Brief Update on Dermatologic Uses of Methotrexate

Radhika Shah, MS, BS; Crystal E. Nwannunu, BS; Allison L. Limmer, BA, BS; Ravi R. Patel, MD; Uyen Ngoc Mui, MD; Stephen K. Tyring, MD, PhD


Skin Therapy Letter. 2019;24(6):5-6. 

In This Article

Abstract and Introduction


Methotrexate (MTX), an agent originally intended for anti-neoplastic use, has been successfully employed in the treatment of a variety of dermatologic conditions. In addition to its multiple clinical indications, variable dosing and modes of administration make it a viable option for patients of all ages and most comorbidities. MTX is a folate analog that antagonizes dihydrofolate reductase, thus inhibiting thymidylate synthesis and, ultimately, the production of pyrimidine. Depending on dosage, MTX can function as an anti-inflammatory agent, immunomodulator, or antimetabolite. Patients suffering from psoriasis have benefited from MTX in addition to those with atopic dermatitis, chronic urticaria, pemphigus vulgaris, bullous pemphigoid, cutaneous lupus erythematosus, cutaneous sarcoidosis, and mycosis fungoides. Although patients with these conditions can benefit from MTX treatment, the drug can cause adverse sequelae, including hematologic, pulmonary, gastrointestinal, and hepatic side effects. Therefore, the drug should be administered under careful physician supervision.


Methotrexate (MTX), an agent originally intended for antineoplastic use, has been successfully employed in the treatment of a variety of dermatologic conditions. It can be administered orally, subcutaneously, or intramuscularly, and depending on its clinical indication, MTX can be given once weekly or on a triple-dose schedule at 12-hour intervals. The drug is a folate analog that antagonizes the enzyme dihydrofolate reductase. Inhibition of dihydrofolate reductase obstructs thymidylate synthesis and, ultimately, inhibits production of pyrimidine, an important nucleic acid base that gives rise to cytosine, thymine, and uracil. At a low dose, MTX acts as an anti-inflammatory agent and immunomodulator. At high doses, it acts as an antimetabolite. Given its mechanism of action, MTX can lead to many adverse events and should be used with caution. Along with nausea, anorexia, fatigue, and malaise, other systemic toxicities can occur, including hematologic, gastrointestinal, reproductive, pulmonary, cardiac, and neurologic complications. It is safe to use low-dose MTX in children, but it should be avoided in pregnant women. Drug interactions may occur and can increase the likelihood of MTX toxicity. For this reason, the American Academy of Dermatology (AAD) strongly recommends folate supplementation with MTX therapy.[1] This review aims to briefly delineate established clinical indications for, as well as recent research regarding the utility of MTX in dermatology.