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

Abstract

Yu-Ting Tseng,1,2 Pei-Yun Chou,1 Ming-Hong Tai,2,3 Chia-Yen Dai,4– 6 Susan Shin-Jung Lee,1,7 Yao-Shen Chen,1,7 Hung-Chin Tsai,1,3,7,8,* Yen-Hsu Chen2,6,9– 13,* 1Division of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 2Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 3Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Taiwan; 4Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 5Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 6School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; 7Faculty of Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 8Department of Parasitology, Kaohsiung Medical University, Kaohsiung, Taiwan; 9Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; 10Sepsis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 11Center of Tropical Medicine and Infectious Diseases, Kaohsiung Medical University, Kaohsiung, Taiwan; 12Department of Biological Science and Technology, College of Biological Science and Technology, National Chiao Tung University, HsinChu, Taiwan; 13Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung, Taiwan*These authors contributed equally to this workCorrespondence: Hung-Chin TsaiDivision of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, TaiwanEmail [email protected] ChenGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, TaiwanEmail [email protected]: 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

Keywords

• c-reactive protein
• jarisch-herxheimer reaction
• syphilis