Comparative outcomes of autologous cultured melanocytes transplantation and non-cultured epidermal cell suspension transplantation in piebaldism patients: A retrospective study.

PURPOSE: To compare the efficacy and safety of autologous cultured melanocytes transplantation (CMT) and non-cultured epidermal cell suspension transplantation (NCES) in the treatment of piebaldism. PATIENTS AND METHODS: A retrospective study was conducted on 30 anatomically based lesions from nine piebaldism patients who underwent either CMT (n = 7) or NCES (n = 23) between 2018 and 2020. The extent of repigmentation and colour matching was evaluated in all recipient sites using a digital imaging analysis system. In addition, adverse effects have also been assessed by follow-up results. RESULTS: More than 75% repigmentation was achieved in 100% (7/7) and 60.9% (14/23) of the 30 lesions with the CMT and NCES, respectively. There were significant differences between the two methods in terms of repigmentation. The majority of patients had colour mismatches, and there was no discernible difference between the two surgical techniques. Adverse reactions rarely occurred. CONCLUSION: The present study suggested that autologous CMT may provide better repigmentation in piebaldism patients than NCES with no significant side effects.

Recipient-to-Donor Ratios in the Surgical Treatment of Vitiligo, Leukoderma, and Piebaldism: A Retrospective Review.

BACKGROUND: The autologous noncultured melanocyte keratinocyte transplant procedure (MKTP) has emerged as a popular grafting technique with proven efficacy for achieving repigmentation. However, there remains no consensus regarding the optimal recipient-to-donor (RD) ratio required to achieve acceptable repigmentation. In this retrospective cohort study of 120 patients, we sought to examine whether expansion ratios impact the repigmentation success rates following MKTP. RESULTS: A total of 69 patients (mean [SD] age was 32.4 [14.3] years, mean follow-up was 30.4 [22.5] months, 63.8% were male; 55% were dark-skinned individuals [Fitzpatrick IV-VI]) were included. The mean percent change in the Vitiligo Area Scoring Index (VASI) was 80.2 (±23.7; RD of 7.3) in patients with focal/segmental vitiligo (SV), 58.3 (±33.0; RD of 8.2) in those with non-segmental vitiligo (NSV), and 51.8 (±33.6; RD of 3.7) in those with leukoderma and piebaldism. Focal/SV was positively associated with a higher percent change in VASI (parameter estimate: 22.6, p value <0.005). In the SV/focal group, non-white patients had a higher RD ratio compared to White individuals (8.2 ± 3.4 vs. 6.0 ± 3.1, respectively, p value = 0.035). DISCUSSION: In our study, we found that patients with SV were significantly more likely to achieve higher repigmentation rates compared to those with NSV. Although repigmentation rates were higher in the low expansion ratio group than in the high expansion ratio group, we did not observe a significant difference between the two groups. CONCLUSION: MKTP is an effective therapy for restoring repigmentation in patients with stable vitiligo. Therapeutic response of vitiligo to MKTP appears to be influenced by the type of vitiligo, rather than a specific RD ratio.

Assessment of Non-cultured Autologous Epidermal Cell Grafting Resuspended in Hyaluronic Acid for Repigmenting Vitiligo and Piebaldism Lesions: A Randomized Clinical Trial.

The aim of this study was to assess the efficacy of non-cultured autologous epidermal cell grafting resuspended in hyaluronic acid, performed using a ready-to-use kit, compared with hyaluronic acid alone (neutral comparator) for repigmenting vitiligo and piebaldism lesions at 6 months. Two identified paired lesions per patient were randomized to be treated by either device. Devices with a ready-to-use kit were prepared by separate health professionals, to maintain blinding. A skin biopsy was digested using trypsin, and cells resuspended in hyaluronic acid solution. Among 38 patients screened, 36 (94.7%) patients, corresponding to 72 lesions, were analysed. For difficult-to-treat lesions, defined as those located on the wrist, elbow, and hands (n = 30), no repigmentation ≥ 50% was observed. For all other locations (n = 42), the success rate was significantly higher (p = 0.021) in the ready-to-use kit group (47.6% vs 9.5%) at 6 months and was maintained until 12 months. In conclusion, a single application of non-cultured epidermal cellular grafting using a ready-to-use kit was efficient at 6 months and at 1-year follow-up.

Donor to recipient ratios in the surgical treatment of vitiligo and piebaldism: a systematic review.

Stabilized vitiligo resistant to conventional therapy (e.g. segmental vitiligo) and piebaldism lesions can be treated with autologous cellular grafting techniques, such as non-cultured cell suspension transplantation (NCST) and cultured melanocyte transplantation (CMT). These methods are preferred when treating larger surface areas due to the small amount of donor skin needed. However, the donor to recipient expansion ratios and outcomes reported in studies with cellular grafting vary widely, and to date, no overview or guideline exists on the optimal ratio. The aim of our study was to obtain an overview of the various expansion ratios used in cellular grafting and to identify whether expansion ratios affect repigmentation and colour match. We performed a systematic literature search in MEDLINE and EMBASE to review clinical studies that reported the expansion ratio and repigmentation after cellular grafting. We included 31 eligible clinical studies with 1591 patients in total. Our study provides an overview of various expansion ratios used in cellular grafting for vitiligo and piebaldism, which varied from 1:1 up to 1:100. We found expansion ratios between 1:1 and 1:10 for studies investigating NCST and from 1:20 to 1:100 in studies evaluating CMT. Pooled analyses of studies with the same expansion ratio and repigmentation thresholds showed that when using the lowest (1:3) expansion ratio, the proportion of lesions achieving >50% or >75% repigmentation after NCST was significantly better than when using the highest (1:10) expansion ratio (χ2 P = 0.000 and χ2 P = 0.006, respectively). Less than half of our included studies stated the colour match between different expansion ratios, and results were variable. In conclusion, the results of our study indicate that higher expansion ratios lead to lower repigmentation percentages after NCST treatment. This should be taken into consideration while determining which expansion ratio to use for treating a patient.

Autologous cell suspension grafting in segmental vitiligo and piebaldism: a randomized controlled trial comparing full surface and fractional CO2 laser recipient-site preparations.

BACKGROUND: Autologous noncultured cell suspension transplantation is an effective treatment for repigmentation in segmental vitiligo and piebaldism. Full surface laser ablation is frequently used to prepare the recipient site before cell suspension transplantation, even though the optimal laser settings and ablation depth are unknown. OBJECTIVES: To assess the efficacy and safety of less invasive recipient-site preparations. METHODS: In a randomized, observer-blinded, controlled trial we compared different recipient-site preparations before cell suspension transplantation in segmental vitiligo and piebaldism. In each patient, we randomly allocated three CO2 laser recipient-site preparations (209 and 144 µm full surface, and fractional) and a control (no treatment) to four depigmentations. After 6 months we assessed repigmentation and side-effects. RESULTS: We included 10 patients with vitiligo (n = 3) and piebaldism (n = 7). Compared with the control site, we found more repigmentation after full surface ablation at 209 µm (median 68·7%, P = 0·01) and 144 µm (median 58·3%, P = 0·007), but no repigmentation after fractional ablation (median 0·0%, P = 0·14). CONCLUSIONS: Superficial full surface ablation with a depth of 144 µm is an effective recipient-site preparation before cell suspension transplantation, while fractional CO2 laser is not.

Optimising size and depth of punch grafts in autologous transplantation of vitiligo and piebaldism: a randomised controlled trial.

BACKGROUND: To date, autologous punch grafting appears to be the easiest and least expensive surgical technique for stable vitiligo and piebaldism. Punch grafting is available worldwide, with no need for specialised instruments. However, no reliable data on efficacy and safety of different punch depths and punch sizes are available. OBJECTIVE/METHODS: To compare the efficacy and safety of different punch depths and punch sizes in autologous punch grafting, a randomised controlled trial was performed in 33 patients with vitiligo or piebaldism. In each patient, four depigmented regions were allocated to: 1.5 mm deep grafts, 1.5 mm superficial grafts, 1.0 mm deep grafts, and 1.0 mm superficial grafts. Primary outcome was the total pigmented surface area. Secondary outcomes were Patients' Global Assessment (PGA) and side effects. RESULTS: Six months after grafting, 1.5 mm grafts showed a significantly larger pigmented surface area compared to 1.0-mm grafts (p < 0.001), though more side effects as well. No significant differences in the total pigmented surface between different punch depths were found. Deep grafts showed more erythema compared to superficial grafts. CONCLUSION: We recommend 1.5 mm superficial grafts in autologous punch grafting for trunk and proximal extremities in patients with stable vitiligo and piebaldism.

Long-term results of noncultured epidermal cellular grafting in vitiligo, halo naevi, piebaldism and naevus depigmentosus.

BACKGROUND: Several surgical techniques are available for the treatment of stable leucoderma. The use of noncultured epidermal cellular grafting was introduced in 1992. Data on long-term follow-up regarding stability of the repigmented area, time to achieve the final repigmentation, colour matching, reaction to sun exposure and patient satisfaction with treatment have been reported only a few times previously. OBJECTIVES: To evaluate the long-term results of the noncultured epidermal cellular grafting technique in patients with different types of leucoderma, including segmental vitiligo (n = 33), generalized vitiligo (n = 33), mixed vitiligo (n = 6), halo naevi (n = 11), piebaldism (n = 3) and naevus depigmentosus (n = 1). METHODS: Patients were evaluated by examination and questionnaire in a retrospective setting after transplantation by autologous noncultured cellular grafting. Percentage of repigmentation was evaluated in 82 patients using a digital imaging analysis system (mean follow-up 15 months). Long-term results were evaluated by 54 patients using a questionnaire up to 7·7 years after treatment (mean 4 years). RESULTS: More than 75% repigmentation was achieved in 71% of patients. Best results were obtained in segmental vitiligo, halo naevi and piebaldism, whereas results in generalized or mixed vitiligo were inferior. According to the patients, final repigmentation was achieved after a mean of 10 months post-treatment. In 80% some colour mismatch (hyperpigmentation and hypopigmentation) was reported between the treated area and the surrounding skin, although this was not disturbing for the majority. This colour mismatch was reported significantly less after sun exposure (P = 0·012). During follow-up 7% of patients, all with generalized vitiligo, observed some loss of the achieved repigmentation. CONCLUSIONS: Autologous epidermal cellular grafting achieved a high percentage of repigmentation, which was maintained during follow-up in the majority of patients. Although it improved quality of life, a perfect colour match was seldom obtained.

Melanocyte transplant in piebaldism: case report.

Piebaldism is a rare genodermatosis in which depigmented skin areas are unresponsive to topical or light treatment. This article describes the importance of transplant techniques using noncultured melanocytes (minigrafting) in the treatment of piebaldism.

Transplante de melanócitos no piebaldismo: relato de caso / Melanocyte transplant in piebaldism: case report

O piebaldismo é uma genodermatose rara onde as lesões acrômicas não respondem aos tratamentos tópico e fototerápico. Este artigo tem como objetivo demonstrar a importância do transplante de melanócitos, usando a técnica de minigrafting no tratamento do piebaldismo.

Piebaldism is a rare genodermatosis in which depigmented skin areas are unresponsive to topical or light treatment. This article describes the importance of transplant techniques using noncultured melanocytes (minigrafting) in the treatment of piebaldism.

Simplified cellular grafting for treatment of vitiligo and piebaldism: the "6-well plate" technique.

BACKGROUND: Vitiligo is a disfiguring depigmenting dermatosis that affects approximately 0.5% to 1% of the general population regardless of race and sex. In patients with stable vitiligo who fail conventional therapies, surgical transplant offers a viable alternative. Noncultured cellular grafting offers the advantage of repigmenting vitiligo 5 to 10 times the size of the donor skin and can be completed on the same day on an outpatient basis. In recent years, ways to simplify this procedure have been explored, including the use of commercially available kits. OBJECTIVES: To simplify the extraction of epidermal cells from donor skin using a 6-well plate and to evaluate the clinical efficacy of this simplified technique in repigmenting stable vitiligo and piebaldism. METHODS: Four patients with focal or segmental vitiligo and one with piebaldism were treated using the simplified noncultured cellular grafting protocol. Percentage of repigmentation 6 months after grafting was objectively measured using digital contour mapping. RESULTS: Patients with stable segmental or focal vitiligo achieved 65% to 92% repigmentation 6 months after grafting; the treated sites involved face or limbs. The patient with piebaldism achieved 86% repigmentation. One year after grafting, the extent of repigmentation remained for all patients. CONCLUSION: This set-up is simple and inexpensive; it reduces cell preparation time, amount of reagents used, and costs, and obviates the need of a laboratory for extraction of epidermal cells.

Permanent repigmentation of piebaldism by erbium:YAG laser and autologous cultured epidermis.

BACKGROUND: Several surgical techniques have been proposed for the treatment of piebaldism. These procedures, however, are poorly suited for the treatment of large leucodermal lesions, can cause scars and require multiple donor sites. Recently, it has been reported that autologous cultured epidermis induces scarless repigmentation of large vitiligo lesions, using a single small donor site. OBJECTIVES: To induce permanent repigmentation of large achromic lesions in patients suffering from piebaldism by means of autologous cultured epidermal grafts using a rapid, simple and non-invasive surgical procedure. METHODS: Six patients with piebaldism were enrolled in this study. Achromic epidermis was removed by means of appropriately set erbium:YAG laser and autologous cultured epidermal grafts were applied on to the recipient bed. Melanocyte content was evaluated by 3,4-dihydroxyphenylalanine reaction. The percentage of repigmentation was calculated using a semiautomatic image analysis system. RESULTS: Autologous cultured epidermis, bearing a controlled number of melanocytes, induced repigmentation of all piebald lesions. The mean percentage repigmentation was 95.45% (2791.5 cm2 repigmented/2924.2 cm2 transplanted). CONCLUSIONS: Autologous cultured epidermal grafts induce permanent and complete repigmentation of piebald lesions, in the absence of scars. Erbium:YAG laser surgery is a rapid and precise tool for disepithelialization, hence allowing treatment of large piebald lesions during a single surgical operation.

Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes, ultrathin epidermal sheets and basal cell layer suspension.

BACKGROUND: In vitiligo and piebaldism the lack of melanin in the epidermis is due to the fact that melanocytes are missing. The patients suffer psychologically and the white areas have lost the part of the skin barrier protection normally provided by the melanocytes. Medical treatments are ineffective in many of the patients, and surgical methods have therefore been developed. OBJECTIVES: It is important to investigate the long-term results and factors that might influence the outcome of melanocyte transplantations in order to form a basis for guidance in the selection of patients who will benefit most from the treatments. METHODS: A follow-up of 132 patients who had been treated by transplantation on 176 occasions in total, 1-7 years previously, was carried out by questionnaires and clinical examinations. We investigated the responses in five types of leucoderma to three different transplantation methods: autologous cultured melanocytes, ultrathin epidermal sheets and basal layer cell suspension. RESULTS: Stable types of leucoderma, i.e. segmental vitiligo and piebaldism, responded in most cases with 100% repigmentation, regardless of the surgical method used. For these types of leucoderma surgery seems to be the method of choice. The largest group, vitiligo vulgaris, was thoroughly scrutinized and three statistical models were used to analyse the data. The ultrathin epidermal sheet method gave somewhat better overall results, but was the method that gave the worst outcome in knee and elbow areas, emphasizing the importance of the right choice of method depending on the anatomical location to be treated. Irrespective of the method, fingers and elbows were the most difficult areas to repigment. The trunk and the arms and legs (not including elbows and knees) responded best. Patients with increasing and/or extensive vitiligo vulgaris more often showed incomplete repigmentation. They also had a lower chance of retaining their repigmentation compared with those with less extensive vitiligo. Patients in whom untreated white lesions had increased in recent years tended to respond less well to transplantation compared with patients with unchanged or decreased lesions. Within the vitiligo vulgaris group, patients with short disease duration or with small total vitiligo area responded best to transplantation. The subgroup of vitiligo vulgaris patients with hypothyroidism tend to respond less well to the transplantation and they were generally older at vitiligo onset. This information is of great importance for the selection of patients and when informing about the chances of improvement after transplantation. Slight hyperpigmentation was common, especially when ultrathin epidermal sheets had been used. No scars or indurations were seen in treated areas. CONCLUSIONS: Transplantations are the methods of choice in stable types of leucoderma. Progressive, widespread vitiligo vulgaris should never be selected for transplantation.

Repigmentation of leucodermic defects in piebaldism by dermabrasion and thin split-thickness skin grafting in combination with minigrafting.

The depigmented skin areas in piebaldism are unresponsive to medical or light treatment. In 12 adult patients (eight women and four men), a method using dermabrasion and thin split-skin grafts was applied initially. Residual leucodermic areas were subsequently treated using a minigrafting method. Additional irradiation with ultraviolet A (10 J/cm2) was performed to enhance melanocyte migration. This combined surgical therapy led to 95-100% repigmentation of the leucodermic defects. A perfect colour match with the surrounding non-lesional skin was achieved in all cases. Complications were minor and easy to correct. Dermabrasion and split-skin grafting followed by minigrafting should be considered as the first choice of therapy in piebaldism.

Epidermal sheet grafts for repigmentation of vitiligo and piebaldism, with a review of surgical techniques.

Thin epidermal sheets, obtained by a high-speed air-driven dermatome, were used to repigment white areas in 19 patients with vitiligo and one boy with piebaldism. In the depigmented skin to be treated the epidermis was removed by a rotating diamond fraise under topical and/or local anaesthesia injections. The method was used on most parts of the body, including the eyelids and genitalia. The maximum total area treated on each occasion was 190 cm2. Excellent results could be obtained if the vitiligo had been stable and had not increased anywhere during the last 2 years. Lack of immobilization could explain a poor result in some areas. The donor area on the buttocks healed quickly without depigmentation. In the transplanted area milia were observed in the first 6 months. No scarring was seen. The technique has a niche in the treatment of depigmented skin, especially in larger areas.