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The Jarisch-Herxheimer reaction describes the release of endotoxin when large numbers of organisms are killed by antibiotics. It is seen in 50% of patients with primary syphilis and about 90% of patients with secondary syphilis. It is not a dose related phenomenon; thus giving a smaller dose is of no value.

It occurs about 8 hours after the first injection and usually consists of mild fever, malaise and headache lasting a few hours.

Rarely, in quarternary syphilis, a severe reaction can occur, prednisolone is therefore given to reduce its effects. 30-40 mg /day is given in divided doses for 2-3 days before and after the first dose of antibiotics, reducing by 5mg/day thereafter.

It can be seen in other conditions also, for example in the treatment of leptospirosis, tetracycline therapy in brucellosis, dapsone therapy in leprosy (Lepra reaction), antibiotic treatment of Lyme disease