Clinical heterogeneity in vitiligo: Identification of clinical markers based patient clusters.

Background: Vitiligo (non-segmental) is a chronic autoimmune skin disease leading to white patches. Although vitiligo has been delineated previously, the endophenotypes of the disease are still to be defined.

Objective: The aim of this study was to investigate, without prior hypotheses, whether different clinical phenotypes of vitiligo could be identified and differ based on their demographic and clinical characteristics.

Progressive repigmentation of hypopigmented lesions in discoid lupus erythematosus with anifrolumab: A report of two cases.

We report two cases of patients with refractory discoid lupus erythematosus (DLE) and dark skin phototypes who experienced progressive perifollicular repigmentation of depigmented lesions under anifrolumab therapy, with sustained improvement over 18 months. These observations highlight a potential novel effect of anifrolumab on cicatricial dyspigmentation in DLE. This effect may represent a valuable therapeutic option for DLE-related damage, particularly in patients with darker skin types.

Unveiling the Unseen: Exploring Cellular Dynamics in Nonlesional Vitiligo Skin.

Vitiligo is a multifactorial disease involving genetic predispositions, intrinsic melanocyte abnormalities, and deregulated immune response. Recent studies show nonlesional skin involvement. Nonlesional melanocytes display mitochondrial dysfunction and increased oxidative stress affecting their adhesion and function and contribute to immune activation.

Combination of Baricitinib and Phototherapy in Adults With Active Vitiligo: A Randomized Clinical Trial.

Importance: Vitiligo is a chronic autoimmune disorder leading to skin depigmentation and reduced quality of life (QOL). Patients with extensive and very active disease are the most difficult to treat.

Objective: To assess the efficacy and adverse events of baricitinib combined with narrowband UV-B in adults with severe, active, nonsegmental vitiligo.

Type I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade.

Programmed cell death 1 (PD-1) is a premier cancer drug target for immune checkpoint blockade (ICB). Because PD-1 receptor inhibition activates tumor-specific T-cell immunity, research has predominantly focused on T-cell-PD-1 expression and its immunobiology. In contrast, cancer cell-intrinsic PD-1 functional regulation is not well understood.

Type-2 immunity associated with type-1 related skin inflammatory diseases: friend or foe?

Chronic inflammatory skin diseases are multifactorial diseases that combine genetic predisposition, environmental triggers, and metabolic disturbances associated with abnormal immune responses. From an immunological perspective, the better understanding of their physiopathology has demonstrated a large complex network of immune cell subsets and related cytokines that interact with both epidermal and dermal cells. For example, in type-1-associated diseases such as alopecia areata, vitiligo, and localized scleroderma, recent evidence suggests the presence of a type-2 inflammation that is well known in atopic dermatitis.

Aetiopathogenesis of Vitiligo.

Vitiligo is a chronic auto-immune disease characterized by skin depigmentation due to the loss of melanocytes. The better understanding of the disease mechanisms is currently undergoing a significant dynamism, opening a new era in therapeutic development. The pathophysiology of vitiligo has attracted the attention of researchers for years and many advances have been made in clarifying the crosstalk between the cellular players involved in the development of vitiligo lesions.

Vitiligo: Current Therapies and Future Treatments.

The current management of vitiligo remains challenging; however, different strategies can be proposed to patients with a good efficacy in many cases. First, it is important to identify patients in the active phase of the disease because treatment should start as soon as possible to halt its progression. For patients with a stable disease, the treatment strategy is now well-stratified and is based on a combination of phototherapy (natural or in a cabin) and topical immunomodulatory agents.

Resident memory T cells in nonlesional skin and healed lesions of patients with chronic inflammatory diseases: Appearances can be deceptive.

Tissue-resident memory T (T) cells serve as a first line of defense in peripheral tissues to protect the organism against foreign pathogens. However, autoreactive T cells are increasingly implicated in autoimmunity, as evidenced in chronic autoimmune and inflammatory skin conditions. This highlights the need to characterize their phenotype and understand their role for the purpose of targeting them specifically without affecting local immunity.

Evaluation of Facial Vitiligo Severity with a Mixed Clinical and Artificial Intelligence Approach.

Vitiligo is the most common depigmenting skin disorder. Given the ongoing development of new targeted therapies, it has become important to evaluate adequately the surface area involved. Assessment of vitiligo scores can be time consuming, with variations between investigators.

Impact of house dust mite in vitiligo skin: environmental contribution to increased cutaneous immunity and melanocyte detachment.

Background: Vitiligo is an autoimmune skin disorder characterized by loss of melanocytes. Protease-mediated disruption of junctions between keratinocytes and/or keratinocyte intrinsic dysfunction may directly contribute to melanocyte loss. House dust mite (HDM), an environmental allergen with potent protease activity, contributes to respiratory and gut disease but also to atopic dermatitis and rosacea.

Cytokine-Mediated Crosstalk Between Keratinocytes and T Cells in Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by barrier dysfunction, dysregulated immune response, and dysbiosis with increased colonization. Infiltration of various T helper cell subsets into lesional skin and subsequent cytokine release are a hallmark of AD. Release of cytokines by both T cells and keratinocytes plays a key role in skin inflammation and drives many AD features.

Analysis of tumor response and clinical factors associated with vitiligo in patients receiving anti-programmed cell death-1 therapies for melanoma: A cross-sectional study.

Background: Clinical factors associated with vitiligo in patients receiving anti-programmed cell death-1 (PD-1) remain unknown.

Objective: To better characterize the occurrence of vitiligo in patients receiving anti-PD-1.

Methods: The present single-center ambispective cohort study included patients with melanoma treated with anti-PD-1.

Vitiligo Skin T Cells Are Prone to Produce Type 1 and Type 2 Cytokines to Induce Melanocyte Dysfunction and Epidermal Inflammatory Response Through Jak Signaling.

Vitiligo is a T cell-mediated inflammatory skin disorder characterized by the loss of epidermal melanocytes. However, the contribution of melanocytes to the physiopathology of the disease in response to the T-cell microenvironment remains unclear. Here, using NanoString technology and multiplex ELISA, we show that active vitiligo perilesional skin is characterized by prominent type 1 and 2 associated immune responses.

Targeting Innate Immunity to Combat Cutaneous Stress: The Vitiligo Perspective.

Multiple factors are involved in the process leading to melanocyte loss in vitiligo including environmental triggers, genetic polymorphisms, metabolic alterations, and autoimmunity. This review aims to highlight current knowledge on how danger signals released by stressed epidermal cells in a predisposed patient can trigger the innate immune system and initiate a cascade of events leading to an autoreactive immune response, ultimately contributing to melanocyte disappearance in vitiligo. We will explore the genetic data available, the specific role of damage-associated-molecular patterns, and pattern-recognition receptors, as well as the cellular players involved in the innate immune response.

An update on Vitiligo pathogenesis.

Vitiligo, the most common depigmenting disorder of the skin, is undergoing a period of intense advances in both disease understanding and therapeutic possibilities leading the way to the beginning of a new era for the disorder. Its pathophysiology has gathered the attention of researchers for years, and many advances have been made in the clarification of the interaction between different factors that result in depigmented macule formation. The complex interplay between non-immunological and immunological factors in vitiligo is key for the development of the disease, and the participation of cells other than melanocytes, such as keratinocytes, fibroblasts, natural killer cells, and innate lymphoid cells, has been shown.

Vitiligo, From Physiopathology to Emerging Treatments: A Review.

Vitiligo is a chronic inflammatory skin disease leading to the loss of epidermal melanocytes. To date, treatment options for vitiligo patients are limited, lack sustained efficacy, and are mainly based on off-label use of immunosuppressive agents, such as systemic or topical steroids or topical calcineurin inhibitors, in association with the use of ultraviolet light. However, recent insights into the understanding of the immune pathogenesis of the disease have led to the identification of several therapeutic targets and the development of targeted therapies that are now being tested in clinical trials.

Type-1 cytokines regulate MMP-9 production and E-cadherin disruption to promote melanocyte loss in vitiligo.

Loss of melanocytes is the pathological hallmark of vitiligo, a chronic inflammatory skin depigmenting disorder induced by exaggerated immune response, including autoreactive CD8 T cells producing high levels of type 1 cytokines. However, the interplay between this inflammatory response and melanocyte disappearance remains to be fully characterized. Here, we demonstrate that vitiligo skin contains a significant proportion of suprabasal melanocytes, associated with disruption of E-cadherin expression, a major protein involved in melanocyte adhesion.

NKG2D Defines a Subset of Skin Effector Memory CD8 T Cells with Proinflammatory Functions in Vitiligo.

Vitiligo is an autoimmune disease that results from the loss of melanocytes, associated with skin infiltration of CD8 effector memory T cells with a Tc1 skewed immune response. NKG2D is an activating receptor found on immune cells, in particular natural killer and activated CD8 T cells, that are able to produce a high amount of IFN-γ. Here we found that NKG2D expression was increased in vitiligo skin CD8 effector memory T cells and was promoted by IL-15.

Disrupting the IL-36 and IL-23/IL-17 loop underlies the efficacy of calcipotriol and corticosteroid therapy for psoriasis.

Psoriasis is one of the most common skin inflammatory diseases worldwide. The vitamin D3 analog calcipotriol has been used alone or in combination with corticosteroids in treating plaque psoriasis, but how it suppresses psoriatic inflammation has not been fully understood. Using an experimental mouse psoriasis model, we show that topical calcipotriol inhibited the pivotal IL-23/IL-17 axis and neutrophil infiltration in psoriatic skin, and interestingly, such effects were mediated through the vitamin D receptor (VDR) in keratinocytes (KCs).