Dilantin for esophageal strictures??

[Pilot]

Enlighten me.

I currently have a patient in the hospital with Dystrophic Epidermolysis Bullosa (DEM), a rare genetic condition which results in bulla formation with subsequent scarring. Not only does this occur on the skin, but also can occur in the esophagus and GI tract. Scarring in the esophagus generally results in strictures and dysphagia. During my reading on this disease, I found an article which states that dilantin can be used with moderate success to ease strictures. What is the mechanism of dilantin for this specific complication? I could not figure it out, and neither could 5 other pharmacists I have spoken to in the last 2 days (and yes, 3 of them were clinical hospital pharmacists). None of us have heard of Dilantin being used for esophageal strictures, and F&C does not mention this usage as well. Has anyone heard of this? Perhaps some of you students could ask your instructors to speculate on a mechanism.

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[bananaface]

"Dystrophic Epidermolysis Bullosa" and "phenytoin" brought up several directly relevant hits on PubMed. This article in particular took the most recent stab at answering your question. I am not sure if the link to the full text article will work for you or not. The abstract is publicly available. This particular article discusses topical use. But, work has also been done with oral phenytoin therapy.

Talas G, Adams TS, Eastwood M, Rubio G, Brown RA. Phenytoin reduces the contraction of recessive dystrophic epidermolysis bullosa fibroblast populated collagen gels. Int J Biochem Cell Biol. 1997 Jan;29(1):261-70.
http://www.sciencedirect.com/scienc...d=582538&md5=c12c08293ae95df2d482cb4f16f2858c

Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) is a group of genetic disorders in which blistering occurs below the basement membrane, in many cases resulting in extensive scar formation, contractures and mitten deformities. Our aim was to compare quantitatively the contraction forces generated by normal and RDEB fibroblasts and to investigate the effect of Phenytoin (5,5-diphenyl-2,4-imidazolidinedione, sodium salt; PHT). PHT is an anticonvulsant agent, that causes fibrosis as a side effect. This study utilised conventional untethered fibroblast populated collagen lattice contraction and a quantitative force measurement instrument, the culture force monitor (CFM). The RDEB cell lines were hypercontractile, generating 2.5 times the force of normal fibroblasts, though they appeared morphologically normal. In untethered collagen gels PHT (20 g/ml) significantly reduced contraction of both normal and RDEB fibroblasts over 7 days. Pre-treatment of RDEB cells for 5 days also produced a 40% reduction in contraction as measured in the CFM. One suggested mechanism of PHT action is through inhibition of matrix metalloproteinase activity, but the similar effects of PHT and Colchicine (an inhibitor of microtubule polymerisation) in the CFM, indicate that it may act on contraction through disruption of microfilaments and changes to cell shape. These findings show that isolated RDEB fibroblasts retain the hypercontractile features of many of the patient's lesion sites and imply that local application of PHT may have a therapeutic effect in controlling contraction.

 

[Oneday_9]

"Dystrophic Epidermolysis Bullosa" and "phenytoin" brought up several directly relevant hits on PubMed. This article in particular took the most recent stab at answering your question. I am not sure if the link to the full text article will work for you or not. The abstract is publicly available. This particular article discusses topical use. But, work has also been done with oral phenytoin therapy.

Talas G, Adams TS, Eastwood M, Rubio G, Brown RA. Phenytoin reduces the contraction of recessive dystrophic epidermolysis bullosa fibroblast populated collagen gels. Int J Biochem Cell Biol. 1997 Jan;29(1):261-70.
http://www.sciencedirect.com/scienc...d=582538&md5=c12c08293ae95df2d482cb4f16f2858c

Abstract
Recessive dystrophic epidermolysis bullosa (RDEB) is a group of genetic disorders in which blistering occurs below the basement membrane, in many cases resulting in extensive scar formation, contractures and mitten deformities. Our aim was to compare quantitatively the contraction forces generated by normal and RDEB fibroblasts and to investigate the effect of Phenytoin (5,5-diphenyl-2,4-imidazolidinedione, sodium salt; PHT). PHT is an anticonvulsant agent, that causes fibrosis as a side effect. This study utilised conventional untethered fibroblast populated collagen lattice contraction and a quantitative force measurement instrument, the culture force monitor (CFM). The RDEB cell lines were hypercontractile, generating 2.5 times the force of normal fibroblasts, though they appeared morphologically normal. In untethered collagen gels PHT (20 g/ml) significantly reduced contraction of both normal and RDEB fibroblasts over 7 days. Pre-treatment of RDEB cells for 5 days also produced a 40% reduction in contraction as measured in the CFM. One suggested mechanism of PHT action is through inhibition of matrix metalloproteinase activity, but the similar effects of PHT and Colchicine (an inhibitor of microtubule polymerisation) in the CFM, indicate that it may act on contraction through disruption of microfilaments and changes to cell shape. These findings show that isolated RDEB fibroblasts retain the hypercontractile features of many of the patient's lesion sites and imply that local application of PHT may have a therapeutic effect in controlling contraction.

Thanks, bananaface, I was wondering about this last night and was going ask about it. PubMed is the best.