Serum Sickness Syndrome Reaction
Serum sickness syndrome was first recognized in the pre antibiotic era when heterologous antiserum was used as passive immunization for treatment of a number of infectious and toxic illnesses. Today, specific serum therapy with heterologous (usually equine) serum or gamma globulin is restricted to passive immunization for a very few toxic diseases and the use of antilymphocyte (ALG) or antithymocyte (ATG) globulin for immunosuppressive therapy. This is not applicable to active immunization.
Murine monoclonal antibodies to cytokines and similar agents are being used for treatment of cancer, sepsis, and so on. Serum sickness occurs infrequently and often in a mild form to the administration of other protein and non protein drugs, vaccines, and even to insect stings and bites.
Serum sickness is an acute, self-limited allergic disease caused by immune complex-activated complement-generated inflammation after injection of a protein or haptenic drug. The cardinal features are fever, dermatitis, lymphadenopathy, and joint pains.
Serum sickness is caused by the therapeutic injection of foreign material that is potentially antigenic, so the prevalence of this disease depends on the prevalence of certain forms of medical treatment. Therapeutic injections of large quantities of heterologous serum produce serum sickness in proportion to the dose. The attack rate was approximately 90% when a 200-mL dose of horse serum was given. The gamma globulin fraction of foreign serum containing the therapeutic antibodies is only marginally less antigenic with attfsack rates of the disease from ALG or ATG generally 50% or higher. The reason that certain drugs (eg, minocycline, cefaclor) are more likely to cause this reaction than are others within their class (tetracyclines, cephalosporins) is unknown. No prevalence statistics are available today, but reports of serum sickness are now uncommon.
The pathogenesis of human serum sickness is believed to be similar to the mechanism of one shoot serum sickness produced experimentally in immunized rabbits. Following a single large dose of injected antigen a brief period of equilibration occurs between blood and tissues followed by slow degradation of antigen over several days as the primary antibody response is initiated. Antibody synthesis leads to its release into the circulation, where antigen-antibody complexes gradually form under conditions of moderate antigen excess. Intermediate-size complexes deposit in small blood vessels in various organs, triggering the events previously described for the Arthus reaction. This gives rise to the clinical and pathologic manifestations of disease.
Free antigen is removed more rapidly from the circulation as antibody production and immune-complex formation increases. The circulating complexes then shift to antibody excess, thereby decreasing in size and clearing more rapidly. Finally, free antibody circulates, no further lesions appear, and healing takes place.
The optimal conditions for serum sickness occur during the initial antibody response of the previously immunized host. With subsequent exposures to the same antigen, the anamnestic antibody response facilitates rapid antigen clearance and greatly reduces the amount and persistence of immune complexes in the circulation.