latest research on vitiligo

FDA Approves New Vitiligo Treatment, Ruxolitinib (Opzelura)

The JAK inhibitor cream is the first medication that can restore pigment in people with this autoimmune disease.

On July 18, the U.S. Food and Drug Administration (FDA) approved ruxolitinib ( Opzelura ) cream 1.5 percent as a treatment for the most common form of vitiligo, according to a statement by Incyte, the manufacturer of the drug.

Vitiligo is a chronic autoimmune condition that causes patches of skin to lose pigment and turn milky white. The most prevalent form is nonsegmental (also known as generalized) vitiligo, in which white patches appear symmetrically on both sides of the body, such as on both hands or both knees, often covering large areas.

Ruxolitinib is the first medication that can restore pigment in patients with nonsegmental vitiligo. The FDA approved Incyte’s ruxolitinib cream for adults and children ages 12 and up.

“This approval is monumental,” says Daniel Gutierrez, MD , assistant professor of dermatology at NYU Grossman School of Medicine and dermatologist at NYU Langone Health in New York City, who was not involved in the drug development. “With Opzelura, we will have an FDA-approved pharmaceutical treatment option that can actually bring back color in patients who have vitiligo,” says Dr. Gutierrez.

He adds that prior to ruxolitinib, the only FDA-approved medication for vitiligo was monobenzyl ether of hydroquinone, a topical drug that removes pigment from skin to even out tones.

What Is Vitiligo?

Researchers estimate that between 1.9 and 2.8 million adults in the United States have vitiligo, with perhaps 40 percent of adults with vitiligo going undiagnosed.

Vitiligo causes immune cells to destroy melanocytes, the skin cells that produce pigment, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases . “This makes vitiligo much more noticeable in patients of color — people whose skin is much more richly pigmented — because there is going to be much more of a contrast between the unaffected skin and the skin affected by the vitiligo,” says Gutierrez.

Vitiligo can occur at any age, but most people experience the initial symptoms before age 30.

About 50 Percent of People Using Ruxolitinib Had Significant Repigmentation After One Year

Ruxolitinib belongs to a class of drugs called Janus kinase (JAK) inhibitors. While doctors prescribe oral JAK inhibitors for diseases such as rheumatoid arthritis, ruxolitinib is the only topical JAK inhibitor approved in the United States.

The FDA previously approved ruxolitinib for mild to moderate atopic dermatitis (eczema) , in the fall of 2021.

JAK inhibitors work by decreasing the activity of the immune system, blocking certain enzymes that cause inflammation.

Patients using ruxolitinib apply the cream twice daily to the affected areas, covering up to 10 percent of their body’s surface area. It may take 24 weeks or more for people with vitiligo to see satisfactory results, according to Incyte.

The FDA based its approval on data from a clinical trial program that compared ruxolitinib to a placebo cream in more than 600 people (age 12 and older) with nonsegmental vitiligo. Investigators used the Vitiligo Area Scoring Index (VASI), a tool used to gauge disease severity and to measure improvements in face and body repigmentation.

In the two trials, by week 24 approximately 30 percent of people treated with ruxolitinib experienced significant improvements (at least 75 percent) as measured by VASI, which was the goal of the study. At one year, about 50 percent of those using the medication achieved that level of repigmentation.

“People using Opzelura had much more improvement in their vitiligo — very meaningful — compared to the placebo,” says Gutierrez.

The most common side effects seen in the trials were application-site acne, redness and itchiness, pharynx and nasal cavity inflammation, headache, urinary tract infection, and fever.

Ruxolitinib Comes With a Black Box Warning

The FDA added a black box warning to ruxolitinib, based on data showing that people taking oral JAK inhibitors faced a small increased risk of serious infections, major heart issues, clotting (thrombosis), cancer, and even death.

“However, in the clinical trials for people using ruxolitinib as a topical cream, the concentrations of the drug found in the blood were observed to be much lower compared to people who take ruxolitinib orally,” says Gutierrez. The same risks were not observed in the ruxolitinib trials, but the FDA is taking a “better safe than sorry” approach by including a warning on the box, he adds.

A conversation with your healthcare provider is the best way to determine whether the benefits of ruxolitinib outweigh the potential risks, as well as the need for any baseline and/or ongoing monitoring.

Patients Can Use Ruxolitinib on Their Face

Although dermatologists sometimes prescribe topical steroids off-label for vitiligo, there are risks when applying these medications to the face — the area where loss of pigment can impact appearance the most, says Gutierrez.

When used on the face, topical steroids can cause an acne-like rash that can persist for many months, called perioral dermatitis . Plus, “they can cause atrophy or dispigmentation, meaning you can have skin color changes. They can also thin the skin, cause stretch marks, and cause the growth of small blood vessels in the area,” Gutierrez says.

Ruxolitinib does not pose these risks, notes Gutierrez.

FDA Approval Means Better Access to Vitiligo Treatment

The FDA’s approval of ruxolitinib will definitely improve access to the drug by validating it as medically necessary. “Because vitiligo just creates a color change in the skin — there’s no itching or dermatitis under normal circumstances — sometimes it’s considered a cosmetic condition, meaning it’s not medically necessary to treat,” Gutierrez says. As a result, some insurers have declined to cover vitiligo treatments , according to the Vitiligo Research Foundation .

“However, this condition can dramatically impact how a patient sees themselves and how they present to the world. Vitiligo can cause significant psychological distress and negatively impact quality of life,” says Gutierrez.

“Vitiligo disproportionately impacts patients of color,” he adds. “This approval is an important step in improving a health disparity that does exist, and hopefully there will be more treatment options for vitiligo in the pipeline.”

How Much Will Ruxolitinib Cost?

The current Wholesale Acquisition Cost pricing is $1,950 for a 60 gram tube of Opzelura, according to Gabriella Greig, a spokesperson for Incyte. The actual cost to the consumer will vary depending on insurance coverage and how much of the cream is required for treatment.

“Incyte is committed to working with insurance providers in the U.S. to ensure eligible patients who can benefit from Incyte’s products have access to them,” says Greig. The company offers a  copay savings card on its website for people with commercial insurance.

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

• View all journals
• Explore content
• About the journal
• Publish with us
• Sign up for alerts
• 30 June 2020
• Correction 06 July 2020

Temprian Therapeutics: developing a gene-based treatment for vitiligo

• Charles Schmidt 0

Charles Schmidt is a freelance writer in Portland, Maine.

You can also search for this author in PubMed   Google Scholar

Temprian Therapeutics is a spin-off from Northwestern University in Chicago, Illinois.

Access options

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

24,99 € / 30 days

cancel any time

Subscribe to this journal

Receive 51 print issues and online access

185,98 € per year

only 3,65 € per issue

Rent or buy this article

Prices vary by article type

Prices may be subject to local taxes which are calculated during checkout

doi: https://doi.org/10.1038/d41586-020-01808-5

This article is part of Nature Outlook: The Spinoff Prize 2020 , an editorially independent supplement produced with the financial support of third parties. About this content .

Updates & Corrections

Correction 06 July 2020 : An earlier version of this profile gave the wrong specialty for Caroline Le Poole and the wrong campus for Northwestern University.

Mosenson, J. A. et al. Sci. Transl. Med. 5 , 174ra28 (2013).

Article   PubMed   Google Scholar  

Henning, S. W. et al. J. Invest. Dermatol. 138 , 2531–2539 (2018).

Download references

Related Articles

• Biotechnology
• Drug discovery
• Therapeutics

Vaccine-enhancing plant extract could be mass produced in yeast

News & Views 08 MAY 24

Computationally restoring the potency of a clinical antibody against Omicron

Article 08 MAY 24

Complete biosynthesis of QS-21 in engineered yeast

How to kill the ‘zombie’ cells that make you age

News Feature 15 MAY 24

Dual-action obesity drug rewires brain circuits for appetite

News & Views 15 MAY 24

Experimental obesity drug packs double punch to reduce weight

News 15 MAY 24

Lab-grown sperm and eggs: ‘epigenetic’ reset in human cells paves the way

News 21 MAY 24

In vitro reconstitution of epigenetic reprogramming in the human germ line

Article 20 MAY 24

Airway hillocks are injury-resistant reservoirs of unique plastic stem cells

Article 01 MAY 24

Assistant Professor in Plant Biology

The Plant Science Program in the Biological and Environmental Science and Engineering (BESE) Division at King Abdullah University of Science and Te...

Saudi Arabia (SA)

King Abdullah University of Science and Technology

Postdoctoral Fellow

New Orleans, Louisiana

Tulane University School of Medicine

Postdoctoral Associate - Immunology

Houston, Texas (US)

Baylor College of Medicine (BCM)

Postdoctoral Associate

Vice president, nature communications portfolio.

This is an exciting opportunity to play a key leadership role in the market-leading journal Nature Portfolio and help drive its overall contribution.

New York City, New York (US), Berlin, or Heidelberg

Springer Nature Ltd

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Quick links

• Explore articles by subject
• Guide to authors
• Editorial policies

Advances in vitiligo: Update on therapeutic targets

Affiliation.

• 1 Department of Dermatology, Jiangsu Province People's Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China.
• PMID: 36119071
• PMCID: PMC9471423
• DOI: 10.3389/fimmu.2022.986918

Vitiligo, whose treatment remains a serious concern and challenge, is an autoimmune skin disease characterized by patches of depigmentation. The increasing application of molecular-targeted therapy in skin diseases, such as psoriasis and systemic lupus erythematosus, has dramatically improved their condition. Besides, there is a favorable effect of repigmentation in the treatment of the above diseases combined with vitiligo, implying that molecular-targeted therapy may also have utility in vitiligo treatment. Recently, the role of cytokine and signaling pathways in vitiligo pathogenesis are increasingly recognized. Thus, investigations are underway targeting the molecules described above. In this paper, we present a synopsis of current practices in vitiligo treatment and introduce the improvement in identifying new molecular targets and applying molecular-targeted therapies, including those under development in vitiligo treatment, providing valuable insight into establishing further precision medicine for vitiligo patients.

Keywords: JAK inhibitors; Treg; biological; miRNA - microRNA; targeted therapy; treatment; vitiligo.

Copyright © 2022 Feng and Lu.

Publication types

• Autoimmune Diseases*
• Cytokines / therapeutic use
• Vitiligo* / drug therapy

Vitiligo Research

Vitiligo Advancements and Discoveries

There has been an increase in the amount of research being undertaken in vitiligo over recent years and dermatologists have an improved understanding of the natural history and different types of the condition. Here you will find a brief summary of research into several areas, with references to the original research articles, for those of you who wish to follow these up.

Researchers are looking at:

• The effectiveness of existing treatments;
• Possible causes of vitiligo;
• How the condition develops;
• Segmental vitiligo;
• The association of vitiligo with other conditions;
• The psychological effects of vitiligo.

It is hoped that the improvements in scientific understanding will in future lead to more effective treatments for vitiligo.

Are psychological interventions important for vitiligo patients?

Yes, a survey of vitiligo patients and healthcare professionals found that psychological interventions are important for managing the impact of vitiligo on patients’ lives.

A survey was conducted to identify psychological interventions for vitiligo. The survey was funded by the UK Dermatology Clinical Trials Network and involved patients and health professionals. The survey recorded personal data and focused on the effect of vitiligo on normal life, as well as the most difficult problems faced by patients and which approaches would be helpful.

• Patients with vitiligo reported key issues such as acceptance of their disease, the duration of the disease and managing embarrassment.
• Other concerns were participating in sporting activities and exposure to sunlight.
• Interventions considered useful by professionals to address these issues included cognitive behavioural therapy (CBT), acceptance and commitment therapy (ACT), and mindfulness therapy.

Psychological interventions for vitiligo are a research priority, but there is little published on appropriate therapy from both patient and clinician perspectives. The unique survey referenced here is therefore of value to the future treatment of vitiligo patients.

Will piperine treat vitiligo?

Although promising results have been seen in cell and animal studies, and early work toward clinical trials in humans is underway, the effectiveness and safety of piperine as a treatment for vitiligo in humans has yet to be fully established.

Ongoing research is being conducted, but funding is needed to support further studies. Therefore, it is unclear at this time whether piperine will ultimately prove to be an effective treatment for vitiligo.

Amala Soumyanath led the research that discovered piperine as a potential treatment for vitiligo. In her own words, she shares the story of her research journey and provides an update on the latest developments. Become a member today and access more resources and stories like this.

How was piperine discovered as a potential treatment for vitiligo?

Piperine was discovered as a potential treatment for vitiligo through research and testing of herbal extracts , where a water extract of black pepper was found to stimulate melanocyte growth and dendrite formation. The compound responsible for this effect was identified as piperine, which could be developed for use in treating vitiligo.

How was piperine validated as a “lead” molecule for the treatment of vitiligo?

Piperine was validated as a “lead” molecule for the treatment of vitiligo through studies conducted at King’s College London. They tested extracts from various herbs and found that piperine from black pepper was the most effective at stimulating the growth of pigment cells. Further studies were conducted to make chemical variations (analogs) of piperine and two of these analogs showed good activity.

All three compounds, piperine, THP, and RCHP, were found to stimulate the growth of pigment cells in mice, causing their skin to visibly darken. These studies allowed the researchers to secure international patents for the use of piperine and its analogs to treat vitiligo.

How was piperine’s effectiveness and safety in treating vitiligo validated?

Piperine’s effectiveness and safety in treating vitiligo were validated through a detailed plan for a clinical trial of piperine in patients with vitiligo. Prior to the clinical study, experiments were conducted to investigate the effects of piperine on human pigment cells, including melanocytes from the uninvolved skin of a vitiligo patient.

Piperine was found to stimulate the replication of human melanocytes in culture and when grown within a reconstructed skin model. Colleagues in OHSU’s Biomedical Engineering and Dermatology departments used innovative optical methods to image pigmentation and melanocytes in the skin models.

What were its effects on human pigment cells and melanoma?

Experiments funded by AdPharma, Inc. showed that piperine has an inhibitory effect on cultured melanoma cells and prevents melanoma cell growth in a reconstructed full-skin model. To further study this aspect, the HGF mouse model of melanoma was introduced to OHSU.

The effects of piperine in this model are currently being studied with pilot funding from the Department of Dermatology’s Jesse Ettelson Fund for the Advancement of Dermatology Research. These ongoing studies are essential to establish the safety of piperine.

What is the status of piperine for treating vitiligo in humans?

In 2013, the appointment of Professor Sancy Leachman, a dermatologist and expert in pigment cell biology, gave a significant boost to the project of developing piperine as a new treatment for vitiligo. Dr. Pamela Cassidy and Eric Smith also joined the team, and a core group is working to bring this discovery to the clinic. The current status of piperine as a treatment for vitiligo in humans remains unclear.

Amala Soumyanath’s Personal and Professional Journey to Develop a Treatment for Vitiligo

Amala Soumyanath’s journey began when she received a phone call from Maxine Whitton, an MBE-awarded vitiligo service provider, sparking an idea to develop piperine as a potential treatment for vitiligo. With dedication and persistence, Amala’s knowledge of drug development processes led her to develop piperine to the point of being tested in humans.

Her personal experience with vitiligo, developing noticeable patches in 2006, fueled her drive to find a treatment for this difficult condition. Alongside a team of talented researchers at OHSU, they continue to evaluate piperine’s efficacy and understand its effects on melanocytes, with Dr. Sancy Leachman leading the project and Amala as the ongoing champion.

Is piperine the new treatment for vitiligo?

Amala Soumyanath and her team at OHSU are developing piperine as a potential treatment for vitiligo. A “proof of concept” human study demonstrating piperine’s safety and efficacy could attract large pharmaceutical companies to move forward with the project, but funding is needed. Donations of any size can make a real difference to the project’s progress. While piperine shows promise as a treatment for vitiligo, further research is required before it can be established as a new treatment.

How can you help?

The team at OHSU is reaching out to the general community for funding to support their ongoing studies on piperine for vitiligo at both the clinical and basic science levels. Donations of any size from those affected by vitiligo or anyone interested in supporting the research can be made online to the Vitiligo Research Fund .

Read Amala Soumyanath’s full story here .

What impact does vitiligo have on a person’s quality of life?

Vitiligo can have a moderate to severe impact on a person’s quality of life, including depression, stigmatization, and impaired sex lives. The location of the lesions and cultural values related to appearance and status may also play a role. Research has found that:

• Quality of life is closely related to the patients’ apprehensions about their disease, psychosocial adjustment, and psychiatric morbidity.
• British Asian women with vitiligo often feel visibly different and have experienced stigmatization due to cultural values related to appearance, status, and myths linked to the cause of the condition.
• Quality of life impairment in women affected with vitiligo assessed using the DLQI was equal to the impairment caused by psoriasis.
• Vitiligo had a negative impact on the sex lives of women with vitiligo.

To learn more about the impact vitiligo has on an individual and their quality of life you can find the full articles below:

• Quality of life of patients with vitiligo attending the Regional Dermatology Training Center in Northern Tanzania
• Depression, anxiety and health‐related quality of life in children and adolescents with vitiligo
• Quality of life and psychological adaptation of Korean adolescents with vitiligo
• Vitiligo linked to stigmatization in British South Asian women: a qualitative study of the experiences of living with vitiligo
• Effect of vitiligo on self‐reported health‐related quality of life
• The Problems in Sexual Functions of Vitiligo and Chronic Urticaria Patients

Can thyroid issues cause vitiligo?

There is evidence to suggest that thyroid issues can be associated with vitiligo. The frequency of thyroid disease in vitiligo patients is higher compared to the general population, and it is recommended that all patients with vitiligo have their thyroid function checked.

In the course of their clinical work, dermatologists discovered:

• the frequency of thyroid disease in vitiligo patients was 15.1%, 
• autoimmune thyroid disease was 14.3% 
• and the presence of thyroid-specific autoantibodies was 20.8%.

To learn more about the association between thyroid issues and vitiligo you can find the full article here .

Does vitiligo increase your risk of skin cancer?

Although patients with vitiligo have a tendency to burn in the sun, a survey conducted by a team from The Netherlands found that patients with vitiligo have a threefold lower probability of developing malignant melanoma and non-melanoma skin cancer. The reasons for this are not yet fully understood.

Read the entire survey here and learn more about this on BBC iPlayer .

What is segmental vitiligo?

Segmental vitiligo is a form of vitiligo that presents with patches distributed unilaterally and locally . It has been compared with a possible mosaic or neurogenic background, but its distribution pattern is not entirely similar to any other skin condition. Cutaneous mosaicism may be involved in segmental vitiligo. However, the underlying mechanism of segmental vitiligo is still unknown.

Learn more about the distribution pattern of segmental vitiligo here .

How is vitiligo classified?

Segmental vitiligo is classified separately from all other forms of vitiligo, with the term ‘vitiligo’ being used as an umbrella term for all non-segmental forms, including mixed vitiligo in which segmental and non-segmental vitiligo are combined and which is considered a subgroup of vitiligo.

Experts recommend that disease stability is best assessed based on the stability of individual lesions rather than the overall stability of the condition.

Read the entire article about the classification of vitiligo here .

What is the Koebner phenomenon in relation to vitiligo and how can it be assessed?

The Koebner phenomenon (KP) refers to the development of vitiligo within an area of skin that has been damaged by localised, often mild trauma (e.g. an injury). Dr. N van Geel and colleagues of Ghent have looked at this phenomenon. They developed a new assessment method for KP, taking into account both the history and clinical examination of people with vitiligo; this seems to be a useful and valuable tool for assessing KP in daily practice.

The results support the hypothesis that KP may be used to assess and predict the course of vitiligo (access the entire article here ).

What is the relationship between Halo Nevi and vitiligo?

Halo nevi are common moles with a white ring around them, showing the sort of pigment loss that is seen in vitiligo. They may represent a distinct condition, but in some cases, they may be an initiating factor in the development of vitiligo, according to research by Dr. van Geel and researchers (access the entire article here ).

What are the mechanisms of pathogenesis of vitiligo?

The pathogenesis of vitiligo is believed to involve oxidative stress, which leads to an imbalance between reactive oxygen species (ROS) and the body’s ability to detoxify them. (Access the entire article here ).

According to research (access the entire article here ): 

• Mitochondria within melanocytes and blood cells generate reactive oxygen species (ROS) that may be relevant in vitiligo development.
• Modification of membrane lipid components in vitiligo cells may cause mitochondrial impairment and the production of intracellular ROS after exposure to mild stress.
• Autoimmunity plays a role in the pathogenesis of vitiligo, with tyrosine hydroxylase identified as an autoantigen target.
• Tyrosine hydroxylase antibodies are more frequent in people with active non-segmental vitiligo (23%) but not in the segmental type.

How does vitiligo affect the layers of skin?

Genetic studies show that susceptibility to vitiligo is related to proteins or parts of the pigment cell involved in the immune system (access the entire article here ). Research from Dalian, China, reveals that alterations in skin biophysical properties, such as stratum corneum (SC) hydration, melanin and erythema index, are lower in vitiligo-affected skin (access the entire article here ). 

However, no difference in skin surface acidity was observed, and the SC integrity was similar in involved and uninvolved areas. Barrier recovery in vitiligo-involved areas was significantly delayed compared to uninvolved areas.

What are the systemic treatment options for vitiligo?

It is difficult to find a systemic treatment for vitiligo at the moment (one that affects the whole body). Some of the commonly used systemic treatments for vitiligo include:

• Ginkgo biloba – taking 60 mg of Ginkgo biloba BID was associated with a significant improvement in total Vitiligo Area Scoring Index (VASI) and Vitiligo European Task Force (VETF) scores, but more clinical trials are needed (access the entire article here ).
• Piperine – has been suggested as a potential treatment for vitiligo, yet only a few studies have been conducted and most have been on animals (access the entire article here ).
• Cosmetic camouflage – not only conceals the depigmented patches but has been shown to improve the quality of life in patients (access the entire article here )

What are the surgical treatment options for vitiligo?

Surgical treatment options for vitiligo involve transplanting melanocytes from normally pigmented skin to the depigmented areas and are only suitable for patients with stable vitiligo. It has been proven that suspending melanocytes in the patient’s own serum (plasma in the blood) can improve the effectiveness of the transplant (access the entire article here ).

Another new procedure called ReCell involves taking a sample of normal skin, separating out the skin cells, and spraying them onto the vitiligo patches (access the entire article here). Studies comparing Recell with conventional transplantation have shown varying degrees of repigmentation, but it is not widely available in the UK (access the entire article here ).

What are effective topical treatments and light therapies for vitiligo?

Creams or ointments, known as topical immunomodulators, are usually the first line of treatment for vitiligo. Topical tacrolimus and pimecrolimus have been found to be effective for localised vitiligo. Targeted narrow-band ultraviolet B (UVB) light treatment using the Excimer laser is also known to be effective, but not widely available. Other lasers such as the Q-switched ruby laser have been shown to induce depigmentation more quickly, but with more discomfort.

To learn more about effective topical treatments and light therapies for vitiligo you can find the full articles below:

• Comparative Therapeutic Evaluation of Different Topicals and Narrow Band Ultraviolet B Therapy
• Pimecrolimus: a new choice in the treatment of vitiligo?
• Laser for treating vitiligo: a randomized study
• Treatment of vitiligo: advantages and disadvantages, indications for use and outcomes

Table of contents

• Alzheimer's disease & dementia
• Arthritis & Rheumatism
• Attention deficit disorders
• Autism spectrum disorders
• Biomedical technology
• Diseases, Conditions, Syndromes
• Endocrinology & Metabolism
• Gastroenterology
• Gerontology & Geriatrics
• Health informatics
• Inflammatory disorders
• Medical economics
• Medical research
• Medications
• Neuroscience
• Obstetrics & gynaecology
• Oncology & Cancer
• Ophthalmology
• Overweight & Obesity
• Parkinson's & Movement disorders
• Psychology & Psychiatry
• Radiology & Imaging
• Sleep disorders
• Sports medicine & Kinesiology
• Vaccination
• Breast cancer
• Cardiovascular disease
• Chronic obstructive pulmonary disease
• Colon cancer
• Coronary artery disease
• Heart attack
• Heart disease
• High blood pressure
• Kidney disease
• Lung cancer
• Multiple sclerosis
• Myocardial infarction
• Ovarian cancer
• Post traumatic stress disorder
• Rheumatoid arthritis
• Schizophrenia
• Skin cancer
• Type 2 diabetes
• Full List »

share this!

July 21, 2022

FDA approves first topical treatment for vitiligo

The U.S. Food and Drug Administration has approved Opzelura (ruxolitinib) as the first topical treatment for vitiligo.

The 1.5 percent cream is approved for continuous topical use twice daily to affected areas of up to 10 percent of body surface area in patients aged 12 years and older. More than 24 weeks of treatment may be needed for satisfactory patient response.

The approval was based on results from the TRuE-V clinical trials , in which more than 600 patients were randomly assigned to Opzelura or placebo. At week 24, 30 percent of patients treated with Opzelura achieved ≥75 percent improvement from baseline in the facial Vitiligo Area Scoring Index (F-VASI75) versus 8 to 13 percent of patients treated with placebo. Approximately half of Opzelura-treated patients achieved F-VASI75 at week 52.

"There have been no FDA-approved therapies available to date and the approval of Opzelura therefore marks a significant milestone ," David Rosmarin, M.D., from Tufts Medical Center in Boston, said in a company press release. "I welcome a medical treatment that helps my patients with nonsegmental vitiligo who are interested in potentially reversing the depigmentation caused by their disease."

Approval was granted to Incyte.

Copyright © 2022 HealthDay . All rights reserved.

Explore further

Feedback to editors

Study: Newborns whose mother spoke in a mix of languages during pregnancy are more sensitive to a range of sound pitches

3 hours ago

Study finds ultraviolet radiation may affect subcutaneous fat regulation, could lead to new obesity treatments

Regular fish oil supplement use might increase first-time heart disease and stroke risk

9 hours ago

Pedestrians may be twice as likely to be hit by electric/hybrid cars as petrol/diesel ones

Study finds jaboticaba peel reduces inflammation and controls blood sugar in people with metabolic syndrome

10 hours ago

Study reveals how extremely rare immune cells predict how well treatments work for recurrent hives

11 hours ago

Researchers find connection between PFAS exposure in men and the health of their offspring

Researchers develop new tool for better classification of inherited disease-causing variants

12 hours ago

Specialized weight navigation program shows higher use of evidence-based treatments, more weight lost than usual care

Exercise bouts could improve efficacy of cancer drug

Related stories.

Topical cream shows promise in treatment of skin pigmentation disease, vitiligo

Jun 17, 2019

FDA approves first treatment for eosinophilic esophagitis

May 26, 2022

Atogepant prevents migraine in adults

Jun 15, 2022

FDA approves Skyrizi for moderately to severely active Crohn disease

Jun 20, 2022

FDA approves Rinvoq for treatment of atopic dermatitis

Jan 19, 2022

Skyrizi approved for psoriatic arthritis

Jan 26, 2022

Recommended for you

Drug-like inhibitor shows promise in preventing flu

Cancer drug shows powerful anti-tumor activity in animal models of several different tumor types

13 hours ago

Hope for a cure for visceral leishmaniasis, an often fatal infectious disease

16 hours ago

Matcha mouthwash shown to inhibit bacteria that cause periodontitis

18 hours ago

New AI algorithm may improve autoimmune disease prediction and therapies

May 20, 2024

Let us know if there is a problem with our content

Use this form if you have come across a typo, inaccuracy or would like to send an edit request for the content on this page. For general inquiries, please use our contact form . For general feedback, use the public comments section below (please adhere to guidelines ).

Please select the most appropriate category to facilitate processing of your request

Thank you for taking time to provide your feedback to the editors.

Your feedback is important to us. However, we do not guarantee individual replies due to the high volume of messages.

E-mail the story

Your email address is used only to let the recipient know who sent the email. Neither your address nor the recipient's address will be used for any other purpose. The information you enter will appear in your e-mail message and is not retained by Medical Xpress in any form.

Newsletter sign up

Get weekly and/or daily updates delivered to your inbox. You can unsubscribe at any time and we'll never share your details to third parties.

More information Privacy policy

Donate and enjoy an ad-free experience

We keep our content available to everyone. Consider supporting Science X's mission by getting a premium account.

E-mail newsletter

Patient Burden of Nonsegmental Vitiligo: A US Real-World Survey of Dermatologists and Their Patients

• Original Research
• Open access
• Published: 16 May 2024

Cite this article

You have full access to this open access article

• David Rosmarin   ORCID: orcid.org/0000-0003-2786-0708 1 ,
• Jennifer H. Lofland   ORCID: orcid.org/0000-0002-1015-3823 2 ,
• Simran Marwaha   ORCID: orcid.org/0000-0003-0380-0372 3 ,
• James Piercy   ORCID: orcid.org/0000-0001-7015-1021 3 ,
• Peter Anderson   ORCID: orcid.org/0000-0002-2171-8228 3 &
• Jinan Liu   ORCID: orcid.org/0009-0002-6042-5476 2  

176 Accesses

1 Altmetric

Explore all metrics

Introduction

Vitiligo is a chronic autoimmune disease characterized by destruction of melanocytes, leading to skin depigmentation. Vitiligo can have a high quality-of-life burden and profound impact on psychosocial well-being. The objectives of this study were to describe the self-reported patient burden among patients with nonsegmental vitiligo with ≤ 10% affected body surface area, summarize the physician-reported psychosocial and psychological impact of vitiligo on patient lives, and describe disease characteristics and treatment history, goals, and satisfaction.

Data were drawn from the Adelphi Vitiligo Disease Specific Programme™, a real-world, cross-sectional survey with retrospective data collection of physicians and patients with vitiligo, collected in the United States between October 2021 and April 2022. Separate surveys for dermatologists and patients contained questions on clinical and demographic characteristics of patients with vitiligo and burden of vitiligo. Treatment history, goals, and satisfaction were assessed together with the impact of vitiligo on quality of life.

Sixty-one dermatologists provided data for 326 patients with ≤ 10% affected body surface area (adults, n  = 221; adolescents, n  = 105); 90 of those patients also responded to the survey. The most common treatments were topical corticosteroids, topical calcineurin inhibitors, and narrow-band ultraviolet-B phototherapy, with the main treatment goal being repigmentation. Physician-reported treatment satisfaction was 56%; 25% of patients reported frustration with treatment options. Physicians reported impact of vitiligo on everyday life in 46% of patients. Patients reported 12.7% overall work impairment; mean scores for Hospital Anxiety and Depression Scale anxiety and depression domains were 3.5 and 2.2, respectively, and mean Vitiligo-specific Quality of Life index score was 26.9. Patients with facial involvement experienced higher burden than those without.

A high patient burden was reported by dermatologists and their patients with vitiligo who had ≤ 10% affected body surface area, including psychosocial and psychological consequences. These findings highlight an unmet need in the treatment of vitiligo.

Plain Language Summary

Vitiligo is a chronic disease in which cells that produce the skin pigment melanin are attacked, causing patches of skin to lose color and become pale. Vitiligo can have emotional impacts such as social or psychological distress that can affect the day-to-day well-being of individuals. However, there is a lack of studies that assess the ways that vitiligo affects the everyday lives of people with the condition in the United States. Dermatologists and people with vitiligo answered survey questions on treatment goals, any vitiligo treatments currently and previously used, and how satisfied they were with the results of treatment. The surveys also contained questions that assessed the impact of vitiligo on everyday life. Sixty-one dermatologists answered questions about 326 patients and 90 of those patients also provided their own answers to the survey questions. Both dermatologists and patients reported that restoring color to patches of pale skin was their goal in treating vitiligo. However, dermatologists and patients both reported that they were dissatisfied with the results of available treatments. Dermatologists and patients both reported that vitiligo impacted aspects of everyday life. Emotional and psychological impacts such as anxiety and depression were reported, as well as negative effects on patients’ work and social lives due to vitiligo. These results confirm that vitiligo impacts the day-to-day well-being of patients. Furthermore, this study highlights that there is a need for improvements in the treatment of vitiligo.

Similar content being viewed by others

Microneedling and Its Use in Hair Loss Disorders: A Systematic Review

Alopecia Areata: an Update on Etiopathogenesis, Diagnosis, and Management

Lebrikizumab Provides Rapid Clinical Responses Across All Eczema Area and Severity Index Body Regions and Clinical Signs in Adolescents and Adults with Moderate-to-Severe Atopic Dermatitis

Avoid common mistakes on your manuscript.

Vitiligo is a chronic autoimmune disease of the skin that targets melanocytes, causing patches of skin depigmentation [ 1 ]. The diagnosed prevalence of vitiligo is estimated to be approximately 0.1–1.5% of the US population (approximately 1.9 million diagnosed US patients), with estimates suggesting that up to 40% of US adults with vitiligo may be undiagnosed [ 2 , 3 ]. Most patients with vitiligo have lesions affecting ≤ 10% of their body surface area (BSA), with the face being a commonly affected region [ 4 ].

A high level of clinical and emotional burden has been previously associated with vitiligo. Studies have documented a high prevalence of low self-esteem [ 5 , 6 ], social isolation, stigma [ 7 , 8 ], disease-specific discrimination [ 9 , 10 ], and anxiety, hopelessness, depression, and depressive symptoms [ 11 ] among patients with vitiligo. Patients report feeling stigmatized and experience unnecessary negative and antagonistic attention in public, which results in them feeling ostracized. Furthermore, the emotional distress patients with vitiligo experience has been shown to negatively impact their employment, cause social withdrawal, and lead to substance use disorders [ 12 ]. In dermatologic diseases, including atopic dermatitis and psoriasis, the presence of lesions in visible areas (e.g., face) has been associated with particularly high disease burden [ 13 , 14 ].

There is currently no cure for vitiligo and a historical lack of efficacious treatment, leaving patients and physicians frustrated and dissatisfied with available treatment options [ 15 ]. In July 2022, ruxolitinib cream was approved by the US Food and Drug Administration (FDA) for the treatment of nonsegmental vitiligo (NSV) in patients aged 12 years and older, for application to lesions affecting ≤ 10% BSA [ 16 ]. This approval marks the first pharmacologic treatment approved for repigmentation of NSV and augments the current treatment landscape for the disease [ 17 ]. Understanding the disease burden and real-world implications across the spectrum of NSV, not solely among those with higher BSA involvement, is necessary to guide the future evaluation and further research of FDA-approved therapies and products in development for the treatment of NSV.

The objectives of this study were to describe the self-reported patient burden among patients with NSV affecting ≤ 10% BSA, who constitute the majority of real-world patients with vitiligo and would be candidates for ruxolitinib cream treatment. We summarize the physician-reported impact of vitiligo on their patients’ lives, focusing on psychosocial and psychological consequences among patients with and without facial involvement and describe patients’ disease characteristics and treatment history, goals, and satisfaction.

Study Design

This is a secondary analysis of data from the Adelphi Vitiligo Disease Specific Programme™ (DSP) collected in the United States between October 2021 and April 2022, before the FDA approval of ruxolitinib cream for the treatment of NSV. For these analyses, only patients who had NSV with ≤ 10% affected BSA were included.

Data Source

The Vitiligo DSP is a large, multinational, cross-sectional survey with retrospective data collection, including dermatologists and their patients presenting with NSV in a real-world clinical setting. The DSP describes current disease management, disease burden impact, and associated treatment effects, both clinical- and dermatologist-perceived. A complete description of the survey methodology has been previously published and validated [ 18 , 19 , 20 ].

A geographically diverse sample of dermatologists was recruited to participate in the DSP, which received ethics exemption from the Pearl Institutional Review Board (study protocol number #21-ADRW-122) based on the use of aggregated and de-identified patient data. Dermatologists were eligible to participate in the survey if they were personally responsible for treatment decisions and management of patients with vitiligo and had a minimum monthly workload of 6 patients diagnosed with NSV. Patients were eligible for inclusion in the Vitiligo DSP if they were aged ≥ 18 years (adult population) or between 12 and 17 years (adolescent population), had a physician-confirmed diagnosis of NSV, were not involved in ongoing clinical trials, and visited the dermatologist for consultation. Both physicians and patients consented to take part in the research.

Dermatologists were instructed to complete a patient record form (PRF) for their next 6 consecutively consulted patients who visited for routine care. This form contained detailed information including patient demographics, disease characteristics (including affected BSA and facial involvement), treatment history and satisfaction with current treatment regimen, and disease control achieved. Facial involvement was defined as vitiligo affecting the head and neck area including eyes, ears, scalp, and the rest of the face. Completion of the patient record form was undertaken through consultation of existing patient clinical records, as well as the judgment and diagnostic skills of the respondent physician, which is entirely consistent with how decisions are made in routine clinical practice. It should be noted that the survey was designed to facilitate understanding of real-world clinical practice, and thus dermatologists could only report on data they had at hand at the time of the consultation. Therefore, data collected represent the evidence that physicians hold when making any clinical treatment and other management decisions at the time of consultation.

All data were collected in such a way that patients and dermatologists could not be directly identified; all data were aggregated and de-identified before receipt. Each survey was performed in full accordance with relevant legislation at the time of data collection, including the US Health Insurance Portability and Accountability Act of 1996 [ 21 ] and Health Information Technology for Economic and Clinical Health Act legislation [ 22 ]. Each patient for whom the dermatologist completed a form was then invited to voluntarily complete a patient self-completed questionnaire (PSC). PSCs were completed by patients independently from their dermatologist and were returned in a sealed envelope, ensuring the patient response was kept confidential from their dermatologist. The PSC contained detailed questions on current symptomatic burden, disease characteristics (including comorbid conditions), heath-related quality of life, level of satisfaction with their treatment regimen and disease control achieved, over-the-counter therapies, and other patient-reported outcomes. PSCs included the Work Productivity and Activity Impairment (WPAI) questionnaire (completed by adult patients only), the Hospital Anxiety and Depression Scale (HADS), and the Vitiligo-specific Quality of Life instrument (VitiQoL). The WPAI measures time missed from work (absenteeism), impairment at work (presenteeism), and impairment of regular activities. WPAI scores are reported as percentage impairment due to the disease [ 23 ]. The HADS score details symptoms of anxiety and depression, using a 0–3 scale across 7 questions [ 24 ]. For HADS, a total score ≥ 8 out of a possible 21 indicates symptoms of anxiety or depression [ 24 ]. The VitiQoL is a 15-question patient-reported outcome measure assessing vitiligo-specific aspects of life quality using a 7-point Likert scale (0–6), which provides a scoring scale of 0–90; higher scores indicate poorer quality of life [ 25 ].

Data Analysis

For the analysis of patient characteristics, mean, standard deviation, and range were calculated for continuous variables, and frequency counts and percentages for categorical variables. All analyses were conducted in Stata v16 (StataCorp, Texas, USA) [ 26 ]. Missing data were not imputed. Data were analyzed using descriptive statistics.

Study Population and Demographics

In total, 61 US physicians (all dermatologists) completed PRFs for 326 patients with NSV who had ≤ 10% affected BSA. Of these patients, 221 were adults (≥ 18 years) and 105 were adolescents (12–17 years; Table  1 ). Mean (SD) age of all patients was 30.7 (16.4) years, and 199 (61%) had Fitzpatrick skin types I–III. Mean (SD) time since diagnosis was 27.2 (40.8) months, with a mean (SD) affected BSA of 7.6% (5.7%) at diagnosis and 5.6% (3.1%) at time of analysis. Overall, 152 patients (47%) had facial involvement; characteristics for patients with facial involvement are detailed in Table  1 .

A total of 90 patients who had NSV with ≤ 10% affected BSA completed a PSC, of whom 42 (47%) patients had facial involvement. Mean (SD) age of patients completing a PSC was 33.8 (15.9) years, and 65 (72%) of these patients had Fitzpatrick skin types I–III. Mean time since diagnosis was 30.6 (60.0) months, with a mean (SD) affected BSA of 7.3% (4.4%) at diagnosis and 5.5% (2.7%) at time of analysis.

Physician-Reported Regions Affected

For 326 patients with ≤ 10% affected BSA (including those with facial involvement), the physician-reported body regions most affected were head and neck (57%), upper limbs (57%), trunk/torso (31%), and lower limbs (29%; Fig.  1 a). Physicians considered the most bothersome regions to be head and neck for 52% of patients, followed by upper limbs (37%), trunk/torso (15%), and lower limbs for 9% of patients. Among patients with facial involvement, physicians considered the most bothersome regions to be head and neck for 96%, trunk/torso for 4%, upper limbs for 11%, and lower limbs for 1% (Fig.  1 b).

Physician-reported a overall and b most bothersome regions currently affected a ; BSA body surface area. a Physicians could select more than one region

Physician- and Patient-Reported Treatment

At the time of the survey, physicians reported that their 326 patients were receiving an average of 1.4 prescribed treatments, with 61% receiving monotherapy, 35% receiving combination therapy, and 4% not currently receiving prescribed treatment (i.e., untreated). Overall, 38% of patients were receiving topical calcineurin inhibitors (TCI), 30% were receiving moderate-potency topical corticosteroids (TCS), and 12% were receiving narrow-band ultraviolet-B (UVB) phototherapy. Among 152 patients with facial involvement, the prescription of TCIs and narrow-band UVB increased to 43% and 17%, respectively (Fig.  2 a).

Physician-reported most commonly used treatment regimens a currently and b by treatment line a ; BSA body surface area, CS corticosteroid, TCI topical calcineurin inhibitor, TCS topical corticosteroid, UVB ultraviolet-B phototherapy. a Ruxolitinib cream was not approved in the United States at the time of the analysis

Overall, physicians reported that moderate-potency TCS were the most common first-line therapy (37%), and TCI were the most commonly prescribed second- (54%) and third-line therapies (44%; Fig.  2 b). Among patients with facial involvement, TCI were the most commonly prescribed first- (37%), second- (47%), and third-line (53%) therapies. Additionally, prescription of narrow-band UVB increased with each line of therapy. Physicians reported that cosmetics or skin camouflage creams were used by 19% of all patients (facial involvement, 33%).

Furthermore, 37/90 (41%) patients reported using over-the-counter medications. Among these 37 patients, the most commonly reported treatments used were vitamins (38%), creams or oils (35%), and makeup/camouflage cream (22%). Patients also reported spending a mean (SD) of US$17.19 ($36.92) over the last month on pharmacy/drug store nonprescription medicines for their vitiligo.

Physician- and Patient-Reported Treatment Goals

The most common physician-reported treatment goal was repigmentation of lesions for 77% (251/326) of patients, followed by shrinkage of lesions in 47% (154/326; Fig.  3 a). Physicians reported long-term safety of treatment as a goal in 35% (113/326) of patients. For patients with physician-reported data available, repigmentation of lesions was the main physician-reported reason for prescribing the current treatment [50% of patients (146/290); Fig.  3 b]. Reduction of steroid use (36%; 103/290) and overall safety (33%; 95/290) were also considered important reasons for treatment selection.

Physician-reported a treatment goals and b reasons for choice of current treatment for 326 patients with BSA ≤ 10%; BSA body surface area

Repigmentation of lesions was the main treatment goal for 67% (60/90) of patients, which rose to 74% (31/42) for patients with facial involvement (Figure S1 ). Shrinkage of lesions was reported as the main treatment goal by 61% (55/90). Among all patients, 64% (58/90) wanted a treatment that worked quickly, and 54% (49/90) wanted a treatment to stop the spread of their vitiligo; of those patients with facial involvement, 60% (25/42) wanted a treatment that worked well to specifically shrink more noticeable areas. Overall, 42% (38/90) of patients also reported wanting a treatment that was safe to use long term, as did 52% (22/42) of patients with facial involvement.

Physician- and Patient-Reported Satisfaction with Current Treatment

Physicians were satisfied with current treatment outcomes for only 56% of their 326 patients and believed best realistic control had been achieved for only 51% (facial involvement, 45%). Top reasons for treatment dissatisfaction were not initially inducing repigmentation (66%), lack of sustained efficacy (24%), and treatment ineffectiveness for obtaining complete depigmentation (14%).

Among the 90 patients, 14% were dissatisfied with current treatment results (facial involvement, 24%; Figure S2a). Main reasons for dissatisfaction included not liking the way the treatment was taken (23%) and not improving quality of life (21%). For the 42 patients with facial involvement, not improving vitiligo noticeability (27%) and lack of improved quality of life (23%) were most frequently reported as reasons for dissatisfaction. Patients reported feeling frustrated with available treatment options (25%; facial involvement, 37%). Patients reported being fairly (50%) and completely (39%) happy with the way their physician treated their vitiligo (Figure S2b), and were very confident (20%) or somewhat confident (58%) in managing their condition (Figure S2c).

Physician-Reported Psychosocial Impact

Physicians reported that 46% of their 326 patients were impacted by vitiligo in everyday life, with 47% experiencing emotional impact and 44% having low self-esteem (Fig.  4 ). Overall, physicians indicated that 30% avoided social situations, 19% avoided sports or other outdoor activities, and 16% avoided professional situations or intimacy. Physicians also reported that 21% felt socially isolated (facial involvement, 31%), and 14% experienced bullying or abuse (facial involvement, 22%). Physicians also reported that bullying, abuse, or social ostracization were experienced by 22% of all adolescent patients (facial involvement, 39%). Furthermore, physicians reported that 28% of their patients experienced depression and 37% experienced anxiety (facial involvement, 37% and 47%, respectively). Concerningly, 9% of all patients had suicidal ideation (facial involvement, 13%).

Physician-reported a impact of vitiligo on patients’ lives and b situations patients avoid for 326 patients with BSA ≤ 10%; BSA body surface area

Patient-Reported Vitiligo Impact

When patients reported how they felt at the time they received their vitiligo diagnosis, 33% of the 90 patients worried what other people would think (facial involvement, 38%; Figure S3a). Patients reported that their physician understood the impact vitiligo had on their life “quite well” (54%) or “completely” (39%). Overall, 20% reported feeling socially isolated (facial involvement, 29%); however, only 6% reported experiencing bullying or abuse (facial involvement, 10%). Additionally, 53% self-reported having to cover or hide their vitiligo; 31% used makeup to cover vitiligo on their face, and 18% used makeup to cover vitiligo elsewhere on their body (Figure S3b). Patients spent a mean (SD) time of 57 (100) minutes per day covering vitiligo on their face and 30 (48) minutes covering vitiligo on their body. Overall, 21% reported depression (facial involvement, 26%), and 32% reported anxiety (facial involvement, 38%).

Patient-Reported Impact of Vitiligo on Quality of Life and Work Productivity

Work productivity and activity impairment (wpai).

According to the WPAI questionnaire, 43 patients reported a mean (SD) of 12.7% (15.7%) overall work impairment [facial involvement ( n  = 18), 13.5% (15.4%)], and 68 reported a mean (SD) of 14.1% (18.6%) activity impairment due to their vitiligo [facial involvement ( n  = 32), 16.6% (21.0%); Figure S4a].

Hospital Anxiety and Depression Scale (HADS)

For the anxiety domain of the HADS, the mean (SD) score for the 90 patients was 3.5 (3.6), with 4.2 (4.1) in patients with facial involvement (Figure S4b). However, 14% of patients reported a score ≥ 8, suggesting either borderline abnormal or abnormal levels of anxiety (facial involvement, 22%).

For the depression domain of the HADS, the mean (SD) score for all patients was 2.2 (3.2), with 2.9 (3.8) in patients with facial involvement. However, 9% of patients reported a score ≥ 8, suggesting either borderline abnormal or abnormal levels of depression (facial involvement, 14%).

Vitiligo-Specific Quality of Life (VitiQoL) Instrument

The mean (SD) score on the VitiQoL instrument for the 89 patients with data available and the 42 patients with facial involvement was 26.9 (22.9) and 32.5 (25.5), respectively (Figure S4c), indicating moderate quality-of-life impairment [ 27 ].

This study highlights unmet needs in the treatment of vitiligo among patients with ≤ 10% affected BSA. Despite treatment, patients reported minimal or no changes in their vitiligo, exposing them to a high degree of emotional burden. Many patients experienced low self-esteem, avoided social situations, felt socially isolated or experienced bullying/abuse, and reported symptoms of depression and anxiety. Our study was conducted before FDA approval of ruxolitinib cream for topical treatment of NSV, and, in line with treatment guidelines [ 28 , 29 ], physicians prescribed mainly TCI, moderate-potency TCS, or narrow-band UVB phototherapy.

In our study, both physicians and patients reported similar treatment goals, namely repigmentation, shrinkage of lesions (especially noticeable areas), and prevention of the spread of vitiligo. Patients also wanted a treatment that was safe long term and had few or no side effects. However, physicians and patients were dissatisfied with disease control and treatment options available at the time of the study due to a lack of sustained efficacy, including not inducing initial repigmentation and ineffective complete depigmentation. The limited long-term success of current management strategies and the lack of effective treatment options are current barriers in the treatment of vitiligo [ 30 ]. Dissatisfaction rates are often high among physicians and their patients with vitiligo [ 15 , 31 , 32 ], commonly due to issues with sustained repigmentation [ 33 ], as depigmentation recurs in ~ 40% of cases after therapeutic intervention [ 34 ]. Patients, especially those with facial involvement, were also frustrated with treatment outcomes; a quarter of patients reported no improvement in quality of life after treatment.

Nearly half of physicians reported that vitiligo had a negative impact on their patients’ day-to-day life, including low self-esteem, avoidance of social situations, social isolation, bullying, abuse, social ostracization, depression, anxiety, and suicidal ideation. Patients’ reports were consistent with those of their physicians. Recently, the emphasis placed on addressing the emotional burden of vitiligo [ 35 ] and integrating patient-oriented measures in diagnosis and treatment decisions [ 36 ] has been shown to increase treatment adherence, patient satisfaction, and quality of life [ 35 ]. In our study, patients were satisfied with their physician’s awareness of the impact vitiligo had on their daily life, felt fairly or completely happy with the way their physician treated their vitiligo, were involved in treatment decisions, and felt supported by their dermatologists in managing their condition. Patients resorted to over-the-counter medications and spent a significant amount of time using camouflaging makeup to cover or hide their vitiligo. Over a third reported being worried what people would think, and patient-reported low self-esteem, social isolation, and avoidance were high, indicating significant emotional burden. Social avoidance behavior is reported to stem from the fear of negative social encounters including rude remarks and questions about their disease [ 7 , 8 ]. Patients with vitiligo also report feeling embarrassed and disfigured, leading to limited personal relationships [ 7 , 9 ] and sexual disorders [ 37 , 38 ].

Furthermore, our findings are consistent with previous studies indicating depression and anxiety to be the most common psychological comorbidities among patients with vitiligo. A meta-analysis of 29 studies, capturing data on 2530 patients with vitiligo with varying disease severity, found that a quarter of patients had depression and 1 in 7 had anxiety [ 10 ]. In our study, physicians reported depression in nearly one-third of patients and anxiety in two-fifths, with increased suicidal ideation among patients who had facial involvement. These percentages were higher than general population estimates from the United States, where depression and anxiety were reported to affect 19% and 15% of people, respectively [ 39 ]. It is also likely that the prevalence of depression and anxiety is underreported in vitiligo, consistent with other autoimmune conditions [ 40 , 41 , 42 ].

Most studies capturing data on the burden of vitiligo report on patients with a greater extent of affected BSA (often > 25%) [ 43 ], more noticeable lesions (Fitzpatrick skin types IV–VI or lesions on the face, neck, or hands), or those with genital involvement [ 44 ]. However, our study specifically evaluated patients with vitiligo who had ≤ 10% affected BSA and included those with and without facial involvement. As such, our data encompass an underreported cohort of patients with vitiligo and demonstrate that high levels of disease burden occur irrespective of disease extent. Our findings indicate that the disease burden associated with vitiligo is high even among those with a more limited disease extent and may be driven by a lack of efficacious treatment options. Physicians (all dermatologists) were aware of the high disease burden among their patients with vitiligo who had ≤ 10% affected BSA and were dissatisfied with disease control and treatments available at the time of the study. Although patients felt that their dermatologists understood the impact vitiligo had on their daily lives, they were also frustrated with current treatment outcomes and options.

Limitations of this study include that participating patients may not reflect the general population with vitiligo. Firstly, our study included only patients with ≤ 10% affected BSA, consistent with the labeling for ruxolitinib cream. Secondly, data collection was restricted to patients who visited their dermatologist for consultation during the study period. Thirdly, patients who visited their physician more frequently were more likely to be included in the survey than those not consulting their physician as frequently. Additionally, we acknowledge that the results may not be generalizable to patients who are treated by healthcare personnel other than dermatologists or to patients with > 10% affected BSA. To avoid selection bias, physicians were asked to provide data for a consecutive series of patients; however, there were no formal patient selection verification procedures. Recall bias is a common limitation of surveys; however, the data for these analyses were collected at the time of each patient’s appointment, an approach expected to reduce the likelihood of recall bias, particularly since reporting was about current clinical characteristics, treatment experience, and patient burden. Despite the limitations described above, the DSP sample is internally consistent and enables us to accurately describe any differences in clinical or health-related quality-of-life characteristics, management approach, treatment patterns, and burden for patients with vitiligo with or without facial involvement.

Further research would enable identification of additional factors that might be drivers of greater burden among patients with vitiligo. In the global VALIANT survey, patients with vitiligo reported substantial psychosocial burden, which was greatest among patients with > 5% affected BSA, Fitzpatrick skin types IV–VI, and facial or hand lesions versus their counterparts. However, patients with < 1% affected BSA, Fitzpatrick skin types I–III and no facial or hand lesions also reported considerable burden [ 45 ]. Investigation of these and other factors, including affected body regions, age groups, and sex, would help further our understanding of vitiligo burden.

Conclusions

Dermatologists and their patients reported a high patient burden associated with vitiligo limited to ≤ 10% affected BSA, including psychosocial and psychological consequences. Facial involvement was common, with head/neck lesions considered by physicians to be the most bothersome for patients. Repigmentation was the most common dermatologist- and patient-reported treatment goal; however, both dermatologists and patients reported being dissatisfied with disease control and available treatments at the time of the survey. Both dermatologists and patients reported bullying, abuse, and psychosocial comorbidities including depression. Patients also reported spending a considerable amount of time each day covering their vitiligo, experienced work productivity and activity impairment, and had reduced quality of life. Considered together, these findings suggest a significant unmet need concerning treatment and management of this chronic disease in the United States, warranting a focus on managing vitiligo using a full range of treatment options including those more recently approved by the FDA.

Data Availability

Simran Marwaha, James Piercy, Peter Anderson, and Jinan Liu had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All data, i.e., methodology, materials, data and data analysis, that support the findings of this survey are the intellectual property of Adelphi Real World. All requests for access should be addressed directly to Peter Anderson at [email protected].

Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE, Vitiligo Working Group. New discoveries in the pathogenesis and classification of vitiligo. J Am Acad Dermatol. 2017;77(1):1–13.

Article   CAS   PubMed   Google Scholar  

Gandhi K, Ezzedine K, Anastassopoulos KP, et al. Prevalence of vitiligo among adults in the United States. JAMA Dermatol. 2022;158(1):43–50.

Article   PubMed   Google Scholar  

Krüger C, Schallreuter KU. A review of the worldwide prevalence of vitiligo in children/adolescents and adults. Int J Dermatol. 2012;51(10):1206–12.

Hamzavi IH, Bibeau K, Grimes P, 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.

Bergqvist C, Ezzedine K. Vitiligo: a review. Dermatology. 2020;236(6):571–92.

Porter JR, Beuf AH, Lerner A, Nordlund J. Psychosocial effect of vitiligo: a comparison of vitiligo patients with “normal” control subjects, with psoriasis patients, and with patients with other pigmentary disorders. J Am Acad Dermatol. 1986;15(2):220–4.

Krüger C, Schallreuter KU. Stigmatisation, avoidance behaviour and difficulties in coping are common among adult patients with vitiligo. Acta Derm Venereol. 2015;95(5):553–8.

Ongenae K, Beelaert L, van Geel N, Naeyaert JM. Psychosocial effects of vitiligo. J Eur Acad Dermatol Venereol. 2006;20(1):1–8.

Hamidizadeh N, Ranjbar S, Ghanizadeh A, Parvizi MM, Jafari P, Handjani F. Evaluating prevalence of depression, anxiety and hopelessness in patients with vitiligo on an Iranian population. Health Qual Life Outcomes. 2020;18(1):20.

Article   PubMed   PubMed Central   Google Scholar  

Osinubi O, Grainge MJ, Hong L, et al. The prevalence of psychological comorbidity in people with vitiligo: a systematic review and meta-analysis. Br J Dermatol. 2018;178(4):863–78.

Lai Y, Yew Y, Kennedy C, Schwartz R. Vitiligo and depression: a systematic review and meta-analysis of observational studies. Br J Dermatol. 2017;177(3):708–18.

Simons RE, Zevy DL, Jafferany M. Psychodermatology of vitiligo: psychological impact and consequences. Dermatol Ther. 2020;33(3): e13418.

Silverberg JI, Simpson B, Abuabara K, et al. Prevalence and burden of atopic dermatitis involving the head, neck, face, and hand: a cross sectional study from the TARGET-DERM AD cohort. J Am Acad Dermatol. 2023;89(3):519–28.

Lebwohl M, Langley RG, Paul C, et al. Evolution of patient perceptions of psoriatic disease: results from the understanding psoriatic disease leveraging insights for treatment (UPLIFT) survey. Dermatol Ther (Heidelb). 2022;12(1):61–78.

Narayan V, Uitentuis S, Luiten R, Bekkenk M, Wolkerstorfer A. Patients’ perspective on current treatments and demand for novel treatments in vitiligo. J Eur Acad Dermatol Venereol. 2021;35(3):744–8.

Opzelura™ (ruxolitinib cream). Full prescribing information. Incyte Corporation, Wilmington; 2023.

Sidbury R, Alikhan A, Bercovitch L, et al. Guidelines of care for the management of atopic dermatitis in adults with topical therapies. J Am Acad Dermatol. 2023;89(1):e1–20.

Anderson P, Benford M, Harris N, Karavali M, Piercy J. Real-world physician and patient behaviour across countries: Disease-Specific Programmes–a means to understand. Curr Med Res Opin. 2008;24(11):3063–72.

Babineaux SM, Curtis B, Holbrook T, Milligan G, Piercy J. Evidence for validity of a national physician and patient-reported, cross-sectional survey in China and UK: the Disease Specific Programme. BMJ Open. 2016;6(8): e010352.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Higgins V, Piercy J, Roughley A, et al. Trends in medication use in patients with type 2 diabetes mellitus: a long-term view of real-world treatment between 2000 and 2015. Diabetes Metab Syndr Obes. 2016;9:371–80.

US Department of Health and Human Services. Summary of the HIPAA Privacy Rule. 2003 [cited 2023 June 19]; http://www.hhs.gov/sites/default/files/privacysummary.pdf

Health Information Technology (HITECH). Health Information Technology Act. 2009 [cited 2023 June 19]; https://www.healthit.gov/sites/default/files/hitech_act_excerpt_from_arra_with_index.pdf

Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and activity impairment instrument. Pharmacoeconomics. 1993;4(5):353–65.

Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. 1983;67(6):361–70.

Lilly E, Lu PD, Borovicka JH, et al. Development and validation of a vitiligo-specific quality-of-life instrument (VitiQoL). J Am Acad Dermatol. 2013;69(1):e11–8.

StataCorp. Stata Statistical Software: Release 16. College Station: StataCorp LLC 2019.

Picardo M, Huggins RH, Jones H, Marino R, Ogunsola M, Seneschal J. The humanistic burden of vitiligo: a systematic literature review of quality-of-life outcomes. J Eur Acad Dermatol Venereol. 2022;36(9):1507–23.

Eleftheriadou V, Atkar R, Batchelor J, et al. British Association of Dermatologists guidelines for the management of people with vitiligo 2021. Br J Dermatol. 2022;186(1):18–29.

Feng Y, Lu Y. Advances in vitiligo: update on therapeutic targets. Front Immunol. 2022. https://doi.org/10.3389/fimmu.2022.986918 .

Rosmarin D, Pandya AG, Lebwohl M, et al. Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. Lancet. 2020;396(10244):110–20.

Eleftheriadou V, Thomas K, Whitton M, Batchelor J, Ravenscroft J. Which outcomes should we measure in vitiligo? Results of a systematic review and a survey among patients and clinicians on outcomes in vitiligo trials. Br J Dermatol. 2012;167(4):804–14.

Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet. 2015;386(9988):74–84.

Kubelis-López DE, Zapata-Salazar NA, Said-Fernández SL, et al. Updates and new medical treatments for vitiligo. Exp Ther Med. 2021;22(2):1–11.

Article   Google Scholar  

Abdel-Malek ZA, Jordan C, Ho T, Upadhyay PR, Fleischer A, Hamzavi I. The enigma and challenges of vitiligo pathophysiology and treatment. Pigment Cell Melanoma Res. 2020;33(6):778–87.

Huggins RH, Gardner J, Pandya AG. Patient support, education, and compliance. In: Gupta S, Olsson MJ, Parsad D, Lim HW, van Geel N, Pandya AG, eds. Vitiligo: medical and surgical management. Wiley; 2018. pp. 69–75.

van Geel N, Lommerts JE, Bekkenk MW, et al. Development and validation of a patient-reported outcome measure in vitiligo: the Self Assessment Vitiligo Extent Score (SA-VES). J Am Acad Dermatol. 2017;76(3):464–71.

Maamri A, Badri T. Sexual disorders in patients with vitiligo. Tunis Med. 2021;99(5):504.

PubMed   PubMed Central   Google Scholar  

Sarhan D, Mohammed GF, Gomaa AH, Eyada MM. Female genital dialogues: female genital self-image, sexual dysfunction, and quality of life in patients with vitiligo with and without genital affection. J Sex Marital Ther. 2016;42(3):267–76.

Olfson M, Shea S, Feder A, et al. Prevalence of anxiety, depression, and substance use disorders in an urban general medicine practice. Arch Fam Med. 2000;9(9):876–83.

Li N, Chan E, Peterson S. The economic burden of depression among adults with rheumatoid arthritis in the United States. J Med Econ. 2019;22(4):372–8.

Peterson S, Piercy J, Blackburn S, Sullivan E, Karyekar CS, Li N. The multifaceted impact of anxiety and depression on patients with rheumatoid arthritis. BMC Rheumatol. 2019;3:43.

Sruamsiri R, Kaneko Y, Mahlich J. The underrated prevalence of depression in Japanese patients with rheumatoid arthritis—evidence from a Nationwide survey in Japan. BMC Rheumatol. 2017;1:5.

Bibeau K, Pandya A, Ezzedine K, et al. Vitiligo prevalence and quality of life among adults in Europe, Japan and the USA. J Eur Acad Dermatol Venereol. 2022;36(10):1831–44.

Grimes P, Miller M. Vitiligo: patient stories, self-esteem, and the psychological burden of disease. Int J Womens Dermatol. 2018;4(1):32–7.

Bibeau K, Ezzedine K, Harris JE, 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):1124–8.

Download references

Acknowledgements

The authors thank the physicians and their patients with vitiligo who participated in this study.

Medical Writing and Editorial Assistance

Medical writing support under the guidance of the authors was provided by Rebecca Charlton at Adelphi Real World (Bollington, UK) and was funded by Incyte Corporation (Wilmington, DE, USA), in accordance with Good Publication Practice (GPP) guidelines. Editorial assistance was provided by ICON (Blue Bell, PA, USA) and was funded by Incyte.

Data collection was undertaken by Adelphi Real World as part of an independent survey, entitled the Adelphi Vitiligo Disease Specific Programme™ (DSP), a wholly owned Adelphi program. Incyte Corporation (Wilmington, DE, USA) are subscribers to the Adelphi Vitiligo DSP on which this analysis is based. Incyte did not influence the original survey through either contribution to the design of questionnaires or data collection. Sponsorship of the study and the journal’s Rapid Service Fee were funded by Incyte Corporation. Permission to use the Hospital Anxiety and Depression Scale (HADS) was granted prior to its inclusion in this study.

Author information

Authors and affiliations.

Indiana University School of Medicine, Indianapolis, IN, USA

David Rosmarin

Incyte Corporation, 1801 Augustine Cut-Off, Wilmington, DE, 19803, USA

Jennifer H. Lofland & Jinan Liu

Adelphi Real World, Bollington, UK

Simran Marwaha, James Piercy & Peter Anderson

You can also search for this author in PubMed   Google Scholar

Contributions

David Rosmarin, Jennifer H. Lofland, Simran Marwaha, James Piercy, Peter Anderson, and Jinan Liu were involved in 1) conception or design, or analysis and interpretation of data; 2) drafting and revising the article; 3) providing intellectual content of critical importance to the work described; and 4) final approval of the version to be published, and therefore meet the criteria for authorship in accordance with the International Committee of Medical Journal Editors (ICMJE) guidelines. In addition, all named authors take responsibility for the integrity of the work as a whole and have given their approval for this version to be published.

Corresponding author

Correspondence to Jinan Liu .

Ethics declarations

Conflict of interest.

David Rosmarin has received honoraria as a consultant for AbbVie, Abcuro, AltruBio, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Concert, Dermavant Sciences, Dermira, Incyte Corporation, Janssen, Kyowa Kirin, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals, Revolo Biotherapeutics, Sanofi, Sun Pharmaceuticals, UCB, and Viela Bio; has received research support from AbbVie, Amgen, Bristol Myers Squibb, Celgene, Dermira, Galderma, Incyte Corporation, Janssen, Lilly, Merck, Novartis, Pfizer, and Regeneron Pharmaceuticals; and has served as a paid speaker for AbbVie, Amgen, Celgene, Janssen, Lilly, Novartis, Pfizer, Regeneron Pharmaceuticals, and Sanofi. Jennifer H. Lofland and Jinan Liu are employees and stockholders of Incyte Corporation. Simran Marwaha, James Piercy, and Peter Anderson are employees of Adelphi Group, which was contracted by Incyte Corporation to perform this analysis.

Ethical Approval

The Adelphi Vitiligo Disease Specific Programme™ received ethics exemption from the Pearl Institutional Review Board (study protocol number #21-ADRW-122) based on the use of aggregated and de-identified patient data. All data were collected in such a way that patients and dermatologists could not be identified directly; all data were aggregated and de-identified before receipt. Each survey was performed in full accordance with relevant legislation at the time of data collection, including the US Health Insurance Portability and Accountability Act of 1996 and Health Information Technology for Economic and Clinical Health Act legislation. Both physicians and patients consented to take part in the research.

Additional information

Prior Presentation: This manuscript is based on work that has been previously presented at the following conferences: Rosmarin D, Liu J, Marwaha S, et al. Patient Burden of Nonsegmental Vitiligo: Perspectives From US Patients. Presented at Global Vitiligo Foundation Annual Scientific Symposium, March 16, 2023, New Orleans, LA, USA; Joish VN, Rosmarin D, Lofland JH, et al. Management and Impact of Vitiligo on Patient Lives: Survey of US Dermatologists. Presented at Maui Derm NP + PA Summer, June 22–25, 2022, Colorado Springs, CO, USA.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 294 KB)

Rights and permissions.

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, 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 indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ .

Reprints and permissions

About this article

Rosmarin, D., Lofland, J.H., Marwaha, S. et al. Patient Burden of Nonsegmental Vitiligo: A US Real-World Survey of Dermatologists and Their Patients. Dermatol Ther (Heidelb) (2024). https://doi.org/10.1007/s13555-024-01165-5

Download citation

Received : 08 February 2024

Accepted : 10 April 2024

Published : 16 May 2024

DOI : https://doi.org/10.1007/s13555-024-01165-5

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Psychosocial comorbidities
• Disease burden
• Find a journal
• Publish with us
• Track your research

Topical Treatment of Vitiligo in Children and Young Adults

– expert panel releases more than 40 recommendations on topical therapies.

An expert panel has released more than 40 recommendations on managing vitiligo in pediatric, adolescent, and young adult patients.

In their top-line finding, experts identified topical calcineurin inhibitors, topical corticosteroids, and topical JAK inhibitors as effective therapeutics for vitiligo in these populations, with additional decision-making based on location, body surface area, age, and other factors. The consensus statement was published in JAMA Dermatology .

Co-author Nanette Silverberg, MD, is chief of pediatric dermatology for the Mount Sinai Health System and a clinical professor of pediatrics and dermatology at the Icahn School of Medicine at Mount Sinai in New York. She also chairs the Skin of Color and Pigmentary Disorders Study Group of the Pediatric Dermatology Research Alliance. Silverberg discussed the new recommendations with the Reading Room . The exchange has been edited for length and clarity.

What was the impetus for this investigation? How and why did it come about and what were your specific objectives?

Silverberg: We had guidelines for vitiligo from the AAD in the late 1980s, and that was geared as a paper to help physicians get products covered and to support off-label usage -- at that point, of topical corticosteroids. These guidelines are reasonable, but not always applicable completely to today's environment.

Today -- still -- there are really only off-label usages of products for kids under age 12. Our study group was fortunate to receive a grant for this project, which will occur in three parts and is something I hope will evolve into broader AAD guidelines for clinicians as more and more products become approved by the FDA.

We know that only about a third of pediatric or adult patients with vitiligo actually receive treatment from a doctor when they see one. And some of that is about delays. Some of that is because people don't necessarily know that treatments are much more effective than they were years ago.

Would you summarize your conclusions?

Silverberg: The suggestions apply to pediatric, adolescent, and also young adult patients. We did that mindfully because we wanted to be sure that kids were addressed as they go through college years, when they sometimes get lost and don't receive care.

When you boil down our recommendations, it's that any of the treatments -- all the topical therapeutics -- can be effective when used properly.

Are there any takeaways you want to share with clinicians based on the results of this investigation?

Silverberg: We also really want people to understand the nature of how we define vitiligo. Untreated vitiligo can really affect quality of life. It's important to remember that vitiligo is an acquired and progressive disease that includes relapses. It's also important that clinicians think about the chronicity of disease and not just to tell patients 'here's a product.'

We encourage clinicians to pick something that they're comfortable with and then treat. If you're not going to treat, prescribe something you're comfortable with so that there was at least some intervention, and then refer. These kids really do deserve the option for therapy.

Broadly, we have many classes of products that can be used, and the products are individualized. For example, topical calcineurin inhibitors don't atrophy skin, so they're very good for thin skin. They're less effective on thick skin.

I think physicians will find what we discussed and how we looked at it very helpful. But medicine is an art. Vitiligo in particular is an art.

Ultimately, the aspect of time is hard to quantify in an article, but it can take quite some time for vitiligo to re-pigment. We always encourage physicians to counsel patients about this issue.

Over time, we need to think about having patients come back and talk about how they're responding. If they've been treated with therapies that included ultraviolet light, we should be talking about skin exams when they hit adulthood or adolescence. We have to think about the patient, not just who they are today -- but over a lifetime.

• Recommendations: all common topical vitiligo treatments effective in kids and young adults.
• Remind patients that re-pigmentation takes time.
• Experts: clinicians are encouraged to either offer some kind of therapy to these patients and/or refer.

Silverberg reported grants from Incyte; speaking/advisory fees from Regeneron, Sanofi, Verrica, and Novan; and serving on the Vitiligo Support International advisory board.

Primary Source

JAMA Dermatology

Source Reference: Renert-Yuval Y, et al "Expert recommendations on use of topical therapeutics for vitiligo in pediatric, adolescent, and young adult patients" JAMA Dermatol 2024; DOI: 10.1001/jamadermatol.2024.0021.

AAD Publications Corner

MINI REVIEW article

Advances in vitiligo: update on therapeutic targets.

• Department of Dermatology, Jiangsu Province People’s Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing, China

Vitiligo, whose treatment remains a serious concern and challenge, is an autoimmune skin disease characterized by patches of depigmentation. The increasing application of molecular-targeted therapy in skin diseases, such as psoriasis and systemic lupus erythematosus, has dramatically improved their condition. Besides, there is a favorable effect of repigmentation in the treatment of the above diseases combined with vitiligo, implying that molecular-targeted therapy may also have utility in vitiligo treatment. Recently, the role of cytokine and signaling pathways in vitiligo pathogenesis are increasingly recognized. Thus, investigations are underway targeting the molecules described above. In this paper, we present a synopsis of current practices in vitiligo treatment and introduce the improvement in identifying new molecular targets and applying molecular-targeted therapies, including those under development in vitiligo treatment, providing valuable insight into establishing further precision medicine for vitiligo patients.

1 Introduction

Vitiligo is a primary, circumscribed, or generalized depigmentation of the skin and mucosa, related to genetic factors, self-destruction of melanocytes, cytokines, autoimmunity, and oxidative stress ( 1 ). While the detailed molecular mechanisms still require further investigation. In recent years, various studies have showed that the IFN-γ-CXCL9/10-CXCR3 axis appears to be important in vitiligo, via inhibiting melanogenesis, inducing apoptosis of melanocytes, and further recruiting T cells to the skin. These are all involved in the JAK/STAT pathway. In addition, cytokine, including HSP70i, IL-15, IL-17/23, TNF as well as wnt signaling pathway, Tregs, miRNAs have also been proved to be involved in the pathogenesis of vitiligo.

Vitiligo can be treated by different modalities of phototherapy, surgical procedures, and topical therapies, such as glucocorticosteroids, immunosuppressive agents, calcineurin inhibitors, and vitamin D. However, current treatments for vitiligo remain suboptimal, which may not be equally effective in all vitiligo patients, and it would be inconvenient for patients to visit clinics for phototherapy. Targeted therapies, such as biologics targeting cytokines and small-molecule inhibitors targeting intracellular signaling molecules, are recently emerging as promising therapeutics for autoimmune diseases. Their applications also promote our understanding of the detailed molecular mechanism of vitiligo and are essential for guiding a more precise vitiligo treatment. In this article, details of the roles that related cytokines and pathways play as well as the efficacy of targeted therapy have been described.

2 Current treatment

Topical, systemic treatment, and phototherapy are useful for stabilization and repigmentation of vitiligo. Treatment modalities are chosen in the individual patient, based on disease severity, disease activity (stable versus progressive disease), patient preference (including cost and accessibility), and response evaluation. For rapidly progressive disease, low-dose oral glucocorticoids and phototherapy are useful in stabilizing the disease. Therapeutic options for stable, segmental vitiligo include topical therapies (eg, topical corticosteroids, topical calcineurin inhibitors), targeted phototherapy, and surgical therapy (tissue grafts and cellular grafts) ( Table 1 ) ( 14 ). In recent years, attempts have been made to improve the repigmentation of vitiligo phototherapy by combination therapies, including NB-UVB with glucocorticoids ( 15 ), and topical calcineurin inhibitors ( 16 ). While their positive results were not confirmed in all studies. However, the method of treatment described, which were nonspecific, general, off-label, non-targeted with modest efficacy led to the problem of recurrence after stopping treatment. Therefore, efforts should be made to achieve a more comprehensive understanding of vitiligo pathogenesis to develop novel effective therapies ( Table 2 ).

Table 1 Current treatment modalities for vitiligo.

Table 2 Molecular-targeted therapies for the treatment of vitiligo.

3 Small molecules

3.1 emerging therapeutics targeting janus-activated kinase (jak) signaling.

The Janus kinases family consists of JAK1, JAK2, JAK3, and TYK2, which is engaged in the important JAK/STAT pathway, exhibiting pleiotropic effects on transducing multiple extracellular signals involved in regulating proliferative signaling, differentiation, migration, and apoptotic properties ( 28 ).

There are no licensed JAK/STAT inhibitors available against dermatological problems, however, some of them (ruxolitinib and tofacitinib) are used to treat other conditions such as myelofibrosis and RA. However, off-label usage of these medications in the treatment of vitiligo has shown promising outcomes.

JAK-STAT inhibitors promote Sonic Hedgehog and Wnt signaling in epidermal pigmentation, with the former inducing the migration, proliferation, and differentiation of melanocyte ( 29 ). Expanding our knowledge of these medications’ efficacy and safety profiles, as well as their use in dermatological conditions, is critical for establishing their risk-benefit ratio.

3.1.1 Tofacitinib

Tofacitinib is an FDA-cleared JAK1/3 inhibitor for treating RA, PsA, and active ulcerative colitis.

Tofacitinib 5-10 mg QD/BID has demonstrated superior efficacy against vitiligo, with improvement ratios of 5.4% in 5/10 patients with sun-exposed areas or areas treated only with phototherapy ( 30 ), and a reduced rate in vitiligo area scoring index (VASI) score of 4.68 at baseline to 3.95 at 5 months in another trial ( 31 ). In addition, a decline in the number of CD8 + T cells and chemokines, such as CXCL9 and CXCL10 has been observed after tofacitinib treatment, but no variations were observed for the percentage of melanocyte-specific T cells ( 30 ).

Unfortunately, this oral medication is associated with a host of systemic side effects, including infections, malignancies, and cytopenia. Thus, topical JAK inhibitors may be more preferred. 11 vitiligo patients treated with 2% tofacitinib cream twice a day in conjunction with NB-UVB therapy thrice-weekly demonstrated a mean improvement of 70% in facial VASI. There was also a significant difference between facial and non-facial lesions (P=0.022) ( 32 ).

3.1.2 Ruxolitinib

Ruxolitinib, the first Jakinib to get FDA approval, is a JAK1/2 inhibitor designed to deal with polycythemia vera and intermediate- and high-risk primary myelofibrosis ( 33 ).

Studies have shown that except for JAK inhibition, ruxolitinib also inhibited the differentiation and migration of DCs in vitiligo, increasing CD8 + cytotoxic T cell responses ( 34 ). In a double-blind phase 2 trial, 157 recruited vitiligo patients were randomized, in a 1:1:1:1:1 ratio, to receive topical ruxolitinib cream 1.5% BID, 1.5% QD, 0.5% QD, 0.15% QD, or a vehicle for 24 weeks, with the result showing considerably decreased CXCL9 and CXCL10 expression in 1.5% BID and 1.5% QD groups, and more individuals in groups receiving ruxolitinib cream 1.5% BID, 1.5% QD and 0.5% QD achieving F-VASI50, during which 1.5% BID group produced the highest responses in F-VASI50 (58%), F-VASI75 (52%), and F-VASI90 (33%). Besides, three positive responsive groups demonstrated significant repigmentation of vitiligo lesions and acceptable tolerability with a follow-up period of 52 weeks ( 35 ). Vitiligo on the face appears to respond more vigorously to therapy than non-facial lesions, reinforced by a 20-week, open-label trial in which patients with significant facial involvement experienced a 76% improvement in facial VASI scores ( 36 ). Furthermore, better repigmentation rates could be achieved both in oral and topical ruxolitinib treatment combined with phototherapy ( 37 ).

3.1.3 Baricitinib

Baricitinib is a selective JAK1/2 inhibitor that inhibits signal transduction of numerous proinflammatory cytokines ( 38 ), approved for the treatment of RA. To our knowledge, there was only one case report describing repigmentation in vitiligo patients with baricitinib 4 mg daily for the treatment of RA. Besides, an ongoing phase 2 trial (NCT04822584) in which patients received a combination therapy of baricitinib 4mg/d and phototherapy is being performed.

3.1.4 Ifidancitinib (ATI-50002)

Ifidancitinib is another dual JAK1/3 inhibitor for alopecia areata treatment, which is now undergoing phase II clinical trials for its application in vitiligo treatment. Patients with facial NSV(NCT03468855) receiving topical ATI-50002 BID for 24 weeks presented with an improved F-VASI and the Vitiligo Noticeability Scale (VNS) ( 39 ).

3.1.5 Ritlecitinib (PF-06651600) and Brepocitinib (PF-06700841)

Ritlecitinib, an irreversible inhibitor of JAK3 and tyrosine kinase applicable to the treatment of moderate-to-severe RA ( 40 ) and Brepocitinib, a TYK2/JAK1 inhibitor, are currently undergoing evaluation of their efficacy and safety profile in active NSV in combination with phototherapy (NCT03715829) ( 41 ).

3.1.6 Cerdulatinib (PRT062070)

Cerdulatinib, an SYK/JAK dual kinase inhibitor ( 42 ), has been assessed (NCT04103060) for its safety and tolerability for vitiligo treatment in topical formation (0.37% cerudulatinib gel BID).

However, additional studies are needed to determine the best-suited drug regimen and recommended dosage forms and doses to attain the optimum curative effect and minimal toxicity. As the occurrence of depigmentation after the withdrawal of JAK inhibitors, the mechanisms underlying need further exploration, and more work need to be done to corroborate the effectiveness in combination with other therapies.

3.2 Wnt signaling and its agonists

It has been shown that Wnt/β-catenin signaling plays a pivotal role in the proliferation, migration, and differentiation of melanocytes in vitiligo patients ( 29 ), which could be inhibited by oxidative stress ( 43 ). In addition, the Wnt/β-catenin pathway participates in the activation of MITF and its downstream enzymes ( 44 ). Intradermal injection of IWR-1 (inhibitor of Wnt response 1), a chemical inhibitor of β-catenin activation, and small interfering RNA (siRNA) against Wnt7α suppressed the number of epidermal melanocytes ( 45 ). This evidence suggested that stimulation of Wnt signaling may be an adjuvant therapy for vitiligo treatment. Micro-injury ( 46 ) as well as some phenanthridine-derived Wnt-specific agonists binding with the Axin protein have been proved to promote melanogenesis ( 47 ) and induce repigmentation.

3.3 Emerging therapeutics targeting microRNAs (miRNAs)

MiRNAs, which are a highly conservative small class of non-coding RNA molecules, participate in mRNA expression regulation via degradation or repression of mRNA translation ( 48 ). Previous studies have demonstrated that miRNAs were associated with genetic polymorphisms (e.g., miR-196a-2 rs11614913), immune response (e.g., miR-133b, miR-224-3p, miR-4712-3p, miR-3940-5p, miR-21−5p), oxidative stress (e.g., miR-135a, miR-9, miR-34a, miR-183, miR-184, miR-1, miR-25, miR-211, miR-383, miR-577, miR-421) and melanocyte functions (e.g., miR-434-5p, miR-330-5p, miR-137, miR-148, miR-145, miR-155, miR-203, miR-125, miR-377, miR-2909, miR-200c, hsa-miR-149-5p) ( 49 – 54 ), participating in pathological mechanism of vitiligo. These findings suggest that miRNAs may be involved in vitiligo pathogenesis via the modulation of vital genes expression in melanocytes and serve as novel therapeutic targets for vitiligo therapy.

There are two strategies for the therapeutic application of miRNAs: 1) anti-miRNAs, locked-nucleic acids (LNA), or antagomiRs ( 55 ) can be used to counteract the over-activation of miRNA. Short tandem target mimic (STTM)- miR-508-3p has been validated to upregulate SOX6 expression, leading to increased expression of key melanogenic genes CREB, MITF, TYR, and TYRP1/2 with increased melanogenesis ( 56 ). Besides, STTM-miR-143-5p also upregulates the expression of MYO5A, leading to an increase in the level of MITF, TYR, TYRP1, melanin, and Rab27a ( 57 ). 2) miRNA replacement, involving the reintroduction of a gene-suppressor miRNA mimic or AAV (adeno-associated virus)-mediated miRNA gain-of-function to modulate gene expression ( 55 ). A study demonstrated that the migratory capacity of melanocytes was altered by the application of miR-211 mimic through the p53-TRPM1/miR-211-MMP9 axis ( 58 ).

3.4 Emerging therapeutics targeting regulatory T-cells (Tregs)

Tregs are a suppressive CD4 + T cell subset that possesses a capacity to suppress self-reactive T cell activation and expansion ( 59 ). A clear decrease in Treg cells was observed in vitiligo skin within lesional, non-lesional, and perilesional sections ( 60 ), indicating that increasing the number of Tregs with normal function might be an important therapeutic intervention for vitiligo treatment.

Infusing purified populations of Tregs is the most direct way for the supply of Tregs. The current methods mainly include polyclonally-expanded Tregs, antigen-specific Tregs, and engineered Treg cells. In a mouse model of vitiligo, adoptive transfer of polyclonal Tregs may be effective in the short-term ( 61 ), which might however impart systemic immunosuppression ( 62 ). Besides, a TCR transgenic mouse with spontaneous vitiligo, receiving CAR Tregs treatment, developed a significant delay in depigmentation ( 63 ).

However, a limitation of infusing purified populations of Tregs might be the technical difficulty for therapeutic agent delivery to specific cells. A topical application of Tregs or the combination with CCR4 Treg homing receptor ligand CCL22 ( 64 ) by local needle-free jet injection of DNA ( 20 ) or CCL22-encoding plasmid DNA ( 64 ) may help resolve that issue. Besides, various strategies have been applied towards the modulation of Tregs function by targeting Treg-intrinsic pathways and functional modulators for Tregs. HO-1, a functional modulator of Tregs, was decreased in vitiligo Tregs. Treatment with Hemin, an agonist of HO-1, was found to enhance HO-1-induced restoration of Tregs function by up-regulating IL-10 expression ( 65 ). In addition, therapeutic method for microbiota modulation, such as neomycin treatment can significantly delay depigmentation in vitiligo mice and promote the infiltration of Tregs to the skin ( 66 ). Rapamycin, an inhibitor of PI3Kakt-mTORC1 signaling ( 67 ), efficiently halts the depigmentation process by increasing the abundance of Treg in h3TA2 mice, which effect lasted till 6 weeks after treatment ( 61 ). At present, a phase 2 clinical trial(NCT05342519) is underway for assessing the efficacy of the application of 0.1% topical rapamycin ( 68 ) (2022). In addition, nanoparticles containing rapamycin and autoantigen HEL46-61(NPHEL46-61/Rapa) were synthesized, the administration of which halted the disease progression ( 69 ). Also, the calcium-NFATc1-signaling pathway may be involved in defective Tregs function, indicating a potential therapeutic target for vitiligo treatment ( 70 ).

4 Cytokine-targeted therapies

Multiple monoclonal antibodies are available for vitiligo treatment, targeting IFN-γ, CXCL10, CXCR3, HSP70i, IL-15, IL-17/23, and TNF. In addition to full-size immunoglobulin, affibodies and nanobodies, composed of considerably smaller proteins, are currently being developed, which have higher bioavailability as well as affinity and specificity to the targeted molecules.

4.1 IFN-γ and the inhibitors

The IFN-γ-CXCL9/10-CXCR3 axis may be crucial for vitiligo pathogenesis, contributing to disease progression by inhibiting melanogenesis, inducing apoptosis of melanocytes, and further recruiting T cells to the skin ( Figure 1 ) ( 71 ). A study showed a higher expression of IFN-γ mRNA in non-lesional and perilesional skin, especially in active vitiligo ( 72 ), which is associated with disease activity ( 73 ).

Figure 1 1) The immune pathogenesis of vitiligo: (A) CD8 + T cell expression of IFN-γ in vitiligo lesions activated the JAK/STAT pathway after binding to IFN-γ receptor, thus facilitating the release of CXCL9/10. The binding of CXCL9/10 to CXCR3 increased CXCR3+ T cells recruitment; (B) Maintenance of vitiligo lesions was influenced by the function of IL-15-dependent TRM cells, which produce IFN-γ and TNF-α. 2)Targeted therapeutic interventions in vitiligo mainly include therapies targeting IFN-γ-CXCL9/10-CXCR3 axis (IFN-γ neutralizing antibody, CXCL10 neutralizing antibody, and CXCR3 depleting antibody, as well as JAK inhibitors), anti-CD122 antibody (IL-15 receptor subunit) to decrease IFN-γ production and deplete autoreactive CD8 + TRM cells, TNF inhibitor to inhibit autoantibody production, and PD-L1 fusion protein to reduce the numbers of melanocyte-reactive T cells.

Anti-IFN-γ can have been proved to be effective in rheumatoid arthritis (RA), multiple sclerosis (MS), prevention of corneal rejection, autoimmune skin diseases, and others. In a recent study, vitiligo induction mice, treated with intraperitoneal injection with IFN-γ neutralizing antibody (XMG-6) at a dose of 100-500 μg twice a week, presented with significant improvement of depigmentation ( 17 ), with the same trend observed in vitiligo patients. Four patients who received intradermal perilesional injections presented with repigmentation of the treated area and boundary retreat ( 74 ). More research is warranted to be initiated for further definition of the role that IFN-γ plays in vitiligo and to examine whether IFN-γ neutralization would be more viable in reversing skin depigmentation.

4.2 CXCL10 and the inhibitors

Recent studies report a Th1/IFN-γ immune response in both human and a mouse model of vitiligo that involves elevated CXCL9, 10, and 11 productions, among which CXCL10 participated in the targeted migration of T cells ( 18 ), triggering an immune cell infiltration at the early stage ( 72 ), and involved in the downregulation of keratinocyte glycoprotein non-metastatic melanoma protein B (GPNMB) ( 75 ). A study showed that mice receiving CXCL10 neutralizing antibodies developed more repigmentation after 4 weeks’ treatment, which continued for an additional 4 weeks ( 18 ), thereby supporting CXCL10 suppression as a great therapeutic strategy.

4.3 CXCR3 antibodies

CXCR3 has been proved to be expressed in skin lesions, autoreactive T cells ( 18 ), and the vast majority of skin infiltrating CD8 + resident memory T cells (TRM), which stimulate the secretion of IFN-γ and TNF-α ( 76 ).

In a study, vitiligo mice with >75% depigmentation on their tails are treated with CXCR3 depleting antibodies for 7-8 weeks, which significantly reversed the clinical disease in a perifollicular pattern and a diminution of PMEL in the epidermis, with slightly reduced host CD8 + T cell numbers ( 19 ) compared to neutralizing antibody treatment ( 18 ). Although these results are preliminary, they may provide justification for further studies in targeting CXCR3 in vitiligo ( 19 ), which proposes the use of a depleting Ab to create a greater clinical efficacy by removing autoreactive cells rather than modulating their migration phenotype.

4.4 Inducible HSP70 (HSP70i) DNA

Indeed, HSP70i is the core participant in vitiligo predominantly through HSP70i-plasmacytoid dendritic cells (pDCs)-IFN-α-CXCL9 and CXCL10-cytotoxic T lymphocyte (CTL) axis. Pmel-1 mice vaccinated with HSP70i encoding DNA exhibited significant depigmentation, rarely seen in models knockout for HSP70i, indicating that elevated HSP70i expression alone would be enough to induce depigmentation in vitiligo prone animals ( 77 ). A study revealed that the expression of HSP-70 mRNA in skin lesions of active vitiligo patients was much higher ( 78 ), correlated with the disease activity.

Blocking HSP70i activity might have the potential to reverse vitiligo development. A recent study showed that a Sinclair swine, receiving HSP70iQ435A-encoding DNA treatment, showed remarkable repigmentation with an initial influx of T cells and increased CD4/CD8 ratios ( 20 ), which was also detected in mice with HSP70i Q435A -encoding DNA treatment, resulting in 76% restoration of skin pigmentation. Furthermore, the treatment halted T cells accumulation and transition to T cell phenotype in mice and human skin, engaging HSP70i Q435A DNA delivery as a potent effective therapeutic intervention for vitiligo ( 79 ).

4.5 IL-15 and the inhibitors

It has been established that IL-15 seems to participate in IL-17 regulation and maintenance of TRM signals ( 80 ), with the latter responsible for long-term maintenance and potential relapse of vitiligo ( 81 ). The study has demonstrated a higher serum level of IL-15 in vitiligo patients than in controls, highly associated with epidermal H 2 O 2 content and the disease activity ( 82 , 83 ).

In vitiligo mice, an anti-CD122 antibody that targets IL-15 signaling was reported to effectively reverse depigmentation. Anti-CD122 therapy, either systemically or locally, decreases TRM-induced IFN-γ production and results in long-term repigmentation. These findings consider CD122-targeted drugs as a valid therapy method, which results in effective and long-lasting responses in vitiligo and other tissue-specific autoimmune disorders involving TRM ( 21 ).

4.6 PD-1/PD-L1 pathway

Involvement of the PD-1/PD-L1 pathway has been shown in many autoimmune diseases, including RA, MS, and vitiligo. PD-L1 expression was found limited in normal skin, and only expressed on dermal T cells, and increased in primary melanocytes and fibroblasts after exposure to IFN-γ. No such effect was seen in vitiligo patients, indicating the absence of self-protection ability for melanocytes against T-cell attack during vitiligo pathogenesis. In agreement with this, treatment with PD-L1 fusion protein reduced the numbers of melanocyte-reactive T cells, inhibited the activation of Vβ12-expressing T cells, and increased Tregs numbers, reversing depigmentation in a Pmel-1 T-cell receptor transgenic vitiligo mouse model ( 26 ). However, PD-L1 treatment may still call for extended phototherapy treatment, especially NB-UVB therapy, which likely upregulates PD-L1 expression in an NF-κB-dependent manner ( 84 ), indicating a combination use of local PD-1/PD-L1 agonistic treatment and NB-UVB therapy as a promising option.

4.7 Other cytokine-targeted therapies under investigation

4.7.1 il-17/23 and the inhibitors.

Studies on the effect of IL-17/23 in vitiligo resulted in contradictory findings. On one hand, Th17 cells and IL-17 in vitiligo patients may inhibit function-related factors, repress melanogenesis, and dramatically induct other Th17 type cytokines as well as IL-1β production from dermal fibroblasts and keratinocytes ( 85 ). Elevated Th17 cells and IL-17/23 levels in skin lesions and serum of vitiligo patients, were positively correlated with disease activity ( 86 , 87 ), and decreased after narrowband ultraviolet B (NBUVB) treatment ( 88 ). Primary melanocyte culture showed an increased expression of MITF and its downstream genes, increased melanin pigment, and cell proliferation after blockade with anti-IL-17RA ( 22 ). Besides, incidences of repigmentation have been documented in ustekinumab treatment of vitiligo ( 23 ). However, secukinumab treatment in patients with active non‐segmental vitiligo (NSV) contributed to disease progression in 7/8 patients with no general reduction in CXCL9/10, sCD25/27, Th1 cells, or cytotoxic cells, resulting in early termination of study ( 89 ). There are also reports of ustekinumab-induced new-onset vitiligo and alopecia areata. The above studies showed IL-17/23 signal may not play a direct role in vitiligo pathogenesis, which needs further investigation to confirm this conjecture.

4.7.2 TNF and the inhibitors

As an anti-inflammatory mediator, TNF-α is considered to play a role in vitiligo, which may promote apoptosis in melanocytes, induce B-cell activation, increase autoantibody production, and inhibit melanogenesis ( 90 ). Recent data has shown a significantly higher expression of TNF-α in vitiligo skin. TNF inhibitors are beneficial in the treatment of plaque-type psoriasis, psoriatic arthritis (PsA), RA, and inflammatory bowel disease (IBD), arousing growing interest in their use in vitiligo.

Infliximab is a chimeric anti-TNF-α monoclonal antibody specifically binding to both soluble and membrane-bound TNF ( 91 , 92 ). Intravenous infliximab is widely licensed in the treatment of RA, psoriasis, ankylosing spondylitis (AS), IBD, uveitis, and Behcet’s disease. A 24-year-old patient with ankylosing spondylitis and refractory vitiligo improved significantly following six months of infliximab therapy at a dose of 5mg/kg intravenously in weeks 0, 2, and 6, and then every eight weeks for ten months ( 24 ). Besides, Etanercept is a monoclonal antibody targeted against TNF-α ( 93 ), which has been approved for the treatment of RA, juvenile RA, AS, psoriasis, and PsA. Treatment with etanercept 50 mg subcutaneously once or twice weekly for at least 2 months has shown a great curative effect on established vitiligo ( 94 ).

However, it has been shown that anti‐TNF‐α agents, especially adalimumab and infliximab ( 95 ), may exacerbate established vitiligo and induce new-onset vitiligo during treatment of other autoimmune diseases, including AS ( 96 ), Crohn’s disease ( 97 ), ulcerative colitis ( 98 ), psoriasis ( 99 ), and RA ( 100 ). The mechanism responsible for the TNF-α inhibitors-induced vitiligo is not fully understood. On the one hand, TNF-α inhibitors may increase the nucleosome-mediated autoantibody formation, interfere with the cytotoxic T-cell suppression of autoreactive B cells, and decrease Treg synthesis and activation. Additionally, infliximab increases pDC-produced IFN-γ, participating in further T cells recruiting. Although very rare, new-onset or exacerbations of vitiligo can occur in the anti‐TNF‐α treatment of other autoimmune diseases, the risk of which must not be ignored.

4.7.3 Rituximab

Rituximab has specific affinity for the B-lymphocyte transmembrane protein, CD20, which is expressed on B cells ( 101 ), participating in the activation of the CD8 + T cells and the ensuing autoreactive reaction ( 102 ). Rituximab is licensed for the treatment of lymphomas, leukemias, transplant rejection crisis, and a series of autoimmune diseases ( 103 , 104 ). An intravenous infusion of Rituximab was administered to five active disseminated vitiligo patients, the three of whom exhibited a considerable improvement in both the disease’s symptoms and histology ( 25 ).

4.7.4 Abatacept

Abatacept, a fusion protein consisting of IgG1 coupled to the extracellular domain of CTLA-4 via the immunoglobulin’s Fc region, was licensed for treating moderate to severe RA. Ten eligible patients with active vitiligo have been included to receive self-injections of 125mg abatacept weekly from week 0 to week 24. Secondary endpoints will be evaluated during a 32-week follow-up visit ( 105 ).

5 Future therapeutic prospects

As a future direction, new therapeutic approaches should be developed to reduce vitiligo progression. Among the new approaches being developed, the strategy of targeting the IFN-γ-CXCL9/10-CXCR3 axis has been clinically tested. OPZELURA has been indicated for the topical treatment of nonsegmental vitiligo in adult and pediatric patients 12 years of age and older. MiRNA-based therapeutics are also in development. However, the absence of organ or tissue selectivity may also lead to off-target side effects, which must be considered and excluded in the process of miRNA-based therapeutics development. Besides, a suitable vector system, as well as the assurance of chemical and biological stability should also be taken into account. Adoptive Treg cell therapy has also been the research hotspot in recent years. However, it has always been a difficult point for reassurance for safety and the development of the delivery system.

Treating vitiligo remains a challenge. As is presented in this paper, a greater variety of precision treatments is currently being studied. With a better understanding and further validation of these therapeutic targets, patients can be stratified to achieve individualized treatment.

6 Conclusion

Current models of treatment for vitiligo are often nonspecific and general. Various therapy options are available for active vitiligo patients, including systemic glucocorticoids, phototherapy, and systemic immunosuppressants. While stable vitiligo patients may benefit from topical corticosteroids, topical calcineurin inhibitors, phototherapy, as well as transplantation procedures. Recently, a better understanding of the pathophysiological processes of vitiligo led to the advent of novel targeted therapies. To date, JAK inhibitors are the only category that has been proved to have a good tolerability profile and functional outcomes in vitiligo treatment, even though the risk of activation of latent infection and systemic side effects still existed, like other immunosuppressive agents. Research is in progress to investigate the important cytokines involved in the pathogenesis of vitiligo, including IFN-γ, CXCL10, CXCR3, HSP70i, IL-15, IL-17/23, and TNF, the blockade of which has undergone preliminary attempts in animal models and some patients. In addition, studies on miRNA-based therapeutics as well as adoptive Treg cell therapy are still primary, and more studies are necessary.

Author contributions

YFF and YL contributed to the conceptual design, writing, editing, and generation of figures for this manuscript. All authors contributed to the article and approved the submitted version.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

1. Ezzedine K, Eleftheriadou V, Whitton M, van Geel N. Vitiligo. Lancet (London England) (20159988) 386:74–84. doi: 10.1016/S0140-6736(14)60763-7

CrossRef Full Text | Google Scholar

2. Bishnoi A, Vinay K, Kumaran MS, Parsad D. “Oral mycophenolate mofetil as a stabilizing treatment for progressive non-segmental vitiligo: results from a prospective, randomized, investigator-blinded pilot study”. Arch Dermatol Res (2021) 313(5):357–65. doi: 10.1007/s00403-020-02108-8

PubMed Abstract | CrossRef Full Text | Google Scholar

3. Garza-Mayers AC, Kroshinsky D. “Low-dose methotrexate for vitiligo”. Drugs Dermatol (2017) 16(7):705–6.

Google Scholar

4. Singh H, Kumaran MS, Bains A, Parsad D. A randomized comparative study of oral corticosteroid minipulse and low-dose oral methotrexate in the treatment of unstable vitiligo. Dermatology (2015) 231(3):286–90. doi: 10.1159/000433424

5. Taieb A, Alomar A, Bohm M, Dell'anna ML, De Pase A, Eleftheriadou V, et al. Guidelines for the management of vitiligo: The European dermatology forum consensus. Br J Dermatol (2013) 168(1):5–19. doi: 10.1111/j.1365-2133.2012.11197.x

6. Lee JiH, Kwon HS, Jung HMi, Lee H, Kim GM, Yim HW, et al. Treatment outcomes of topical calcineurin inhibitor therapy for patients with vitiligo: A systematic review and meta-analysis. JAMA Dermatol (2019) 155(8):929–38. doi: 10.1001/jamadermatol.2019.0696

7. Lopes C, Trevisani VF, Melnik T. Efficacy and safety of 308-nm monochromatic excimer lamp versus other phototherapy devices for vitiligo: A systematic review with meta-analysis. Am J Clin Dermatol (2016) 17(1):23–32. doi: 10.1007/s40257-015-0164-2

8. Zubair R, Hamzavi IH. Phototherapy for vitiligo. Dermatol Clinics (2020) 38(1):55–62. doi: 10.1016/j.det.2019.08.005

9. Mohammad TF, Hamzavi IH. Surgical therapies for vitiligo. Dermatol Clinics (2017) 35(2):193–203. doi: 10.1016/j.det.2016.11.009

10. Mohammad TF, Al-Jamal M, Hamzavi IH, Harris JE, Leone G, Cabrera R, et al. The vitiligo working group recommendations for narrowband ultraviolet b light phototherapy treatment of vitiligo. J Am Acad Dermatol (2017) 76(5):879–88. doi: 10.1016/j.jaad.2016.12.041

11. Grimes PE, Nashawati R. Depigmentation therapies for vitiligo. Dermatol Clinics (2017) 35(2):219.

12. Mulekar SV, Al Eisa A, Delvi MB, Al Issa A, Al Saeed AH. Childhood vitiligo: A long-term study of localized vitiligo treated by noncultured cellular grafting. Pediatr Dermatol (2010) 27(2):132–6. doi: 10.1111/j.1525-1470.2009.00978.x

13. Mulekar SV. Long-term follow-up study of segmental and focal vitiligo treated by autologous, noncultured melanocyte-keratinocyte cell transplantation. Arch Dermatol (2004) 140(10):1211–5. doi: 10.1001/archderm.140.10.1211

14. Bohm M, Schunter JA, Fritz K, Salavastru C, Dargatz S, Augustin M, et al. S1 guideline: Diagnosis and therapy of vitiligo. J Dtsch Dermatol Ges (2022) 20(3):365–78. doi: 10.1111/ddg.14713

15. Batchelor JM, Thomas KS, Akram P, Azad J, Bewley A, Chalmers JR, et al. Home-based narrowband UVB, topical corticosteroid or combination for children and adults with vitiligo: HI-light vitiligo three-arm RCT. Health Technol Assess (2020) 24(64):1–128. doi: 10.3310/hta24640

16. Li R, Qiao M, Wang X, Zhao X, Sun Q. Effect of narrow band ultraviolet b phototherapy as monotherapy or combination therapy for vitiligo: A meta-analysis. Photodermatol Photoimmunol Photomed (2017) 33(1):22–31. doi: 10.1111/phpp.12277

17. Harris JE, Harris TH, Weninger W, Wherry EJ, Hunter CA, Turka LA. A mouse model of vitiligo with focused epidermal depigmentation requires IFN-gamma for autoreactive CD8(+) T-cell accumulation in the skin. J Invest Dermatol (2012) 132(7):1869–76. doi: 10.1038/jid.2011.463

18. Rashighi M, Agarwal P, Richmond JM, Harris TH, Dresser K, Su M-W, et al. CXCL10 is critical for the progression and maintenance of depigmentation in a mouse model of vitiligo. Sci Trans Med (2014) 6(223):223ra23. doi: 10.1126/scitranslmed.3007811

19. Richmond JM, Masterjohn E, Chu R, Tedstone J, Youd ME, Harris JE. CXCR3 depleting antibodies prevent and reverse vitiligo in mice. J Invest Dermatol (2017) 137(4):982–5. doi: 10.1016/j.jid.2016.10.048

20. Henning SW, Fernandez MF, Mahon JP, Duff R, Azarafrooz F, Guevara-Patino JA, et al. HSP70iQ435A-encoding DNA repigments vitiligo lesions in Sinclair swine. J Invest Dermatol (2018) 138(12):2531–9. doi: 10.1016/j.jid.2018.06.186

21. Richmond JM, Strassner JP, Zapata L, Garg M, Riding RL, Refat MA, et al. Antibody blockade of IL-15 signaling has the potential to durably reverse vitiligo. Sci Trans Med (2018) 10(450):eaam7710. doi: 10.1126/scitranslmed.aam7710

22. Bhardwaj S, Bhatia A, Kumaran MS, Parsad D. Role of IL-17A receptor blocking in melanocyte survival: A strategic intervention against vitiligo. Exp Dermatol (2019) 28(6):682–9. doi: 10.1111/exd.13773

23. Elkady A, Bonomo L, Amir Y, Vekaria AS, Guttman-Yassky E. Effective use of ustekinumab in a patient with concomitant psoriasis, vitiligo, and alopecia areata. JAAD Case Rep (2017) 3(6):477–9. doi: 10.1016/j.jdcr.2017.07.009

24. Simon JA, Burgos-Vargas R. Vitiligo improvement in a patient with ankylosing spondylitis treated with infliximab. Dermatology (2008) 216(3):234–5. doi: 10.1159/000112932

25. Ruiz-Arguelles A, Garcia-Carrasco M, Jimenez-Brito G, Sanchez-Sosa S, Perez-Romano B, Garces-Eisele J, et al. Treatment of vitiligo with a chimeric monoclonal antibody to CD20: A pilot study. Clin Exp Immunol (2013) 174(2):229–36. doi: 10.1111/cei.12168

26. Miao X, Xu R, Fan B, Chen J, Li X, Mao W, et al. PD-L1 reverses depigmentation in pmel-1 vitiligo mice by increasing the abundance of tregs in the skin. Sci Rep (2018) 8(1):1605. doi: 10.1038/s41598-018-19407-w

27. Zou DP, Chen YM, Zhang LZ, Yuan XH, Zhang YJ, Inggawati A, et al. SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the wnt/beta-catenin signaling. Genes Dis (2021) 8(5):677–88. doi: 10.1016/j.gendis.2020.06.003

28. Rawlings JS, Rosler KM, Harrison DA. The JAK/STAT signaling pathway. J Cell Sci (2004) 117(Pt 8):1281–3. doi: 10.1242/jcs.00963

29. Birlea SA, Costin GE, Roop DR, Norris DA. Trends in regenerative medicine: Repigmentation in vitiligo through melanocyte stem cell mobilization. Med Res Rev (2017) 37(4):907–35. doi: 10.1002/med.21426

30. Liu LY, Strassner JP, Refat MA, Harris JE, King BA. Repigmentation in vitiligo using the janus kinase inhibitor tofacitinib may require concomitant light exposure. J Am Acad Dermatol (2017) 77(4):675–82.e1. doi: 10.1016/j.jaad.2017.05.043

31. Vu M, Heyes C, Robertson SJ, Varigos GA, Ross G. Oral tofacitinib: A promising treatment in atopic dermatitis, alopecia areata and vitiligo. Clin Exp Dermatol (2017) 42(8):942–4. doi: 10.1111/ced.13290

32. Mobasher P, Guerra R, Li SJ, Frangos J, Ganesan AK, Huang V. Open-label pilot study of tofacitinib 2% for the treatment of refractory vitiligo. Br J Dermatol (2020) 182(4):1047–9. doi: 10.1111/bjd.18606

33. Deisseroth A, Kaminskas E, Grillo J, Chen W, Saber H, Lu HL, et al. U.S. food and drug administration approval: ruxolitinib for the treatment of patients with intermediate and high-risk myelofibrosis. Clin Cancer Res (2012) 18(12):3212–7. doi: 10.1158/1078-0432.CCR-12-0653

34. Heine A, Held SA, Daecke SN, Wallner S, Yajnanarayana SP, Kurts C, et al. The JAK-inhibitor ruxolitinib impairs dendritic cell function in vitro and in vivo . Blood (2013) 122(7):1192–202. doi: 10.1182/blood-2013-03-484642

35. Rosmarin D, Pandya AG, Lebwohl M, Grimes P, Hamzavi I, Gottlieb AB, et al. Ruxolitinib cream for treatment of vitiligo: A randomised, controlled, phase 2 trial. Lancet (2020) 396(10244):110–20. doi: 10.1016/S0140-6736(20)30609-7

36. Rothstein B, Joshipura D, Saraiya A, Abdat R, Ashkar H, Turkowski Y, et al. Treatment of vitiligo with the topical janus kinase inhibitor ruxolitinib. J Am Acad Dermatol (2017) 76(6):1054–60.e1. doi: 10.1016/j.jaad.2017.02.049

37. Gianfaldoni S, Tchernev G, Wollina U, Roccia MG, Fioranelli M, Lotti J, et al. Micro - focused phototherapy associated to janus kinase inhibitor: A promising valid therapeutic option for patients with localized vitiligo. Open Access Maced J Med Sci (2018) 6(1):46–8. doi: 10.3889/oamjms.2018.042

38. Norman P. Selective JAK inhibitors in development for rheumatoid arthritis. Expert Opin Investig Drugs (2014) 23(8):1067–77. doi: 10.1517/13543784.2014.918604

39. A study of ATI-50002 topical solution for the treatment of vitiligo (2018). Available at: https://clinicaltrials.gov/ct2/show/NCT03468855 .

40. Robinson MF, Damjanov N, Stamenkovic B, Radunovic G, Kivitz A, Cox L, et al. Efficacy and safety of PF-06651600 (Ritlecitinib), a novel JAK3/TEC inhibitor, in patients with moderate-to-Severe rheumatoid arthritis and an inadequate response to methotrexate. Arthritis Rheumatol (2020) 72(10):1621–31. doi: 10.1002/art.41316

41. A phase 2b study to evaluate the efficacy and safety profile of PF-06651600 and PF-06700841 in active non-segmental vitiligo subjects (2018). Available at: https://clinicaltrials.gov/ct2/show/NCT03715829 .

42. Coffey G, Betz A, DeGuzman F, Pak Y, Inagaki M, Baker DC, et al. The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and b-cell cancer. J Pharmacol Exp Ther (2014) 351(3):538–48. doi: 10.1124/jpet.114.218164

43. Regazzetti C, Joly F, Marty C, Rivier M, Mehul B, Reiniche P, 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(12):3105–14. doi: 10.1038/jid.2015.335

44. Harris JE. Melanocyte regeneration in vitiligo requires WNT beneath their wings. J Invest Dermatol (2015) 135(12):2921–3. doi: 10.1038/jid.2015.372

45. Yamada T, Hasegawa S, Inoue Y, Date Y, Yamamoto N, Mizutani H, et al. Wnt/beta-catenin and kit signaling sequentially regulate melanocyte stem cell differentiation in UVB-induced epidermal pigmentation. J Invest Dermatol (2013) 133(12):2753–62. doi: 10.1038/jid.2013.235

46. Han X, Chang Li, Qiu Z, Lin M, Wang Y, Liu D, et al. Micro-injury induces hair regeneration and vitiligo repigmentation through wnt/β-catenin pathway. Stem Cells Dev (2022) 31(5-6):111–8. doi: 10.1089/scd.2021.0276

47. Yang BJ, Fan SR, Zhang XF, Cai JY, Ruan T, Xiang ZR, et al. Design, synthesis and structure-activity relationship optimization of phenanthridine derivatives as new anti-vitiligo compounds. Bioorg Chem (2022) 119:105582. doi: 10.1016/j.bioorg.2021.105582

48. Baek D, Villen J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature (2008) 455(7209):64–71. doi: 10.1038/nature07242

49. Li L. The role of MicroRNAs in vitiligo: Regulators and therapeutic targets. Ann Dermatol (2020) 32(6):441–51. doi: 10.5021/ad.2020.32.6.441

50. Huo J, Liu T, Li F, Song X, Hou X. MicroRNA215p protects melanocytes via targeting STAT3 and modulating Treg/Teff balance to alleviate vitiligo. Mol Med Rep (2021) 23(1):51. doi: 10.3892/mmr.2020.11689

51. Vaish U, Kumar AA, Varshney S, Ghosh S, Sengupta S, Sood C, et al. Micro RNAs upregulated in vitiligo skin play an important role in its aetiopathogenesis by altering TRP1 expression and keratinocyte-melanocytes cross-talk. Sci Rep (2019) 9(1):10079. doi: 10.1038/s41598-019-46529-6

52. Zhao C, Wang D, Wang X, Mao Y, Xu Z, Sun Y, et al. Down-regulation of exosomal miR-200c derived from keratinocytes in vitiligo lesions suppresses melanogenesis. J Cell Mol Med (2020) 24(20):12164–75. doi: 10.1111/jcmm.15864

53. Li L, Xie Z, Qian X, Wang T, Jiang M, Qin J, et al. Identification of a potentially functional circRNA-miRNA-mRNA regulatory network in melanocytes for investigating pathogenesis of vitiligo. Front Genet (2021) 12:663091. doi: 10.3389/fgene.2021.663091

54. Shang Z, Li H. Altered expression of four miRNA (miR-1238-3p, miR-202-3p, miR-630 and miR-766-3p) and their potential targets in peripheral blood from vitiligo patients. J Dermatol (2017) 44(10):1138–44. doi: 10.1111/1346-8138.13886

55. Kwekkeboom RF, Lei Z, Doevendans PA, Musters RJ, Sluijter JP. Targeted delivery of miRNA therapeutics for cardiovascular diseases: opportunities and challenges. Clin Sci (Lond) (2014) 127(6):351–65. doi: 10.1042/CS20140005

56. Liu B, Zhang J, Yang S, Ji K, Liu X, Du B, et al. Effect of silencing microRNA-508 by STTM on melanogenesis in alpaca (Vicugna pacos). Gene (2018) 678:343–8. doi: 10.1016/j.gene.2018.08.011

57. Qi S, Liu B, Zhang J, Liu X, Dong C, Fan R. Knockdown of microRNA1435p by STTM technology affects eumelanin and pheomelanin production in melanocytes. Mol Med Rep (2019) 20(3):2649–56. doi: 10.3892/mmr.2019.10492

58. Su M, Miao F, Jiang S, Shi Y, Luo L, He X, et al. Role of the p53−TRPM1/miR−211−MMP9 axis in UVB−induced human melanocyte migration and its potential in repigmentation. Int J Mol Med (2020) 45(4):1017–26. doi: 10.3892/ijmm.2020.4478

59. Levings MK, Sangregorio R, Roncarolo MG. Human cd25(+)cd4(+) t regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med (2001) 193(11):1295–302.

PubMed Abstract | Google Scholar

60. Klarquist J, Denman CJ, Hernandez C, Wainwright DA, Strickland FM, Overbeck A, et al. Reduced skin homing by functional treg in vitiligo. Pigment Cell Melanoma Res (2010) 23(2):276–86. doi: 10.1111/j.1755-148X.2010.00688.x

61. Chatterjee S, Eby JM, Al-Khami AA, Soloshchenko M, Kang HK, Kaur N, et al. A quantitative increase in regulatory T cells controls development of vitiligo. J Invest Dermatol (2014) 134(5):1285–94. doi: 10.1038/jid.2013.540

62. Alzhrani A, Bottomley M, Wood K, Hester J, Issa F. Identification, selection, and expansion of non-gene modified alloantigen-reactive tregs for clinical therapeutic use. Cell Immunol (2020) 357:104214. doi: 10.1016/j.cellimm.2020.104214

63. Mukhatayev Z, Dellacecca ER, Cosgrove C, Shivde R, Jaishankar D, Pontarolo-Maag K, et al. Antigen specificity enhances disease control by tregs in vitiligo. Front Immunol (2020) 11:581433. doi: 10.3389/fimmu.2020.581433

64. Eby JM, Kang HK, Tully ST, Bindeman WE, Peiffer DS, Chatterjee S, et al. CCL22 to activate treg migration and suppress depigmentation in vitiligo. J Invest Dermatol (2015) 135(6):1574–80. doi: 10.1038/jid.2015.26

65. Zhang Q, Cui T, Chang Y, Zhang W, Li S, He Y, et al. HO-1 regulates the function of treg: Association with the immune intolerance in vitiligo. J Cell Mol Med (2018) 22(9):4335–43. doi: 10.1111/jcmm.13723

66. Dellacecca ER, Cosgrove C, Mukhatayev Z, Akhtar S, Engelhard VH, Rademaker AW, et al. Antibiotics drive microbial imbalance and vitiligo development in mice. J Invest Dermatol (2020) 140(3):676–687 e6. doi: 10.1016/j.jid.2019.08.435

67. Powell JD, Delgoffe GM. The mammalian target of rapamycin: linking T cell differentiation, function, and metabolism. Immunity (2010) 33(3):301–11. doi: 10.1016/j.immuni.2010.09.002

68. Daily topical rapamycin for vitiligo (2022). Available at: https://clinicaltrials.gov/ct2/show/NCT05342519 .

69. Zhang X, Liu D, He M, Lin M, Tu C, Zhang B. Polymeric nanoparticles containing rapamycin and autoantigen induce antigen-specific immunological tolerance for preventing vitiligo in mice. Hum Vaccin Immunother (2021) 17(7):1923–9. doi: 10.1080/21645515.2021.1872342

70. Giri PS, Bharti AH, Begum R, Dwivedi M. Calcium controlled NFATc1 activation enhances suppressive capacity of regulatory T cells isolated from generalized vitiligo patients. Immunology (2022). doi: 10.1111/imm.13538

71. Yang L, Wei Y, Sun Y, Shi W, Yang J, Zhu L, et al. Interferon-gamma inhibits melanogenesis and induces apoptosis in melanocytes: A pivotal role of CD8+ cytotoxic T lymphocytes in vitiligo. Acta Derm Venereol (2015) 95(6):664–70. doi: 10.2340/00015555-2080

72. Maouia A, Sormani L, Youssef M, Helal AN, Kassab A, Passeron T. Differential expression of CXCL9, CXCL10, and IFN-gamma in vitiligo and alopecia areata patients. Pigment Cell Melanoma Res (2017) 30(2):259–61. doi: 10.1111/pcmr.12559

73. Shi F, Erf GF. IFN-gamma, IL-21, and IL-10 co-expression in evolving autoimmune vitiligo lesions of smyth line chickens. J Invest Dermatol (2012) 132(3 Pt 1):642–9. doi: 10.1038/jid.2011.377

74. Skurkovich S, Skurkovich B, Kelly J. Anticytokine therapy, particularly anti-IFN-gamma, in Th1-mediated autoimmune diseases. Expert Rev Clin Immunol (2005) 1(1):11–25. doi: 10.1586/1744666X.1.1.11

75. Biswas KB, Takahashi A, Mizutani Y, Takayama S, Ishitsuka A, Yang L, et al. GPNMB is expressed in human epidermal keratinocytes but disappears in the vitiligo lesional skin. Sci Rep (2020) 10(1):4930. doi: 10.1038/s41598-020-61931-1

76. Boniface K, Jacquemin Clément, Darrigade A-S, Dessarthe Benoît, Martins C, Boukhedouni N, et al. Vitiligo skin is imprinted with resident memory CD8 T cells expressing CXCR3. J Invest Dermatol (2018) 138(2):355–64. doi: 10.1016/j.jid.2017.08.038

77. Mosenson JA, Zloza A, Klarquist J, Barfuss AJ, Guevara-Patino JA, Poole ICLe. HSP70i is a critical component of the immune response leading to vitiligo. Pigment Cell melanoma Res (2012) 25(1):88–98. doi: 10.1111/j.1755-148X.2011.00916.x

78. Doss RW, El-Rifaie AA, Abdel-Wahab AM, Gohary YM, Rashed LA. Heat shock protein-70 expression in vitiligo and its relation to the disease activity. Indian J Dermatol (2016) 61(4):408–12. doi: 10.4103/0019-5154.185704

79. Mosenson JA, Zloza A, Nieland JD, Garrett-Mayer E, Eby JM, Huelsmann EJ, et al. Mutant HSP70 reverses autoimmune depigmentation in vitiligo. Sci Transl Med (2013) 5(174):174ra28. doi: 10.1126/scitranslmed.3005127

80. Tokura Y, Phadungsaksawasdi P, Kurihara K, Fujiyama T, Honda T. Pathophysiology of skin resident memory T cells. Front Immunol (2020) 11:618897. doi: 10.3389/fimmu.2020.618897

81. Richmond JM, Strassner JP, Rashighi M, Agarwal P, Garg M, Essien KI, et al. Resident memory and recirculating memory T cells cooperate to maintain disease in a mouse model of vitiligo. J Invest Dermatol (2019) 139(4):769–78. doi: 10.1016/j.jid.2018.10.032

82. Chen X, Guo W, Chang Y, Chen J, Kang P, Yi 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. doi: 10.1016/j.freeradbiomed.2019.05.011

83. Atwa MA, Ali SMM, Youssef N, Mahmoud Marie RE. Elevated serum level of interleukin-15 in vitiligo patients and its correlation with disease severity but not activity. J Cosmet Dermatol (2021) 20(8):2640–4. doi: 10.1111/jocd.13908

84. Wang W, Chapman NM, Zhang B, Li M, Fan M, Laribee RN, et al. Upregulation of PD-L1 via HMGB1-activated IRF3 and NF-kappaB contributes to UV radiation-induced immune suppression. Cancer Res (2019) 79(11):2909–22. doi: 10.1158/0008-5472.CAN-18-3134

85. Kotobuki Y, Tanemura A, Yang L, Itoi S, Wataya-Kaneda M, Murota H, et al. Dysregulation of melanocyte function by Th17-related cytokines: significance of Th17 cell infiltration in autoimmune vitiligo vulgaris. Pigment Cell Melanoma Res (2012) 25(2):219–30. doi: 10.1111/j.1755-148X.2011.00945.x

86. Bassiouny DA, Shaker O. Role of interleukin-17 in the pathogenesis of vitiligo. Clin Exp Dermatol (2011) 36(3):292–7. doi: 10.1111/j.1365-2230.2010.03972.x

87. Vaccaro M, Cannavo SP, Imbesi S, Cristani M, Barbuzza O, Tigano V, et al. Increased serum levels of interleukin-23 circulating in patients with non-segmental generalized vitiligo. Int J Dermatol (2015) 54(6):672–4. doi: 10.1111/ijd.12392

88. Hegazy RA, Fawzy MM, Gawdat HI, Samir N, Rashed LA. T helper 17 and tregs: A novel proposed mechanism for NB-UVB in vitiligo. Exp Dermatol (2014) 23(4):283–6. doi: 10.1111/exd.12369

89. Speeckaert R, Mylle S, van Geel N. IL-17A is not a treatment target in progressive vitiligo. Pigment Cell melanoma Res (2019) 32(6):842–7. doi: 10.1111/pcmr.12789

90. Birol A, Kisa U, Kurtipek GS, Kara F, Kocak M, Erkek E, et al. Increased tumor necrosis factor alpha (TNF-alpha) and interleukin 1 alpha (IL1-alpha) levels in the lesional skin of patients with nonsegmental vitiligo. Int J Dermatol (2006) 45(8):992–3. doi: 10.1111/j.1365-4632.2006.02744.x

91. Chan AC, Carter PJ. Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol (2010) 10(5):301–16.

92. Horiuchi T. Transmembrane TNF-α: structure, function and interaction with anti-TNF agents. Rheumatology (2010) 49(7):1215–28.

93. Spencer-Green and G. Etanercept (Enbrel): update on therapeutic use. Ann Rheum Dis (2000) 59 Suppl 1(90001):i46–9.

94. Webb KC, Tung R, Winterfield LS, Gottlieb AB, Eby JM, Henning SW, et al. Tumour necrosis factor-α inhibition can stabilize disease in progressive vitiligo. Br J Dermatol (2015) 173(3):641–50. doi: 10.1111/bjd.14016

95. Bae JM, Kim M, Lee HH, Kim KJ, Shin H, Ju HJ, et al. Increased risk of vitiligo following anti-tumor necrosis factor therapy: A 10-year population-based cohort study. J Invest Dermatol (2018) 138(4):768–74. doi: 10.1016/j.jid.2017.11.012

96. Toussirot E, Salard D, Algros MP, Aubin F. [Occurrence of vitiligo in a patient with ankylosing spondylitis receiving adalimumab]. Ann Dermatol Venereol (2013) 140(12):801–2. doi: 10.1016/j.annder.2013.09.158

97. Jung JM, Lee YJ, Won CH, Chang SE, Lee MW, Choi JH, et al. Development of vitiligo during treatment with adalimumab: A plausible or paradoxical response?". Ann Dermatol (2015) 27(5):620–1. doi: 10.5021/ad.2015.27.5.620

98. Ryu TH, Lee DW, Choi JE, Ahn HH, Kye YC, Seo SH. A type II segmental vitiligo developed under infliximab treatment for ulcerative colitis. Ann Dermatol (2017) 29(6):826–7. doi: 10.5021/ad.2017.29.6.826

99. Smith DI, Heffernan MP. Vitiligo after the resolution of psoriatic plaques during treatment with adalimumab. J Am Acad Dermatol (2008) 58(2 Suppl):S50–2. doi: 10.1016/j.jaad.2006.05.035

100. Carvalho CLDB, Ortigosa LCM. Segmental vitiligo after infliximab use for rheumatoid arthritis–a case report. Anais bras dermatol (2014) 89(1):154–6. doi: 10.1590/abd1806-4841.20142887

101. Banchereau J, Rousset F. Human b lymphocytes: phenotype, proliferation, and differentiation. Adv Immunol (1992) 52:125–262. doi: 10.1016/s0065-2776(08)60876-7

102. Lin X, Tian H, Xianmin M. Possible roles of b lymphocyte activating factor of the tumour necrosis factor family in vitiligo autoimmunity. Med Hypotheses (2011) 76(3):339–42. doi: 10.1016/j.mehy.2010.10.034

103. Eisenberg R, Albert D. B-cell targeted therapies in rheumatoid arthritis and systemic lupus erythematosus. Nat Clin Pract Rheumatol (2006) 2(1):20–7. doi: 10.1038/ncprheum0042

104. Ioannou Y, Isenberg DA. Current concepts for the management of systemic lupus erythematosus in adults: A therapeutic challenge. Postgrad Med J (2002) 78(924):599–606. doi: 10.1136/pmj.78.924.599

105. Open-label pilot study of abatacept for the treatment of vitiligo . Available at: https://clinicaltrials.gov/ct2/show/NCT02281058 .

Keywords: vitiligo, targeted therapy, JAK inhibitors, biological, treatment, miRNA - microRNA, Treg

Citation: Feng Y and Lu Y (2022) Advances in vitiligo: Update on therapeutic targets. Front. Immunol. 13:986918. doi: 10.3389/fimmu.2022.986918

Received: 05 July 2022; Accepted: 04 August 2022; Published: 31 August 2022.

Reviewed by:

Copyright © 2022 Feng and Lu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Yan Lu, [email protected]

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

News Center

Children with skin diseases suffer stigma, bullying and depression, first large study to look at mental health problems in children with chronic skin conditions.

When someone walks briskly past David Artz, 16, on the sidewalk, he immediately thinks they are trying to get away from him. This is how his young mind works. He has a chronic skin disease that makes his skin red, scaly and rough. He has alopecia and is bald. 

David has grown up feeling stigmatized and teased–someone to be avoided because he might be “contagious.”

“It makes me sad and tearful when I think people are avoiding me because of how I look,” Artz said. “It’s hard to be different.” 

A new Northwestern Medicine study published in JAMA Dermatology shows Artz’s experience is common for children and teens with chronic skin diseases.

The majority of children and teens with chronic skin diseases such as acne, eczema, psoriasis, alopecia areata (hair loss) and vitiligo (pigment loss) feel stigmatized by peers for their condition and are sometimes bullied, the study reports. As a result, these children have a poor quality of life that includes suffering from depression, anxiety and impaired relationships with their peers. 

“These chronic skin conditions can be tremendously life-altering, including shaping psychosocial development,” said corresponding study author Amy Paller, MD, MS , the chair and Walter J. Hamlin Professor of Dermatology and a pediatric dermatologist at the Ann & Robert H. Lurie Children’s Hospital of Chicago.

Having a chronic skin disease during childhood is not uncommon. Eczema affects more than 10 percent of school-aged children. Among teenagers, acne affects more than 90 percent and psoriasis 1 percent.

This is the first large, multi-site study of the psychosocial impact of skin diseases in children and teens.

The study showed that 73 percent of 1,671 children had experienced a measurable stigma, which was strongly associated with poor quality of life.

The disease severity and visibility as rated by the child (age eight and older) was quite different from that of the doctor’s ratings, suggesting the need to ask the child about the disease and its impacts.

The investigators used a newly developed scoring tool for stigma in school-aged children (PROMIS Pediatric Stigma) and collaborated with 31 sites in the Pediatric Dermatology Research Alliance to measure the extent of stigma, depression, anxiety, and poor peer relationships — and their association with an impaired quality of life.

“Stigma, which is when something false and negative is attached to an individual, can have a profound effect on children’s and teens’ mental health,” Paller said. “For example, a child with dark scales on the body can be called ‘dirty’ by other kids or a child with a hair loss issue can be shunned by other children who fear the hair loss is contagious.”

That can lead the child to internalize these thoughts, so these become their own perceptions. The false beliefs can convince other people around them that it’s true when it’s not. These kids often feel embarrassed or ashamed.”

The majority of the bullying and teasing occurs in school, Paller said.

“These painful experiences can shape a child’s personality into adulthood and erode self-confidence,” Paller said. “Children may underestimate their abilities and worry about taking social risks. They don’t feel good enough and this shame may affect them lifelong.”

Kids also may not be able to concentrate because they are worried in school, affecting their performance, Paller said.

“The study results should encourage clinicians to aggressively treat skin disorders in children and consider referral to evaluation and counseling of the child and potentially family if mental health issues occur,” Paller said.

Doctors need to ask children and parents about the impact of these diseases — stigma, mental health, how it impacts life — not just note the observable clinical manifestations.

It’s important to refer families to dermatologists for optimal treatment to decrease severity and visibility, which contribute to psychosocial impacts.”

Paller also suggested parents ask teachers to discuss the skin disease in the classroom, so other children understand it better. “Try to diminish the stigma through education and talk about and recognize bullying,” Paller said.

Meantime, things are looking up for David this year. He has made a new friend, a buddy he goes fishing with after school. “I found a friend who doesn’t care about me having a skin issue. He sees me on the inside for who I am. These are the friends you need to be around.”

Related Posts

Gene therapies could transform treatment of rare blood disorders, tech can’t replace human coaches in obesity treatment, new mechanisms underlying tumor variety in brain cancers discovered.

Comments are closed.

Type above and press Enter to search. Press Esc to cancel.

Mental wellbeing of patients who have Vitiligo: Tips, tricks, ways to motivate patients

V itiligo is a skin condition that causes white patches to appear on the skin due to loss of pigmentation and has a significant impact on the mental well-being of an affected individual because coming to terms with the changes in appearance, daily social ostracization, non-inclusion and the resulting sense of isolation can be emotionally draining for vitiligo patients. It is essential to acknowledge that these challenges stem from ignorance and stigma and that collective action is essential to remedy the situation.

In an interview with HT Lifestyle, Dr Vikram Vora, Medical Director at Indian Subcontinent – International SOS, shared, “There are numerous strategies to help promote self-acceptance and foster resilience in those impacted by this condition. However, these need to be credible, comprehensive and coordinated. Due to prior experiences, vitiligo sufferers may have a lesser degree of faith in people. Building trust and empathy with the affected individuals, demonstrating a genuine understanding of their experiences and acknowledging the emotional impact of living with vitiligo is a good start. Many vitiligo sufferers may have developed self-stigma about their condition and educating them is crucial to help manage their mental well-being effectively. Accurate information about causes, symptoms and available management options, along with clearing any misconceptions about the condition can alleviate their anxiety. With increased awareness and knowledge, these individuals can develop a better understanding of their condition and feel more in control.”

He highlighted, “As vitiligo impacts one’s self-esteem and body image, the development of a positive self-image can be achieved by helping them focus on their strengths and talents rather than solely their appearance. Psychologists suggest that self-compassion and reducing negative self-talk can assist in building a more realistic and positive self-perception. Acceptance of the condition can be achieved by encouraging overall well-being rather than a singular focus on physical appearance. Regular exercise, healthy eating, and engaging in hobbies or creative pursuits are self-care strategies that definitely help. Encouraging adoption of relaxation techniques and the practice of mindfulness reduces stress and anxiety and helps to challenge and counter negative thought patterns.”

According to him, having a robust support network comprising of family, friends, colleagues and managers provides a sense of belonging and support, through experience-sharing. Dr Vikram Vora revealed, “ This support can be in-person or even online via multiple available forums. Local support groups, counselling services in the community and EAPs at the workplace can also offer ways for patients to share their stories, gain insights, develop adaptive coping mechanisms and receive validation of their efforts. Empathy can create a safe space for expressing emotions and begin the healing process. Addressing the mental well-being challenges of those who have vitiligo requires an honest and empathetic approach. Keeping them away from normal social discourse and interactions is something that should not and cannot be accepted in today’s world. All sections of society need to work together, towards promoting a society that embraces diversity and inclusion. For those impacted, self-acceptance, resilience, and a positive self-image that ensures a fulfilling life, can only happen when we make this effort.”

Adding to the list of few simple methods to motivate patients with vitiligo, Dr Sushil Tahiliani, Consultant Dermatologist at PD Hinduja Hospital and Medical Research Centre in Mumbai, suggested, “Post-diagnosis, it is extremely important to normalise the disease as only the loss of colour from the body. It is crucial to establish that their bodies are healthy and because it does not affect their health, if they don't get bogged down psychologically, they can achieve goals which a lot of vitiligo patients have achieved in their life because they did not look at vitiligo as a very serious disease which should finish their aspersions and aspirations in life but rather continues to follow and achieve them. The second most important thing that I have definitely incorporated in my practice is examining the patients without gloves if not required. By touching the lesions and trying to win their confidence and reassure them about the non-contagious nature of this condition.”

He explained, “By also sharing statistics and success stories of patients being affected by vitiligo would create a sense of confidence in the patients. Translating that into figures to tell them that at least 28 million Indians must be having vitiligo - would help in reducing the feeling of being the odd one out. Additionally, inform them about the modern ways of treating vitiligo and give them guarded optimism because in good 60% odd cases, you can re-pigment them. While they are being re-pigmented, they are also given options of using camouflage creams on the open areas of the body, because it goes a long way in building confidence because when they look at the world, they can discuss what they've gone to discuss, they can study what they're going to study and the topic doesn't get diverted to vitiligo, which can be an irritant and harm the self-confidence.”

He concluded, “While also highlighting to them that in case the medicines don't work in some of the stable vitiligo cases, especially the segmental vitiligo cases, we have surgical options which work very well. And in those cases where everything fails, and they got two colours, and about 40, or 50% of the body turns white, I give them the option of removing the balance pigmentation to give them a uniform colour. Added-on tips would include protecting their skin against excessive sun exposure because they don't have melanin to protect their skin, and thus will be at a higher risk of skin ageing. The challenge is bigger if we have a child as a patient because we had to do hand holding and counselling for the parents first so that they don't cry in front of the child and they don't have drop jaws and sad faces. It's very important for the child to have encouragement and support from the parents and for the parents to keep the child happy and give the child a lot of confidence that does half the job done. The more you normalise the disease, the better it would be for those affected.”

Read more news like this on HindustanTimes.com

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• J Cutan Aesthet Surg
• v.6(2); Apr-Jun 2013

A New Era of Vitiligo Research and Treatment

Davinder parsad.

Department of Dermatology, Post-graduate Institute of Medical Education and Research, Chandigarh, India

This is a very exciting phase of vitiligo research in which vitiligo is being tackled by multipronged attacks in the form of advancement in basic research, genetics and treatment including surgical management. In order to achieve the ultimate goal of total stability and complete repigmentation, there is a need to define a roadmap and roadblocks.

Vitiligo Global Issues Consensus Conference (VGICC) recently revised the classification of the disease.[ 1 ] There are still several unmet needs as pathophysiology or prognosis based classifications would be more useful. Recent progress in genetics of generalized vitiligo provide insights into underlying pathogenetic mechanisms and incrimination of vitiligo susceptibility genes that controls important aspects of immune regulation.[ 2 ] Recent data has clearly supported that vitiligo is a T-cell mediated autoimmune disease.[ 3 , 4 ] Heat shock protein 70 (HSP70) plays a central non redundant role in precipitating of depigmentation in vitiligo.[ 5 ] Mosenson et al . in a very promising study recently showed that vitiligo can be reversed through immune targeting with mutant HSP70.[ 6 ]

The bottle neck in vitiligo research is defining stability in vitiligo. Many attempts have been made to define it based on clinical, histological or immunological parameter with variable results.[ 7 , 8 ] It seems that disease activity in vitiligo is a dynamic process and only predictable thing about stability in non-segmental vitiligo is its unpredictability. VGICC recommends disease stability be best assessed based on the stability of individual lesions rather than the overall stability of the disease as the latter is difficult to define precisely and reliably.[ 1 ]

There are two main goals of any vitiligo treatment; first is to stop the arrest of further depigmentation and second is to induce repigmentation. The first goal can only be archived fully if we could unravel the mechanisms underlying the disappearance of melanocytes in vitiligo. If this can be achieved repigmentation should be rather simple to accomplish with a combination of medical and/or surgical treatment. Unfortunately, in the literature there are only few studies which have taken into consideration the disease activity as most of the published studies discussed repigmentation as the main outcome. Phototherapy, topical calcineurin inhibitors and topical steroids are still the mainstay of medical treatment of vitiligo. In a recent preliminary study, afamelanotide (16 mg subcutaneous implant) along with Narrowband UVB has given promising results.[ 9 ] Further, controlled studies are required to confirm its efficacy and define its role in the management of vitiligo.

Surgical methods are emerging as an important solution for stable vitiligo refractory to medical treatment. Over the years vitiligo surgery has gained steady importance with more and more improved techniques proving their effectiveness. Non-cultured epidermal cell suspension (NCES) is emerging as the first line of surgical management of stable vitiligo.[ 10 ] Major advantages of NCES are that a smaller amount of donor skin is needed to cover large recipient area, little postoperative pain and discomfort, easier placement of cellular graft, excellent color match. Mohanty et al . used follicular unit extraction to tap the melanocytes reservoir in the hair follicle in the surgical management of vitiligo.[ 11 ] There are many differences between epidermal and hair follicle melanocytes. Epidermal melanocytes mainly consist of a homogeneous population of highly dendritic and uniformly weakly pigmented cells, whereas hair follicle melanocyte consists of at least three distinct sub-populations, including highly pigmented/dendritic bulbar melanocytes, less-differentiated tripolar cells, and an undifferentiated amelanotic bipolar sub-population. In addition, hair follicle melanocytes expressed some antigens associated with alopecia areata, but not antigens associated with vitiligo. This could be an added advantage of repigmentation induced by using hair follicle melanocytes and long-term follow-up is required for assessing the stability of repigmentation.

In this new era of vitiligo research we are looking forward to the development of new molecules aimed at vitiligo rather than borrowing from the agents used for other diseases. New exciting options are being explored as more reservoirs of melanocytes are being unravelled like dermal stem cells.