Scurvy Following Folic Acid Antagonist Therapy

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Abstract
Although folic acid antagonists have been widely used in recent years, there have been only a few reports of their effects on Vitamin C metabolism. Recently, we have seen a patient with widespread neuroblastoma in whom typical scorbutic changes developed in the long bones during the course of aminopterin therapy. Case Report B. P., a 16-month-old white girl, was admitted to the University Hospital on Dec. 16, 1952, with progressive bilateral exophthalmos, more marked on the left; edema, venous engorgement and capillary dilatation of the upper eyelids; hepatomegaly; and otitis media of the right ear. Admission roentgen studies revealed multiple osteolytic lesions (Fig. 1) considered to be those of a metastatic neuroblastoma, in the skull, pelvis, and long bones. The latter diagnosis was confirmed by bone-marrow studies and a biopsy of the right tibia. The otitis media was treated with penicillin, streptomycin, and hydrogen peroxide irrigations. Beginning on Jan. 14, 1953, cortisone was given in doses of 50 mg. every eight hours until Feb. 4, after which the amount was decreased by ,50 per cent every two days until discontinuance of the drug on Feb. 14. On Feb. 9, in conjunction with the cortisone, the patient was started on 0.5 mg. of aminopterin daily. This dosage was increased to 1 mg. daily on Feb. 18, but was again reduced to 0.5 mg. daily on Feb. 26. Clinically, the patient improved and on March 1 was discharged from the University Hospital, to be followed in the OutPatient Department. Following her discharge, the child was given not only 0.5 mg. of aminopterin daily, but also 100 mg. of ascorbic acid. Her general physical condition continued to improve, with increase in appetite, recession of the hepatomegaly, decrease in exophthalmos, and increased activity. Radiographically, the metastatic lesions in the skull and long bones diminished in number and showed evidence of recalcification. On April 21, 1953, however, roentgen studies of the long bones revealed the development of a ground-glass appearance and beginning fragmentation in the epiphyseal plates (Fig. :2). A diagnosis of scurvy was made but the therapeutic regime was not altered. On three occasions during May and June 1953, the patient had oral ulcers, which promptly responded to the discontinuance of aminopterin for three or four days. On June 11. roentgen studies of the long bones revealed more pronounced scorbutic changes, with an increased ground-glass appearance and fragmentation of the epiphyseal plates, transverse bands of diminished density in the metaphyses, and demineralization, with “halo effect,” of the epiphyses (Fig. 3). The aminopterin therapy was continued and the ascorbic acid was increased from 100 to ,300 mg. daily. From June 11 to July 14, following the increase in ascorbic acid intake to 500 mg. daily the scorbutic changes in the long bones showed moderate improvement radiographically (Fig. 4).

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