Transitioning Steroid-Dependent Erythema Nodosum Leprosum to Methotrexate-Based Management: A Literature Review
Achmad Syarifhidayatullah1, Medhi Denisa Alinda2*, Tri Pudy Asmarawati3, Linda Astari2
Abstract
Erythema nodosum leprosum (ENL) is a devastating immune system disorder that affects up to 50% of lepromatous leprosy patients. It causes recurring painful nodules and body-wide inflammation. Current treatment focuses mainly on long-term glucocorticoid medication, but 82% of patients become reliant on steroids, causing metabolic abnormalities, osteoporosis, infections, and lower quality of life. Thalidomide works, but its teratogenicity, legal constraints, and side effects make it difficult to obtain worldwide. Due to the need for effective steroid-sparing alternatives, methotrexate (MTX) is being investigated. Neutrophil activation, neutrophil extracellular trap formation, and cytokine networks are key mechanisms in ENL pathogenesis, and MTX’s adenosine-mediated anti-inflammatory activities directly affect them. MTX controls the disease and makes glucocorticoids lowerable, according to recent clinical trials like the MaPs in ENL experiment and a French multicenter investigation. In fact, 54–61% of patients achieved steroid-sparing results. As an alternative to standard techniques, low-dose weekly MTX is safe, cost-effective, widely available, and monitored. This review draws on current ENL pathophysiology, rigorously evaluates steroid dependency, analyzes the mechanistic justification and clinical evidence for MTX-based treatment, and provides a pragmatic framework for switching patients from glucocorticoids to MTX. This promising treatment for one of leprosy’s most difficult sequelae needs further study to define effective dose regimes, discover predictive biomarkers, and evaluate long-term outcomes.
Keywords
erythema nodosum leprosum; methotrexate; steroid therapy
Cite This Article
Syarifhidayatullah, A., Alinda, M. D., Asmarawati, T. P., Astari, L. (2025). Transitioning Steroid-Dependent Erythema Nodosum Leprosum to Methotrexate-Based Management: A Literature Review. International Journal of Scientific Advances (IJSCIA), Volume 6| Issue 6: Nov – Dec 2025, Pages 1118-1125 URL: https://www.ijscia.com/wp-content/uploads/2025/11/Volume6-Issue6-Nov-Dec-No.983-1118-1125.pdf
Volume 6 | Issue 6: Nov – Dec 2025
