DRESS syndrome therefore differs from the other SCARs disorders in that it involves the tissue-injuring action of CD4+ cells and the cell- and tissue-injuring action of eosinophils as well as the release of the following cytokines: Interleukins 5 and 13 which simulate the growth, longevity, and activation of eosinophils; Interleukin 4 which promotes the differentiation of naive helper T cells into Th2 helper cells that then serve to activate eosinophils as well as other types of pro-inflammatory cells; IFNγ which activates macrophages and induces the expression of Class II MHC molecules; and TNFα which promotes inflammation but also has cell-killing actions. Like other SCARs-inducing drugs, DRESS syndrome-inducing drugs or their metabolites stimulate CD8+ T or CD4+ T cells to initiate autoimmune responses. Studies indicate that the mechanism by which a drug or its metabolites accomplishes this stimulation involves subverting the antigen presentation pathways of the innate immune system. The drug or metabolite covalently binds with a host protein to form a non-self, drug-related epitope. An antigen-presenting cell (APC) takes up these alter proteins; digests them into small peptides; places the peptides in a groove on the human leukocyte antigen (i.e. HLA) component of their major histocompatibility complex (i.e. MHC); and presents the MHC-associated peptides to the T-cell receptor on CD8+ T or CD4+ T cells. Those peptides expressing a drug-related, non-self epitope on their HLA-A, HLA-B, HLA-C, HLA-DM, HLA-DO, HLA-DP, HLA-DQ, or HLA-DR proteins may bind to a T-cell receptor to stimulate the receptor-bearing parent T cell to initiate attacks on self tissues. Alternatively, a drug or metabolite may stimulate these T cells by inserting into the groove on a HLA protein to serve as a non-self epitope or bind outside of this groove to alter a HLA protein so that it forms a non-self epitope. Importantly, however, non-self epitopes must bind to specific HLA serotypes in order to stimulate T cells. Since the human population expresses some 13,000 different HLA serotypes while an individual expresses only a fraction of them and since a DRESSs-inducing drug or metabolite interacts with only one or a few HLA serotypes, a drug's ability to induce SCARs is limited to those individuals who express HLA serotypes targeted by the drug or its metabolite. Thus, only rare individuals are predisposed to develop SCARs in response to a particular drug on the basis of their expression of HLA serotypes. Studies have identified several HLA serotypes associated