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Volume 96, Issue 1
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Abstract

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.

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References

  1. Aronson IK, Soltani K, , 1976. The enigma of the pathogenesis of the Jarisch-Herxheimer reaction. Br J Vener Dis 52: 313315.
  2. Belum GR, Belum VR, Arudra SKC, Reddy BSN, , 2013. The Jarisch-Herxheimer reaction revisited. Travel Med Infect Dis 11: 231237.[Crossref]
  3. Pound MW, May DB, , 2005. Proposed mechanisms and preventative options of Jarisch-Herxheimer reactions. J Clin Pharm Ther 30: 291295.[Crossref]
  4. Takamizawa S, Gomi H, Shimizu Y, Isono H, Shirokawa T, Kato M, , 2015. Leptospirosis and Jarisch-Herxheimer reaction. QJM 108: 967968.[Crossref]
  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: 872876.
  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: 571573.[Crossref]
  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: 427433.[Crossref]
  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.[Crossref]
  11. Yang C-J, Lee N-Y, Lin Y-H, Lee H-C, Ko W-C, Liao C-H, Wu C-H, Hsieh C-Y, Wu P-Y, Liu W-C, Chang Y-C, Hung C-C, , 2010. Jarisch-Herxheimer reaction after penicillin therapy among patients with syphilis in the era of the HIV infection epidemic: incidence and risk factors. Clin Infect Dis 51: 976979.[Crossref]
  12. Miller WM, Gorini F, Botelho G, Moreira C, Barbosa AP, Pinto ARSB, Dias MF, Sousa LM, Asensi MD, da Costa Nery JA, , 2010. Jarisch-Herxheimer reaction among syphilis patients in Rio de Janeiro, Brazil. Int J STD AIDS 21: 806809.[Crossref]
  13. Klein VR, Cox SM, Mitchell MD, Wendel GD, , 1990. The Jarisch-Herxheimer reaction complicating syphilotherapy in pregnancy. Obstet Gynecol 75: 375380.
  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: 859864.
  15. Silberstein P, Lawrence R, Pryor D, Shnier R, , 2002. A case of neurosyphilis with florid Jarisch-Herxheimer reaction. J Clin Neurosci 9: 689690.[Crossref]
  16. Davis LE, Oyer R, Beckham JD, Tyler KL, , 2013. Elevated CSF cytokines in the Jarisch-Herxheimer reaction of general paresis. JAMA Neurol 70: 10601064.[Crossref]
  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: 10451048.[Crossref]
  19. Eppes SC, Childs JA, , 2002. Comparative study of cefuroxime axetil versus amoxicillin in children with early lyme disease. Pediatrics 109: 11731177.[Crossref]
  20. Luger SW, Paparone P, Wormser GP, Nadelman RB, Grunwald E, Gomez G, Wisniewski M, Collins JJ, , 1995. Comparison of cefuroxime axetil and doxycycline in treatment of patients with early lyme disease associated with erythema migrans. Antimicrob Agents Chemother 39: 661667.[Crossref]
  21. Nadelman RB, Luger SW, Frank E, Wisniewski M, Collins JJ, Wormser GP, , 1992. Comparison of cefuroxime axetil and doxycycline in the treatment of early lyme disease. Ann Intern Med 117: 273280.[Crossref]
  22. Steere AC, Hutchinson GJ, Rahn DW, Sigal LH, Craft JE, DeSanna ET, Malawista SE, , 1983. Treatment of the early manifestations of lyme disease. Ann Intern Med 99: 2226.[Crossref]
  23. 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: 8388.[Crossref]
  24. Strle F, Maraspin V, Lotric-Furlan S, Ružić-Sabljić E, Cimperman J, , 1996. Azithromycin and doxycycline for treatment of Borrelia culture-positive erythema migrans. Infection 24: 6670.
  25. Strle F, Ružić E, Cimperman J, , 1992. Erythema migrans: comparison of treatment with azithromycin, doxycycline and phenoxymethylpenicillin. J Antimicrob Chemother 30: 543550.[Crossref]
  26. Guerrier G, D'Ortenzio E, , 2013. The Jarisch-Herxheimer reaction in leptospirosis: a systematic review. PLoS One 8: e59266.[Crossref]
  27. MacKay-Dick J, Robinson JF, , 1957. Penicillin in the treatment of 84 cases of leptospirosis in Malaya. J R Army Med Corps 103: 186197.
  28. Dworkin MS, Shoemaker PC, Fritz CL, Dowell ME, Anderson DE, , 2002. The epidemiology of tick-borne relapsing fever in the United States. Am J Trop Med Hyg 66: 753758.
  29. Asi HM, Goya MM, Vatandoost H, Zahraei SM, Mafi M, Asmar M, Piazak N, Aghighi Z, , 2009. The epidemiology of tick-borne relapsing fever in Iran during 1997–2006. Travel Med Infect Dis 7: 160164.[Crossref]
  30. Guerrier G, Doherty T, , 2011. Comparison of antibiotic regimens for treating louse-borne relapsing fever: a meta-analysis. Trans R Soc Trop Med Hyg 105: 483490.[Crossref]
  31. Butler T, Jones PK, Wallace CK, , 1978. Borrelia recurrentis infection: single-dose antibiotic regimens and management of the Jarisch-Herxheimer reaction. J Infect Dis 137: 573577.[Crossref]
  32. Warrell DA, Perine PL, Krause DW, Bing DH, MacDougal SJ, , 1983. Pathophysiology and immunology of the Jarisch-Herxheimer-like reaction in louse-borne relapsing fever: comparison of tetracycline and slow-release penicillin. J Infect Dis 147: 898909.[Crossref]
  33. Seboxa T, Rahlenbeck SI, , 1995. Treatment of louse-borne relapsing fever with low dose penicillin or tetracycline: a clinical trial. Scand J Infect Dis 27: 2931.[Crossref]
  34. Rac MWF, Greer LG, Wendel GD, , 2010. Jarisch-Herxheimer reaction triggered by group B Streptococcus intrapartum antibiotic prophylaxis. Obstet Gynecol 116: 552556.[Crossref]
  35. Hori H, Sato Y, Shitara T, , 2015. Congenital syphilis presenting as Jarisch-Herxheimer reaction at birth. Pediatr Int 57: 299301.[Crossref]
  36. See S, Scott EK, Levin MW, , 2005. Penicillin-induced Jarisch-Herxheimer reaction. Ann Pharmacother 39: 21282130.[Crossref]
  37. Cooper C, MacPherson P, Angel JB, , 2005. Liver toxicity resulting from syphilis and Jarisch-Herxheimer reaction in cases of co-infection with HIV and hepatitis C virus. Clin Infect Dis 40: 12111212.[Crossref]
  38. Berger EM, Galadari HI, Gottlieb AB, , 2008. Case reports: unilateral facial paralysis after treatment of secondary syphilis. J Drugs Dermatol 7: 583585.
  39. Bucher JB, Golden MR, Heald AE, Marra CM, , 2011. Stroke in a patient with human immunodeficiency virus and syphilis treated with penicillin and antiretroviral therapy. Sex Transm Dis 38: 442444.[Crossref]
  40. Kojan S, Van Ness PC, Diaz-Arrastia R, , 2000. Nonconvulsive status epilepticus resulting from Jarisch-Herxheimer reaction in a patient with neurosyphilis. Clin Electroencephalogr 31: 138140.[Crossref]
  41. Zifko U, Lindner K, Wimberger D, Volc B, Grisold W, , 1994. Jarisch-Herxheimer reaction in a patient with neurosyphilis. J Neurol Neurosurg Psychiatry 57: 865867.[Crossref]
  42. Zhang S-Q, Wan B, Ma X-L, Zheng H-M, , 2008. Worsened MRI findings during the early period of treatment with penicillin in a patient with general paresis. J Neuroimaging 18: 360363.[Crossref]
  43. Hagiya H, Deguchi K, Kawada K, Otsuka F, , 2015. Neurosyphilis is a long-forgotten disease but still a possible etiology for dementia. Intern Med 54: 27692773.[Crossref]
  44. Maloy AL, Black RD, Segurola RJ, , 1998. Lyme disease complicated by the Jarisch-Herxheimer reaction. J Emerg Med 16: 437438.[Crossref]
  45. Vaughn C, Cronin CC, Walsh EK, Whelton M, , 1994. The Jarisch-Herxheimer reaction in leptospirosis. Postgrad Med J 70: 118121.[Crossref]
  46. Tattevin P, Jaureguiberry S, Michelet C, , 2003. Meningitis as a possible feature of the Jarisch-Herxheimer reaction. Eur J Clin Microbiol Infect Dis 22: 449.[Crossref]
  47. Hashimoto T, Akata S, Park J, Harada Y, Hirayama Y, Otaki J, Tokuuye K, , 2012. High-resolution computed tomography findings in a case of severe leptospira infection (Weil disease) complicated with Jarisch-Herxheimer reaction. J Thorac Imaging 27: W24W26.[Crossref]
  48. Markham R, Slack A, Gerrard J, , 2012. The Jarisch-Herxheimer reaction in a patient with leptospirosis: a foreseeable problem in managing spirochaete infections. Med J Aust 197: 276277.[Crossref]
  49. Friedland JS, Warrell DA, , 1991. The Jarisch-Herxheimer reaction in leptospirosis: possible pathogenesis and review. Rev Infect Dis 13: 207210.[Crossref]
  50. Garcia-Soler P, Nunez-Cuadros E, Milano-Manso G, Sanchez PR, , 2011. Severe Jarisch-Herxheimer reaction in tick-borne relapsing fever. Enferm Infecc Microbiol Clin 29: 710711.[Crossref]
  51. Wilting KR, Stienstra Y, Sinha B, Braks M, Cornish D, Grundmann H, , 2015. Louse-borne relapsing fever (Borrelia recurrentis) in asylum seekers from Eritrea, The Netherlands, July 2015. Euro Surveill 20: 20.30.21196.[Crossref]
  52. Badger MS, , 2008. Tick talk: unusually severe case of tick-borne relapsing fever with acute respiratory distress syndrome—case report and review of literature. Wild Env Med J 19: 280286.[Crossref]
  53. Colebunders R, De Serrano P, Van Gompel A, Wynants H, Blot K, Van Den Enden E, Van Den Ende J, , 1993. Imported relapsing fever in European tourists. Scand J Infect Dis 25: 533536.[Crossref]
  54. Jongen VHWM, van Roosmalen J, Tiems J, Holten JV, Wetsteyn JCFM, , 1997. Tick-borne relapsing fever and pregnancy outcome in rural Tanzania. Acta Obstet Gynecol Scand 76: 834838.[Crossref]
  55. Rustenhoven-Spaan I, Melkert P, Nelissen E, van Roosmalen J, Stekelenburg J, , 2013. Maternal mortality in a rural Tanzanian hospital: fatal Jarisch-Herxheimer reaction in a case of relapsing fever in pregnancy. Trop Doct 43: 138141.[Crossref]
  56. Melkert PWJ, Stel HV, , 1991. Neonatal Borrelia infections (relapsing fever): report of 5 cases and review of the literature. East Afr Med J 68: 9991005.
  57. Bryceson ADM, Cooper KE, Warrell DA, Perine PL, Parry EHO, , 1972. Studies of the mechanism of the Jarisch-Herxheimer reaction in louse-borne relapsing fever: evidence for the presence of circulating Borrelia endotoxin. Clin Sci 43: 343354.[Crossref]
  58. Bryceson ADM, , 1976. Clinical pathology of the Jarisch-Herxheimer reaction. J Infect Dis 133: 696704.[Crossref]
  59. Gelfand JA, Elin RJ, Berry FW, Frank MM, , 1976. Endotoxemia associated with the Jarisch-Herxheimer reaction. N Engl J Med 295: 211213.[Crossref]
  60. Takayama K, Rothenberg RJ, Barbour AG, , 1987. Absence of lipopolysaccharide in the lyme disease spirochete, Borrelia burgdorferi . Infect Immun 55: 23112313.
  61. Young EJ, Weingarten NM, Baughn RE, Duncan WC, , 1982. Studies on the pathogenesis of the Jarisch-Herxheimer reaction: development of an animal model and evidence against a role for classical endotoxin. J Infect Dis 146: 606615.[Crossref]
  62. Shenep JL, Feldman S, Thornton D, , 1986. Evaluation for endotoxemia in patients receiving penicillin therapy for secondary syphilis. JAMA 256: 388390.[Crossref]
  63. Hardy PH, Levin J, , 1983. Lack of endotoxin in Borrelia hispanica and Treponema pallidum . Proc Soc Exp Biol Med 174: 4752.[Crossref]
  64. Akins DR, Purcell BK, Mitra MM, Norgard MV, Radolf JD, , 1993. Lipid modification of the 17-kilodalton membrane immunogen of Treponema pallidum determines macrophage activation as well as amphiphilicity. Infect Immun 61: 12021210.
  65. Bulut Y, Faure E, Thomas L, Equils O, Arditi M, , 2001. 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. J Immunol 167: 987994.[Crossref]
  66. Butler T, Hazen P, Wallace CK, Awoke S, Habte-Michael A, , 1979. Borrelia recurrentis infection: pathogenesis of fever and petechiae. J Infect Dis 140: 665675.[Crossref]
  67. Yang C-W, Hung C-C, Wu M-S, Tian Y-C, Chang C-T, Pan M-J, Vandewalle A, , 2006. Toll-like receptor 2 mediates early inflammation by leptospiral outer membrane proteins in proximal tubule cells. Kidney Int 69: 815822.[Crossref]
  68. Negussie Y, Remick DG, DeForge LE, Kunkel SL, Eynon A, Griffin GE, , 1992. Detection of plasma tumor necrosis factor, interleukins 6, and 8 during the Jarisch-Herxheimer reaction of relapsing fever. J Exp Med 175: 12071212.[Crossref]
  69. Butler T, Aikawa M, Habte-Michael A, Wallace CK, , 1980. Phagocytosis of Borrelia recurrentis by polymorphonuclear leukocytes is enhanced by antibiotic treatment. Infect Immun 28: 10091013.
  70. Galloway RE, Levin J, Butler T, Naff GB, Goldsmith GH, Saito H, Awoke S, Wallace CK, , 1977. Activation of protein mediators on inflammation and evidence for endotoxemia in Borrelia recurrentis infection. Am J Med 63: 933938.[Crossref]
  71. Loveday C, Bingham JS, , 1985. Changes in intravascular complement, kininogen, and histamine during Jarisch-Herxheimer reaction in secondary syphilis. Genitourin Med 61: 2732.
  72. Fekade D, Knox K, Hussein K, Melka A, Lalloo DG, Coxon RE, Warrell DA, , 1996. Prevention of Jarisch-Herxheimer reactions by treatment with antibodies against tumor necrosis factor α. N Engl J Med 335: 311315.[Crossref]
  73. Coxon RE, Fekade D, Knox K, Hussein K, Melka A, Daniel A, Griffin GG, Warrell DA, , 1997. The effect of antibody against TNF alpha on cytokine response in Jarisch-Herxheimer reactions of louse-borne relapsing fever. QJM 90: 213221.[Crossref]
  74. Wooten RM, Ma Y, Yoder RA, Brown JP, Weis JH, Zachary JF, Kirschning CJ, Weis JJ, , 2002. Toll-like receptor 2 is required for innate, but not acquired, host defense to Borrelia burgdorferi . J Immunol 168: 348355.[Crossref]
  75. Oosting M, ter Hofstede H, Sturm P, Adema GJ, Kulberg B-J, van der Meer JWM, Netea MG, Joosten LAB, , 2011. TLR1/TLR2 heterodimers play an important role in the recognition of Borrelia spirochetes. PLoS One 6: e25998.[Crossref]
  76. Cooper PJ, Fekade D, Remick DG, Grint P, Wherry J, Griffin GE, , 2000. Recombinant human interleukin-10 fails to alter proinflammatory production or physiogic changes associated with the Jarisch-Herxheimer reaction. J Infect Dis 181: 203209.[Crossref]
  77. Cruz AR, Moore MW, La Vake CJ, Eggers CH, Salazar JC, Radolf JD, , 2008. Phagocytosis of Borrelia burgdorferi, the lyme disease spirochete, potentiates innate immune activation and induces apoptosis in human monocytes. Infect Immun 76: 5670.[Crossref]
  78. Petnicki-Ocwieja T, Chung E, Acosta DI, Ramos LT, Shin OS, Ghosh S, Kobzik L, Li X, Hu LT, , 2013. TRIF mediates Toll-like receptor 2-dependent inflammatory responses to Borrelia burgdorferi . Infect Immun 81: 402410.[Crossref]
  79. Shin OS, Isberg RR, Akira S, Uematsu S, Behera AK, Hu LT, , 2008. Distinct roles for MyD88 and toll-like receptors 2, 5, and 9 in phagocytosis of Borrelia burgdorferi and cytokine induction. Infect Immun 76: 23412351.[Crossref]
  80. Dennis VA, Dixit S, O'Brien SM, Alvarez X, Pahar B, Philipp MT, , 2009. Live Borrelia burgdorferi spirochetes elicit inflammatory mediators from human monocytes via the Toll-like receptor signaling pathway. Infect Immun 77: 12381245.[Crossref]
  81. Castilla-Guerra L, Alvarez-Suero J, Fernandez-Moreno MDC, Fontana ER, , 2009. Tick-borne relapsing fever: conjunctival haemorrhages. BMJ Case Rep 2009: pii:bcro6.2008.0114.[Crossref]
  82. Cuevas LE, Borgnolo G, Hailu B, Smith G, Almaviva M, Hart CA, , 1995. Tumour necrosis factor, interleukin-6, and C-reactive protein in patients with louse-borne relapsing fever in Ethiopia. Ann Trop Med Parasitol 89: 4954.[Crossref]
  83. Skog E, Gudjonsson H, , 1966. On the allergic origin of the Jarisch-Herxheimer reaction. Acta Derm Venereol 46: 136143.
  84. De Koning J, Hoogkamp-Korstanje JAA, , 1986. Diagnosis of lyme disease by demonstration of spirochetes in tissue biopsies. Zbl Bakt Hyg A 263: 179188.
  85. Luft BJ, Gorevic PD, Halperin JJ, Volkman DJ, Dattwyler RJ, , 1989. A perspective on the treatment of lyme borreliosis. Rev Infect Dis 11 (Suppl 6): S1518S1525.[Crossref]
  86. Kadam P, Gregory NA, Zelger B, Carlson JA, , 2015. Delayed onset of the Jarisch-Herxheimer reaction in doxycycline-treated disease: a case report and review of its histopathology and implications for pathogenesis. Am J Dermatopathol 37: e68e74.[Crossref]
  87. Luger A, Pavlik F, , 1971. Der einfluss von korticosteroiden auf die Jarisch-Herxheimer-reacktion. Wien Klin Wochenschr 83: 208212.
  88. Muller G, , 1983. Suppression of the Jarisch-Herxheimer reaction by means of prednisolone. Dermatol Monatsschr 169: 232234.
  89. Gudjonsson H, Skog E, , 1968. The effect of prednisolone on the Jarisch-Herxheimer reaction. Acta Derm Venereol 48: 1518.
  90. Sheldon WH, Heyman A, , 1949. Morphologic changes in syphilitic lesions during the Jarisch-Herxheimer reaction. Amer J Syphilis 33: 213224.
  91. Teklu B, Habte-Michael A, Warrell DA, White NJ, Wright DJM, , 1983. Meptazinol diminishes the Jarisch-Herxheimer reaction of relapsing fever. Lancet 1: 835839.[Crossref]
  92. Remick DG, Negussie Y, Fekade D, Griffin G, , 1996. Pentoxifylline fails to prevent the Jarisch-Herxheimer reaction or associated cytokine release. J Infect Dis 174: 627630.[Crossref]
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  • Received : 31 May 2016
  • Accepted : 20 Sep 2016

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