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It also seems that the synergism between predisposition to a certain HLA allele and polymorphism in drug metabolism is necessary to trigger DRESS, as in the case of patients with increased risk of reaction who are exposed to allopurinol, express HLA-B*58:01 and have decreased renal function, which leads to an increase in serum levels of allopurinol or its toxic metabolites.19 Immunological pathways There are several models by which the drug can stimulate the immune response and cause DRESS: (i) The hapten model, where antigen-presenting cells (APCs) and their HLA have a neoantigen to the TCR of a T nave cell through a strong covalent bond