Effect of "aminopterin" on epithelial tissues.
The folic acid antagonist, 4-aminopteroyl glutamic acid ("aminopterin"), is a potent inhibitor of growth and of connective tissue proliferation. The present study indicates that the suppressive effects of "aminopterin" on epithelial structures are more striking than on connective tissue, as revealed by observation of interference with wound healing and epithelization, atrophy and ulceration of mucosa, alopecia, and prompt suppressive effects in such dermatologic disorders as psoriasis and chronic indurative dermatoses. "Aminopterin" was administered orally in daily doses of 1.5 to 2.0 mg. to thirteen patients with psoriasis (of whom six had associated arthritis) and to five patients with chronic indurative dermatoses. The latter included one patient with chronic atopic eczematoid dermatitis with associated asthma, one with chronic eczematoid seborrheic dermatitis, one with chronic discoid lupus erythematosus involving the face, and two with scleroderma. In all patients there were remissions in cutaneous lesions, which appeared most commonly between the 5th and 10th day of "aminopterin" therapy. Treatment was interrupted in most patients after an initial course of 14 to 28 mg. because of the regular occurrence of shallow ulceration of the buccal mucosa and frequent development of abdominal cramps. Remissions persisted for periods ranging from two weeks to several months, after which lesions returned which responded to further courses of "aminopterin." The therapeutic response was more complete in the seven patients with psoriatic arthritis than in in six subjects with uncomplicated psoriasis. In four patients with psoriatic arthritis in whom the responses to "aminopterin" and cortisone were compared, arthritic manifestations were considerably more relieved by cortisone, but improvement in psoriasis was consistently more complete and more sustained with "aminopterin." No evidence of a summative effect of cortisone and "aminopterin" on psoriasis was observed when the two were employed concomitantly, although amelioration of arthritic symptoms was more complete than when cortisone was given alone. Topical application of "aminopterin" in a 1% ointment was found to be ineffective. "Aminopterin" is a toxic drug, and its administration must be carefully supervised. The citrovorum factor has proved useful in overcoming "aminopterin" toxicity but interferes with its therapeutic effects. It is suggested that "aminopterin" may prove useful in other dermatologic disorders and in cutaneous manifestations of some systemic diseases which, in certain instances, have been temporarily benefited by cortisone.[1]References
- Effect of "aminopterin" on epithelial tissues. Gubner, R. Archives of dermatology. (1983) [Pubmed]
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