Prospective clinical and immunological study of serum sickness in the recipients of equine rabies immunoglobulin (ERIG)

Abstract

The study attempted to determine the incidence of serum sickness following the administration of equine rabies immune globulin (ERIG). A total of 131 recipients of ERIG and post-exposure rabies vaccination were sequentially followed up to 2 weeks both for the development of serum sickness and the changes in the third compartment of complement (C₃), circulating immune complex (CIC) levels and heterophile antibody. Before ERIG administration, immediate skin test was performed and 19 (14.5%), were found positive according to the strict criteria. However, none of the skin test-positive individuals experienced any anaphylactic reactions upon ERIG administration. Therefore, replacement of ERIG by HRIG in skin test-positive individuals may be an unnecessary medical expenditure. Serum sickness occurred in only 2 out of the 131 patients (1.5%). Heterophile antibody was found 66.7% (12/18) and 45% (45/100) of serum sickness and asymptomatic patients respectively. C₃ levels as determined by radial immunodiffusion and CIC as determined by C1q binding assay of the serum sickness group were not significantly different from the asymptomatic group. Our results indicate that immediate skin testing was invalid in predicting horse gamma globulin-related anaphylactic reaction. Clinical serum sickness is a relatively rare complication of ERIG administration. The diagnosis of serum sickness is mainly a clinical diagnosis with very little help from laboratory confirmation. C₃ and CIC levels are generally not useful whereas differential heterophile antibody may be of some help. The reasons may be due to the insensitivity of the tests, the transient nature of the disease or to the subclinical changes of the immunologic parameters as result of heterologous protein administration. In fact, our prospective study confirms that administration of ERIG can indeed result in CIC formation, C₃ activation and formation of heterophile antibody in a certain number of patients even though they are asymptomatic.