A positive syphilis test result can be alarming, but it does not always mean a person has the infection. A false positive occurs when a test indicates the presence of syphilis-related antibodies, even though the bacterium, Treponema pallidum, is not present. This is a common occurrence, especially with initial screening procedures, and is often termed a biological false positive. Understanding the testing process and the reasons for these misleading results is key to accurate diagnosis.
The Two Categories of Syphilis Tests
Syphilis testing relies on detecting antibodies the immune system produces in response to the infection, and these tests fall into two categories. The first is the Non-Treponemal test, which includes the Rapid Plasma Reagin (RPR) and the Venereal Disease Research Laboratory (VDRL) tests. These are used primarily for screening because they measure antibodies directed against cardiolipin, a non-specific antigen released from damaged host cells during an infection. The second category is the Treponemal test, which includes assays like the Fluorescent Treponemal Antibody Absorption (FTA-ABS) and Treponema pallidum Particle Agglutination (TP-PA). These tests are designed to be confirmatory, as they detect antibodies specific to the proteins of the Treponema pallidum bacterium itself.
Common Causes in Screening Tests
False positives from Non-Treponemal screening tests occur due to cross-reactivity, where antibodies created for another purpose mistakenly bind to the test’s non-specific cardiolipin antigen. These biological false positives are broadly classified as either acute, meaning they disappear within six months, or chronic, persisting for longer periods.
One significant group of causes involves autoimmune conditions, where the body mistakenly targets its own tissues. Systemic Lupus Erythematosus (SLE) and Antiphospholipid Syndrome (APS) are primary examples, as they involve the production of antibodies similar to those generated in response to syphilis. These conditions can lead to persistent false positive RPR or VDRL results.
Acute infections are a common source of temporary false positives, as the immune system’s widespread response can create cross-reacting antibodies. Conditions that can transiently cause a positive Non-Treponemal result include:
- Mononucleosis
- Viral hepatitis
- Measles
- Malaria
- Recent vaccinations
- Chronic liver disease
- Bacterial infections such as pneumonia and tuberculosis
Physiological states and other factors can also interfere with the test’s accuracy. Pregnancy, particularly in the later stages, is a known cause of transient false positives, affecting about one to two percent of cases due to associated hormonal and immune changes. Other contributing factors include intravenous drug use, advanced age, and certain malignancies.
Rare False Positives in Confirmatory Tests
Treponemal tests, such as the FTA-ABS and TP-PA, are designed to be highly specific by targeting antibodies unique to the Treponema pallidum bacterium. Consequently, false positive results from these confirmatory tests are much rarer than those from Non-Treponemal screens. When they occur, they are often due to cross-reactivity with other spirochete bacteria that share similar antigen structures.
Infections with other members of the Treponema genus, such as the bacteria that cause the non-sexually transmitted diseases yaws, pinta, or bejel, can trigger a positive Treponemal test result. These conditions, primarily found in tropical and developing regions, cause the immune system to produce cross-reacting antibodies. Lyme disease, caused by the spirochete Borrelia burgdorferi, is another infection that has been reported to cause occasional false positive Treponemal tests.
Certain underlying chronic conditions, including autoimmune disorders like Systemic Lupus Erythematosus, can also interfere with Treponemal test results. Factors like age, with higher rates observed in people under 18 and over 45, have been linked to an increased risk of false positive Treponemal results.
Confirming the Diagnosis and Follow-Up
The primary method for resolving a potential false positive result is the use of a testing sequence, or algorithm, which combines both types of assays. If the initial Non-Treponemal screening test (RPR/VDRL) is reactive, a Treponemal confirmatory test (e.g., TP-PA, FTA-ABS) is performed. The combination of results from this two-step process determines whether the initial positive screen was a true infection or a biological false positive.
The diagnosis of a true positive for syphilis is confirmed when both the Non-Treponemal screening test and the Treponemal confirmatory test are reactive. In contrast, a biological false positive is confirmed when the screening test is reactive, but the subsequent Treponemal test is non-reactive. This discordant result indicates the reaction was caused by non-specific antibodies.
For a confirmed biological false positive, no treatment for syphilis is necessary, as the infection is not present. However, a persistent false positive result may prompt a medical professional to investigate the underlying cause, especially if the screening test remains reactive over time. Further clinical evaluation may be recommended to check for an undiagnosed autoimmune disorder or other chronic condition.