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The Jarisch–Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis
Thomas Butler
Thomas Butler
Department of Microbiology and Immunology, Ross University School of Medicine, Portsmouth, Dominica, West Indies.
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Within 24 hours after antibiotic treatment of the spirochetal infections syphilis, Lyme disease, leptospirosis, and relapsing fever (RF), patients experience shaking chills, a rise in temperature, and intensification of skin rashes known as the Jarisch–Herxheimer reaction (JHR) with symptoms resolving a few hours later. Case reports indicate that the JHR can also include uterine contractions in pregnancy, worsening liver and renal function, acute respiratory distress syndrome, myocardial injury, hypotension, meningitis, alterations in consciousness, seizures, and strokes. Experimental evidence indicates it is caused by nonendotoxin pyrogen and spirochetal lipoproteins. Mediation of the JHR in RF by the pro-inflammatory cytokines tumor necrosis factor (TNF), interleukin (IL)-6, and IL-8 has been proposed, consistent with measurements in patients' blood and inhibition by anti-TNF antibodies. Accelerated phagocytosis of spirochetes by polymorphonuclear (PMN) leukocytes before rise in cytokines is responsible for removal of organisms from the blood, suggesting an early inflammatory signal from PMNs. Rarely fatal, except in neonates and in pregnancy for African women whose babies showed high perinatal mortality because of low birth weight, the JHR can be regarded as an adverse effect of antibiotics, necessary for achieving a cure of spirochetal infections.
Author Notes
Author's address: Thomas Butler, Department of Microbiology and Immunology, Ross University School of Medicine, Portsmouth, Dominica, West Indies, E-mail: tbutler@rossu.edu.
ProCite
RefWorks
Reference Manager
BibTeX
Zotero
EndNote
-
1.
Aronson IK, Soltani K, 1976. The enigma of the pathogenesis of the Jarisch-Herxheimer reaction. Br J Vener Dis 52: 313–315.
-
2.
Belum GR, Belum VR, Arudra SKC, Reddy BSN, 2013. The Jarisch-Herxheimer reaction revisited. Travel Med Infect Dis 11: 231–237.
-
3.
Pound MW, May DB, 2005. Proposed mechanisms and preventative options of Jarisch-Herxheimer reactions. J Clin Pharm Ther 30: 291–295.
-
4.
Takamizawa S, Gomi H, Shimizu Y, Isono H, Shirokawa T, Kato M, 2015. Leptospirosis and Jarisch-Herxheimer reaction. QJM 108: 967–968.
-
5.
Pimenta D, Democratis J, 2013. Risky behaviour: a rare complication of an uncommon disease in a returning traveller. BMJ Case Rep 2013: pii:bcr-2013-201075.
-
6.
Gallardo C, Williams-Smith J, Jaton K, Asner S, Cheseaux JJ, Troillet N, Manuel O, Berthod D, 2015. Leptospirosis in a family after whitewater rafting in Thailand. Rev Med Suisse 11: 872–876.
-
7.
Webster G, Schiffman JD, Dosanjh AS, Amieva MR, Gans HA, Sectish TC, 2002. Jarisch-Herxheimer reaction associated with ciprofloxacin administration for tick-borne relapsing fever. Pediatr Infect Dis J 21: 571–573.
-
8.
Hoekstra KA, Kelly MT, 2011. Elevated troponin and Jarisch-Herxheimer reaction in tick-borne relapsing fever: a case report. Case Rep Infect Dis 2011: 950314.
-
9.
Nizič T, Velikanje E, Ružić-Sabljić E, Arnež M, 2012. Solitary erythema migrans in children: comparison of treatment with clarithromycin and amoxicillin. Wien Klin Wochenschr 124: 427–433.
-
10.
Tsai M-S, Yang C-J, Lee N-Y, Hsieh S-M, Lin Y-H, Sun H-Y, Sheng W-H, Lee K-Y, Yang S-P, Liu W-C, Wu P-Y, Ko W-C, Hung C-C, 2014. Jarisch-Herxheimer reaction among HIV positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy. J Int AIDS Soc 17: 18993.
-
11.
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-
12.
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-
13.
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-
14.
Myles TD, Elam G, Park-Hwang E, Nguyen T, 1998. The Jarisch-Herxheimer reaction and fetal monitoring changes in pregnant women treated for syphilis. Obstet Gynecol 92: 859–864.
-
15.
Silberstein P, Lawrence R, Pryor D, Shnier R, 2002. A case of neurosyphilis with florid Jarisch-Herxheimer reaction. J Clin Neurosci 9: 689–690.
-
16.
Davis LE, Oyer R, Beckham JD, Tyler KL, 2013. Elevated CSF cytokines in the Jarisch-Herxheimer reaction of general paresis. JAMA Neurol 70: 1060–1064.
-
17.
Punia V, Rayi A, Sivaraju A, 2014. Stroke after initiating IV penicillin for neurosyphilis: a possible Jarisch-Herxheimer reaction. Case Rep Neuro Med 2014: 548179.
-
18.
Arnež M, Ružić-Sabljić E, 2015. Azithromycin is equally effective as amoxicillin in children with solitary erythema migrans. Pediatr Infect Dis 34: 1045–1048.
-
19.
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-
20.
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-
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-
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-
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Strle F, Preac-Mursic V, Cimperman J, Ružić E, Maraspin V, Jereb M, 1993. Azithromycin versus doxycycline for treatment of erythema migrans: clinical and microbiological findings. Infection 21: 83–88.
-
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