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Fatal Drug Toxicity Induced by Oral Methotrexate (A lesson to learn)

Take Home message: Methotrexate (MTX) is often supplemented with folic acid like ANY other systemic drug (oral or injected) can induce toxiderma which presented here on the skin as erosive dermatitis (along with systemic symptoms)…unrecognized, it was lethal 13 days after the medication was started. (Case Report from the Philippines) … proper monitoring is ALWAYS a necessity.




-Methotrexate is an immunosuppressive drug used in the treatment of many diseases as a stand-alone drug (for example in psoriasis) as well as a steroid sparing agent (for example in autoimmune diseases such as bullous pemphigoid)

-Although some skin reaction patterns  are more frequent for certain drugs, any skin reaction can occur:

“Always include a drug history before examining a patient “

-MTX is a folate antagonist and folic acid supplementation is often done. It decreased liver enzymes but does prevent toxicity. Also MTX efficacy can be decreased which requires increase in dosage. To read more about this lack of consensus topic, click HERE

-To read more about drug-induced skin reactions:

  1. For General information on drug reactions presenting on the skin: click HERE 
  2. For Professionals: click HERE
  3. To read General information about oral methotrexate: click HERE
  4. To read all of our articles on methotrexate: click HERE 




Introduction: Methotrexate is being given by Dermatologist in only extreme cases of skin disorders such as in severe Psoriasis Vulgaris. Strict precautionary measures are done to avoid its well-known adverse effects. An early but less common sign of its toxicity are painful erosions on plaques.

Case Summary: A case of a 57-year old male with a 2-day history of painful erosions on plaques on both upper and lower extremities after eleven days of taking Methotrexate 2.5mg/tablet one tablet three times a day without folate supplementation. He was then being treated by a general physician as a case of Psoriasis Vulgaris. He was subsequently admitted under the Internal Medicine service due to epigastric pain, nausea, anorexia, generalized body weakness and passage of black tarry stools. He was referred to the Department of Dermatology for the painful erosions on plaques. He expired two days after admission due to Acute Respiratory Failure. Post-mortem Skin biopsy was done revealed chronic eczematous dermatitis consistent with Lichen Simplex Chronicus with superimposed drug induced hypersensitivity reaction.

Conclusion: Methotrexate is an effective but potentially toxic treatment for different severe dermatologic disorders such as in severe Psoriasis Vulgaris. Meticulous and complete history-taking, physical examination and laboratory work-up to come up with a correct diagnosis as well as, knowledge of indications for treatment, proper dosing, and folate supplementation are a must in order to avoid cutaneous and systemic adverse effects including death.

Reference: Regional Congress of Dermatology (RCD) 2016 – Singapore. ONE MISTAKE, ONE LIFE AT STAKE: A MORTALITY CASE OF METHOTREXATE TOXICITY IN A 57-YEAR OLD MALE PRESENTING WITH PAINFUL PLAQUES WITH EROSIONS M.F. Quinio1, E. Prieto1 1East Avenue Medical Center, Dermatology, Quezon City, Philippines