Commentary: Three Decades of Folic Acid Antagonists in Dermatology

A little longer than 30 years ago, Gubner et al¹ made the serendipitous observation that the folic acid antagonist aminopterin had a beneficial effect in the treatment of psoriasis. In the early 1950s, the inhibitory effects of aminopterin on the inflammatory and proliferative responses of the connective tissue in mesenchymal disorders were being investigated.¹ Similar effects were being found with the administration of cortisone, also a newly used drug. Animal and clinical experiments showed that aminopterin was producing a greater inhibitory effect on epithelial tissues, whereas the major effects of cortisone therapy were appearing in mesenchymal tissues.² This unexpected finding occurred while Gubner et al1 were looking for an anti-inflammatory effect of aminopterin therapy in patients with rheumatoid arthritis, one of whom also had severe psoriasis. The beneficial response in this one patient (patient 3) led to the investigation of the use of aminopterin therapy in other