Triple combination of systemic corticosteroids, excimer laser, and topical tacrolimus in the treatment of recently developed localized vitiligo.

Dear Editor:

The treatment of localized vitiligo usually involves a stepwise strategy; the first-line treatment is topical corticosteroids or calcineurin inhibitors, and a combination strategy has been proposed for patients with refractory lesions1. However, these schemes require many months to years of treatment and can result in disappointing outcomes. Moreover, previous studies have demonstrated that the longer the duration of the disease, the worse the prognosis were for the treatment, including surgical treatment2. Therefore, delay in treatment initiation may make treatment more difficult, and thus there is a strong need for early intervention for a successful treatment. Multiple combination modalities have been suggested, including topical agents and phototherapy, or systemic corticosteroid and surgery3. In this open pilot study, we investigated the efficacy of a triple combination treatment, consisting of systemic corticosteroids, excimer laser, and topical tacrolimus, in patients with recently developed localized vitiligo.

Fourteen patients (eight men, six women; mean age, 28.9 years) were enrolled in this study. Five patients had segmental vitiligo, whereas nine had focal vitiligo. All patients had recent-onset vitiligo lesions that had been evident for at least 6 months. The average duration of the vitiligo was 6.6 weeks. The mean body surface area of the vitiligo was <3%. None of the patients had a family history of vitiligo or had received another additional therapy for the disease before entry or during the study. One patient had Hashimoto's thyroiditis. This study was approved by the institutional review board of Ajou University Hospital (AJIRB-MED-MDB-12-158). All patients were treated with low-dose oral prednisolone (0.3 mg/kg/day) for 4~8 weeks, 0.1% topical tacrolimus (Protopic; Fujisawa Healthcare Inc., Deerfield, IL, USA) twice daily, and excimer laser twice a week for 12 weeks. The excimer laser (Xtrac; Photomedex, Radnor, PA, USA) was initiated at 100~200 mJ/cm2, and the dose was increased by 50 mJ/cm2. The size of the treated lesions was documented at study entry and every 4 weeks thereafter, by using digital photography. The endpoint of primary efficacy was the repigmentation rate of the lesion after 12 weeks, whereas the endpoint of secondary efficacy was complete repigmentation. Treatment efficacy was classified by using a visual grading system: weak effect, 0%~25% repigmentation; moderate effect, >25%~50% repigmentation; good effect, >50%~75% repigmentation; excellent effect, >75%~99% repigmentation; and complete effect, 100% repigmentation. Repigmentation was confirmed by the examination of treated lesions under a Wood's lamp; three dermatologists performed the photographic assessments. The treatment was ceased early in patients who showed complete repigmentation before 12 weeks. All patients were followed for 7 months to assess the stability of the pigmentation. Safety profiles were assessed simultaneously throughout the study.

All patients completed the 12-week treatment period. The lesions were located on the head and neck (n=12) and on the trunk (n=3). Among the 14 patients, repigmentation was scored as complete in five (35.7%) (Fig. 1), excellent in four (28.6%), good in one (7.1%), moderate in two (14.3%), and weak in two (14.3%) patients. There was no difference in treatment efficacy between the focal type and the segmental type. Complete repigmentation was achieved in 3 of 10 lesions in the focal type and in 2 of 5 lesions in the segmental type.

Fig. 1

Complete repigmentation. (A) Before treatment and (B) after 3 months of triple combination treatmentin patients 1, 8, 10, and 11. (C) At the end of the 7-week follow up, patient 6 with Hashimoto's thyroiditis had developed some areas of depigmentation over the repigmented sites. (D) However, this lesion was also completely repigmented after 1 month of combination treatment with excimer laser and topical tacrolimus. The black arrows indicate depigmented lesions.

Initial repigmentation was noted within 2 weeks in most of the patients. Among the five patients with complete repigmentation, two showed complete repigmentation within 1 month (patients 10 and 11). The response to treatment was generally poor in lesions accompanied by poliosis (good in one, moderate in two, and weak in two). At the 7-month follow-up, patient 6 (with Hashimoto's thyroiditis) had developed some areas of depigmentation over the repigmented sites, whereas the pigmentation remained stable in the other patients. Three patients complained of adverse effects, including slight pain and bulla due to laser therapy, and abnormal menstruation, which may be due to the systemic steroid. However, the adverse effects were not serious and were reversible, and therefore did not affect the treatment schedule. The demographics of the patients and a summary of the treatment results are presented in Table 1.

Table 1

Demographics and treatment results in 14 patients with recent onset vitiligo

*No or weak effect, 0%~25% repigmentation; moderate effect, >25%~50% repigmentation; good effect, >50%~75% repigmentation; excellent effect, >75%~99% repigmentation; complete effect, 100% repigmentation.

Previous studies have consistently reported that combination interventions of topical therapy and phototherapy were superior to monotherapies1. Phototherapy induces a predominantly perifollicular pattern of repigmentation, whereas topical agents exhibit a diffuse type, acting synergistically when combined4. A significant finding of this study is that complete repigmentation occurred in 35.7% of the patients, which was much higher than that reported for other modalities of current vitiligo therapy. One previous study revealed that the combination of excimer laser and topical 0.1% tacrolimus ointment achieved >75% repigmentation in 70% of patients. However, complete repigmentation occurred in only 2 of 23 lesions within 2 months5. When excimer laser was combined with topical hydrocortisone for the treatment of vitiligo of the face and neck, >75% repigmentation was observed in 42.8% of the patients and complete repigmentation occurred in 21.4% of the patients6. Therefore, the higher rate of complete repigmentation in this study is meaningful, as most patients do not favor inhomogeneous repigmentation. In addition, complete repigmentation was more rapid and was achieved within 1 month in two patients. The rapid onset of repigmentation improved the patients' motivation and their compliance to therapy.

We added a systemic corticosteroid that had been suggested to suppress disease activity or progression without any noticeable adverse effects7,8. It was suggested that early dynamic events in vitiligo, including for the segmental type, are characterized by the infiltration of inflammatory cells on histological examination, which is implicated in the development of vitiligo9. The combination of a systemic corticosteroid and topical tacrolimus was also reported in two cases of recent-onset vitiligo10. These cases were treated successfully and suggest the necessity of early intervention.

The limitation of this study was the small population size. In conclusion, we propose that the triple combination treatment with systemic corticosteroids, excimer laser, and topical tacrolimus is effective for recent-onset vitiligo as a first-line therapy. It is likely that early intervention with this combination treatment can prevent disease progression, and achieve a more rapid and complete repigmentation.