Diagnostic Issues of Asymptomatic Neurosyphilis in HIV-Positive Patients: A Retrospective Study

Introduction: Asymptomatic neurosyphilis (ANS) is a disease that is difficult to diagnose in people living with HIV (PLWH). The European Guidelines on the management of syphilis suggest that ANS should be suspected and thus the lumbar puncture (LP) should be performed in cases of (1) late syphilis (acquired >2 years previously), (2) CD4⁺ cells ≤ 350/mm³ and/or a serum Venereal Disease Research Laboratory/Rapid Plasma Reagin (VDRL/RPR) title > 1:32, (3) "serological failure" after syphilis therapy, and (4) the use of alternative treatment for syphilis. In the present study, we aimed to verify the accuracy of the guideline's criteria for the indication of LP in the suspicion of ANS in a cohort of PLWH. Methods: This retrospective study was carried out in a cohort of PLWH referred at a single medical center of a large academic hospital in Italy. Clinical and laboratory data of patients diagnosed with late syphilis were extracted from the cohort and analyzed. The European Guidelines of syphilis were adopted for patient management. Results: Out of a cohort of 713 PLWH, only 51 (7%) had a diagnosis of late syphilis and were therefore included in the study. Thirty-one subjects (61%) met one or more diagnostic criteria to perform LP: 39% (12/31) of patients undergoing LP had a diagnosis of ANS. The accuracy of predictive criteria for ANS, suggested by the guidelines, was 62% for RPR > 1:32 and 74% for CD4⁺ ≤ 350 cc/µL. The simultaneous occurrence of both criteria (RPR > 1:32 plus CD4⁺ ≤ 350 cc/µL) achieved a diagnostic accuracy of 59%. Interestingly, only 17% of patients who underwent LP for serological failure were eventually diagnosed positive for ANS. Conclusion: Asymptomatic neurosyphilis represents a challenging, but not uncommon, diagnosis. Therefore, it requires a careful investigation. Low CD4⁺ cell count and RPR > 1:32 remain excellent predictors of neurosyphilis, but have become the only acceptable predictors of ANS in PLWH. "Serologic failure" should be regarded with caution as a criterion to perform LP in order to investigate possible ANS in HIV-syphilis coinfected patients asymptomatic for neurological disorders. The retrospective nature of this single-site study may represent a limit to the interpretation of the data. Thus, larger clinical studies on the topic are warranted.