High Baseline C-Reactive Protein Level Can Predict the Occurrence of the Jarisch–Herxheimer Reaction in Patients with Active Syphilis

BACKGROUND: The Jarisch–Herxheimer reaction (JHR) is an inflammatory reaction that can occur after treatment for syphilis. The mechanism of JHR is unknown. The level of C-reactive protein (CRP) increases during infection and inflammation. We hypothesized that CRP may be involved in the JHR in syphilitic patients at initial syphilis infection and also through interactions with benzathine penicillin-induced phagocytosis. METHODS: This prospective cohort study enrolled syphilitic adult patients with/without JHR between July 2018 and October 2020. Serum samples before and after the administration of the first dose of benzathine penicillin were obtained. The serum level of CRP was determined by ELISA. The Kruskal–Wallis test was used to compare the levels of CRP in different groups, and the Wilcoxon signed-rank test was used to compare changes in CRP before and after benzathine penicillin treatment. RESULTS: Twenty-nine syphilitic patients and three control groups (10 men who have sex with men (MSM) taking pre-exposure prophylaxis, 10 HIV-infected patients without syphilis, and 12 HIV-infected patients with previous syphilis) were enrolled. All 29 syphilitic patients were MSM, and 21 patients (72%) were infected with HIV. Overall, 41% (12/29) of the patients developed the JHR. The active syphilis groups had significantly higher serum levels of CRP (median 11,761 ng/mL, IQR 2986–19,061 ng/mL). There were no significant differences in the serum levels of CRP before or after benzathine penicillin treatment. The 12 patients with the JHR had significantly higher CRP levels before benzathine penicillin treatment (16,262 ng/mL [IQR 12,033–26,150 ng/mL] vs 3489 ng/mL [IQR 924–160,640] ng/mL, p = 0.0059, 95% CI 4002–17,098 ng/mL, area under the curve 0.799, 95% CI 0.632–0.966, sensitivity 1, specificity 0.647, with a CRP cut-off value of 4569.32 ng/mL). CONCLUSION: A high baseline CRP level can predict the occurrence of the JHR in syphilitic patients treated with benzathine penicillin.