**2. Clinical situations with false-positive syphilis reactions**

A substantial problem is presented now by discordant serologic reactions for syphilis in different clinical situations [27–31]. Huh et al. [32] pointed to the growth of false-positive reactions in syphilis screening assays and proved that the reverse algorithm using Automated Mediace Treponema pallidum latex agglutination (TPLA) as a screening serologic test is preferred over rapid plasma reagin (RPR) assays [32, 33]. Furthermore, the biological false-positive Venereal Disease Research Laboratory (VDRL)—cerebrospinal fluid test is often used in cases when patients are examined without a previous serological diagnosis of syphilis [20]. Palamar et al. retrospectively explored the serologic blood sample and microbiological culture media analysis results of all cornea donors. False-positive serologic results among cornea donors were high [34], which underlines the importance of the improvement of serologic diagnostic in this field. Last year, different clinical situations confirmed the actual need for further serologic investigations [24, 35–37].

Dunseth et al. underlined the necessity of differentiation between analytical false-positive results of lues tests from clinical false-positive results. A positive syphilis IgG screen with negative RPR and T. pallidum particle agglutination assay (TP-PA) confirmatory testing could be considered an analytical false-positive. A positive syphilis IgG with positive TP-PA and negative RPR might be an analytical false-positive due to cross-reacting antibodies or analytical true-positive result in late/latent syphilis or past/treated syphilis with persistent anti-syphilis IgG. Nontreponemal tests may show false-positive screens due to a variety of reasons [38]. Ishihara et al. presented a retrospective study of patients tested for syphilis in a tertiary academic hospital. Among 94,462 subjects, 588 patients had falsepositive tests (0.62%). Such cases were noted in patients aged over 60 years, with a history of malignancy and autoimmune diseases [36]. But the false-positive tests for syphilis were noted in children as well [37]. Over all 90% of biologically falsepositive reactions are low titer (≤1:4), but (1%) are high-titer (≥1:32) [24]. Such reactions are categorized as either acute (occurring for less than 6 months) or chronic [19, 28]. Acute false-positive reactions are noted in febrile illnesses, immunizations, and pregnancy [29–31, 38–40]. For example, Nwosu et al. examined 2156 women, VDRL was positive in 15 cases (0.70%). Confirmatory T. pallidum hemagglutination assay was positive in 4 of the 15 cases, giving an overall prevalence of 0.19% and a false-positive rate of 73.3%. There was no significant difference in the prevalence of syphilis in relation to maternal age and parity (P > 0.05) [41].
