10.5826/dpc.1304S2a313S
The current management of vitiligo remains challenging; however, different strategies can be proposed to patients with a good efficacy in many cases. First, it is important to identify patients in the active phase of the disease because treatment should start as soon as possible to halt its progression. For patients with a stable disease, the treatment strategy is now well-stratified and is based on a combination of phototherapy (natural or in a cabin) and topical immunomodulatory agents. Surgical treatments are useful for localized and stable vitiligo, as well as for segmental vitiligo. Depigmentation remains indicated in very extensive forms. The recent approval of topical ruxolitinib cream in both the US and Europe brings new approaches for the management of vitiligo and paves the way for the development of new topical or oral targeted drugs.
text/xml
2160-9381
3893
en
Katia Boniface
https://creativecommons.org/licenses/by-nc/4.0
Dermatology Practical & Conceptual
treatment
Vitiligo: Current Therapies and Future Treatments
Text.Serial.Journal
https://dpcj.org/index.php/dpc
Review
2023-12-19
2023-09-26
2023-12-19
2024-01-25
e2023313S
Dermatol Pract Concept
The current management of vitiligo remains challenging; however, different strategies can be proposed to patients with a good efficacy in many cases. First, it is important to identify patients in the active phase of the disease because treatment should start as soon as possible to halt its progression. For patients with a stable disease, the treatment strategy is now well-stratified and is based on a combination of phototherapy (natural or in a cabin) and topical immunomodulatory agents. Surgical treatments are useful for localized and stable vitiligo, as well as for segmental vitiligo. Depigmentation remains indicated in very extensive forms. The recent approval of topical ruxolitinib cream in both the US and Europe brings new approaches for the management of vitiligo and paves the way for the development of new topical or oral targeted drugs.
Katia Boniface
2023/12/19
10.5826/dpc.1304S2a313S
e2023313S
University of Bordeaux, CNRS, Immuno ConcEpT, UMR 5164, Bordeaux, France 
2160-9381
treatment
en
e2023313S
Regazzetti C, Joly F, Marty C, et al. Transcriptional Analysis of Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promising Target for Repigmenting Vitiligo Patients. J Invest Dermatol 2015;135:3105–14.
Vitiligo: Current Therapies and Future Treatments
https://dpcj.org/index.php/dpc/article/download/3893/2437
   Vitiligo: Current Therapies and Future Treatments
                                             Julien Seneschal1,2, Katia Boniface2


1 Department of Dermatology and Pediatric Dermatology, National Reference Center for Rare Skin disorders, Hôpital Saint-André,
  Bordeaux, France
2 University of Bordeaux, CNRS, Immuno ConcEpT, UMR 5164, Bordeaux, France



Key words: vitiligo, management, treatment
Citation: Seneschal J, Boniface K. Vitiligo: Current Therapies and Future Treatments. Dermatol Pract Concept. 2023;13(4)S2:e2023313S.
DOI: https://doi.org/10.5826/dpc.1304S2a313S
Accepted: December 13, 2023; Published: December 2023
Copyright: ©2023 Seneschal et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-
NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use,
distribution, and reproduction in any medium, provided the original authors and source are credited.
Funding: None.
Competing Interests: Julien Seneschal: received grants and/or honoraria from AbbVie, Bristol Myers Squibb, Calypso Biotech, Eli Lilly,
Incyte, LEO Pharma, Novartis, Pfizer, Pierre Fabre, Sanofi, Sun Pharmaceuticals, and Viela Bio; and has a patent on MMP9 inhibitors and
uses thereof in the prevention or treatment of a depigmenting disorder and three-dimensional model of depigmenting disorder.
Katia Boniface: received grants from Calypso Biotech, LEO Pharma, Pfizer, Pierre Fabre, Sanofi, and has a patent on MMP9 inhibitors and
uses thereof in the prevention or treatment of a depigmenting disorder and three-dimensional model of depigmenting disorder.
Authorship: Both the authors have contributed significantly to this publication.
Corresponding Author: Julien Seneschal, Department of Dermatology, Hôpital Saint-André, CHU de Bordeaux, Bordeaux, France.
Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France. Phone : +33(0)5 56 79 47 05 Fax : +33(0)5 56 79 49
75 E-mail: julien.seneschal@chu-bordeaux.fr




  ABSTRACT             The current management of vitiligo remains challenging; however, different strategies can be proposed
                       to patients with a good efficacy in many cases. First, it is important to identify patients in the active
                       phase of the disease because treatment should start as soon as possible to halt its progression. For pa-
                       tients with a stable disease, the treatment strategy is now well-stratified and is based on a combination
                       of phototherapy (natural or in a cabin) and topical immunomodulatory agents. Surgical treatments
                       are useful for localized and stable vitiligo, as well as for segmental vitiligo. Depigmentation remains
                       indicated in very extensive forms. The recent approval of topical ruxolitinib cream in both the US and
                       Europe brings new approaches for the management of vitiligo and paves the way for the development
                       of new topical or oral targeted drugs.




Introduction                                                            for treatment among patients. Advances in understanding
                                                                        the pathomechanisms of vitiligo led to the development of
Vitiligo is a common chronic depigmenting skin disease                  targeted therapies. For example, ruxolitinib, a topical JAK1/
that can have a significant impact on the quality of life of            JAK2 inhibitor, is now approved for the management of vit-
those affected. Consequently, there is often a high demand              iligo both in the US and Europe. This review aims to provide



Review | Dermatol Pract Concept. 2023;13(4)S2:e2023313S                                                                                 1
a practical guidance on managing patients with vitiligo and          6 to 24 months of treatment to achieve significant repigmen-
to explore potential future therapies currently in develop-          tation. Patients must be clearly warned that the treatment is
ment. Recent worldwide expert recommendations for the                long and often tedious, as many patients stop the treatment
diagnosis and management of vitiligo have been recently              after 1 to 2 months without seeing any results.
published [1,2]. Part 1 of the recommendations provides a               Topical immunomodulatory treatments are important.
practical algorithm for the treatment of vitiligo.                   On the face and other sensitive areas, tacrolimus 0.1% (in-
                                                                     cluding in infants) or pimecrolimus 1% should be used twice

Objectives of Treatments                                             a day. Unfortunately, this prescription is still off-label despite
                                                                     numerous very robust methodological studies [10,11]. On
Treatment strategies depend on several clinical characteris-         the body, a strong topical steroid can be used instead of tacro-
tics, such as disease subtype, the extent of vitiligo, and disease   limus, once a day, preferably in the evening, and sequentially
activity. These factors should be systematically assessed be-        (e.g. 5 days a week) [12]. The topical JAK-inhibitor ruxoli-
fore deciding on a specific therapy. The management of vitil-        tinib is the first treatment approved for vitiligo both in US
igo should encompass three main complementary objectives:            and Europe for the management of vitiligo affecting the face
1) halting disease progression, 2) inducing repigmentation,          and less than 10% of the body surface area for adults and
melanocyte regeneration and proliferation, and 3) maintain-          adolescents (≥12 years old). Two randomized, double blind,
ing repigmentation and preventing disease recurrence.                phase III studies were conducted in 674 patients. Patients
                                                                     applied ruxolitinib cream 1.5% twice a day. Response rates
Treating Patients with Active Disease                                were much better than in the placebo group, with 50.3%
Vitiligo is a chronic condition that often progresses in flare-      and 74.6% of patients achieving a Facial-VASI (F-VASI) 75
ups. It is impossible to predict the long-term evolution of          and 50, respectively, at week 52. Moreover, 51.1% of pa-
vitiligo, and to date there are no reliable biological markers       tients achieved a total VASI (T-VASI) of 50 at week 52 [13].
of activity. However, clinical signs of disease activity have        Head and neck responded the best, followed by upper and
been identified, such as inflammatory borders, the Koebner           lower limbs, and by trunk. Hands and feet remained the
phenomenon, hypochromic areas/borders, and confetti-like             most difficult areas to repigment. Interestingly, all the areas,
depigmentation. It is essential to detect active forms of vit-       excepted for hands and feet, did not reach a plateau, sug-
iligo because a treatment aiming to block flare-ups must be          gesting that longer treatment will allow further improvement
initiated urgently [3–7].                                            that was confirmed in long-term extension studies. Adverse
    While data are primarily based on open or retrospective          events were mainly mild or moderate. The most common ad-
studies, it is now widely accepted that the treatment for pa-        verse events were acneiform reactions located on site of the
tients with highly progressive disease should combine sys-           application as well as pruritus. Clinical trials are ongoing to
temic therapies and phototherapy [8]. To date, the systemic          see whether the efficacy could be better in combination with
therapy mainly relies on mini-pulses of systemic steroids for        UV lights (NCT05247489).
3 to 6 months (e.g methylprednisolone 16mg (or dexametha-               Indeed, currently, without UV (whether natural, cabin,
sone 5mg) two consecutive days in adults, the dose should be         lamp or laser), the repigmentation is long to obtain. If pos-
adapted for children) [9]. For children in the growth phase,         sible, UVB should be preferred to PUVA therapy. For local-
a paediatric advice should be given after 3 months of treat-         ized vitiligo, excimer lamps and lasers are of great interest
ment. Systemic steroids should be combined with photother-           [14–17]. It is important to note that there are now narrow
apy: e.g Narrow band UVB 2-3 times/week for 6 months.                spectrum UVB lamps available that are finally affordable for
This combination blocks relapses in over 80% of cases. In            patients [18,19]. These lamps allow home phototherapy and
small children, phototherapy cannot be used and the mini-            are very useful for localized lesions of vitiligo. Sun exposure
pulses are used as a monotherapy. Depending on the season,           can be offered during the summer season. Patients should be
moderate but regular exposure to the sun is recommended to           advised to expose moderately themselves at least 3 or 4 times
stimulate repigmentation.                                            a week, without sunscreen, until their skin turns pink.
                                                                        A combination of sun exposure with immunomodulating
Treatment for Patients with a Stable Disease                         agents is crucial to achieve good repigmentation. There are
With current strategies, complete or near complete repig-            now well-established recommendations for using photother-
mentation could be achieved (e.g. 70 to 80% of repigmen-             apy in patients with vitiligo [17]. Regarding the sun exposure
tation of lesions located on the face; 50% of repigmentation         in patients with vitiligo, it is important to note that patients
of lesions located on the body; hands and/or feet remain             with vitiligo have a lower risk of developing skin cancer and
difficult to treat). Importantly, the treatment should be eval-      in particular a lower risk of developing melanoma. There is
uated after at least 6 months. Indeed, it can take between           also no increased risk of skin cancer with narrow-spectrum



2                                                                            Review | Dermatol Pract Concept. 2023;13(4)S2:e2023313S
UVB phototherapy in vitiligo (up to at least 400 sessions). In    proportion of F-VASI change from baseline was significantly
addition, no increased risk of skin cancers has been shown if     different in the ritlecitinib 50 mg group compared to pla-
NB-UVB is combined with tacrolimus [20–22].                       cebo for the with (-21.2% vs 2.1%, P<0.001). Strategies to
                                                                  target IL-15 or its receptor CD122 to inhibit the generation
What is the Place of Melanocyte-Grafting?                         and the maintenance of skin resident memory T cells demon-

Transplants have two main indications in vitiligo. They can       strated durable treatment responses in a pre-clinical mouse

be proposed after the failure of medical treatments for: vitil-   model of vitiligo and clinical trials using this strategy are un-

igo that has been stable for at least 12 months and segmental     der way [30]. Blocking the initiation of the disease could be

vitiligo.                                                         also an important step for future therapies in vitiligo. HP70i

    Several techniques have been described: – epidermal           seems to be a critical Danger Associated Molecular Pattern

­suspensions; – epidermal suction and then grafting; – thin       (DAMP) important for the initiation of the disease. Block-

skin grafting; – mini-grafting; – in vitro culture of keratino-   ing HSP70i activity might offer a good strategy as shown in

cyte and melanocyte suspensions. Epidermal suspensions are        pre-clinical animal models [31–33]. Preventing melanocyte

preferred and now approved commercial tissue-dissociation         detachment by using matrix metalloproteinase-9 inhibitors

kits can be used in the clinic [23,24].                           could also be effective [34]. Recent data suggest a dysbiosis
                                                                  in the skin and the gut of vitiligo patients. Modulating the

How can Recurrences be Prevented?                                 vitiligo microbiome offers potential new strategies [35]. In
                                                                  addition, to induce a better repigmentation, it will be import-
Almost 50% of vitiligo lesions recur in the first year after
                                                                  ant to combine topical and/or oral immunomodulators with
repigmentation without a maintenance therapy [25]. For in-
                                                                  strategies that will promote the differentiation and prolifer-
stance for the face, it has been shown than the use of tacroli-
                                                                  ation of melanocyte stem cells in vitiligo lesions, especially
mus 0.1% twice weekly (without the need of sun exposure)
                                                                  located on acral areas or in areas with poliosis [36]. In this
reduces the risk of relapse from 40% to 9.7% [26]. Topical
                                                                  line, the WNT signaling, which is repressed in depigmented
steroids on the same schedule are probably also effective
                                                                  skin of vitiligo patients, may be an important pathway to
but this has not been yet demonstrated. For patients with a
                                                                  target to induce melanocyte differentiation.
larger extent of the disease, the use of NB-UVB once or twice
a month as a maintenance treatment could be discussed [17].
However, data supporting this procedure are still lacking.        Conclusion
Some systemic treatments currently under development may
be of interest to block the recurrence of vitiligo.               Patients with vitiligo should be informed on therapeutic op-
                                                                  tions available to treat their conditions. Topical ruxolitinib
                                                                  cream is now approved for vitiligo and this will open the
When and How to Propose Depigmentation?
                                                                  development of other topical and/or systemic treatments for
Depigmentation can be discussed for patients with de-
                                                                  the disease. It is now important to recognize patients with
pigmented areas affecting more than 50% of the body.
                                                                  progressive disease that will require urgent treatment to stop
Chemical depigmenting products such as MEBH (hydroqui-
                                                                  the spreading of the disease.
none monobenzylether) are no longer available in most of
­European countries. Depigmenting lasers have shown simi-
lar approximately a 70% success rate after 1 to 3 sessions.       References
Maintenance sessions after the summer are often necessary,
                                                                   1. Geel N, Speeckaert R, Taïeb A, et al. Worldwide expert recom-
especially on light exposed areas such as the face. For small         mendations for the diagnosis and management of vitiligo: Posi-
areas, cryotherapy is an interesting option [27,28].                  tion statement from the International Vitiligo Task Force Part
                                                                      1: towards a new management algorithm. J Eur Acad Dermatol
                                                                      Venereol 2023.
Future Therapies in Development
                                                                   2. Seneschal J, Speeckaert R, Taïeb A, et al. Worldwide expert rec-
Vitiligo patients can be strongly encouraged to participate           ommendations for the diagnosis and management of vitiligo:
in the latest clinical trials to promote the development of           Position statement from the international Vitiligo Task Force—
new and more efficient therapies. Besides the approval of             Part 2: Specific treatment recommendations. J Eur Acad Derma-
topical ruxolitinib both in US and Europe, the oral JAK in-           tol Venereol 2023.
                                                                   3. Zhang L, Chen S, Kang Y, et al. Association of Clinical Markers
hibitors baracitinib (a JAK1/2 inhibitor), upadacitinib and
                                                                      With Disease Progression in Patients With Vitiligo From China.
povorcitinib (JAK1 inhibitors are currently being tested in
                                                                      Jama Dermatol 2020;156.
phase II ongoing trials. Ritlecitinib (a JAK3/TEC inhibi-          4. Sosa JJ, Currimbhoy SD, Ukoha U, et al. Confetti-like depigmen-
tor) was recently evaluated with different doses in a phase           tation: A potential sign of rapidly progressing vitiligo. J Am Acad
II trial that included 364 patients [29]. After 24 weeks, the         Dermatol 2015;73:272–5.



Review | Dermatol Pract Concept. 2023;13(4)S2:e2023313S                                                                                3
 5. Geel N van, Speeckaert R, Wolf JD, et al. Clinical signifi-               21. Bae JM, Ju HJ, Lee RW, et al. Evaluation for Skin Cancer and
    cance of Koebner phenomenon in vitiligo. Brit J Dermatol                      Precancer in Patients With Vitiligo Treated With Long-term Nar-
    2012;167:1017–24.                                                             rowband UV-B Phototherapy. Jama Dermatol 2020;156:529–37.
 6. Geel N van, Grine L, Wispelaere PD, Mertens D, Prinsen CAC,               22. Ju HJ, Han JH, Kim M-S, et al. The long-term risk of lymphoma
    Speeckaert R. Clinical visible signs of disease activity in vitiligo:         and skin cancer was not increased after topical calcineurin inhib-
    a systematic review and meta‐analysis. J Eur Acad Dermatol                    itor use and phototherapy in a cohort of 25,694 patients with
    ­Venereol 2019;33:1667–75doi:10.1111/jdv.15604.                               vitiligo. J Am Acad Dermatol 2021.
 7. Geel N van, Passeron T, Wolkerstorfer A, Speeckaert R, Ezzedine           23. Mohammad TF, Hamzavi IH. Surgical Therapies for Vitiligo.
     K. Reliability and validity of the Vitiligo Signs of Activity Score          Dermatologic clinics 2017;35:193–203.
     (VSAS). Brit J Dermatol 2020.                                            24. Ju HJ, Bae JM, Lee RW, et al. Surgical Interventions for Patients
 8. Passeron T. Medical and Maintenance Treatments for Vitiligo.                  With Vitiligo. JAMA Dermatol 2021;157:307–16.
     Dermatol Clin 2017;35:163–70.                                            25. Nicolaidou E, Antoniou C, Stratigos AJ, Stefanaki C, Katsambas
 9. Tovar-Garza A, Hinojosa JA, Hynan LS, Pandya AG. Addition of                  AD. Efficacy, predictors of response, and long-term follow-up in
     oral minipulse dexamethasone to narrowband ultraviolet B photo-              patients with vitiligo treated with narrowband UVB photother-
     therapy and topical steroids helps arrest disease activity in patients       apy. J Am Acad Dermatol 2007;56:274–8.
     with vitiligo. The British journal of dermatology 2019;180:193–4.        26. Cavalié M, Ezzedine K, Fontas E, et al. Maintenance therapy
10. Passeron T, Ostovari N, Zakaria W, et al. Topical tacrolimus                  of adult vitiligo with 0.1% tacrolimus ointment: a randomized,
     and the 308-nm excimer laser: a synergistic combination for the              double blind, placebo-controlled study. The Journal of investiga-
     treatment of vitiligo. Arch Dermatol 2004;140:1065–9.                        tive dermatology 2015;135:970–4.
11. Seneschal J, Duplaine A, Maillard H, et al. Efficacy and Safety of        27. Komen L, Zwertbroek L, Burger SJ, Veen JPW, Rie MA,
     Tacrolimus 0.1% for the Treatment of Facial Vitiligo: A Multi-               ­Wolkerstorfer A. Q‐switched laser depigmentation in vitiligo, most
     center Randomized, Double-Blinded, Vehicle-Controlled Study.                  effective in active disease. Brit J Dermatol 2013;169:1246–51.
     J Investig Dermatol 2021;141:1728–34.                                    28. MOSHER DB, PARRISH JA, FITZPATRICK TB. Monobenzyle-
12. Lepe V, Moncada B, Castanedo-Cazares JP, Torres-Alvarez MB,                   ther of hydroquinone. Brit J Dermatol 1977;97:669–79.
    Ortiz CA, Torres-Rubalcava AB. A double-blind randomized                  29. Ezzedine K, Peeva E, Yamaguchi Y, et al. Efficacy and safety of
    trial of 0.1% tacrolimus vs 0.05% clobetasol for the treatment                oral ritlecitinib for the treatment of active nonsegmental vitil-
    of childhood vitiligo. Archives of Dermatology 2003;139:581–5.                igo: A randomized phase 2b clinical trial. J Am Acad Dermatol
13. Rosmarin D, Passeron T, Pandya AG, et al. Two Phase 3,                        2023;88:395–403.
    ­Randomized, Controlled Trials of Ruxolitinib Cream for ­Vitiligo.        30. Richmond JM, Strassner JP, Zapata L, et al. Antibody blockade
     New Engl J Med 2022;387:1445–55.                                             of IL-15 signaling has the potential to durably reverse vitiligo. Sci
14. Esmat SM, El‐Mofty M, Rasheed H, et al. Efficacy of narrow                    Transl Med 2018;10:eaam7710.
     band UVB with or without OMP in stabilization of vitiligo                31. Jacquemin C, Rambert J, Guillet S, et al. Heat shock protein
     ­
     activity in skin photo‐types (III–V): A double‐blind, randomized,            70 potentiates interferon alpha production by plasmacytoid den-
     placebo‐controlled, prospective, multicenter study. Photoderma-              dritic cells: relevance for cutaneous lupus and vitiligo pathogene-
     tol Photoimmunol Photomed 2021.                                              sis. The British journal of dermatology 2017;177:1367–75.
15. Esmat S, Hegazy RA, Shalaby S, Hu SC-S, Lan C-CE.                         32. Mosenson JA, Eby JM, Hernandez C, Poole ICL. A central role
     ­Phototherapy and Combination Therapies for Vitiligo. Derma-                 for inducible heat-shock protein 70 in autoimmune vitiligo.
      tologic clinics 2017;35:171–92.                                             ­Experimental Dermatology 2013;22:566–9.
16. Esmat S, Mostafa W, Hegazy RA, et al. Phototherapy: The vitil-            33. Mosenson JA, Zloza A, Nieland JD, et al. Mutant HSP70
      igo management pillar. Clin Dermatol 2016;34:594–602.                        ­Reverses Autoimmune Depigmentation in Vitiligo. Science trans-
17. Mohammad TF, Al-Jamal M, Hamzavi IH, et al. The Vitiligo                        lational medicine 2013;5:174ra28-174ra28.
      Working Group recommendations for narrowband ultraviolet B              34. Boukhedouni N, Martins C, Darrigade A-S, et al. Type-1 cytokines
      light phototherapy treatment of vitiligo. Journal of the American             regulate matrix metalloprotease-9 production and E-cadherin dis-
      Academy of Dermatology 2017;76:879–88.                                        ruption to promote melanocyte loss in vitiligo. Jci Insight 2020.
18. Mohammad TF, Silpa-Archa N, Griffith JL, Lim HW, Hamzavi                  35. Bzioueche H, Sjödin KS, West CE, et al. Analysis of Matched
      IH. Home phototherapy in vitiligo. Photodermatology, Photoim-                 Skin and Gut Microbiome of Patients with Vitiligo Reveals Deep
      munology & Photomedicine 2017;33:241–52.                                      Skin Dysbiosis: Link with Mitochondrial and Immune Changes.
19. Batchelor JM, Millington A, Thomas KS, et al. Home-based nar-                   J Invest Dermatol 2021;141:2280–90.
      rowband UVB, topical corticosteroid or combination for chil-            36. Regazzetti C, Joly F, Marty C, et al. Transcriptional Analysis of
      dren and adults with vitiligo: HI-Light Vitiligo three-arm RCT.               Vitiligo Skin Reveals the Alteration of WNT Pathway: A Promis-
      Heal Technol Assess 2020;24:1–128.                                            ing Target for Repigmenting Vitiligo Patients. J Invest Dermatol
20. Teulings HE, Overkamp M, Ceylan E, et al. Decreased risk of mel-                2015;135:3105–14.
      anoma and nonmelanoma skin cancer in patients with vitiligo: a
      survey among 1307 patients and their partners. British Journal of
      Dermatology 2012;168:162–71doi:10.1111/bjd.12111.




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