Rapidly and successful improvement of nail psoriasis with risankizumab.

This clinical case demonstrates quick resolution of nail psoriasis in a patient treated with risankizumab, highlighting the role of IL-23 in the pathogenesis of nail psoriasis.

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. Recently we have described several metabolic abnormalities in cells from pigmented skin of vitiligo patients, including alterations of glucose metabolism. Therefore, we conducted a study to evaluate the effect of Pioglitazone (PGZ), a Peroxisome proliferator-activated receptor-γ (PPARγ) agonist, on cells from pigmented vitiligo skin. We treated vitiligo melanocytes and fibroblasts with low doses of PGZ and evaluated the effects on mitochondrial alterations, previously reported by our and other groups. Treatment with PGZ significantly increased mRNA and protein levels of several anaerobic glycolytic enzymes, without increasing glucose consumption. The PGZ administration fully restored the metabolic network, replacing mitochondrial membrane potential and mitochondrial DNA (mtDNA) copy number. These effects, together with a significant increase in ATP content and a decrease in reactive oxygen species (ROS) production, provide strong evidence of an overall improvement of mitochondria bioenergetics in vitiligo cells. Moreover, the expression of HMGB1, Hsp70, defined as a part of DAMPs, and PD-L1 were significantly reduced. In addition, PGZ likely reverts premature senescence phenotype. In summary, the results outline a novel mode of action of Pioglitazone, which may turn out to be relevant to the development of effective new vitiligo therapeutic strategies.

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. 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.

Diet-Related Phototoxic Reactions in Psoriatic Patients Undergoing Phototherapy: Results from a Multicenter Prospective Study.

Vegans and vegetarians often consume foods containing photosensitizers capable of triggering phytophotodermatitis. The potential effect of vegan and vegetarian diets on the response of psoriatic patients undergoing phototherapy is not well characterized. We assessed clinical outcomes of vegan, vegetarian and omnivore adult psoriatic patients undergoing band ultraviolet B phototherapy (NB-UVB). In this multicenter prospective observational study, we enrolled 119 adult, psoriatic patients, of whom 40 were omnivores, 41 were vegetarians and 38 were vegans, with phototherapy indication. After determining the minimum erythemal dose (MED), we performed NB-UVB sessions for 8 weeks. The first irradiation dosage was 70.00% of the MED, then increased by 20.00% (no erythema) or by 10.00% (presence of erythema) until a maximum single dose of 3 J/cm2 was reached and constantly maintained. All the enrolled patients completed the 8 weeks of therapy. Severe erythema was present in 16 (42.11%) vegans, 7 (17.07%) vegetarians and 4 (10.00%) omnivores (p < 0.01). MED was lowest among vegans (21.18 ± 4.85 J/m2), followed by vegetarians (28.90 ± 6.66 J/m2) and omnivores (33.63 ± 4.53 J/m2, p < 0.01). Patients with severe erythema were more likely to have a high furocumarin intake (OR 5.67, 95% CI 3.74-8.61, p < 0.01). Vegans consumed the highest amount of furocumarin-rich foods. A model examining erythema, adjusted for gender, age, skin type, MED, phototherapy type, number of phototherapies and furocumarin intake, confirmed that vegans had a lower number of treatments. Vegans had more frequent severe erythema from NB-UVB, even after adjustment of the phototherapy protocol for their lower MED. Assessing diet information and adapting the protocol for vegan patients may be prudent.

Metabolic Comorbidities in Vitiligo: A Brief Review and Report of New Data from a Single-Center Experience.

Among disorders of pigmentation, vitiligo is the most common, with an estimated prevalence between 0.5% and 1%. The disease has gathered increased attention in the most recent years, leading to a better understanding of the disease's pathophysiology and its implications and to the development of newer therapeutic strategies. A better, more integrated approach is already in use for other chronic inflammatory dermatological diseases such as psoriasis, for which metabolic comorbidities are well-established and part of the routine clinical evaluation. The pathogenesis of these might be linked to cytokines which also play a role in vitiligo pathogenesis, such as IL-1, IL-6, TNF-α, and possibly IL-17. Following the reports of intrinsic metabolic alterations reported by our group, in this brief review, we analyze the available data on metabolic comorbidities in vitiligo, accompanied by our single-center experience. Increased awareness of the metabolic aspects of vitiligo is crucial to improving patient care.

A protective role for autophagy in vitiligo.

A growing number of studies supports the existence of a dynamic interplay between energetic metabolism and autophagy, whose induction represents an adaptive response against several stress conditions. Autophagy is an evolutionarily conserved and a highly orchestrated catabolic recycling process that guarantees cellular homeostasis. To date, the exact role of autophagy in vitiligo pathogenesis is still not clear. Here, we provide the first evidence that autophagy occurs in melanocytes and fibroblasts from non-lesional skin of vitiligo patients, as a result of metabolic surveillance response. More precisely, this study is the first to reveal that induction of autophagy exerts a protective role against the intrinsic metabolic stress and attempts to antagonize degenerative processes in normal appearing vitiligo skin, where melanocytes and fibroblasts are already prone to premature senescence.

Italian expert-based recommendations on the use of photo(chemo)therapy in the management of mycosis fungoides: Results of an e-Delphi consensus.

BACKGROUND: Phototherapy is a mainstay for the treatment of MF. However, there is scarce evidence for its use, mostly due to the lack of a unified schedule. AIMS: The primary aim of this study was to establish the first structured, expert-based consensus regarding the indications and technical schedules of NB-UVB and PUVA for MF. The secondary aim was to determine the consensus level for each specific item. MATERIALS & METHODS: E-delphi study. Item-specific expert consensus was defined as the number of "Totally Agree" results to ≥80% of the panelists. Cronbach alpha index ≥0.7 was used as a measure of homogeneity in the responses among questions related to the same topic. RESULTS: Overall, there was a high homogeneity among responders (0.78). On specific topics, the highest grade was observed for technical items (0.8) followed by indications for early (0.73) and advanced stages (0.7). CONCLUSIONS: Items related to the most canonical indications of phototherapy and to treatment schedules showed the highest agreements rates. There is consensus about the use of standardized treatment schedules for the induction and consolidation phases for NB-UVB and PUVA in MF.

NB-UVB plus oral Polypodium leucotomos extract display higher efficacy than NB-UVB alone in patients with vitiligo.

Polypodium leucotomos displayed a synergic effect with NB-UVB in psoriasis, but its application on vitiligo remains understudied. The aim of this study was to investigate whether oral supplementation with leaves extract of Polypodium leucotomos (PL) improves narrow band (NB) UVB phototherapy-induced repigmentation. Forty-four patients with generalized vitiligo were enrolled in this randomized, prospective, placebo controlled study. Twenty-three patients were randomly selected to receive combined treatment with NB-UVB phototherapy and 480 mg oral PL twice daily while 21 patients received NB-UVB phototherapy combined with placebo. All subjects were treated with NB-UVB twice weekly for 6 months. Our results demonstrated that oral PL combined with NB-UVB improved repigmentation as well as increased the response rate compared with patients treated with NB-UVB alone (47.8% vs 22%). Our study suggests that oral supplementation of PL and NB-UVB phototherapy enhance the extent of repigmentation.

Involvement of non-melanocytic skin cells in vitiligo.

Despite melanocytes are the key players in vitiligo, a continuous cross-talk between epidermal and dermal cells may strictly affect their functionality, in both lesional skin and non-lesional skin. Focusing on this interplay, we have reviewed existing literature supporting evidence on cellular and functional alterations of surrounding epidermal keratinocytes, extracellular matrix (ECM) proteins and fibroblasts in the underlying dermal compartment that may contribute to melanocyte disappearance in vitiligo. We have also examined some clinical and therapeutic aspects of the disease to sustain the non-exclusive involvement of melanocytes within vitiligo. As a result, a different and more complex scenario has appeared that may enable to provide better understanding about origins and progress of vitiligo and that should be considered in the evaluation of new treatment approaches.

Relevance of thyroiditis and of other autoimmune diseases in children with vitiligo.

BACKGROUND: Studies that clearly define the possible association of childhood vitiligo with autoimmune and/or endocrine diseases are lacking. OBJECTIVE: To examine the presence of autoimmune disorders, in particular of thyroid disease, in paediatric patients with vitiligo and investigate the utility of such screening in these patients. METHODS: One hundred and twenty-one paediatric patients (40 males, 81 females) with vitiligo were grouped in segmental and non-segmental vitiligo. All patients were screened for thyroid disease. RESULTS: 13 out of 121 patients had different degrees of thyroid parameter alterations. These patients were all affected by the non-segmental type while none of those with the segmental form presented thyroid alterations. CONCLUSION: In paediatric patients with non-segmental vitiligo, a significant incidence of thyroid dysfunction was found. Since vitiligo usually appears before the development of the thyroid disease, it may be useful to screen thyroid autoantibodies in all paediatric patients with non-segmental vitiligo who present symptoms related to thyroid disease.

Alterations of mitochondria in peripheral blood mononuclear cells of vitiligo patients.

The possible role for a defective mitochondrial functionality in the pathogenesis of vitiligo was investigated by measuring intracellular levels of reactive oxygen species and of antioxidants, the activity of Krebs cycle enzymes, as well as the effects of inhibitors of the electron transport chain, in peripheral blood mononuclear cells from patients with active or stable disease vs. normal subjects. Plasma glyoxal levels were also determined in the same groups of subjects as an index of systemic oxidative stress. In patients with vitiligo in active phase, we observed an increased intracellular production of reactive oxygen species with a consequent imbalance of the prooxidant/antioxidant equilibrium, whereas plasma did not show apparent alterations in glyoxal levels, ruling out a systemic oxidative stress. In patients with stable disease, the balance between pro-oxidants and anti-oxidants seems to be maintained. Moreover, a marked increase in the expression of mitochondrial malate dehydrogenase activity and a specific sensitivity to electron transport chain complex I inhibitor were observed. Overall, these data provide further evidence for an altered mitochondrial functionality in vitiligo patients.