Therapeutic success of epidermal grafting in generalized vitiligo is limited by the Koebner phenomenon

Eighteen patients with vitiligo (two with localized type, five with segmental type, and 11 with generalized type) were treated with an epidermal graft using the roof of a suction blister. In all patients with localized and segmental lesions and in seven with generalized lesions, successful repigmentation without scarring was observed at the grafted sites approximately 2 to 3 weeks after grafting, and a subsequent two- to threefold expansion of the pigmented area occurred within 3 to 4 months. On the other hand, no repigmentation could be achieved in four patients with generalized vitiligo in whom depigmentation (i.e., the Koebner phenomenon) occurred at the donor sites. Our results suggest that the Koebner phenomenon occurs in an all-or-none pattern only in patients with generalized vitiligo. Thus, although epidermal grafting is a simple and useful method, successful repigmentation at the recipient sites depends on the selection of patients with localized lesions in whom the Koebner phenomenon does not develop.     

Combination treatment by 10 600 nm ablative fractional carbon dioxide laser and narrowband ultraviolet B in refractory nonsegmental vitiligo: a prospective, randomized half-body comparative study

Background Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed. Objectives To investigate the effects of fractional carbon dioxide (CO₂) laser therapy followed by systemic narrowband ultraviolet B (NB‐UVB) phototherapy on nonsegmental vitiligo (NSV) as a prospective and randomized left‐right comparative study. Methods Ten patients with NSV who presented symmetrical vitiligo lesions with no further improvement despite more than 1 year of conventional treatment were enrolled. Two sessions of half‐body fractional CO₂ laser therapy were performed at a 2‐month interval. NB‐UVB phototherapy was then administered to the entire body 5 days after each fractional laser treatment twice a week, increasing the dose incrementally by 15% at each session. Objective clinical assessments were made by two blinded dermatologists using a quartile grading scale, and the patients’ overall satisfaction was evaluated using a 10‐point visual analogue scale. Results Two months after the last treatment, mean improvement scores, assessed by physicians, were significantly higher for those treated with half‐body fractional CO₂ laser therapy followed by NB‐UVB phototherapy, compared with those treated with NB‐UVB alone (P = 0·034). In addition, according to subjective assessment, the half‐body laser treatment followed by NB‐UVB showed significantly higher improvements compared with NB‐UVB treatment alone (P = 0·023). Noticeable adverse events, such as infection, scarring and Koebner phenomenon, were not found in any patient. Conclusions This study suggests that fractional CO₂ laser therapy followed by NB‐UVB phototherapy could be used effectively and safely as an alternative modality for the treatment of refractory vitiligo.     

Depigmentation of the normally pigmented patches in universal vitiligo patients by cryotherapy

BACKGROUND: Complete depigmentation may occur, albeit rarely, in patients with universal vitiligo. They usually have one or more pigmented patches that remain normal, most frequently over the malar area of the face and dorsal aspects of forearms. Total repigmentation may not occur in these patients, even after receiving 150 session of PUVA therapy alone or in conjunction with other medical or surgical procedures, and there is possibility of recurrence after cessation of therapy. These patients are usually more interested in depigmentation rather than trying for repigmentation. OBJECTIVE: Because of the relatively high sensitivity of melanocytes to cryotherapy and the possibility of isomorphic phenomenon in vitiligo patients, removal of the remaining normally pigmented patches was attempted in patients with universal vitiligo using cryotherapy. METHOD: Five volunteer patients with universal vitiligo were chosen, all of whom wished to have their pigmented patches removed. In all five patients a small area was tested first in order to assure the patients of what the procedure involved and to show its likely result. All pigmented areas were then treated to 1-3 sessions of cryotherapy using a closed contact CO2 cryogun, with 4-6-week intervals. RESULTS: Complete and permanent depigmentation was achieved in all five patients with excellent cosmetic results and no complications or scarring. CONCLUSION: Cryotherapy is a cost effective, non-complicating, easily available procedure which can be used for depigmentation of normally pigmented patches in patients with universal vitiligo.     

Vitiligo at the Site of Radiotherapy for Nasopharyngeal Carcinoma

Cases of vitiligo following radiotherapy have been reported in patients with a history of vitiligo, possibly resulting from the Koebner phenomenon. As vitiligo in general is caused by melanocyte depletion, there is an increased radiosensitivity of this cell type in this disorder. However, vitiligo at sites of irradiation may be linked to a proposed auto-cytotoxic mechanism that may occur through inhibition of thioredoxin reductase by high extracellular calcium levels observed in keratinocytes of vitiligo patients. High levels of thioredoxin and thioredoxin reductases have been shown to protect from ionizing radiation-induced cell death. Thus, inhibition of thioredoxin reductase in vitiligo might account for the increased radiosensitivity of melanocytes in this disorder. We describe a patient who developed depigmentation at the site of radiation following radiotherapy for nasopharyngeal carcinoma. She had no history of vitiligo. Occurrence of depigmentation on the irradiated skin seemed to be related to radiation injury in our patient. Our case suggests that radiation injury to the skin can trigger vitiligo in patients who have no history of vitiligo. Thus, prior to therapy, the possibility of development of vitiligo should be taken into account for patients who are candidates for radiotherapy, even if they have no history of vitiligo.     

Repigmentation in vitiligo vulgaris by autologous minigrafting: Results in nineteen patients

Background: Minigrafting is a successful therapy for localized vitiligo but has never been reported for vitiligo vulgaris.Objective. Our purpose was to evaluate the efficacy of minigrafting in vitiligo vulgaris.Methods: In 59 patients with stable vitiligo vulgaris, a minigraft test was done by implanting two minigrafts in the lesion to be grafted. Patients were selected for grafting when spread of pigment was observed within 3 months. The rate of repigmentation was evaluated by digital image analysis.Results: Twenty-three patients (36 lesions), of 24 with a positive minigraft test, were grafted. The results of 19 patients were analyzed, showing 80% to 99% repigmentation in 14 lesions, 50% to 80% repigmentation in 10 lesions, and zero to 50% repigmentation in 12 lesions. Time of observation varied from 3 to 12 months after grafting. Best results were observed after 9 to 12 months. In all patients with a positive Koebner phenomenon depigmentation of the minigrafts developed.Conclusion: Autologous minigrafting is an effective therapy for stable vitiligo vulgaris in a selected group of patients.     

Koebner现象研究进展

Koebner现象最初是指银屑病患者无病变处皮肤经各种类型的创伤后也会产生银屑病的病变。随后发现很多其他的皮肤病也可出现Koebner现象，如白癜风、扁平苔藓等。目前Koebner现象的机制尚未明确，除创伤外很多其他因素，如目光、药物过敏、激光治疗等都可以引起Koebner现象。     

Narrow-band UV-B micro-phototherapy: a new treatment for vitiligo

BACKGROUND: Vitiligo is a common, acquired, often familial, melanocytopenic disorder with focal depigmentation of the skin. There are several new treatments, that appear to have higher success rates than previous therapies for the treatment of vitiligo. Among these, the most promising one appears to be narrow-band UV-B therapy. OBJECTIVE: The aim of this open study is to evaluate the efficacy of the BIOSKIN micro-phototherapy in the treatment of vitiligo in 734 patients. SUBJECTS AND METHODS: Seven hundred and thirty-four individuals affected by vitiligo (segmental and non-segmental) were treated for 12 months with a new device called BIOSKIN that can produce a focused beam of narrow UV-B (microphoto-therapy) on vitiligo patches only. Photographs of the subjects were taken at the beginning of the therapy and every month thereafter for 12 months. The response to treatment was estimated in two comparable photographs using planimetry. The duration of the clinical study was of 2 years and 8 months. At the end of this period 734 patients had received each a mean of 24 sessions of treatment during a period of 12 months. RESULTS: Five hundred and ten subjects (69.48%) of the 734 achieved normal pigmentation on more than 75% of the treated areas. In particular, 112 of these were totally repigmented. One hundred and fifty-five (21.12%) individuals achieved 50-75% pigmentation of the treated areas, and 69 (9.40%) showed less than 50% repigmentation. No patients showed acute or chronic relevant adverse effects. CONCLUSION: BIOSKIN UV-B microphototherapy seems highly effective in restoring pigmentation in patients affected by vitiligo. As no side-effects have been observed, this could represent the treatment of choice for vitiligo limited to less than 30% of the skin surface.     

UV-B radiation microphototherapy. An elective treatment for segmental vitiligo

BACKGROUND: Vitiligo is a common disease of unknown cause that produces disfiguring white patches of depigmentation. Previous studies have suggested the effectiveness of UV-B radiation in generalized vitiligo (GV) therapy, but there was no evidence to support the same role for segmental vitiligo (SV). OBJECTIVE: The purpose of this study was to use UV-B radiation exclusively on vitiligo patches of individuals affected by SV to evaluate the effectiveness of this therapy. SUBJECTS AND METHODS: Eight individuals with SV were treated for 6 months with a new device called BIOSKIN that can produce a focused beam of UV-B (microphoto-therapy) on vitiligo patches only. Photographs of the subjects were taken at the beginning of the therapy and once a month thereafter for 6 months. The response to treatment was estimated in two comparable photographs using planimetry. A control group of eight individuals matched for sex and age was treated with placebo, using the same device but not releasing any kind of detectable light. RESULTS: After 6 months of microphototherapy five subjects of the eight studied achieved normal pigmentation on more than 75% of the treated areas. In particular, three of these were totally repigmented. Two individuals achieved 50-75% pigmentation of the treated areas, and only one showed less than 50% repigmentation. In the control group only one patient showed moderate repigmentation (less than 50%). CONCLUSION: UV-B microphototherapy seems highly effective in restoring pigmentation in patients affected by vitiligo. As no side-effects have been observed, this could represent the treatment of choice in the limited (segmental) forms of vitiligo.     

Enhanced bleaching treatment: opportunities for immune‐assisted melanocyte suicide in vitiligo

Depigmentation in vitiligo occurs by progressive loss of melanocytes from the basal layer of the skin, and can be psychologically devastating to patients. T cell‐mediated autoimmunity explains the progressive nature of this disease. Rather than being confronted with periods of rapid depigmentation and bouts of repigmentation, patients with long‐standing, treatment‐resistant vitiligo can undergo depigmentation treatment. The objective is to remove residual pigmentation to achieve a cosmetically acceptable result – that of skin with a uniform appearance. In the United States, only the use of mono‐benzyl ether of hydroquinone (MBEH) is approved for this purpose. However, satisfactory results can take time to appear, and there is a risk of repigmentation. MBEH induces necrotic melanocyte death followed by a cytotoxic T‐cell response to remaining, distant melanocytes. As cytotoxic T‐cell responses are instrumental to depigmentation, we propose that combining MBEH with immune adjuvant therapies will accelerate immune‐mediated melanocyte destruction to achieve faster, more definitive depigmentation than with MBEH alone. As Toll‐like Receptor (TLR) agonists – imiquimod, CpG, and Heat Shock Protein 70 (HSP 70) – all support powerful Th1 responses, we propose that using MBEH in combination with these agents can achieve superior depigmentation results for vitiligo patients.     

Laser hair removal in a patient with polycystic ovarian syndrome and vitiligo

It is well recognized that vitiligo displays the Koebner phenomenon. However, the impact of this phenomenon on hair removal in these patients has little been considered. This is a challenging case of a woman with hirsutism and vitiligo who opted to have laser hair removal treatment.     

Accelerating bleaching in vitiligo: balancing benefits versus risks

While the goal of available treatment in vitiligo is to regain pigmentation, some patients affected by extensive and treatment‐resistant vitiligo, with a major social and emotional impact, may benefit from depigmentation therapy. However, results from such therapy may not always be satisfactory. So to achieve better, faster and complete bleaching, Webb et al. propose a synergistic approach that combines topical application of bleaching phenols which targets melanocytes and initiate local inflammation with immune adjuvants so as to obtain an enhanced immune response against remaining melanocytes. This strategy could be reliable, but should be evaluated cautiously in future studies, in terms of potential side effects and induction of undesired autoimmunity.     

Site‐oriented depigmentation in vitiligo patients using Q‐switched Nd:YAG laser (1,064/532 nm), cryotherapy and chemical peels: A comparative study

Depigmentation emerges as a feasible solution for vitiligo universalis and refractory cases of vitiligo vulgaris that hinder patients' quality of life. A range of depigmenting modalities has previously been developed. However, each has its own limitations. Based on skin sensitivity, this study sets out to compare the efficacy and tolerability of “trichloroacetic acid (TCA) peels 25% and 50% and Qs Nd:YAG laser (1,064/532 nm)” for facial depigmentation and “cryotherapy, phenol 88% and Qs Nd:YAG (1,064/532 nm)” for extrafacial skin depigmentation. Forty vitiligo patients were examined and equally divided into facial & extrafacial groups. Regular sessions were performed. Patients' responses were assessed after 3 months or when excellent/complete depigmentation was attained through assessing “depigmentation grade”, “extent of depigmented skin”, “patient satisfaction” and “overall response”. Patients were observed for a six‐month follow‐up period. In facial depigmentation, Qs Nd:YAG showed the highest significant response followed by TCA 50% and 25%. In extrafacial depigmentation cryotherapy, phenol 88% and Qs Nd:YAG laser displayed positive outcomes without significant difference. Among the modalities tested Qs Nd:YAG yielded superior results in facial residual pigmentation in vitiligo when compared to TCA 50% and 25%, whereas in extrafacial sites Qs Nd:YAG, cryotherapy and phenol were equally effective.     

Erbium:YAG laser and cultured epidermis in the surgical therapy of stable vitiligo

OBJECTIVE: To induce complete and reproducible repigmentation of large "stable" vitiligo lesions by means of autologous cultured epidermal grafts using a rapid, simple, and minimally invasive surgical procedure. DESIGN: Achromic epidermis was removed by means of appropriately settled erbium:YAG laser, and autologous epidermal grafts were applied onto the recipient bed. Melanocyte content was evaluated by dopa reaction. The percentage of repigmentation was calculated using a semiautomatic image analysis system. SETTING: A biosafety level 3-type cell culture facility, a surgical ambulatory department, and a dermatological department in a hospital. PATIENTS: Twenty-one patients with different types of vitiligo were admitted to the study and treated with autologous cultured epidermal grafts. Inclusion criteria were failure of at least 2 standard medical approaches; no therapy for at least 12 months; no progression of old lesions or appearance of new lesions; no Koebner phenomenon within the past 18 months; and no autoimmune disorders. RESULTS: The average percentage of repigmentation in 21 patients was 75.9% (1759.7 cm2 repigmented/2315.8 cm2 transplanted). Three patients showed a reactivation of their vitiligo and did not show repigmentation. The remaining 18 patients, with 43 distinct lesions, showed an average percentage of repigmentation of 90% (1759.7 cm2 repigmented/1953.4 cm2 transplanted). CONCLUSIONS: Under appropriate conditions, cultured epidermal grafts induce complete repigmentation of stable vitiligo lesions. Erbium:YAG laser surgery can supply a fast and precise tool for disepithelialization, hence allowing treatment of large vitiligo lesions during a single surgical operation.     

Treatment of stable and recalcitrant vitiligo by autologous miniature punch grafting: a prospective study of 1,000 patients.

BACKGROUND: Stable and refractory vitiligo may be unresponsive to medical therapy. Melanocyte transplantation by punch grafting (PG) can restore the normal pigmentation. OBJECTIVE: To evaluate the efficacy of PG on repigmentation of vitiligo patches. METHODS: Autologous miniature PG was undertaken in 1,000 patients with stable and recalcitrant vitiligo. Test grafting (TG) was done in all the patients. Those who showed negative TG results were excluded from the study. RESULTS: Of the 1,000 patients, 880 (88%) showed positive TG results. In 656 (74.55%) patients, 90-100% repigmentation was achieved. In 93 (10.57%) patients, there was no spread of pigment, while in 21 (2.39%) patients depigmentation of the graft(s) was notices. Of various complications, polka dot appearance (43.98%) and colour mismatch (34.32%) were most frequent. CONCLUSION: Partial to near-total repigmentation of a vitiligo patch can be achieved by PG.     

Depigmentation therapy

ABSTRACT: Depigmentation therapy is a treatment option for patients with widespread, treatment-resistant vitiligo. The most commonly employed technique is the application of monobenzylether of hydroquinone (MBEH), also known as monobenzone, to areas with residual pigment. Prior to instituting therapy, the patient must be aware of the cost, treatment time course, risk of distant sites of depigmentation, probable permanency of depigmentation, side effects such as contact dermatitis, and the potential for repigmentation via follicular melanocytes. The social ramifications of depigmentation therapy also must be discussed, especially for patients with skin types IV and V. The sequential use of 4-methoxyphenol and Q-switched ruby laser also has been reported as a successful form of depigmentation therapy.     

Retinoic acid synergistically enhances the melanocytotoxic and depigmenting effects of monobenzylether of hydroquinone in black guinea pig skin

Monobenzylether of hydroquinone (MBEH) has long been utilized for the depigmentation therapy of patients with extensive vitiligo. In this approach, the normally pigmented areas surrounding vitiligo lesions are depigmented to achieve a uniform skin tone. One of the important disadvantages of MBEH therapy, however, is the resistance of a considerable number of vitiligo patients against the depigmenting effect of this agent. We have previously proposed that the glutathione-dependent cytoprotection of melanocytes can be impaired through the inhibition of the enzyme glutathione S-transferase by retinoic acid (RA). The combination of RA with melanocytotoxic agents could thus lead to increased susceptibility of melanocytes to such compounds. In this study we have shown, for the first time, that the melanocytotoxic and depigmenting effects of MBEH are synergistically enhanced when it is combined with RA. The treatment of black guinea pig skin with RA (0.025%) alone induced no significant changes in the number of epidermal melanocytes and no skin depigmentation. On the other hand, MBEH (10%) produced mild to moderate skin depigmentation and reduced the average number of melanocytes from 76 (+/-5)/field (magnification: x 40) in control sites, to 42 (+/-6)/field in the depigmented skin. The RA (0.025%)-MBEH (10%) combination, however, produced a complete degree of depigmentation in the majority of treated sites after 10 days of application and reduced the average number of melanocytes to only 6 (+/-6)/field. RA-MBEH combination serves as a very potent skin depigmenting formula and now awaits future assessments of its potential use for the treatment of extensive vitiligo.     

308nm准分子激光联合胡椒碱治疗白癜风疗效观察

目的评价308nm准分子激光联合胡椒碱对白癜风的临床疗效和安全性。方法将入选的87例白癜风患者按就诊顺序随机分为2组,共80例患者完成试验观察,治疗组予308nm准分子激光局部照射每周2次,联合胡椒碱酊局部外用2次/d治疗,对照组予308nm准分子激光局部照射每周2次,联合8-甲氧基补骨脂素(8-MOP)溶液局部外用2次/d治疗。治疗时间为4周一疗程,治疗3个疗程,比较2组患者在白癜风皮损复色上的差异。结果治疗组的显效率90%,对照组为77.5%。2组显效率差异有统计学意义(P0.05),治疗中未出现严重的不良反应。结论 308nm准分子激光联合胡椒碱对于治疗白癜风有明显的效果,且无明显不良反应,对白癜风的治疗是一个很好的选择。     

Vitiligo: new and emerging treatments

ABSTRACT:  Vitiligo is a cosmetically disfiguring condition, and, although there is no therapeutic full solution yet, some treatment may induce good results in most patients. The disease can be successfully treated with various medical options. Both nonfocused or focused narrowband ultraviolet B phototherapy represents the current treatment of choice, to minimize side effects and reach optimal clinical results. Topical novel approaches are also considered. Surgical methods, consisting of autologous transplantation methods, is generally recommended for focal/stable vitiligo, after medical therapy has failed. Finally, for patients with extensive vitiligo, depigmentation of the residual melanin should be taken into account.     

Suction blister grafting for stable vitiligo using pulsed erbium:YAG laser ablation for recipient site

BACKGROUND: Suction blister grafting was performed via a modified simple technique using a 20-mL syringe to create the donor graft and pulsed erbium:YAG laser ablation of the recipient site. METHODS: Two patients with stable vitiligo and one with postinflammatory depigmentation were studied. RESULTS: The grafts took well in all three patients and pigmentation was retained at 20 weeks. No complications occurred. CONCLUSIONS: The erbium:YAG laser is an ideal tool for creating graft recipient sites, given its precision in terms of width and depth of ablation. A 20-mL syringe can be used to create a blister of adequate size.     

Striae: stretching the long list of precipitating factors for ‘true koebnerization’ of vitiligo,lichen planus and psoriasis

Aims: To document the role of striae distensae and striae gravidarum in causing Koebner phenomenon in cases of vitiligo, psoriasis and lichen planus. Results: Striae are documented to cause Koebner phenomenon in patients with preexisting vitiligo, psoriasis and lichen planus, the three conditions where ‘true kobenerisation’ has been suggested according to Boyd and Nelder classification. Conclusions: Striae distensae and striae gravidarum are examples of blunt trauma. Just as happens with penetrating trauma, striae too are shown to be responsible for causing the Koebner phenomenon.