Rafael Falabella

Update on skin repigmentation therapies in vitiligo

Treatment for vitiligo is difficult and prolonged. Nevertheless, at present considerable knowledge accumulated during several decades on the pathogenic mechanisms, revealed important clues for designing new strategies to improve vitiligo depigmentation. With available medical therapies, high repigmentation percentages mostly on facial and neck lesions are achieved, although they are less effective on trunk and limbs and poor on the acral parts of the extremities. Narrow band UVB and psoralens and UVA are the two most important treatments for generalized vitiligo affecting more than 10–20% of the cutaneous surface, and topical corticosteroids, or calcineurin inhibitors are the most valuable treatments for localized vitiligo. Persistence of achieved regimentation is variable and an undefined percentage of patients may have variable recurrence. When vitiligo becomes refractory, surgical methods may improve depigmentation as effectively as with medical therapy; in segmental (unilateral) or long standing, non‐segmental (bilateral) stable vitiligo, repigmentation with surgical methods is usually permanent.

The minigrafting test for vitiligo: Detection of stable lesions for melanocyte transplantation

BACKGROUND Selected patients with stable and refractory vitiligo may consider melanocyte transplantation as a therapeutic alternative. A method to anticipate the response to surgical repair is not available. OBJECTIVE We evaluated the pigment spread of minigrafts when implanted within achromic lesions of stable vitiligo as a test to identify good candidates for surgical repigmentation. METHODS Four to six minigrafts of 1.0 to 1.2 mm were implanted within lesions of patients with unilateral (localized) and bilateral (generalized) vitiligo. Pigment spread was assessed 3 months later. RESULTS Forty-seven subjects were examined. In unilateral vitiligo 19 of 20 patients (95%) had a positive test result in comparison with only 13 of 27 patients (48%) with bilateral vitiligo (p = 0.002). CONCLUSION The minigrafting test is a reliable tool to identify patients with stable vitiligo who may respond to melanocyte transplantation. Unilateral (localized) vitiligo is the best indication for surgical repigmentation.

Treatment of refractory and stable vitiligo by transplantation of in vitro cultured epidermal autografts bearing melanocytes

BACKGROUND Previous reports demonstrated the usefulness of in vitro cultured epidermis for repigmenting vitiligo. OBJECTIVE Our purpose was to determine the potential of in vitro cultured epidermal sheets to treat extensive areas of intractable vitiligo. METHODS In nine patients with long-standing, stable, and refractory vitiligo, autologous epidermis was cultured in vitro in H-MEM but without growth enhancers or hormones and transplanted onto previously denuded achromic lesions. RESULTS Repigmentation was achieved to almost 100% in three subjects, 60% improvement was seen in two patients, and 30% to 40% in three additional cases. Only one patient had almost no response. Long-term observations in these patients indicate that repigmentation obtained by this method is permanent. CONCLUSION Transplantation of in vitro cultured epidermis bearing melanocytes is potentially effective to treat extensive areas of vitiligo, but this method is presently at an experimental stage.

Repigmentation of segmental vitiligo by autologous minigrafting

Segmental vitiligo (SV) shows distinct clinical, physiologic, and therapeutic characteristics as opposed to those seen in generalized vitiligo (GV). Three patients affected with SV, a relatively unresponsive dermatosis, were successfully repigmented by autologous minigrafting. The achieved results demonstrate a new therapeutic approach for SV.

An epidemiologic case-control study in a population with vitiligo

BACKGROUND Previous epidemiologic studies of vitiligo have not included a sex- and age-matched population. OBJECTIVE Our purpose was to attempt to determine possible risk factors and clinical differences associated with unilateral and bilateral vitiligo. METHODS Two hundred thirty-four patients and 234 normal control subjects were examined and questioned. RESULTS Patients with unilateral vitiligo were younger and had an earlier age at onset. Koebners phenomenon and halo nevus were infrequent in the total vitiligo group, but no difference between vitiligo types was observed. Subjects with bilateral vitiligo more frequently had light skin (types I, II, and III) and more commonly had an associated autoimmune disease. CONCLUSION Unilateral and bilateral vitiligo differ substantially in several clinical aspects, which suggests a different pathogenic mechanism for each condition.

Transplantation of in vitro-cultured epidermis bearing melanocytes for repigmenting vitiligo.

A new method for repigmenting vitiligo by transplantation of in vitro-cultured epidermis bearing melanocytes is described. The artificially grown epidermis was implanted after vitiliginous skin was denuded with liquid nitrogen. Satisfactory repigmentation was attained. This technique offers a new approach for treating refractory vitiligo.

MELANOCYTE RESERVOIR IN VITILIGO

Background. Dopa‐negative, inactive melanocytes, present in the middle portion of the hair follicle, but also in hair bulbs, have been reported as a source of pigment cells, when repopulation of epidermal melanocytes occurs. A melanocyte reservoir in these anatomical sites has been suggested. Our objective was to investigate the ability of the lower third of the hair follicle (hair bulb) to repigment achromic skin in vitiligo.

On the pathogenesis of idiopathic guttate hypomelanosis

Idiopathic guttate hypomelanosis is a common leukodermic dermatosis of obscure origin, consisting of small 2- to 5-mm achromic or hypopigmented macules, mainly affecting the exposed upper and lower extremities. In a group of 400 consecutive dermatologic patients, idiopathic guttate hypomelanosis was much more prevalent in women than in men. However, in both sexes this prevalence became more common with advancing age. In another group of fifteen patients with idiopathic guttate hypomelanosis and fifteen normal controls matched by age, sex, and skin type, the following was found: A cause-effect relationship between chronic actinic exposure and the development of idiopathic guttate hypomelanosis could not be established by statistical studies. A family aggregation survey disclosed a higher prevalence of idiopathic guttate hypomelanosis in the family of patients with idiopathic guttate hypomelanosis than in the control group. Epithelial atrophy, patchy absence of melanocytes and melanin, flattening of the rete pegs, and basket weave hyperkeratosis were the most prominent histologic findings of idiopathic guttate hypomelanosis. Minigrafts of normal skin implanted in idiopathic guttate hypomelanosis lesions did not modify the achromic defects, whereas intralesional triamcinolone with or without grafts improved the appearance of these lesions.

Vitiligo and the melanocyte reservoir.

Repigmentation of vitiligo depends on available melanocytes from three possible sources: from the hair follicle unit which is the main provider of pigment cells, from the border of vitiligo lesions, and from unaffected melanocytes within depigmented areas; pigment cells at these locations originate a perifollicular, border spreading and a diffuse repigmentation pattern. In order for repigmentation to take place under stimulation with diverse therapies, melanocytes should be present in appropriate numbers. Melanocyte tissue stem cells located in the niche at the bulge region of the hair follicle are the most important sources for providing immature pigment cells that undergo terminal differentiation and originate repigmentation, but cytokines, UVR and other molecules acting in melanogenesis with adequate regulation mechanisms contribute to successful recovery in vitiligo. The presence of keratinocyte stem cells in the interfollicular epidermis raises the question on the possibility of melanocyte stem cells in a similar location and the development of future strategies for therapeutic purposes.

A double-blind, randomized trial of 0.05% betamethasone vs. topical catalase/dismutase superoxide in vitiligo.

Background  Among all the topical immunomodulators, vitiligos mainstay therapy includes topical corticosteroids. Many other non‐immune theories have also been suggested for vitiligos pathogenesis, but the role of oxidative stress has gained more importance in recent years.