Changes in circulating immune complexes during the Jarisch Herxheimer reaction in secondary syphilis

A cohort of 16 patients with early secondary syphilis were recruited to investigate the role of circulating immune complexes in the pathogenesis of the Jarisch Herxheimer reaction. Eleven of 16 patients had a reaction (68.75%) following initial therapy, characterised by rash potentiation, pyrexia, cardiovascular changes and a number of less specific symptoms. Circulating immune complexes were measured by a standard polyethylene glycol precipitation method and a new sensitive conglutinin binding assay that measured the proportion of IgG, IgM and IgA in complexes, in the first 8 hours after initial therapy. In the latter assay, resting levels of IgG (range 46-700 micrograms/ml) and IgM (range 100-410 micrograms/ml) containing complexes were raised in all patients prior to treatment, but levels were not predictive of those who subsequently had a Jarisch Herxheimer reaction. All patients having a reaction demonstrated a mean fourfold or greater rise in IgG (mean rise 712 micrograms/ml; range 180-1506 micrograms/ml) and IgM (mean rise 804 micrograms/ml; range 200-1120 micrograms/ml) containing complexes between two and eight hours after initial therapy. No such effect was seen in the five patients having no reaction or in a control subject. All these results were confirmed using the polyethylene glycol precipitation method for complex detection.