Guideline for the Diagnosis and Management of Vitiligo

D.J. Gawkrodger; A.D. Ormerod; L. Shaw; I. Mauri-Sole; M.E. Whitton; M.J. Watts; A.V. Anstey; J. Ingham; K. Young

Disclosures

The British Journal of Dermatology. 2008;159(5):1051-1076. 

In This Article

In Patients With Vitiligo, What is the Efficacy of a Skin Graft and of Various Forms of Placebo in Terms of Condition Progression, Area Reduction and Quality of Life Score? This May Include Punch Grafts, Full-thickness Skin Graft, Split-thickness Skin Graft, Autologous Epidermal Cell Suspension, and Autologous Skin Equivalent (Commercial Skin Equivalent)

Surgical interventions are based on the idea of transplanting functional melanocytes to the depigmented area. To be successful this requires preparation of the affected area with debridement, laser peeling of the skin, suction blisters or removal of punch biopsies. There are several methods of varied sophistication for harvesting melanocytes, the simplest being by punch biopsy. These techniques require a donor site, which may be scarred and in which vitiligo may be induced by the Koebner phenomenon.

It is difficult to design RCTs for treatments that use skin grafts. Many papers refer to methodology or small patient series. Case series, cohorts or randomized clinical trials of 20 or more patients were included. A systematic review has looked at a set of 39 nonrandomized studies carried out prior to 1998, so only papers that followed were selected. Eleven papers were identified, of which five were RCTs, five case series and one a systematic review.

Njoo etal. performed a systematic review that evaluated 39 studies assessing split-thickness graft, minigraft using punch biopsies, epidermal suction blisters as preparation and donor and transplantation of noncultured cell suspension or cultured melanocytes.[110] The highest mean success rates (87%) were achieved with split-skin grafting (95% CI 82-91%) and epidermal blister grafting (87%; 95% CI 83-90%). The mean success rate of five culturing techniques varied from 13% to 53%. However, in four of the five culturing methods, fewer than 20 patients were studied and there was insufficient evidence. Minigrafting had the highest rates of adverse effects, with poor colour match in <10%, cobblestone appearance in 27%, milia in 13%, partial take in 11% and thick margins in 5%. Split-skin grafting and epidermal blister grafting were recommended as the most effective and safest techniques. Barman etal. studied 50 patients in an RCT comparing punch graft followed by PUVA with punch graft followed by topical fluocinolone acetonide and found spread of pigment similar in each group, both of which had significant side-effects as above.[111] Khandpur etal., in an RCT of 64 patients, compared minipunch grafting with split-skin grafting: 15 of 34 (44%) punch grafts had excellent (>75%) repigmentation, compared with 25 of 30 (83%) of the split-skin grafts.[112] Cosmetic results were better with split-skin grafts.

Ozdemir and colleagues, in an unblended RCT, studied 20 patients comparing, within patients, suction blister alone with suction blister grafting, suction and a split-skin graft or area of thin split-skin graft.[113] Using suction blisters, repigmentation was 25-65% as compared with 90% with split-skin graft.[114] Gupta and Kumar, in a retrospective series of 143 patients, evaluated suction blister transfer supplemented by PUVA.[114] The success rate was 50% and was higher in segmental or focal disease and in patients under 20years. The results were not affected by site. Kim and Kang reported a case series of 40 patients using suction blister transfer who were followed up for 3months-2·5years.[115] Of these, 71-73% had complete repigmentation but relapse was more common in patients with progressive disease (40%) than in those with stable vitiligo (10%).

Van Geel and colleagues, in a high-quality RCT that included 28 patients, looked at autologous cell suspension applied to laser-debrided skin followed by NB-UVB or PUVA, compared with a placebo application to another area, and analysed images of the outcome.[116] Pigmentation was seen only in sites receiving cell suspension and progressed from 55% to 77%, showing >70% repigmentation between 3 and 12months. Pianigiani etal. reported a case series of 93 patients treated with laser abrasion and grafting of cultured epidermal cells and NB-UVB and followed for 18months.[117] Complete repigmentation was seen in 60% and partial (>50%) in 30%. Relapses were not seen at 18months. Pandya and colleagues studied 27 patients in a case series allocated to dermabrasion and application of cultured melanocytes or dermabrasion with application of autologous disaggregated epidermal cell suspension.[118] Excellent responses of >90% repigmentation were seen in 50% and 52%, respectively, with no scarring. There were more good responses in the noncultured group.

Chen etal., in a case series of 120 patients treated with laser abrasion followed by application of cultured epidermal cells, observed >90% repigmentation in 84%, 90-100% coverage in localized disease, 54% in stable generalized vitiligo, and only 14% in active generalized vitiligo.[119] Guerra etal. reported 32 patients treated with programmed diathermy (TIMED surgery) to prepared sites followed by the application of autologous cultured epidermal cells, and found 88-96% repigmentation, with less successful repigmentation on the extremities (8%) and in a periorificial distribution (35%).[120] Guerra etal. also evaluated the use of skin preparation using erbium-YAG laser followed by application of cultured epidermal cells in 21 patients with vitiligo.[121] Repigmentation was noted in 76%. The same authors treated six patients with piebaldism using this technique, with good results.[122]

Surgical techniques were among the most effective interventions in the systematic review and have been assessed in RCTs. They are limited by their invasive nature and often studies applied only to a target area which may not equate to any perceived benefit for the patient, unless the area is particularly disfiguring, e.g. lips or eyelids. There was some evidence for successful treatment of such difficult sites, but results are less good in the extremities and around orifices. The least scarring is seen with the method using laser-abraded skin preparation and application of cell suspensions. This requires special facilities. A 'lab in a box' kit for producing cell suspensions has been produced recently (Recell®; Clinical Cell Culture Europe Ltd, Cambridge, U.K.) but has not been evaluated in any meaningful studies. Surgical treatment gives a high rate of successful repigmentation that appears to be durable in patients with stable inactive vitiligo. Patient selection is important.

  1. Surgical treatments in vitiligo should be used only for cosmetically sensitive sites where there have been no new lesions, no Koebner phenomenon and no extension of the lesion in the previous 12months.

    Grade of recommendation A
    Level of evidence 1++

  2. Split-skin grafting is the best option when a surgical treatment is required.

    Grade of recommendation A
    Level of evidence 1+

  3. Minigraft is not recommended due to a high incidence of side-effects and poor cosmetic results including cobblestone appearance and polka dot appearance.

    Grade of recommendation A
    Level of evidence 1+

  4. Autologous epidermal suspension applied to laser-abraded lesions followed by NB-UVB or PUVA therapy is the optimal surgical transplantation procedure but does require special facilities.

    Grade of recommendation A
    Level of evidence 1+

  5. Expanding the autologous cells in tissue culture prior to grafting is feasible and treats larger areas successfully, without the need for additional phototherapy. However, the culturing introduces growth factors leading to uncertain risks and cultures can fail, reducing the value of the procedure.

    Grade of recommendation D
    Level of evidence 3

  6. Transfer of suction blisters is an alternative transplantation method, which shows evidence of benefit over placebo but gives less good coverage than split-skin grafting or laser and cell suspension.

    Grade of recommendation B
    Level of evidence 1+

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