Increased Serum APOC3 in Patients with Syphilis Can Predict the Absence of Jarisch-Herxheimer Reaction after Benzathine Penicillin Treatment

Sep 29, 2026

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A prospective cohort study examined whether apolipoprotein C3 (APOC3) relates to Jarisch–Herxheimer reaction (JHR) in adults with active syphilis receiving benzathine penicillin. Serum APOC3 levels were measured before and after the first dose, using ELISA and nonparametric comparisons. The study found higher baseline APOC3 in syphilis cases versus controls and identified an optimal cutoff for predicting absence of JHR. Results support baseline APOC3 as a predictive biomarker for JHR non-occurrence after initial therapy.

LanguageEnglish

CategoryHealthcare

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Pages8

Reading Time20 min

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Abstract

Background

Methods

Results

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Introduction

J Chin MedAssoc Original article Increased serum APOC3 in patients with syphilis can predict the absence of Jarisch–Herxheimer reaction after benzathine penicillin treatment Hung-Chin Tsaia,b,c,d,e,*, Pei-Yun Choua, Hui-Min Changf,g,h, Susan Shin-Jung Leea,b, Yao-Shen Chena,b aDivision of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; bFaculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC; cInstitute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC; dSchool of Medicine, College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan, ROC; eShu-Zen Junior College of Medicine and Management, Kaohsiung, Taiwan, ROC; fDepartment of Pharmacy, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC; gInstitute of Clinical Pharmacy and Pharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; hDepartment of Pharmacy, Chia Nan University of Pharmacy and Science, Tainan, Taiwan, ROC Abstract Background: Apolipoprotein C3 (APOC3) was found to induce inflammation in human monocytes. Jarisch–Herxheimer reaction (JHR) was perceived to be caused by immune reactions of dividing spirochaetes to penicillin treatment. The aim of this study was to investigate the role of APOC3 in patients with syphilis and JHR. Methods: This prospective cohort study enrolled adult patients with active syphilis with/without JHR. Serum samples were collected before and after administration of the first dose of benzathine penicillin and the serum levels of APOC3 were determined by enzyme-linked immunosorbent assay (ELISA) . The APOC3 level and changes in APOC3 level before and after benzathine penicillin treatment in different groups were compared with the Mann-Whitney U test or Kruskal-Wallis test. Results: Forty adult patients with syphilis and 32 controls were enrolled. All 40 patients with syphilis were men who have sex with men, and 30 (75%) were people living with human immunodeficiency virus (HIV) . Overall, 19 patients (47%) developed JHR. The active syphilis group had a significantly higher serum APOC3 level (median 38.3 µg/mL, interquartile range [IQR]: 34.5-48.0 µg/mL) than the controls (p = 0.020) . The serum levels of APOC3 were higher in the 21 patients without JHR before and after benzathine penicillin treatment compared with the controls (38 .9 µg/mL [IQR: 34.5-66.7 µg/mL] and 39.4 µg/mL [IQR: 33.7-62.9] µg/mL vs 31.8 µg/mL [IQR: 27.5-42.2 µg/mL]) . Receiving operating characteristic curve analysis showed that the best cutoff value of APOC3 to predict the absence of JHR before benzathine penicillin therapy compared to the controls was 34.2 µg/mL (area under the curve 0.695, p = 0.017, CI = 0.544-0.846, sensitivity = 0.81, specificity = 0.406) . Conclusion: A high baseline serum APOC3 level can predict the absence of JHR in patients with syphilis treated with the first dose of benzathine penicillin. Keywords: APOC3; Diagnostics; Jarisch–Herxheimer reaction; Syphilis Lay Summary: Jarisch–Herxheimer reaction (JHR) is an inflammatory response to spirochaetal infections. The clinical manifestations include fever, chills, myalgia, headache and exacerbations of skin rashes. Apolipoprotein C3 (APOC3) is involved in lipid metabolism and its main effect is to inhibit the function of lipoprotein lipase, delaying lipid metabolism and causing lipid deposition. Recently, APOC3 was found to be able to activate *Address correspondence. Dr. Hung-Chin Tsai, Section of Infectious Diseases, Department of Medicine, Kaohsiung Veterans General Hospital, 386, Ta-Chung 1st Road, Kaohsiung 813, Taiwan, ROC. E-mail address: tsaihungchin@gmail. com (H.-C. Tsai). Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. Journal of Chinese Medical Association. (2025) 88

FAQs

What was the study’s goal regarding APOC3 and JHR in syphilis patients?

To investigate the role of APOC3 in patients with syphilis and Jarisch–Herxheimer reaction (JHR), especially in relation to outcomes after benzathine penicillin treatment.

How were serum APOC3 levels measured in the study?

Serum samples were collected before and after administration of the first dose of benzathine penicillin, and APOC3 levels were determined by ELISA.

What did the study conclude about baseline APOC3 and JHR absence?

A high baseline serum APOC3 level can predict the absence of JHR in patients with syphilis treated with the first dose of benzathine penicillin.

Sep 29, 2026

Uploaded by Eliana