{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:49:32Z","timestamp":1792648172553,"version":"4.5.0"},"reference-count":92,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,1,11]]},"abstract":"<jats:p>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\u2013Herxheimer 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.<\/jats:p>","DOI":"10.4269\/ajtmh.16-0434","type":"journal-article","created":{"date-parts":[[2016,10,24]],"date-time":"2016-10-24T22:29:06Z","timestamp":1477348146000},"page":"46-52","source":"Crossref","is-referenced-by-count":182,"title":["The Jarisch\u2013Herxheimer Reaction After Antibiotic Treatment of Spirochetal Infections: A Review of Recent Cases and Our Understanding of Pathogenesis"],"prefix":"10.4269","volume":"96","author":[{"given":"Thomas","family":"Butler","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, Ross University School of Medicine, Portsmouth, Dominica, West 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traveller","volume":"2013","author":"Pimenta","year":"2013"},{"key":"ref6","series-title":"Rev Med Suisse","first-page":"872","article-title":"Leptospirosis in a family after whitewater rafting in Thailand","volume":"11","author":"Gallardo","year":"2015"},{"key":"ref7","series-title":"Pediatr Infect Dis J","first-page":"571","article-title":"Jarisch-Herxheimer reaction associated with ciprofloxacin administration for tick-borne relapsing fever","volume":"21","author":"Webster","year":"2002"},{"key":"ref8","series-title":"Case Rep Infect Dis","first-page":"950314","article-title":"Elevated troponin and Jarisch-Herxheimer reaction in tick-borne relapsing fever: a case report","volume":"2011","author":"Hoekstra","year":"2011"},{"key":"ref9","series-title":"Wien Klin Wochenschr","first-page":"427","article-title":"Solitary erythema migrans in children: comparison of treatment with clarithromycin and amoxicillin","volume":"124","author":"Nizi\u010d","year":"2012"},{"key":"ref10","series-title":"J Int AIDS Soc","first-page":"18993","article-title":"Jarisch-Herxheimer reaction among HIV positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy","volume":"17","author":"Tsai","year":"2014"},{"key":"ref11","series-title":"Clin Infect Dis","first-page":"976","article-title":"Jarisch-Herxheimer reaction after penicillin therapy among patients with syphilis in the era of the HIV infection epidemic: incidence and risk factors","volume":"51","author":"Yang","year":"2010"},{"key":"ref12","series-title":"Int J STD AIDS","first-page":"806","article-title":"Jarisch-Herxheimer reaction among syphilis patients in Rio de Janeiro, Brazil","volume":"21","author":"Miller","year":"2010"},{"key":"ref13","series-title":"Obstet Gynecol","first-page":"375","article-title":"The Jarisch-Herxheimer reaction complicating syphilotherapy in pregnancy","volume":"75","author":"Klein","year":"1990"},{"key":"ref14","series-title":"Obstet Gynecol","first-page":"859","article-title":"The Jarisch-Herxheimer reaction and fetal monitoring changes in pregnant women treated for syphilis","volume":"92","author":"Myles","year":"1998"},{"key":"ref15","series-title":"J Clin Neurosci","first-page":"689","article-title":"A case of neurosyphilis with florid Jarisch-Herxheimer reaction","volume":"9","author":"Silberstein","year":"2002"},{"key":"ref16","series-title":"JAMA Neurol","first-page":"1060","article-title":"Elevated CSF cytokines in the Jarisch-Herxheimer reaction of general paresis","volume":"70","author":"Davis","year":"2013"},{"key":"ref17","series-title":"Case Rep Neuro Med","first-page":"548179","article-title":"Stroke after initiating IV penicillin for neurosyphilis: a possible Jarisch-Herxheimer reaction","volume":"2014","author":"Punia","year":"2014"},{"key":"ref18","series-title":"Pediatr Infect Dis","first-page":"1045","article-title":"Azithromycin is equally effective as amoxicillin in children with solitary erythema migrans","volume":"34","author":"Arne\u017e","year":"2015"},{"key":"ref19","series-title":"Pediatrics","first-page":"1173","article-title":"Comparative study of cefuroxime axetil versus amoxicillin in children with early lyme disease","volume":"109","author":"Eppes","year":"2002"},{"key":"ref20","series-title":"Antimicrob Agents Chemother","first-page":"661","article-title":"Comparison of cefuroxime axetil and doxycycline in treatment of patients with early lyme disease associated with erythema migrans","volume":"39","author":"Luger","year":"1995"},{"key":"ref21","series-title":"Ann Intern Med","first-page":"273","article-title":"Comparison of cefuroxime axetil and doxycycline in the treatment of early lyme disease","volume":"117","author":"Nadelman","year":"1992"},{"key":"ref22","series-title":"Ann Intern Med","first-page":"22","article-title":"Treatment of the early manifestations of lyme disease","volume":"99","author":"Steere","year":"1983"},{"key":"ref23","series-title":"Infection","first-page":"83","article-title":"Azithromycin versus doxycycline for treatment of erythema migrans: clinical and microbiological findings","volume":"21","author":"Strle","year":"1993"},{"key":"ref24","series-title":"Infection","first-page":"66","article-title":"Azithromycin and doxycycline for treatment of Borrelia culture-positive erythema migrans","volume":"24","author":"Strle","year":"1996"},{"key":"ref25","series-title":"J Antimicrob Chemother","first-page":"543","article-title":"Erythema migrans: comparison of treatment with azithromycin, doxycycline and phenoxymethylpenicillin","volume":"30","author":"Strle","year":"1992"},{"key":"ref26","series-title":"PLoS One","first-page":"e59266","article-title":"The Jarisch-Herxheimer reaction in leptospirosis: a systematic review","volume":"8","author":"Guerrier","year":"2013"},{"key":"ref27","series-title":"J R Army Med Corps","first-page":"186","article-title":"Penicillin in the treatment of 84 cases of leptospirosis in Malaya","volume":"103","author":"MacKay-Dick","year":"1957"},{"key":"ref28","series-title":"Am J Trop Med Hyg","first-page":"753","article-title":"The epidemiology of tick-borne relapsing fever in the United States","volume":"66","author":"Dworkin","year":"2002"},{"key":"ref29","series-title":"Travel Med Infect Dis","first-page":"160","article-title":"The epidemiology of tick-borne relapsing fever in Iran during 1997\u20132006","volume":"7","author":"Asi","year":"2009"},{"key":"ref30","series-title":"Trans R Soc Trop Med Hyg","first-page":"483","article-title":"Comparison of antibiotic regimens for treating louse-borne relapsing fever: a meta-analysis","volume":"105","author":"Guerrier","year":"2011"},{"key":"ref31","series-title":"J Infect Dis","first-page":"573","article-title":"Borrelia recurrentis infection: single-dose antibiotic regimens and management of the Jarisch-Herxheimer reaction","volume":"137","author":"Butler","year":"1978"},{"key":"ref32","series-title":"J Infect Dis","first-page":"898","article-title":"Pathophysiology and immunology of the Jarisch-Herxheimer-like reaction in louse-borne relapsing fever: comparison of tetracycline and slow-release penicillin","volume":"147","author":"Warrell","year":"1983"},{"key":"ref33","series-title":"Scand J Infect Dis","first-page":"29","article-title":"Treatment of louse-borne relapsing fever with low dose penicillin or tetracycline: a clinical trial","volume":"27","author":"Seboxa","year":"1995"},{"key":"ref34","series-title":"Obstet Gynecol","first-page":"552","article-title":"Jarisch-Herxheimer reaction triggered by group B Streptococcus intrapartum antibiotic prophylaxis","volume":"116","author":"Rac","year":"2010"},{"key":"ref35","series-title":"Pediatr Int","first-page":"299","article-title":"Congenital syphilis presenting as Jarisch-Herxheimer reaction at birth","volume":"57","author":"Hori","year":"2015"},{"key":"ref36","series-title":"Ann Pharmacother","first-page":"2128","article-title":"Penicillin-induced Jarisch-Herxheimer reaction","volume":"39","author":"See","year":"2005"},{"key":"ref37","series-title":"Clin Infect Dis","first-page":"1211","article-title":"Liver toxicity resulting from syphilis and Jarisch-Herxheimer reaction in cases of co-infection with HIV and hepatitis C virus","volume":"40","author":"Cooper","year":"2005"},{"key":"ref38","series-title":"J Drugs Dermatol","first-page":"583","article-title":"Case reports: unilateral facial paralysis after treatment of secondary syphilis","volume":"7","author":"Berger","year":"2008"},{"key":"ref39","series-title":"Sex Transm Dis","first-page":"442","article-title":"Stroke in a patient with human immunodeficiency virus and syphilis treated with penicillin and antiretroviral therapy","volume":"38","author":"Bucher","year":"2011"},{"key":"ref40","series-title":"Clin Electroencephalogr","first-page":"138","article-title":"Nonconvulsive status epilepticus resulting from Jarisch-Herxheimer reaction in a patient with neurosyphilis","volume":"31","author":"Kojan","year":"2000"},{"key":"ref41","series-title":"J Neurol Neurosurg Psychiatry","first-page":"865","article-title":"Jarisch-Herxheimer reaction in a patient with neurosyphilis","volume":"57","author":"Zifko","year":"1994"},{"key":"ref42","series-title":"J Neuroimaging","first-page":"360","article-title":"Worsened MRI findings during the early period of treatment with penicillin in a patient with general paresis","volume":"18","author":"Zhang","year":"2008"},{"key":"ref43","series-title":"Intern Med","first-page":"2769","article-title":"Neurosyphilis is a long-forgotten disease but still a possible etiology for dementia","volume":"54","author":"Hagiya","year":"2015"},{"key":"ref44","series-title":"J Emerg Med","first-page":"437","article-title":"Lyme disease complicated by the Jarisch-Herxheimer reaction","volume":"16","author":"Maloy","year":"1998"},{"key":"ref45","series-title":"Postgrad Med J","first-page":"118","article-title":"The Jarisch-Herxheimer reaction in leptospirosis","volume":"70","author":"Vaughn","year":"1994"},{"key":"ref46","series-title":"Eur J Clin Microbiol Infect Dis","first-page":"449","article-title":"Meningitis as a possible feature of the Jarisch-Herxheimer reaction","volume":"22","author":"Tattevin","year":"2003"},{"key":"ref47","series-title":"J Thorac Imaging","first-page":"W24","article-title":"High-resolution computed tomography findings in a case of severe leptospira infection (Weil disease) complicated with Jarisch-Herxheimer reaction","volume":"27","author":"Hashimoto","year":"2012"},{"key":"ref48","series-title":"Med J Aust","first-page":"276","article-title":"The Jarisch-Herxheimer reaction in a patient with leptospirosis: a foreseeable problem in managing spirochaete infections","volume":"197","author":"Markham","year":"2012"},{"key":"ref49","series-title":"Rev Infect Dis","first-page":"207","article-title":"The Jarisch-Herxheimer reaction in leptospirosis: possible pathogenesis and review","volume":"13","author":"Friedland","year":"1991"},{"key":"ref50","series-title":"Enferm Infecc Microbiol Clin","first-page":"710","article-title":"Severe Jarisch-Herxheimer reaction in tick-borne relapsing fever","volume":"29","author":"Garcia-Soler","year":"2011"},{"key":"ref51","series-title":"Euro Surveill","article-title":"Louse-borne relapsing fever (Borrelia recurrentis) in asylum seekers from Eritrea, The Netherlands, July 2015","volume":"20","author":"Wilting","year":"2015"},{"key":"ref52","series-title":"Wild Env Med J","first-page":"280","article-title":"Tick talk: unusually severe case of tick-borne relapsing fever with acute respiratory distress syndrome\u2014case report and review of literature","volume":"19","author":"Badger","year":"2008"},{"key":"ref53","series-title":"Scand J Infect Dis","first-page":"533","article-title":"Imported relapsing fever in European tourists","volume":"25","author":"Colebunders","year":"1993"},{"key":"ref54","series-title":"Acta Obstet Gynecol Scand","first-page":"834","article-title":"Tick-borne relapsing fever and pregnancy outcome in rural Tanzania","volume":"76","author":"Jongen","year":"1997"},{"key":"ref55","series-title":"Trop Doct","first-page":"138","article-title":"Maternal mortality in a rural Tanzanian hospital: fatal Jarisch-Herxheimer reaction in a case of relapsing fever in pregnancy","volume":"43","author":"Rustenhoven-Spaan","year":"2013"},{"key":"ref56","series-title":"East Afr Med J","first-page":"999","article-title":"Neonatal Borrelia infections (relapsing fever): report of 5 cases and review of the literature","volume":"68","author":"Melkert","year":"1991"},{"key":"ref57","series-title":"Clin Sci","first-page":"343","article-title":"Studies of the mechanism of the Jarisch-Herxheimer reaction in louse-borne relapsing fever: evidence for the presence of circulating Borrelia endotoxin","volume":"43","author":"Bryceson","year":"1972"},{"key":"ref58","series-title":"J Infect Dis","first-page":"696","article-title":"Clinical pathology of the Jarisch-Herxheimer reaction","volume":"133","author":"Bryceson","year":"1976"},{"key":"ref59","series-title":"N Engl J Med","first-page":"211","article-title":"Endotoxemia associated with the Jarisch-Herxheimer reaction","volume":"295","author":"Gelfand","year":"1976"},{"key":"ref60","series-title":"Infect Immun","first-page":"2311","article-title":"Absence of lipopolysaccharide in the lyme disease spirochete, Borrelia burgdorferi","volume":"55","author":"Takayama","year":"1987"},{"key":"ref61","series-title":"J Infect Dis","first-page":"606","article-title":"Studies on the pathogenesis of the Jarisch-Herxheimer reaction: development of an animal model and evidence against a role for classical endotoxin","volume":"146","author":"Young","year":"1982"},{"key":"ref62","series-title":"JAMA","first-page":"388","article-title":"Evaluation for endotoxemia in patients receiving penicillin therapy for secondary syphilis","volume":"256","author":"Shenep","year":"1986"},{"key":"ref63","series-title":"Proc Soc Exp Biol Med","first-page":"47","article-title":"Lack of endotoxin in Borrelia hispanica and Treponema pallidum","volume":"174","author":"Hardy","year":"1983"},{"key":"ref64","series-title":"Infect Immun","first-page":"1202","article-title":"Lipid modification of the 17-kilodalton membrane immunogen of Treponema pallidum determines macrophage activation as well as amphiphilicity","volume":"61","author":"Akins","year":"1993"},{"key":"ref65","series-title":"J Immunol","first-page":"987","article-title":"Cooperation of Toll-like receptor 2 and 6 for cellular activation by soluble tuberculosis factor and Borrelia burgdorferi outer surface protein A lipoprotein: role of toll-interacting protein and IL-1 receptor signaling molecules in Toll-like receptor 2 signaling","volume":"167","author":"Bulut","year":"2001"},{"key":"ref66","series-title":"J Infect Dis","first-page":"665","article-title":"Borrelia recurrentis infection: pathogenesis of fever and petechiae","volume":"140","author":"Butler","year":"1979"},{"key":"ref67","series-title":"Kidney Int","first-page":"815","article-title":"Toll-like receptor 2 mediates early inflammation by leptospiral outer membrane proteins in proximal tubule cells","volume":"69","author":"Yang","year":"2006"},{"key":"ref68","series-title":"J Exp Med","first-page":"1207","article-title":"Detection of plasma tumor necrosis factor, interleukins 6, and 8 during the Jarisch-Herxheimer reaction of relapsing fever","volume":"175","author":"Negussie","year":"1992"},{"key":"ref69","series-title":"Infect Immun","first-page":"1009","article-title":"Phagocytosis of Borrelia recurrentis by polymorphonuclear leukocytes is enhanced by antibiotic treatment","volume":"28","author":"Butler","year":"1980"},{"key":"ref70","series-title":"Am J Med","first-page":"933","article-title":"Activation of protein mediators on inflammation and evidence for endotoxemia in Borrelia recurrentis infection","volume":"63","author":"Galloway","year":"1977"},{"key":"ref71","series-title":"Genitourin Med","first-page":"27","article-title":"Changes in intravascular complement, kininogen, and histamine during Jarisch-Herxheimer reaction in secondary syphilis","volume":"61","author":"Loveday","year":"1985"},{"key":"ref72","series-title":"N Engl J Med","first-page":"311","article-title":"Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor \u03b1","volume":"335","author":"Fekade","year":"1996"},{"key":"ref73","series-title":"QJM","first-page":"213","article-title":"The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever","volume":"90","author":"Coxon","year":"1997"},{"key":"ref74","series-title":"J Immunol","first-page":"348","article-title":"Toll-like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi","volume":"168","author":"Wooten","year":"2002"},{"key":"ref75","series-title":"PLoS One","first-page":"e25998","article-title":"TLR1\/TLR2 heterodimers play an important role in the recognition of Borrelia spirochetes","volume":"6","author":"Oosting","year":"2011"},{"key":"ref76","series-title":"J Infect Dis","first-page":"203","article-title":"Recombinant human interleukin-10 fails to alter proinflammatory production or physiogic changes associated with the Jarisch-Herxheimer reaction","volume":"181","author":"Cooper","year":"2000"},{"key":"ref77","series-title":"Infect Immun","first-page":"56","article-title":"Phagocytosis of Borrelia burgdorferi, the lyme disease spirochete, potentiates innate immune activation and induces apoptosis in human monocytes","volume":"76","author":"Cruz","year":"2008"},{"key":"ref78","series-title":"Infect Immun","first-page":"402","article-title":"TRIF mediates Toll-like receptor 2-dependent inflammatory responses to Borrelia burgdorferi","volume":"81","author":"Petnicki-Ocwieja","year":"2013"},{"key":"ref79","series-title":"Infect Immun","first-page":"2341","article-title":"Distinct roles for MyD88 and toll-like receptors 2, 5, and 9 in phagocytosis of Borrelia burgdorferi and cytokine induction","volume":"76","author":"Shin","year":"2008"},{"key":"ref80","series-title":"Infect Immun","first-page":"1238","article-title":"Live Borrelia burgdorferi spirochetes elicit inflammatory mediators from human monocytes via the Toll-like receptor signaling pathway","volume":"77","author":"Dennis","year":"2009"},{"key":"ref81","series-title":"BMJ Case Rep","article-title":"Tick-borne relapsing fever: conjunctival haemorrhages","volume":"2009","author":"Castilla-Guerra","year":"2009"},{"key":"ref82","series-title":"Ann Trop Med Parasitol","first-page":"49","article-title":"Tumour necrosis factor, interleukin-6, and C-reactive protein in patients with louse-borne relapsing fever in Ethiopia","volume":"89","author":"Cuevas","year":"1995"},{"key":"ref83","series-title":"Acta Derm Venereol","first-page":"136","article-title":"On the allergic origin of the Jarisch-Herxheimer reaction","volume":"46","author":"Skog","year":"1966"},{"key":"ref84","series-title":"Zbl Bakt Hyg A","first-page":"179","article-title":"Diagnosis of lyme disease by demonstration of spirochetes in tissue biopsies","volume":"263","author":"De Koning","year":"1986"},{"issue":"(Suppl 6)","key":"ref85","series-title":"Rev Infect Dis","first-page":"S1518","article-title":"A perspective on the treatment of lyme borreliosis","volume":"11","author":"Luft","year":"1989"},{"key":"ref86","series-title":"Am J Dermatopathol","first-page":"e68","article-title":"Delayed onset of the Jarisch-Herxheimer reaction in doxycycline-treated disease: a case report and review of its histopathology and implications for pathogenesis","volume":"37","author":"Kadam","year":"2015"},{"key":"ref87","series-title":"Wien Klin Wochenschr","first-page":"208","article-title":"Der einfluss von korticosteroiden auf die Jarisch-Herxheimer-reacktion","volume":"83","author":"Luger","year":"1971"},{"key":"ref88","series-title":"Dermatol Monatsschr","first-page":"232","article-title":"Suppression of the Jarisch-Herxheimer reaction by means of prednisolone","volume":"169","author":"Muller","year":"1983"},{"key":"ref89","series-title":"Acta Derm Venereol","first-page":"15","article-title":"The effect of prednisolone on the Jarisch-Herxheimer reaction","volume":"48","author":"Gudjonsson","year":"1968"},{"key":"ref90","series-title":"Amer J Syphilis","first-page":"213","article-title":"Morphologic changes in syphilitic lesions during the Jarisch-Herxheimer reaction","volume":"33","author":"Sheldon","year":"1949"},{"key":"ref91","series-title":"Lancet","first-page":"835","article-title":"Meptazinol diminishes the Jarisch-Herxheimer reaction of relapsing fever","volume":"1","author":"Teklu","year":"1983"},{"key":"ref92","series-title":"J Infect Dis","first-page":"627","article-title":"Pentoxifylline fails to prevent the Jarisch-Herxheimer reaction or associated cytokine release","volume":"174","author":"Remick","year":"1996"}],"container-title":["The American Society of Tropical Medicine and 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