The story of melanocyte: a long way from bench to bedside.

Skin is composed of major layers, namely a superficial epidermis and a deeper dermis. The color of skin is influenced by a number of pigments, including melanin, which is produced by cells called melanocytes. Most skin disorders are relatively benign, but a few, including melanomas, can be fatal. A number of more noticeable disorders, namely albinism and vitiligo, affect the appearance of the skin and its accessory organs. Vitiligo is associated with significant psycho-social morbidity and a major effect on quality of life. Topical steroids, calcineurin inhibitors, phototherapy and surgery are the most common treatments for melanoma. However, there are many patients who do not respond to any of these modalities. The transplantation of cultured or non-cultured melanocyte is the most important treatment for hypopigmentory disorders. This study aims at reviewing the history of melanocyte cultivation, and evaluating the effectiveness of transplantation of cultured cells. For this purpose, the authors examined the initial process of isolation, characterization, and transplantation of epidermal cells. This review, thus, summarizes the current understanding of the cutaneous pigmentary system from the start of synthesis in the pigment cells, along with the response of repigmentation. During the production of melanin, melanosomes are transferred to neighboring keratinocyte in order to form perinuclear melanin caps. The objective of this review is to analyze the melanocytes transplantation in the last century to date, and explore the methods epidermal cells can increase pigmentation in hypo-pigmented areas in skin disorders. Moreover, the focus is on the story of the melanocyte back to 1950s. In addition, prior systemic therapy was associated with a significant increase, based on combined additional therapy, achieving desired results and improved outcomes. Despite the short study of a long way of melanocyte assessment and following up patient treatment, results of the all reports confirmed the efficacy of the method used in the treatment of stable vitiligo patients, who did not respond to the common algorithms of non-invasive treatments.

Utilization of Our Toolkit: A Systematic Review and Meta-analysis of Surgical Therapies in Vitiligo Treatment.

BACKGROUND: Although vitiligo is often treated medically, there is increasing evidence for surgical therapies. Overlap with in-office surgical therapies that are already employed for other dermatologic conditions suggest that there is a significant opportunity to expand dermatologists' therapeutic repertoire for vitiligo. OBJECTIVE: To systematically review the efficacy of nonphototherapy surgical treatments for vitiligo in comparative or placebo-controlled trials. METHODS: A systematic review for surgical treatments for vitiligo was conducted. Primary outcomes were treatment success (>75% repigmentation) and failure (<25% repigmentation) for which meta-analyses were performed. Adverse effects were noted. The Cochrane risk of bias tool was used to assess study quality. RESULTS: Surgical treatments reviewed included platelet-rich plasma, microneedling, ablative therapies, and surgical modalities. Seventy-three studies with 2,911 patients were included. The repigmentation benefits and adverse events are summarized. Meta-analyses suggest benefits for ablative laser therapies or microneedling in combination with narrowband ultraviolet B (NB-UVB) and for suction blister epidermal grafting over punch grafting. CONCLUSION: The addition of microneedling or ablative laser therapy to NB-UVB phototherapy may improve repigmentation with minimal adverse effects. Surgical therapies, such as suction blister grafting and punch grafting, may offer the highest likelihood of repigmentation but have a risk of adverse effects including scarring and hyperpigmentation.

Clinical and dermoscopic evaluation of follicular unit transplantation vs. Mini-Punch grafting in the repigmentation of resistant and stable vitiligo: A comparative study.

BACKGROUND: Various surgical modalities and transplantation techniques had been evolved for the treatment of recalcitrant stable vitiligo. Each of these techniques has its own limitations and side effects. There are insufficient studies evaluating the efficacy of transplantation of hair follicle (HF) units as a surgical modality for vitiligo treatment in comparison with the classic mini-punch grafting. OBJECTIVES: To compare the efficacy and safety of follicular unit transplantation (FUT) with mini-punch grafting (mPG) in cases of resistant and stable vitiligo. METHODS: Twenty-five patients with stable vitiligo were included. Treated areas were classified into 2 groups: group I: Areas were treated with the FUT technique and group II: Areas were treated with mPG technique. Treated areas were exposed to narrowband ultraviolet B phototherapy for 6 months. After 3 months, follow-up patients' response was evaluated clinically and by dermoscopy. RESULTS: Both techniques showed efficacy in repigmentation of stable vitiligo. Group II showed a statistically significant higher percentage of repigmentation and significant earlier repigmentation than group I. Cobblestone-like appearance was the major complication in group II, while no serious side effect was reported in group I. Leukotrichia was present in 8 patients, and 6 of them showed hair repigmentation evidently in group I. CONCLUSION: Both techniques are effective, safe, and inexpensive methods of surgical repigmentation of stable localized/segmental vitiligo. mPG gives earlier and better percent of repigmentation, with higher incidence of cobblestoning. FUT is a good alternative for mPG, especially in hairy areas with better cosmetic outcome and minimal complications.

Efficacy and safety of traditional and surgical treatment modalities in segmental vitiligo: A review article.

BACKGROUND: Segmental vitiligo (SV) is a distinctive variant of vitiligo that is usually resistant to traditional treatments. Therefore, surgical therapies are mainstay of treatment in this type of vitiligo. To date, there is no review article or systematic review that evaluates specifically efficacy of treatment modalities on SV. AIM: To evaluate current evidence regarding efficacy and safety of traditional and surgical treatment modalities in SV. METHODS: We conducted a search in PubMed, Embase, Web of science, and Google Scholar for key words of "vitiligo" AND "segmental" AND "treatment" OR "therapy" OR "surgical treatments" OR "medical treatments" OR "laser" OR "phototherapy". Inclusion criteria were English literature that investigated efficacy of different treatments on three or more cases on SV from January 2000 until July 2021. RESULTS: A total of thirty-four articles were selected for detailed assessment. Different treatment modalities include medical treatment [systemic corticosteroid (SCS), topical CS (TCS), and topical calcineurin inhibitors (TCI)], phototherapy [narrow band-ultraviolet B (NB-UVB), psoralen and UVA (PUVA) and psoralen+solar exposure (PUVASOL)], laser/lights [helium-neon and Excimer laser/light (EL)] and surgical treatments [punch graft (PG), follicular graft, suction blister epidermal grafting (SBEG), spilt-thickness skin graft (STSG), and cultured/non-cultured-melanocytes-keratinocytes transplantation (MKTP)]. CONCLUSION: There were few randomized controlled trials (RCT) evaluating the efficacy of treatments in SV. Therefore, future high quality studies are required for better assessment of various treatment modalities in SV. Results of current evidence indicate resistance of SV to traditional therapies unless in patients with short duration of vitiligo. Therefore, surgical interventions are the first-line of treatment in refractory cases, long-standing disease, or presence of leukotrichia in depigmented patches.

Outcomes of autologous non-cultured melanocyte keratinocyte transplantation in vitiligo and nevus depigmentosus.

BACKGROUND: Melanocyte-keratinocyte transplantation procedure (MKTP) is an effective surgical technique for restoring skin pigmentation in all types of vitiligo and leukoderma patients who are unresponsive to medical and/or phototherapy treatment. Data specific to the outcomes of MKTP among Thai vitiligo and nevus depigmentosus patients are currently scarce. OBJECTIVES: To evaluate the efficacy and safety of MKTP in patients with vitiligo or nevus depigmentosus at the short-term (≤6 months) and long-term (≥12 months) follow-up. MATERIALS AND METHODS: A retrospective review of the medical records of vitiligo or nevus depigmentosus patients who underwent MKTP at the Department of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during 2016 to 2019 was conducted. Repigmentation outcomes were evaluated by Vitiligo Area Scoring Index (VASI). RESULTS: Twenty-five patients had 27 MKTP surgeries on 32 anatomically-based lesions. The mean age was 32.4 years, the mean age at onset was 25.5 years, and 19 patients were male. Segmental vitiligo, non-segmental vitiligo, and nevus depigmentosus had significantly improved VASI scores at the short-term follow-up (-74.2% ± 23.2%, -100%, and -62.5% ± 17.6%, respectively) and the long-term follow-up (-81% ± 27.7%, -95.0% ± 7.0%, and -83.3% ± 14.4%, respectively). CONCLUSION: MKTP is a safe and effective method for treating refractory vitiligo and nevus depigmentosus in Thai patients.

A retrospective study of long term follow-up of 2283 vitiligo patients treated by autologous, non-cultured melanocyte-keratinocyte transplantation.

BACKGROUND: Autologous non-cultured melanocyte-keratinocyte transplantation (MKTP) can be used to treat stable vitiligo cases, but there were insufficient clinical data to evaluate its safety and efficacy. OBJECTIVE: To assess the influence of various factors on the therapeutic outcome of MKTP. METHOD: The single-center retrospective study included stable vitiligo patients who underwent MKTP between June 2009 and June 2018. Univariate and/or multivariable analysis were used to determine the factors affecting the outcome of repigmentation. RESULT: The study comprised 2283 patients who had long-term follow-up data (12-108months). Excellent repigmentation was achieved in 400/606 (66%),788/1341 (58.8%),437/684 (63.9%),18/24 (75%) patients with segmental vitiligo, pre-MKTP phototherapy, younger than 24 years, the lesion on the perineum and scrotum, respectively. However, the patients with a positive family history, Koebner phenomenon responded worse(χ2=29.417, P<0.001; χ2=107.397, P<0.001; respectively). Overall, a significant positive correlation between duration of stability and percentage of repigmentation was found (χ2=42.053, P<0. 001). CONCLUSION: MKTP is efficient and well tolerated for stable vitiligo treatment. Various factors such as duration of disease stability, vitiligo type, family history, site of lesion should be carefully assessed before using MKTP, as it would further improve the post-operative repigmentation.

Effect of platelet-rich plasma on the outcome of mini-punch grafting procedure in localized stable vitiligo: Clinical evaluation and relation to lesional basic fibroblast growth factor.

Surgical methods are favorably used for treatment of stable vitiligo, and platelet-rich plasma (PRP) can be added to augment the effect. The additive value of PRP, however, remains elusive. Basic fibroblast growth factor (bFGF) is released from activated platelets with a capacity for stimulating melanocyte proliferation and migration. The treatment outcomes for the mini-punch grafting (MPG)/phototherapy treatment with and without PRP were assessed and the relation between bFGF and the obtained results were evaluated. Thirty-four vitiliginous patches, two per each patient with stable vitiligo, were enrolled in this intrapatient-controlled study and treated with autologous MPG and subsequent exposure to phototherapy with and without enhancement via PRP procedure at the time of the procedure, and monthly for the subsequent 3 months. Re-pigmentation assessment via vitiligo scores as well as measurement of lesional bFGF were done. PRP assistance to MPG/phototherapy treatment resulted in earlier re-pigmentation at week 8. However, this enhancement effect vanished at the study end (week 20) as ideal re-pigmentation (>75% re-pigmentation) was encountered in 10 patches (58.8%) treated with MPG/phototherapy modality, and in 12 patches (70.6%) treated with PRP-assisted method without significant difference between them. Lesional bFGF increased after both treatments with a higher expression with PRP assistance but without clinical reflection on the final outcome. PRP can speed the re-pigmentation response for MPG/phototherapy procedure without any significant effect on the final outcome.

Effectiveness of dermabrasion plus 5-fluorouracil vs suction blister in treating vitiligo: A comparative study.

Vitiligo is a prevalent destructive melanocyte skin disease that negatively affects the patients' life in terms of self-esteem. Suction blister and dermabrasion plus 5-fluorouracil are effective treatments for vitiligo. The present study was conducted to compare the outcomes of these two techniques. The present clinical trial was conducted on 36 patients with persistent refractory vitiligo which defined as the lack of any new or progressed lesion during the previous year as well as no responding to conventional therapies of vitiligo including topical treatments and phototherapy. Individuals with two vitiligo patches, with similar baseline Vitiligo Area Severity Index (VASI) scores were randomly allocated to dermabrasion plus 5-fluorouracil or suction blister treatments. VASI and repigmentation scores were measured and compared at the baseline, four, and 12 weeks after performing the procedures. Both of the approaches accompanied with significant improvement in both entities of VASI and repigmentation scores (P value < .05) at the end of the study, besides the trend of VASI and repigmentation scores between the two groups revealed insignificant difference (P > .05). The short-term follow-up of the patients was the limitation of this study. The present findings suggested that both surgical techniques of dermabrasion plus 5-fluorouracil and suction blister posed acceptable outcomes within 12-week follow-up.

The efficacy of fractional carbon dioxide laser combined with narrow-band ultraviolet B phototherapy for non-segmental vitiligo: a systematic review and meta-analysis.

Fractional carbon dioxide (CO2) laser has been used with conventional treatments for vitiligo, demonstrating more effectiveness compared with conventional treatments alone. Especially, fractional CO2 laser combined with narrow-band ultraviolet B (NB-UVB) was shown to induce more improvement compared with NB-UVB monotherapy for treating stable non-segmental vitiligo. However, the effectiveness of fractional CO2 laser plus NB-UVB for the treatment of non-segmental vitiligo remains controversial. Therefore, this study aimed to confirm the safety and efficacy of fractional CO2 laser combined with NB-UVB compared with NB-UVB monotherapy in stable non-segmental vitiligo. We searched the data from different databases, including Cochrane, Embase, and PubMed up to January 2020. Four randomized controlled trials (RCTs) for comparison between fractional CO2 laser plus NB-UVB and NB-UVB monotherapy in patients with stable non-segmental vitiligo were included. We performed meta-analyses for repigmentation improvement and patient satisfaction as well as subgroup analyses based on acral or non-acral vitiligo, according to the PRISMA guidelines. The combination treatment showed more superior results than NB-UVB monotherapy (≥ 75% repigmentation, RR 4.60, 95% CI 1.19-17.74; ≥ 50% repigmentation, RR 2.24, 95% CI 0.45-11.17; < 25% repigmentation, RR 0.81, 95% CI 0.60-1.08). Also, fractional CO2 laser plus NB-UVB significantly improved acral and non-acral vitiligo compared with NB-UVB monotherapy (standard mean difference (SMD) 1.24, 95% CI 0.66-1.82; SMD 1.14, 95% CI 0.67-1.60, respectively), while it increased markedly patient satisfaction compared with NB-UVB monotherapy (SMD 1.12, 95% CI 0.66-1.58). Collectively, this meta-analysis suggested that fractional CO2 laser combined with NB-UVB might be more effective for treating non-segmental vitiligo than NB-UVB monotherapy.

A comparative study between suction blistering graft, mini punch graft, and hair follicle transplant in treatment of patients with stable vitiligo.

Background: Vitiligo is an acquired disfiguring common depigmented skin disease. Objectives: This study aimed to compare the clinical efficacy and safety of suction blistering graft, mini punch and hair follicle techniques in treatment of patients with stable vitiligo. Methods: Thirty patients with stable vitiligo were included. Patients were divided into 3 groups, in group (A) 10 patient underwent suction blistering technique, in group (B) 10 patients underwent mini punch technique and in group (C) 10 patients underwent hair follicle technique. Then all patients in the three techniques were subjected to narrow-band ultraviolet B (NB-UVB) phototherapy for 3 months. All patients were assessed by determining the percentage of repigmentation and Dermatology Life Quality Index (DLQI) before and 3 months after the operation. Results: The percentage of repigmentation of vitiligo in suction blister technique was significantly higher than both mini punch and hair follicle techniques (p value .001 and .0001 respectively). There was a statistically significant difference between the three techniques regarding DLQI score after operation (p value = .0001). Conclusion: This study concluded that suction blistering technique is more effective and safe than mini punch technique and hair follicle technique in treatment of stable vitiligo.

Motorized 0.8-mm micropunch grafting for refractory vitiligo: A retrospective study of 230 cases.

BACKGROUND: Punch grafting for vitiligo is time-consuming and can result in cobblestone-like appearances. We devised a motorized 0.8-mm micropunch grafting procedure to overcome these limitations. OBJECTIVE: To assess the therapeutic effectiveness and adverse events associated with micropunch grafting in refractory vitiligo. METHODS: We retrospectively reviewed 230 cases in 208 patients with stable vitiligo who underwent motorized 0.8-mm micropunch grafting during January 2015-August 2017. Treatment success was defined as ≥75% repigmentation, and factors associated with the outcome were assessed. RESULTS: Overall, 181 of 230 lesions (78.7%) achieved treatment success after a median of 6 months with postoperative excimer therapy. Lesions on the face and neck, and disease stability of ≥12 months were good prognostic factors for treatment success. Common adverse events were color mismatch (24.8%) and cobblestone appearance (18.3%). Overall, the treatment was tolerable. LIMITATIONS: This was a retrospective study. CONCLUSION: Micropunch grafting using a motorized 0.8-mm punch can successfully treat refractory vitiligo with short procedure times and excellent outcomes. This technique could be a rapid and convenient surgical option with acceptable adverse events and is promising for treating refractory vitiligo on an outpatient basis, particularly in patients who are unlikely to tolerate prolonged surgery.

Syringes versus Chinese cups in harvesting suction-induced blister graft: a randomized split-body study.

BACKGROUND: Suction blister grafting (SBG) is a technique where the pigmented epidermis is harvested from the donor site by induction of a blister using different suction methods as syringes, Chinese cups, suction device, etc. However, pain, time consumption, incomplete blister formation, and failure of blister development are the main limitations. OBJECTIVE: To compare between cups and syringes of similar diameter in inducing suction blisters. PATIENTS AND METHODS: In 30 patients with stable nonsegmental vitiligo, 2-cm-diameter (20 ml) syringe was applied on the anterolateral aspect of one thigh and a 2-cm-diameter cup on the corresponding site of the other thigh where right and left sides were chosen randomly. Patients were observed untill complete blister development or for a maximum of 3 hours. Suction blister induction time (SBIT) and the blister diameter were recorded for each patient. Pain during the process of induction was evaluated. RESULTS: Incomplete blister development was noted in 9 out of 30 (30%) with 2 cm syringes and 6 out of 30 (20%) with the similar diameter cups with no significant difference (P = 0.49). No significant difference was found between SBIT induced by the 2 cm syringes and the similar size cups (101.17 ± 68.14 minutes, 98 ± 56.84 minutes, respectively) (P = 0.85). Meanwhile, blister diameter induced by either syringe or cup was not significantly different (P = 0.37). Anesthesia was for short duration with xylocaine, and pain was intolerable in both sides in the first seven patients. A combination of xylocaine and bupivacaine was used with prolonged loss of pain in 17 of the remaining 23 patients and tolerable pain in six patients similarly in both sides. CONCLUSION: According to present results, the differences in SIBT, diameter of blisters, and number of complete blister formation induced by either syringes or cups of similar size were not significant. Therefore, whatever the available and feasible technique for the surgeon will be the ideal choice. A combination of xylocaine and bupivacaine is recommended to overcome the accompanying pain of the procedure.

Efficacy and safety of noncultured melanocyte-keratinocyte transplant procedure for vitiligo and other leukodermas: a critical analysis of the evidence.

Vitiligo is an acquired pigmentary skin of depigmentation occurring secondary to melanocyte destruction. Vitiligo and other leukodermas have a profound impact on quality of life. Current therapies include medical options, such as phototherapy, topical and systemic corticosteroids, topical calcineurin inhibitors, immunomodulators, and antioxidiants, and surgical options. Surgical options provide melanocytic cells to previously depigmented areas and use either tissue grafting or cellular grafting methods. Topical treatments are often insufficient, and many of the current surgical procedures have shown variable response rates. In this review, we discuss the process of the cellular grafting melanocyte-keratinocyte transplantation procedure (MKTP) and critically analyze its efficacy and safety in the treatment of vitiligo and other leukodermas. PubMed was searched for studies (2001-2017) describing the use of MKTP in patients with vitiligo or other leukodermas. Articles or trials discussing the use of MKTP for these patients were selected for in-depth review. Clinically relevant results regarding efficacy and safety of MKTP in vitiligo and leukoderma patients were analyzed. Numerous trials and case series/reports have demonstrated tolerability and efficacy of MKTP with repigmentation for patients with refractory, stable vitiligo. However, the response rates have been variable, likely influenced by vitiligo type and affected areas. Future research and clinical reporting will provide more insight on which phenotypes may benefit from MKTP.

Effect of combination of fractional CO2 laser and narrow-band ultraviolet B versus narrow-band ultraviolet B in the treatment of non-segmental vitiligo.

The present study was designed to evaluate the effect of combining fractional CO2 laser with narrow-band ultraviolet B (NB-UVB) versus NB-UVB in the treatment of non-segmental vitiligo. The study included 20 patients with non-segmental stable vitiligo. They were divided into two groups. Group I received a single session of fractional CO2 laser therapy on the right side of the body followed by NB-UVB phototherapy twice per week for 8 weeks. Group II received a second session of fractional CO2 laser therapy after 4 weeks from starting treatment with NB-UVB. The vitiligo lesions were assessed before treatment and after 8 weeks of treatment by VASI. At the end of the study period, the vitiligo area score index (VASI) in group I decreased insignificantly on both the right (-2.6%) and left (-16.4%) sides. In group II, VASI increased insignificantly on the right (+14.4%) and left (+2.5%) sides. Using Adobe Photoshop CS6 extended program to measure the area of vitiligo lesions, group I showed a decrease of -1.02 and -6.12% in the mean area percentage change of vitiligo lesions on the right and left sides, respectively. In group II the change was +9.84 and +9.13% on the right and left sides, respectively. In conclusion, combining fractional CO2 laser with NB-UVB for the treatment of non-segmental vitiligo did not show any significant advantage over treatment with NB-UVB alone. Further study of this combination for longer durations in the treatment of vitiligo is recommended.

Ultrathin Skin Grafting in Resistant Stable Vitiligo: A Follow-up Study of 8 Years in 370 Patients.

BACKGROUND: Ultrathin skin grafting (UTSG) is a tissue grafting technique used in resistant stable vitiligo. OBJECTIVE: To assess long-term follow-up results achieved with UTSG in vitiligo. METHODS: Over a span of 8 years, a total of 415 patients with stable vitiligo were treated with UTSG at the authors' institute. Retrospective analysis of results achieved in these patients was performed, and primary end points assessed included the extent and quality of repigmentation achieved and adverse effects from the procedure. Results were correlated with the site, morphological type of vitiligo, duration of stability, postprocedure treatment used, and the age and sex of the patient. RESULTS: Follow-up results were available with 554 lesions in 370 patients. Excellent response (≥90% repigmentation) was documented in 78.9% (437/554) lesions whereas 8.67% (48/554) lesions demonstrated poor results. Pigmentation was retained in >98% (112/114) cases over 4-year follow-up. The commonest adverse effect noted was "perigraft halo" in 12.3% (68/554) lesions. Site and morphological type of vitiligo as well as the postoperative use of phototherapy showed statistically significant correlation with response. Age and sex of the patient and duration of stability beyond 1 year did not influence the outcome. CONCLUSION: Ultrathin skin grafting provides long-term beneficial results in stable resistant vitiligo.

Twelve-month and sixty-month outcomes of noncultured cellular grafting for vitiligo.

BACKGROUND: Noncultured cellular grafting is a known surgical technique for vitiligo. OBJECTIVE: This study evaluated our center's 12-month repigmentation outcome and its maintenance up to 60 months, factors influencing repigmentation and safety data. METHODS: Clinicoepidemiologic and repigmentation data were reviewed for patients with vitiligo who had undergone noncultured cellular grafting from March 2006 to December 2012 at the National Skin Center, Singapore. RESULTS: All 177 patients who received noncultured cellular grafting during the study period were included. For those with available data, good to excellent repigmentation was present in 83% at 60 months. At 12 months, 88% of patients (n = 52) with segmental vitiligo achieved good to excellent repigmentation compared with 71% (n = 55) with nonsegmental vitiligo (P < .05). More patients on collagen dressings (82%) achieved good to excellent repigmentation compared with those who received hyaluronic acid (63%) (P < .05). Sites of lesions and postgrafting phototherapy did not significantly affect repigmentation outcome. Adverse reactions were uncommon and mild. LIMITATIONS: The study is limited by its retrospective nature, the progressive loss to follow-up of patients, the absence of blinding, and the lack of use of standardized assessment tools. CONCLUSION: Noncultured cellular grafting was successful in allowing more than 80% of patients to achieve good to excellent repigmentation for at least 60 months.