Vitiligo in a Patient Receiving Adalimumab for Idiopathic Uveitis.

In recent years, adalimumab has been increasingly used in the chronic treatment of non-infectious uveitis. This case report aimed to describe a drug-induced adverse event in a 34-year-old man who presented with blurred vision and floaters in the right eye and was being treated for intermediate uveitis. The patient had started topical treatment with a diagnosis of uveitis at another center. Best corrected visual acuity at presentation was 0.8 (decimal) in the right eye and 1.0 in the left eye. On examination, the anterior chamber in the right eye was clear, with anterior vitreous cells and mild haze, and snow banking and vitreous opacities in the inferior periphery. Fluorescein angiography (FA) showed hyperfluorescence in the right disc and leakage in the inferior periphery. As the inflammation did not resolve with local treatment, systemic cyclosporine was administered, after which the patient exhibited vomiting and weakness. Cyclosporine was discontinued and adalimumab treatment was started. On examination 5 months later, bilateral vitreous cells and mild vitreous opacity were noted, and FA showed mild leakage in the inferior periphery bilaterally. In addition, a depigmented patchy vitiligo lesion was observed on the chin. Due to the persistence of intraocular inflammation and on the recommendation of the dermatology clinic, adalimumab treatment was continued and topical tacrolimus was started for the lesion. On examination 3 months later, the inflammatory findings had resolved and there was no progression of the vitiligo lesion. The patient's treatment was continued. Taken together with the previous literature findings, no pathology was found in the patient's systemic examination, suggesting that this lesion was a side effect of the treatment. Ophthalmologists should be alert for this side effect in patients receiving adalimumab.

Transcutaneous Auricular Vagus Nerve Stimulation Alleviates Monobenzone-Induced Vitiligo in Mice.

Vitiligo is a complex skin disorder that involves oxidative stress and inflammatory responses and currently lacks a definitive cure. Transcutaneous auricular vagus nerve stimulation (taVNS) is a noninvasive method for targeting the auricular branch of the vagus nerve and has gained widespread attention for potential intervention in the autonomic nervous system. Although previous research has suggested that vagus nerve stimulation can potentially inhibit inflammatory responses, its specific role and mechanisms in vitiligo treatment remain unknown. This study aimed to explore the therapeutic effects of taVNS in a mouse model of vitiligo induced by monobenzone. Initially, a quantitative assessment of the treatment effects on vitiligo mice was conducted using a scoring system, revealing that taVNS significantly alleviated symptoms, particularly by reducing the depigmented areas. Subsequent immunohistochemical analysis revealed the impact of taVNS treatment on melanocyte granules, mitigating pigment loss in the skin of monobenzone-induced vitiligo mice. Further analysis indicated that taVNS exerted its therapeutic effects through multiple mechanisms, including the regulation of oxidative stress, enhancement of antioxidant capacity, promotion of tyrosine synthesis, and suppression of inflammatory responses. The conclusions of this study not only emphasize the potential value of taVNS in vitiligo therapy, but also lay a foundation for future research into the mechanisms and clinical applications of taVNS.

Multi-center retrospective review of vitiligo-like lesions in breast cancer patients treated with cyclin-dependent kinase 4 and 6 inhibitors.

PURPOSE: Cutaneous adverse effects from cyclin-dependent 4 and 6 kinase inhibitors (CDK4/6i) used in metastatic breast cancer are prevalent and well described. Vitiligo-like lesions have been reported and are rare. They can negatively impact patients' quality of life and may be associated with survival benefits. We describe the clinical characteristics of vitiligo-like lesions in an international cohort of patients treated with CDK4/6i to help improve recognition and management. METHODS: Retrospective review of patients diagnosed with vitiligo-like lesions from CDK4/6i from five academic institutions in the USA and Europe was performed. Ten patients were included in the study. RESULTS: Median age of our patients was 55 (range 37-86). Median progression-free survival was 24 months in 5 patients. The median time to rash was 10 months. Sun-exposed areas such as the arms and face were the most affected areas. Multiple skin-directed therapies such as topicals, laser, and phototherapy were trialed with minor success. Mild repigmentation was seen in one patient treated with ruxolitinib cream. CDK4/6 treatment was discontinued due to the vitiligo-like lesions in one patient. CONCLUSION: Clinical characteristics are similar to previously reported findings in case reports and series. We add topical ruxolitinib as a potential treatment option for these patients and include data regarding progression-free survival that should continue to be collected. No definitive conclusions can be made regarding survival benefits from our cohort. Clinicians should refer these patients to dermatologists to aid with management.

ViCEKb: Vitiligo-linked Chemical Exposome Knowledgebase.

Vitiligo is a complex disease wherein the environmental factors, in conjunction with the underlying genetic predispositions, trigger the autoimmune destruction of melanocytes, ultimately leading to depigmented patches on the skin. While genetic factors have been extensively studied, the knowledge on environmental triggers remains sparse and less understood. To address this knowledge gap, we present the first comprehensive knowledgebase of vitiligo-triggering chemicals namely, Vitiligo-linked Chemical Exposome Knowledgebase (ViCEKb). ViCEKb involves an extensive and systematic manual effort in curation of published literature and subsequent compilation of 113 unique chemical triggers of vitiligo. ViCEKb standardizes various chemical information, and categorizes the chemicals based on their evidences and sources of exposure. Importantly, ViCEKb contains a wide range of metrics necessary for different toxicological evaluations. Notably, we observed that ViCEKb chemicals are present in a variety of consumer products. For instance, Propyl gallate is present as a fragrance substance in various household products, and Flutamide is used in medication to treat prostate cancer. These two chemicals have the highest level of evidence in ViCEKb, but are not regulated for their skin sensitizing effects. Furthermore, an extensive cheminformatics-based investigation revealed that ViCEKb chemical space is structurally diverse and comprises unique chemical scaffolds in comparison with skin specific regulatory lists. For example, Neomycin and 2,3,5-Triglycidyl-4-aminophenol have unique chemical scaffolds and the highest level of evidence in ViCEKb, but are not regulated for their skin sensitizing effects. Finally, a transcriptomics-based analysis of ViCEKb chemical perturbations in skin cell samples highlighted the commonality in their linked biological processes. Overall, we present the first comprehensive effort in compilation and exploration of various chemical triggers of vitiligo. We believe such a resource will enable in deciphering the complex etiology of vitiligo and aid in the characterization of human chemical exposome. ViCEKb is freely available for academic research at: https://cb.imsc.res.in/vicekb.

Association between acetaminophen use and vitiligo in US women and men.

BACKGROUND/OBJECTIVES: Exposure to chemical phenols, which can act as tyrosine analogues and result in anti-melanocyte autoimmunity, has been associated with vitiligo. Acetaminophen (N-acetyl-p-aminophenol) is an over-the-counter analgesic of phenolic origin. The risk of vitiligo with systemic exposure to acetaminophen has not yet been evaluated. METHODS: We examined the risk of vitiligo with regular use acetaminophen in women, the Nurses' Health Study (NHS) and in men, the Health Professionals Follow-up Study (HPFS). Regular acetaminophen use was asked biennially from 1990 in NHS and from 1986 in HPFS, and the year of clinician-diagnosed vitiligo was asked retrospectively in 2012 in the cohorts. RESULTS: In NHS, a total of 161 vitiligo cases were identified during a follow-up of 571,724 person-years; in HPFS, a total of 183 vitiligo cases were identified during a follow-up of 680,313 person-years. Regular use of acetaminophen was associated with an increased vitiligo risk in NHS but not HPFS. The multivariable relative risk (RR) was 1.52 (95% confidence interval [CI] 1.03-2.25) in NHS and 1.09 (95% CI 0.76-1.55) in HPFS. The higher risk of vitiligo was similar by duration of acetaminophen use in women; the multivariable RRs were 1.47 (95% CI 0.98-2.21) for acetaminophen use under 5 years, and 1.78 (95% CI 1.11-2.84) for acetaminophen use over 5 years. CONCLUSIONS: Acetaminophen may be associated with a higher risk of vitiligo in women.

Vitiligo-like lesions induced by cyclin-dependent kinase 4/6 inhibitor Palbociclib: a case report and literature review.

Endocrine therapy has played an essential role in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. With the continuous development of endocrine targeting drugs, especially the emergence of selective cyclin-dependent kinase (CDK4/6) inhibitors, the overall survival time in patients with HR+HER2- advanced breast cancer has been greatly improved. Their adverse reactions also need more attention in response to the climbing number of CDK4/6 inhibitors. The common side effects of CDK4/6 inhibitors were hematological toxicity, diarrhea, and liver function damage. Skin toxicity related to CDK4/6 inhibitors was rare. We describe herein our preliminary observation of one HR+HER2- advanced metastatic breast cancer patient diagnosed with vitiligo-like lesions after 10 months of taking Palbociclib. Hoping to share our experience to increase the clinician awareness of this unusual adverse and contribute to the information in the literature.

Restraint stress promotes monobenzone-induced depigmentation in mice via the activation of glucocorticoid receptor/macrophage migration inhibitory factor signaling pathway.

Psychological stress triggers onset and development of vitiligo in humans. However, the mechanism of psychological stress on vitiligo remains unclear. The study aims to investigate whether psychological stress promotes vitiligo and explore the underlying mechanism. A depigmentation mouse model induced by applying a skin-bleaching reagent monobenzone to dorsal skin and an in vitro HaCaT keratinocyte death model induced by monobenzone were employed to explore the effect of restraint stress, which mimics psychological stress, on depigmentation. The results indicated that restraint stress promoted vitiligo-related depigmentation, vacuolisation, spongiosis, CD8+ T lymphocyte infiltration, and loss of melanocytes in the skin. Restraint stress activated cutaneous NLR family containing pyrin domain protein 3 (NLRP3) inflammasome. In addition, restraint stress aggravated anxiety-like behaviors and increased levels of macrophage migration inhibitory factor (MIF) and corticosterone in the circulation, accompanied with decreasing the expression of cutaneous 8-oxoguanine DNA glycosylase (OGG1) in depigmentation mice. In vitro experiments demonstrated that activation of glucocorticoid receptor (GR) by cortisol upregulated NLRP3 expression dependent on MIF, and directly decreased the transcription of OGG1. Blockade of MIF reversed the NLRP3 signal in restraint stress-induced depigmentation mice. In conclusion, restraint stress promotes vitiligo-related depigmentation in mice via the activation of GR/MIF signaling pathway. The findings provide a theoretical basis for prevention and treatments of vitiligo with therapies of targeting GR, MIF, and OGG1.

COVID-19 vaccine-associated vitiligo: A cross-sectional study in a tertiary referral center and systematic review.

As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus continues to infect patients globally, vaccination remains one of the primary methods to combat this prolonged pandemic. However, there are growing reports of coronavirus disease 2019 (COVID-19) vaccines possibly triggering autoimmunity, irrespective of the vaccine's design. This phenomenon has been observed in patients with vitiligo, with a rising number of cases reporting new-onset or worsening vitiligo following COVID-19 vaccinations. In this study, the authors present the most extensive case series of COVID-19 vaccine-associated vitiligo to date, along with a systematic review of the literature. The aim is to assist physicians in the clinical evaluation of patients with vitiligo with regard to future vaccinations.