The Jarisch-Herxheimer reaction is ascribed to the sudden massive destruction of spirochetes by drugs and release of toxic products and is manifested by fever and aggravation of the existing clinical picture. It is most likely to occur in early syphilis. It usually begins within the first 24 hours and subsides spontaneously within the next 24 hours of penicillin treatment. Treatment should not be discontinued unless the symptoms become severe or threaten to be fatal or unless syphilitic laryngitis, auditory neuritis, or labyrinthitis is present, where the reaction may cause irreversible damage.

The reaction may be prevented or modified by simultaneous administration of antipyretics or corticosteroids, though no proved method of prevention exists.

Follow-Up Care

Because treatment failures can occur and reinfection is always a possibility, patients treated for syphilis should be followed clinically and serologically. Response to therapy is difficult to assess, and no definite criteria exist for cure in patients with primary or secondary syphilis. In primary and secondary syphilis, failure of nontreponemal antibody titers to decrease fourfold by 6 months may identify a group at high risk of treatment failure. Optimal management of these patients is unclear, but at a minimum close clinical and serologic follow-up is indicated. If titers fail to decrease fourfold by 6 months, an HIV test should be repeated (all patients with syphilis should have an HIV test at the time of diagnosis); a lumbar puncture should be considered since unrecognized neurosyphilis can be a cause of treatment failure; and, if careful follow-up cannot be ensured (3-month intervals for HIV-positive individuals and 6-month intervals for HIV-negative patients), treatment should be repeated with 2.4 million units of benzathine penicillin intramuscularly weekly for 3 weeks. If symptoms or signs persist or recur after initial therapy or there is a fourfold or greater increase in nontreponemal titers, the patient has either failed therapy or has been reinfected. In those individuals, an HIV test should be performed, a lumbar puncture done (unless reinfection is a certainty), and retreatment given as indicated above. In patients with latent syphilis, nontreponemal serologic tests should be repeated at 6, 12, and 24 months. If titers increase fourfold or if initially high titers (? 1:32) fail to decrease fourfold by 12-24 months - or if symptoms or signs consistent with syphilis develop - an HIV test and lumbar puncture should be performed and retreatment given according to the stage of the disease.