A Critical Appraisal of Vitiligo Etiologic Theories. Is Melanocyte Loss a Melanocytorrhagy? (original) (raw)

Melanocytes are not absent in lesional skin of long duration vitiligo

The Journal of Pathology, 2000

This paper provides evidence that melanocytes are still present in the depigmented epidermis of patients with vitiligo even after stable disease of 25 years' duration. Melanocyte cultures were successfully established from depigmented epidermal suction blister tissue of all 12 randomly selected patients and these cells produced melanin. Even under in vitro conditions, vacuolation of melanocytes was demonstrated in ®ve patients with active disease, which was reversible upon exogenous addition of bovine catalase to the culture medium. Full skin biopsies from 17 patients with vitiligo, obtained from depigmented and normally pigmented areas, con®rmed the involvement of melanocytes, keratinocytes, and Langerhans cells in this disorder. In addition, the presence of clustered and single pre-melanosomes in basal and supra-basal keratinocytes of lesional and normal epidermis, as well as the retention of single melanocytes in lesional epidermis, was demonstrated by light and electron microscopy. Upon topical application of a narrow band UVB-activated pseudocatalase, vacuolation, granulation, and dilatation of the endoplasmic reticulum completely recovered, but the ectopic pre-melanosome shedding remained. Taken together, these observations indicate that melanocytes are never completely absent in the depigmented epidermis and that these melanocytes can recover their functionality in vivo and in vitro upon the removal of hydrogen peroxide. Furthermore, this study supports the concept that vitiligo involves the entire epidermal unit in both depigmented and`normal' pigmented skin.

The melanocytorrhagic hypothesis of vitiligo tested on pigmented, stressed, reconstructed epidermis

Pigment Cell Research, 2007

Common generalized vitiligo is an acquired depigmenting disorder characterized by a chronic and progressive loss of melanocytes from the epidermis and hair follicles. We previously proposed a new theory that vitiligo involves the chronic detachment and transepidermal loss of melanocytes caused by autoimmune, neural and impaired redox mechanisms associated with mechanical trauma. In this study, we reconstructed epidermis on dead de-epidermized dermis with normal and ⁄ or non-segmental nonlesional vitiligo (NSV) cells and tested catecholamines or sera or hydrogen peroxide. Under unstressed conditions, the number of melanocytes located in the basal layer was significantly lower in reconstructs made with melanocytes from non-lesional NSV skin and normal keratinocytes compared with controls made with autologous normal melanocytes. The number of non-lesional NSV melanocytes was even lower in reconstructs made with keratinocytes from non-lesional NSV skin. Epinephrine and H 2 O 2 could trigger the transepidermal loss of normal and vitiligo melanocytes. Some sera induced melanocyte detachment but without any clear correlation with disease activity in the donors. In conclusion, our results are the first step to obtaining a reproducible melanocytorrhagic model in vitro with some of the stressors investigated. They support the hypothesis that NSV melanocytes have an intrinsic defect, which limits their adhesion in a reconstructed epidermis, with an enhancer effect of the vitiligo keratinocyte milieu.

Concise review of recent studies in vitiligo

Qatar Medical Journal, 2013

Vitiligo is an acquired pigmentry disorder of the skin and mucous membranes which manifests as white macules and patches due to selective loss of melanocytes. Etiological hypotheses of vitiligo include genetic, immunological, neurohormonal, cytotoxic, biochemical, oxidative stress and newer theories of melanocytorrhagy and decreased melanocytes survival. There are several types of vitiligo which are usually diagnosed clinically and by using a Wood's l& also vitiligo may be associated with autoimmune diseases, audiological and ophthalmological findings or it can be a part of polyendocrinopathy syndromes. Several interventions are available for the treatment for vitiligo to stop disease progression and/or to attain repigmentation or even depigmentation. In this article, we will present an overall view of current standing of vitiligo research work especially in the etiological factors most notably the genetic components, also, types and associations and various and newer treatment ...

Vitiligo – from Clinical Manifestations to Pathophysiological Mechanisms and Cell Death

2021

Corresponding author: Elena Bălășescu E-mail: elena.balasescu@umfcd.ro ABSTRACT The pathogenesis of vitiligo is still unclear. The complexity of the disease seems to be based on the intervention of environmental factors in the background of genetic predisposition which will determine the response of the immune system, the involvement of the nervous and endocrine systems, altered metabolisms and increased oxidative stress all these elements leading to melanocytic dysfunction and their subsequent destruction. Melanocytic death has a clinical correspondent that embraces the form of white macules on the skin, associated or not with leucotrichia. A better understanding of vitiligo' s pathophysiology and mechanisms of cell death at the skin level can be a step to some appropriate treatment strategies.

Frontiers and controversies in the pathobiology of vitiligo: separating the wheat from the chaff

Experimental Dermatology, 2009

The pathogenesis of vitiligo is complex and not well understood. Genes play a role in all aspects of vitiligo pathogenesis, and studies are ongoing to identify these genes and understand their biology. There is a body of interlocking, compelling evidence supporting an autoimmune basis for most or all cases of generalized vitiligo. The development of an autoimmune disease generally involves three components; the immune system, environmental triggers and other exogenous precipitating factors, and the target tissue. In vitiligo, precipitating factors could induce melanocyte damage in genetically susceptible individuals and consequent cell death, loss of tolerance, and induction of melanocytedirected autoimmunity. Future research will more precisely define the multiple biological events that regulate development of vitiligo.

Involvement of non melanocytic skin cells in vitiligo

Experimental Dermatology

Despite melanocytes are the key players in vitiligo, a continuous cross-talk between epidermal and dermal cells may strictly affect their functionality, in both lesional and non-lesional skin. Focusing on this interplay, we have reviewed existing literature supporting evidence on cellular and functional alterations of surrounding epidermal keratinocytes, extracellular matrix (ECM) proteins and fibroblasts in the underlying dermal compartment that may contribute to melanocyte disappearance in vitiligo. We have also examined some clinical and therapeutic aspects of the disease to sustain the non-exclusive involvement of melanocytes within vitiligo. As a result, a different and more complex scenario has appeared that may enable to provide better understanding about origins and progress of vitiligo and that should be considered in the evaluation of new treatment approaches.

Vitiligo Skin: Exploring the Dermal Compartment

Journal of Investigative Dermatology

There is an increasing interest in the apparently normal skin in vitiligo. Altered expression of the adhesion molecule E-cadherin and persistent deregulated intracellular redox status that promotes the acquisition of a stress-induced senescent phenotype in melanocytes of normally pigmented skin from patients with vitiligo have been described. Growing evidence has shown that such cellular and functional alterations are not necessarily restricted to melanocytes but may be extended to other cutaneous cell populations in both lesional and nonlesional areas. However, whether dermal fibroblasts exhibit related alterations that may contribute to the defects associated with melanocytes in vitiligo is not known. Here we reveal within the dermal compartment cells a myofibroblast phenotype and a predisposition to premature senescence, indicating the existence of altered cross-talk between dermal and epidermal components that may affect melanocyte functionality even in the apparently normal skin of patients with vitiligo.

The convergence theory for vitiligo: A reappraisal

Experimental dermatology, 2018

Vitiligo is characterized by progressive loss of skin pigmentation. The search for etiologic factors has led to the biochemical, the neurologic and the autoimmune theory. The convergence theory was then proposed several years ago to incorporate existing theories of vitiligo development into a single overview of vitiligo etiology. The viewpoint that vitiligo is not caused only by predisposing mutations, or only by melanocytes responding to chemical/radiation exposure, or only by hyperreactive T cells, but rather results from a combination of etiologic factors that impact melanocyte viability, has certainly stood the test of time. New findings have since informed the description of progressive depigmentation. Understanding the relative importance of such etiologic factors combined with a careful selection of the most targetable pathways will continue to drive the next phase in vitiligo research: the development of effective therapeutics. In that arena it is likewise important to ackno...