Why is the VDRL (Venereal Disease Research Laboratory) test often positive in elderly patients?

Why VDRL Tests Are Often Positive in Elderly Patients

The VDRL test shows a significantly higher rate of biological false-positive (BFP) results in elderly patients—approximately 0.34% in those over 60 years compared to 0.25% in younger adults—making age-related false positivity a well-documented phenomenon that must be considered when interpreting results in this population. 1

Understanding Biological False-Positive Reactions

The term "biological false positive" refers to a positive VDRL result in patients who do not have syphilis infection, confirmed by negative treponemal-specific testing (such as FTA-ABS or TP-PA). 1

Age-Related Increase in False Positivity

• Elderly patients (>60 years) demonstrate statistically significant higher BFP rates compared to younger populations, with the difference being clinically meaningful (0.34% vs 0.25%, P<0.001). 1
• In a large retrospective analysis of 300,000 sera, BFP reactions comprised 26% of all VDRL-positive results, highlighting that roughly one in four positive VDRL tests may not represent true syphilis infection. 1
• The specificity of VDRL testing is reduced in elderly and ill persons compared to healthy younger populations, though it remains high in general screening contexts. 2

Mechanism Behind Age-Related False Positivity

• VDRL detects antiphospholipid antibodies (not treponemal-specific antibodies) that are produced in response to cellular damage during active Treponema pallidum infection. 3
• Elderly patients accumulate various medical conditions that can trigger antiphospholipid antibody production independent of syphilis, including autoimmune diseases, chronic infections, and age-related tissue damage. 3, 1
• The test's reliance on detecting nonspecific antibodies makes it inherently susceptible to cross-reactivity with conditions more prevalent in older age. 4

Critical Diagnostic Algorithm for Elderly Patients

When an elderly patient has a positive VDRL:

1. Always confirm with a treponemal-specific test (FTA-ABS, TP-PA, or treponemal EIA/CLIA) before making any diagnosis of syphilis. 5, 6
2. If the treponemal test is negative, the VDRL result represents a biological false positive and does not indicate syphilis. 5, 6
3. If the treponemal test is positive, proceed with clinical staging and appropriate treatment based on disease stage. 5, 6
4. Request quantitative VDRL titers (not just positive/negative), as titers ≥1:8 are more likely to represent true infection, while lower titers (1:1 to 1:4) are more commonly false positive. 3, 7

Additional Risk Factors That Compound Age-Related False Positivity

Beyond age alone, elderly patients often have comorbidities that further increase BFP risk:

• HIV infection increases BFP rates 10-fold (2.1% vs 0.24% in HIV-negative patients), and HIV prevalence may be underrecognized in older adults. 1
• Hepatitis B and C infections show elevated BFP rates (8.3% and 4.5% respectively). 3
• Autoimmune conditions, which accumulate with age, are well-established causes of false-positive nontreponemal tests. 3, 4

Common Pitfalls to Avoid

• Never diagnose syphilis based on VDRL alone in any patient, but especially in elderly individuals where false positivity is more common. 5, 6
• Do not assume a positive VDRL in an elderly patient represents past treated syphilis without confirming with treponemal testing and reviewing treatment history. 5
• Avoid using VDRL as the sole screening test in elderly populations; treponemal-first algorithms may be more appropriate in settings with low syphilis prevalence and older patient demographics. 1
• Remember that VDRL sensitivity is also reduced in late syphilis (61-75% in late latent disease), so a negative VDRL does not exclude syphilis in elderly patients with positive treponemal tests. 3, 5