Safety and Efficacy of Autologous Melanocyte/Keratinocyte Transplantation in Patients with Refractory Stable Vitiligo.

BACKGROUND: Vitiligo is a common depigmentation skin disease associated with significant psychosocial morbidity and profound effect on the quality of life. The treatment of vitiligo is still a major challenge in the field of dermatology. Currently, topical steroids, calcineurin inhibitors, ultraviolet phototherapy, surgery, and cultured and non-cultured epidermal melanocyte transplantation are used for the treatment of vitiligo. However, the effectiveness of these treatment modalities is limited by the lack of response, long-term treatment periods, high cost, and inevitable adverse effects. OBJECTIVES: In this study, we aimed to evaluate the efficacy of intraepidermal injection of autologous non-cultured melanocytes and keratinocytes as an alternative therapy for the refractory and stable (RS) vitiligo. METHODS: The treatment procedure was performed on thirty-nine RS vitiligo patients. The autologous skin grafts obtained from the buttock area and epidermis were separated from dermis using dispase. Single-cell autologous melanocytes and keratinocytes were prepared from the epidermis by trypsin/ethylene diamine tetra acetic acid and injected at the concentration of 100-400 × 103 cells/cm2, intra-epidermally to the selected vitiligo lesions. Vitiligo re-pigmentation was monitored employing photography. Photographs were taken prior to and 2, 4, and 6 months after the cell transplantation. Improvement of the skin depigmentation was classified as follows: <25% as minimal response, 26-50% as moderate response, 51-75% as good response, and finally 76-100% as excellent response. RESULTS: Cell infusion appeared to be safe as none of the patients exhibited any adverse effects. At the end of the sixth month follow-up period, of the treated patients, 12.8% demonstrated an excellent response, 36% exhibited a good response, and 51.2% showed a moderate to minimal response to the administered therapy. Obtained significant p value for Wilcoxon test over the checkpoints at 2nd, 4th, and 6th month (p = 0.03, 0.04, and 0.039, respectively) post-cell transplantation confirmed notable growing trend in the re-pigmentation. CONCLUSION: Our findings provide a strong support for the therapeutic efficacy of autologous non-cultured melanocytes and keratinocytes in patients with RS vitiligo.

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.

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.

Subacute cutaneous lupus erythematosus leukoderma treated with melanocyte-keratinocyte transplantation procedure.

Depigmented lesions may occur as postinflammatory sequelae of subacute cutaneous lupus erythematosus (SCLE), leading to great psychosocial impact. A 53-year-old male patient presented with post-SCLE depigmented facial lesions after five years of disease stability. We proposed surgical treatment with melanocyte-keratinocyte transplantation procedure (MKTP), and after five months the patient achieved 90% repigmentation, without Koebner phenomenon (KP). In theory, KP is a possible complication of MKTP procedure since the preparation of the receptor area involves the use of dermabrasion. In an attempt to avoid it, we suggest to maintain the treatment of the underlying disease and wait for a minimum period of disease stability before the procedure.

Disorders of Hypopigmentation

Hypopigmentation and depigmentation of the skin can be due to multiple causes and has a broad differential diagnosis. The most common cause of depigmentation worldwide is vitiligo. This disorder affects 1-2% of the world's population and is seen in all races. Vitiligo is an autoimmune disorder in which the predominant cause is an attack by CD8+ cytotoxic T cells on melanocytes in the epidermis. This condition can have a significant negative impact on the quality of life of affected individuals. Treatment options currently include psychological counseling, topical therapy, systemic therapy, phototherapy, surgical therapy, and depigmentation. In patients with stable, refractory disease, successful repigmentation has been achieved using mini-punch grafting, blister grafting, and non-cultured epidermal suspension (NCES) grafting. Emerging therapies include the Janus kinase (JAK) inhibitors ruxolitinib and tofacitinib. Further studies exploring the pathogenesis of vitiligo are warranted in order to optimize treatment for affected patients. J Drugs Dermatol. 2019;18(3 Suppl):s115-116.

What's New in Pigmentary Disorders.

Pigmentary disorders are common and can be very distressing to patients. There is a need for better, standardized therapies. The authors review the most recent data for topical, systemic, light, and laser treatments for vitiligo, melasma, and postinflammatory hyperpigmentation. There is a paucity of large-scale, well-designed, randomized, controlled trials for these treatments. Treatment options are often drawn from smaller trials and case series. The treatments described in this article are promising candidates for larger follow-up studies.

Nevus depigmentosus: review of a mark of distinction.

Nevus depigmentosus (ND), also known as nevus achromicus or achromic nevus, is an uncommon congenital hypomelanosis of the skin that is often characterized as being nonprogressive and having serrated borders. It needs to be distinguished from other hypopigmented skin conditions such as nevus anemicus, hypomelanosis of Ito, Fitzpatrick patches (ash leaf spots) of tuberous sclerosis, vitiligo, indeterminate leprosy, and pigment demarcation lines. Treatment may be desired for aesthetic and possible psychosocial considerations. We review and update knowledge about ND and its simulants.

The effect of NB-UVB on noncultured melanocyte and keratinocyte transplantation in treatment of generalized vitiligo using two different donor-to-recipient ratios.

BACKGROUND: The melanocyte and keratinocyte transplantation procedure (MKTP) is a safe and effective procedure in treatment of vitiligo. Major advantage of this technique is that a small area of donor skin is needed to cover a large recipient area. To date, there is no consensus on the optimal donor-to-recipient ratio (D/R) required to achieve acceptable repigmentation following melanocyte and keratinocyte transplantation procedure (MKTP) in generalized vitiligo. It has been postulated that the addition of post-transplantation phototherapy may enhance the results. This is first study to assess two different (D/R) ratios with or without adjuvant phototherapy. OBJECTIVE: To compare the repigmentation after MKTP using two different D/R ratios (1/3 and 1/10) with and without adjuvant phototherapy (NB-UVB). METHODS AND MATERIALS: In this non randomized prospective clinical trial, 42 patients with stable generalized vitiligo bilateral and symmetrical in distribution were included. Patients were divided into two groups, 21 patients with a total of 50 lesions were treated with MKTP using a D/R ratio of 1/3 (Group I; 3000 ± 500 cell/mm2 ) and the other 21 patients with a total of 52 lesions were treated by MKTP using a D/R ratio of 1/10 (Group II; 1000 ± 200 cell/mm2 ). To study the role of adjuvant phototherapy on repigmentation, lesions in each patient were divided into two subgroups (a and b): lesions in subgroups Ia and IIa (did not receive NB-UVB) and lesions in subgroups Ib and IIb (received adjuvant phototherapy NB-UVB, two sessions per week for 6 months). The overall grading of repigmentation used was excellent (90%-100% repigmentation), good (75%-89%), fair (50%-74%), and poor (<50%). Also, the percentage of VASI change and color matching were used to assess the results. The study design was approved by the ethical committee of the Faculty of Medicine, Assiut University (IRB attached). RESULTS: The mean percentage of repigmentation was significantly better in group I than group II cases in both areas with or without adjuvant NB-UVB. It was 86.00 ± 16.21 and 87.62 ± 11.66 in subgroups Ia and Ib, respectively, vs 24.14 ± 18.08 and 29.98 ± 16.34 in subgroups IIa and IIb, respectively (P value was 0.000). The percent of excellent response was significantly better in group I than group II. It was 60% and 64% in subgroups Ia and Ib, respectively, and 7.6 and 11.5 in subgroups IIa and IIb, respectively (P value was 0.000). The mean percentage of VASI change was significantly better in group I than group II cases in both areas. It was -90.74 ± 15.84 and -92.06 ± 11.86 in subgroups Ia and Ib, respectively, vs -23.10 ± 32.85 and -26.03 ± 35.15 in subgroups IIa and IIb, respectively (P value was 0.000). The percent of excellent color match was better in group I than group II. It was 84% and 88% in subgroups Ia and Ib, respectively, vs 34.6 in both subgroups IIa and IIb (P < 0.05). A higher density of epidermal cells was transplanted in the recipient area in group I (3000 ± 500 cell/mm2 ) compared to group II (1000 ± 200 cell/mm2 ). There were no statistically significant differences between subgroups (Ia vs Ib and IIa vs IIb) although percentage of repigmentation was slightly better in NB-UVB subgroups. CONCLUSIONS: The higher density of epidermal cells used in the suspension, the higher the percentage of repigmentation obtained. The usage of adjuvant phototherapy following NKMT can enhance the repigmentation response.

The role of phototherapy in the surgical treatment of vitiligo: a systematic review.

Vitiligo is frequently treated with the combination of phototherapy and melanocyte transplantation. However, the additional benefit of phototherapy is unclear. Moreover, the optimal type and regimen of phototherapy are unknown. The objective of this systematic review was to identify whether phototherapy improves the outcome of melanocyte transplantation in vitiligo. We searched and screened for eligible studies in the databases of MEDLINE, EMBASE and CENTRAL. We included all clinical studies investigating melanocyte transplantation combined with phototherapy. After screening and selection of abstracts and full-texts, we found 39 eligible clinical studies with 1624 patients. The eligible studies investigated several phototherapy modalities, such as NBUVB (n = 9), PUVA (n = 19), UVA (n = 1), MEL (n = 4) and active sunlight exposure (n = 9). Four studies directly compared phototherapy versus no phototherapy and two studies confirmed the benefit of phototherapy for melanocyte transplantation. We found no significant differences in repigmentation in studies directly comparing phototherapy modalities. The overall quality of the studies was moderate to poor and high heterogeneity between studies was found. We found limited evidence that phototherapy improves the outcome of melanocyte transplantation in vitiligo. There is insufficient evidence to recommend a specific type or regimen of phototherapy. More studies should be performed investigating the additional benefit of different phototherapies and the preferred moment of phototherapy.

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.

Management of vitiligo patients with surgical interventions.

Vitiligo is an acquired depigmentation disorder of unknown etiology. Medical treatments are usually reasonably effective for nonstable vitiligo patches; however, for vitiligo patches that have been stable for a substantial period of time, surgical intervention should be considered. In this article, surgical interventions for vitiligo are reviewed, including split-thickness skin grafting, suction blister grafting, miniature punch grafting, and cultured melanocyte transplantation.

Vitiligo treatment update.

Vitiligo is a common depigmenting disease that can affect the skin and mucosal surfaces. Various treatments have been used over the years with varying repigmentation rates. This review looks at the evidence of commonly used therapies for vitiligo.

Vitiligo surgical, laser, and alternative therapies: a review and case series.

INTRODUCTION: Vitiligo is a condition caused by the destruction of melanocytes, resulting in areas of skin without pigmentation. While many topical therapies exist for its treatment, not all patients respond to such treatments. Various surgical, laser and other alternative therapies are available for use as well. OBJECTIVE: The objective of this review was to describe the various surgical, laser, and alternative therapies available for vitiligo. A literature review was conducted through Pubmed and Ovid using the search terms "Vitiligo treatment", "Vitiligo surgery", "Vitiligo laser". Since no articles were available about needling on both Pubmed and Ovid using the search criteria, individual articles were sought out through Google. RESULTS: The literature review yielded many possible surgical interventions including autologous mini-punch grafting, suction epidermal blister grafting, split-thickness grafting, and cultured and noncultured melanocyte keratinocyte transfer. Laser options included the helium-neon and xenon-chloride lasers, with tattooing and needling serving as other options. While all the above techniques can provide improvement to pigmentation in vitiliginous patches, physician comfort and experience are important factors with regards to outcome. Our case series of four patients treated with the needling method yielded favorable results, with repigmentation rates ranging from 25-50%, with one patient having 90% repigmentation. CONCLUSION: There are many surgical, laser, and alternative treatment options available for vitiligo when conventional medical therapy fails or for use in conjunction with medical therapies. Autologous mini punch grafting and needling both have minimal equipment requirements and are easy to learn. Physician experience and comfort play a large role in outcome and availability of services.

Advanced treatment modalities for vitiligo.

BACKGROUND: Vitiligo is an acquired multifocal and polygenic dyschromia that affects 1% to 3% of the world and presents as multiple depigmented macules and patches. Traditionally, the treatment of vitiligo has focused on pharmacologic interventions, but nearly half of all treated patients fail to respond successfully. OBJECTIVE: Several advanced techniques exist that can aid dermatologists in treating vitiligo in patients who do not respond favorably to traditional pharmacologic treatments. These advanced interventions include the use of the 308-nm excimer laser, total body depigmentation therapy with monobenzyl ether of hydroquinone, microdermabrasion, micropigmentation, khellin-UVA therapy, and surgical management using miniature punch grafting, suction blister grafting, and epidermal cultures. MATERIALS AND METHODS: This article reviews the current literature on these advanced treatment modalities for vitiligo and provides a practical guide for application of these techniques. RESULTS AND CONCLUSION: Our ability to treat vitiligo may be imperfect, but through appropriate patient selection and careful application of one or more of these advanced therapies, successful treatment of vitiligo, even in patients refractory to treatment, can be achieved.

Vitiligo: current medical and scientific understanding.

Vitiligo is a relatively common acquired skin depigmentary disease with a complex presentation, therapy, and etiology. Both the prognosis and therapeutic response for patients with vitiligo is unpredictable. Multiple current therapies exist however the efficacy of these are not optimal. The cause of vitiligo appears to be a combination of genetic effects in both the immune system and the melanocyte itself with a precipitating factor instigating their interaction and resulting in the melanocyte destruction. Headway is being made in understanding the etiology of vitiligo that should culminate in new and improved therapies.

Operative treatment for segmental eyelid vitiligo.

PURPOSE: The purpose of this article is to describe a safer method of removing the epithelium from the eyelid in preparation for melanocyte transplantation in treating segmental eyelid vitiligo. METHODS: The Erbium yttrium-aluminum-garnet (YAG) laser was used for ablation of the epithelium on the nonpigmented skin of the eyelid. Subsequently, an epithelial skin graft containing melanocytes was applied to the affected area. An occlusive dressing was applied for 2 days. RESULTS: The skin graft was found to be viable on removal of the dressing, and pigment was evident within the first week. No scarring developed, and an outstanding result was evident within a few weeks and has persisted. CONCLUSIONS: Use of the Erbium YAG laser enabled us to perform the procedure safely in less than half an hour. The procedure was performed in an outpatient setting, using topical and local anesthesia. Previously, we were unwilling to offer treatment for depigmentation of the eyelid. This case demonstrates a safe method for treatment of eyelid vitiligo that can be performed by a surgeon experienced in use of the laser and epithelial grafting.

Keratinocyte-melanocyte graft technique followed by PUVA therapy for stable vitiligo.

BACKGROUND: Various surgical procedures for correcting stable vitiligo exist but these have their own limitations. Autologous, non-cultured, non-trypsinized, melanocyte plus keratinocyte grafting is a new and simple method of vitiligo surgery. OBJECTIVE: The study aimed to evaluate efficacy of a new grafting technique in vitiligo patches. METHODS: Eighteen vitiligo patches underwent this procedure. The upper layer of epidermis was removed by superficial dermabrasion using a dermabrader micromotor until the epidermis appeared wet and shiny. Then, antibiotic ointment was applied and dermabrasion was continued up to the whitish area of the upper dermis. The paste-like material (ointment with entangled epidermal particles) was collected and spread over the dermabraded recipient site. RESULTS: Pigmentation usually started at 4-6 weeks. Complete uniform pigmentation took 16-20 weeks. CONCLUSION: For smaller vitiligo patches this method gives cosmetically acceptable results. It is easy to perform and does not require specific laboratory setup.

Autologous cultured melanocytes in vitiligo treatment.

BACKGROUND: Surgical treatment of vitiligo is indicated when lesions are localized in poorly responding areas. OBJECTIVES: The objectives were: (1) to establish the melanocyte culture obtained from the epidermis of vitiligo patients for future treatment; (2) to estimate the influence of selected factors on the formation of suction blisters and the results of culture; and (3) to compare the results of treatment of vitiliginous macules localized in the dorsum of the hands and lower limbs by transplantation of cultured autologous melanocytes plus psoralen and ultraviolet A (PUVA) therapy (CMP), suction blister transplantation plus PUVA therapy (SBP), cryotherapy plus PUVA-therapy (CP), and only PUVA therapy (OP). METHODS: Forty patients were qualified for the study. The roofs of the suction blisters were used as a melanocyte source for culture establishment or were directly transplanted. RESULTS: The CMP procedure was successfully performed on only 10 of 20 patients because of the difficulties in cell culture establishment. The SBP method was carried out on all 20 patients. A total lack of effectiveness was found in CP and OP methods. CONCLUSIONS: The effectiveness of culture depends on time of suction blister forming, phototype, and previous PUVA therapy. This study demonstrated the advantage of the SBP over the CMP method.

New and experimental treatments of vitiligo and other hypomelanoses.

This article deals with new and experimental treatments that can be used to treat various forms of depigmenting disorders. Ultraviolet B-focused therapies and new surgical approaches are analyzed in this article. These therapies were mainly or only developed to treat vitiligo, which is the most studied and probably the most challenging of all the hypomelanoses, but the results obtained in trials and clinical experiences about vitiligo sometimes can be referred to other depigmenting disorders.