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Exploring Therapeutic Approaches for Vitiligo: An Inclusive Review from Translational Modalities to Alternative Therapies

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Abstract

Purpose of Review

The primary objective of this extensive literature review was to explore emerging therapeutic modalities for Vitiligo, with the aim of identifying promising avenues for treatment. These modalities encompass various techniques such as melanocyte transplantation for repopulation and innovative pharmacological interventions aimed at modulating immune responses. This review aims to shed light on the theories underlying Vitiligo pathogenesis and evaluate the efficacy of a range of therapeutic interventions and preventive measures associated with the condition.

Recent Findings

Cutting-edge research in the field of Vitiligo has uncovered several promising avenues for future investigation. These include the detection of catecholamines in the urine and blood of affected individuals, which may be associated with neural dysfunction and contribute to melanocyte destruction. Another intriguing theory centers on epidermal immune infiltration, which triggers an autoimmunity that targets and eliminates melanocytes. Additionally, regulating the levels of X-box protein 1 (XBP1), which is elevated during oxidative and endoplasmic reticulum stress, may reduce cytokine production, a critical factor in the demise of melanocytes. Finally, the application of genome-wide association studies (GWAS) offers new prospects for simultaneously addressing both the degenerative and autoimmune dimensions of the condition.

Summary

Recognizing the increasing importance of patient-centered care, which considers the emotional and social aspects of Vitiligo, calls for a thorough approach to its management. Exploring the complexities of Vitiligo and investigating innovative treatment options hold promise for improved outcomes and enhanced quality of life for those affected.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Katz EL, Harris JE. Translational research in vitiligo Front Immunol. 2021;12:624517.

    Article  CAS  PubMed  Google Scholar 

  2. Bertolani M, Rodighiero E, De Felici del Giudice MB, Lotti T, Feliciani C, Satolli F. Vitiligo: what’s old, what’s new. Dermatol Rep. 2021;13:9142.

    Article  CAS  Google Scholar 

  3. Sarma N, Chakraborty S, Poojary S, Shashi Kumar BM, Gupta LK, Budamakuntla L, et al. A Nationwide, Multicentric Case-Control Study on Vitiligo (MEDEC-V) to elicit the magnitude and correlates. Indian J Dermatol. 2020;65:473–82.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ramot Y, Böhm M, Paus R. Translational neuroendocrinology of human skin: concepts and perspectives. Trends Mol Med. 2021;27:60–74.

    Article  CAS  PubMed  Google Scholar 

  5. He Y, Li S, Zhang W, Dai W, Cui T, Wang G, et al. Dysregulated autophagy increased melanocyte sensitivity to H2O2-induced oxidative stress in vitiligo. Sci Rep. 2017;7:42394.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  6. Silverberg JI, Silverberg NB. Vitiligo disease triggers: psychological stressors preceding the onset of disease. Cutis. 2015;95:255–62.

    PubMed  Google Scholar 

  7. Bergqvist C, Ezzedine K. Vitiligo: a review. Dermatology. 2020;236:571–92.

    Article  PubMed  Google Scholar 

  8. Frisoli ML, Essien K, Harris JE. Vitiligo: mechanisms of pathogenesis and treatment. Annu Rev Immunol. 2020;38:621–48.

    Article  CAS  PubMed  Google Scholar 

  9. Jamal Y, Alshahrani AM, Arif JM, Almarshad FM. Robots in cancer surgery: a boon or bane. J Cancer Ther. 2020;11:803–23.

    Article  Google Scholar 

  10. Narahari SR, Aggithaya MG, Suraj KR. A protocol for systematic reviews of Ayurveda treatments. Int J Ayurveda Res. 2010;1:254–67.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Magitta NF, Bøe Wolff AS, Johansson S, Skinningsrud B, Lie BA, Myhr K-M, et al. A coding polymorphism in NALP1 confers risk for autoimmune Addison’s disease and type 1 diabetes. Genes Immun. 2009;10:120–4.

    Article  CAS  PubMed  Google Scholar 

  12. Richmond JM, Frisoli ML, Harris JE. Innate immune mechanisms in vitiligo: danger from within. Curr Opin Immunol. 2013;25:676–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. •• He S, Xu J, Wu J. The promising role of chemokines in vitiligo: from oxidative stress to the autoimmune response. Song P, editor. Oxid Med Cell Longev. 2022;2022:8796735. This paper presents a thorough professional analysis that offers insights into the interplay between oxidative stress and autoimmunity, particularly in the context of vitiligo. The focus is placed on examining the role of chemotactic signals in this interaction.

  14. D’Osualdo A, Reed JC. NLRP1, a regulator of innate immunity associated with vitiligo. Pigment Cell Melanoma Res. 2012;25:5–8.

    Article  PubMed  Google Scholar 

  15. Mosenson JA, Flood K, Klarquist J, Eby JM, Koshoffer A, Boissy RE, et al. Preferential secretion of inducible HSP70 by vitiligo melanocytes under stress. Pigment Cell Melanoma Res. 2014;27:209–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Yu R, Broady R, Huang Y, Wang Y, Yu J, Gao M, et al. Correction: transcriptome analysis reveals markers of aberrantly activated innate immunity in vitiligo lesional and non-lesional skin. PLoS One. 2013;8:e51040.

    Google Scholar 

  17. Zhang W, Wang X, He X, Xu Y. Editorial: adaptive immunity in local tissues. Front Immunol. 2023;14:1200663.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. • Bullock TNJ. The essential elements of adaptive immunity and their relevance to cancer immunology. In: Clinical immuno-oncology. Elsevier; 2024. p. 129–56. This paper offers a comprehensive review of alterations in the immune system associated with aging, exploring their possible implications for cancer and immunotherapy. Furthermore, it delves into the effects of chronic viral infections and frailty on these aspects.

  19. Kotobuki Y, Tanemura A, Yang L, Itoi S, Wataya-Kaneda M, Murota H, et al. Dysregulation of melanocyte function by Th17-related cytokines: significance of Th17 cell infiltration in autoimmune vitiligo vulgaris. Pigment Cell Melanoma Res. 2012;25:219–30.

    Article  CAS  PubMed  Google Scholar 

  20. Bassiouny DA, Shaker O. Role of interleukin-17 in the pathogenesis of vitiligo. Clin Exp Dermatol. 2011;36:292–7.

    Article  CAS  PubMed  Google Scholar 

  21. Rahimi A, Hossein-Nataj H, Hajheydari Z, Aryanian Z, Shayannia A, Ajami A, et al. Expression analysis of PD-1 and Tim-3 immune checkpoint receptors in patients with vitiligo; positive association with disease activity. Exp Dermatol. 2019;28:674–81.

    Article  CAS  PubMed  Google Scholar 

  22. Yang Q, Zhang G, Su M, Leung G, Lui H, Zhou P, et al. Vitiligo skin biomarkers associated with favorable therapeutic response. Front Immunol. 2021;12:613031.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. • Zhang Q, Wang Q, Zhang L-X. Granzyme B: a novel therapeutic target for treatment of atopic dermatitis. Indian J Dermatol Venereol Leprol. 2022;89:166. This review investigates the relationship between granzyme B and atopic dermatitis with the goal of identifying a novel therapeutic target for the clinical management of this condition.

  24. Voskoboinik I, Whisstock JC, Trapani JA. Perforin and granzymes: function, dysfunction and human pathology. Nat Rev Immunol. 2015;15:388–400.

    Article  CAS  PubMed  Google Scholar 

  25. Schwartz DM, Bonelli M, Gadina M, O’Shea JJ. Type I/II cytokines, JAKs, and new strategies for treating autoimmune diseases. Nat Rev Rheumatol. 2016;12:25–36.

    Article  CAS  PubMed  Google Scholar 

  26. Rashighi M, Harris JE. Interfering with the IFN-γ/CXCL10 pathway to develop new targeted treatments for vitiligo. In: Annals of translational medicine. AME Publishing Company; 2015.

    Google Scholar 

  27. Yang L, Wei Y, Sun Y, Shi W, Yang J, Zhu L, et al. Interferon-gamma inhibits melanogenesis and induces apoptosis in melanocytes: a pivotal role of CD8+ cytotoxic T lymphocytes in vitiligo. Acta Derm Venereol. 2015;95:664–70.

    Article  CAS  PubMed  Google Scholar 

  28. Rashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K, Su M-W, et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med. 2014;6:223ra23.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Sayoc-Becerra A, Krishnan M, Fan S, Jimenez J, Hernandez R, Gibson K, et al. The JAK-inhibitor tofacitinib rescues human intestinal epithelial cells and colonoids from cytokine-induced barrier dysfunction. Inflamm Bowel Dis. 2020;26:407–22.

    Article  PubMed  Google Scholar 

  30. Yan Z, Gibson SA, Buckley JA, Qin H, Benveniste EN. Role of the JAK/STAT signaling pathway in regulation of innate immunity in neuroinflammatory diseases. Clin Immunol. 2018;189:4–13.

    Article  CAS  PubMed  Google Scholar 

  31. Roberts GHL, Santorico SA, Spritz RA. The genetic architecture of vitiligo. Pigment Cell Melanoma Res. 2020;33:8–15. https://doi.org/10.1111/pcmr.12848.

    Article  CAS  PubMed  Google Scholar 

  32. Jin Y, Birlea SA, Fain PR, Ferrara TM, Ben S, Riccardi SL, et al. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nat Genet. 2012;44:676–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Spritz RA, Santorico SA. The genetic basis of vitiligo. J Invest Dermatol. 2021;141:265–73.

    Article  CAS  PubMed  Google Scholar 

  34. Khopkar U, Shankarkumar U, Ghosh K, Misri R. Comparative case control study of clinical features and human leukocyte antigen susceptibility between familial and nonfamilial vitiligo. Indian J Dermatol Venereol Leprol. 2009;75:583.

    Article  PubMed  Google Scholar 

  35. Chen J, Li S, Li C. Mechanisms of melanocyte death in vitiligo. Med Res Rev. 2021;41:1138–66.

    Article  PubMed  Google Scholar 

  36. Xu M, Liu Y, Liu Y, Li X, Chen G, Dong W, et al. Genetic polymorphisms of GZMB and vitiligo: A genetic association study based on Chinese Han population. Sci Rep. 2018;8:13001.

    Article  ADS  PubMed  PubMed Central  Google Scholar 

  37. Jin Y, Andersen GHL, Santorico SA, Spritz RA. Multiple functional variants of IFIH1, a gene involved in triggering innate immune responses, protect against vitiligo. J Investig Dermatol. 2017;137:522–4.

    Article  CAS  PubMed  Google Scholar 

  38. Denat L, Kadekaro AL, Marrot L, Leachman SA, Abdel-Malek ZA. Melanocytes as instigators and victims of oxidative stress. J Investig Dermatol. 2014;134:1512–8.

    Article  CAS  PubMed  Google Scholar 

  39. Wagner RY, Luciani F, Cario-André M, Rubod A, Petit V, Benzekri L, et al. Altered e-cadherin levels and distribution in melanocytes precede clinical manifestations of vitiligo. J Investig Dermatol. 2015;135:1810–9.

    Article  CAS  PubMed  Google Scholar 

  40. Abdel-Malek ZA, Jordan C, Ho T, Upadhyay PR, Fleischer A, Hamzavi I. The enigma and challenges of vitiligo pathophysiology and treatment. Pigment Cell Melanoma Res. 2020;33:778–87.

    Article  PubMed  Google Scholar 

  41. • Cao X, Li Y, Luo Y, Chu T, Yang H, Wen J, et al. Transient receptor potential melastatin 2 regulates neutrophil extracellular traps formation and delays resolution of neutrophil-driven sterile inflammation. J Inflamm. 2023;20:7. This review examines the pathophysiological involvement of TRPM2 in inflammation induced by MSU crystals, with a specific emphasis on its impact on the formation of neutrophil extracellular traps (NETs).

  42. Yamamoto S, Shimizu S. Targeting TRPM2 in ROS-coupled diseases. Pharmaceuticals. 2016;9:57.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Li S, Dai W, Wang S, Kang P, Ye Z, Han P, et al. Clinical significance of serum oxidative stress markers to assess disease activity and severity in patients with non-segmental vitiligo. Front Cell Dev Biol. 2021;9:739413.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Vaccaro M, Bagnato G, Cristani M, Borgia F, Spatari G, Tigano V, et al. Oxidation products are increased in patients affected by non-segmental generalized vitiligo. Arch Dermatol Res. 2017;309:485–90.

    Article  CAS  PubMed  Google Scholar 

  45. Mitra S, De Sarkar S, Pradhan A, Pati AK, Pradhan R, Mondal D, et al. Levels of oxidative damage and proinflammatory cytokines are enhanced in patients with active vitiligo. Free Radic Res. 2017;51:986–94.

    Article  CAS  PubMed  Google Scholar 

  46. Xiong S, Chng W-J, Zhou J. Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma. Cell Mol Life Sci. 2021;78:3883–906.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Hetz C, Papa FR. The unfolded protein response and cell fate control. Mol Cell. 2018;69:169–81.

    Article  CAS  PubMed  Google Scholar 

  48. Ramirez MU, Hernandez SR, Soto-Pantoja DR, Cook KL. Endoplasmic reticulum stress pathway, the unfolded protein response, modulates immune function in the tumor microenvironment to impact tumor progression and therapeutic response. Int J Mol Sci. 2019;21:169.

    Article  PubMed  PubMed Central  Google Scholar 

  49. •• Chang W-L, Ko C-H. The role of oxidative stress in vitiligo: an update on its pathogenesis and therapeutic implications. Cells. 2023;12:936. The objective of this review is to emphasize the importance of oxidative stress in the development of vitiligo, highlighting its pivotal role in initiating subsequent autoimmune responses linked to the condition.

  50. •• Panieri E, Telkoparan‐Akillilar P, Saso L. NRF2, a crucial modulator of skin cells protection against vitiligo, psoriasis, and cancer. BioFactors. 2023;49:228–50. The Nrf2/Keap1 pathway is a crucial signaling cascade responsible for providing resistance against oxidative damage induced by external chemicals, thereby playing a pivotal role in promoting cell survival.

  51. •• Lin Y, Ding Y, Wu Y, Yang Y, Liu Z, Xiang L, et al. The underestimated role of mitochondria in vitiligo: from oxidative stress to inflammation and cell death. Exp Dermatol. 2024;33:e14856. This analysis provides perspectives on the supporting evidence that substantiates the role of mitochondria in the development of vitiligo.

  52. van Geel NAC, Mollet IG, De Schepper S, Tjin EPM, Vermaelen K, Clark RA, et al. First histopathological and immunophenotypic analysis of early dynamic events in a patient with segmental vitiligo associated with halo nevi. Pigment Cell Melanoma Res. 2010;23:375–84.

    Article  PubMed  Google Scholar 

  53. Bertheloot D, Latz E, Franklin BS. Necroptosis, pyroptosis and apoptosis: an intricate game of cell death. Cell Mol Immunol. 2021;18:1106–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dikic I, Elazar Z. Mechanism and medical implications of mammalian autophagy. Nat Rev Mol Cell Biol. 2018;19:349–64.

    Article  CAS  PubMed  Google Scholar 

  55. Collier JJ, Guissart C, Oláhová M, Sasorith S, Piron-Prunier F, Suomi F, et al. Developmental consequences of defective ATG7-mediated autophagy in humans. N Engl J Med. 2021;384:2406–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. • Kumar AV, Mills J, Lapierre LR. Selective autophagy receptor p62/SQSTM1, a pivotal player in stress and aging. Front Cell Dev Biol. 2022;10:793328. Selective autophagy depends on autophagy receptors to enable the breakdown of cargos, including those tagged with ubiquitin, underscoring its involvement in targeted cargo degradation.

  57. Bastonini E, Kovacs D, Raffa S, delle Macchie M, Pacifico A, Iacovelli P, et al. A protective role for autophagy in vitiligo. Cell Death Dis. 2021;12:318.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Dixon SJ, Stockwell BR. The hallmarks of ferroptosis. Annu Rev Cancer Biol. 2019;3:35–54.

    Article  Google Scholar 

  59. Dodson M, Castro-Portuguez R, Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol. 2019;23:101107.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: an iron-dependent form of nonapoptotic cell death. Cell. 2012;149:1060–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. • Mbah NE, Lyssiotis CA. Metabolic regulation of ferroptosis in the tumor microenvironment. J Biol Chem. 2022;298:101617. This review investigates intrinsic and extrinsic factors that amplify the susceptibility of cancer cells to ferroptosis. It concludes by examining strategies to maximize the potential of ferroptotic agents as promising therapeutic avenues for cancer treatment.

  62. Wang H, Sun L, Su L, Rizo J, Liu L, Wang L-F, et al. Mixed lineage kinase domain-like protein MLKL causes necrotic membrane disruption upon phosphorylation by RIP3. Mol Cell. 2014;54:133–46.

    Article  CAS  PubMed  Google Scholar 

  63. Sun L, Wang H, Wang Z, He S, Chen S, Liao D, et al. Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell. 2012;148:213–27.

    Article  CAS  PubMed  Google Scholar 

  64. Li B, Yi X, Zhuang T, Zhang S, Li S, Yang Y, et al. RIP1-mediated necroptosis facilitates oxidative stress-induced melanocyte death, offering insight into vitiligo. J Investig Dermatol. 2021;141:2921–31.

    Article  CAS  PubMed  Google Scholar 

  65. Jorgensen I, Miao EA. Pyroptotic cell death defends against intracellular pathogens. Immunol Rev. 2015;265:130–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Fink SL, Cookson BT. Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol. 2006;8:1812–25.

    Article  CAS  PubMed  Google Scholar 

  67. Shen X, Wang H, Weng C, Jiang H, Chen J. Caspase 3/GSDME-dependent pyroptosis contributes to chemotherapy drug-induced nephrotoxicity. Cell Death Dis. 2021;12:186.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Wang Y, Gao W, Shi X, Ding J, Liu W, He H, et al. Chemotherapy drugs induce pyroptosis through caspase-3 cleavage of a gasdermin. Nature. 2017;547:99–103.

    Article  ADS  CAS  PubMed  Google Scholar 

  69. Hu L, Chen M, Chen X, Zhao C, Fang Z, Wang H, et al. Chemotherapy-induced pyroptosis is mediated by BAK/BAX-caspase-3-GSDME pathway and inhibited by 2-bromopalmitate. Cell Death Dis. 2020;11:281.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Burdette BE, Esparza AN, Zhu H, Wang S. Gasdermin D in pyroptosis. Acta Pharm Sin B. 2021;11:2768–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Cao H, Liang J, Liu J, He Y, Ke Y, Sun Y, et al. Novel effects of combination therapy through inhibition of caspase-1/gasdermin D induced-pyroptosis in lupus nephritis. Front Immunol. 2021;12:720877.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Aglietti RA, Estevez A, Gupta A, Ramirez MG, Liu PS, Kayagaki N, et al. GsdmD p30 elicited by caspase-11 during pyroptosis forms pores in membranes. Proc Nat Acad Sci. 2016;113:7858–63.

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  73. Banerjee I, Behl B, Mendonca M, Shrivastava G, Russo AJ, Menoret A, et al. Gasdermin D restrains type I interferon response to cytosolic DNA by disrupting ionic homeostasis. Immunity. 2018;49:413–26.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Fitzgerald KA, Kagan JC. Toll-like receptors and the control of immunity. Cell. 2020;180:1044–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Lee C, Do HTT, Her J, Kim Y, Seo D, Rhee I. Inflammasome as a promising therapeutic target for cancer. Life Sci. 2019;231:116593.

    Article  CAS  PubMed  Google Scholar 

  76. • Santoni K, Pericat D, Gorse L, Buyck J, Pinilla M, Prouvensier L, et al. Caspase-1-driven neutrophil pyroptosis and its role in host susceptibility to Pseudomonas aeruginosa. Lee VT, editor. PLOS Pathogens. 2022;18:e1010305. The study outcome indicates a substantial role of neutrophil caspase-1 in the generation of interleukin-1 beta (IL-1β) and its impact on susceptibility to in vivo pyroptosis induced by Pseudomonas aeruginosa strains.

  77. Paul S, Jakhar R, Bhardwaj M, Chauhan AK, Kang SC. Fumonisin B1 induces poly (ADP-ribose) (PAR) polymer-mediated cell death (parthanatos) in neuroblastoma. Food Chem Toxicol. 2021;154:112326.

    Article  CAS  PubMed  Google Scholar 

  78. Zheng T, Zheng C, Gao F, Huang F, Hu B, Zheng X. Dexmedetomidine suppresses bupivacaine-induced parthanatos in human SH-SY5Y cells via the miR-7-5p/PARP1 axis-mediated ROS. Naunyn-Schmiedebergs Arch Pharmacol. 2021;394:783–96.

    Article  CAS  PubMed  Google Scholar 

  79. Dong K, Yan Y, Lu L, Wang Y, Li J, Zhang M, et al. PJ34 protects photoreceptors from cell death by inhibiting PARP-1 induced parthanatos after experimental retinal detachment. Curr Eye Res. 2021;46:115–21.

    Article  CAS  PubMed  Google Scholar 

  80. • Haga S, Kanno A, Morita N, Jin S, Matoba K, Ozawa T, et al. Poly(ADP-ribose) Polymerase (PARP) is critically involved in liver ischemia/reperfusion-injury. J Surg Res. 2022;270:124–38. This review explores the involvement of PARP (Poly(ADP-ribose) polymerase) in programmed necrosis, highlighting its potential as a promising therapeutic target for addressing post-ischemic liver injury.

  81. Liu S, Luo W, Wang Y. Emerging role of PARP-1 and PARthanatos in ischemic stroke. J Neurochem. 2022;160:74–87.

    Article  CAS  PubMed  Google Scholar 

  82. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25:486–541.

    Article  PubMed  PubMed Central  Google Scholar 

  83. Hamby AM, Suh SW, Kauppinen TM, Swanson RA. Use of a poly(ADP-ribose) polymerase inhibitor to suppress inflammation and neuronal death after cerebral ischemia-reperfusion. Stroke. 2007;38:632–6.

    Article  CAS  PubMed  Google Scholar 

  84. Lou J, Zhou Y, Feng Z, Ma M, Yao Y, Wang Y, et al. Caspase-independent regulated necrosis pathways as potential targets in cancer management. Front Oncol. 2021;10:616952.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Scaturro P, Pichlmair A. Oxeiptosis: a discreet way to respond to radicals. Curr Opin Immunol. 2019;56:37–43.

    Article  CAS  PubMed  Google Scholar 

  86. Holze C, Michaudel C, Mackowiak C, Haas DA, Benda C, Hubel P, et al. Oxeiptosis, a ROS-induced caspase-independent apoptosis-like cell-death pathway. Nat Immunol. 2018;19:130–40.

    Article  CAS  PubMed  Google Scholar 

  87. Thakur V, Bishnoi A, Vinay K, Kumaran SM, Parsad D. Vitiligo: Translational research and effective therapeutic strategies. Pigment Cell Melanoma Res. 2021;34:814–26.

    Article  PubMed  Google Scholar 

  88. Gellatly KJ, Strassner JP, Essien K, Refat MA, Murphy RL, Coffin-Schmitt A, et al. scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function. Sci Transl Med. 2021;13:eabd8995.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Malathi M, Thappa D. Topical therapy in vitiligo: what is new? Pigment Int. 2016;3:1.

    Article  Google Scholar 

  90. • Nurfaiqoh E, Arie Kusumawardani. Pulse dose corticosteroid therapy in vitiligo: a narrative literature review. Biosci Med J Biomed Transl Res. 2022;6:2721–9. The review assesses the effectiveness of pulse dose corticosteroid treatment in slowing down the progression of vitiligo and reducing both the expansion of the disease and related side effects.

  91. • Dharmayani GADDA, Pemayun TD. Topical corticosteroid as a treatment for vitiligo. Int J Health Sci. 2022;876–81. A case study about a 43-year-old woman with vitiligo focusing on the application of topical corticosteroids.

  92. • Nurfaiqoh E, Arie Kusumawardani. Pulse dose corticosteroid therapy in vitiligo: a narrative literature review. Biosci Med J Biomed Transl Res. 2022;6:2721–9. The objective of this literature review is to assess the application of pulse dose corticosteroid therapy in the management of vitiligo.

  93. Pacifico A, Damiani G, Iacovelli P, Conic RRZ, Young Dermatologists Italian Network (YDIN), Gonzalez S, et al. NB-UVB plus oral Polypodium leucotomos extract display higher efficacy than NB-UVB alone in patients with vitiligo. Dermatol Ther. 2021;34:e14776.

    Article  CAS  PubMed  Google Scholar 

  94. • Ezzedine K, Peeva E, Yamaguchi Y, Cox LA, Banerjee A, Han G, et al. Efficacy and safety of oral ritlecitinib for the treatment of active nonsegmental vitiligo: a randomized phase 2b clinical trial. J Am Acad Dermatol. 2023;88:395–403. The study is ongoing to evaluate the effectiveness and safety of ritlecitinib, an oral JAK3/TEC inhibitor, in patients with active nonsegmental vitiligo as part of a phase 2b trial (NCT03715829).

  95. Mehta H, Kumar S, Parsad D, Bishnoi A, Vinay K, Kumaran MS. Oral cyclosporine is effective in stabilizing active vitiligo: results of a randomized controlled trial. Dermatol Ther. 2021;34:e15033.

    Article  CAS  PubMed  Google Scholar 

  96. Li L, Li L, Wu Y, Gao X-H, Chen H-D. Triple-combination treatment with oral α-lipoic acid, betamethasone injection, and NB-UVB for non-segmental progressive vitiligo. J Cosmet Laser Ther. 2016;18:182–5.

    Article  PubMed  Google Scholar 

  97. Bishnoi A, Vinay K, Kumaran MS, Parsad D. Oral mycophenolate mofetil as a stabilizing treatment for progressive non-segmental vitiligo: results from a prospective, randomized, investigator-blinded pilot study. Arch Dermatol Res. 2021;313:357–65.

    Article  CAS  PubMed  Google Scholar 

  98. Khemis A, Fontas E, Moulin S, Montaudié H, Lacour J-P, Passeron T. Apremilast in combination with narrowband UVB in the treatment of vitiligo: a 52-week monocentric prospective randomized placebo-controlled study. J Investig Dermatol. 2020;140:1533–7.

    Article  CAS  PubMed  Google Scholar 

  99. Patra S, Khaitan BK, Sharma VK, Khanna N. A randomized comparative study of the effect of betamethasone oral mini-pulse therapy versus oral azathioprine in progressive nonsegmental vitiligo. J Am Acad Dermatol. 2021;85:728–9.

    Article  CAS  PubMed  Google Scholar 

  100. Mou KH, Han D, Liu WL, Li P. Combination therapy of orally administered glycyrrhizin and UVB improved active-stage generalized vitiligo. Braz J Med Biol Res. 2016;49:e5354.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Singh H, Kumaran MS, Bains A, Parsad D. A randomized comparative study of oral corticosteroid minipulse and low-dose oral methotrexate in the treatment of unstable vitiligo. Dermatology. 2015;231:286–90.

    Article  CAS  PubMed  Google Scholar 

  102. •• Pazyar N, Hatami M, Yaghoobi R, Parvar SY, Radmanesh M, Hadibarhaghtalab M. The efficacy of adding topical 5-fluorouracil to micro-needling in the treatment of vitiligo: a randomized controlled trial. J Cosmet Dermatol. 2023;22:1513–20. This paper outlines a study designed to compare the effectiveness of micro-needling combined with topical 5-fluorouracil (5-FU) versus the application of topical tacrolimus ointment in treating vitiligo patches.

  103. •• Basak AK, Debnath J, Das A. Effectiveness of topical tacrolimus treatment in vitiligo patients. Cent Med Coll J. 2023;6:44–8. The effectiveness of topical tacrolimus treatment in individuals with vitiligo is assessed in this paper, and the conclusion suggests that tacrolimus ointment may serve as a safe and effective choice for managing the condition.

  104. Watabe A, Yamasaki K, Asano M, Kanbayashi Y, Nasu-Tamabuchi M, Terui H, et al. Efficacy of oral cholecalciferol on rhododendrol-induced vitiligo: a blinded randomized clinical trial. J Dermatol. 2018;45:456–62.

    Article  CAS  PubMed  Google Scholar 

  105. • Rosmarin D, Passeron T, Pandya AG, Grimes P, Harris JE, Desai SR, et al. Two phase 3, randomized, controlled trials of ruxolitinib cream for vitiligo. N Engl J Med. 2022;387:1445–55. The outcomes from two phase 3 trials indicate that the use of ruxolitinib cream led to more significant repigmentation of vitiligo lesions compared to the control vehicle over 52 weeks. However, it was associated with acne and pruritus at the application site.

  106. Juntongjin P, Sangganjanavanich P. Efficacy of the combined excimer light and topical calcipotriol for acral vitiligo: a randomized double-blind comparative study. Dermatol Ther. 2021;34:e14886.

    Article  CAS  PubMed  Google Scholar 

  107. Udompataikul M, Boonsupthip P, Siriwattanagate R. Effectiveness of 0.1% topical tacrolimus in adult and children patients with vitiligo. J Dermatol. 2011;38:536–40.

    Article  CAS  PubMed  Google Scholar 

  108. Ho N, Pope E, Weinstein M, Greenberg S, Webster C, Krafchik BR. A double-blind, randomized, placebo-controlled trial of topical tacrolimus 0·1% vs. clobetasol propionate 0·05% in childhood vitiligo. Br J Dermatol. 2011;165:626–32.

    Article  CAS  PubMed  Google Scholar 

  109. Nguyen S, Chuah SY, Fontas E, Khemis A, Jhingan A, Thng STG, et al. Autologous cell suspension grafting using recell in vitiligo and piebaldism patients. Dermatol Ther. 2017;30(1).

  110. Lim HW, Grimes PE, Agbai O, Hamzavi I, Henderson M, Haddican M, et al. Afamelanotide and narrowband UV-B phototherapy for the treatment of vitiligo: a randomized multicenter trial. JAMA Dermatol. 2015;151:42–50.

    Article  PubMed  Google Scholar 

  111. Grimes PE, Hamzavi I, Lebwohl M, Ortonne JP, Lim HW. The efficacy of afamelanotide and narrowband UV-B phototherapy for repigmentation of vitiligo. JAMA Dermatol. 2013;149:68.

    Article  CAS  PubMed  Google Scholar 

  112. • Bouceiro Mendes R, Alpalhão M, Filipe P. UVB phototherapy in the treatment of vitiligo: state of the art and clinical perspectives. Photodermatol Photoimmunol Photomed. 2022;38:215–23. This article discusses the progress in technology for creating novel phototherapy devices, along with various medical and surgical therapeutic options. The integration of these advancements with phototherapy can result in achieving optimal treatment outcomes.

  113. Esmat S, Hegazy RA, Shalaby S, Chu-Sung Hu S, Lan C-CE. Phototherapy and combination therapies for vitiligo. Dermatol Clin. 2017;35:171–92.

    Article  CAS  PubMed  Google Scholar 

  114. Bae JM, Jung HM, Hong BY, Lee JH, Choi WJ, Lee JH, et al. Phototherapy for vitiligo: a systematic review and meta-analysis. JAMA Dermatol. 2017;153:666–74.

    Article  PubMed  PubMed Central  Google Scholar 

  115. Hossain C, Porto DA, Hamzavi I, Lim HW. Camouflaging agents for vitiligo patients. J Drugs Dermatol. 2016;15:384–7.

    CAS  PubMed  Google Scholar 

  116. Elbuluk N, Ezzedine K. Quality of life, burden of disease, co-morbidities, and systemic effects in vitiligo patients. Dermatol Clin. 2017;35:117–28.

    Article  CAS  PubMed  Google Scholar 

  117. Kikuchi K, Tagami H. Dermatological benefits of cosmetics. In: Cosmetic science and technology. Elsevier; 2017. p. 115–9.

    Chapter  Google Scholar 

  118. • Grochocka M, Wełniak A, Białczyk A, Marek-Jozefowicz L, Tadrowski T, Czajkowski R. Management of stable vitiligo—a review of the surgical approach. J Clin Med. 2023;12:1984. This review provides a comprehensive look at clinical evidence related to the efficacy of vitiligo treatment approaches, whether they involve cellular or tissue-based methods.

  119. Bilal A, Anwar I. Guidelines for the management of vitiligo. J Pak Assoc Dermatol. 2014;24:68–78.

    Google Scholar 

  120. Budania A, Parsad D, Kanwar AJ, Dogra S. Comparison between autologous noncultured epidermal cell suspension and suction blister epidermal grafting in stable vitiligo: a randomized study. Br J Dermatol. 2012;167:1295–301.

    Article  CAS  PubMed  Google Scholar 

  121. •• Grossmann MC, Haidari W, Feldman SR. A review on the use of topical ruxolitinib for the treatment of vitiligo. J Drugs Dermatol 2023;22:664–7. This article outlines the clinical trial, focusing on the safety and efficacy of ruxolitinib 1.5% cream for inducing repigmentation in individuals with vitiligo.

  122. •• Liang J, Yu Y, Li C, Li Q, Chen P, Li W, et al. Tofacitinib combined with melanocyte protector α-MSH to treat vitiligo through dextran based hydrogel microneedles. Carbohydr Polym. 2023;305:120549. This study demonstrated a significant buildup of melanin in the epidermis and hair follicles, leading to a notable acceleration in both skin and hair pigmentation.

  123. • Muddebihal A, Khurana A, Sardana K. JAK inhibitors in dermatology: the road travelled and path ahead, a narrative review. Expert Rev Clin Pharmacol. 2023;16:279–95. A literature review on the effectiveness of JAK inhibitors in conditions like alopecia areata, vitiligo, atopic dermatitis, psoriasis, and other inflammatory diseases shows increasing evidence. While some conditions have well-supported studies, the application of JAK inhibitors in many cases remains largely empirical.

  124. • Frede N, Lorenzetti R, Hüppe JM, Janowska I, Troilo A, Schleyer MT, et al. JAK inhibitors differentially modulate B cell activation, maturation and function: a comparative analysis of five JAK inhibitors in an in-vitro B cell differentiation model and in patients with rheumatoid arthritis. Front Immunol. 2023;14:1087986. The ongoing study aims to characterize the effect of JAK inhibition on B cell homeostasis.

  125. •• Mattsson J, Israelsson E, Björhall K, Yrlid LF, Thörn K, Thorén A, et al. Selective Janus kinase 1 inhibition resolves inflammation and restores hair growth offering a viable treatment option for alopecia areata. Skin Health Dis. 2023;3:e209. The study's outcome, rooted in JAK inhibition, indicates its therapeutic effectiveness in resolving inflammation in Alopecia areata.

  126. Brito PS. On Leucoderm, Vitiligo, Ven Kuttam (Tamil) or Cabbare (Singhalese), and several new methods of treatment. BMJ. 1885;1:834–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Mastan A. A systemic review on vitiligo (baraṣ) and role of Unani medicines towards its treatment. TMR Integr Med. 2021;5:e21002.

    Article  Google Scholar 

  128. Shadab M, Shamsi S. Original research article (experimental): design and development of Unani Emulgel for vitiligo. J Ayurveda Integr Med. 2020;11:199–205.

    Article  PubMed  Google Scholar 

  129. Prusty AK, Bhandari P. A Co-morbid condition of warts and vitiligo treated with individualized homeopathy: an evidence-based case report. Homeopathy. 2022;111:139–46.

    Article  PubMed  Google Scholar 

  130. • Mahajan N, Mahajan A, Singh A, Gupta S. Homoeopathic treatment of sensitive scalp: a case report. Adv Homeopath Res 2023;8:54–60. This report explores the efficacy of homeopathy as an alternative treatment option for addressing a sensitive scalp.

  131. Krüger C, Smythe J, Spencer J, Hasse S, Panske A, Chiuchiarelli G, et al. Significant immediate and long-term improvement in quality of life and disease coping in patients with vitiligo after group climatotherapy at the Dead Sea. Acta Derm Venereol. 2011;91:152–9.

    Article  PubMed  Google Scholar 

  132. Czarnowicki T, Harari M, Ruzicka T, Ingber A. Dead Sea climatotherapy for vitiligo: a retrospective study of 436 patients. J Eur Acad Dermatol Venereol. 2011;25:959–63.

    Article  CAS  PubMed  Google Scholar 

  133. Pang Y, Wu S, He Y, Nian Q, Lei J, Yao Y, et al. Plant-derived compounds as promising therapeutics for vitiligo. Front Pharmacol. 2021;12:685116.

    Article  PubMed  PubMed Central  Google Scholar 

  134. Zhang X, Qin Y, Ruan W, Wan X, Lv C, He L, et al. Targeting inflammation-associated AMPK//Mfn-2/MAPKs signaling pathways by baicalein exerts anti-atherosclerotic action. Phytother Res. 2021;35:4442–55.

    Article  PubMed  Google Scholar 

  135. Jiang W, Li S, Chen X, Zhang W, Chang Y, He Y, et al. Berberine protects immortalized line of human melanocytes from H2O2-induced oxidative stress via activation of Nrf2 and Mitf signaling pathway. J Dermatol Sci. 2019;94:236–43.

    Article  CAS  PubMed  Google Scholar 

  136. Hwang YS, Kim Y-J, Kim MO, Kang M, Oh SW, Nho YH, et al. Cannabidiol upregulates melanogenesis through CB1 dependent pathway by activating p38 MAPK and p42/44 MAPK. Chem Biol Interact. 2017;273:107–14.

    Article  CAS  PubMed  Google Scholar 

  137. Hu Y, Huang J, Li Y, Jiang L, Ouyang Y, Li Y, et al. Cistanche deserticola polysaccharide induces melanogenesis in melanocytes and reduces oxidative stress via activating NRF2/HO-1 pathway. J Cell Mol Med. 2020;24:4023–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Zhang B, Wang J, Zhao G, Lin M, Lang Y, Zhang D, et al. Apigenin protects human melanocytes against oxidative damage by activation of the Nrf2 pathway. Cell Stress Chaperones. 2020;25:277–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Basnet B, Bhushan A, Khan R, Kumar G, Sharma VK, Sharma A, et al. Plasma & urinary catecholamines & urinary vanillylmandelic acid levels in patients with generalized vitiligo. Indian J Med Res. 2018;147:384–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Riding RL, Harris JE. The role of memory CD8+ T cells in vitiligo. J Immunol. 2019;203:11–9.

    Article  CAS  PubMed  Google Scholar 

  141. Wang Z, Luan C, Hu Y, Ju M. Advances in the targeted therapy of vitiligo. Chin J Lepr Skin Dis. 2021;37:477–80.

    Google Scholar 

  142. Xu W, Wang C, Hua J. X-box binding protein 1 (XBP1) function in diseases. Cell Biol Int. 2021;45:731–9.

    Article  CAS  PubMed  Google Scholar 

  143. Caliskan M, Brown CD, Maranville JC. A catalog of GWAS fine-mapping efforts in autoimmune disease. Am J Hum Genet. 2021;108:549–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank the Research and Development Committee (RDC) of Integral University for their generous allocation of the manuscript communication number ((IU/R&D/2024-MCN0002455). The authors wish to thank Dr. Jamal Arif for reviewing their manuscript.

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IK contributed to planning and technical assistance, while MKAK played a vital role in revising, reviewing, and providing overall supervision. FMA contributed to the revision process and provided valuable input from a clinical perspective.

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Correspondence to Mohammad Kalim Ahmad Khan.

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Khan, I., Khan, M.K.A. & Almarshad, F.M. Exploring Therapeutic Approaches for Vitiligo: An Inclusive Review from Translational Modalities to Alternative Therapies. Curr Derm Rep (2024). https://doi.org/10.1007/s13671-024-00425-z

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