Evaluation of the effect and mechanism of action of local phenytoin in treatment of vitiligo

Abstract

There are many theories explaining vitiligo such as genetic, autoimmune, neural, free radicals, biochemical, intrinsic defect, melanocytorrhagy, and convergent theories. Phenytoin is a widely used anticonvulsant, which is used in cutaneous medicine for treatment of ulcers and epidermolysis bullosa. The aim of this study is to assess the effectiveness of topical phenytoin gel in the treatment of vitiligo patients and explaining the underlying mechanism using immunohistochemistry for evaluation of HMB45, CD4, and CD8. Only 9 patients out of 28 experienced response to phenytoin in the form of dull, white color change and light brown color. Post-phenytoin treatment biopsies showed decreased density of inflammation, increased melanin and increased HMB45 positive cells together with an increased number of CD4 positive lymphocytes and decreased number of CD8 positive lymphocytes. These observations did not reach significant level (P > 0.05). A high percentage of CD4 positive lymphocytes was significantly associated with a long duration of vitiligo (p = 0.03) and segmental vitiligo type (p = 0.02). The current study applied phenytoin as 2% concentrated gel for 3 months, which is a relatively short duration without observed side effects throughout the period. These results indicate that topical phenytoin of low concentrations may have beneficial effects through immunomodulatory activity by affecting CD4 and CD8 counts and subsequently the ratio between them. Further studies are recommended to combine phenytoin with other antivitiligo agents as local corticosteroids or phototherapy to clarify if it could potentiate their effects.

Histological and Immunohistochemical Study of the Effect of Topically Applied Phenytoin on Chemically Induced Buccal Mucosal Ulcer in Albino Rats

“…Topical application of phenytoin was chosen in the current study rather than systemic administration due to entrance of the drug directly to the targeted site without getting systemic adverse effects [13] . Gel formulation has been prepared and used in this study, as it was reported to be the most appropriate for clinical trials [14] .…”

Evaluation of the Langerhans cells role in vitiligo and its relationship to NB‐UVB

“…11 Response to therapy was estimated clinically by observing the changes in color of the vitiliginous patches, 1 (no response, milky white color still present or erythematous color change), 2 (dull white color change), 3(Light brown color change), and 4 (Normal skin color). 12 For statistical purpose, cases achieving scores 2, 3, and 4 were lumped together and designated as responding versus score 1 as nonresponding.…”

“…Response to therapy was estimated clinically by observing the changes in color of the vitiliginous patches, 1 (no response, milky white color still present or erythematous color change), 2 (dull white color change), 3(Light brown color change), and 4 (Normal skin color) 12 …”

Evaluation of combination use of phenytoin cream 1% and fractional CO 2 laser in treatment of stable nonsegmental vitiligo: A pilot study

“…Phenytoin is documented to significantly suppress the mitogen‐induced activation of cytotoxic T‐lymphocyte and cell‐mediated immunity. Moreover, phenytoin was shown to induce a successful proliferation of melanocytes and a stabilization of melanosomes membranes in the treatment of vitiligo 10 …”