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Methotrexate (MTX), a cornerstone treatment for rheumatoid arthritis (RA), is associated with drug-induced hypersensitivity syndrome (DIHS), including rare instances of methotrexate-induced pneumonitis. We report a significant case of a 65-year-old woman with RA, treated with MTX for over two decades, who presented with fever, headache, nausea, and malaise and was later diagnosed with DIHS, manifesting as pneumonitis and hepatosplenomegaly. Despite initial suspicion of bacterial pneumonia, her condition deteriorated, leading to the consideration of DIHS. The diagnosis was confirmed through a drug lymphocyte stimulation test (DLST), and she responded well to prednisolone. This case underlines the complexity of long-term MTX therapy, emphasizing the need for vigilance towards DIHS even after years of treatment. The findings prompt a reconsideration of ongoing treatments for RA, particularly in settings where long-term MTX use is prevalent. Early intervention and diagnostic tests like the DLST are crucial for preventing severe outcomes. This case adds to the growing evidence of MTX's potential for causing DIHS even in long-term usage. It stresses the importance of balancing therapeutic benefits with the risks of significant adverse reactions in stable RA patients.
Fujimori et al. (Sat,) studied this question.