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The symposium and publication of this article were sponsored by Incyte Biosciences International Sàrl
Vitiligo, Beyond White Patches
Hannah Moir1,2 1
1. EMJ, London, UK; 2. School of Life Sciences, Pharmacy and Chemistry, Faculty of Health, Science, Social Care and Education, Kingston University, London, UK
Vitiligo, Beyond White Patches
This review is based on an industry-sponsored satellite symposium that took place at the European Academy of Dermatology and Venereology (EADV) Congress 2024, held between 25th–28th September 2024 in Amsterdam, the Netherlands, and is intended for healthcare professionals only.
Chairperson:
Khaled Ezzedine1,2
Speakers: Albert Wolkerstorfer,3 Curdin Conrad,4 Markus Böhm5
1. Department of Dermatology, Hôpital Henri-Mondor, Assistance Publique – Hôpitaux de Paris (AP-HP), France
2. University Paris-Est Créteil Val-de-Marne (UPEC), France
3. Department of Dermatology, Netherlands Institute for Pigment Disorders, University of Amsterdam
(UMC), the Netherlands
4. Polyclinic and Centre for Psoriasis, Lausanne University Hospital (CHUV), Switzerland
5. Department of Dermatology, University Hospital Münster, Germany
Acknowledgements: Medical writing assistance was provided by Hannah Moir, EMJ, London, UK.
Disclaimer: This symposium was intended for healthcare professionals only. The views and opinions expressed herein are those of the speakers. Not all medicines and/or indications presented in this report may be approved for use in all countries.
Keywords: Autoimmune disease, disease burden, JAK-STAT, long-term management, non-segmental vitiligo, real-world data, repigmentation, ruxolitinib cream, shared decision-making, tissue-resident memory T (TRM) cells.
Original Article Citation: EMJ Dermatol. 2024;12[1]:38-49. https://doi.org/10.33590/emjdermatol/MHBY1943.
Support statement: The symposium and publication of this article were sponsored by Incyte Biosciences International Sàrl.
Open Meeting Summary
Intended for Healthcare Professionals Only
Meeting Summary
- This article reviews an industry-sponsored satellite symposium that took place at the European Academy of Dermatology and Venereology (EADV) Congress 2024 held in Amsterdam, the Netherlands, on 27th September 2024.
- The session, chaired by Khaled Ezzedine, Professor of Dermatology at Hôpital Henri-Mondor, France, addressed understanding the disease burden of vitiligo and the challenges of accessing optimal care. The session established vitiligo as an autoimmune disease requiring both early and long-term management, as well as utilising shared decision-making in treatment options.
- Albert Wolkerstorfer, Professor of Dermatology at Amsterdam University Medical Centres, the Netherlands, discussed the underestimated burden of vitiligo disease, including psychological comorbidities, and the impact on quality of life (QoL) compared to other chronic diseases such as psoriasis. He also identified the challenges such as delayed diagnosis and lack of knowledge, and how this impacts access to optimal care.
- Curtin Conrad, Professor of Dermatology and Head of the Polyclinic and Centre for Psoriasis Lausanne University Hospital, Switzerland, then considered the pathogenesis of non-segmental vitiligo, focusing on the role of the JAK-signal STAT pathway and how it drives the disease mechanisms and maintenance t, emphasising the important need for early intervention and long-term considerations for the management of vitiligo.
- Finally, Markus Böhm, Professor of Dermatology at the University Hospital Münster, Germany, identified the importance of utilising shared decision-making in vitiligo treatment strategies, especially for long-term commitment, and how ruxolitinib cream fits into this shared decision-making and overall treatment strategy.
Q:
YES
NO
Do you consider vitiligo to be a serious medical disease?
INTRODUCTION
Vitiligo is a chronic autoimmune disease caused by a deregulation of the immune response that results in epidermal melanocyte destruction.1
The characteristic depigmented lesions are often associated with psychological distress for patients, resulting in negative effects on mental health and QoL, with vitiligo being associated with social isolation, stigma, depression, and anxiety.2
- With a variable and unpredictable disease course, vitiligo consists of stable periods, spontaneous repigmentation, and new patches or flares.
- Vitiligo is a serious medical condition and therefore should be treated as a priority.
How the Underestimated Vitiligo Burden Impacts Optimal
Care Albert Wolkerstorfer
Wolkerstorfer opened the session by considering the burden of vitiligo and what it is to live with vitiligo, including its impact on appearance, unpredictable flare-ups, itching, and association with autoimmune disorders.
He said that patients are ”desperate because of their vitiligo,”
explaining that even those patients who look self-confident, self-assured, beautiful, and strong, “all had difficult times in life,” with regards to their vitiligo, stating that “appearance does matter” to those with vitiligo.3
Wolkerstorfer supported this view by sharing data from a study in which strangers scored photos of those with facial abnormalities as being judged more often as dishonest, unsuitable for employment, unintelligent, or unattractive compared to edited images without abnormalities.4
Living with the Burden of Vitiligo, Including Psychological Comorbidities
The global VALIANT study indicated that the extent of vitiligo matters. The more extensive the affected BSA, the higher the rate of moderate-to-severe depressive symptoms, highlighting the urgency to treat as early as possible.5
Parallels Between Vitiligo and Other Skin Disorders
Acne
Wart
Psoriasis
Vitiligo
Eczema
Urticaria
- Wolkerstorfer drew parallels to other chronic skin disorders like psoriasis and eczema, emphasising similarities such as chronic course,15 unpredictable flare-ups,5 physical comorbidities,10-12 psychosocial comorbidities,13 disease burden,5,13 and the need for long-term treatment.15
- In comparison vitiligo has similar, if not higher percentages of psychosocial comorbidities such as depression and anxiety.13
- The session noted differences in the evolution of skin disorder care. Until recently, the treatment response has been limited, and the primary endpoint of treatment has been at least vitiligo area scoring index 50 (VASI50) i.e., 50% repigmentation.16,17 Whereas in psoriasis the primary endpoint is typically psoriasis area and severity index 90 (PASI90) i.e., 90%.18
- Also, treatment response is delayed, taking 6–24 months of treatment to achieve significant repigmentation.17 This, Wolkerstorfer said, “makes it quite frustrating, both for physicians and for patients.”
- Another important difference, compared to nearly all other skin disorders, is that the skin has a loss of melanocytes,19 meaning that vitiligo can be particularly difficult to re-pigment in certain regions.
Click to view examples of chronic skin disorders
Psychosocial co-morbidities
Physical co-morbidities
Figure 3: International statement of diagnosis and care of nonsegmental vitiligo.52
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, van Geel N, et al. © 2023 The Authors. Reproduced with permission of John Wiley & Sons Inc.
- Highlighting the global VALIANT study, an international cross-sectional online population-based survey of mental health conditions and psychosocial QoL burden among patients with vitiligo (n=3,541).5,15
- Diagnosed mental health conditions were common in 58.7% of patients with vitiligo, including anxiety (28.8%) and depression (24.5%).5 Moderate-to-severe symptoms of depression were common (55.0% globally), with the highest rates seen in India (89.4%).5
- The study also indicated that the extent of vitiligo matters. The more extensive the affected BSA (more than 5%), the higher the rate of moderate-to-severe depressive symptoms (72.0%).5
- The same was also seen for patients with darker skin types (68.3%; as per Fitzpatrick skin phototypes), and the presence of facial lesions (64.4%).5
Psychosocial co-morbidities
Physical co-morbidities
Figure 3: International statement of diagnosis and care of nonsegmental vitiligo.52
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, van Geel N, et al. © 2023 The Authors. Reproduced with permission of John Wiley & Sons Inc.
- Wolkerstorfer emphasised the impact of psychosocial comorbidities, which he referred to as “the dark side of white patches,” including depression, anxiety and anxiety-related disorders, stigmatisation, adjustment disorders, sleep disturbance, low self-esteem, and relationship difficulties.13
- A large systematic review of 168 observational studies reported depression was more likely to occur in patients with vitiligo compared to controls, showed an association to anxiety, and emotional and behavioural impairment.11
- A systematic review and meta-analysis reported that patients with vitiligo are approximately five times more likely to have depression compared to controls (pooled odds ratio: 5.05; 95% CI: 2.21–11.51).6
- The session also highlighted the need for HCPs to look for signs of depression in their patients with vitiligo.
- A meta-analysis of 20 eligible cohorts (N=1,965 patients) identified a pooled prevalence of depression of 29% (95% CI: 20–39) in those with vitiligo compared with controls (across 17 unique populations [n=1,711]).14
- Patients with vitiligo were 4.96 times (95% CI: 1.80–13.68) more likely to display depression, and sub-group analysis showed the prevalence was higher in female patients compared with males (standardised mean difference: 0.87; 95% CI: 0.52–1.22) and those of Asian ethnicity (pooled prevalence: 35% compared to 24% of Caucasians).14
Physical co-morbidities
Psychosocial co-morbidities
Figure 3: International statement of diagnosis and care of nonsegmental vitiligo.52
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, van Geel N, et al. © 2023 The Authors. Reproduced with permission of John Wiley & Sons Inc.
- It is not only appearance that matters, but also unpredictable flare-ups and itching, the latter of which Wolkerstorfer stated occurred in one out of five patients.7
- Those with flare-ups have a poorer QoL6 and are impacted by vitiligo disease progression, particularly in those that were stable and then rapidly depigment.8
84
.
1
%
- A study from Belgium reported that 84.1% of patients were highly motivated to follow treatment if the stability of vitiligo could be attained.9
- As such, this can be an important treatment goal, especially when the extent of vitiligo is not so large, i.e., when the affected body surface area (BSA) was less than 10%, patients were more highly motivated to follow a treatment.9
- The session noted that healthcare professionals (HCP) do not fully understand the physical comorbidities of vitiligo, which include the association with thyroid disease and other autoimmune disorders, including alopecia areata, pernicious anaemia, and diabetes.9-11
- For example, that sensorineural hearing loss is six times more likely in those with vitiligo compared to controls, as reported in a meta-analysis (odds ratio: 6.02; 95% CI: 3.41–10.62).12
X5
more likely to
have depression.6
1
Living With the Burden of Vitiligo, Including Psychological Comorbidities
2
Parallels Between Vitiligo and Other Skin Disorders
Access to Optimal Care and Hurdles in Vitiligo Care
Wolkerstorfer stated that “the patient journey starts long before the diagnosis,” and there are many issues along the patient journey which decrease access to optimal vitiligo care (Figure 1).20
Changing the Trajectory of Vitiligo in Europe
- The European white paper is a recent initiative aimed at identifying the gaps in the diagnosis, management, and care of vitiligo.23
- A Delphi consensus, which gathered recommendations from patient organisations and experts, aims to improve health outcomes and access to optimal care.23 It included officially classifying vitiligo as a chronic autoimmune disease and calls on policymakers and European authorities to drive initiatives and facilitate best practices for sharing information, as a matter of urgency.23 A link for more information, which is available in the reference list, was provided.24
When there is a diagnosis of vitiligo, patients often hear that it cannot be treated.
- Of patients, 56.7% are told that vitiligo is untreatable, with higher rates among those with darker skin types (66%), those with extensive vitiligo affecting more than 5% BSA (65.2%), and those treated by a non-dermatologist (68.8%).15
- This lack of knowledge of management options further adds to the burden of the disease, noted Wolkerstorfer.
- A survey study conducted in the Netherlands (325 patients with vitiligo), considered the patients’ perspective regarding current treatments and the demand for novel treatments.21
- The results indicated that half of the patients were dissatisfied with their current treatment, with 49% reporting that current treatments were not effective. Additionally, 94% of patients expressed the need for new and improved treatments.21
Access to specialist care and therefore treatment is poor for many patients across many countries.
- The VALIANT study, which surveyed skin disorders in Europe, the USA, and Japan (N=35,694 participants), estimated a 1.3% prevalence of vitiligo, with many patients undiagnosed (0.4%; including 0.3% vitiligo signs).8
- Wolkerstorfer believes that the delay in diagnosis, which on average takes 2.4 years following the appearance of the first lesions,15 was due to a lack of HCP knowledge and
awareness about the disease.
44
.
9
%
- Misdiagnosis is also very common, with 44.9% of patients reporting an earlier misdiagnosis.15
A statement from a patient who got frustrated with their healthcare experience said:
I went from dermatologist to dermatologist. Each told me there was no cure and no really effective treatment…seemed disinterested when I spoke of the dramatic change I saw in the mirror.”22
Many receive no treatment.8 Insufficient information about treatment options, and a lack of shared decision-making.15
Disease management 1: Treatment initiation
Public knowledge,15 and understanding of the condition in general.20
Symptom recognition / pre-diagnosis
Disease management 1: Treatment initiation
Diagnosis
Delay in diagnosis, misdiagnosis, HCPs downplaying the disease as a cosmetic issue, that ‘vitiligo is untreatable.’15
No adequate information.21
A European White Paper, along with the speakers at the symposium, highlighted the official classification of vitiligo as a chronic autoimmune disease.23,24
Changing
the Trajectory of Vitiligo in Europe
Wolkerstorfer concluded that the burden of vitiligo is significant. Though there are many parallels to other chronic skin disorders, some specific items make vitiligo very resistant and difficult to treat. Access to optimal care is sometimes very difficult, and there are some hurdles still to tackle.
As an Autoimmune Disease, Vitiligo Warrants Both Early and Long-Term Considerations Curdin Conrad
The Role of JAK-STAT Pathway Inhibition in Vitiligo
- The session identified targeting the Th-1 cytokine receptors,
IL. 15 and interferon-γ, which are both important in the pathogenesis of alopecia areata and vitiligo, through the associated signalling JAK-STAT pathways.27,29 - Interferon-γ receptor signalling in keratinocytes activates the JAK-STAT pathway via JAK1 and JAK2, resulting in transcription and production of CXCL9 and CXCL10, which induces CD-8 positive T cell recruitment which are capable of melanocyte destruction.30,31 By inhibiting JAK1, this would impact the response of TRM cells and interferon-γ.26,29
- Conrad stated that by targeting these inflammatory processes we can diminish autoimmune attacks on melanocytes and lead to re pigmentation over time, as damaged melanocytes are replaced by new melanocytes.2,31,32
The Role of JAK-STAT Pathway Inhibition in Vitiligo
- The pathogenesis of vitiligo is driven by auto-reactive CD8+ cytotoxic T cells that produce interferon-γ, which in turn signals the JAK pathway to promote the production of IL-15 which is critical in the activation and maintenance of skin keratinocytes and relapses.27,28 Within these cells form tissue-resident memory T cells (TRM) in the lesions, which are recruited by the IL-15 signalling.27,28
- Conrad expressed the challenges in eliminating TRM cells and the potential for preventing their entry into the skin through early intervention. Therefore, he suggested the role of IL-15 and interferon-γ as central in the pathogenesis of non-segmental vitiligo and identified the need to target these with treatment.
- Considering the treatment of chronic inflammatory diseases, Conrad highlighted the importance of finding treatment options that balance improving skin lesions while minimising side effects. He said this involved considering factors such as efficacy, benefits, risks, side effects, and inconveniences.25
- The session emphasised the need to understand the pathogenesis of the deregulation of the immune system in order to understand the disease and then identify treatment opportunities.
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Non-segmental vitiligo is a chronic T helper (Th)-1 autoimmune disease.26,27 Conrad drew comparison to other immune diseases such as psoriasis, which is a Th-17 driven disease, and lupus which is driven by Type I-interferon; alopecia areata and vitiligo are driven by Th-1 via interferon-γ, which was demonstrated by the overexpression seen in gene expression profiles.
2. The Role of Tissue Resident Memory T Cells in the Skin
- Furthermore, the session noted the challenges with disease memory, not just T cell memory but also inflammatory memory through epigenetic changes.38-40 Conrad discussed the concept of epigenetic memory and its role in disease persistence and the need for long-term treatment options.
- For example, during infection, inflammatory cells such as monocytes undergo epigenetic modifications, such as through histone methylations or DNA methylations, which ‘train’ or ‘tolerise’ the cell.41 However, Conrad highlighted that you cannot reverse the damage from epigenetic changes.
- As such, TRM cells are critical in mediating disease, therefore highlighting the importance of early interventions for the opportunity to bring about disease modification in certain patients.
- Identified by Wolkerstorfer, vitiligo is a chronic disease with patients having delayed diagnosis or late intervention.
- Conrad identified the need for alternative long-term treatment options.
- The Role of Tissue Resident Memory T Cells in the Skin
- TRM cells remain in the skin even when clinically healed or re-pigmented, or as seen in conditions such as psoriasis where you have clinically normal skin.33-36
- Conrad provided an example of vitiligo, where initial T cell activation leads to melanocyte elimination and subsequent depigmentation. Although treatment may result in clinical normalcy and re-pigmentation, he stated that the TRM cells remain. Following treatment cessation, subsequent local reactivation of these TRM cells by a disease trigger can recruit further T cells, resulting in a clinical relapse.33-36 It was suggested that for disease modification and prevention of relapse, it would be necessary to eliminate these TRM cells.
- However, Conrad cautioned that eliminating all TRM cells may not only remove disease-specific cells but also those providing protection against pathogens.
- In previously unaffected, non-lesional psoriasis skin, TRM cells accumulate over the course of the disease.37 Conrad identified that an alternative is to prevent TRM cells from populating the skin through early intervention. However, there is limited data on this.
Disease course and the memory of vitiligo and long-term options
- The challenge with current treatment options is that after successful therapy, such as phototherapy, many patients relapse within 12 months with recurrent depigmentation that typically occurs in the same lesions. This Conrad highlighted, indicated the “development of a disease memory within the skin.” He proposed that a longer disease duration may be a risk factor for (earlier) relapse.
- Therefore, “early intervention, we have a higher chance to tackle that problem,” and have a higher chance of the patient going into remission and avoiding a relapse. Conrad said that this could potentially “reverse disease memory or prevent its establishment.”
The role of tissue resident memory T cells in the skin
Objectives for Long-term Vitiligo Treatment
- The need to halt depigmentation, slow the disease progression, prevent relapses, and have time to induce re-pigmentation can take 6 months up to 2 years or more.20 Conrad concluded that the aim for early intervention, to enable disease modification by preventing or reversing the skin population of TRM and preventing or reversing epigenetic changes is still yet to be seen.
- However, there is a need to tackle the burden of disease through early intervention and as early as possible so that we have treatment options available, and that there is a need for long-term management.
- Considering the pathogenesis of vitiligo, the session identified potential treatment targets to block early depigmentation by targeting interferon-γ and to prevent relapses by blocking IL-15 to prevent TRM cell activation or maintenance, which can be achieved through JAK1 inhibition (Figure 2).2,30,42-50 Conrad summarised that it makes sense to inhibit Th-1 through JAK1 inhibition as an option to achieve vitiligo remission and long-term control.
Figure 2: The vitiligo pathogenesis and objectives in vitiligo treatment.2,30,42-50
Figure adapted from Qi F et al.46 CC-BY-4.0
Which JAK member(s) are inhibited by ruxolitinib cream?
Q:
JAK 1
JAK 2
JAK 3
TY2K
SUBMIT
Which JAK member(s) are inhibited by ruxolitinib cream?
Q:
JAK 1
JAK 2
JAK 3
TY2K
How Ruxolitinib Cream Fits in Shared Decision-Making Strategies for Effective Vitiligo Management Markus Böhm
In the final presentation, Böhm highlighted the importance of shared decision-making strategies in treating patients with nonsegmental vitiligo.
Targeted Therapy for Vitiligo with Ruxolitinib Cream
- The two Phase III randomised controlled trials (TRuE-V1 and TRuE-V2) and long-term extension study (TRuE-V LTE) demonstrated the role of ruxolitinib, highlighting its effectiveness in achieving meaningful facial re-pigmentation (demonstrated by improved facial-VASI [F-VASI]) in long-standing vitiligo disease.53,54
- The two Phase III randomised controlled trials (TRuE-V1 and TRuE-V2) and long-term extension study (TRuE-V LTE) demonstrated the role of ruxolitinib, highlighting its effectiveness in achieving meaningful facial re-pigmentation (demonstrated by improved facial-VASI [F-VASI]) in long-standing vitiligo disease.53,54
- These studies recruited 674 patients (n=330 in TRuE-V1 and n=344 in TRuE-V2) aged 12 years and above with non-segmental vitiligo and a 10% or less BSA, from 101 centres in North America and Europe.53
- The primary endpoint was an improvement in F-VASI75 (i.e., 75% re-pigmentation) after Week 24.53
- Those patients who were responders with F-VASI90 (i.e., 90% repigmentation) were invited to the extension and 2-year follow-up as part of the TRuE-V LTE.54,55
- This cohort was randomised into two arms, one where ruxolitinib cream was applied throughout the trial, and the other was a withdrawal arm where patients stopped applying the treatment to evaluate relapse rate.54,55
Figure 3: International statement of diagnosis and care of nonsegmental vitiligo.51
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, van Geel N, et al.51 © 2023 The Authors. Reproduced with permission of John Wiley & Sons Inc.
Shared decision-making strategies
- The session highlighted that the role of shared decision-making is important as it enables patients to better adhere to a given treatment, avoiding treatment failure and improving QoL.51
- Böhm also noted the tools to support this, whether they are paper-based resources or mobile applications, the importance is to provide the information.
- This was also highlighted by the recent treatment algorithm by the International Vitiligo Task Force (Figure 3), where under the established diagnosis there are defined treatment goals, expectations, and prognosis, shared decisions based on treatment pros and cons, disease impact, disease activity, and lesion location.52 These points, Böhm noted, are what should be explained to the patient, as well as discussion of the therapy options.52
- The session also emphasised the importance of HCPs knowing the clinical data of treatments to answer patient questions. Böhm stressed the significance of using a shared decision-making process to communicate to the patient.
Discover figure 3
1
Shared Decision-Making Strategies
Shared decision-making is an important tool in long-term management of chronic conditions such as vitiligo.51
2
Targeted Therapy for Vitiligo with Ruxolitinib Cream
To support HCPs' understanding of treatment options, Böhm presented data from the first vitiligo-specific immunomodulatory therapy, a selective JAK1 and JAK2 inhibitor, ruxolitinib topical cream.
Shared decision-making is an important tool in long-term management of chronic conditions such as vitiligo.51
Put simply, Böhm said shared decision-making is the “provision of information to the patient, and also to listen to the patient.” This includes considering patient expectations, providing clinically relevant information, considering the nature of the disease, diagnosis and consequences, and treatment options, including what areas are difficult to treat, expectations of available therapies, and that some areas may not respond well.51
Another point identified by Böhm is that when explaining clinical data to patients, is to explain that it takes time. He said that unlike psoriasis or atopic dermatitis, with endpoints within 16 weeks or 24 weeks, it takes from 24 up to 52 weeks for vitiligo. Böhm indicated that if patients are not responding immediately, they should be persistent with the treatment.
- Böhm concluded that shared decision-making is a important tool for the successful therapeutic management of patients with vitiligo, particularly when considering newly approved therapies.
- Long-term treatment is usually needed in vitiligo, making shared decision-making an even more important tool considering the burden of using treatment against the need to get improved responses when treated for longer.
References
1. Rashighi M, Harris JE. Interfering with the IFN-γ/CXCL10 pathway to develop new targeted treatments for vitiligo. Ann Transl Med. 2015;3(21):343.
2. Frisoli ML et al. Vitiligo: mechanisms of pathogenesis and treatment. Annu Rev Immunol. 2020;38:621-48.
3. Kent G. Understanding the experiences of people with disfigurements: an integration of four models of social and psychological functioning. Psychol Health Med. 2000;5(2):117-29.
4. Rankin M, Borah GL. Perceived functional impact of abnormal facial appearance. Plast Reconstr Surg. 2003;111(7):2140-6.
5. Bibeau 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(10):1124-28.
6. Lai YC et al. Vitiligo and depression: a systematic review and meta-analysis of observational studies. Br J Dermatol. 2017;177(3):708-18.
7. van Geel N et al. Clinical visible signs of disease activity in vitiligo: a systematic review and meta-analysis. J Eur Acad Dermatol Venereol. 2019;33(9):1667-75.
8. Bibeau K et a. Vitiligo prevalence and quality of life among adults in Europe, Japan and the USA. J Eur Acad Dermatol Venereol. 2022;36(10):1831-44.
9. van Geel N et al. Cessation of spread as a treatment objective in vitiligo: perception from the patients' point of view. Br J Dermatol. 2016;174(4):922-4.
10. Cunliffe WJ et al. Vitiligo, thyroid disease and autoimmunity. Br J Dermatol. 1968;80(3):135-9.
11. Dahir AM, Thomsen SF. Comorbidities in vitiligo: comprehensive review. Int J Dermatol. 2018;57(10):1157-64.
12. Ma SH et al. Association between vitiligo and hearing loss. J Am Acad Dermatol. 2021;85(6):1465-72.
13. Ezzedine K et al. Psychosocial effects of vitiligo: a systematic literature review. Am J Clin Dermatol. 2021;22(6):757-74.
14. Wang G et al. The prevalence and odds of depression in patients with vitiligo: a meta-analysis. J Eur Acad Dermatol Venereol. 2018;32(8):1343-51.
References
15. Hamzavi IH et al. Exploring the natural and treatment history of vitiligo: perceptions of patients and healthcare professionals from the global VALIANT study. Br J Dermatol. 2023;189(5):569-77.
16. Rosmarin D et al. Disease course, treatment patterns and goals among patients with non-segmental vitiligo across Europe and the United States. Dermatol Ther (Heidelb). 2024;14(7):1945-57.
17. Seneschal J, Boniface K. Vitiligo: current therapies and future treatments. Dermatol Pract Concept. 2023;13(4S2):e2023313S.
18. Mahil SK et al.; BADBIR study group and the PSORT consortium. Psoriasis treat to target: defining outcomes in psoriasis using data from a real-world, population-based cohort study (the British Association of Dermatologists Biologics and Immunomodulators Register, BADBIR). Br J Dermatol. 2020;182(5):1158-66.
19. Wańkowicz-Kalińska A et al. Immunopolarization of CD4+ and CD8+ T cells to Type-1-like is associated with melanocyte loss in human vitiligo. Lab Invest. 2003;83(5):683-95.
20. Taieb A et al. Guidelines for the management of vitiligo: the European dermatology forum consensus. Br J Dermatol. 2013;168(1):5-19.
21. Narayan VS et al. Patients' perspective on current treatments and demand for novel treatments in vitiligo. J Eur Acad Dermatol Venereol. 2021;35(3):744-8.
22. Austin M. Fighting and living with vitiligo. J Am Acad Dermatol. 2004;51(Suppl 1):S7-8.
23. Misery L et al. White paper on psychodermatology in Europe: a position paper from the EADV psychodermatology task force and the European society for dermatology and psychiatry (ESDaP). J Eur Acad Dermatol Venereol. 2023;37(12):2419-27.
24. Vitiligo International Patient Organisations Committee (VIPOC). Rewriting the vitiligo experience: a white paper. 2024. Available at: https://www.vipoc.org/european-vitiligo-white-paper/?utm_source=events&utm_medium=QR-code&utm_campaign=dermatologist-conference-vitiligo-paper. Last accessed: 1 October 2024.
References
25. Dubertret L. Strategy for treatment of psoriasis: systemic treatments. J Dermatol. 1998;25(12):788-92.
26. Divito SJ, Kupper TS. Inhibiting Janus kinases to treat alopecia areata. Nat Med. 2014;20(9):989-90.
27. Katz EL, Harris JE. Translational research in vitiligo. Front Immunol. 2021;12:624517.
28. Chen X et al. Oxidative stress-induced IL-15 trans-presentation in keratinocytes contributes to CD8+ T cells activation via JAK-STAT pathway in vitiligo. Free Radic Biol Med. 2019;139:80-91.
29. Schlapbach C, Conrad C. TYK-ing all the boxes in psoriasis. J Allergy Clin Immunol. 2022;149(6):1936-9.
30. Strassner JP, Harris JE. Understanding mechanisms of autoimmunity through translational research in vitiligo. Curr Opin Immunol. 2016;43:81-8.
31. Bishnoi A, Parsad D. Clinical and molecular aspects of vitiligo treatments. Int J Mol Sci. 2018;19(5):1509.
32. Migayron L et al. Vitiligo, from physiopathology to emerging treatments: a review. Dermatol Ther (Heidelb). 2020;10(6):1185-98.
33. Cheuk S et al. CD49a expression defines tissue-resident CD8+ T cells poised for cytotoxic function in human skin. Immunity. 2017;46(2):287-300.
34. Richmond JM et al. Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo. Sci Transl Med. 2018;10(450):eaam7710.
35. Boniface K et al. Vitiligo skin is imprinted with resident memory CD8 T cells expressing CXCR3. J Invest Dermatol. 2018;138(2):355-64.
36. Jacquemin C et al. NKG2D defines a subset of skin effector memory CD8 T cells with proinflammatory functions in vitiligo. J Invest Dermatol. 2020;140(6):1143-53.e5.
37. Vo S et al. CD8 resident memory T cells with interleukin 17A-producing potential are accumulated in disease-naïve nonlesional sites of psoriasis possibly in correlation with disease duration. Br J Dermatol. 2019;181(2):410-2.
CONCLUSION
- The burden of vitiligo and the challenges of accessing optimal care highlight the importance of both early and long-term management.
- Vitiligo is a chronic autoimmune disease that is characterised by melanocyte loss, which results in depigmented skin, driven by the JAK-STAT pathway.
- Dermatologists have the opportunity to lead the way in the successful development of therapeutic management, with shared decision-making as an important cornerstone.
- Ruxolitinib cream is a JAK inhibitor that facilitates quality repigmentation by inhibiting the JAK-STAT pathway.
- Patients receiving any treatment for vitiligo should be advised that repigmentation is gradual due to melanocyte regeneration, and requires persistence of 6–12 months+ for satisfactory re-pigmentation.
References
EU/RUXO/NP/24/0009