Advancing Vitiligo Treatment: Insights on Current and Emerging Therapies by Dr. Rebecca Vasquez

At the Skin of Color Update 2024, we had the honor to learn from Dr. Rebecca Vasquez, Associate Professor at UT Southwestern Medical Center, regarding the evolving field of vitiligo management. Vitiligo affects between 0.5% to 2% of the global population, with no racial or gender preference, yet it carries a significant psychological burden for affected individuals.¹ Dr. Vasquez emphasized that vitiligo is not merely a cosmetic issue but rather a medical condition that impacts mental and emotional well-being similarly to other chronic skin diseases such as psoriasis and atopic dermatitis.

Pathogenesis

Dr. Vasquez outlined the pathogenesis of vitiligo, highlighting the role of immune-mediated destruction of melanocytes which is primarily driven by autoreactive CD8+ T cells.^2,3 Environmental factors such as exposure to phenolic compounds found in household products, and physical trauma to the skin (e.g., sunburns), can also trigger or exacerbate the condition. Importantly, Dr. Vasquez noted that while vitiligo can affect any area of the body, lesions tend to appear in areas exposed to friction or trauma, such as the elbows, knees, and hands.

Clinical Presentation of Vitiligo

Vitiligo is characterized by depigmentation of the skin and hair follicles, which can be highly variable in presentation. Signs of progressive disease include inflammatory, trichrome, and confetti-like lesions. Dr. Vasquez emphasized that the pattern of vitiligo lesions plays an essential role in predicting the course of the disease and the patient’s response to treatment.

There are two primary types of vitiligo: nonsegmental vitiligo (NSV) and segmental vitiligo (SV), each with distinct characteristics:

• • Nonsegmental Vitiligo (NSV): This is the most common form, accounting for 85-90% of cases. NSV can occur at any age but is more commonly diagnosed later in life. It is progressive, with frequent flare-ups and a tendency to affect areas of the body prone to trauma, such as pressure points and friction-prone regions. NSV is often associated with autoimmune conditions and may run in families with a history of autoimmunity.
  • Segmental Vitiligo (SV): SV is less common, representing about 10% of cases. It typically appears earlier in life, with an average onset age of 15 years. SV is unilateral and follows a more linear or block-like distribution. Unlike NSV, SV usually progresses rapidly over 6 months to two years before stabilizing. Dr. Vasquez explained that SV rarely progresses to generalized vitiligo and tends to affect the face, trunk, neck, and extremities.

Psychological and Social Impacts

Dr. Vasquez stressed the psychological and social impact of vitiligo, particularly in individuals with skin of color. The contrast between vitiligo-affected areas and naturally pigmented skin can be especially pronounced, often leading to emotional distress and stigmatization. Many patients experience anxiety, depression, and a diminished quality of life.¹ Dr. Vasquez highlighted that addressing these psychosocial aspects is a critical part of comprehensive vitiligo management, as patients often suffer silently from the emotional toll of the disease.

Treatment Approaches

The core goals of vitiligo treatment, as outlined by Dr. Vasquez, are to arrest disease progression, to repigment affected areas, and to maintain the repigmentation.⁴ Several factors influence the approach to treatment including disease stability, extent of disease, treatment costs, accessibility, and response to prior therapy. Current treatments include:

• • Topical Immunosuppressants: Topical corticosteroids and calcineurin inhibitors, such as tacrolimus, are commonly used to reduce inflammation and halt the immune attack on melanocytes. These are often first-line treatments for localized vitiligo.
  • Phototherapy: Narrowband ultraviolet B (NbUVB) phototherapy is a widely used treatment that stimulates melanocyte activity. Dr. Vasquez explained that NbUVB can be particularly effective when combined with topical treatments. Long-term use, typically over six months, is required to see significant repigmentation, and ongoing treatment is often necessary to maintain results.⁵
  • JAK Inhibitors: Emerging therapies involving Janus kinase (JAK) inhibitors are showing promise. Dr. Vasquez presented data from clinical trials on topical ruxolitinib, a JAK inhibitor, which has demonstrated substantial efficacy in repigmenting vitiligo lesions. The TRuE-V1 and TRuE-V2 phase 3 trials reported that patients using ruxolitinib cream achieved a 75% improvement in facial Vitiligo Area Scoring Index (F-VASI) after 24 weeks.⁶ These improvements were sustained and even increased with continued treatment.
  • Surgical Options: For stable cases of vitiligo, surgical interventions like autologous skin cell suspension transplantation (ASCS) can offer effective repigmentation. Dr. Vasquez reviewed data from a U.S. multicenter trial where ASCS showed 80% repigmentation in treated areas after 24 weeks, with durability lasting up to 52 weeks.⁷ This method involves harvesting the patient’s own skin cells, preparing a suspension of melanocytes, keratinocytes, and fibroblasts, and then applying it to the depigmented area.⁸
  • Combination Therapies: Dr. Vasquez emphasized that combining treatments can enhance repigmentation outcomes. For example, the addition of NB-UVB to ruxolitinib cream has shown promising results, with a majority of patients achieving significant repigmentation in both facial and total body scores.⁹

Emerging Therapies and Research

Exciting advancements in vitiligo treatment are on the horizon. Dr. Vasquez discussed the development of oral JAK inhibitors, such as ritlecitinib, povorcitinib, and upadacitinib which are currently in phase 3 clinical trials.³ These drugs have shown the potential for substantial repigmentation, particularly in patients with more extensive vitiligo. Early results indicate that these treatments are well tolerated, with adverse effects limited primarily to mild respiratory infections and headaches.

Another promising area of research involves targeting tissue-resident memory T cells. These immune cells are thought to be responsible for the recurrence of vitiligo after treatment discontinuation. Blocking interleukin-15 (IL-15), a key cytokine involved in the survival of these T cells, could offer a more durable solution to vitiligo management.³ Dr. Vasquez highlighted that clinical trials targeting IL-15 signaling are currently in phase 2 trials, with the hope that this could lead to more permanent treatment outcomes.

Conclusion: No Universal Cure, but Progress is Being Made

Dr. Vasquez concluded her presentation by reiterating that there is no universal cure for vitiligo. Treatment must be individualized, with careful consideration of the patient’s disease stability, lesion extent, response to prior therapies, and psychosocial needs. While new treatments like JAK inhibitors and IL-15 targeted therapies offer hope for more durable repigmentation, long-term management and patient education remain crucial. Dr. Vasquez’s presentation underscored the importance of a multidisciplinary approach, combining medical, psychological, and cosmetic therapies to improve the quality of life for those living with vitiligo.

References

1. 1. Ezzedine K, Eleftheriadou V, Jones H, et al. Psychosocial Effects of Vitiligo: A Systematic Literature Review. Am J Clin Dermatol. 2021;22(6):757-774. doi:10.1007/s40257-021-00631-6
   2. Pala V, Ribero S, Quaglino P, Mastorino L. Updates on Potential Therapeutic Approaches for Vitiligo: Janus Kinase Inhibitors and Biologics. J Clin Med. 2023;12(23):7486. Published 2023 Dec 4. doi:10.3390/jcm12237486
   3. Seong SH, Oh SH. Up-and-Coming Drugs for the Treatment of Vitiligo. Ann Dermatol. 2024;36(4):197-208. doi:10.5021/ad.24.038
   4. 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(11):2173-2184. doi:10.1111/jdv.19451
   5. Bae JM, Jung HM, Hong BY, et al. Phototherapy for Vitiligo: A Systematic Review and Meta-analysis. JAMA Dermatol. 2017;153(7):666-674. doi:10.1001/jamadermatol.2017.0002
   6. Rosmarin D, Passeron T, Pandya AG, et al. Two Phase 3, Randomized, Controlled Trials of Ruxolitinib Cream for Vitiligo. N Engl J Med. 2022;387(16):1445-1455. doi:10.1056/NEJMoa2118828
   7. Hamzavi IH, Ganesan AK, Mahmoud BH, et al. Effective and durable repigmentation for stable vitiligo: A randomized within-subject controlled trial assessing treatment with autologous skin cell suspension transplantation. J Am Acad Dermatol. Published online September 7, 2024. doi:10.1016/j.jaad.2024.08.027
   8. Zhao H, Chen Y, Zhang C, Fu X. Autologous epidermal cell suspension: A promising treatment for chronic wounds. J Tissue Viability. 2016;25(1):50-56. doi:10.1016/j.jtv.2015.11.003
   9. Pandya AG, Harris JE, Lebwohl M, et al. Addition of Narrow-Band UVB Phototherapy to Ruxolitinib Cream in Patients With Vitiligo. J Invest Dermatol. 2022;142(12):3352-3355.e4. doi:10.1016/j.jid.2022.05.1093

This information was presented by Dr. Rebecca Vasquez during the 2024 Skin of Color Update conference. The above session highlights were written and compiled by Dr. Nidhi Shah.

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