Unraveling Vitiligo: From Immune Mechanisms to Promising Therapeutic Strategies
Artur Kovenskiy 1,
Nurlubek Katkenov 1,
Zhussipbek Mukatayev 1,
Almagul Kushugulova 1 * More Detail
1 National Laboratory Astana, Nazarbayev University, Astana, Kazakhstan
* Corresponding Author
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Author Contributions: Conceptualization, A.K., N.K., Z.M. and A.K.; methodology – A.K., Z.M, and A.K.; validation – not applicable; formal analysis – not applicable; investigation, A.K. and N.K.; resources, A.K.; data curation, Z.M.; writing – original draft preparation A.K. and N.K.; writing – review and editing, Z.M. and A.K.; visualization, A.K.; supervision, A.K.; project administration – not applicable.; funding acquisition – Z.M. All authors have read and agreed to the published version of the manuscript.
ABSTRACT
Vitiligo is a dermatological condition affecting 1% of the global population, characterized by the loss of skin pigmentation. It appears in two main forms: nonsegmental (symmetrical depigmentation) and segmental (localized depigmentation). Oxidative stress and mitochondrial dysfunction in melanocytes cause vitiligo, while immune privilege protects hair follicle melanocytes, allowing for possible repigmentation. Genetic factors and associations with other autoimmune diseases, such as type 1 diabetes and thyroiditis, suggest a heritable autoimmune component. CD8+ T cells play a crucial role in vitiligo, targeting melanocytes and promoting apoptosis. These cells, along with IFN-γ signaling, contribute to disease progression. Therapies targeting these pathways, such as JAK inhibitors, have shown promise in repigmentation, particularly when combined with narrowband UVB phototherapy, a gold standard treatment. Surgical interventions, including punch grafting and suction blister grafting, show high efficiency but bring high risks of skin damage and hyperpigmentation. Vitiligo patients experience significant emotional suffering, requiring both a psychological and medical treatment approach. Dietary interventions, specifically those rich in antioxidants, may support disease treatment. Vitamin D, in particular, is a promising therapeutic agent by protecting melanocytes from oxidative stress via the WNT/β-catenin pathway. This review points out the need for more research on targeted therapies that combine immune regulation, phototherapy, and dietary strategies for effective vitiligo treatment.
CITATION
Kovenskiy A, Katkenov N, Mukatayev Z, Kushugulova A. Unraveling Vitiligo: From Immune Mechanisms to Promising Therapeutic Strategies. J Clin Med Kaz. 2024.
https://doi.org/10.23950/jcmk/15715
REFERENCES
- Frisoli ML, Essien K, Harris JE. Vitiligo: Mechanisms of Pathogenesis and Treatment. Annu Rev Immunol. 2020; 38: 621–648. https://doi.org/10.1146/annurev-immunol-100919-023531.
- Vitiligo. Nat Rev Dis Primers. 2015; 1: 15046. https://doi.org/10.1038/nrdp.2015.46.
- Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015; 386(9988): 74–84. https://doi.org/10.1016/s0140-6736(14)60763-7.
- Frisoli ML, Harris JE. Vitiligo: Mechanistic insights lead to novel treatments. J Allergy Clin Immunol. 2017; 140(3): 654–662. https://doi.org/10.1016/j.jaci.2017.07.011.
- Spritz RA, Andersen GH. Genetics of Vitiligo. Dermatol Clin. 2017; 35(2): 245–255. https://doi.org/10.1016/j.det.2016.11.013.
- Hadi A, Wang JF, Uppal P, Penn LA, Elbuluk N. Comorbid diseases of vitiligo: A 10-year cross-sectional retrospective study of an urban US population. J Am Acad Dermatol. 2020; 82(3): 628–633. https://doi.org/10.1016/j.jaad.2019.07.036.
- Gill L, Zarbo A, Isedeh P, Jacobsen G, Lim HW, Hamzavi I. Comorbid autoimmune diseases in patients with vitiligo: A cross-sectional study. J Am Acad Dermatol. 2016; 74(2): 295–302. https://doi.org/10.1016/j.jaad.2015.08.063.
- Bibeau K, Pandya AG, Ezzedine K, Jones H, Gao J, Lindley A, et al. Vitiligo prevalence and quality of life among adults in Europe, Japan and the USA. J Eur Acad Dermatol Venereol. 2022; 36(10): 1831–1844. https://doi.org/10.1111/jdv.18257.
- Piotrowska A, Wierzbicka J, Żmijewski MA. Vitamin D in the skin physiology and pathology. Acta Biochim Pol. 2016; 63(1): 17–29. https://doi.org/10.18388/abp.2015_1104.
- Naughton GK, Eisinger M, Bystryn JC. Antibodies to normal human melanocytes in vitiligo. J Exp Med. 1983; 158(1): 246–251. https://doi.org/10.1084/jem.158.1.246.
- Cui J, Arita Y, Bystryn JC. Cytolytic antibodies to melanocytes in vitiligo. J Invest Dermatol. 1993; 100(6): 812–815. https://doi.org/10.1111/1523-1747.ep12476636.
- Gilhar A, Zelickson B, Ulman Y, Etzioni A. In vivo destruction of melanocytes by the IgG fraction of serum from patients with vitiligo. J Invest Dermatol. 1995; 105(5): 683–686. https://doi.org/10.1111/1523-1747.ep12324456.
- Merimsky O, Shoenfeld Y, Baharav E, Altomonte M, Chaitchik S, Maio M, et al. Melanoma-associated hypopigmentation: where are the antibodies? Am J Clin Oncol. 1996; 19(6): 613–618. https://doi.org/10.1097/00000421-199612000-00017.
- Kroon MW, Kemp EH, Wind BS, Krebbers G, Bos JD, Gawkrodger DJ, et al. Melanocyte antigen-specific antibodies cannot be used as markers for recent disease activity in patients with vitiligo. J Eur Acad Dermatol Venereol. 2013; 27(9): 1172–1175. https://doi.org/10.1111/j.1468-3083.2012.04501.x.
- Le Poole IC, van den Wijngaard RM, Westerhof W, Das PK. Presence of T cells and macrophages in inflammatory vitiligo skin parallels melanocyte disappearance. Am J Pathol. 1996; 148(4): 1219–1228.
- Strassner JP, Rashighi M, Ahmed Refat M, Richmond JM, Harris JE. Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity. J Am Acad Dermatol. 2017; 76(5): 847-55.e5. https://doi.org/10.1016/j.jaad.2016.12.021.
- Ogg GS, Rod Dunbar P, Romero P, Chen JL, Cerundolo V. High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo. J Exp Med. 1998; 188(6): 1203–1208. https://doi.org/10.1084/jem.188.6.1203.
- Palermo B, Campanelli R, Garbelli S, Mantovani S, Lantelme E, Brazzelli V, et al. Specific cytotoxic T lymphocyte responses against Melan-A/MART1, tyrosinase and gp100 in vitiligo by the use of major histocompatibility complex/peptide tetramers: the role of cellular immunity in the etiopathogenesis of vitiligo. J Invest Dermatol. 2001 Aug; 117(2): 326–332. https://doi.org/10.1046/j.1523-1747.2001.01408.x.
- Kirkin AF, Dzhandzhugazyan K, Zeuthen J. Melanoma-associated antigens recognized by cytotoxic T lymphocytes. Apmis. 1998 Jul; 106(7): 665–679. https://doi.org/10.1111/j.1699-0463.1998.tb00210.x.
- Rashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K, Su MW, et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Transl Med. 2014; 6(223): 223ra23. https://doi.org/10.1126/scitranslmed.3007811.
- Richmond JM, Bangari DS, Essien KI, Currimbhoy SD, Groom JR, Pandya AG, et al. Keratinocyte-Derived Chemokines Orchestrate T-Cell Positioning in the Epidermis during Vitiligo and May Serve as Biomarkers of Disease. J Invest Dermatol. 2017 Feb; 137(2): 350–358. https://doi.org/10.1016/j.jid.2016.09.016.
- Harris JE, Rashighi M, Nguyen N, Jabbari A, Ulerio G, Clynes R, et al. Rapid skin repigmentation on oral ruxolitinib in a patient with coexistent vitiligo and alopecia areata (AA). J Am Acad Dermatol. 2016; 74(2): 370–371. https://doi.org/10.1016/j.jaad.2015.09.073.
- Craiglow BG, King BA. Tofacitinib Citrate for the Treatment of Vitiligo: A Pathogenesis-Directed Therapy. JAMA Dermatol. 2015 Oct; 151(10): 1110–1112. https://doi.org/10.1001/jamadermatol.2015.1520.
- Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017 Apr; 76(4): 736–744. https://doi.org/10.1016/j.jaad.2016.12.005.
- Cavalié M, Ezzedine K, Fontas E, Montaudié H, Castela E, Bahadoran P, et al. Maintenance therapy of adult vitiligo with 0.1% tacrolimus ointment: a randomized, double blind, placebo-controlled study. J Invest Dermatol. 2015; 135(4): 970–974. https://doi.org/10.1038/jid.2014.527.
- Mueller SN, Mackay LK. Tissue-resident memory T cells: local specialists in immune defence. Nat Rev Immunol. 2016; 16(2): 79–89. https://doi.org/10.1038/nri.2015.3.
- Mosenson JA, Zloza A, Klarquist J, Barfuss AJ, Guevara-Patino JA, Poole IC. HSP70i is a critical component of the immune response leading to vitiligo. Pigment Cell Melanoma Res. 2012; 25(1): 88–98. https://doi.org/10.1111/j.1755-148X.2011.00916.x.
- Klarquist J, Denman CJ, Hernandez C, Wainwright DA, Strickland FM, Overbeck A, et al. Reduced skin homing by functional Treg in vitiligo. Pigment Cell Melanoma Res. 2010; 23(2): 276–286. https://doi.org/10.1111/j.1755-148X.2010.00688.x.
- Trovato E, Pellegrino M, Filippi F, Mancini V, Pimpinelli N, Fimiani M. Clinical and histological evaluation in patients with mycosis fungoides treated with UVA1. G Ital Dermatol Venereol. 2020; 155(3): 306–311. https://doi.org/10.23736/s0392-0488.18.05867-4.
- Böhm M, Schunter JA, Fritz K, Salavastru C, Dargatz S, Augustin M, et al. S1 Guideline: Diagnosis and therapy of vitiligo. J Dtsch Dermatol Ges. 2022; 20(3): 365–378. https://doi.org/10.1111/ddg.14713.
- Bae JM, Jung HM, Hong BY, Lee JH, Choi WJ, Kim GM. Phototherapy for Vitiligo: A Systematic Review and Meta-analysis. JAMA Dermatol. 2017; 153(7): 666–674. https://doi.org/10.1001/jamadermatol.2017.0002.
- Phan K, Phan S, Shumack S, Gupta M. Repigmentation in vitiligo using janus kinase (JAK) inhibitors with phototherapy: systematic review and Meta-analysis. J Dermatolog Treat. 2022; 33(1): 173–177. https://doi.org/10.1080/09546634.2020.1735615.
- Qi F, Liu F, Gao L. Janus Kinase Inhibitors in the Treatment of Vitiligo: A Review. Front Immunol. 2021; 12: 790125. https://doi.org/10.3389/fimmu.2021.790125.
- Harris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-γ for autoreactive CD8⁺ T-cell accumulation in the skin. J Invest Dermatol. 2012; 132(7): 1869–1876. https://doi.org/10.1038/jid.2011.463.
- Mobasher P, Guerra R, Li SJ, Frangos J, Ganesan AK, Huang V. Open-label pilot study of tofacitinib 2% for the treatment of refractory vitiligo. Br J Dermatol. 2020; 182(4): 1047–1049. https://doi.org/10.1111/bjd.18606.
- Mumford BP, Gibson A, Chong AH. Repigmentation of vitiligo with oral baricitinib. Australas J Dermatol. 2020; 61(4): 374–376. https://doi.org/10.1111/ajd.13348.
- Hoisnard L, Lebrun-Vignes B, Maury S, Mahevas M, El Karoui K, Roy L, et al. Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. Scientific Reports. 2022; 12(1): 7140. https://doi.org/10.1038/s41598-022-10777-w.
- McCrary MR, Gibbs DC, Alharthi M, Krueger LD. Utilization of Our Toolkit: A Systematic Review and Meta-analysis of Surgical Therapies in Vitiligo Treatment. Dermatol Surg. 2022; 48(8): 815–821. https://doi.org/10.1097/dss.0000000000003503.
- Post NF, Narayan VS, Bekkenk MW, Wolkerstorfer A. Meek micrografting, a novel surgical technique for the treatment of vitiligo and piebaldism: A case series. J Eur Acad Dermatol Venereol. 2023; 37(4): e460-e2. https://doi.org/10.1111/jdv.18829.
- Dev A, Vinay K, Bishnoi A, Kumaran MS, Dogra S, Parsad D. Dermatoscopic assessment of treatment response in patients undergoing autologous non-cultured epidermal cell suspension for the treatment of stable vitiligo: A prospective study. Dermatol Ther. 2021; 34(5): e15099. https://doi.org/10.1111/dth.15099.
- Kussainova A, Kassym L, Akhmetova A, Glushkova N, Sabirov U, Adilgozhina S, et al. Vitiligo and anxiety: A systematic review and meta-analysis. PLoS One. 2020; 15(11): e0241445. https://doi.org/10.1371/journal.pone.0241445.
- Henning SW, Jaishankar D, Barse LW, Dellacecca ER, Lancki N, Webb K, et al. The relationship between stress and vitiligo: Evaluating perceived stress and electronic medical record data. PLoS One. 2020; 15(1): e0227909. https://doi.org/10.1371/journal.pone.0227909.
- Rzepecki AK, McLellan BN, Elbuluk N. Beyond Traditional Treatment: The Importance of Psychosocial Therapy in Vitiligo. J Drugs Dermatol. 2018; 17: 688–691.
- Namazi MR, Chee Leok GO. Vitiligo and diet: a theoretical molecular approach with practical implications. Indian J Dermatol Venereol Leprol. 2009; 75(2): 116–118. https://doi.org/10.4103/0378-6323.48654.
- Jimi Y, Young-Woo S, Tae-Heung K. Complementary and Alternative Medicine for Vitiligo. In: Kelly KyungHwa P, Jenny Eileen M, editors. Vitiligo. Rijeka: IntechOpen; 2011. p. Ch. 10.
- Birlea SA, Costin GE, Norris DA. New insights on therapy with vitamin D analogs targeting the intracellular pathways that control repigmentation in human vitiligo. Med Res Rev. 2009; 29(3): 514–546. https://doi.org/10.1002/med.20146.
- Tang L, Fang W, Lin J, Li J, Wu W, Xu J. Vitamin D protects human melanocytes against oxidative damage by activation of Wnt/β-catenin signaling. Lab Invest. 2018; 98(12): 1527–1537. https://doi.org/10.1038/s41374-018-0126-4.