The Value of Using Methotrexate Therapy Along With Non Cultured Epidermal Cell Suspension (NCES) in Stable Resistant Vitiligo: An Interventional Prospective Randomized Controlled Trial.

Depending on the type, extent, and duration of vitiligo, conventional medical therapies such as topical and systemic corticosteroids, topical immunomodulators, and phototherapy are not always successful, and repigmentation is often incomplete. Acral vitiligo as well as vitiligo over friction sites as elbows and knees are resistant to treatment including surgical procedures. Relatively less melanocyte density as well as higher chances of koebnerization over these friction and injury prone anatomical sites were among the suggestions for poor response to treatment. It was also found that melanocyte growth and migration in acral vitiligo is hindered by several factors such as decreased MMP9, MMP2, c-kit and MHCII expression, together with higher expression of antimelanogenic factors as tenascin and DKK1. Non-cultured epidermal cellular suspension (NCES) is a cellular grafting technique, whose major advantage is permitting treatment of affected skin surface area up to 10 times larger than the donor area without culturing. Methotrexate is an antifolate drug, that decreases the number of T cells. Studies showed that methotrexate has a positive effect on the stabilization of vitiligo. Combined treatment with phototherapy allows better and faster repigmentation than phototherapy alone. Systemic drugs have been previously used perioperatively in vitiligo surgery. Oral betamethasone has been previously used in the peri surgical period and was reported to increase the chances of complete repigmentation in large vitiliginous lesions as activity at the cellular level is still plausible in spite of clinical stability. The aim of this study is to assess whether adding methotrexate therapy to NCES in the peri surgical period would improve repigmentation in acral vitiligo and other resistant sites.

• Inclusion criteria:

• Patients with non-segmental vitiligo (NSV) with acral or resistant lesions over the elbows and knees, that has not responded to conventional treatment

• Stability for ≥ 1 year

• Age ≥18 years

• Lack of topical treatment for at least 1 month prior to surgery and systemic treatment for at least 3 months prior to surgery.

• Exclusion criteria:

• Non acral NSV responsive to conventional treatment modalities

• Active vitiligo; new lesions, expansion of old lesions, confetti like lesions, ill-defined edges or koebnerization in < 1 year

• Age < 18 years.

• Pregnant females.

• Patients with hematologic, hepatic, renal disease or chronic infection.

• Topical treatment in the past month and systemic treatment in the past 3 months.

• Methodology in details:

• forty lesions in patients with stable vitiligo will be recruited (20 size and region matched lesions per group). An informed written consent will be obtained from patients.

• Patients will be randomized using a computer generated list to one of the two groups which are age and sex matched:

Group A will undergo None cultured epidermal suspension (NCES) without methotrexate.