Jarisch–Herxheimer reaction

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Herxheimer reaction
Classification and external resources
ICD-10 T78.2
ICD-9-CM 995.0
DiseasesDB 32939

A Jarisch–Herxheimer reaction (English /ˌjɑːrɪʃ ˈhɛərkshmər/) is a reaction to endotoxin-like products released by the death of harmful microorganisms within the body during antibiotic treatment. The antibiotics are so successful at killing a lot of bacterial cells that now the contents of those burst cells provoke some irritation and must be cleared.

Jarisch–Herxheimer reactions are usually not life-threatening. Often they last only a few hours. They can be uncomfortable, however, and it helps to be forewarned that they might occur, because it allays some of the anxiety (that is, it helps answer the questions of "what is happening, and how bad will it get?").

Signs and symptoms[edit]

It resembles bacterial sepsis and can occur after initiation of antibacterials, such as mild silver protein, penicillin or tetracycline, for the treatment of louse-borne relapsing fever (80–90% of patients) and in tick-borne relapsing fever (30–40%). An association has been found between the release of heat-stable proteins from spirochetes and the reaction. Typically, the death of these bacteria and the associated release of endotoxins or lipoproteins occurs faster than the body can remove the substances. It usually manifests within a few hours of the first dose of antibiotic as fever, chills, rigor, hypotension, headache, tachycardia, hyperventilation, vasodilation with flushing, myalgia (muscle pain), exacerbation of skin lesions and anxiety. The intensity of the reaction indicates the severity of inflammation. Reaction commonly occurs within two hours of drug administration, but is usually self-limiting.


The Jarisch–Herxheimer reaction is classically associated with penicillin treatment of syphilis. Duration in syphilis is normally only a few hours. The reaction is also seen in other diseases caused by spirochetes, such as borreliosis (Lyme disease and tick-borne relapsing fever) and leptospirosis, and in Q fever.[1] Similar reactions have also been reported to occur in bartonellosis (including cat scratch disease),[2][3] brucellosis,[4] typhoid fever,[5] trichinosis,[6] and cerebral trypanosomiasis.[7]


The Herxheimer reaction has shown an increase in inflammatory cytokines during the period of exacerbation, including tumor necrosis factor alpha, interleukin-6 and interleukin-8.[8][9] In an analogy to how the successful killing of a lot of undesirable cells by chemotherapy can present the corollary problem of tumor lysis syndrome, the successful killing of a lot of bacterial cells presents the resultant problem of clearing their constituents from the blood. The analogy is not precise because the cell contents differ; but the concept is instructive.


Prophylaxis and treatment with an anti-inflammatory agent may stop progression of the reaction. Oral aspirin or ibuprofen every four hours for a day or 60 mg of prednisone orally or intravenously has been used as an adjunctive treatment[citation needed]. However, steroids are generally of no benefit. Patients must be closely monitored for the potential complications (collapse and shock) and may require IV fluids to maintain adequate blood pressure. If available, meptazinol, an opioid analgesic of the mixed agonist/antagonist type, should be administered to reduce the severity of the reaction. Anti TNF-a may also be effective.[10][11]


Both Adolf Jarisch,[12] an Austrian dermatologist, and Karl Herxheimer,[13] a German dermatologist, are credited with the discovery of the Jarisch–Herxheimer reaction. Both Jarisch and Herxheimer observed reactions in patients with syphilis treated with mercury. The reaction was first seen following treatment in early and later stages of syphilis treated with Salvarsan, mercury, or antibiotics. Jarisch thought that the reaction was caused by a toxin released from the dying spirochetes.[14] It is observed in 50% of patients with primary syphilis and about 90% of patients with secondary syphilis.[1]


  1. ^ a b Loscalzo, Joseph; Fauci, Anthony S.; Braunwald, Eugene; Dennis L. Kasper; Hauser, Stephen L; Longo, Dan L. (2008). Harrison's Principles of Internal Medicine. McGraw-Hill Medical. pp. 1048–67. ISBN 0-07-146633-9. 
  2. ^ Rolain JM, Brouqui P, Koehler JE, Maguina C, Dolan MJ, Raoult D (June 2004). "Recommendations for treatment of human infections caused by Bartonella species". Antimicrob Agents Chemother. 48 (6): 1921–33. doi:10.1128/AAC.48.6.1921-1933.2004. PMC 415619Freely accessible. PMID 15155180. 
  3. ^ Koehler JE, Duncan LM (September 29, 2005). "Case records of the Massachusetts General Hospital. Case 30-2005. A 56-year-old man with fever and axillary lymphadenopathy". New England Journal of Medicine. 353 (13): 1387–94. doi:10.1056/NEJMcpc059027. PMID 16192484. 
  4. ^ Madkour MM (2003). "Brucellosis". In D. A. Warrell; Timothy M. Cox; John D. Firth. Oxford Textbook of Medicine. Oxford: Oxford University Press. p. 545. ISBN 0-19-262922-0. 
  5. ^ Keith Parker; Laurence Brunton; Goodman, Louis Sanford; Donald Blumenthal; Iain Buxton (2008). "Protein synthesis inhibitors and miscellaneous antibacterial agents". Goodman & Gilman's manual of pharmacology and therapeutics. McGraw-Hill Medical. p. 768. ISBN 0-07-144343-6. 
  6. ^ Grove DI (2003). "Nematode infections of lesser importance". In D. A. Warrell; Timothy M. Cox; John D. Firth. Oxford Textbook of Medicine. Oxford: Oxford University Press. p. 809. ISBN 0-19-262922-0. 
  7. ^ F.P. MacKie (1935). "The Jarisch–Herxheimer reaction in trypanosomiasis with a note on the morular cells of Mott". Trans R Soc Trop Med Hyg. 28 (4): 377–84. doi:10.1016/S0035-9203(35)90132-8. 
  8. ^ Vidal V, Scragg IG, Cutler SJ, et al. (December 1998). "Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever". Nat. Med. 4 (12): 1416–20. doi:10.1038/4007. PMID 9846580. 
  9. ^ Kaplanski G, Granel B, Vaz T, Durand JM (July 1998). "Jarisch–Herxheimer reaction complicating the treatment of chronic Q fever endocarditis: elevated TNFalpha and IL-6 serum levels". J. Infect. 37 (1): 83–4. doi:10.1016/S0163-4453(98)91120-3. PMID 9733392. 
  10. ^ Fekade, D; Knox, K; Hussein, K; Melka, A; Lalloo, DG; Coxon, RE; Warrell, DA (Aug 1, 1996). "Prevention of Jarisch–Herxheimer reactions by treatment with antibodies against tumor necrosis factor alpha.". The New England Journal of Medicine. 335 (5): 311–5. doi:10.1056/NEJM199608013350503. PMID 8663853. 
  11. ^ Coxon, RE; Fekade, D; Knox, K; Hussein, K; Melka, A; Daniel, A; Griffin, GG; Warrell, DA (Mar 1997). "The effect of antibody against TNF alpha on cytokine response in Jarisch–Herxheimer reactions of louse-borne relapsing fever." (PDF). QJM : monthly journal of the Association of Physicians. 90 (3): 213–21. doi:10.1093/qjmed/90.3.213. PMID 9093599. 
  12. ^ Jarisch A (1895). "Therapeutische Versuche bei Syphilis". Wien Med Wochenschr. 45: 721–42. 
  13. ^ Herxheimer K, Krause D (1902). "Ueber eine bei Syphilitischen vorkommende Quecksilberreaktion". Deutsch Med Wochenschr. 28 (50): 895–7. doi:10.1055/s-0028-1139096. 
  14. ^ "The Jarisch–Herxheimer reaction". Lancet. 1 (8007): 340–1. February 1977. doi:10.1016/s0140-6736(77)91140-0. PMID 64863. 

See also[edit]