Diagnostic Accuracy of Treponema pallidum Immunostaining in a Cohort of Patients With Secondary Syphilis

Abstract

Immunohistochemical (IHC) staining/Immunohistochemistry (IHC) for spirochetes in skin specimens can be used to diagnose secondary syphilis. In the last decade, IHC has replaced silver staining as the primary histochemical diagnostic tool, given its greater sensitivity and specificity [1]. Traditionally, nontreponemal serologic testing, such as the rapid plasma reagin (RPR) test, has served as the primary screening method for diagnosing syphilis, despite its somewhat limited specificity [2]. Limited data are available assessing IHC's diagnostic accuracy compared to standard serologic testing. Our objective is to determine the diagnostic accuracy of IHC in comparison to RPR serology.

In our study, we identified 175 patients in a private practice whose skin eruption generated a differential diagnosis including secondary syphilis, and who also underwent skin biopsies with additional anti-Treponema pallidum IHC from January 1, 2014 to December 31, 2022. The anti-T. pallidum IHC (Biocare Medical, no dilution [ready to use], Ref APA135AA, Pacheco, CA, USA) was assessed by two independent reviewers ensuring inter-rater reliability (Figure 1). Those patients who did not have a contemporaneous (RPR) test or underwent anti-T. pallidum immunostaining for other diseases were excluded (Figure 2). We determined the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of anti-T. pallidum IHC in this cohort.

The enrolled cohort consisted of 26 patients, of whom 17 (65%) were male with an average age of 42.54 ± 13.39 years (SD). All of these skin biopsies were analyzed as pre-treatment samples, with the exception of one patient. In comparison to RPR serology, anti-T. pallidum IHC showed sensitivity of 80.00%, specificity of 90.48%, PPV of 66.67%, and NPV of 95.00%.

Our findings support IHC as a potentially valid method for diagnosing syphilis when compared to nontreponemal serologic testing. Previous studies have shown similar results, with a range of documented sensitivities of 60%–94% for anti-T. pallidum immunostaining [1, 3-5]. Reasons for the variations in prior sensitivities include the sample size of our cohort, exclusion of specimen without an associated RPR test and our sample only consisting of lesions of secondary syphilis. In our study, one patient who had a positive RPR and negative IHC result had been recently treated for syphilis and developed a “new” skin eruption which was determined to be a Jarisch–Herxheimer reaction. It would be expected that the spirochetes in his skin would disappear before the serologic response normalized. Occasional false positives for IHC have been seen in borreliosis and other spirochete infections but were not observed in our study [6, 7].

The Centers for Disease Control and Prevention does not currently recognize IHC as a diagnostic method for syphilis despite its widespread use among dermatopathologists and its proven efficacy. In clinical practice, dermatologists and dermatopathologists often encounter situations where confirmatory tests like FTA-ABS or even RPR/VDRL are unavailable. Frequently, dermatopathologists must rely solely on IHC for diagnosis. Our data, despite the limitation of small sample size, suggests that if anti-T. pallidum IHC is used in conjunction with clinical suspicion (i.e., ruling out other potential spirochetal infections) and/or histopathologic findings, it can be a reliable diagnostic tool. Our study suggests that T. pallidum IHC is a potentially valid method for detecting secondary syphilis, even in cases when serologic studies (i.e., RPR) are not available.

The authors declare no conflicts of interest.