Methotrexate and diclofenac are commonly used drugs for the treatment of rheumatoid arthritis. Methotrexate is a disease modifying antirheumatic drug utilized for managing rheumatoid arthritis for long term disease control, while diclofenac is frequently used for symptomatic relief of pain and inflammation. Low dose weekly treatments are generally regarded as safe and effective; however, significant side effects may arise due to dosing mistakes, older age, folate deficiency or accompanying health issues. On the other hand, diclofenac can cause rare but serious adverse hypersensitivity reactions like DRESS syndrome. We describe a 68- year- old man with rheumatoid arthritis who experienced severe leukopenia, thrombocytopenia, mucocutaneous ulcerations, and a secondary bacterial infection after unintentionally taking an extra dose of methotrexate while having discontinued folic acid supplementation for an extended period. Furthermore, the patient had a recent history of diclofenac usage for aggravated joint pain and then presented with a widespread skin rash, eosinophilia, liver involvement and other systemic inflammatory response aligning with DRESS syndrome. The patient was treated with intravenous leucovorin rescue, granulocyte colony- stimulating factor, and broad spectrum antibiotics when methotrexate was stopped right away. With supportive care, a gradual hematologic recovery was accomplished. This instance highlights how crucial it is for patients using methotrexate to receive regular laboratory testing, folic acid therapy and patient education and not to self- medicate.
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John et al. (2026) studied this question.
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