Detailed immunohistologic evaluation of a methotrexate-induced nodule

Accelerated nodulosis in patients with rheumatoid arthritis who are receiving methotrexate has become a well-recognized phenomenon, and it appears to occur in both individuals with seropositive and seronegative findings. No histologic differences permit a distinction between seronegative and seropositive nodulosis--either occurring during the natural history of rheumatoid arthritis or when "induced" by methotrexate. We examined such a nodule in a man with seronegative rheumatoid arthritis. Results of immunofluorescence examination were not contributory, but studies of the inflammatory cell populations within the nodule showed 5% of the cells to be lymphocytes with a CD4/CD8 ratio of 25:1. Of the total mononuclear cells, 85% were reactive for Leu-10 (HLA-DQ) and 95% were reactive for HLA-DR, and about 75% of the macrophages were reactive for CD4+. The strong expression of CD4, in conjunction with macrophage markers, and the high T-helper/suppression ratio are of note. We discuss the implications of these findings and the role that they play in the pathogenesis of methotrexate-induced nodules.