GME Patient Safety Quality and Innovation Symposium

Background: America is in the midst of a syphilis epidemic. The CDC documented 207,255 new cases of syphilis in 2022, representing the highest incidence of disease observed since 1950 and a 17.3% increase from 2021. Treponemal central nervous system (CNS) invasion is estimated to occur in approximately 25-60% of infections, however, the current standard of care for non-neurologic syphilis does not provide antimicrobial dosing sufficient to achieve CNS clearance. This raises concern for a preventable burden of neurologic morbidity secondary to treponemal CNS persistence and subsequent neurosyphilis. Our central hypothesis is that individuals with a history of syphilis infection will experience greater odds of neurologic morbidity relative to their uninfected counterparts.

Methods: A preliminary 10-year retrospective analysis (01/2013-12/31/2022) of deidentified electronic medical records (EMR) from an academic health system was undertaken. The exposure of interest consisted of grouped ICD-10 codes representative of syphilis infection, with neurologic outcomes defined as ICD-10 diagnoses reflective of the principle clinical manifestations of neurosyphilis. Exploratory analysis of psychiatric outcomes was performed understanding psychiatry to be a property emergent of neurology. Unadjusted, bivariate analysis was performed for preliminary assessment of exposure-outcome association.

Results: 3,619,941 distinct patient EMR were included in the final analysis. 5,943 patients were found to have a diagnosis of syphilis. Patients with a history of syphilis had a higher prevalence of diabetes mellitus (DM), hyperlipidemia (HLD), and HIV relative to patients without a history of syphilis. Additionally, patients with syphilis exposure were found to have significantly higher odds of neurologic morbidity outcomes including stroke (OR = 5.14; 95%CI = 4.71-5.61), dementia (OR = 20.68 ; 95%CI = 19.27–22.19 ), sensorineural hearing loss (OR= 5.75; 95% CI= 5.07-6.2), and blindness (OR= 15.74 ; 95%CI = 14.31-16.54) relative to unexposed patients. Exposed patients also had significantly higher odds of psychiatric morbidity across all mental health outcomes assessed. Sensitivity analysis was performed whereby bivariate exposure-outcome associations were reassessed within a cohort restricted to patients without the potential confounding diagnoses of DM, HLD, and HIV. All neurologic and psychiatric outcomes studied were observed to retain significance during confounder-restricted sensitivity analysis.

Conclusion: Syphilis infection was associated with significantly increased odds of neurologic and psychiatric morbidity across all outcome measures queried after controlling for several potential confounders. These data are concerning as they suggest the possibility of a clinically significant limitation to the neurologic coverage provided by the current standard of care for non-neurologic syphilis. We plan to more rigorously evaluate our hypothesis in a follow-up study that will utilize multivariate logistic regression analysis to more precisely determine the independent effect of syphilis exposure while adjusting for a number of potential confounders.