2023 Volume 35 Issue 4 Pages 234-247
Among disease-modifying anti-rheumatic drugs, methotrexate（MTX）is the anchor, being prescribed for over 60–70% of the rheumatoid arthritis（RA）patients. Adverse event related to MTX use in RA is most frequently lymphoproliferative disorders（LPD）, accounting for one third of the whole adverse events reported to Japanese Adverse Drug Event Report database（JADER）, in contrast to that the most is infectious pneumonitis in TAC, ADA, TCZ and ABT users. EB virus infection to B lymphocyte, sometimes to T or NK cell, has been considered as the etiology. However, as 90% of the whole world population has lifelong EB virus infection, through mother to baby transmission, immune-suppression or immune-escape would be additionally crusial for LPD to develop. Diffuse large B-cell lymphoma（DLBCL）is the most, followed by Hodgikin lymphoma, and both intra-nodal and extra-nodal ones are observed. Risks for or concurrent findings with LPD development include a higher dose, good response, lymphocytopenia, sIL-2R level increase, and IgE level increase. Spontaneous regression after MTX withdrawal may occur in nearly half of the cases, but re-worsening is seen even without re-use. In case without a regression, R-CHOP immunochemotherapy is adopted. Immune checkpoint inhibitor would be an issue in the future. In conclusion, intra- and extra-nodal lesions should be especially monitored during MTX use for RA.
