To the Editor.—
The evidence presented that led the International Cooperative Study Group on Methotrexate and the Subcommittee on Methotrexate of the Psoriasis Task Force of the National Program for Dermatology to warn that the daily oral dose schedule for methotrexate may be associated with some increased hazard and increased incidence of liver damage is threefold in nature.Review of the pharmacologic effects of methotrexate in animals by Rall et al1 shows that methotrexate is less toxic when given in large single doses than when administered in small daily doses. Experience with methotrexate and other chemotherapeutic drugs in the treatment of leukemia and lymphomas has shown the superiority of the large loading dose and long rest periods over the low daily dosage methods.Dahl,2,3 in evaluating cases of psoriasis treated with methotrexate in England, found that a higher proportion of those patients treated with frequent small dosage showed