Syphilis testing identifies infection with the bacterium Treponema pallidum. However, a positive test result doesn’t always confirm an active infection. This article explores why false positives occur, clarifying situations where a positive test might not indicate syphilis.
How Syphilis Tests Work
Syphilis diagnosis typically involves two main types of blood tests: nontreponemal and treponemal tests. Nontreponemal tests, such as the Rapid Plasma Reagin (RPR) and Venereal Disease Research Laboratory (VDRL) tests, are often used for initial screening. These tests detect antibodies that the body produces in response to substances released from cells damaged by the syphilis bacteria, as well as substances from the bacteria itself, like cardiolipin. However, these antibodies are not specific to Treponema pallidum and can be generated due to other conditions.
Treponemal tests, including TP-PA (Treponema pallidum particle agglutination), EIA (enzyme immunoassay), CIA (chemiluminescence immunoassay), and FTA-ABS (fluorescent treponemal antibody absorption), are used to confirm a syphilis diagnosis. These tests specifically look for antibodies produced only in response to the Treponema pallidum bacterium. While nontreponemal tests are more prone to false positives, treponemal tests are more specific and remain reactive for life, even after successful treatment.
What a False Positive Means
A false positive result in syphilis testing indicates the presence of syphilis antibodies, even though the person has never been infected with the bacteria. This occurs because the body can produce antibodies that mimic those seen in syphilis due to various other health conditions or factors.
Receiving a false positive can lead to emotional distress, including anxiety and stress, and may result in additional, unnecessary testing. It can also create a financial burden due to further medical evaluations. Healthcare providers use confirmatory tests to differentiate true syphilis infections from these false positive results.
Underlying Health Conditions
Several medical conditions can trigger the immune system to produce antibodies that cross-react with syphilis tests, leading to a false positive. Autoimmune diseases, where the body mistakenly attacks its own tissues, are a common cause. Conditions like lupus (systemic lupus erythematosus) and rheumatoid arthritis can result in false positive syphilis tests because they generate antibodies that interfere with the testing process. Antiphospholipid syndrome, an autoimmune disorder, can also cause false positives, particularly with VDRL tests, due to its associated antibodies reacting with cardiolipin.
Other infections can also lead to false positive syphilis results, including Lyme disease, malaria, HIV, hepatitis C, and mononucleosis. Infections caused by other treponemal bacteria, such as yaws and pinta, can cross-react with syphilis tests because they are closely related. Certain cancers, including lymphoma, have also been associated with false positive syphilis tests.
Other Non-Medical Causes
Beyond specific medical conditions, various non-medical factors can contribute to a false positive syphilis test. Pregnancy is a notable cause, with false positives occurring in about 1-2% of cases due to hormonal changes and increased antibody activity. These changes can affect nontreponemal tests, causing them to react positively even without syphilis.
Recent vaccinations, particularly those that provoke a strong immune response, can also lead to temporary false positive results. Intravenous drug use is another factor associated with false positives, as it can stimulate the production of antibodies that interfere with syphilis testing. Advanced age has been linked to an increased likelihood of false positive results, with very high-titer false positives being more common in individuals over 60. While less common, technical errors in laboratory processing, such as cross-contamination or improper sample handling, can also contribute to inaccurate results.
Confirming a Positive Result
When an initial syphilis test yields a positive result, healthcare providers do not rely on this single result for diagnosis. It is standard practice to perform additional, more specific tests to confirm whether a true infection is present or if it is a false positive. Typically, if a nontreponemal screening test like RPR or VDRL is reactive, a treponemal confirmatory test (such as TP-PA, EIA, CIA, or FTA-ABS) will be used. These confirmatory tests specifically detect antibodies that target the Treponema pallidum bacterium.
If the initial nontreponemal test is positive but the treponemal confirmatory test is negative, it strongly suggests a false positive. Consulting with a doctor for follow-up testing and interpretation of results is important. Confirmatory tests provide clarity and reassurance, guiding appropriate next steps, which for a false positive, means no syphilis treatment is needed.