheumatoid arthritis, are common causes of biological false positives. These conditions cause the immune system to attack the body’s own tissues, producing anti-lipid antibodies that mimic those from a syphilis infection. Chronic false positive reactions, persisting for more than six months, are frequently associated with these long-term inflammatory states.
Acute, temporary conditions can also cause a transient false positive result, often reverting to negative once the condition resolves. These conditions include:
- Other infections (e.g., mononucleosis, malaria, or Lyme disease).
- Recent vaccinations.
- Pregnancy, due to hormonal and immunological changes.
- Intravenous drug use.
- Older age.
A reactive screening test always necessitates further investigation to determine the true cause of the antibody reaction.
Confirming the Diagnosis After a Positive Result
The clinical process following a positive screening test resolves whether the result is a true infection or a false positive. If the initial non-treponemal test is reactive, the sample is immediately sent for a treponemal test to confirm the diagnosis. The interpretation of these two results determines patient care.
If both tests are reactive, it indicates a current or recently treated syphilis infection. If the screening test is reactive but the treponemal test is non-reactive, the result is a biological false positive. In this scenario, the specific treponemal test confirmed the absence of the actual infection.
Some laboratories utilize a “reverse sequence screening” algorithm, beginning with the automated treponemal test. If positive, it is followed by the non-treponemal test. If results are discordant, a second, different treponemal test is used to resolve the discrepancy, as the initial treponemal screening test can sometimes yield a false positive result.
For confirmed syphilis cases, non-treponemal test results are reported with a quantitative titer (e.g., 1:4 or 1:32), which indicates the concentration of antibodies. This titer is crucial for monitoring the patient’s response to treatment. A successful course should lead to a significant drop in the titer, tracking disease activity.