Comprehensive Overview of Cytokine Interplay in Vitiligo: A Decade of Meta-Analyses Systematically Reviewed.

(1) Background: Vitiligo is an autoimmune skin disorder characterized by melanocyte destruction. Despite metabolic disturbances and oxidative stress also playing a key role in its pathogenesis, accumulating evidence highlights a prominent role for cytokine dysregulation. (2) Methods: A systematic search was conducted to identify meta-analyses published in the last decade that investigated cytokine involvement in vitiligo.

Metabolic anomalies in vitiligo: a new frontier for drug repurposing strategies.

Vitiligo is a chronic autoimmune condition characterized by the destruction of melanocytes, leading to patchy loss of skin depigmentation. Although its precise cause remains unclear, recent evidence suggests that metabolic disturbances, particularly oxidative stress and mitochondrial dysfunction, may play a significant role in the pathogenesis of the disease. Oxidative stress is thought to damage melanocytes and trigger inflammatory responses, culminating in melanocyte immune-mediate destruction.

Defective Intracellular Insulin/IGF-1 Signaling Elucidates the Link Between Metabolic Defect and Autoimmunity in Vitiligo.

Vitiligo is featured by the manifestation of white maculae and primarily results from inflammatory/immune-selective aggression to melanocytes. The trigger mechanism leading to the activation of resident immune cells in the skin still lacks a molecular description. There is growing evidence linking altered mitochondrial metabolism to vitiligo, suggesting that an underlying metabolic defect may enable a direct activation of the immune system.

Vitiligo in the 19-century dermatological works of Vincenzo Chiarugi, Robert Willan, Jean-Louis Alibert, and Ferdinand von Hebra.

Vitiligo is an iconic dermatological pathology, as its clinical manifestations indelibly mark the patient through the appearance of white spots all over the body. The oldest written testimonies referring to vitiligo are the first texts of Ayurveda, the Ebers Papyrus, and the Leviticus of the Old Testament. During the Roman Empire, the doctors Aulus Cornelius Celsus and Galen, respectively, in the I and II centuries AD, were the first to describe this skin disease, and their statements were used by all subsequent authors.

Focusing on the Dark Side of the Moon: Involvement of the Nonlesional Skin in Vitiligo.

Research over the last decade has revealed that the normally pigmented skin of patients with vitiligo is not normal at all, as evidenced by alterations in cutaneous morphology and modifications in cellular and metabolic functions that ultimately drive immune activation against melanocytes. Furthermore, nonlesional skin is in a state of subclinical inflammation until triggered by internal and/or external exposomal events. Therefore, targeting early processes that drive immune dysregulation in normally pigmented skin may avoid or reduce melanocyte loss.

Biosignatures of defective sebaceous gland activity in sebum-rich and sebum-poor skin areas in adult atopic dermatitis.

Atopic dermatitis (AD) is a composite disease presenting disruption of the skin permeability barrier (SPB) in the stratum corneum (SC). Recent evidence supports derangement of the sebaceous gland (SG) activity in the AD pathomechanisms. The objective of this study was to delineate profiles of both sebaceous and epidermal lipids and of aminoacids from SG-rich (SGR) and SG-poor (SGP) areas in AD.

Emerging Role of Fibroblasts in Vitiligo: A Formerly Underestimated Rising Star.

Vitiligo is a disfiguring depigmentation disorder characterized by loss of melanocytes. Although numerous studies have been conducted on the pathogenesis of vitiligo, the underlying mechanisms remain unclear. Although most studies have focused on melanocytes and keratinocytes, growing evidence suggests the involvement of dermal fibroblasts, residing deeper in the skin.

Skin Anti-Inflammatory Potential with Reduced Side Effects of Novel Glucocorticoid Receptor Agonists.

Glucocorticoids (GCs) are commonly used in the treatment of inflammatory skin diseases, although the balance between therapeutic benefits and side effects is still crucial in clinical practice. One of the major and well-known adverse effects of topical GCs is cutaneous atrophy, which seems to be related to the activation of the glucorticoid receptor (GR) genomic pathway. Dissociating anti-inflammatory activity from atrophogenicity represents an important goal to achieve, in order to avoid side effects on keratinocytes and fibroblasts, known target cells of GC action.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the International Vitiligo Task Force Part 1: towards a new management algorithm.

Background: The treatment of vitiligo can be challenging and depends on several factors such as the subtype, disease activity, vitiligo extent, and treatment goals. Vitiligo usually requires a long-term approach. To improve the management of vitiligo worldwide, a clear and up-to-date guide based on international consensus with uniform stepwise recommendations is needed.

Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the international Vitiligo Task Force-Part 2: Specific treatment recommendations.

Background: The treatment of vitiligo can be challenging. Up-to-date agreed consensus recommendations on the use of topical and systemic therapies to facilitate the clinical management of vitiligo are currently lacking.

Objectives: To develop internationally agreed-upon expert-based recommendations for the treatment of vitiligo.

The Activation of PPARγ by (2Z,4E,6E)-2-methoxyocta-2,4,6-trienoic Acid Counteracts the Epithelial-Mesenchymal Transition Process in Skin Carcinogenesis.

Cutaneous squamous cell carcinoma (cSCC) is the most common UV-induced keratinocyte-derived cancer, and its progression is characterized by the epithelial-mesenchymal transition (EMT) process. We previously demonstrated that PPARγ activation by 2,4,6-octatrienoic acid (Octa) prevents cutaneous UV damage. We investigated the possible role of the PPARγ activators Octa and the new compound (2Z,4E,6E)-2-methoxyocta-2,4,6-trienoic acid (A02) in targeting keratinocyte-derived skin cancer.

Sebaceous immunobiology - skin homeostasis, pathophysiology, coordination of innate immunity and inflammatory response and disease associations.

This review presents several aspects of the innovative concept of sebaceous immunobiology, which summarizes the numerous activities of the sebaceous gland including its classical physiological and pathophysiological tasks, namely sebum production and the development of seborrhea and acne. Sebaceous lipids, which represent 90% of the skin surface lipids in adolescents and adults, are markedly involved in the skin barrier function and perifollicular and dermal innate immune processes, leading to inflammatory skin diseases. Innovative experimental techniques using stem cell and sebocyte models have clarified the roles of distinct stem cells in sebaceous gland physiology and sebocyte function control mechanisms.

A Possible Modulator of Vitiligo Metabolic Impairment: Rethinking a PPARγ Agonist.

Vitiligo is a complex disease wherein derangements in multiple pathways determine the loss of functional melanocytes. Since its pathogenesis is not yet completely understood, vitiligo lacks a definitive safe and efficacious treatment. At present, different therapies are available; however, each modality has its baggage of disadvantages and side effects.

Regenerative Medicine-Based Treatment for Vitiligo: An Overview.

Vitiligo is a complex disorder with an important effect on the self-esteem and social life of patients. It is the commonest acquired depigmentation disorder characterized by the development of white macules resulting from the selective loss of epidermal melanocytes. The pathophysiology is complex and involves genetic predisposition, environmental factors, oxidative stress, intrinsic metabolic dysfunctions, and abnormal inflammatory/immune responses.

Shining Light on Autophagy in Skin Pigmentation and Pigmentary Disorders.

Autophagy is a vital process for cell survival and it preserves homeostasis by recycling or disassembling unnecessary or dysfunctional cellular constituents. Autophagy ameliorates skin integrity, regulating epidermal differentiation and constitutive pigmentation. It induces melanogenesis and contributes to skin color through melanosome turnover.

Altered epidermal proliferation, differentiation, and lipid composition: Novel key elements in the vitiligo puzzle.

Vitiligo is an acquired skin depigmentation disease involving multiple pathogenetic mechanisms, which ultimately direct cytotoxic CD8 cells to destroy melanocytes. Abnormalities have been described in several cells even in pigmented skin as an expression of a functional inherited defect. Keratinocytes regulate skin homeostasis by the assembly of a proper skin barrier and releasing and responding to cytokines and growth factors.

Efficacy and safety of N-acetyl-GED-0507-34-LEVO gel in patients with moderate-to severe facial acne vulgaris: a phase IIb randomized double-blind, vehicle-controlled trial.

Background: Preliminary in vitro and in vivo studies have supported the efficacy of the peroxisome proliferator-activated receptor-γ (PPARγ) modulator N-acetyl-GED-0507-34-LEVO (NAC-GED) for the treatment of acne-inducing sebocyte differentiation, improving sebum composition and controlling the inflammatory process.

Objectives: To evaluate the efficacy and safety of NAC-GED (5% and 2%) in patients with moderate-to-severe facial acne vulgaris.

Methods: This double-blind phase II randomized controlled clinical trial was conducted at 36 sites in Germany, Italy and Poland.

Sebocytes contribute to melasma onset.

Melasma is a hyperpigmentary disorder with photoaging features, whose manifestations appear on specific face areas, rich in sebaceous glands (SGs). To explore the SGs possible contribution to the onset, the expression of pro-melanogenic and inflammatory factors from the SZ95 SG cell line exposed to single or repetitive ultraviolet (UVA) radiation was evaluated. UVA up-modulated the long-lasting production of α-MSH, EDN1, b-FGF, SCF, inflammatory cytokines and mediators.

Research update of adipose tissue-based therapies in regenerative dermatology.

Mesenchymal stromal/stem cells (MSCs) have a spontaneous propensity to support tissue homeostasis and regeneration. Among the several sources of MSCs, adipose-derived tissue stem cells (ADSCs) have received major interest due to the higher mesenchymal stem cells concentration, ease, and safety of access. However, since a significant part of the natural capacity of ADSCs to repair damaged tissue is ascribable to their secretory activity that combines mitogenic factors, cytokines, chemokines, lipids, and extracellular matrix components, several studies focused on cell-free strategies.