Antifolics are rational for psoriasis.
Normal renal clearance is of vital importance; this may be true of normal liver functions as well.
No fatal or near fatal reactions occurred in our series. We have reviewed two deaths following aminopterin (Aminopterin Sodium) therapy, apparently from inadequate renal clearance, one severe reaction for the same reason, and one death apparently due to inadequacy of bone marrow function. One death after parenteral methotrexate was from sepsis following leukopenia.
Fatal reactions may occur after leukopenia develops; it is therefore vital to select patients carefully and to make certain that there are no contraindications at the onset.
Antifolics should not be used when there is any possibility of pregnancy, because of possible fetal malformation. However, normal full-term pregnancies have occurred following administration of these compounds to either the father or the mother before the pregnancy started.
Most dermatologic teaching services in this country use antifolics for severe psoriasis and would support a petition to the Food and Drug Administration to include listing of severe psoriasis as an indication for these drugs. Most services also would support the continued manufacture of aminopterin.
There are many variables to account for relative unpredictability of toxic and beneficial effects, such as instability of the compounds, presence or absence of relative folic acid deficiency in the patient, variable absorption and excretion, and all the other variables which affect the action of any drug.
Elderly patients, possibly due to occult decline in renal and liver function, are poor candidates for antifolic therapy.
Rare hypersensitivity reactions may occur.
Only about 10% of our original group of patients still take antifolics for psoriasis. Reasons for discontinuation of the drugs include lasting remission in about 10%, response to other treatment in some instances, advanced age, unwillingness to undergo necessary safeguards in some, and unknown reasons in others.
Two patients have developed leukemia, one of an aleukemic nonclassified variety, and the other an acute leukemia. Neither case of leukemia occurred in close relationship to antifolic therapy.
Some of the reactions encountered in the past apparently may now be explained on the basis of impaired renal clearance.
Liver function tests (serum glutamic pyruvic transaminase and cephalin flocculation) performed on 31 patients receiving over 100 tablets of aminopterin or in those who have had reactions in the past have showed normal readings for the most part. Three patients showed abnormality in 48-hour cephalin flocculation test reading.
Methotrexate for psoriasis needs further investigation, both for oral and parenteral use, because this compound might possibly be safer and more effective than aminopterin if adequate and safe dosage schedules can be found.
For summary of standard approach, see Table.