ReviewVitiligo: Pathogenesis, clinical variants and treatment approaches☆
Introduction
Vitiligo is a common chronic acquired disease of pigmentation. Its etiology is unknown, but it is characterized by destruction of melanocytes in the skin that causes hypopigmented and asymptomatic macules with sharply demarcated margins (Fig. 1) [1]. However, recent clinical and experimental studies suggest that there is a systemic destruction of melanocytes, especially in the mucous membranes, eyes, and the membranous labyrinth of the inner ear. Indeed, several authors reported an association between vitiligo, ocular manifestation, hearing loss and autoimmune diseases [2], [3]. Hearing loss is one of the most common associated symptoms with an incidence estimated in a range from 4% to 20% of vitiligo patients [2], [3].
The term vitiligo derives from latin and was first used by Celsus in his De Medicina [4]. However, in the nineteenth century both Brocq and Kaposi described the clinical features of vitiligo [5]. Furthermore, Kaposi showed that in the basal layer cells of the epidermis affected by vitiligo there were no pigment granules [5].
According to Ezzedine et al. [1], a segmental vitiligo which is the commonest form, and a non-segmental vitiligo can be distinguished. However, several subsets of this condition have been reported in the literature, including localized, generalized and universal types [1].
Although several hypotheses have been described in the literature, the leading theory is still the autoimmune one [6], [7], [8], [9].
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Epidemiology
By far, vitiligo is the most frequent disorder of pigmentation. India shows the highest incidence in the world (up to 8.8%) [10]. In the U.S.A. the incidence is about 1% [11]. However, the largest epidemiological study was conducted in 1977 in Denmark, showing an incidence of 0.38% [12]. In addition, it is reported in the literature that about 1% of the world's population has vitiligo [1]. Vitiligo affects both genders equally, although is a common observation that women complain earlier and
Genetic features in vitiligo
Vitiligo is a complex genetic disease. Fifty genes at least have already been evaluated in order to identify a link with vitiligo. However, only a few genes present a clear association with vitiligo. On the one hand, there are non-HLA genes, including DDR1, XBP1, NLRP1, PTPN22 and COMT [14]; on the other hand, there are HLA-associated genes, including HLA-A2, HLA-DR4 and HLA-DR7 alleles [15], [16], [17].
The DDR1 gene, on the chromosome region 6p21, is involved in melanocyte adhesion to the
Etiopathogenesis
Although the etiology of vitiligo remains unclear, several theories have been developed. However, the autoimmune hypothesis remains the leading one.
Classification
Vitiligo is divided clinically into two main forms, segmental vitiligo (SV) and non-segmental vitiligo respectively. The latter also includes three major subsets, namely generalized vitiligo, acrofacial vitiligo, and universal vitiligo [1]. Recently, mixed vitiligo (MV) has been described as an initial SV, which later (usually several months) spreads bilateral NSV patches [56]. However, because the progress of vitiligo is unpredictable, it is not uncommon for NSV to evolve over time, modifying
Histopathology
Vitiligo is characterized mainly by typical findings in the dermal–epidermal junction. While borders of white macules still demonstrate residual melanocytes and a few granules of melanin, the rest of the lesion show no melanocytes and the absence of melanin: sometimes, a lymphoid infiltrate may be evident in the outer active part of the lesion [91]. Some authors reported that the healthy skin near the hypopigmented macule showed isolated areas of vacuolization at the dermal–epidermal junction
Diagnosis and differential diagnosis
Diagnosis is mainly based on clinical features. In fact, there are no particular tests to identify vitiligo. However, evaluation of the presence of organ-specific autoantibodies, especially those directed against thyroid and adrenal glands could be useful. A Wood's lamp could be used for the optimal evaluation of some uncertain lesions.
Differential diagnosis includes some acquired hypopigmented disorders, like pityriasis versicolor, pityriasis alba, lichen sclerosus et atrophicus, leprosy,
Therapy
The aim of the treatment is to obtain skin repigmentation. It is a common observation that some areas, especially those damaged by a chronic physical trauma (e.g. the hands), are less responsive to the therapy. However, spontaneous repigmentation occurs in between 1% and 25% of patients [81].
Conclusions
Vitiligo is a common systemic disease that mainly involves the skin. The majority of the authors favor the theory of an autoimmune etiopathogenesis, which is further supported by the frequent association of vitiligo with autoimmune diseases.
Ocular and inner ear involvements frequently occur in this disease. Sensorineural hearing loss is the most frequently reported symptom and should always be investigated. In our opinion, hearing loss should be evaluated by pure tone audiometry at vitiligo
Take-home messages
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Vitiligo is a common, but a complex disease, that could arise at any age.
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Its pathogenesis is still not clear although several hypotheses have been proposed.
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The autoimmune theory is now the leading theory.
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Vitiligo is mainly a skin disease, but can also involve the eye and the inner ear.
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The association with hearing loss was detected in a range from 4% to 20% of vitiligo patients.
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Nowadays, several types of therapy are available. However, topical medication and NBUVB are the safest and most
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All authors declare no conflicts of interest, grants or other founding supports.