In this study, we explored the correlation between the RPR titer and GP. Serum RPR titer ≥1:32 has been described as a risk factor for neurosyphilis with HIV infection regardless of the stage of syphilis [7,8,9]. In this study, we also found that the number of CSF RPR+ patients with serum RPR titer ≥1:32 was significantly higher when compared with CSF RPR- patients.
When patients have symptomatic neurosyphilis, the success of therapy is assessed by normalization of CSF abnormalities, including pleocytosis, elevated protein concentration, or a reactive CSF VDRL test, and by resolution of symptoms and signs . Repeated determination of serum RPR titer is recommended to evaluate treatment response, with a four-fold decrease from baseline and/or seroreversion in 12–24 months after treatment representing an appropriate response to therapy/serologic cure . Marra et al. found that a four-fold decline in serologic RPR titers correlated with resolution of CSF parameters in persons with neurosyphilis, and normalization of serum RPR titer correctly predicted treatment success of neurosyphilis . However, we found a four-fold decline in CSF RPR titer is more likely to occur than four-fold decline in serum RPR titer among these CSF RPR+ GP patients after penicillin treatment. Reactive non-treponemal test in non-HIV-infected late (latent) syphilis patients often remains stable after adequate therapy . Many studies have found the serological response of nontreponemal tests (ie, VDRL, RPR) to treatment was influenced by syphilis stage but not by HIV infection or reinfection [11,12,13,14]. Compared to primary syphilis, later stages of syphilis showed a significantly slower treatment response [11, 13,14,15,16,17]. In this study, all the GP patients were late syphilis, which probably explains the 4-fold decline in serum RPR titers might not adequately predict treatment efficacy in GP patients. The majority of patients were early neurosyphilis in the study by Marra et al. , which could partially explain why a four-fold decline in CSF RPR titer instead of the serum RPR normalization found by Marra is a good predictor of treatment efficacy in HIV-negative CSF RPR+ GP patients in our finding. According to these results, it should be emphasized that the disease stage of syphilis might lead to different treatment response. Different recommendations may be needed for the follow-up of neurosyphilis depending on the stage of the disease.
During the follow-up at 12 months after penicillin treatment, no significant difference was found in the four-fold decline in serum RPR titer between CSF RPR+ and CSF RPR- patients. According to our data and our analyses, for CSF RPR- patients, normalization of CSF measures, not serum RPR titer value, is a sensible way of assessing treatment efficacy. A cutoff of greater than or equal to 5 cells/μL has been the standard for determining normal CSF values. For CSF RPR- GP patients, CSF WBC count was often normal before treatment, so it is difficult to evaluate the treatment efficacy by assessing the recovery of CSF WBC. CSF protein concentration in neurosyphilis is slow to normalize and may remain elevated even after the normalization of other CSF and clinical abnormalities [10, 18]. Thus, the decision to re-treat should not be based solely on failure of CSF protein concentration to normalize . Importantly, our study found that the number of CSF RPR- patients (91%) with CSF protein concentration > 45 mg/dl was significantly higher when compared with CSF RPR+ patients (74%) (P = 0.028). The normalization of CSF protein concentration occurred in most of CSF RPR- GP patients by follow-up, which suggested that it may be a good indicator of the success of therapy in GP, although the number of this patient group by follow-up is relatively small. Further studies should be conducted to provide more evidence on this question.
Some limitations of our study should be considered. Specifically, a) the study is a retrospective study, in which case the association may be confounded or modified by patient characteristics; b) the large percentage of loss of follow-up leads to small number of the patients with follow-up, which has limited the statistical power; c) further studies are required to assess an association between RPR titers and the clinical features of these cases, and to identify an ideal indicator of the success of therapy for CSF-RPR- GP patients.