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. Recent advances have also brought to the understanding of the complex part played by a specific subtype of T cells: T‐resident memory cells. This review analyzes some of the most recent insights in vitiligo pathogenesis underlining the interactions between different cell types, which are the basis for the therapeutic approaches under development.

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. Alterations in epidermal proliferation, differentiation, and lipid composition as triggers for immune response activation in vitiligo have not yet been investigated. By applying cellular and lipidomic approaches, we revealed a deregulated keratinocyte differentiation with altered lipid composition, associated with impaired energy metabolism and increased glycolytic enzyme expression. Vitiligo keratinocytes secreted inflammatory mediators, which further increased following mild mechanical stress, thus evidencing immune activation. These findings identify intrinsic alterations of the nonlesional epidermis, which can be the prime instigator of the local inflammatory milieu that stimulates immune responses targeting melanocytes.

Background: Chemotherapy-induced alopecia (CIA) is one of the most dramatic side effects of chemotherapy. Currently no guidelines are available for its prevention and treatment. Several devices and drugs are used, but results are often disappointing. Aims: Our aim is to analyze drugs and devices proposed in the literature for prevention and treatment of CIA induced by cytotoxic drugs and to discuss the evidenced-based opinion. Methods and Results: Scalp cooling is the only agent that has been approved by the US Food and Drug Administration for CIA prevention. Minoxidil and bimatoprost should not be used during chemotherapy administration, but they can be used after chemotherapy discontinuation to obtain greater regrowth. Conclusions: Therapy should always be modulated for the patient and no fixed protocol should be used. Trichoscopy and trichogram could be useful tools in supporting this treatment.

Objective: Psychiatric disorders and suicide risk (especially in psoriasis) are frequent and disabling conditions in patients with skin diseases. The aim of this study was to examine the risk of suicide and stressful life events in a sample of patients with skin disease. Methods: A sample of 242 dermatological patients (142 women and 100 men), 112 of which had psoriasis, 77 had melanoma, and 53 were suffering with chronic allergic diseases. Patients were administered the MINI International Neuropsychiatric Interview (MINI), Hamilton Depression Rating Scale (HDRS), Hamilton Anxiety Rating Scale (HARS), and the Columbia-Suicide Severity Rating Scale (C-SSRS). Patients were also asked about their experiences with stressful life events. Results: Patients with psoriasis were more likely to have a history of psychiatric disorders (36.6% vs. 13.2% χ²₍₁₎ = 9.55; p = 0.002) compared to patients with allergies. Specifically, patients with psoriasis more likely had a diagnosis of a mood disorder (16.1% vs. 3.9% χ²₍₁₎ = 6.85; p = 0.009; 16.1% vs. 0% χ²₍₁₎ = 9.56; p = 0.002) and reported past suicidal ideation (33.9% vs. 15.6% χ²₍₁₎ = 7.89; p = 0.005; 33.9% vs. 18.9% χ²₍₁₎ = 3.96; p = 0.047) as compared to those with melanoma and allergy. Conclusions: The results from this study suggest that patients affected by psoriasis have an increased risk of psychiatric comorbidities and suicidal ideation compared to those who have other dermatological disorders.

Aging is a natural intrinsic process associated with the loss of fibrous tissue, a slower cell turnover, and a reduction in immune system competence. In the skin, the continuous exposition of environmental factors superimposes extrinsic damage, mainly due to ultraviolet radiation causing photoaging. Although not usually considered a pathogenic event, photoaging affects cutaneous biology, increasing the risk of skin carcinogenesis. At the cellular level, aging is typified by the rise of senescence cells a condition characterized by reduced or absent capacity to proliferate and aberrant hyper-secretory activity. Senescence has a double-edged sword in cancer biology given that senescence prevents the uncontrolled proliferation of damaged cells and favors their clearance by paracrine secretion. Nevertheless, the cumulative insults and the poor clearance of injured cells in the elderly increase cancer incidence. However, there are not conclusive data proving that aged skin represents a permissive milieu for tumor onset. On the other hand, tumor cells are capable of activating resident fibroblasts onto a pro-tumorigenic phenotype resembling those of senescent fibroblasts suggesting that aged fibroblasts might facilitate cancer progression. This review discusses changes that occur during aging that can prime neoplasm or increase the aggressiveness of melanoma and non-melanoma skin cancer.

While vitiligo is primarily caused by melanocyte deficiency or dysfunction, recent studies have revealed a notable prevalence of metabolic syndrome (MetS) among patients with vitiligo. This suggests shared pathogenic features between the two conditions. Individuals with vitiligo often exhibit variations in triglyceride levels, cholesterol, and blood pressure, which are also affected in MetS. Given the similarities in their underlying mechanisms, genetic factors, pro-inflammatory signalling pathways, and increased oxidative stress, this study aims to highlight the common traits between vitiligo and metabolic systemic disorders. Serum analyses confirmed increased low-density lipoprotein (LDL) levels in patients with vitiligo, compared to physiological values. In addition, we reported significant decreases in folate and vitamin D (Vit D) levels. Oxidative stress is one of the underlying causes of the development of metabolic syndromes and is related to the advancement of skin diseases. This study found high levels of inflammatory cytokines, such as interleukin-6 (IL-6) and chemokine 10 (CXCL10), which are markers of inflammation and disease progression. The accumulation of insulin growth factor binding proteins 5 (IGFBP5) and advanced glycation end products (AGEs) entailed in atherosclerosis and diabetes onset, respectively, were also disclosed in vitiligo. In addition, the blood-associated activity of the antioxidant enzymes catalase (Cat) and superoxide dismutase (SOD) was impaired. Moreover, the plasma fatty acid (FAs) profile analysis showed an alteration in composition and specific estimated activities of FAs biosynthetic enzymes resembling MetS development, resulting in an imbalance towards pro-inflammatory n6-series FAs. These results revealed a systemic metabolic alteration in vitiligo patients that could be considered a new target for developing a more effective therapeutic approach.