Recent Advances in the Diagnosis, Pathogenesis and Treatment of Vitiligo: A Review

Öz

Vitiligo is a condition that affects approximately 1-2 out of every 100 people in the general population and can lead to significant psychosocial burdens. Both genetic and environmental factors are implicated in its etiology. While genetic factors are estimated to account for about 75% of disease development, the remaining portion is attributed to environmental influences. Vitiligo is generally classified as either segmental or non-segmental. Segmental vitiligo is less common, tends to remain stable, and is more resistant to treatment. Non-segmental vitiligo, on the other hand, is more progressive and more frequently encountered. Clinically, vitiligo is characterized by depigmented macules and patches. Although diagnosis is typically made clinically, additional methods such as Wood’s lamp examination, dermoscopy, and biopsy may occasionally be employed. Vitiligo must be differentiated from other conditions that cause depigmented or hypopigmented lesions, which can usually be distinguished through further evaluation by a dermatologist. A wide range of treatment options are available, with topical and systemic medications and phototherapy being the most commonly used approaches. In addition to long-established and evidence-based therapies, various novel treatments are currently under investigation. As our understanding of the disease continues to grow, it is clear that innovative therapies will emerge to improve vitiligo management.

Anahtar Kelimeler

• Vitiligo
• advances
• treatment

Vitiligo Patogenez, Tanı ve Tedavisinde Güncel Gelişmeler: Bir Gözden Geçirme

Öz

Vitiligo, toplumda ortalama 100 kişiden 1-2’sini etkileyen ve ciddi psikososyal yüklere neden olabilen bir hastalıktır. Klinik olarak depigmente makül ve yamalarla karakterizedir. Etiyolojisinde genetik ve çevresel faktörler suçlanmaktadır. Vitiligo genel olarak segmental ve non-segmental olarak sınıflandırılır. Segmental vitiligo daha nadir görülen, stabil kalma eğiliminde olan ve tedaviye daha zor yanıt veren türdür. Non-segmental vitiligo ise daha ilerleyici olan ve sık görülen alt tiptir. Tanısı genelde klinik olarak konulmakla birlikte Wood incelemesi, dermatoskopi, biyopsi gibi yöntemlere de nadiren başvurulabilmektedir. Vitiligo, depigmente bazen de hipopigmente lezyonlara sebep olan birçok hastalık ile ayırıcı tanıya girmektedir. Tedavide birçok farklı seçenek bulunmaktadır. Topikal ve sistemik ilaçlar ve fototerapi en sık kullanılanlardır. Uzun süredir kullanılan ve etkileri kanıtlanmış tedaviler dışında günümüzde hala çalışmaları devam eden birçok farklı ilaç bulunmaktadır. Özellikle son yıllarda topikal ve sistemik JAK inhibitörleri ile ilgili çok sayıda çalışma yapılmaktadır. Artan bilgi birikimi ile birlikte vitiligo tedavisinde ilerleme sağlanacak yeniliklerin geliştirileceği açıktır.

Anahtar Kelimeler

• Vitiligo
• tedavi
• gelişmeler

Kaynakça

1. 1. Feng Y, Lu Y. Advances in vitiligo: Update on therapeutic targets. Front Immunol. 2022; 13: 986918.
2. 2. Zhang Y, Cai Y, Shi M, Jiang S, Cui S, Wu Y, et al. The Prevalence of Vitiligo: A Meta-Analysis. PLoS One. 2016; 11: e0163806.
3. 3. Perez-Bootello J, Cova-Martin R, Naharro-Rodriguez J, Segurado-Miravalles G. Vitiligo: Pathogenesis and New and Emerging Treatments. Int J Mol Sci. 2023; 24: 17306.
4. 4. Bergqvist C, Ezzedine K. Vitiligo: A Review. Dermatology. 2020; 236: 571-592.
5. 5. Millington GWM, Levell NJ. Vitiligo: The historical curse of depigmentation. Int J Dermatol. 2007; 46: 990-995.
6. 6. Seneschal J. Clinical Features of Vitiligo and Social Impact on Quality of Life. Dermatol Pract Concept. 2023; 13: e2023312S.
7. 7. Villegas-Calzada MF, Acatitla-Acevedo GA, Anda-Ortiz ND, Morales-Sánchez MA. Prognostic factors in childhood vitiligo. Bol Med Hosp Infant Mex. 2024; 81: 73-78.
8. 8. Vora RV, Patel BB, Chaudhary AH, Mehta MJ, Pilani AP. A Clinical Study of Vitiligo in a Rural Set up of Gujarat. Indian J Community Med. 2014; 39: 143-146.

9. 9. Ramot Y, Rosenberg V, Zhou L, Harbers S. Epidemiology and Treatment Patterns of Patients with Vitiligo: A Real- World Analysis. Adv Ther. 2024; 41: 2890-2906.
10. 10. Marchioro HZ, Silva de Castro CC, Fava VM, Sakiyama PH, Dellatorre G, Miot HA. Update on the pathogenesis of vitiligo. An Bras Dermatol. 2022; 97: 478-490.
11. 11. Spritz RA, Santorico SA. The Genetic Basis of Vitiligo. J Invest Dermatol. 2021; 141: 265-273.
12. 12. Iwanowski T, Kołkowski K, Nowicki RJ, Sokołowska- Wojdyło M. Etiopathogenesis and Emerging Methods for Treatment of Vitiligo. Int J Mol Sci. 2023; 24: 9749.
13. 13. Jin Y, Andersen G, Yorgov D, Ferrara TM, Ben S, Brownson KM, et al. Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants. Nat Genet. 2016; 48: 1418-1424.
14. 14. Gawkrodger DJ. Pseudocatalase and narrowband ultraviolet B for vitiligo: clearing the picture. Br J Dermatol. 2009; 161: 721-722.
15. 15. Katz EL, Harris JE. Translational Research in Vitiligo. Front Immunol. 2021; 12: 624517.
16. 16. Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. Vitiligo: a comprehensive overview Part I. Introduction, epidemiology, quality of life, diagnosis, differential diagnosis, associations, histopathology, etiology, and work-up. J Am Acad Dermatol. 2011; 65: 473-491.
17. 17. Al-smadi K, Imran M, Leite-Silva VR, Mohammed Y. Vitiligo: A Review of Aetiology, Pathogenesis, Treatment, and Psychosocial Impact. Cosmetics. 2023; 10: 84.
18. 18. Boukhedouni N, Martins C, Darrigade AS, Drullion C, Rambert J, Barrault C, Garnier J, Jacquemin C, Thiolat D, Lucchese F, Morel F, Ezzedine K, Taieb A, Bernard FX, Seneschal J, Boniface K. Type-1 cytokines regulate MMP- 9 production and E-cadherin disruption to promote melanocyte loss in vitiligo. JCI Insight. 2020; 5: e133772.
19. 19. Montes LF, Abulafia J, Wilborn WH, Hyde BM, Montes CM. Value of histopathology in vitiligo. Int J Dermatol. 2003; 42: 57-61.
20. 20. Dwivedi M, Laddha NC, Begum R. The Immunogenetics of Vitiligo: An Approach Toward Revealing the Secret of Depigmentation. Adv Exp Med Biol. 2022; 1367: 61-103.
21. 21. Frisoli ML, Harris JE. Vitiligo: Mechanistic insights lead to novel treatments. J Allergy Clin Immunol. 2017; 140: 654- 662.
22. 22. Kang P, Wang Y, Chen J, Chang Y, Zhang W, Cui T, Yi X, Li S, Li C. TRPM2-dependent autophagy inhibition exacerbates oxidative stress-induced CXCL16 secretion by keratinocytes in vitiligo. J Pathol. 2024; 262: 441-453.
23. 23. Schmidt C. Temprian Therapeutics: Developing a genebased treatment for vitiligo. Nature. 2020 Jun 30.
24. 24. Zhao C, Wang D, Wang X, Mao Y, Xu Z, Sun Y, Mei X, Song J, Shi W. Down-regulation of exosomal miR-200c derived from keratinocytes in vitiligo lesions suppresses melanogenesis. J Cell Mol Med. 2020; 24: 12164-12175.
25. 25. Dong Li, Ting Zhou, et al. Circulating Exosomal miR-493-3p Affects Melanocyte Survival and Function by Regulating Epidermal Dopamine Concentration in Segmental Vitiligo. Journal of Investigative Dermatology. 2022; 142: 3262- 3273.e11.
26. 26. Li W, Pang Y, He Q, Song Z, Xie X, Zeng J, Guo J. Exosomederived microRNAs: emerging players in vitiligo. Front Immunol. 2024; 15: 1419660.
27. 27. Lu L, He H, Feng J, Hu Z, Zhang S, Yang L, Liu Y, Wang T. Post-translational modification in the pathogenesis of vitiligo. Immunol Res. 2024; 72: 1229-1237.
28. 28. Bergqvist C, Ezzedine K. Vitiligo: A focus on pathogenesis and its therapeutic implications. J Dermatol. 2021; 48: 252-270.
29. 29. Eltaweel AI, Salem RM, Abdelrahman AM, Hegazy HA. Provocating factors of vitiligo. Benha Journal of Applied Sciences. 2021.
30. 30. Silverberg JI, Silverberg NB. Vitiligo disease triggers: psychological stressors preceding the onset of disease. Cutis. 2015; 95: 255-262.
31. 31. Cupertino F, Niemeyer-Corbellini JP, Ramos ES. Psychosomatic aspects of vitiligo. Clin Dermatol. 2017; 35: 2927-2937.
32. 32. Liu X, Liu J. Vitiligo: are microbes to blame? Biosci Microbiota Food Health. 2025; 44: 16-25.
33. 33. Plensdorf S, Livieratos M, Dada N. Pigmentation Disorders: Diagnosis and Management. Am Fam Physician. 2017; 96: 797-804.
34. 34. Sosa JJ, Currimbhoy SD, Ukoha U, Sirignano S, O'Leary R, Vandergriff T, Hynan LS, Pandya AG. Confetti-like depigmentation: A potential sign of rapidly progressing vitiligo. Journal of the American Academy of Dermatology. 2015; 73: 272-275.
35. 35. Böhm M, Schunter JA, Fritz K, Salavastru C, Dargatz S, Augustin M, Tanew A. S1 Guideline: Diagnosis and therapy of vitiligo. JDDG: Journal der Deutschen Dermatologischen Gesellschaft. 2022; 20: 365-378.
36. 36. Gan EY, Cario-André M, Pain C, Goussot JF, Taïeb A, Seneschal J, Ezzedine K. Follicular vitiligo: A report of 8 cases. J Am Acad Dermatol. 2016; 74: 1178-1184.
37. 37. Ahmed jan N, Masood S. Vitiligo. [Updated 2023 Aug 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi. nlm.nih.gov/books/NBK559149/
38. 38. Adhikari M, Ali A, Kaushik N, Choi E. Perspective in Pigmentation Disorders. 2018.
39. 39. Givler DN, Saleh HM, Givler A. Pityriasis Alba. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.
40. 40. Madu PN, Syder N, Elbuluk N. Postinflammatory hypopigmentation: a comprehensive review of treatments. J Dermatolog Treat. 2022; 33: 704-708.
41. 41. Aranha MFAC, Santos MALD, et al. Hypopigmented mycosis fungoides: an important differential diagnosis of hypochromias in childhood. Rev Paul Pediatr. 2025; 43: e2024181.
42. 42. Gomez-Martinez S, Ibaceta Ayala J, Morgado-Carrasco D. Wood's Light in Inflammatory And Autoimmune Dermatoses, Infections and Skin Cancer. Actas Dermosifiliogr. 2025; 116: 281-290.
43. 43. Brown F, Crane JS. Idiopathic Guttate Hypomelanosis. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.
44. 44. Ahmed jan N, Masood S. Vitiligo. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.
45. 45. Seneschal J, Boniface K. Vitiligo: Current Therapies and Future Treatments. Dermatol Pract Concept. 2023; 13: e2023313S.
46. 46. Seneschal J, Duplaine A, Maillard H, et al. Efficacy and Safety of Tacrolimus 0.1% for the Treatment of Facial Vitiligo: A Multicenter Randomized, Double-Blinded, Vehicle-Controlled Study. J Investig Dermatol. 2021; 141: 1728-1734.
47. 47. Esmat SM, El-Mofty M, Rasheed H, et al. Efficacy of narrow band UVB with or without OMP in stabilization of vitiligo activity in skin photo-types (III-V): A double-blind, randomized, placebo-controlled, prospective, multicenter study. Photodermatol Photoimmunol Photomed. 2022; 38: 277-287.
48. 48. van Geel N, Speeckaert R, Taïeb A, et al. Worldwide expert recommendations for the diagnosis and management of vitiligo: Position statement from the International Vitiligo Task Force Part 1: towards a new management algorithm. J Eur Acad Dermatol Venereol. 2023; 37: 2173-2184.
49. 49. White C, Miller R. A Literature Review Investigating the Use of Topical Janus Kinase Inhibitors for the Treatment of Vitiligo. J Clin Aesthet Dermatol. 2022; 15: 20-25.
50. 50. Guttman-Yassky E, Del Duca E, Da Rosa JC, Bar J, Ezzedine K, Ye Z, He W, Hyde C, Hassan-Zahraee M, Yamaguchi Y, Peeva E. Improvements in immune/melanocyte biomarkers with JAK3/TEC family kinase inhibitor ritlecitinib in vitiligo. J Allergy Clin Immunol. 2024; 153: 161-172.e8.
51. 51. Liu LY, Strassner JP, Refat MA, Harris JE, King BA. Repigmentation in vitiligo using the Janus kinase inhibitor tofacitinib may require concomitant light exposure. J Am Acad Dermatol. 2017; 77: 675-682.e1.
52. 52. Dong J, Huang X, Ma LP, Qi F, Wang SN, Zhang ZQ, et al. Baricitinib is effective in treating progressing vitiligo in vivo and in vitro. Dose Response. 2022; 20: 15593258221105370.
53. 53. Su X, Luo R, Ruan S, Zhong Q, Zhuang Z, Xiao Z, et al. Efficacy and tolerability of oral upadacitinib monotherapy in patients with recalcitrant vitiligo. J Am Acad Dermatol. 2023; 89: 1257-1259.
54. 54. A study to assess adverse events and effectiveness of upadacitinib oral tablets in adult and adolescent participants with vitiligo 2023.
55. 55. Aclaris Therapeutics, Inc. A study of ATI-50002 topical solution for the treatment of vitiligo 2018.
56. 56. Atwa MA, Ali SM, Youssef N, Mahmoud Marie RE. Elevated serum level of interleukin-15 in vitiligo patients and its correlation with disease severity but not activity. J Cosmet Dermatol. 2021; 20: 2640-2644.
57. 57. National Institute of Allergy and Infectious Diseases (NIAID); Immune Tolerance Network (ITN); PPD; Rho Federal Systems Division, Inc.; Amgen. Evaluation of AMG 714 for vitiligo 2020.
58. 58. Kumar Jha A, Sonthalia S, Lallas A, Chaudhary RKP. Dermoscopy in vitiligo: diagnosis and beyond. Int J Dermatol. 2018; 57: 50-54.
59. 59. Taneja N, Sreenivas V, Sahni K, Gupta V, Ramam M. Disease Stability in Segmental and Non-Segmental Vitiligo. Indian Dermatol Online J. 2021; 13: 60-63.
60. 60. van Geel N, Speeckaert R, Taieb A, et al. Koebner's phenomenon in vitiligo: European position paper. Pigment Cell Melanoma Res. 2011; 24: 564-573.
61. 61. Ceresnie MS, et al. Diagnosing Disorders of Hypopigmentation and Depigmentation in Patients with Skin of Color. Dermatologic Clinics. 2023; 41: 407-416.
62. 62. Ramachandran V, Kim KM, Zhang L. Disseminated Nonsegmental Vitiligo Associated With Halo Nevi and Premature Gray Hair. Cureus. 2021; 13: e13868.
63. 63. Kolb L, Troxell T, Krishnamurthy K. Nevus Anemicus. 2024 Jul 19. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-.
64. 64. Altalhab S. Modalities of treatment for Nevus depigmentosus: review of the literature. J Dermatolog Treat. 2023; 34: 2258241.
65. 65. Frisoli ML, Essien K, Harris JE. Vitiligo: mechanisms of pathogenesis and treatment. Annu Rev Immunol. 2020; 38: 621-648.
66. 66. Merck Sharp & Dohme LLC. A clinical study of MK-6194 for the treatment of vitiligo (MK-6194-007) 2023.
67. 67. Speeckaert R., van Geel N. The Real-Life Efficacy of Methotrexate in Vitiligo: A Retrospective Study and Literature Review. J Eur Acad Dermatol Venereol. 2023; 37: 2267-2269.
68. 68. Kim HJ, Del Duca E, Pavel AB, Singer GK, Abittan BJ, Chima MA, et al. Apremilast and narrowband ultraviolet B combination therapy suppresses Th17 axis and promotes melanogenesis in vitiligo skin: a randomized, split-body, pilot study in skin types IV-VI. Arch Dermatol Res. 2023; 315: 215-221.
69. 69. 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.
70. 70. Clinuvel, Inc. A study to compare the efficacy and safety of SCENESSE and narrow-band ultraviolet (NB-UVB) light versus NB-UVB light alone in patients with vitiligo 2023.
71. 71. Seong SH, Oh SH. Up-and-Coming Drugs for the Treatment of Vitiligo. Ann Dermatol. 2024; 36: 197-208.
72. 72. Białczyk A, Wełniak A, Kamińska B, Czajkowski R. Oxidative Stress and Potential Antioxidant Therapies in Vitiligo: A Narrative Review. Mol Diagn Ther. 2023; 27: 723-739.
73. 73. Hu Z, Lu L, Feng J, Song H, Zhang S, Yang L, Liu Y, Wang T. Low-Dose Baricitinib Plus Narrow-Band Ultraviolet B for the Treatment of Progressive Non-Segmental Vitiligo: A Prospective, Controlled, Open-Label Study. Pigment Cell Melanoma Res. 2025; 38: e13209.
74. 74. Song H, Hu Z, Zhang S, Yang L, Liu Y, Wang T. Effectiveness and safety of tofacitinib combined with narrowband ultraviolet B phototherapy for patients with refractory vitiligo in real‐world clinical practice. Dermatol Ther. 2022; 35: e15821.
75. 75. Biswal A, Agrawal I, Panda M. Use of Oral Tofacitinib in the Treatment of Pediatric Vitiligo: A Case Series. Indian J Dermatol. 2024; 69: 366.
76. 76. Kang C. Ruxolitinib Cream 1.5%: A Review in Non- Segmental Vitiligo. Drugs. 2024; 84: 579-586.
77. 77. Sharma A, Gupta V, Bhatia S, Upadhyay A, Challa A, Gupta S. Apremilast versus betamethasone oral mini-pulse in the treatment of progressive non-segmental vitiligo: A randomised pilot trial. Indian J Dermatol Venereol Leprol. Indian J Dermatol Venereol Leprol. 2025; 91: 398-401.
78. 78. Mansouri P, Rahbar M, Nilforoushzadeh MA, Shati M, Amirkhani MA. Fractional CO2 Laser Versus Microneedling Combined with Narrowband Ultraviolet and Topical Steroid for Treating Non-Segmental Vitiligo in Treatment- Resistant Localizations: A Comparative Randomized Clinical Trial Study. J Lasers Med Sci. 2024; 15:e38.
79. 79. Ezzedine K, Eleftheriadou V, Jones H, Bibeau K, Kuo FI, Sturm D, Pandya AG. Psychosocial Effects of Vitiligo: A Systematic Literature Review. Am J Clin Dermatol. 2021; 22: 757-774.
80. 80. Bibeau K, Ezzedine K, et al. Mental Health and Psychosocial Quality-of-Life Burden Among Patients With Vitiligo: Findings From the Global VALIANT Study. JAMA Dermatol. 2023; 159: 1124-1128.
81. 81. Cadmus SD, Riddle AO, Sebastian KR, Reddy PS, Ahmed AM. Psychosocial and quality-of-life factors associated with depigmentation therapy for vitiligo. Arch Dermatol Res. 2023; 315: 2283-2288.
82. 82. Salama AH, Alnemr L, Khan AR, Alfakeer H, Aleem Z, Ali-Alkhateeb M. Unveiling the Unseen Struggles: A Comprehensive Review of Vitiligo's Psychological, Social, and Quality of Life Impacts. Cureus. 2023; 15: e45030.
83. 83. Rosmarin D, Lofland JH, Marwaha S, Piercy J, Anderson P, Liu J. Patient Burden of Nonsegmental Vitiligo: A US Real-World Survey of Dermatologists and Their Patients. Dermatol Ther (Heidelb). 2024; 14: 1531-1546.
84. 84. Strouphauer E, Suhail S, Mulinda C, et al. Prevalence of psychiatric comorbidities and treatment initiation in African American pediatric patients with vitiligo: A retrospective, single-center, case-control study. JAAD Int. 2024; 17: 104-110.
85. 85. Noori M, Fard R. The Relationship Between Body Dysmorphic Disorder and Depressive Symptoms with Health-Related Quality of Life in Women with Vitiligo. J Clin Res Paramed Sci. 2024; 13: 148595.
86. 86. Molla A, Jannadi R, Alayoubi H, Altouri H, Balkhair M, Hafez D. Assessing the Relationship Between Vitiligo and Major Depressive Disorder Severity: Cross-Sectional Study. JMIR Dermatol. 2024; 7: e60686.
87. 87. Heidarian P, Jalali A, Ghasemianrad M, Jalali R, Ezzati E. Global prevalence of sexual dysfunction in women with skin diseases: a systematic review and meta-analysis. BMC Womens Health. 2025; 25: 101.