Studies of the Mechanism of the Jarisch—Herxheimer Reaction in Louse-Borne Relapsing Fever: Evidence for the Presence of Circulating Borrelia Endotoxin

Abstract

1.Certain aspects of the Jarisch-Hemheimer reaction (JHR) after treatment of louse-borne relapsing fever have been studied in nine patients. Peripheral vasoconstriction immediately preceded the chill phase and profound vasodilation accompanied the flush phase.2. From four patients 50-150 ml of blood was taken at the onset of the chill and reinjected intravenously into the same patient the next day. One patient experienced a reaction identical with JHR 40-60 min after reinjection, suggesting that the mediator of JHR was present in that blood. 3.From five patients 40 ml of blood were taken serially throughout JHR and 2-ml samples of plasma, free of cells and spirochaetes, were injected into pairs of normal rabbits. All samples taken while the patients had fever were pyrogenic. After incubation with normal rabbit plasma these samples failed to produce fever in endotoxin-refractory rabbits.4. These results suggest that in the plasma of patients with relapsing fever there is a powerful endotoxin. We were unable to show that the concentration of endotoxin increased during JHR, nor could we demonstrate the presence of leucocyte pyrogen. This failure could be a problem of quantity of plasma used or of an endotoxinrefractory state.5. The bearing of these observations on the mechanism of JHR and the uselessness of cortisol in modifying the reaction are discussed.The reaction which follows the treatment of louse-borne relapsing fever with antibiotics is the most violent example of the Jarisch-Herxheimer reaction (JHR) (Schofield, Talbot, Bryceson & Parry, 1968). The salient features of the reaction are (Bryceson, 1970): 1. A rise and then a fall in body temperature; the rise is accompanied by a chill and the fall by sweating.2. Aggravation of pre-existing lesions and their attendent symptoms and signs; e.g. flaring of the rash in syphilis, acute myocarditis in relapsing fever.3. Characteristic physiological changes which include early vasoconstriction, hyperventilation and rise in blood pressure and cardiac output and later a fall in blood pressure associated with low peripheral resistance. These changes have been described in detail by Warrell(l970) and Warrell, Pope, Parry, Perine & Bryceson (1970).

Antibiotic-Induced Release of Endotoxin A therapeutic Paradox

“…It is possible that some of the clinical observations and endotoxin assay data of 1 study [50] could have been confounded by concurrent (undocumented) infections which were a common problem in this particular patient group (Perine PL, personal communication, 1993).…”

“…The nature of the bacterial mediator of JHR is elusive, with evidence both for [48,[50][51][52] and against [53][54][55][56] a role for endotoxin. It is possible that some of the clinical observations and endotoxin assay data of 1 study [50] could have been confounded by concurrent (undocumented) infections which were a common problem in this particular patient group (Perine PL, personal communication, 1993).…”

Action of penicillin on Borrelia hermsii

“…Blebbing of the outer membrane is said to occur A possible consequence of penicillin-induced membrane vesicle formation is the Jarisch-Herxheimer reaction, the systemic reaction that often follows treatment of relapsing fever with antibiotics (22). Some investigators have demonstrated endotoxin-like material in the sera of humans and animals with borrelial infections (6,12,31) and in the sera of humans with Jarisch-Herxheimer reaction after treatment with penicillin for secondary syphilis (13). A release of numerous blebs containing such material conceivably could precipitate the Jarisch-Herxheimer reaction.…”

Jarisch‐Herxheimer Reaction after Penicillin Therapy among Patients with Syphilis in the Era of the HIV Infection Epidemic: Incidence and Risk Factors

“…In accordance with current treatment guidelines [5], patients with early syphilis are recommended to receive a single dose of benzathine penicillin G; those with late latent syphilis or unknown duration are treated with 3 weekly doses of benzathine penicillin G. Following penicillin treatment of syphilis and other spirochetal diseases, a substantial proportion of patients may develop Jarisch-Herxheimer (JH) reaction, a syndrome composed of some of the following features: abrupt onset of fever, chills, myalgias, tachycardia, vasodilatation with flushing, exacerbated skin rash, or mild hypotension [6][7][8]. The reaction was described originally by Jarisch in 1895 and several years later by Herxheimer and Krause [9].…”