白癜风的管理加拿大共识指南（2025)

ABSTRACT

Introduction : Vitiligo remains a highly bur‑ densome disease associated with significant autoimmune and psychosocial comorbidi‑ ties. Although the therapeutic landscape has long been dominated by off-label therapy, new

Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s13555-025-01402-5 .

treatments are emerging. Limited guidance on how to safely and effectively utilize available therapies poses challenges for healthcare pro‑ viders. Herein, we provide generally accepted principles, consensus recommendations, and a treatment algorithm for the management of vitiligo, as developed by a panel of ten Cana‑ dian dermatologists with expertise in managing vitiligo.

Methods : The three-phase process consisted of identifying themes and research questions;

V.H.Prajapati Division ofDermatology, Department ofMedicine, University ofCalgary, Calgary, AB, Canada

V.H.Prajapati Section ofCommunity Pediatrics, Department ofPediatrics, University ofCalgary, Calgary, AB, Canada V.H.Prajapati Section ofPediatric Rheumatology, Department ofPediatrics, University ofCalgary, Calgary, AB, Canada

V.H.Prajapati $(\triangleright\triangle)$ Dermatology Research Institute, Suite 310, 8500 Blackfoot Trail S.E., Meadows Mile Professional Building, Calgary, ABT7J2E1, Canada e-mail: vimal@dermatologyresearch.ca

V.H.Prajapati Skin Health andWellness Centre, Calgary, AB, Canada

V.H.Prajapati Probity Medical Research, Calgary, AB, Canada

H.Lui· H.C.Hong Department ofDermatology andSkin Science, University ofBritish Columbia, Vancouver, BC, Canada H.Lui Vancouver Coastal Health Research Institute, Vancouver, BC, Canada

Y.Miller‑Monthrope· K.A.Papp· J.Yeung Division ofDermatology, Temerty School ofMedicine, University ofToronto, Toronto, ON, Canada

Y.Miller‑Monthrope· J.Yeung Women’s College Hospital, Toronto, ON, Canada

J.Ringuet Centre de Recherche Dermatologique du Québec Métropolitain, QuebecCity, QC, Canada

J.Ringuet McGill University, Montreal, QC, Canada

I.Turchin· K.A.Papp Probity Medical Research, Waterloo, ON, Canada

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conducting a systematic literature review; and discussing/voting on generally accepted prin‑ ciples, consensus statements, and a treatment algorithm using an iterative consensus process. Results : Experts agreed to 27 generally accepted principles, ten consensus statements, and a treatment algorithm. Education about vitiligo pathogenesis and repigmentation biol‑ ogy can help patients, caregivers, and healthcare providers set realistic expectations for treatment. Treatment should focus on repigmentation or stabilizing progression, rather than on depig‑ mentation. Topical therapies include topical corticosteroids, topical calcineurin inhibitors, and the topical Janus kinase inhibitor ruxoli‑ tinib cream. Phototherapy, such as narrow-band ultraviolet B and excimer laser/lamp, can be

used as monotherapy or in combination with other treatments. Off-label systemic therapies may be appropriate for patients with unstable or rapidly progressing disease. Surgical therapy may be suitable for patients with localized or stable recalcitrant disease. Maintenance therapy may help mitigate the risk of disease relapse.

Conclusion : Improved clarity around the ben‑ efits, risks, and limitations of available therapies has supported the development of robust guide‑ lines and a treatment algorithm for vitiligo. Dis‑ ease stabilization and repigmentation are goals that can largely be achieved, particularly when patients share a mutual understanding of vitiligo and its treatment options.

A Graphical Abstract is available for this article.

I.Turchin Brunswick Dermatology Center, Fredericton, NB, Canada I.Turchin Department ofMedicine, Dalhousie University, Halifax, NS, Canada H.C.Hong Probity Medical Research, Surrey, BC, Canada C.Lynde Lynde Institute forDermatology, Markham, ON, Canada C.Lynde Probity Medical Research, Markham, ON, Canada K.A.Papp Alliance Clinical Research, Waterloo, ON, Canada J.Yeung Probity Medical Research, Toronto, ON, Canada M.J.Gooderham SKiN Centre forDermatology, Peterborough, ON, Canada M.J.Gooderham Probity Medical Research, Peterborough, ON, Canada M.J.Gooderham Queen’s University, Peterborough, ON, Canada

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Graphical Abstract:

## Canadian Consensus Guidelines for the Managementof Vitiligo

Vimal H.Prajapati -Harvey Lui - Yvette Miller-Monthrope - Julien Ringuet Irina Turchin - H.Chih-ho Hong - Charles Lynde -Kim A. Papp - Jensen Yeung Melinda V Gooderham

 The graphical abstract represents the opinion of the authors. For a full list of declarations, including funding and author disclosure statements, please see the full text online. ? The authors, CC-BY-NC 2025

Keywords: Guidelines; Janus kinase inhibitor; Phototherapy; Topical calcineurin inhibitor; Topical corticosteroid; Vitiligo

|Key Summary Points| |---| |Why carry out this study?| |This study was undertaken to address a lack| |of guidance on the management of vitiligo| |with currently available treatment options in| || |The study asked how a panel of ten Canadian| |dermatologists with expertise in managing| |vitiligo would propose managing the disease.| |What was learned from the study?| |The panel provided generally accepted prin-| |ciples, consensus recommendations, and a| |treatment algorithm for the management| |of vitiligo that reflect the changing vitiligo| |treatment landscape.| |Healthcare providers will have a better| |understanding of patient disease burden and| |assessment tools for vitiligo and be better| |prepared to use a wide variety of treatments| |in conjunction with education to optimize| |therapeutic outcomes for their patients.|

negatively affect mental health and quality of life (QoL) [ 3 ]. The degree of the effect of vitiligo on mental health and QoL can be influenced by factors such as skin tone as well as ethnic and cultural backgrounds [ 3 , 4 ].

Vitiligo is rarely associated with physical symp‑ toms, such as pruritus and skin pain, that are characteristic of other immune-mediated inflam‑ matory diseases (IMIDs) of the skin [ 5 ]. Many persons with vitiligo are underrecognized, mis‑ diagnosed, and undertreated, due in part to mis‑ conceptions that there are very limited efficacious therapies and/or that the condition is primarily “cosmetic” [ 6 , 7 ]. These challenges can cause sub‑ stantial delays in formal diagnosis and treatment [ 8 ], which may lead to worse outcomes.

Various off-label therapies may be prescribed for patients with vitiligo, including topical cor‑ ticosteroids (TCS), topical calcineurin inhibitors (TCI), phototherapy, and systemic corticoster‑ oids [ 9 , 10 ]. Emerging treatments include topical and systemic Janus kinase inhibitors (JAKi) [ 11 ]; systemic biologics, particularly those focusing on interleukin-15 (IL-15) inhibition, are in the exploratory stages of development [ 12 ]. Ruxoli‑ tinib cream, a topical JAK1/JAK2 inhibitor, is cur‑ rently the only approved repigmentation therapy for the treatment of vitiligo in Canada [ 13 ], the USA [ 14 ], the UK [ 15 ], and the European Union [ 16 ]. Several systemic JAKi are currently being investigated in phase 3 clinical trials [ 17 – 19 ]. Repigmentation rates vary across all treatments, and the disease will frequently relapse upon dis‑ continuation of treatment [ 9 , 20 ].

DIGITAL FEATURES

This article is published with digital features, including a Graphical Abstract to facilitate understanding of the article. To view digital fea‑ tures for this article, go to https://doi.org/10. 6084/m9.figshare.28660781 .

A clear set of consensus treatment guidelines can facilitate optimal management of vitiligo. Herein we provide generally accepted principles, consensus recommendations, and a practical treatment algorithm for the management of viti‑ ligo, as developed by a panel of ten Canadian der‑ matologists with expertise in managing vitiligo.

INTRODUCTION

Vitiligo is a chronic autoimmune disease char‑ acterized by melanocyte destruction that leads to skin depigmentation [ 1 , 2 ]. Vitiligo is associ‑ ated with autoimmune and psychosocial comor‑ bidities, including stigmatization, which can

METHODS

An expert panel of ten Canadian dermatologists with extensive clinical and research experience in vitiligo developed practical statements and a treatment algorithm based on current scientific

evidence and expert opinion. The process con‑ sisted of three phases. In the first phase of the project, themes and clinical questions were pro‑ posed at a meeting of all ten experts in Novem‑ ber 2022.

In the second phase, a systematic literature review was conducted on the basis of specific clinical questions and population, intervention, control, and outcomes (PICO) terms identified by the experts. It aimed to address the question, “What is the range of disease burden of viti‑ ligo?” (Supplementary Material Table1). It also aimed to address the question, “What treatment options are available for vitiligo?” (Supplemen‑ tary Material Table2). Data extracted from the literature and expert opinion were used to draft generally accepted principles, consensus state‑ ments, and a treatment algorithm. These items were developed, validated, and then further refined by a subgroup of five of the experts (VHP, HL, IT, JR, and YM-M) at a meeting in August 2023. After this meeting, additional revisions were made asynchronously, with agreement reached among the five experts. An online sur‑ vey was conducted for this subgroup to catego‑ rize statements as generally accepted principles or consensus statements.

In the third phase of the project, all ten experts attended an in-person meeting in Sep‑ tember 2023 to discuss the generally accepted principles, as well as to vote on the final consen‑ sus statements and treatment algorithm using an iterative consensus process. Because the generally accepted principles for vitiligo were uniformly considered as foundational aspects of medical care, they were not subjected to vot‑ ing. For the consensus statements and treatment algorithm, the level of agreement was assessed on a 5-point Likert scale (1, “strongly disagree”; 5, “strongly agree”). Consensus was defined as $\geq75\%$ agreement (i.e., a mean Likert score $\ge3.75$ out of 5).This article is based on previously con‑ ducted studies and does not contain any new studies with human participants or animals per‑ formed by any of the authors.

RESULTS AND DISCUSSION

Literature Search and Expert Statements

The literature search for the first question (“What is the range of disease burden of viti‑ ligo?”) resulted in ten sources for data extrac‑ tion. The literature search for the second ques‑ tion (“What treatment options are available for vitiligo?”) resulted in 57 sources for data extrac‑ tion. Following discussions and an iterative con‑ sensus process, 27 generally accepted principles (Table 1 ) and ten consensus statements (Table 2 ) were adopted, details of which are provided in the next sections to guide recommendations for management. The treatment algorithm (Fig. 1 ) had unanimous $(100\%)$ agreement.

General Disease Considerations and Epidemiology

Vitiligo is a heterogeneous disease that is classi‑ fied into distinct clinical subtypes according to morphology and distribution [ 2 , 21 ]. The most common subtype included in clinical studies is nonsegmental vitiligo, wherein affected areas are present bilaterally [ 22 ]. Within nonsegmental vitiligo, many additional variants exist, includ‑ ing acrofacial, generalized, and mixed [ 21 ]. Seg‑ mental vitiligo is typically distinguished from nonsegmental vitiligo by its unilateral distribu‑ tion and clinical stability over time [ 21 ].

Current prevalence rates estimate that vitiligo affects approximately $0.5{-}2.0\%$ of the popula‑ tion worldwide [ 23 , 24 ]; however, this may be an underestimation of the actual global burden [ 23 ]. Many cases likely go underrecognized, undiagnosed/misdiagnosed, and undertreated, due in part to pervasive misconceptions about vitiligo, such as the beliefs that vitiligo cannot be treated effectively and that it is essentially “cosmetic” in nature [ 6 – 8 ]. Patients and their healthcare providers may have limited under‑ standing of the immune processes underlying vitiligo and be unaware that beneficial treat‑ ments are available [ 7 , 8 ].

Table1 Generally accepted principles for vitiligo

|Statement| |---| |General disease considerations/epidemiology| | Current estimates of incidence and prevalence are likely to underrepresent the actual burden of vitiligo, which tends to be underrecognized/underdiagnosed, undertreated, and poorly understood | || | It is important to recognize that vitiligo manifests with distinct clinical subtypes and is a heterogeneous disease. Vitiligo (nonsegmental) is the most studied clinical subtype in clinical trials | || |Understanding the burden of vitiligo should include the consideration of clinical subtypes, age, gender, distribution, skin| |Vitiligo is noteworthy among immune-mediated inflammatory diseases as it manifests primarily through changes in the| |appearance of the skin without physical symptoms yet significantly impacts patients QoL| |Lack of disease recognition, patient validation, and access to treatment add to the burden of vitiligo| |Psychosocial mental health, and QoL impact| |Patients with vitiligo experience increased psychosocial, mental health, and QoL impact that is often underrecognized| |Patients with vitiligo often experience discrimination; pediatric and adolescent populations can also struggle with teasing.| |bullying, and feeling self-conscious| |Comorbidities| |Patients with vitiligo have a higher prevalence of anxiety, depression, and suicidal ideation/behavior| |Assessment tools| || | Although DLQI and CDLQI are health-related QoL assessment tools that have been validated in vitiligo, they do not holistically capture its burden on patients | |Notwithstanding the availability of asessment tools that evaluate various quantitative aspects of vitiligo, the patient experi-| || |General management considerations| | Management of vitiligo is multimodal and should be individualized based on disease extent, location, level, and pattern as well as psychosocial, mental health, and QoL impact | | The treatment of vitiligo will not affect associated autoimmune conditions and vice versa, unless the treatment targets a similar pathomechanism | || | There is a lack of evidence on how well patients with segmental or mixed clinical subtypes of vitiligo will respond to treat- ment | || | Affrmation and assessment ofpsychosocial, mental health, and QoL impact ofvitilio on patients is an essntial aspect of the ongoing management | |The progression of vitiligo may be rapid or slow,but repigmentation tends to be slow| |Patients with vitiligo should be educated about minimizing physical trauma to the skin to avoid Koebnerization| |Patients with vitiligo should be encouraged to use sun protection to avoid sunburn and/or minimize contrast between|

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Table1 continued

|Statement|| |---|---| ||| | Evidence supporting the effcacy and safety of complementary and alternative therapies is insuffcient for the treatment of vitiligo | Monitoring of disease activity and treatment response for vitiligo can include baseline and serial photography by patient and/or practitioner, if available Evidence supporting the effcacy and safety of complementary and alternative therapies is insuffcient for the treatment of | ||| |Relapse with vitiligo is common and can be treated by reinitiating therapy|| |Camouflage may be appropriate as monotherapy or as an adjunctive therapy in patients with vitiligo|| |Repigmentation and/or stabilization strategies—topical therapies|| |Physicians should be aware and patients should be informed of the official warning against the concomitant use of topical|| |Repigmentation and/or stabilization strategies—phototherapy|| | Narrow-band ultraviolet B phototherapy and excimer laser/lamp therapy are the recommended forms oflight treatment fon patients with vitiligo Intentional sun exposure or use of recreational tanning beds are generally not recommended for the treatment of vitiligo || ||| | Unlike phototherapy for other dermatoses, phototherapy for vitiligo typically requires a protracted treatment course of ≥6-12 months || |There are effcacy and safety data to support the use of clinic-based excimer laser/lamp therapy either alone or in combina-|| |tion with other therapies for the treatment of patients with vitiligo|| |Repigmentation and/or stabilization strategies—surgical therapy|| ||| | There are efficacy and safety data to support the use of surgical therapy for the treatment of vitiligo in patients with localize stable recalcitrant disease ||

CDLQI Children’s Dermatology Life Quality Index, DLQI Dermatology Life Quality Index, QoL quality of life

Unlike many other IMIDs of the skin, vitiligo can negatively impact a patient’s QoL without physical symptoms in the majority of patients [ 25 ]. Some patients may experience pruritus within affected areas early in the disease course, and some patients may experience burning sensations with UV light exposure [ 6 , 26 , 27 ]. The burden of vitiligo and its impact on QoL are largely affected by disease- and patientrelated factors. Disease-related factors associated with higher overall QoL burden include longer duration, rapid progression, more extensive affected body surface area, and involvement of visible or sensitive sites, such as the face, hands, and genitals [ 3 , 28 ]. Patient-related factors eliciting greater QoL burden include age (pediatric versus adult), sex (women versus men), skin tone (Fitzpatrick skin types IV–VI

versus I–III), race (non-white versus white), and culture [ 3 , 28 – 30 ]. Women often experience greater QoL impairment than men, which may be due to higher perceived stigma as it relates to physical appearance, relationships, and decreased prospects for marriage in some cultures [ 29 , 31 ]. Lack of disease recognition, patient validation, and access to effective treatments further add to the burden of vitiligo [ 7 ].

Comorbidities and Impact on QoL

Patients with vitiligo are more likely to have other autoimmune comorbidities, such as thyroid disease, type 1 diabetes mellitus, alopecia areata, and pernicious anemia (Consensus

a

Table2 Consensus statements for vitiligo

| Statement| Level of agreement, % Likert sco1 || |---|---|---| |Comorbidities||| |1. Patients with vitiligo are at a higher risk of having coexisting autoimmune disorders,|86|| |including, but not limited to, thyroid disease,type 1 diabetes mellitus, alopecia areata, and||4.3(1.3)| |||| |Assessment tools|Assessment tools|Assessment tools| | 2. Vitiligo-specific assessment tools such as VASI, VESplus, VitiQoL, VIS, and VIPs have|98|4.9(0.3)| | been used in clinical trials but are neither essential nor practical in day-to-day clinical patient management |98|| |||| |General management considerations||| | 3. Treatment of patients with vitiligo is directed toward repigmentation and/or stabilization. 96 In exceptional cases, depigmentation may be a therapeutic option ||4.8(0.4)| ||96|| | 4. Healthcare providers are encouraged to consider screening for concomitant autoimmune and mental health disorders in patients with vitiligo and refer to other healthcare providers when appropriate ||4.8 (0.4)| |5. Maintenance therapy reduces the risk of relapse in patients with vitiligo|84|4.2(0.7)| |Repigmentation and/or stabilization strategies—topical tberapies||| |6. Topical therapy with corticosteroids, calcineurin inhibitors, and JAKi can be considered 100||5.0(0)| |as first-line monotherapy for the treatment of any form of vitiligo||| |7. The off-label use of topical corticosteroids, calcineurin inhibitors, and JAKi in|94|4.7(0.5)| |combination with phototherapy may be used for treating patients with vitiligo||| |Repigmentation and/or stabilization strategies—pbototberapy||| | 8. Phototherapy can be used alone or in combination with other therapies for the treatment ofvitiligo ||¥94 4.7(0.6)| |||| |Repigmentation and/or stabilization strategies—systemic therapy||| |9. In exceptional cases, off-label use of systemic immunomodulatory therapies can be||92| |considered for patients with unstable or rapidly progressive vitiligo. There are currently no||92| |approved systemic therapies for vitiligo||| |Depigmentation strategies—topical therapy||| |10. Although monobenzone (monobenzyl ether of hydroquinone) is approved for|¥98|4.9(0.3)| |depigmentation therapy in the treatment of vitiligo, it should only be prescribed in||| |exceptional circumstances by dermatologists experienced with this therapy|||

JAKi Janus kinase inhibitor, VASI Vitiligo Area Scoring Index, VES Vitiligo Extent Score, VIPs Vitiligo Impact Patient scale, VIS Vitiligo Impact Scale, VitiQoL Vitiligo-specific quality of life a Likert scale ranges from 1 to 5, with higher scores indicating more agreement

 Fig.1 Algorithm for the management of vitiligo (nonsegmental) in children, adolescents, and adults. a Visible/sensitive areas include the head/neck (especially face), hands, axilla/inguinal region, and genital area. b Narrow-band ultraviolet B phototherapy alone or in combination with other treatment modalities (e.g., topical corticosteroids,

topical calcineurin inhibitors, and topical JAK inhibitors). c Corticosteroids as oral mini pulse. d Immunomodulators include methotrexate, cyclosporine, azathioprine, minocycline, and JAK inhibitors. JAK Janus kinase, QoL quality of life

Statement 1 [Table 2 ]) [ 32 , 33 ]. Associations between vitiligo and autoimmune comorbidities may result from shared heritability genes [ 33 , 34 ].

Patients with vitiligo are also at higher risk for psychosocial comorbidities [ 3 , 28 ]. Prevalence rates of mental health disorders, such as anxiety, depression, sexual dysfunction, and suicidal

ideation/behavior, are higher among patients with vitiligo compared with healthy control groups or those with other skin diseases (e.g., alopecia areata, atopic dermatitis, and psoriasis) [ 3 , 35 – 39 ]. The psychosocial, mental health, and QoL burden may be higher with diseaserelated factors [ 3 , 28 ], patient-related factors, and discrimination or bullying, particularly in the case of children and adolescents [ 40 ]. Anxiety, depression, and impaired QoL have also been reported among caregivers of patients with vitiligo [ 3 , 28 ], particularly in cases of progressive versus stable vitiligo [ 41 ].

Assessment Tools

For healthcare providers to more effectively guide disease management, the patient’s per‑ spective must be considered alongside quali‑ tative and quantitative assessment tools (i.e., shared decision-making). In routine clinical practice, clinicians often use rapidity of disease progression, disease extent and distribution (including involvement of visible and sensi‑ tive sites), and disease effect on QoL, as well as patient motivations and preferences, to guide management [ 42 ].

Vitiligo-specific assessment tools are available for evaluation of physician-rated measures, such as disease extent and progression or repigmen‑ tation with treatment (e.g., the Vitiligo Area Scoring Index [VASI] [ 43 ], the Vitiligo Extent Score [VES] [ 44 ], and VESplus [ 45 ]) and patientreported outcomes (e.g., Vitiligo-specific quality of life [VitiQoL] [ 25 ]; Vitiligo Impact Scale [VIS] [ 46 ]; Vitiligo Impact Patient scale [VIPs] [ 47 ]; and Vitiligo Noticeability Scale [VNS] [ 48 ]). Wood’s lamp examination of the skin can be a simple and reliable adjunctive tool for visualizing cuta‑ neous depigmentation in vitiligo, particularly in patients with lighter constitutive skin color [ 49 ] where affected areas may be less apparent. The Dermatology Life Quality Index (DLQI) [ 50 ] and Children’s DLQI (CDLQI) [ 28 , 51 ] questionnaires may also be used to assess QoL in patients with vitiligo [ 28 ]. Although these formal assessment tools are often obligatory for clinical trials [ 52 ], they may not be practical for everyday clinical

practice (Consensus Statement 2). The DLQI and CDLQI, for example, may not sufficiently cap‑ ture disease burden, despite being validated for use in vitiligo [ 52 ].

Patient Education

Effective management of vitiligo can be aided by facilitating patient awareness of measures that can be taken to reduce the risk of progression. Because of the underlying pathomechanisms of vitiligo, repigmentation tends to be a slow pro‑ cess regardless of disease progression speed [ 53 ]. This can be a source of frustration for patients [ 7 ]. Thus, education about vitiligo pathogenesis and repigmentation biology can help patients, caregivers, and healthcare providers set realistic expectations for treatment.

Lifestyle management strategies may also be helpful for patients. Sun safety, including sun‑ screen, sun-protective clothing, and sun avoid‑ ance is recommended [ 8 ]. Not only can these measures reduce the risk of sunburn within areas affected by vitiligo but also they can limit the contrast between depigmented (affected) and pigmented (unaffected) areas, and may prevent new sites of involvement from Koebnerization [ 54 ]. Avoiding skin trauma in general is impor‑ tant [ 54 ].

Patients can also be educated about adjunc‑ tive options to prescribed treatments. Camou‑ flage may be used as monotherapy or an adjunc‑ tive therapy option [ 55 ]. Coverage of vitiligo with clothing or cosmetics has been found to improve overall QoL, although patients may find some methods ineffective, time-consuming, and/or expensive [ 55 , 56 ]. Limited data are avail‑ able regarding the efficacy of other complemen‑ tary and alternative therapies for vitiligo, such as herbal remedies or dietary supplements [ 57 ].

Treatment Considerations

For most patients who desire therapy, treat‑ ment will primarily focus on repigmentation and/or stabilizing progression, rather than on depigmentation (Consensus Statement 3). Treat‑ ment approaches differ depending on the goal

of therapy, and a variety of factors warranting individualized management of vitiligo should be considered by healthcare providers when recom‑ mending a treatment plan [ 58 ]. Clinical subtype, as well as disease extent and distribution, vary among patients and can impact QoL; thus, these factors should be considered when determin‑ ing treatment (Fig. 1 ). Currently, there is lim‑ ited evidence regarding response to treatment in patients with segmental or mixed clinical subtypes, although responses may be observed in patients with short disease duration (i.e., ${<}6$ months) [ 59 ]. Regardless of vitiligo subtype, patients and healthcare providers can moni‑ tor disease progression and treatment response by taking baseline and serial photographs of affected skin for direct comparisons over time.

Given increased risks for autoimmune and psychosocial comorbidities in patients with vitiligo, healthcare providers should take into consideration concomitant disorders and refer to other healthcare providers as necessary (Con‑ sensus Statement 4). Mental health and QoL impact of vitiligo should be considered for the successful ongoing management of vitiligo. Some patients may not be aware of concomitant disorders and may require additional screening. For vitiligo treatments that specifically target its underlying immunopathogenesis, associ‑ ated comorbid medical conditions will only be improved or stabilized if they progress through a similar mechanism. Less-targeted treatments, such as systemic corticosteroids, may temporar‑ ily abate multiple diseases regardless of patho‑ mechanism [ 60 ].

It is common for vitiligo to relapse if treat‑ ment is discontinued, often within 2years after stopping therapy, although the extent and rate of depigmentation may vary [ 20 , 61 ]. Mainte‑ nance therapy may help mitigate the risk of dis‑ ease relapse (Consensus Statement 5) [ 42 ], and there is evidence for some therapies (e.g., ruxoli‑ tinib cream [ 62 ] and tacrolimus ointment [ 63 ]) that this is the case. In many cases, repigmenta‑ tion occurs again when therapy is reinitiated.

Repigmentation and Stabilization Strategies

Topical Therapy

Historically, first-line monotherapy for treat‑ ment of vitiligo has included TCS and TCI (Consensus Statement 6) [ 58 ]. Ruxolitinib cream (JAK1/JAK2 selective inhibitor [ 64 ]; Con‑ sensus Statement 6) is currently the only repig‑ mentation therapy approved for the treatment of nonsegmental vitiligo in patients aged $\geq12$ years in Canada [ 13 ], the USA [ 14 ], the UK [ 15 ], and the European Union [ 16 ]. Twice-daily treat‑ ment with $1.5\%$ ruxolitinib cream is generally well tolerated and has demonstrated significant facial and body skin repigmentation versus vehi‑ cle within 24 weeks, with continued improve‑ ment through 52 weeks [ 65 ]. These findings may reflect the key role of the JAK-signal transducer and activator of transcription (STAT) pathway in vitiligo pathogenesis, including the media‑ tion of interferon- $\cdot\gamma$ and IL-15 signaling [ 66 ]. In general, topical therapies may be used in com‑ bination with phototherapy [ 42 ]. Twice-daily treatment with $1.5\%$ ruxolitinib cream com‑ bined with narrow-band ultraviolet B (NB-UVB) was well tolerated and effective in a phase 2 study [ 67 ]. However, there is an official warning against using TCI in combination with UV light exposure as it is not known whether TCI inter‑ feres with the skin’s response to UV damage [ 68 ]. Off-label use of topical therapies approved for other indications, such as TCS [ 69 ] and TCI [ 70 ], as well as compounded prescriptions of the topi‑ cal JAKi, tofacitinib [ 71 ], may also be effective in managing vitiligo (Consensus Statement 7), although prolonged or continuous use of some treatments are associated with local and sys‑ temic adverse events [ 58 ]. Treatment regimens following an intermittent or alternative sched‑ ule (e.g., 2weeks on/2 weeks off) may mitigate safety concerns associated with prolonged TCS use [ 9 ].

Phototherapy

Phototherapy can be used as monotherapy or in combination with other treatments (Con‑ sensus Statement 8) to achieve greater levels of

therapeutic success [ 72 , 73 ]. The recommended forms of phototherapy for patients with vitiligo include NB-UVB and excimer laser/lamp, which have been proven to be safer and more effica‑ cious than psoralen UVA (PUVA) or UVA1 [ 74 , 75 ].

In general, a minimum course of 6–12 months is required for the treatment of vitiligo with phototherapy [ 76 ]. Initial therapy should ide‑ ally be administered two or three times per week until adequate repigmentation is achieved [ 61 , 76 ]. Responses should be reassessed periodically with a decision for ongoing maintenance ther‑ apy or discontinuation being made only after 6–12 months of phototherapy. Maintenance therapy regimens may vary from once to twice weekly, and treatment can be discontinued if the repigmentation response is deemed adequate [ 76 ]. Office-based phototherapy with proper supervision is preferred over home-based pho‑ totherapy; however, home-based phototherapy may be acceptable in special circumstances [ 77 , 78 ], although patients should be closely moni‑ tored to prevent misuse.

Patients should be educated on the effects of phototherapy before undergoing treatment. Phototherapy can tan unaffected skin and para‑ doxically render vitiligo more noticeable [ 76 ]. Patients should also be advised that tanning parlor use is not recommended for treatment of vitiligo as it may cause Koebner phenomena if sunburn occurs [ 54 ] and can lead to increased risk of skin cancer [ 79 ].

Systemic Therapy

Although no systemic therapies are currently approved for the treatment of vitiligo, off-label use of systemic immunomodulators may be appropriate for patients with unstable or rap‑ idly progressing vitiligo (Consensus Statement 9). These agents should be used with caution owing to their risk–benefit profile, and may include corticosteroids (either transient or via pulse therapy) [ 80 ], JAKi (currently being inves‑ tigated in phase 3 clinical trials) [ 17 – 19 ], cyclo‑ sporine [ 81 ], or methotrexate [ 82 , 83 ].

Surgical Therapy

In patients with localized or stable recalcitrant vitiligo, efficacy and safety data support the use of surgical therapy as an appropriate treatment option [ 84 – 86 ]. Surgical techniques such as nee‑ dling, cellular suspension or punch grafts, suc‑ tion blister grafts, and melanocyte transplanta‑ tion [ 87 ] are suitable for cases of vitiligo that have been stable for $\geq\!12$ months and are resist‑ ant to topical therapy or phototherapy [ 42 ] Sur‑ gical therapy may be particularly useful in cases of segmental vitiligo, which is often resistant to other forms of treatment [ 9 ]. Other clinical characteristics (e.g., disease extent and distribu‑ tion) should also be taken into account when determining the appropriate surgical technique [ 9 ]. However, surgical therapies are not widely accessible in Canada.

Depigmentation Strategies

Although repigmentation to restore a patient’s native constitutive skin color is typically the goal of vitiligo treatment, intentional depig‑ mentation may be considered in exceptional cases, such as patients with treatment-resistant extensive disease [ 9 ]. Monobenzone (monoben‑ zyl ether of hydroquinone) [ 88 ] is approved in certain jurisdictions as a depigmentation ther‑ apy for patients with vitiligo; however, it should only be used by dermatologists who are experi‑ enced with this type of treatment (Consensus Statement 10). Further, it may be difficult to obtain. Additional depigmentation strategies include pigment-specific ablative laser therapy (e.g., Q-switched ruby, alexandrite, or neodym‑ ium-doped yttrium aluminum garnet [Nd:YAG]) and cryotherapy (e.g., liquid nitrogen) [ 89 , 90 ]. Depigmentation should be considered irrevers‑ ible, although spontaneous repigmentation may occur and is unpredictable [ 91 ].

Limitations

These guidelines are widely applicable but most closely approximate clinical practice in Canada

given that all experts who participated in the study practice in Canada.

CONCLUSIONS

Clinical data and experience support the development of an evidence-based algorithm to guide clinicians in the management of vitiligo. Disease stabilization and repigmentation are treatment goals that can be achieved to a certain extent with appropriate therapies, though factors such as disease duration and sites of involvement may influence the response. As ongoing research efforts evaluate the burden and treatment of vitiligo, new therapeutic options continue to emerge. Healthcare providers are encouraged to discuss new treatment options with patients to develop and facilitate an individualized and realistic treatment plan.

Medical Writing, Editorial and Other Assistance. Medical writing support was provided by Emily Mesev, PhD, and Andrew Barszczyk, PhD, from The Curry Rockefeller Group, LLC, a Citrus Health Group, Inc., company (Chicago, Illinois, USA), and was funded by Incyte Corpo‑ ration. The authors thank Christine Jean, Kait‑ ryn Campbell, and Jean-François Dicaire from Pinnacle Marketing & Education Inc. (Hudson, QC, Canada) for their contributions to this initiative.

Author Contributions. Vimal H. Praja‑ pati, Harvey Lui, Yvette Miller-Monthrope, Julien Ringuet, Irina Turchin, H. Chih-ho Hong, Charles Lynde, Kim A. Papp, Jensen Yeung, and Melinda J. Gooderham contributed to the dis‑ cussions, research, and validation of the gener‑ ally accepted principles and consensus state‑ ments reported in this manuscript. Vimal H. Prajapati, Harvey Lui, Yvette Miller-Monthrope, Julien Ringuet, Irina Turchin, H. Chih-ho Hong, Charles Lynde, Kim A. Papp, Jensen Yeung, and Melinda J. Gooderham critically reviewed and revised the draft manuscript for important

intellectual content and approved the final ver‑ sion for submission.

Funding. This study and the Rapid Service Fee for this journal were funded by Incyte Cor‑ poration (Wilmington, DE, USA). Incyte had no editorial control or influence on the content of the manuscript or output from the expert panel.

Data Availability. Data sharing is not applicable to this article as no new datasets were generated or analyzed during the current study.

Declarations

Conflict of interest. Vimal H. Prajapati has served as an advisor, consultant, and/or speaker for AbbVie, Actelion, Amgen, Apogee Therapeutics, Aralez, Arcutis, Aspen, Bausch Health, BioScript Solutions, Boehringer Ingelheim, Bristol Myers Squibb, Canadian Psoriasis Network, Celgene, Celltrion, Cipher, Concert, CorEvitas, Eczema Society of Canada, Eli Lilly, Galderma, GlaxoSmithKline, Homeocan, Incyte Corporation, JAMP Pharma, Janssen, Johnson & Johnson, LEO Pharma, Medexus, Novartis, Organon, Pediapharm, Pfizer, Sanofi Genzyme, Sun Pharma, Tribute, UCB, and Valeant; served as an investigator for AbbVie, AnaptysBio, Arcutis, Arena, Asana, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, CorEvitas, Dermavant, Dermira, Eli Lilly, Galderma, Incyte Corporation, Janssen, LEO Pharma, Meiji Pharma, Nektar Therapeutics, Nimbus Lakshmi, Novartis, Pfizer, RAPT Therapeutics, Regeneron, Reistone, Sanofi Genzyme, Sun Pharma, Takeda, and UCB; and received grants from AbbVie, Bausch Health, Janssen, LEO Pharma, Novartis, and Sanofi Genzyme. Harvey Lui has served as an advisor, consultant, investigator, and/or speaker for AbbVie, Incyte Corporation, L’Oréal, Novartis, and Vita Imaging. Yvette Miller-Monthrope has served as an advisor, consultant, and/or speaker for AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Fresenius Kabi, Galderma, Incyte Corporation, Janssen, Sanofi, Sun Pharma,

Novartis, and UCB. Julien Ringuet has served as an advisor, consultant, and/or speaker for AbbVie, Amgen, Apogee, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galderma, Incyte Corporation, Janssen, LEO Pharma, L’Oréal, NKS Health, Novartis, Organon, Pfizer, Sandoz, Sanofi Genzyme, Sun Pharma, and UCB; and served as an investigator for AbbVie, Alumis, Amgen, Apogee, Aristea, Aslan, Bristol Myers Squibb, Celgene, Concert Pharmaceuticals, Correvitas, DICE Therapeutics, Incyte Corporation, Innovaderm, Janssen, Kyowa Kirin, LEO Pharma, Merck, Pfizer, Sanofi Genzyme, Sun Pharma, and UCB. Irina Turchin has served as a speaker, advisor, consultant, or investigator for AbbVie, Amgen, Arcutis, Aristea, Bausch Health, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Galderma, Horizon Therapeutics, Incyte Corporation, Janssen, Kiniksa, LEO Pharma, Mallinckrodt, MoonLake, Novartis, Pfizer, Sanofi, Sun Pharma, UCB, and Ventyx Biosciences. H. Chih-ho Hong has served as a speaker, advisor, consultant, and/or investigator for AbbVie, Amgen, Arcutis, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cutanea, Dermira, Dermavant, DS Biopharma, Eli Lilly, Galderma, GlaxoSmithKline, Incyte Corporation, Janssen, LEO Pharma, Medimmune, Merck, Mirimar, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Roche, and UCB. Charles Lynde has served as a speaker and/or consultant for AbbVie, Amgen, Aralez, Arcutis, Bausch Health, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cipher, Dermavant, Eli Lilly, Fresnius Kabi, Galderma, GlaxoSmithKline, Incyte Corporation, Innovaderm, Intega Skin, Janssen, Kyowa Kirin, La Roche Posay, LEO Pharma, L’Oréal, Medexus, MedX, Merck, Novartis, P&G, Pediapharm, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sandoz, Sentrex, Sun Pharma, TEVA, Tribute, UCB, Valeant, Viatris, and Volo Health; and has served as a principal investigator for AbbVie, Acelyrin, Akros, Altius, Amgen, Aralez, Arcutis, Avillion, Bausch Health, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Celltrion, Cipher, Concert, Dermavant, Devonian, Eli Lilly, Evelo, Galderma, GlaxoSmithKline, Incyte Corporation, Innovaderm, Intega Skin, Janssen, Kyowa Kirin, La Roche Posay, LEO Pharma,

L’Oréal, Medexus, MedX, Merck, MoonLake, Novartis, P&G, Pediapharm, Pfizer, Regeneron, Roche, Sanofi Genzyme, Sandoz, Sentrex, Sun Pharma, TEVA, Tribute, UCB, Valeant, Viatris, and Volo Health. Kim A. Papp has received honoraria and/or grants as a consultant, speaker, investigator, or scientific officer from AbbVie, Acelyrin, Akros, Alumis, Amgen, Arcutis, Bausch Health/Valeant, Boehringer Ingelheim, Bristol Myers Squibb, Can-Fite Biopharma, Celltrion, Concert Pharmaceuticals, Dermavant, Dermira, DICE Pharmaceuticals, DICE Therapeutics, Eli Lilly and Company, Evelo Biosciences, Forbion, Galderma, Horizon Therapeutics, Incyte Corporation, Janssen, Kymab, Kyowa Hakko Kirin, LEO Pharma, Meiji Seika Pharma, Mitsubishi Pharma, Nimbus Therapeutics, Novartis, Pfizer, Reistone, SanofiAventis/Genzyme, Sandoz, Sun Pharma, Takeda, Tarsus Pharmaceuticals, UCB Pharma, and Zai Lab. Jensen Yeung has served as a consultant, investigator, or speaker or received honoraria from AbbVie, Amgen, Acrutis, Apogee, Bausch Health, Boehringer Ingelheim, Bristol Myers Squibb, Celltrion, Fresenius Kabi, Galderma, Incyte Corporation, JAMP Pharma, Janssen, LEO Pharma, Lilly, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda, and UCB. Melinda J. Gooderham has served as a principal investigator for AbbVie, Alumis, Amgen, AnaptysBio, Apogee, Arcutis, Aristea, Aslan, Bausch Health, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Cara Therapeutics, Coherus Biosciences, Dermira, Eli Lilly, Galderma SA, GlaxoSmithKline, Incyte Corporation, InMagene, JAMP, Janssen, LEO Pharma, MedImmune, Meiji, MoonLake, Nektar Therapeutics, Nimbus, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, Takeda Pharmaceutical Company, Tarsus, UCB, Ventyx, and Vyne; a consultant for AbbVie, Amgen, Apogee, Aslan, Bausch Health, Boehringer Ingelheim International GmbH, Eli Lilly, Janssen, Novartis Pharmaceuticals, Sanofi Genzyme, Sun Pharma, and UCB; an advisory board member for AbbVie, Amgen, Apogee, Arena Pharmaceuticals, Asana BioSciences, Aslan, Bausch Health, Boehringer Ingelheim International GmbH, Eli Lilly, Galderma SA, Incyte Corporation, Janssen, LEO Pharma, Novartis, Pfizer, Regeneron, Sanofi

Genzyme, Sun Pharma, UCB, and Union; and a paid speaker for AbbVie, Amgen, Bausch Health, Bristol Myers Squibb, Boehringer Ingelheim International GmbH, Eli Lilly, Galderma SA, Janssen, JAMP, LEO Pharma, L’Oréal, Novartis, Pfizer, Regeneron, Sanofi Genzyme, Sun Pharma, and UCB.

Ethical approval. This article is based on pre‑ viously conducted studies and does not contain any new studies with human participants or ani‑ mals performed by any of the authors.

Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distri‑ bution and reproduction in any medium or for‑ mat, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indi‑ cated otherwise in a credit line to the material. If material is not included in the article’s Crea‑ tive Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain per‑ mission directly from the copyright holder. To view a copy of this licence, visit http://creativeco mmons.org/licenses/by-nc/4.0/ .

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