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Diphenylhydantoin Gingival Hyperplasia FREE

Samuel Livingston, MD; Herbert L. Livingston, DDS
[+] Author Affiliations

Received for publication July 17, 1968.

Reprint requests to The Johns Hopkins Hospital, Baltimore 21205 (Dr. S. Livingston).


Am J Dis Child. 1969;117(3):265-270. doi:10.1001/archpedi.1969.02100030267002.
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DIPHENYLHYDANTOIN (Dilantin) sodium was synthesized in 1908 by Biltz1 and introduced as an antiepileptic agent in 1938 by Merritt and Putnam.2 Extensive subsequent use of this drug has confirmed its efficacy in controlling epileptic seizures, particularly major motor (grand mal) convulsions.

A number of untoward reactions have been observed in patients receiving diphenylhydantoin,3 one of the most common being hyperplastic enlargement of the gingivae.

The prime purpose of this writing is to discuss this reaction in general and, more importantly, to designate the types of patients with epilepsy in whom, because of this reaction, we believe the use of diphenylhydantoin as the drug of first choice is contraindicated.

The information presented in this paper is based on direct clinical observations of approximately 15,000 patients of all ages who were studied in our clinic while receiving this drug and, also, on an extensive review of the literature.

Incidence 

REFERENCES

Biltz, H.:  Uber die Konstitution der Einwirkungsprodukte von substituierten Harnstoffen auf Benzil und uber einige neue Methoden zur Darstellung der 5,5-Diphenylhydantoine , Berischte der Deutschen Chemischen Gesellschaft 41:1379-1393, 1908;.
Merritt, H.H., and Putnam, T.J.:  Sodium Diphenyl Hydantoinate in the Treatment of Convulsive Disorders , JAMA 111:1068-1073, 1938;.
Livingston, S.: Drug Therapy for Epilepsy , Springfield, Ill: Charles C Thomas, Publisher, 1966;, pp 137-138, 1966.
Lennox, W.G.:  The Drug Therapy of Epilepsy , JAMA 114:1347-1354 ( (April 6) ) 1940;.
Gardner, A.F.; Gross, S.G.; and Wynne, L.E.:  An Investigation of Gingival Hyperplasia Resulting From Diphenylhydantoin Sodium Therapy in Seventy-Seven Mentally-Retarded Patients , Exp Med Surg 20:133-158 ( (Sept) ) 1962;.
Babcock, J.R.:  Incidence of Gingival Hyperplasia Associated With Dilantin Therapy , J Amer Dent Assoc 71:1447-1450 ( (Dec) ) 1965;.
Panuska, H.J., et al:  The Effect of Anticonvulsant Drugs Upon the Gingiva , J Periodont 32: 15-28 ( (Jan) ) 1961;.
Livingston, S., and Pauli, L.L.: The Relationship of Diphenylhydantoin-Induced Gingival Hyperplasia to Drug Dosage and Serum Concentration, to be published.
Glickman, I.: Clinical Periodontology , Philadelphia: W. B. Saunders Co., 1965;, pp 76-78.
Goldman, H.M., et al: Periodontal Therapy , ed 2, St. Louis: C. V. Mosby Co., 1960;, p 637.
Gaillard, R.A.:  Antihistaminic Therapy for Gingival Hyperplasia Due to Dilantin , New Eng J Med 256:76-77 ( (Jan 10) ) 1957;.
Breg, W.R., and Falcetti, J.P.:  Ineffectiveness of Antihistamine Therapy for Gingival Hyperplasia Due to Diphenylhydantoin Sodium , New Eng J Med 257:1128 ( (Dec 5) ) 1957;.
Davis, R.K.; Baer, P.N.; and Palmer, J.H.:  A Preliminary Report on a New Therapy for Dilantin Gingival Hyperplasia , J Periodont 34: 17-22 ( (Jan) ) 1963;.
Babcock, J.R.:  The Successful Use of a New Therapy for Dilantin Gingival Hyperplasia , Periodontics 3:196-199 ( (July) -Aug) 1965;.
Spira, cited by Staple, P.H.:  Some Tissue Reactions Associated With 5,5-Diphenylhydantoin (Dilantin) Sodium Therapy , Brit Dent J 95:289-302 ( (Dec 15) ) 1953;.
Sackler, A.M., et al:  Hydrocortisone Acetate in the Treatment of Dilantin Gingival Enlargement , New York Dent J 20:125-126 ( (March) ) 1954;.
Kimball, O.P.:  The Treatment of Epilepsy With Sodium Diphenyl-Hydantoinate , JAMA 112: 1244-1245 ( (April 1) ) 1939;.
Milhon, J.A., and Osterberg, A.E.:  Relationship Between Gingival Hyperplasia and Ascorbic Acid in the Blood and Urine in Epileptic Patients Undergoing Treatment With Sodium 5,5-Diphenyl Hydantoinate , J Amer Dent Assoc 29:207-212 ( (Feb) ) 1942;.
Bonnycastle, D.D., and Bradley, A.J.:  Diphenylhydantoin and the Release of Adrenocorticotropic Hormone in the Albino Rat , Endocrinology 66:355-363 ( (March) ) 1960;.
Staple, P.H., and Emslie, R.D.:  Some Tissue Reactions Associated With Dilantin Sodium , Int Dent J 3:190 ( (Dec) ) 1952;.
Reader, Z.A.:  Gingival Hyperplasia Resulting From Diphenylhydantoin Sodium: A Review of the Literature , J Oral Surg 8:25-37 ( (Jan) ) 1950;.
Van der Kwast, A.M.:  Speculations Regarding the Nature of Gingival Hyperplasia Due to Diphenylhydantoin-Sodium , Acta Med Scand 153: 399-405, 1956;.
Francis, L.E., and Melville, K.I.:  Effects of Diphenylhydantoin on Gingival Histamine and Serotonin , J Canad Dent Assoc 25:608-620, 1959;.
Babcock, J.R., and Nelson, G.H.:  Gingival Hyperplasia and Dilantin Content of Saliva: A Pilot Study , J Amer Dent Assoc 68:195-198, 1964;.
Haury, V.G., and Cantarow, A.:  Variations of Serum Magnesium in 52 Normal and 440 Pathologic Patients , J Lab Clin Med 27:616-622, 1942;.
Klein, H.; Orent, E.R.; and McCollum, E.V.:  The Effects of Magnesium Deficiency on the Teeth and Their Supporting Structures in Rats , Amer J Physiol 112:256-262 ( (June) ) 1935;.
Baer, P.N.; Davis, R.K.; and Merritt, A.D.:  Studies on Dilantin Hyperplastic Gingivitis: The Role of Magnesium , J Dent Res 44:1055, 1965;.
Shafer, W.G.; Beatty, R.E.; and Davis, W.B.:  Effect of Dilantin Sodium on Tensile Strength of Healing Wounds , Proc Soc Exp Biol Med 98:348-350 ( (June) ) 1958;.
Simpson, G.M.; Kunz, E.; and Slafta, J.:  Use of Sodium Diphenylhydantoin in Treatment of Leg Ulcers , New York J Med 65:886-888 ( (April) ) 1965;.

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References

Biltz, H.:  Uber die Konstitution der Einwirkungsprodukte von substituierten Harnstoffen auf Benzil und uber einige neue Methoden zur Darstellung der 5,5-Diphenylhydantoine , Berischte der Deutschen Chemischen Gesellschaft 41:1379-1393, 1908;.
Merritt, H.H., and Putnam, T.J.:  Sodium Diphenyl Hydantoinate in the Treatment of Convulsive Disorders , JAMA 111:1068-1073, 1938;.
Livingston, S.: Drug Therapy for Epilepsy , Springfield, Ill: Charles C Thomas, Publisher, 1966;, pp 137-138, 1966.
Lennox, W.G.:  The Drug Therapy of Epilepsy , JAMA 114:1347-1354 ( (April 6) ) 1940;.
Gardner, A.F.; Gross, S.G.; and Wynne, L.E.:  An Investigation of Gingival Hyperplasia Resulting From Diphenylhydantoin Sodium Therapy in Seventy-Seven Mentally-Retarded Patients , Exp Med Surg 20:133-158 ( (Sept) ) 1962;.
Babcock, J.R.:  Incidence of Gingival Hyperplasia Associated With Dilantin Therapy , J Amer Dent Assoc 71:1447-1450 ( (Dec) ) 1965;.
Panuska, H.J., et al:  The Effect of Anticonvulsant Drugs Upon the Gingiva , J Periodont 32: 15-28 ( (Jan) ) 1961;.
Livingston, S., and Pauli, L.L.: The Relationship of Diphenylhydantoin-Induced Gingival Hyperplasia to Drug Dosage and Serum Concentration, to be published.
Glickman, I.: Clinical Periodontology , Philadelphia: W. B. Saunders Co., 1965;, pp 76-78.
Goldman, H.M., et al: Periodontal Therapy , ed 2, St. Louis: C. V. Mosby Co., 1960;, p 637.
Gaillard, R.A.:  Antihistaminic Therapy for Gingival Hyperplasia Due to Dilantin , New Eng J Med 256:76-77 ( (Jan 10) ) 1957;.
Breg, W.R., and Falcetti, J.P.:  Ineffectiveness of Antihistamine Therapy for Gingival Hyperplasia Due to Diphenylhydantoin Sodium , New Eng J Med 257:1128 ( (Dec 5) ) 1957;.
Davis, R.K.; Baer, P.N.; and Palmer, J.H.:  A Preliminary Report on a New Therapy for Dilantin Gingival Hyperplasia , J Periodont 34: 17-22 ( (Jan) ) 1963;.
Babcock, J.R.:  The Successful Use of a New Therapy for Dilantin Gingival Hyperplasia , Periodontics 3:196-199 ( (July) -Aug) 1965;.
Spira, cited by Staple, P.H.:  Some Tissue Reactions Associated With 5,5-Diphenylhydantoin (Dilantin) Sodium Therapy , Brit Dent J 95:289-302 ( (Dec 15) ) 1953;.
Sackler, A.M., et al:  Hydrocortisone Acetate in the Treatment of Dilantin Gingival Enlargement , New York Dent J 20:125-126 ( (March) ) 1954;.
Kimball, O.P.:  The Treatment of Epilepsy With Sodium Diphenyl-Hydantoinate , JAMA 112: 1244-1245 ( (April 1) ) 1939;.
Milhon, J.A., and Osterberg, A.E.:  Relationship Between Gingival Hyperplasia and Ascorbic Acid in the Blood and Urine in Epileptic Patients Undergoing Treatment With Sodium 5,5-Diphenyl Hydantoinate , J Amer Dent Assoc 29:207-212 ( (Feb) ) 1942;.
Bonnycastle, D.D., and Bradley, A.J.:  Diphenylhydantoin and the Release of Adrenocorticotropic Hormone in the Albino Rat , Endocrinology 66:355-363 ( (March) ) 1960;.
Staple, P.H., and Emslie, R.D.:  Some Tissue Reactions Associated With Dilantin Sodium , Int Dent J 3:190 ( (Dec) ) 1952;.
Reader, Z.A.:  Gingival Hyperplasia Resulting From Diphenylhydantoin Sodium: A Review of the Literature , J Oral Surg 8:25-37 ( (Jan) ) 1950;.
Van der Kwast, A.M.:  Speculations Regarding the Nature of Gingival Hyperplasia Due to Diphenylhydantoin-Sodium , Acta Med Scand 153: 399-405, 1956;.
Francis, L.E., and Melville, K.I.:  Effects of Diphenylhydantoin on Gingival Histamine and Serotonin , J Canad Dent Assoc 25:608-620, 1959;.
Babcock, J.R., and Nelson, G.H.:  Gingival Hyperplasia and Dilantin Content of Saliva: A Pilot Study , J Amer Dent Assoc 68:195-198, 1964;.
Haury, V.G., and Cantarow, A.:  Variations of Serum Magnesium in 52 Normal and 440 Pathologic Patients , J Lab Clin Med 27:616-622, 1942;.
Klein, H.; Orent, E.R.; and McCollum, E.V.:  The Effects of Magnesium Deficiency on the Teeth and Their Supporting Structures in Rats , Amer J Physiol 112:256-262 ( (June) ) 1935;.
Baer, P.N.; Davis, R.K.; and Merritt, A.D.:  Studies on Dilantin Hyperplastic Gingivitis: The Role of Magnesium , J Dent Res 44:1055, 1965;.
Shafer, W.G.; Beatty, R.E.; and Davis, W.B.:  Effect of Dilantin Sodium on Tensile Strength of Healing Wounds , Proc Soc Exp Biol Med 98:348-350 ( (June) ) 1958;.
Simpson, G.M.; Kunz, E.; and Slafta, J.:  Use of Sodium Diphenylhydantoin in Treatment of Leg Ulcers , New York J Med 65:886-888 ( (April) ) 1965;.

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