VIDEO TRANSCRIPT
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Video Title: Understanding Vitiligo Progression and Pathogenesis
With Dr. Amit G Pandya, MD
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This video is sponsored by Incyte Corporation and Dr. Amit G Pandya has been compensated for his time.
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Amit G Pandya, MD
Dermatology Practice
Sunnyvale and Mountain View, CA
Global Vitiligo Foundation President and Medical Advisory Board Chair
[SPEECH – DR. PANDYA]
Hello. My name is Dr. Amit Pandya, and I’m here to share the current understanding of the pathogenesis of vitiligo.
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What is the role of autoimmunity in non-segmental vitiligo?
[SPEECH – DR. PANDYA]
Vitiligo is an autoimmune disease, in which a patient's own T-cells destroy melanocytes, causing depigmentation.
We know that there are over 30 susceptibility genes for vitiligo.
In addition, you need activation of the immune system.
In response to genetic factors and environmental triggers, immune mediators are released by stressed melanocytes, typically leading to T-cell activation in the lymph nodes.
Large numbers of autoreactive melanocyte-specific cytotoxic T-cells are then produced and circulate in the bloodstream. In response to additional triggers, these T-cells migrate to the skin, find melanocytes and kill them.
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What is the role of JAK-STAT signaling in vitiligo?
[SPEECH – DR. PANDYA]
The JAK-STAT pathway plays a key role in the molecular underpinnings of vitiligo pathogenesis.
In keratinocytes, the JAK-STAT pathway becomes activated by IFN-γ released by cells in the skin, including CD8+ T-cells. JAK-STAT pathway activation leads to the production of CXCL9 and CXCL10 by keratinocytes. CXCL9/10 attract more of the cytotoxic T-cells that I mentioned earlier.
The CD8+ T-cells, through the JAK-STAT pathway, release more IFN-γ—creating a positive feedback loop—leading to a greater accumulation of T-cells, which then attack and destroy melanocytes.
That's why JAK-STAT signaling is so important.
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How does the pathogenesis just described present clinically?
[SPEECH – DR. PANDYA]
Some clinical signs that identify progressive disease are confetti-like lesions, trichrome lesions, and the Koebner phenomenon.
Sometimes it can be difficult to notice vitiligo progression. You can use photography to document the lesions during clinic visits so that you can monitor progression.
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Is repigmentation possible, and under what conditions?
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Repigmentation may be possible. It would require stopping the T-cell mediated immune attack, so the melanocytes can recover.
You have two ways that the melanocytes recover leading to repigmentation: One is from the margins of a lesion, but that’s limited. The pigmentation can migrate in from the margins for several millimeters but then usually stops.
The other way is from hair.
Melanocytes at the bottom of the hair follicles migrate upward towards the epidermis and then outward to fill in the skin around the follicles.
Certain conditions are more favorable to repigmentation, such as earlier intervention, younger age, darker skin, or if the lesions have pigmented hairs within them. These could be very small or microscopic hairs, as in the case of vellus hairs on the face.
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Time to repigmentation may vary between patients. And while we know repigmentation can take time, it can be achieved to some extent in both stable and progressive disease, depending on which part of the body is affected.
I want to thank you for taking the time to join me in learning about the current understanding of the pathogenesis of vitiligo.
I hope you’ll take some time to explore the rest of this site, which has a lot of great information about vitiligo.
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VitiligoDeeper.com
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References:
1. Ezzedine K; Harris JE. Chapter 76: Vitiligo. In: Kang S, Amagai M; Bruckner AL, et al, eds. Fitzpatrick's Dermatology. 9th ed. McGraw Hill; 2019.
2. Zhang Z, Xiang LF. Genetic susceptibility to vitiligo: Recent progress from genome-wide association studies. Dermatologica Sinica. 2014;32(4):225-232. doi:10.1016/j.dsi.2014.09.004
3. Shen C, Gao J, Sheng Y, et al. Genetic Susceptibility to Vitiligo: GWAS Approaches for Identifying Vitiligo Susceptibility Genes and Loci. Front Genet. 2016;7:3. Published 2016 Feb 1. doi:10.3389/fgene.2016.00003
4. Manga P, Elbuluk N, Orlow SJ. Recent advances in understanding vitiligo. F1000Res. 2016;5:F1000 Faculty Rev-2234. doi:10.12688/f1000research.8976.1
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7. Howell MD, Kuo FI, Smith PA. Targeting the Janus kinase family in autoimmune skin diseases. Front Immunol. 2019;10:2342. doi:10.3389/fimmu.2019.02342
8. Frisoli ML, Essien K, Harris JE. Vitiligo: mechanisms of pathogenesis and treatment. Annu Rev Immunol. 2020;38:621-648. doi:10.1146/annurev-immunol-100919-023531
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10. Byrne KT, Côté AL, Zhang P, et al. Autoimmune melanocyte destruction is required for robust CD8+ memory T cell responses to mouse melanoma. J Clin Invest. 2011;121(5):1797-1809. doi:10.1172/JCI44849
11. Eleftheriadou V, Atkar R, Batchelor J, et al. British Association of Dermatologists guidelines for the management of people with vitiligo 2021. Br J Dermatol. 2022;186(1):18-29. doi:10.1111/bjd.20596
12. Birlea SA, Goldstein NB, Norris DA. Repigmentation through melanocyte regeneration in vitiligo. Dermatol Clin. 2017;35(2):205-218. doi:10.1016/j.det.2016.11.015
13. Udompataikul M, Boonsupthip P, Siriwattanagate R. Effectiveness of 0.1% topical tacrolimus in adult and children patients with vitiligo. J Dermatol. 2011;38(6):536-540. doi:10.1111/j.1346-8138.2010.01067.x
14. Park JH, Park SW, Lee DY, Lee JH, Yang JM. The effectiveness of early treatment in segmental vitiligo: retrospective study according to disease duration. Photodermatol Photoimmunol Photomed. 2013;29(2):103-105. doi:10.1111/phpp.12029
15. Sendrasoa FA, Ranaivo IM, Sata M, et al. Treatment responses in patients with vitiligo to very potent topical corticosteroids combined with vitaminotherapy in Madagascar. Int J Dermatol. 2019;58(8):908-911. doi:10.1111/ijd.14510
16. Kanwar AJ, Mahajan R, Parsad D. Low-dose oral mini-pulse dexamethasone therapy in progressive unstable vitiligo. J Cutan Med Surg. 2013;17(4):259-268. doi:10.2310/7750.2013.12053
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© 2022, Incyte Corporation. MAT-DRM-00440 04/22
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