Pathogenesis of the Jarisch-Herxheimer Reaction: A REVIEW OF CLINICAL AND EXPERIMENTAL OBSERVATIONS

Abstract

During the past few years we have been engaged in a clinical and experimental study of the pathogenesis of the Jarisch-Herxheimer reaction in syphilis. The results of this investigation have been published in a series of papers (Sheldon and Heyman, 1949; Evans, 1951a, b, 1952). The present report summarizes our observations and presents our concepts of the pathogenesis of the Herxheimer reaction in syphilis, as well as in other infections. We shall use this opportunity to speculate upon the significance of the reaction as a manifestation of a hypersensitivity phenomenon.The Herxheimer reaction has long been known to be a common occurrence in the treatment of syphilis, but its pathogenesis has evoked little interest. The reaction is generally attributed to the release of endotoxins or spirochaetal breakdown substances following the initial administration of spirochaeticidal agents. These substances are thought to produce systemic manifestations, such as fever, chills, and malaise, as well as an exacerbation of syphilitic lesions. The results of our studies seem to indicate that the Herxheimer reaction is a hypersensitivity phenomenon of the delayed type similar to the focal hypersensitivity type of tuberculin reaction.

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

“…Hypersensitivity reaction has also been proposed to contribute to JH reaction, because the reaction develops with the same severity among patients at different stages of syphilis, even though late latent syphilis has been considered to contain fewer treponemal spirochetes than early syphilis [14]. Our finding that prior penicillin therapy for syphilis reduces the risk for JH reaction by 61% suggests that desensitization may occur after the previous course of treatment.…”

An unusual Jarisch-Herxheimer reaction.

“…The work of Farmer (1948) and of Heyman, Sheldon, and Evans (1952) and more recent studies, such as those of Viegas, Lisboa, and Aguiar (1969), indicate that the release of antigenic material by the sudden death of treponemes is an important part of the reaction. The fact that only one obvious generalized reaction usually occurs suggests that normally most of the treponemes are destroyed by the first dose, but because a single dose of 600,000 units procaine penicillin is insufficient to cure syphilis, viable organisms must persist after one such dose.…”

The Light of Many Minds: ROYAL FACULTY OF PHYSICIANS AND SURGEONS OF GLASGOW GLASGOW LOCK HOSPITAL TRUST PRIZE ESSAY

“…Iodides are still sometimes used in syphilis in an attempt to prevent the potentially dangerous exacerbations of the syphilitic process which are liable to occur when late syphilis is treated for the first time (Jarisch, 1895;Herxheimer and Krause, 1902;Heyman, Sheldon, and Evans, 1952).…”