Desensitization for hypersensitivity reactions to medications.

ABSTRACT

Rapid drug desensitization (RDD) is a technique that induces temporary tolerance to a drug, allowing a medication-allergic patient to receive the optimal agent for his or her disease. Through RDD, patients with IgE and non-IgE hypersensitivity reactions (HSRs) including anaphylaxis can safely be administered important medications while minimizing or completely inhibiting adverse reactions. Adverse reactions to drugs are increasingly recognized as important contributors to disease as well as impediments to the best treatment of dermatological, infectious, autoimmune, and neoplastic disorders. With the development of novel pharmacologic agents and the evolution of personalized treatments based on pharmacogenetic profiling, clinicians must decide which agent is the best for a particular patient with a given disease. Biological agents have greatly improved the treatment of chronic inflammatory diseases and malignancies while limiting some medication-associated toxicities. Because of better outcomes, longer patient survival, and extended treatment courses, patients are exposed to drugs more frequently and for longer time periods, increasing the risk of sensitization and the potential for HSRs. The frequency of adverse drug reactions has therefore increased in the last 10 years. Because of the severity of some reactions and the fear of inducing a potentially lethal reaction in highly sensitized patients, first-line treatments are sometimes abandoned, relegating hypersensitive patients to secondary, less effective, therapy. Some of these reactions are mast cell-mediated HSRs, a subset of which occur through an IgE-dependent mechanism, and are thus true allergies. Others involve mast cells, but an IgE mechanism cannot be demonstrated. Both types of reactions are amenable to RDD, and our group has successfully performed several hundred desensitizations to chemotherapy, antibiotics and biological agents including monoclonal antibodies with a standardized 12-step protocol that can be universally applied to all desensitizations. The molecular basis of RDD has now been studied, and an in vitro mouse mast cell model has shown that RDD is an antigen-specific process that does not induce subclinical mast cell mediator release, and that blocks the release of acute and late mast cell mediators by preventing calcium influx and antigen/IgE/and IgE receptor internalization.