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The possible deleterious effects of folic acid antagonist methotrexate on the fertility potential have been investigated in 26 male psoriatic patients. Examination for semen, testicular histology, and spermatogenic function using radioactive phosphorus revealed that methotrexate had no unfavorable effect on male fertility. A long follow up of the patients and their offspring is needed to exclude the possible teratogenic effect of the drug.
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The folic acid antagonists, aminopterin and then methotrexate, have been the primary systemically administered drugs for the treatment of severe psoriasis for 25 years. Methotrexate was finally approved by the FDA 5 years ago and was recently estimated to be used for approximately 25,000 psoriatic patients annually. With the small but chronic doses used for psoriasis, methotrexate has been relatively safe, except for a limited occurrence of significant hepatotoxicity. The good to excellent results obtained in most patients must, therefore, be weighted against the small risk of liver damage. Methotrexate has also been used with some effectiveness in several other dermatologic conditions, including mycosis fungoides, dermatomyositis, pityriasis rubra pilaris, and others, although they are not yet FDA-approved indications. The recent successful introduction of photochemotherapy (psoralen and ultraviolet light) for moderate and severely affected psoriatics will probably lead to a substantial decrease in the number of patients requiring methotrexate.
While much attention has been devoted to cytotoxic drugs and radiation therapy in the pregnant cancer patient, the drugs used for management of symptoms and complications related to cancer during pregnancy have been overlooked. There is substantial overlap between the symptoms of cancer and cancer management and the symptoms related to pregnancy. The mainstay of symptom management is drug therapy and the potential for a drug to be embryotoxic or teratogenic depends on when it is given. In general, drugs not proven safe in pregnancy should be withheld, especially during the first trimester. The few drugs that have been proven to be teratogenic are alcohol, thalidomide, the folic acid antagonists (which includes methotrexate), diethylstilbestrol, and the vitamin A isomers, but there is a good deal of uncertainty about many other therapeutic agents. Placental transport of drugs from mother to fetus must be taken into consideration from the fifth week of gestation to parturition. Although the first trimester is the time of most organ development in the fetus, the brain continues to develop throughout pregnancy and may be damaged later in pregnancy, resulting in diminished intelligence or behavioral problems. This review will focus on the treatment of the most common symptoms of cancer in a pregnant patient and the potential for fetal damage.
The effect of several lipid-soluble folic acid antagonists on DNA synthesis in psoriatic and normal skin was studied. The skin samples were incubated in vitro with methotrexate, dichloromethotrexate, and their respective dimethyl esters, followed by exposure to deoxyuridine-3H to assay DNA synthesis radioautographically. Psoriatic epidermal cells were found to be selectively inhibited at lower concentrations (2 times 10-7 M) of these drugs than was normal skin. The ester derivatives were more active than the parent compounds, suggesting that increased lipid solubility of the compounds may potentiate their activity.
In this presentation the scope of the problem of teratogenesis and the essentials of teratology are briefly reviewed. The teratogenicity of any compound is a reflection of a complex interaction of the compound with both the maternal and fetal tissues, the genetic background of the fetus, and the time sequence of gestational events. Under such circumstances the implication of a single compound as a teratogen is difficult, a fact reflected in the high percentage of congenital morphologic abnormalities for which no cause can be ascribed. Four compounds--thalidomide, anticonvulsants, alcohol, and folic acid antagonists--with a known teratogenetic effect on the musculoskeletal system are discussed, as is the role of the orthopedic surgeon in teratology.
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Latent psoriasis is a state which exists before the development of clinical psoriasis and wherein probably some as yet undiscovered defect exists. Investigation concerning a group of persons with latent psoriasis might disclose basic aberrations. The natural course of psoriasis may be altered by therapy. Folic acid antagonists and intradermal corticosteroids may at times eclipse psoriatic lesions. Oral adrenal corticosteroids may prove morbidistatic but on discontinuance a rebound flare may occur which is both protracted and recalcitrant. Antimalarial agents when employed as therapy for coexistent arthridites may cause psoriasis to become more severe. The Goeckerman regimen which employs topical tar and ultraviolet light therapy produces in some 75 per cent of patients a prolonged remission. As it is safe and repeatable it is favored for the usual severe case of psoriasis. Psoriasis therapy is better assessed by considering its effect on the natural evolution of the disease.
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