The expanding role of methotrexate for treating skin disease

This is the authors' abstract. We don't add key points for this paper.

This month's issue of the Journal contains the British Association of Dermatologists’ updated guidelines for prescribing methotrexate.1 The main focus of the guidelines is directed at psoriasis but a range of other inflammatory dermatoses for which methotrexate is used is also covered. Despite the introduction over the past 30 years of dramatically effective new agents for treating severe psoriasis, methotrexate has retained a pivotal role in this debilitating disease. Because of its very modest costs it is in many parts of the world the only systemic therapy available to a majority of psoriasis sufferers. Furthermore, the range of other skin diseases for which it is now being advocated has been steadily expanding. Sixty‐five years have passed since it was reported that aminopterin, a synthetic analogue of folic acid with antifolate properties, might be beneficial for psoriasis.2 Folate antagonists had been investigated in the 1940s for possible antineoplastic activity in experimental murine sarcoma and then had subsequently been administered to patients with a wide variety of incurable malignant neoplasms. Aminopterin, in particular, appeared to retard progression in patients with both solid and haematological malignancies.3 It was also in the 1940s that corticosteroids first began to be studied. Recognizing that both aminopterin and cortisone appeared to suppress cellular proliferation, the former in neoplastic and the latter in inflammatory diseases such as rheumatoid arthritis, Gubner and colleagues asked themselves the question whether the therapeutic effect of cortisone might be due to ‘a specific hormonal regulatory influence’ or merely to its suppression of ‘connective tissue proliferation’.2 They chose to investigate this in eight patients with severe inflammatory arthritis. They observed a marked reduction in pain and increase in mobility in seven of their eight patients. The dramatic response of long‐standing severe psoriasis in one of them prompted the investigators to administer aminopterin to a further eight patients with psoriasis, all of whom showed marked clearing over 3 weeks. When the closely related but more stable compound methotrexate became available, similar responses in patients with psoriasis were observed. In view of recent interest in the use of methotrexate for atopic eczema, it is noteworthy that they also reported a good response in the single patient with the latter disorder to whom they gave aminopterin. Furthermore, the latter drug is once again receiving attention as a potential treatment for inflammatory diseases including psoriasis.4