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

Yu-Ting Tseng; Pei-Yun Chou; Ming-Hong Tai; Chia-Yen Dai; Susan Shin-Jung Lee; Yao-Shen Chen; Hung-Chin Tsai; Yen-Hsu Chen

doi:10.2147/IDR.S335121

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

Infect Drug Resist. 2021 Dec 2:14:5121-5129. doi: 10.2147/IDR.S335121. eCollection 2021.

Authors

Yu-Ting Tseng^{1

2}, Pei-Yun Chou¹, Ming-Hong Tai^{2

3}, Chia-Yen Dai^{4

5

6}, Susan Shin-Jung Lee^{1

7}, Yao-Shen Chen^{1

7}, Hung-Chin Tsai^#^{1

3

7

8}, Yen-Hsu Chen^#^{2

6

9

10

11

12

13}

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.
² Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
³ Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan.
⁴ Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
⁵ Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁶ School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁷ Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan.
⁸ Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan.
⁹ Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹⁰ Sepsis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹¹ Center of Tropical Medicine and Infectious Diseases, Kaohsiung Medical University, Kaohsiung, Taiwan.
¹² Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan.
¹³ Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan.

^# Contributed equally.

Abstract

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.

Keywords: C-reactive protein; Jarisch-Herxheimer reaction; syphilis.