Histopathologic Features in Vitiligo

Kim, You Chan; Kim, Yun Jeon; Kang, Hee Young; Sohn, Seonghyang; Lee, Eun‐So

doi:10.1097/dad.0b013e3181651511

Cited by 77 publications

(41 citation statements)

References 14 publications

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“…Previous studies have shown that histamine stimulates melanocyte proliferation and melanogenesis in vitro [24,25,26,27,28,29,30,31,32]. We now show here that topical histamine consistently induces repigmentation in stable, nonsegmental vitiligo in humans, in parallel with increased melanin indices in histamine-treated normal mouse skin.…”

Section: Discussionsupporting

confidence: 55%

“…Because prior studies have shown that histamine stimulated melanogenesis via H2r in vitro [30,31,32], we next determined whether topical histamine increases the melanin index via H2r in vivo. We measured the melanin index in mouse ears cotreated with histamine and an H2r antagonist, cimetidine.…”

Section: Resultsmentioning

confidence: 99%

“…The pathological changes in the involved skin of vitiligo include loss of melanocytes, and reduced expression of histamine receptor 2 (H2r), but neither H1r nor H3r [30,31,32]. Because histamine stimulates melanogenesis and melanocyte proliferation in vitro [32,33,34], we hypothesized that topical histamine could be efficacious in vitiligo.…”

Section: Introductionmentioning

confidence: 99%

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Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a Receptor-Dependent Mechanism

Li¹,

Xu²,

Lin

et al. 2017

Skin Pharmacol Physiol

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Background: Though vitiligo is a common depigmentary disorder, it still represents a substantial therapeutic challenge. Therapeutic options are limited in part due to its uncertain etiology. Objective: Because recent studies suggest that histamine stimulates melanogenesis in vitro, we determined here whether topical histamine stimulates repigmentation in patients with stable, nonsegmental vitiligo. Methods: A total of 23 otherwise normal volunteers with vitiligo, including 14 males and 9 females aged 6-59 years (mean age 29.2 ± 2.8), were enrolled in this study. 1% histamine in distilled water was applied to the lesions twice daily for 5 weeks, while comparable lesions, treated with distilled water alone, served as the controls. The melanin index was measured on the uninvolved and lesional skin sites before and after 5 weeks of treatments using the melanin/erythema probe connected to a Courage-Khazaka MPA5 (Cologne, Germany). Changes in epidermal permeability barrier were also assessed at the same time point. To determine whether histamine-induced repigmentation is receptor-dependent, both ears of C57BL/6J mice were treated topically with 5% cimetidine, a histamine type 2 receptor (H2r) antagonist, twice daily for 10 days. One hour after each cimetidine application, the right ear was treated topically with 10% histamine, while vehicle alone was applied to the left ear. Changes in melanin index were measured 24 h after the last application of histamine and vehicle as described in the human study. Results: In patients with vitiligo treated with vehicle alone for 5 weeks, the melanin index remained unchanged, while topical histamine treatment increased the melanin index by 38% (p < 0.001 vs. both vehicle and pretreatment), which was paralleled by a >60% reduction in lesion surface area. Moreover, topical histamine accelerated permeability barrier recovery. No adverse events were observed following histamine applications. In mice, topical histamine significantly increased the melanin index, while topical co-applications of the H2r antagonist (cimetidine) prevented the expected histamine-induced increase in melanin index. Conclusions: These studies indicate that topical histamine or an H2r agonist could be useful for treating nonsegmental vitiligo, but further clinical studies in large populations will be required to validate the efficacy and safety of this approach.

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Section: Discussionsupporting

confidence: 55%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a Receptor-Dependent Mechanism

Li¹,

Xu²,

Lin

et al. 2017

Skin Pharmacol Physiol

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“…As poorly functioning melanocytes have been isolated from lesional vitiligo skin and cultured in vitro, [48][49][50][51] the deterioration of melanocyte function may be an early and crucial event in vitiligo. We found that miR-25 downregulated the expression of TYR, TYRP1 and TYRP2, as well as tyrosinase activity in melanocytes, thus impairing melanin synthesis.…”

Section: Discussionmentioning

confidence: 99%

Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

et al. 2015

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Oxidative stress has a critical role in the pathogenesis of vitiligo. However, the specific molecular mechanism involved in oxidative stress-induced melanocyte death is not well characterized. Given the powerful role of microRNAs (miRNAs) in the regulation of cell survival as well as the fact that the generation of miRNAs can be affected by oxidative stress, we hypothesized that miRNAs may participate in vitiligo pathogenesis by modulating the expression of vital genes in melanocytes. In the present study, we initially found that miR-25 was increased in both serum and lesion samples from vitiligo patients, and its serum level was correlated with the activity of vitiligo. Moreover, restoration of miR-25 promoted the H 2 O 2 -induced melanocyte destruction and led to the dysfunction of melanocytes. Further experiments proved that MITF, a master regulator in melanocyte survival and function, accounted for the miR-25-caused damaging impact on melanocytes. Notably, other than the direct role on melanocytes, we observed that miR-25 inhibited the production and secretion of SCF and bFGF from keratinocytes, thus impairing their paracrine protective effect on the survival of melanocytes under oxidative stress. At last, we verified that oxidative stress could induce the overexpression of miR-25 in both melanocytes and keratinocytes possibly by demethylating the promoter region of miR-25. Taken together, our study demonstrates that oxidative stress-induced overexpression of miR-25 in vitiligo has a crucial role in promoting the degeneration of melanocytes by not only suppressing MITF in melanocytes but also impairing the paracrine protective effect of keratinocytes. Therefore, it is worthy to investigate the possibility of miR-25 as a potential drug target for anti-oxidative therapy in vitiligo. Vitiligo is a disfiguring dermatosis with an incidence rate of approximately 0.5-1.0% in the populations worldwide. 1 Characterized by patchy depigmentation of the skin, the disease can affect the patients' self-image, or even cause depression, thus substantially decreasing life quality among vitiligo patients. 2 Although several etiological theories, including genetic predisposition, 3-5 autoimmunity, 6,7 melanocytorrhagy 8,9 and toxic metabolites 10 have been proposed to participate in the pathogenesis of vitiligo, the exact mechanism of melanocyte degeneration in depigmented lesions still remains unclear.The generation of oxidative stress has long been demonstrated to have a crucial role in the onset and progression of vitiligo. 11,12 Owing to the pro-oxidant state generated during melanin synthesis, melanocytes are particularly vulnerable to oxidative stress. 13 In vitiligo, accumulation of toxic intermediates such as 6-and 7-BH4 and catecholamine, 14,15 concomitant with reduced levels and activity of catalase and several other antioxidant enzymes [16][17][18] have been demonstrated in patients' epidermis. Because of these intracellular metabolic disorder and compromised intrinsic antioxidant defenses, hydrogen peroxide (H 2 O ...

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“…12% der Patienten noch einzelne Melanozyten, während vollständig depigmentierte Areale in der Regel keine epidermalen Melanozyten aufweisen [14]. Follikuläre Melanozyten sind in vielen Fällen noch vorhanden (.…”

Section: Histologieunclassified

Vitiligo

Hartmann

2009

Hautarzt

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Vitiligo is characterized by patches of depigmented skin in a localized to generalized distribution. Up to now, vitiligo is not curable and mostly has a chronic and progressive course. The disorder may be part of a polygenic, multifactorial transmitted disease with an increased disposition to autoimmune disorders, which should be screened for. Depending on the age of the patient, the psychological strain, the location, the body surface area involved, and the disease activity, several conservative as well as surgical therapeutic options may be partially successful. How long the induced repigmentation remains and the effect of the available therapeutic options on the natural history of vitiligo remain to be clarified.

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Histopathologic Features in Vitiligo

Cited by 77 publications

References 14 publications

Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a Receptor-Dependent Mechanism

Topical Histamine Stimulates Repigmentation of Nonsegmental Vitiligo by a Receptor-Dependent Mechanism

Oxidative stress-induced overexpression of miR-25: the mechanism underlying the degeneration of melanocytes in vitiligo

Vitiligo

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