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June 1972

Diphenylhydantoin Effects on Human Lymphocytes in Vitro and in Vivo: An Hypothesis to Explain Some Drug Reactions

Author Affiliations

Madison, Wis

From the Veterans Administration Hospital, Department of Medicine (Dr. MacKinney) and Epilepsy Center, Department of Neurology, University of Wisconsin School of Medicine (Dr. Booker), Madison.

Arch Intern Med. 1972;129(6):988-992. doi:10.1001/archinte.1972.00320060136020

We investigated the problem of idiosyncratic reactions to diphenylhydantoin sodium (Dilantin) using tissue culture techniques and measurement of absolute peripheral lymphocyte numbers and immunoglobulin serum values. Diphenylhydantoin was used as antigen to stimulate peripheral blood lymphocyte cultures of 8 patients with serious reactions to the drug, 23 patients without reactions, and 8 normal controls. Diphenylhydantoin inhibited thymidine incorporation in cultures of patients with serious reactions to diphenylhydantoin. Patients who were taking diphenylhydantoin without reaction had lower proportions of DNA synthesizing cells in seven-day unstimulated cultures than normal controls. Sixty-six patients receiving the drug were shown to have negative correlation between serum diphenylhydantoin level and the absolute peripheral blood lymphocyte numbers. Immunoglobulin quantitation of matched groups of 20 patients showed decrease in IgG levels in serum of those receiving diphenylhydantoin. An hypothesis relating these data to the development of lymphoma and autoimmune phenomena is offered.