Faculty Bibliography

Vitiligo is an acquired depigmentation disorder of the skin. Patients with vitiligo often face a challenging disease course, having to cope with a condition that is known to be physically disfiguring, psychologically devastating, and socially stigmatizing. Although an extensive amount of research has been directed towards the dermatologic treatment of vitiligo, an overall lack of data exists investigating treatment of the psychological and emotional burden of patients with vitiligo. This paper reviews the literature for treatment options in patients with vitiligo that specifically target the psychosocial domain. Despite being limited in quantity, several studies have proven the benefits of adjuvant care in the form of group therapy, cognitive behavioral therapy, and self-help programs. Although preliminary evidence is promising, larger prospective studies are needed to further define the role of these psychosocial interventions before integrating them in a more official capacity into the standard of care for patients with vitiligo. Because of the considerable impact of vitiligo beyond its physical symptoms, dermatologists ought to consider the utility of adjuvant therapies to adequately address impairments in self-esteem, body image, and quality of life in patients with vitiligo. J Drugs Dermatol. 2018;17(6):688-691.

<p>Background: While most of the attention regarding skin pigmentation has focused on the effects of ultraviolet radiation, the cutaneous effects of visible light (400 to 700nm) are rarely reported.

Interfollicular epidermal melanocytes are continually subjected to environmental challenges and activate protective stress responses for survival. Dysregulation of these responses may increase susceptibility to autoimmune-mediated destruction resulting in progressive skin depigmentation typical of vitiligo. We have shown that challenging melanocytes from normally pigmented individuals (NMs) with chemicals known to trigger vitiligo, such as monobenzone, results in activation of the unfolded protein response (UPR). In this study, we investigated the impact of the PERK-eIF2alpha (activated PERK phosphorylates eIF2alpha) and IRE1alpha-XBP1 (activated IRE1alpha promotes splicing and expression of XBP1) axes of the UPR on melanocyte viability and sensitivity to monobenzone. NMs exhibited high basal PERK-eIF2alpha signaling compared to keratinocytes and dermal fibroblasts, and PERK knockdown substantially reduced melanocyte viability (p < 0.01), even in the absence of challenge. PERK inhibition increased sensitivity to monobenzone, while inhibition of IRE1alpha kinase activity, did not affect melanocyte toxicity. NMs that survive PERK knockdown were used to establish long-term cultures (shPERKLT), which exhibited a paradoxical increase in phospho-eIF2alpha with reduced sensitivity to monobenzone. Sustained eIF2alpha phosphorylation was reduced with downregulation of PKR and GCN2, alternative eIF2alpha kinases, suggesting a role for these kinases in melanocyte adaptation. Melanocytes from individuals with idiopathic vitiligo (VMs) exhibited increased sensitivity to monobenzone compared to NMs. VMs markedly activated the IRE1alpha/XBP1 pathway, reflected by an increase in XBP1 splicing. VMs also did not phosphorylate eIF2alpha in response to monobenzone treatment. Dysfunction of this protective response in VMs, in combination with increased IRE1alpha/XBP1 activity which promotes expression of chemokines, such as interleukin 6, that recruit immune cells to the skin, may contribute to the onset of autoimmunity in vitiligo. The UPR may thus represent a novel therapeutic target for vitiligo

Melasma is a common acquired condition of symmetric hyperpigmentation, typically occurring on the face, with higher prevalence in females and darker skin types. Multiple etiologies, including light exposure, hormonal influences, and family history, have been implicated in the pathogenesis of this disorder. Overall prevalence ranges widely at 1-50%, since values are typically calculated within a specific ethnic population within a geographic region. Histologically, melasma can display increased epidermal and/or dermal pigmentation, enlarged melanocytes, increased melanosomes, solar elastosis, dermal blood vessels, and, occasionally, perivascular lymphohistiocytic infiltrates. Various topical, oral, and procedural therapies have been successfully used to treat melasma. Traditional topical therapies including hydroquinone, tretinoin, corticosteroids, and triple combination creams; however, other synthetic and natural topical compounds have also shown varying efficacies. Promising oral therapies for melasma include tranexamic acid, Polypodium leucotomos, and glutathione. Procedures, including chemical peels, microneedling, radiofrequency, and lasers, are also often used as primary or adjunctive treatments for melasma. Notably, combination therapies within or across treatment modalities generally result in better efficacies than monotherapies. This review serves as a comprehensive update on the current understanding of the epidemiology, pathogenesis, clinical and histologic features of melasma, as well as treatments for this common, yet therapeutically challenging, condition.

Vitiligo, characterized by progressive melanocyte death, can be initiated by exposure to vitiligo-inducing phenols (VIPs). VIPs generate oxidative stress in melanocytes and activate the master antioxidant regulator NRF2. While NRF2-regulated antioxidants are reported to protect melanocytes from oxidative stress, the role of NRF2 in the melanocyte response to monobenzone, a clinically relevant VIP, has not been characterized. We hypothesized that activation of NRF2 may protect melanocytes from monobenzone-induced toxicity. We observed that knockdown of NRF2 or NRF2-regulated antioxidants NQO1 and PRDX6 reduced melanocyte viability, but not viability of keratinocytes and fibroblasts, suggesting that melanocytes were preferentially dependent upon NRF2 activity for growth compared to other cutaneous cells. Furthermore, melanocytes activated the NRF2 response following monobenzone exposure and constitutive NRF2 activation reduced monobenzone toxicity, supporting NRF2's role in the melanocyte stress response. In contrast, melanocytes from individuals with vitiligo (vitiligo melanocytes) did not activate the NRF2 response as efficiently. Dimethyl fumarate-mediated NRF2 activation protected normal and vitiligo melanocytes against monobenzone-induced toxicity. Given the contribution of oxidant-antioxidant imbalance in vitiligo, modulation of this pathway may be of therapeutic interest

BACKGROUND: While most of the attention regarding skin pigmentation has focused on the effects on ultraviolet radiation, the cutaneous effects of visible light (400 to 700nm) are rarely reported. In this report, we describe a case of painful erythema and induration that resulted from direct irradiation of UV-naive skin with visible LED light in a patient with Fitzpatrick type II skin

METHODS AND RESULTS: A 24-year-old healthy woman with Fitzpatrick type II skin presented to our department to participate in a clinical study. As part of the study, the subject underwent visible light irradiation with an LED and halogen incandescent visible light source. After 5 minutes of exposure, the patient complained of appreciable pain at the LED exposed site. Evaluation demonstrated erythema and mild induration. There were no subjective or objective findings at the halogen incandescent irradiated site, which received equivalent fluence (0.55 Watts / cm2). The study was halted as the subject was unable to tolerate the full duration of visible light irradiation

CONCLUSION: This case illustrates the importance of recognizing the effects of visible light on skin. While the vast majority of investigational research has focused on ultraviolet light, the effects of visible light have been largely overlooked and must be taken into consideration, in all Fitzpatrick skin types

J Drugs Dermatol. 2017;16(4):388-392

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Vitiligo is a complex, systemic disease associated with many autoimmune and autoinflammatory conditions. Additionally, the cutaneous changes of vitiligo have significant effects on quality of life and self-esteem. Further efforts are needed to increase our understanding of vitiligo comorbidities as well as to increase awareness of the psychological effects of vitiligo.

BACKGROUND: Microneedling is a minimally invasive procedure that uses fine needles to puncture the epidermis. The microwounds created stimulate the release of growth factors and induce collagen production. The epidermis remains relatively intact, therefore helping to limit adverse events. The indications for microneedling therapy have grown significantly, and it is becoming a more widely used treatment in dermatology. OBJECTIVE: A comprehensive review of microneedling in human subjects and its applications in dermatology. METHODS AND MATERIALS: A search was performed using PubMed/MEDLINE and Science Direct databases. Search terms included "microneedling," "needling," and "percutaneous collagen induction." All available studies involving human subjects were included in the discussion, with priority given to prospective, randomized trials. RESULTS: Studies demonstrate microneedling efficacy and safety for the treatment of scars, acne, melasma, photodamage, skin rejuvenation, hyperhidrosis and alopecia and for facilitation of transdermal drug delivery. While permanent adverse events are uncommon, transient erythema and postinflammatory hyperpigmentation are more commonly reported. CONCLUSION: Microneedling appears to be an overall effective and safe therapeutic option for numerous dermatologic conditions. Larger and more randomized controlled trials are needed to provide greater data on the use of microneedling for different dermatologic conditions in different skin types.

Vitiligo is one of the most common cutaneous disorders of depigmentation. Although its underlying causes are still being studied and no definitive cure currently exists, recent research has provided insight into pathogenic mechanisms and new treatment options. Objective: The aim of this paper is to provide a comprehensive overview of the medical and surgical therapies for vitiligo with emphasis on the most recent treatment modalities. Design: This review was conducted through a literature search using PubMed and the National institutes of Health's clinicalTrials.gov databases from January 2010 to July 2015. This yielded 86 studies, 12 of which were excluded, and 74 of which were reviewed. Results: Recent studies and ongoing clinical trials indicate that there are many promising new medical and surgical treatment modalities for this chronic condition. Conclusion: A combination of traditional and newer treatments may work synergistically to provide additional improvement in patients' disease state and quality of life.