We administered phenytoin (diphenylhydantoin) by mouth to 17 unselected patients to assess its ability to reduce blistering in recessive dystrophic epidermolysis bullosa (RDEB). Therapeutic response was correlated with blood levels of the drug. Although there was a decrease in blistering of 53 +/- 6 per cent (mean +/- S.E.) among all patients at levels of more than 8 microgram of phenytoin per milliliter, the response was variable, with 12 of 17 patients having a decrease in blistering of more than 40 per cent. Since increased collagenase in human skin has been implicated in the pathogenesis of blistering in RDEB, we examined the effect of phenytoin on this enzyme. Although the drug did not inhibit collagenase activity directly, its addition to human-skin explant and fibroblast cultures produced a 50 to 60 per cent decrease in collagenase activity and immunoreactive protein concentrations. These in vitro studies suggest that phenytoin inhibits synthesis or secretion of collagenase of both, and that the favorable clinical response can be explained by this inhibition.
This article has been cited by other articles:
Fine, J.-D., Eady, R. A. J.
(1999). Tetracycline and Epidermolysis Bullosa Simplex: A New Indication for One of the Oldest and Most Widely Used Drugs in Dermatology?. Arch Dermatol
135: 981-982
[Full Text]
O'Toole, M. J., Kolb, J. E., Lindblad, W. J., Cohen, I. K., McKneally, M. F.
(1996). Pneumothorax and Wound Dehiscence Related to Collagenase Deregulation: Treatment With Diphenylhydantoin. Ann. Thorac. Surg.
61: 1646-1650
[Abstract][Full Text]
McAllister, B. S., Walters, J. D., Olson, M. S.
(1994). Signal Transduction Mechanisms in Mesenchymal Cells. CROBM
5: 291-310
[Abstract][Full Text]
Golub, L. M., Ramamurthy, N.S., McNamara, T. F., Greenwald, R. A., Rifkin, B. R.
(1991). Tetracyclines Inhibit Connective Tissue Breakdown: New Therapeutic Implications for an Old Family of Drugs. CROBM
2: 297-321
[Abstract][Full Text]
Fine, J.-D., Johnson, L.
(1988). Efficacy of Systemic Phenytoin in the Treatment of Junctional Epidermolysis Bullosa. Arch Dermatol
124: 1402-1406
[Abstract]
Bauer, E. A., Tabas, M.
(1988). A Perspective on the Role of Collagenase in Recessive Dystrophic Epidermolysis Bullosa. Arch Dermatol
124: 734-736
[Abstract]
Gryboski, J. D., Touloukian, R., Campanella, R. A.
(1988). Gastrointestinal Manifestations of Epidermolysis Bullosa in Children. Arch Dermatol
124: 746-752
[Abstract]
Fine, J.-D.
(1988). Changing Clinical and Laboratory Concepts in Inherited Epidermolysis Bullosa. Arch Dermatol
124: 523-526
[Abstract]
Destro, M., Wallow, I. H. L., Brightbill, F. S.
(1987). Recessive Dystrophic Epidermolysis Bullosa. Arch Ophthalmol
105: 1248-1252
[Abstract]
Armoni, M., Schlesinger, M., Vardy, P. A., Metzker, A.
(1985). Phenytoin and Junctional Epidermolysis Bullosa. Arch Dermatol
121: 168-169
[Abstract]
Moy, L. S., Tan, E. M. L., Holness, R., Uitto, J.
(1985). Phenytoin Modulates Connective Tissue Metabolism and Cell Proliferation in Human Skin Fibroblast Cultures. Arch Dermatol
121: 79-83
[Abstract]
Cooper, T. W., Bauer, E. A.
(1984). Therapeutic Efficacy of Phenytoin in Recessive Dystrophic Epidermolysis: A Comparison of Short- and Long-term Treatment. Arch Dermatol
120: 490-495
[Abstract]
Rogers, R. B., Yancey, K. B., Allen, B. S., Guill, M. F.
(1983). Phenytoin Therapy for Junctional Epidermolysis Bullosa. Arch Dermatol
119: 925-926
[Abstract]
Guill, M. F., Wray, B. B., Rogers, R. B., Yancey, K. B., Allen, B. S.
(1983). Junctional Epidermolysis Bullosa: Treatment With Phenytoin. Arch Pediatr Adolesc Med
137: 992-994
[Abstract]
Bull, M. J., Norins, A. L., Weaver, D. D., Weber, T., Mitchell, M.
(1983). Epidermolysis Bullosa--Pyloric Atresia: An Autosomal Recessive Syndrome. Arch Pediatr Adolesc Med
137: 449-451
[Abstract]
Bauer, E. A., Cooper, T. W.
(1981). Therapeutic Considerations in Recessive Dystrophic Epidermolysis Bullosa. Arch Dermatol
117: 529-530
[Abstract]
Previous
