1. Aetna considers the following established methods medically necessary for the treatment of vitiligo:

   1. Topical and systemic corticosteroids 
   2. Topical and oral psoralen photochemotherapy (PUVA) 
   3. Narrow-band ultraviolet B (UVB)

   4. Excimer laser (e.g., XTRAC, PhotoMedex, Radnor, PA; EX-308, Ra Medical Systems, Inc., Carlsbad, CA).

2. Aetna considers continued PUVA or narrow-band UVB therapy not medically necessary unless there is significant follicular pigmentation after 6 months of therapy (8 to 10 treatments per month).

3. Aetna considers home phototherapy experimental and investigational for the treatment of vitiligo because there is a lack of evidence regarding the safety and effectiveness of home phototherapy for this condition.

4. Aetna considers treatments for vitiligo cosmetic if they do not affect the underlying condition and do not result in improved protection against skin cancer; specifically micropigmentation (tattooing) and depigmentation (with monobenzylether of hydroquinone/monobenzone) are considered cosmetic.

5. Aetna considers melanocyte transplantation for the treatment of vitiligo experimental and investigational.

Vitiligo is an acquired pigmentary disorder of skin and mucous membranes, manifesting itself by expanding depigmented lesions. While the cause is not well understood, the observed variation in clinical manifestations of the condition has suggested several possible etiologies, including association with other medical conditions. The three prevailing theories of the pathogenesis of vitiligo include an immune hypothesis, a neural-mediated hypothesis, and a “self-destruct” hypothesis. These three, plus newer hypotheses suggesting that vitiligo may be due to a melanocyte growth factor deficiency or to an abnormal melatonin receptor on melanocytes, have not been definitively proven, and it is likely that the loss of epidermal and follicular melanocytes in vitiligo may be the result of several different pathogenic mechanisms.

Psoralen photochemotherapy (psoralen and ultraviolet light A or PUVA) is appropriate for properly selected patients with vitiligo. The treatment involves taking oral psoralen or applying it topically followed by carefully timed exposure to ultraviolet A. Repigmentation may begin after 15 to 25 treatments. Approximately 50% of patients will develop repigmentation after 150-200 PUVA treatments over 12 to 24 months. The response is slow and repigmentation may not be complete. Response to PUVA is unlikely to occur if follicular pigmentation has not appeared after three months of PUVA therapy. Dark-skinned patients respond better than fair skin patients do; the latter are unlikely to benefit from PUVA unless there is marked disfigurement. Most patients who respond do not develop new areas of pigment loss; furthermore, maintenance with PUVA therapy is not necessary.

Children under age 10 are generally not treated with oral phototherapy; instead, a mild topical corticosteroid cream is often prescribed. A stronger topical corticosteroid cream can be prescribed for adults. Patients must apply the cream (e.g., triamcinolone 0.1%, desonide 0.05%) once a day to the white patches on their skin for at least 3-4 months before seeing any results. Systemic corticosteroids can stop the progression of vitiligo for some patients, but may also produce unacceptable side effects. Oral mini-pulse therapy with 5 mg betamethasone/dexamethasone may stop the progression and induce spontaneous repigmentation in some vitiligo patients.

A number of recently published studies have demonstrated that narrow-band UVB is an effective treatment for vitiligo, and compares favorably to UVA and psoralens (see, e.g., Westerhof, 1997; Njoo, et al., 2000; Scherschun, et al., 2001). Unlike PUVA, narrow-band UVB does not involve the use of sensitizing agents. Narrow-band UVB is typically administered two to three times per week for several months. However, there is a lack of evidence regarding the safety and effectiveness of home narrow-band UVB phototherapy for the treatment of vitiligo.

In a randomized controlled study, Ada et al (2005) concluded that narrow-band UVB phototherapy is effective in treating vitiligo, and the addition of topical calcipotriol does not improve treatment outcome.

In a double-blind randomized study, Yones et al (2007) compared the effectiveness of oral psoralen-UV-A (PUVA) with that of narrowband-UV-B (NB-UVB) phototherapy in patients with non-segmental vitiligo. A total of 56 patients received twice-weekly therapy with PUVA or NB-UVB. The change in body surface area affected by vitiligo and the color match of repigmented skin compared with unaffected skin were assessed after 48 sessions of therapy, at the end of the therapy course, and 12 months after the end of therapy. The results in the 25 patients each in the PUVA and NB-UVB groups who began therapy were analyzed. The median number of treatments was 47 in the PUVA-treated group and 97 in the NB-UVB-treated group (p = 0.03); this difference was probably due to differences in effectiveness and adverse effects between the two modalities, such that patients in the NB-UVB group wanted a longer course of treatment. At the end of therapy, 16 (64 %) of 25 patients in the NB-UVB group showed greater than 50 % improvement in body surface area affected compared with 9 (36 %) of 25 patients in the PUVA group. The color match of the repigmented skin was excellent in all patients in the NB-UVB group but in only 11 (44 %) of those in the PUVA group (p < 0.001). In patients who completed 48 sessions, the improvement in body surface area affected by vitiligo was greater with NB-UVB therapy than with PUVA therapy (p = 0.007). Twelve months after the cessation of therapy, the superiority of NB-UVB tended to be maintained. The authors concluded that in the treatment of non-segmental vitiligo, NB-UVB therapy is superior to oral PUVA therapy.

In a randomized, investigator-blinded and half-side comparison study, Casacci and colleagues (2007) compared the effectiveness of NB-UVB phototherapy and 308-nm monochromatic excimer light (MEL) in patients with vitiligo. A total of 21subjects with symmetrical vitiligo lesions were enrolled in this study. Vitiligo lesions on one body side were treated twice-weekly for 6 months with 308-nm MEL, while NB-UVB phototherapy was used to treat lesions on the opposite side. At the end of the study, 6 lesions (37.5 %) treated with 308-nm MEL and only 1 lesion (6 %) treated with NB-UVB achieved an excellent repigmentation (score 4) while 4 lesions (25 %) treated with 308-nm MEL and 5 lesions (31 %) treated with NB-UVB showed a good repigmentation (score 3). The authors concluded that it appears that 308-nm MEL is more effective than NB-UVB in treating vitiligo lesions and it induces repigmentation more rapidly.

Several clinical studies have demonstrated that the Xenon-Chloride excimer laser is effective in repigmentation of vitiligo patches (Hadi, et al., 2004; Choi, et al., 2004; Esposito, et al., 2004; Kawalek, et al., 2004; Taneja, et al., 2003; Spencer, et al., 2002). The excimer laser may be especially useful in treatment of localized vitiligo that is refractory to topical corticosteroids. Treatments are typically administered twice weekly and up to 60 treatments may generally be medically necessary. Recent studies have also suggested that combination treatment with excimer laser and topical methoxypsoralen resulted in better repigmentation than excimer laser alone. However, due to the small sample sizes in these studies, their findings need to be validated by additional studies (Grimes, 2005).

Transplantation of autologous pigment cells is considered experimental and investigational for the treatment of vitiligo because of a lack of adequate clinical evidence of effectiveness from randomized controlled clinical trials.

van Geel and colleagues (2006) investigated the the effectiveness of non-cultured epidermal cell transplantation in treating stabilized vitiligo using objective and subjective evaluation methods. Non-cultured autologous melanocytes and keratinocytes were grafted in a hyaluronic-acid-enriched suspension on superficially laser-abraded vitiligo lesions in 40 patients with refractory stable vitiligo (30 with generalized and 10 with localized vitiligo). The repigmentation was evaluated 3 to 12 months after grafting using a digital image analysis system. Furthermore, the treatment was evaluated from patients' point of view with the DLQI (Dermatology Life Quality Index) and a global assessment. The mean percentage of repigmentation, evaluated at the last follow-up visit, was 72 % (median of 84 %), and a repigmentation of greater than or equal to 70 % was observed in 62 % of patients. The best results were achieved in the neck and the pre-sternal region. A subjective evaluation was performed in 50 % of the subjects. The mean DLQI score at inclusion (6.95, SD = 6.68, n = 20) was significantly lowered after treatment (p = 0.013, mean 3.85, SD = 4.13, n = 20). The patients were satisfied with the achieved result, and they found it worthwhile to undergo the treatment and would choose it again. The authors concluded that according to both subjective and objective evaluation methods, non-cultured epidermal cell transplantation is promising in patients with stable vitiligo.