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Efficacy of Systemic Phenytoin in the Treatment of Junctional Epidermolysis Bullosa

Efficacy of Systemic Phenytoin in the Treatment of Junctional Epidermolysis Bullosa Abstract • Oral phenytoin has been shown to be effective in the treatment of recessive dystrophic epidermolysis bullosa (EB). To determine the possible efficacy of this drug in junctional forms of this disease, we treated four children (two with generalized atrophic benign EB [GABEB] and two with Herlitz disease) with two 16- to 20-week treatment periods with phenytoin separated by an eight- to 12-week drug-free period. Phenytoin was administered to achieve serum levels similar to those previously proved effective in treating recessive dystrophic EB. Serial counts were made of lesions (blisters, crusts, and erosions); surface areas of granulation tissue, when present, were also serially measured. In addition, changes in the percentage of surface area involved with scarring as well as changes in extracutaneous disease activity were similarly assessed. Both patients with GABEB showed excellent response during each course of phenytoin, with average reductions in lesion counts of 70% and 38%. In addition, subjectively, the healing times also appeared to be reduced. During the "wash-out" period, total lesional counts returned toward pretreatment levels. Both patients with GABEB subsequently have received phenytoin for an additional two years off of protocol, with continued excellent response. In contrast, the conditions of both patients with the Herlitz variant worsened while taking phenytoin, with increases in overall lesional counts of 31% and 72%. Also, the surface areas of exuberant granulation tissue either remained unchanged or increased during the course of phenytoin treatment. We conclude that phenytoin is effective in at least some patients with the GABEB subset of junctional EB, whereas no efficacy has been noted in patients with the more severe Herlitz variant. (Arch Dermatol 1988;124:1402-1406) References 1. Fine JD: Epidermolysis bullosa, clinical aspects, pathology, and recent advances in research . Int J Dermatol 1986;25:143-157.Crossref 2. Cooper TW, Bauer EA, Briggaman RA: The mechanobullous diseases (epidermolysis bullosa) , in Fitzpatrick TB, Eisen AZ, Wolff K, et al (eds): Dermatology in General Medicine , ed 3. New York, McGraw-Hill International Book Co, 1987, pp 610-626. 3. Eisenberg M, Stevens LH, Schofield PJ: Epidermolysis bullosa: New therapeutic approaches . Australas J Dermatol 1978;19:1-8.Crossref 4. Bauer EA, Cooper TW, Tucker DR, et al: Phenytoin therapy of recessive dystrophic epidermolysis bullosa: Clinical trial and proposed mechanism of action on collagenase . N Engl J Med 1980;303:776-781.Crossref 5. Cooper TW, Bauer EA: Therapeutic efficacy of phenytoin in recessive dystrophic epidermolysis: A comparison of short- and long-term treatment . Arch Dermatol 1984;120:490-495.Crossref 6. Eisen AZ: Human skin collagenase: Relationship to the pathogenesis of epidermolysis bullosa dystrophica . J Invest Dermatol 1969;52:449-453. 7. Lazarus GS: Collagenase and connective tissue metabolism in epidermolysis bullosa . J Invest Dermatol 1972;58:242-248.Crossref 8. Bauer EA, Gedde-Dahl T Jr, Eisen AZ: The role of human skin collagenase in epidermolysis bullosa . J Invest Dermatol 1977;68:119-124.Crossref 9. Bauer EA, Eisen AZ: Recessive dystrophic epidermolysis bullosa: Evidence for increased collagenase as a genetic characteristic in cell culture . J Exp Med 1978;148:1378-1387.Crossref 10. Valle K-J, Bauer EA: Enhanced biosynthesis of human skin collagenase in fibroblast cultures from recessive dystrophic epidermolysis bullosa . J Clin Invest 1980;66:176-187.Crossref 11. Stricklin GP, Welgus HG, Bauer EA: Human skin collagenase in recessive dystrophic epidermolysis bullosa: Purification of a mutant enzyme from fibroblast cultures . J Clin Invest 1982;69:1373-1383.Crossref 12. Bauer EA: Abnormalities in collagenase expression as in vitro markers for recessive dystrophic epidermolysis bullosa . J Invest Dermatol 1982;79( (suppl) ):105s-108s.Crossref 13. Rogers RB, Yancey KB, Allen BS, et al: Phenytoin therapy for junctional epidermolysis bullosa . Arch Dermatol 1983;119:925-926.Crossref 14. Guill MF, Wray BB, Rogers RB, et al: Junctional epidermolysis bullosa—treatment with phenytoin . AJDC 1983;137:992-994. 15. Kero M: Epidermolysis bullosa in Finland: Clinical features, morphology and relation to collagen metabolism . Acta Derm Venereol Suppl 1984;110:1-51. 16. Kero M, Palotic A, Peltonen L: Collagen metabolism in two rare forms of epidermolysis bullosa . Br J Dermatol 1984;110:177-184.Crossref 17. Paller AS, Fine JD, Kaplan S, et al: The generalized atrophic benign form of junctional epidermolysis bullosa: Experience with four patients in the United States . Arch Dermatol 1986;122:704-710.Crossref 18. Pearson R: Histopathologic and ultrastructural findings in certain genodermatoses . Clin Dermatol 1985;3:143-174.Crossref 19. Hintner H, Stingl G, Schuler G, et al: Immunofluorescence mapping of antigenic determinants within the dermal-epidermal junction in mechanobullous diseases . J Invest Dermatol 1981; 76:119-124.Crossref 20. Weber L, Krieg T, Muller P, et al: Immunofluorescent localization of type IV collagen and laminin in human skin and its application in junctional zone pathology . Br J Dermatol 1983; 106:267-273.Crossref 21. Fine JD, Breathnach S, Hintner H, et al: KF-1 monoclonal antibody defines a specific basement membrane antigenic defect in dystrophic forms of epidermolysis bullosa . J Invest Dermatol 1984;82:35-38.Crossref 22. Fine JD, Gay S: LDA-1 monoclonal antibody: An excellent reagent for immunofluorescence mapping studies in patients with epidermolysis bullosa . Arch Dermatol 1986;122:48-51.Crossref 23. Heagerty AHM, Kennedy AR, Eady RAJ, et al: GB3 monoclonal antibody for diagnosis of junctional epidermolysis bullosa . Lancet 1986;1:860.Crossref 24. Bergfeld WF, Orlowski JP: Epidermolysis bullosa retalis and phenytoin . J Am Acad Dermatol 1982;7:275-276.Crossref 25. Hintner H, Wolff K: Generalized atrophic benign epidermolysis bullosa . Arch Dermatol 1982;118:375-384.Crossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Dermatology American Medical Association

Efficacy of Systemic Phenytoin in the Treatment of Junctional Epidermolysis Bullosa

Fine, Jo-David; Johnson, Lorraine
Archives of Dermatology , Volume 124 (9) – Sep 1, 1988
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References (28)

Publisher
American Medical Association
Copyright
Copyright © 1988 American Medical Association. All Rights Reserved.
ISSN
0003-987X
eISSN
1538-3652
DOI
10.1001/archderm.1988.01670090058012
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Abstract

Abstract • Oral phenytoin has been shown to be effective in the treatment of recessive dystrophic epidermolysis bullosa (EB). To determine the possible efficacy of this drug in junctional forms of this disease, we treated four children (two with generalized atrophic benign EB [GABEB] and two with Herlitz disease) with two 16- to 20-week treatment periods with phenytoin separated by an eight- to 12-week drug-free period. Phenytoin was administered to achieve serum levels similar to those previously proved effective in treating recessive dystrophic EB. Serial counts were made of lesions (blisters, crusts, and erosions); surface areas of granulation tissue, when present, were also serially measured. In addition, changes in the percentage of surface area involved with scarring as well as changes in extracutaneous disease activity were similarly assessed. Both patients with GABEB showed excellent response during each course of phenytoin, with average reductions in lesion counts of 70% and 38%. In addition, subjectively, the healing times also appeared to be reduced. During the "wash-out" period, total lesional counts returned toward pretreatment levels. Both patients with GABEB subsequently have received phenytoin for an additional two years off of protocol, with continued excellent response. In contrast, the conditions of both patients with the Herlitz variant worsened while taking phenytoin, with increases in overall lesional counts of 31% and 72%. Also, the surface areas of exuberant granulation tissue either remained unchanged or increased during the course of phenytoin treatment. We conclude that phenytoin is effective in at least some patients with the GABEB subset of junctional EB, whereas no efficacy has been noted in patients with the more severe Herlitz variant. (Arch Dermatol 1988;124:1402-1406) References 1. Fine JD: Epidermolysis bullosa, clinical aspects, pathology, and recent advances in research . Int J Dermatol 1986;25:143-157.Crossref 2. Cooper TW, Bauer EA, Briggaman RA: The mechanobullous diseases (epidermolysis bullosa) , in Fitzpatrick TB, Eisen AZ, Wolff K, et al (eds): Dermatology in General Medicine , ed 3. New York, McGraw-Hill International Book Co, 1987, pp 610-626. 3. Eisenberg M, Stevens LH, Schofield PJ: Epidermolysis bullosa: New therapeutic approaches . Australas J Dermatol 1978;19:1-8.Crossref 4. Bauer EA, Cooper TW, Tucker DR, et al: Phenytoin therapy of recessive dystrophic epidermolysis bullosa: Clinical trial and proposed mechanism of action on collagenase . N Engl J Med 1980;303:776-781.Crossref 5. Cooper TW, Bauer EA: Therapeutic efficacy of phenytoin in recessive dystrophic epidermolysis: A comparison of short- and long-term treatment . Arch Dermatol 1984;120:490-495.Crossref 6. Eisen AZ: Human skin collagenase: Relationship to the pathogenesis of epidermolysis bullosa dystrophica . J Invest Dermatol 1969;52:449-453. 7. Lazarus GS: Collagenase and connective tissue metabolism in epidermolysis bullosa . J Invest Dermatol 1972;58:242-248.Crossref 8. Bauer EA, Gedde-Dahl T Jr, Eisen AZ: The role of human skin collagenase in epidermolysis bullosa . J Invest Dermatol 1977;68:119-124.Crossref 9. Bauer EA, Eisen AZ: Recessive dystrophic epidermolysis bullosa: Evidence for increased collagenase as a genetic characteristic in cell culture . J Exp Med 1978;148:1378-1387.Crossref 10. Valle K-J, Bauer EA: Enhanced biosynthesis of human skin collagenase in fibroblast cultures from recessive dystrophic epidermolysis bullosa . J Clin Invest 1980;66:176-187.Crossref 11. Stricklin GP, Welgus HG, Bauer EA: Human skin collagenase in recessive dystrophic epidermolysis bullosa: Purification of a mutant enzyme from fibroblast cultures . J Clin Invest 1982;69:1373-1383.Crossref 12. Bauer EA: Abnormalities in collagenase expression as in vitro markers for recessive dystrophic epidermolysis bullosa . J Invest Dermatol 1982;79( (suppl) ):105s-108s.Crossref 13. Rogers RB, Yancey KB, Allen BS, et al: Phenytoin therapy for junctional epidermolysis bullosa . Arch Dermatol 1983;119:925-926.Crossref 14. Guill MF, Wray BB, Rogers RB, et al: Junctional epidermolysis bullosa—treatment with phenytoin . AJDC 1983;137:992-994. 15. Kero M: Epidermolysis bullosa in Finland: Clinical features, morphology and relation to collagen metabolism . Acta Derm Venereol Suppl 1984;110:1-51. 16. Kero M, Palotic A, Peltonen L: Collagen metabolism in two rare forms of epidermolysis bullosa . Br J Dermatol 1984;110:177-184.Crossref 17. Paller AS, Fine JD, Kaplan S, et al: The generalized atrophic benign form of junctional epidermolysis bullosa: Experience with four patients in the United States . Arch Dermatol 1986;122:704-710.Crossref 18. Pearson R: Histopathologic and ultrastructural findings in certain genodermatoses . Clin Dermatol 1985;3:143-174.Crossref 19. Hintner H, Stingl G, Schuler G, et al: Immunofluorescence mapping of antigenic determinants within the dermal-epidermal junction in mechanobullous diseases . J Invest Dermatol 1981; 76:119-124.Crossref 20. Weber L, Krieg T, Muller P, et al: Immunofluorescent localization of type IV collagen and laminin in human skin and its application in junctional zone pathology . Br J Dermatol 1983; 106:267-273.Crossref 21. Fine JD, Breathnach S, Hintner H, et al: KF-1 monoclonal antibody defines a specific basement membrane antigenic defect in dystrophic forms of epidermolysis bullosa . J Invest Dermatol 1984;82:35-38.Crossref 22. Fine JD, Gay S: LDA-1 monoclonal antibody: An excellent reagent for immunofluorescence mapping studies in patients with epidermolysis bullosa . Arch Dermatol 1986;122:48-51.Crossref 23. Heagerty AHM, Kennedy AR, Eady RAJ, et al: GB3 monoclonal antibody for diagnosis of junctional epidermolysis bullosa . Lancet 1986;1:860.Crossref 24. Bergfeld WF, Orlowski JP: Epidermolysis bullosa retalis and phenytoin . J Am Acad Dermatol 1982;7:275-276.Crossref 25. Hintner H, Wolff K: Generalized atrophic benign epidermolysis bullosa . Arch Dermatol 1982;118:375-384.Crossref

Journal

Archives of Dermatology – American Medical Association

Published: Sep 1, 1988

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