Genetic susceptibility has been described in patients carrying the polymorphic variants of methionine synthase reductase (MTR) or haplotype HLA-DRB1*0401 [15, 16], and some authors have demonstrated that treatment with MTX is associated with the reactivation of Epstein–Barr virus, which may be responsible for the development of lymphoproliferative disorders or subcutaneous nodules [17]. This evidence concerns the gene MTRR and lymphoproliferative syndrome.