recent research in vitiligo

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

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.

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Temprian Therapeutics: developing a gene-based treatment for vitiligo

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Therapeutic efficacy of cell-based therapy in vitiligo: a research letter systematically reviewed using meta-analysis

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• Published: 22 May 2024
• Volume 316 , article number  198 , ( 2024 )

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• Xue Wang 1   na1 ,
• Hai Ci 2   na1 ,
• Cheng Chen 3 ,
• Songen Chen 3 ,
• Hanluo Li 3 ,
• Bin Xie 4 ,
• Simin Li 5 ,
• Yongsheng Li 6 &
• Weishan Wang   ORCID: orcid.org/0009-0005-5201-4038 7  

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Dear Editors,

Vitiligo is an auto-immune intractable disorder characterized by the loss of functioning epidermal melanocytes, which is treated either conservatively or surgically. When vitiligo becomes refractory to medical treatment and stable, surgical techniques using cell therapies become an important alternative [ 1 ]. The rational basis of surgical methods is the transfer of melanocytes from uninvolved skin to the stable vitiligo patch in the form of either a tissue graft or a cellular graft, including epidermal blister grafts, split-thickness grafts, and full-thickness punch grafts [ 2 ]. Cellular grafting includes transplantation of cultured pure melanocytes, co-cultured melanocyte–keratinocyte cell suspensions, cultured epidermal cell suspensions, Non-Cultured Epidermis-derived Cell (NCEC) suspensions and Non-Cultured Extracted Hair Follicle Outer Root Sheath Cell Suspensions (NCFCS) [ 3 ].

To estimate the treatment outcome of various types of cellular transfer therapy (epidermal cell suspension, melanocyte suspension, extracted hair follicle root sheath cell suspension) in stable vitiligo, we are systematically meta-analysis the treatments to resolve discrepancies of these results. We searched 4 electronic databases (PubMed, EMBASE, Cochrane, and NCBI) with reports of randomized- and non-randomized controlled trials (RCT and non-RCT) in cellular transfer for the treatment of stable vitiligo (Fig.  1 ). The meta-analysis included 17 RCT studies, 7 non-RCTs, and 4 comparisons.

Meta-analysis of 22 studies involving 592 unique patients including 16 RCTs and 6 non-RCTs. A Flow diagram of the meta-analysis study selection process. B Risk of bias summary of all included RCTs. C Risk-of-bias graph of all included RCTs: comparison of epidermis-derived cellular transfer and placebo/no treatment control. D List of 22 studies with 16 RCTs and 6 non-RCTs

It was found that there was no significant difference between epidermal tissue grafting(ETG) and NCES in the outcomes of ≥ 75% repigmentation (RR = 1.18, 95% CI 0.93, 1.49) and ≥ 90% repigmentation (RR = 1.06, 95% CI 0.92, 1.23) (Fig.  2 ). Epidermal melanocyte transplantation is not an inferior alternative to the conventional ETG, which is more suitable for treatments of the larger depigmented areas. No significant difference was demonstrated between cultured epidermis-derived cells and NCEC suspension transfer in the outcome of ≥ 50% repigmentation (RR = 2.23, 95% CI 0.61, 8.08) and ≥ 90% repigmentation (RR = 0.98, 95% CI 0.80, 1.21). Therefore, for the small lesion area, NCEC suspension treatment was recommended. No significant difference was found between NCES and NCFCS in the outcome of ≥ 75% repigmentation (RR = 1.26, 95% CI 0.97, 1.64) and ≥ 90% repigmentation (RR = 1.43, 95% CI 0.91, 2.26); but NCEC is better than NCFSC in repigmentation and healing time ( P  = 0.02). Cultured hair follicle root sheath cell suspension seems to be a promising technique to replace conventional epidermal cellular transfer. Combining the two together (NCES + NCFCS) displayed better efficacy than NCES alone in the outcome of ≥ 75% repigmentation (RR = 1.34, 95% CI 1.09, 1.65) and ≥ 90% repigmentation (RR = 1.99, 95% CI 1.32, 2.99), shown that FCS combined with NCEC is significantly superior to the NCEC alone [ 4 ].

Meta-analysis of forest plots using various cellular transplantation with clinical effects over 75% repigmentation and over 90% repigmentation. A Comparison of ETG and NCEC. B Comparison of Cultured Epidermis-derived Cells and NCEC transfer. C Comparison of NCEC suspension and NCFCS. D Comparison between NCFCS + NCEC and NCES alone. E Table of the vitiligo patient information including duration of disease and anatomical sites, etc. With “/” representing no dates

In conclusion, cellular transfer could be an alternative method to epidermal tissue grating. More RCTs with high-quality, large sample size, longer follow-up, and consistent repigmentation scoring system should be performed, and an agreed scaling system of outcome measures for repigmentation should be established in the future [ 5 ]. The combination of epidermis-derived cells and follicular cells could be a promising trend for treating stable vitiligo.

Data availability

The data supporting this study are available on request from the corresponding author, WS Wang.

Falabella R (2005) Surgical approaches for stable vitiligo. Dermatol Surg 31:1277–1284. https://doi.org/10.1111/j.1524-4725.2005.31203

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Khunger N, Kathuria SD, Ramesh V (2009) Tissue grafts in vitiligo surgery—past, present, and future. Indian J Dermatol 54:150–158. https://doi.org/10.4103/0019-5154.53196

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Schneider M, Dieckmann C, Rabe K, Simon JC, Savkovic V (2014) Differentiating the stem cell pool of human hair follicle outer root sheath into functional melanocytes. Methods Mol Biol 1210:203–227. https://doi.org/10.1007/978-1-4939-1435-7_16

Whitton ME, Pinart M, Batchelor J, Leonardi-Bee J, González U, Jiyad Z, Eleftheriadou V, Ezzedine K (2015) Interventions for vitiligo. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD003263.pub5

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This work was supported by grants from the National Natural Science Foundation of China (Grant Nos. 82203956) and and PhD Fund (No. BS202111) of the First Affiliated Hospital of Shihezi University.

Author information

Xue Wang and Hai Ci contributed equally to this work. Hanluo Li and Simin Li contributed equally as the co-senior authors.

Authors and Affiliations

Dermatology Department, First Affiliated Hospital of Shihezi University, Xinjiang, 832008, China

Department of Burn and Plastic Surgery, First Affiliated Hospital of Shihezi University, Xinjiang, 832008, China

National “111” Center for Cellular Regulation and Molecular Pharmaceutics, Cooperative Innovation Center of Industrial Fermentation (Ministry of Education and Hubei Province), Hubei University of Technology, Wuhan, 430068, China

Cheng Chen, Songen Chen & Hanluo Li

Zhejiang Lab, Kechuang Avenue, Zhongtai Sub-District, Yuhang District, Hangzhou, 311121, Zhejiang, China

Stomatological Hospital, School of Stomatology, Southern Medical University, 366 Jiangnan South Avenue, Haizhu District, Guangzhou, 510280, Guangdong, China

School of Chemistry and Chemical Engineering, Pharmacy School, State Key Laboratory Incubation Base for Green Processing of Chemical Engineering, Shihezi University, Xinjiang, 832003, China

Yongsheng Li

Department of Orthopedics Center, First Affiliated Hospital of Shihezi University, Xinjiang, 832008, China

Weishan Wang

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Wang Weishan: Corresponding author, he undertakes the funding, design, writing and control of the project. Hanluo Li, Simin Li, Cheng Cheng: They are responsible for article writing, literature search and article drawing. Wang Xue, Hanluo Li, Wang Weishan: They are responsible for applying for funding. Ci Hai, Li Yongsheng, Songen Chen, Bin Xie: They are responsible for data collection and Revman software support.

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Wang, X., Ci, H., Chen, C. et al. Therapeutic efficacy of cell-based therapy in vitiligo: a research letter systematically reviewed using meta-analysis. Arch Dermatol Res 316 , 198 (2024). https://doi.org/10.1007/s00403-024-02920-6

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Study reveals the economic burden for patients with vitiligo in the US is significant

by Elsevier

A novel study in the Journal of Investigative Dermatology , shows that patients with vitiligo incur significantly higher health care costs than people without this skin condition. The findings reveal an unmet need for cost-effective treatments and highlight the importance of fully identifying the drivers of economic burden for patients with vitiligo.

Lead investigator Khaled Ezzedine, MD, Ph.D., Department of Dermatology, AP-HP, Henri Mondor University Hospital, and Epidemiology in Dermatology and Evaluation of Therapeutics (EpiDermE)—EA 7379, Université Paris-Est Créteil (UPEC), explains, "Data regarding the economic burden of vitiligo are scarce and outdated. Our study quantifies the health care costs and health care resource utilization (HCRU) among patients with vitiligo. Determining medical costs will help identify the main expenditure predictors and spending patterns."

Vitiligo, a chronic autoimmune disorder that affects 0.5-2.0% of the United States population, is characterized by skin depigmentation caused by the loss of melanocytes. Patients with vitiligo incur direct costs associated with their condition through medical fees, pharmacy expenses, and out-of-pocket costs (e.g., sunscreens, protective clothing, cosmetic concealers, and camouflage products). They may also experience indirect costs owing to psychosocial effects, loss of work productivity, and lost opportunities (e.g., marriage, career choice, promotions, salary increases, or education).

Dr. Ezzedine continues, "Patients with vitiligo are often reported to have psychological problems , such as depression, anxiety, and shame, leading to low self-esteem and social isolation. Higher costs for patients with vitiligo than for persons without it may partly be explained by a higher risk of mental health conditions as well as other comorbidities among patients with vitiligo, including thyroid disease, diabetes, and alopecia areata that impact the cost of the disease."

For this retrospective cohort analysis, the Merative MarketScan Commercial Database, health care costs, and HCRU were evaluated for 49,512 patients with vitiligo compared to 99,024 people without vitiligo in the US between January 2007 and December 2021.

Outcomes included all-cause and vitiligo-related costs (2021 dollars) and all-cause HCRU, including mental health-related HCRU. Patients with vitiligo incurred significantly higher all-cause costs ($15,551 vs. $7,735) and vitiligo-related costs ($3,490 vs. $54) costs than controls. Mental health-related HCRU was also significantly higher among patients with vitiligo. Taken together, health care costs and HCRU were significantly higher among patients with vitiligo than among controls.

In this analysis, the increased costs were associated with significantly higher inpatient costs, ER visits, ambulatory visits, number of prescriptions and prescriptions costs, and other costs (e.g., medical equipment and home health care ), illustrating the importance of independently evaluating the economic burden of different skin conditions. The results from this study show that the economic burden of vitiligo was comparable with those of other well-studied dermatologic conditions, such as atopic dermatitis and psoriasis.

This study shows that the increased health care costs for patients with vitiligo versus those of non-vitiligo controls were driven by medical costs rather than pharmacy costs, and the increased HCRU was primarily the result of outpatient visits compared with inpatient or ER visits, which aligns with the main cost drivers identified in studies of the economic burden of atopic dermatitis and psoriasis.

Dr. Ezzedine concludes, "The health care costs and HCRU for patients in the US with vitiligo in this study were significantly higher than for patients without a vitiligo diagnosis. The economic burden was markedly higher for patients receiving treatment with systemic effects or with new mental health diagnoses than for the total vitiligo population. These findings reveal an unmet need for cost-effective treatments and highlight the importance of fully identifying the drivers of economic burden for patients with vitiligo."

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VYN201 for Vitiligo: Promising Data Showcases Potential of BET Inhibition

VYNE Therapeutics' Iain Stuart, PhD, spoke with Dermatology Times to discuss recent phase 1 and pre-clinical data for VYN201 for vitiligo.

VYNE Therapeutics recently presented pre-clinical and phase 1b data demonstrating promise in nonsegmental vitiligo at the Society for Investigative Dermatology Annual Meeting last weekend in Dallas, Texas.

Iain Stuart, PhD, the chief scientific officer at VYNE, recently spoke with Dermatology Times to discuss the potential of BET inhibitors such as VYN201 in the therapeutic landscape of vitiligo.

"This disease state has had marked, marked unmet need for many, many years. It has been overlooked by industry with respect to new therapies, and even the therapies that are coming through now are all based on one pharmacology," Stuart said. "We think that's unacceptable. We think the potential for BET inhibition could be very broad, and not just in vitiligo, but into all the dermatologic and immunologic diseases. The very fact that we have shown the very first clinical dataset in an autoimmune disease, and it happened to be vitiligo, was particularly encouraging."

Iain Stuart, PhD: Hi, I'm Dr Iain Stuart. I'm the Chief Scientific Officer at VYNE Therapeutics.

Dermatology Times: What is VYN201 and its mechanism of action? How does it compare to available therapies for vitiligo?

Stuart: So VYNE's inhibit platform has really 2 verticals: VYN201 and VYN202. VYN201 is a locally-administered pan-bromodomain and extraterminal inhibitor. It's a small molecule. VYN202 is a BD2-selective bromodomain and extraterminal inhibitor.

BET proteins play a key role in the regulation of gene transcription through a phenomena called epigenetic interactions. Now, that really is a science the grew out of a lot of work in oncology. Epigenetic interactions can be viewed through readers, writers, and erasers. Bromodomain and extraterminal proteins recognize acetylated lysines that protrude out the structural chromatin array and the nucleus of a cell. We're obviously focusing on signals or aberrant inflammatory signals, and B cells and T cells. But fundamentally, that's the key mechanism.

As epigenetic readers, they actually recruit transcriptional factors that help with the process of building what's called a transcript for a particular protein. Obviously, we are interested in inflammatory proteins, and then how that's ultimately translated into affiliate foreign protein. That actually has direct applicability in oncology, but also in autoimmune diseases. That's really where we are quite different from any other company that are looking at BET inhibitors. If you want to look specifically at the utility of BET inhibitors in immunoinflammatory disorders and profibrotic diseases.

VYN201 itself is called a soft drug. We specifically selected the molecule to have a very high first pass metabolism, so that anything that passes through the skin; VYN201 is topically applied. We also have formulations for injectable forms into the joint and as an inhaled form. Anything that passes through the skin is rapidly detoxified through the liver. The hope there is obviously to improve, markedly, the benefit-risk profile of BET inhibitors.

With respect to other mechanisms that are being viewed in vitiligo, they are primarily all built around JAK inhibition. The JAK-STAT pathway is obviously very well-established in dermatology and in a wide variety of specialities. But for the most part, most of the meds and early-stage development programs are based around JAK inhibition.

Dermatology Times: How do the phase 1 and pre-clinical data support the development of VYN201?

Stuart: That's a great question. We presented 2 papers at SID: a pre-clinical paper and a clinical paper. The pre-clinical paper really did focus on certain cellular processes that are key to the pathogenesis of vitiligo. Vitiligo is a disease of CD positive T-cell behavior. CD T-cells expand rapidly in patients' skin who have vitiligo, and they're primed towards attacking melanocytes. Melanocytes are obviously the cells that generate melanin and give us our color and our pigment.

What we found in our pre-clinical studies when we compared to another JAK inhibitor called ruxolitinib, is that VYN201 was so superior in preventing that expansion in in-vitro testing. We also found that the ex-vivo model of what's called melanocytology, so this was based on a human recombinant reformed epidermis, where we can actually induce the loss of color. We also saw a decrease in the matrix metalloproteinase called MMP-9. MMP-9 has been implicated and vitiligo as a key pathogenic molecule that drives the depigmentation of skin by detaching, or essentially destabilizing, melanocytes that sit right at the epidermal and dermal junction of your skin. What happens is that this detachment causes melanocytes to drift up through the skin and is lost. That's why when you see patients with vitiligo, the first areas they tend to lose the pigment is around the mouth, the eyes, the axilla, the groin, backs of hands, tops of feet, anywhere where skin rubs or people are scratching, because the melanocytes literally drift to the surface and are last to the mechanical processes. It's very comforting to see that we can reduce that key marker. Correspondingly, E-cadherin, which is a protein that holds melanocytes and keratinocytes together, we could actually prevent that loss as well.

Also in the pre-clinical paper, we showed potential for VYN201 to operate a key process that is dysfunctional in vitiligo. That process, or pathway, is substantially downregulated in patients with vitiligo, and it's actually key to allow melanocytes to differentiate and start to produce melanin or melanogenesis. We actually saw some upregulation of that as well. So that's some data from a pre-clinical paper.

In the clinical paper, we summarized the key data from an open-label phase 1b study with VYN201 where we were treating patients with nonsegmental vitiligo. That was for once-daily treatment for 16 weeks. It was an open-label trial. Obviously being a phase 1 study, the primary objective was safety, tolerability, and pharmacokinetics. We treated up to 29 patients across 3 cohorts, and we treated topically applied medications 0.5%, 1%, and 2%, so we actually saw some substantial improvement on vitiligo on the face. We really used that as our primary endpoint. It's called F-VASI, or Facial Vitiligo Area and Severity Index. We also saw great improvement there at our 1% and our 2% cohorts, and a very rapid onset of action, which was particularly encouraging, particularly when vitiligo studies take so long to see real recovery and pigmentation. That's one of the challenges of managing patients with vitiligo.

At the 16-week timepoint, we saw 39% improvement in our top dose of 2%. We also saw some very healthy movement and some key biomarkers from the non-facial areas. We took biopsies from lesions elsewhere on the body. Again, that helps support the hypothesis that VYN201 could potentially support the recovery of the pathway.

We also saw a nice reduction of MMP-9, which is what we saw in our pre-clinical study. Again, that does support both an anti-inflammatory mechanism but also potentially support a more proactive approach of allowing melanocytes to recover in the skin. So we're really pleased with that.

Safety from that study was very encouraging. Obviously, it's only 16 weeks of treatment for once-daily. We will continue that development program, but it's encouraging to this day.

Dermatology Times: How do these results inform future clinical trials involving VYN201?

Stuart: We certainly think the data supports advancement. VYN201 is a very differentiated therapy, as I said earlier on. The vast majority of drugs that are currently in development for vitiligo are JAK inhibitors and come along with all the associated safety precautions that come along with that class of molecule. There's a tremendous unmet need in vitiligo in general, and within the therapeutic space, there's basically no differentiation. We really think that there's a space here for VYN201.

What was particularly encouraging was this dataset from the phase 1b was the first clinical demonstration of a BET inhibitor in any autoimmune disease, which was very encouraging. Our hypothesis that BET is a key potential new target in immunobiology has been particularly encouraging for us, and to see that in a clinic was very supportive. We are moving into a phase 2b study very shortly this quarter in nonsegmental vitiligo.

The 2b trial will enroll up to 160 patients across 4 arms and will include both what's called active disease and stable disease patients. We will evaluate VYN201 as a topical gel at 1%, 2%, and 3% concentration strengths. Initially, for up to 24 weeks, in a double-blinded manor, and then once we get to the 24 week timepoint, patients receiving the vehicle, sometimes known as placebo, will be re-randomized to 1%, 2%, or 3% for a further 6 months for a total of 1 year of therapy. The first portion of the study we anticipate to read out in 2025.

I think the key thing here is that we hear you. We hear you that this disease state has had marked, marked unmet need for many, many years. It has been overlooked by industry with respect to new therapies, and even the therapies that are coming through now are all based on one pharmacology. We think that's unacceptable. We think the potential for BET inhibition could be very broad, and not just in vitiligo, but into all the dermatologic and immunologic diseases. The very fact that we have shown the very first clinical dataset in an autoimmune disease, and it happened to be vitiligo, was particularly encouraging. We're looking forward to continuing the program and involving the dermatology community in the next steps for VYN201.

[Transcript has been edited for clarity.]

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609-716-7777

Demographic and clinical feature disparity between progress and non-progress patients with vitiligo after COVID-19 vaccination: A cross-sectional study

Affiliations.

• 1 Department of Dermatopathology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
• 2 Clinical Research Center, Shanghai Skin Disease Hospital, Tongji University, Shanghai, China.
• 3 Department of Rheumatology, Shanghai Skin Disease Hospital, Tongji University School of Medicine, Shanghai, China.
• PMID: 37140178
• DOI: 10.1111/exd.14825

There have been several case reports regarding newly developed vitiligo following the coronavirus disease 19 (COVID-19) vaccination. However, the relationship between COVID-19 vaccine and vitiligo progression remains unclear. To explore the relationship between COVID-19 vaccine and vitiligo progression and its potential influencing factors, A cross-sectional study was conducted on 90 patients with vitiligo who received inactivated COVID-19 vaccination. Detailed information covering demographic characteristics (age and sex), vitiligo clinical features (disease subtypes, duration, stage and comorbidities) and disease activity was collected through an electronic questionnaire. Ninety patients with vitiligo included 44.4% males, with an average age of 38.1 years (standard deviation, SD = 15.0). Patients were divided into progress group (29, 32.2%) and normal group (61, 67.8%) based on whether they experienced vitiligo progression after inactivated COVID-19 vaccination. 41.3% of patients in the progress group experienced vitiligo progression within 1 week after vaccination, and disease progression mainly occurred after the first dose inoculation (20, 69.0%). Logistic regression revealed that patients aged <45 years (odds ratio (OR) was 0.87, 95% confidence interval (CI): 0.34-2.22) and male patients (OR = 0.84, 95% CI: 0.34-2.05) had lower risk for vitiligo progression, while patients with segmental vitiligo (SV) subtype (OR = 1.68, 95% CI: 0.53-5.33), with <5 years disease duration (OR = 1.32, 95% CI: 0.51-3.47) had higher risk for vitiligo progression after COVID-19 vaccination, but without statistical significance. Over 30% patients experienced vitiligo progression after inactivated COVID-19 vaccination, and female patients, elder age, shorter disease duration and SV subtype are potential risk factors for vitiligo progression.

Keywords: COVID-19; autoimmunity; disease progression; vaccination; vitiligo.

© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Publication types

• Research Support, Non-U.S. Gov't
• COVID-19 Vaccines / adverse effects
• COVID-19* / complications
• COVID-19* / epidemiology
• COVID-19* / prevention & control
• Cross-Sectional Studies
• Middle Aged
• Vaccination / adverse effects
• Vitiligo* / epidemiology
• Vitiligo* / etiology
• COVID-19 Vaccines

News Details

Edsa: preparing ind for phase 2 trial of eb06 in vitiligo.

By David Bautz, PhD

NASDAQ:EDSA

READ THE FULL EDSA RESEARCH REPORT

Business Update

Readying IND for EB06 in Vitiligo

Edesa Biotech, Inc. (NASDAQ:EDSA) is planning for a Phase 2 study of its anti-CXCL10 monoclonal antibody for the treatment of moderate-to-severe non-segmental vitiligo patients. Vitiligo is a disease that causes areas of the skin to lose color, with non-segmental vitiligo being characterized by patches appearing on both sides of the body. It is caused when pigment-producing cells (melanocytes) die or stop producing melanin as a result of an autoimmune disease, genetics, or a triggering event (e.g., stress, sunburn, skin trauma).

The vitiligo market is projected to reach approximately $650 million by 2030 (EvaluatePharma), and two recent events show the potential for vitiligo treatments in development:

• In October 2022, Villaris Therapeutics was acquired by Incyte (INCY) for $70 million upfront and up to $1.3 billion in potential milestone payments. Villaris was developing auremolimab, an anti-IL-15R monoclonal antibody in preclinical development for the treatment of vitiligo.

• In October 2023, VYNE Therapeutics (VYNE) announced positive results from the Phase 1b trial of VYN201 in patients with non-segmental vitiligo with a mean percentage reduction in F-VASI score for the 1.0% and 2.0% cohort of 30.3% and 39.0%, respectively. In addition, the drug was generally well tolerated with a favorable safety profile. Following the announced results, VYNE raised gross proceeds of $88 million in a private placement financing.

In addition, Opzelura® (ruxolitinib) was approved for the treatment of vitiligo in July 2022 and is projected to have sales of >$500 million for that indication in 2030 (EvaluatePharma). We believe that a successful Phase 2 trial with EB06 in vitiligo patients would result in a significant revaluation of that asset in line with the valuations assigned other vitiligo products as shown above.

Update on EB05 Development in ARDS

Edesa is developing EB05 (paridiprubart) as a treatment for acute respiratory distress syndrome (ARDS). The drug is currently being evaluated in a Phase 3 clinical trial of approximately 600 patients hospitalized with ARDS caused by SARS-CoV-2 infections who are on invasive mechanical ventilation, both with and without additional organ support such as extracorporeal membrane oxygenation (ECMO). The primary endpoint for the study is the mortality rate at 28 days.

To support this Phase 3 study, in October 2023 Edesa secured a commitment of up to CAD$23 million from the Government of Canada via the Strategic Innovation Fund (SIF) to help cover expenses for the Phase 3 trial. The SIF funding will be applied toward study expenses, including hospital and physician expenditures, along with scale-up manufacturing for commercial drug product if development is successful. It will also allow for an expansion of the number of hospitals in the trial so that the company can fine-tune for places with the highest hospitalization rates. The SIF is an initiative by the Canadian government to expand and grow the life sciences sector and money is allocated from the SIF following a competitive review process. The company recently announced it is transitioning the day-to-day management of the ongoing Phase 3 trial to a new clinical research organization (CRO), which should provide access to more powerful analytical tools, expand recruitment capabilities, allow greater visibility of enrollment trends, and have a quicker turnaround of trial results.

The company has plans to evaluate EB05 in a broader ARDS population, however the best regulatory pathway forward for the drug is still being determined. Were the company to amend the current protocol to include all ARDS patients it would likely change the powering assumptions for the study and potentially introduce additional risks and variables. In addition, EB05 has the emergency use authorization (EUA) pathway still available to it in ARDS caused by COVID, and the addition of non-COVID patients to the trial may affect the potential to use the EUA pathway. Edesa is interested in getting EB05 approved in the most expeditious manner possible and the company is continuing to evaluate how best to do that while at the same time maintaining the goal of testing the drug in a general ARDS population.

Plans to File IND for Anti-TLR4 Antibody in IPF

Edesa is planning to file an Investigational New Drug (IND) application such that a Phase 2 trial of paridiprubart (EB07) can be initiated in pulmonary fibrosis (subject to securing funding or securing a partnership), which is the end stage of a broad range of interstitial lung diseases characterized by the progressive scarring of lung tissue. There are more than 200 known causes of pulmonary fibrosis, with idiopathic pulmonary fibrosis (IPF) being the most common form. IPF affects approximately 250,000 individuals in the U.S. (Pulmonary Fibrosis Foundation) and there are only two FDA approved therapies, pirfenidone and nintedanib. The median survival for IPF is 4.5 years ( Kaunisto et al., 2019 ).

Financial Update

On May 10, 2024, Edesa announced financial results for the second quarter of fiscal year 2024 that ended March 31, 2024. There were no revenues reported for the second quarter of fiscal year 2024. R&D expenses in the second quarter of fiscal year 2024 were $1.2 million, compared to $1.5 million for the second quarter of fiscal year 2023. The decrease was primarily due to decreases in external research expenses related to the EB01 trial and a reduction in noncash share-based compensation. G&A expenses totaled $1.0 million for the second quarter of fiscal year 2024 compared to $0.9 million for the second quarter of fiscal year 2023. The increase was primarily due to increased fees for professional services.

As of March 31, 2023, Edesa had approximately $2.8 million in cash and cash equivalents, which does not include the CAD$23 million in potential funding from the Canadian government, the $10 million revolving credit agreement, or the approximately $6.4 million of available capacity on the Canaccord ATM. As of February 9, 2024, Edesa had approximately 3.2 million shares outstanding and, when factoring in stock options and warrants, a fully diluted share count of approximately 4.2 million.

Edesa is currently evaluating the best way to advance its pipeline forward. The company will be filing an IND for EB06 in vitiligo, and will then determine the best path forward for that program through either financing a Phase 2 study itself or looking to partner the asset before initiating clinical trials. For both EB01 and EB07, Edesa will seek a partnership before advancing those programs in the clinic. Lastly, the company is continuing to evaluate how best to advance EB05 in a broader ARDS population.

Based on how the company is re-prioritizing the pipeline we have made a number of changes to our model. For EB05, we believe the ongoing Phase 3 trial can be completed in the next two years and that the compound will still qualify for approval under the EUA. We estimate for peak sales of $500 million seven years after approval. Using a 15% discount rate and a 70% probability of approval leads to an NPV of $62 million. For EB06, we estimate that following a successful Phase 2 readout in 3 years the asset would be valued similarly to auremolimab at $70 million. Using a 15% discount rate and a 65% probability of success leads to an NPV for EB06 of $30 million. For EB01, we calculate an NPV of $10 million based on potential peak sales of $80 million, a 15% discount rate, and a 70% probability of approval. Combining the NPVs for the company’s assets and the company’s cash position leads to a total NPV of $105 million. Dividing by the current number of outstanding shares plus an additional two million shares for the next financing leads to a valuation of $20 per share.

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Psychosocial Effects of Vitiligo: A Systematic Literature Review

Khaled ezzedine.

1 Department of Dermatology, Henri Mondor University Hospital and Université Paris-Est Créteil Val de Marne, 51 Avenue du Maréchal de Lattre de Tassigny, Créteil, 94010 Paris, France

Viktoria Eleftheriadou

2 Department of Dermatology, Queen Elizabeth Hospital, Birmingham, UK

Heather Jones

3 Incyte Corporation, Wilmington, DE USA

Kristen Bibeau

Fiona i. kuo, daniel sturm, amit g. pandya.

4 Palo Alto Foundation Medical Group, Mountain View, CA USA

5 University of Texas Southwestern Medical Center, Dallas, TX USA

Associated Data

Patients with vitiligo experience reduced quality of life.

To comprehensively describe the available evidence for psychosocial burden in vitiligo.

A systematic review of observational studies and clinical trials identified using PubMed, EMBASE, Scopus, and the Cochrane databases was performed through 1 March, 2021, to assess psychosocial comorbidities in vitiligo. Two independent reviewers performed an assessment of articles and extracted data for qualitative synthesis.

Included studies ( N = 168) were published between 1979 and 1 March, 2021; 72.6% were published since 2010. Disorders including or related to depression (41 studies, 0.1–62.3%) and anxiety (20 studies, 1.9–67.9%) were the most commonly reported. The most prevalent psychosocial comorbidities were feelings of stigmatization (eight studies, 17.3–100%), adjustment disorders (12 studies, 4–93.9%), sleep disturbance (seven studies, 4.6–89.0%), relationship difficulties including sexual dysfunction (ten studies, 2.0–81.8%), and avoidance or restriction behavior (12.5–76%). The prevalence of most psychosocial comorbidities was significantly higher vs healthy individuals. Factors associated with a significantly higher burden included female sex, visible or genital lesions, age < 30 years (particularly adolescents), and greater body surface area involvement, among others. The most commonly reported patient coping strategy was lesion concealment.

Limitations

Available studies were heterogeneous and often had limited details; additionally, publication bias is possible.

Conclusions

The results of this systematic review show that vitiligo greatly affects psychosocial well-being. The extent of psychosocial comorbidities supports the use of multidisciplinary treatment strategies and education to address the vitiligo-associated burden of disease.

Protocol Registration

PROSPERO (CRD42020162223).

Graphic Abstract

Supplementary Information

The online version contains supplementary material available at 10.1007/s40257-021-00631-6.

Introduction

Vitiligo is a chronic inflammatory autoimmune disease that results in skin depigmentation due to the loss of melanocytes [ 1 – 3 ]. Lesions can appear at any age, but onset usually occurs at ≤ 30 years of age [ 2 , 4 , 5 ]. Global prevalence is approximately 0.5–2.0% and varies geographically [ 6 ]. Similar prevalence rates have been reported for adult populations as well as children and adolescents [ 6 ].

Vitiligo is commonly misinterpreted as a cosmetic disease [ 2 ]. Patients with vitiligo experience a higher level of burden [ 7 , 8 ] compared with healthy controls [ 7 ], as reflected by quality-of-life (QoL) indicators. Quality-of-life impairment may be comparable to dermatologic (e.g., atopic dermatitis) [ 7 , 8 ] and non-dermatologic diseases (e.g., cancer) [ 9 ]. Importantly, the QoL burden of vitiligo may be largely affected by the presence of psychosocial comorbidities [ 10 – 12 ]. In recent years, a large focus has been placed on depression and/or anxiety in vitiligo [ 10 – 12 ]. The purpose of this systematic literature review was to comprehensively describe the evidence for psychosocial burden in patients with vitiligo, including the prevalence and types of psychosocial comorbidities, factors associated with psychosocial burden, patient coping strategies, perceptions toward vitiligo, and caregiver burden.

Literature Search

The search strategy was established and agreed upon by the authors during protocol development (Appendix 1 of the Electronic Supplementary Material [ESM]). PubMed, EMBASE, Scopus, and the Cochrane database were searched for articles from their earliest available entries through 1 March, 2021. The search string, which was limited to articles published in English, included the keywords vitiligo , quality of life , burden , psychosocial , and anxiety , as well as variants of depression , stigma , psychology , and psychiatry . Duplicate results from the separate databases were subsequently discarded.

Peer-reviewed primary publications, including clinical trials and observational studies (cross-sectional, case-control, prospective, and retrospective analyses), were included. Two independent reviewers (WvdS and KW) performed the title and abstract review; reviews and articles with irrelevant content were excluded. The same reviewers performed the full-text review and data extraction; reviewers independently assessed the risk of bias and resolved any disagreement through discussion. Studies excluded at the full-text review included data sets with fewer than five participants (e.g., patients with vitiligo or their caregivers), editorials, commentaries, articles with irrelevant content (including those that focused only on general QoL and/or that did not report instrument subscales that could be related to psychosocial comorbidity), and articles not available in English. Articles that included the same patient populations but reported different outcomes were retained.

Because data were collected from published articles, no institutional review board approval was required for the study. The study protocol was registered with PROSPERO (CRD42020162223).

Data Extraction and Analysis

Extracted data included study design, geographic region, sample size, detailed patient demographics, prevalence and types of psychosocial comorbidities, extent of psychosocial burden (vs healthy controls and/or patients with other skin diseases), factors associated with psychosocial burden, endpoints (scales) used to assess psychosocial burden, patient coping strategies, perceptions toward vitiligo (by patients and non-patients), and caregiver burden. A qualitative synthesis of evidence was performed to summarize the findings from included primary publications.

Initial database searches yielded 2288 articles, of which 1111 were duplicate records that were excluded from screening; one additional article was identified through other sources. Screening resulted in the exclusion of 919 articles during the title and abstract review; an additional 91 articles were excluded on the full-text review. A total of 168 articles were retained for data extraction and inclusion in the qualitative synthesis (Fig. ​ (Fig.1 1 ).

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram

Study Characteristics

Included studies were published between 1979 and 2021, with 72.6% published between 2010 and 2021 [ 4 , 5 , 9 , 13 – 177 ]. Most included studies were observational (96.4%), with only six clinical trials (3.6%) containing data specific to psychosocial comorbidity in vitiligo; child, adolescent, and adult populations were represented in the included studies (Table ​ (Table1). 1 ). Studies representing populations from most geographic regions were included (Fig. ​ (Fig.2); 2 ); regions with the most studies included the Middle East (29.8%), Europe (28.6%), and Southern Asia (15.5%). All studies included in the systematic review were qualitatively assessed to minimize the risk of bias; included studies were deemed to be of acceptable quality.

Summary of study characteristics

a Multinational studies conducted in 2 geographic regions are listed under both regions

b Includes East (Northeast) Asia and Southeast Asia

c Patient age groups were not reported for 9 (5.4%) studies

d The number of patients with vitiligo was not available for 8 studies, which reported on the perceptions of others toward patients with vitiligo ( n = 5) and caregiver burden ( n = 3)

Number of patients with vitiligo in included studies by country and number of studies. * Number of patients is the sum of patients across studies from each country with multiple populations from the same patient population excluded; the number of unique studies is shown in parentheses after the name of each country. † Includes three studies with populations in the USA and a European country (France, one study [ n = 442]; Germany, two studies [ n = 85 and n = 74]). Within each study, the number of patients in each country was not available in the published studies; thus, the full population is included in both countries on this map. ‡ Includes one study with a population in France and the USA ( n = 442). The number of patients in each country was not available in the published study; thus, the full population is included in both countries on this map. § Includes two studies with populations in Germany and the USA ( n = 85 and n = 74) and one study with a population in Germany and Jordan ( n = 167). Within each study, the number of patients in each country was not available in the published studies; thus, the full population is included in both countries on this map. || Includes one study with a population in Jordan and Germany ( n = 167). The number of patients in each country was not available in the published study; thus, the full population is included in both countries on this map

Instruments Measuring QoL

Among QoL instruments assessing general health, total and/or component scores were most frequently reported for the adult and child versions of the Dermatology Life Quality Index (DLQI, 53 studies) [ 4 , 13 , 14 , 18 , 19 , 22 , 25 , 33 , 35 – 38 , 45 , 64 , 65 , 67 – 70 , 74 , 77 , 81 – 83 , 87 , 89 , 90 , 92 , 93 , 96 , 99 , 100 , 102 , 104 , 112 , 115 , 119 , 120 , 122 , 123 , 140 , 143 , 144 , 146 , 148 , 151 , 156 , 161 , 162 , 164 – 166 , 168 ], Children’s DLQI (seven studies) [ 24 , 67 , 73 , 101 , 103 , 110 , 152 ], 36-Item Short Form Health Survey (SF-36, eight studies) [ 9 , 82 , 83 , 105 – 107 , 161 , 162 ], General Health Questionnaire (eight studies) [ 14 , 30 , 65 , 93 , 95 , 113 , 114 , 124 ], and Skindex-29 (eight studies) [ 29 , 71 , 98 , 106 , 107 , 162 , 174 , 175 ].

The DLQI is widely used across dermatologic diseases. Fifty studies that reported DLQI mean scores for patients with vitiligo were further examined. Mean scores did not differ vastly by region, but there were trends for higher mean scores (i.e., increased burden of disease) in the Middle East (4.7–14.7) [ 14 , 45 , 64 , 74 , 82 , 83 , 87 , 104 , 112 , 140 , 144 , 164 , 166 ], Southern Asia (4.1–12.4) [ 18 , 22 , 38 , 100 , 120 , 143 , 146 , 168 ], and Eastern Asia (4.0–8.4) [ 35 , 68 – 70 , 119 , 156 , 161 , 162 ] compared with Europe (1.8–8.7) [ 4 , 77 , 89 , 90 , 92 , 93 , 96 , 99 , 102 , 104 , 122 , 123 , 148 ] and North America (5.2–6.6) [ 115 , 151 , 165 ]. The lowest DLQI mean scores were reported in Italy (1.8 [ 89 ] and 4.3 [ 90 ]), Singapore (4.0 [ 69 ] and 4.4 [ 68 ]), and Nepal (4.1 [ 38 ]), whereas the highest DLQI mean scores were reported in Saudi Arabia (14.7 [ 45 ] and 9.0 [ 64 ]) and Egypt (13.0 [ 144 ], 12.4 [ 87 ], 12.2 [ 25 ], and 11.2–11.9 [ 19 ]). Factors affecting DLQI scores were not examined.

In contrast, the Vitiligo-specific QoL (VitiQoL) instrument has only been reported in eight studies [ 13 , 16 , 29 , 32 , 67 , 80 , 88 , 115 ] using our search parameters; half were published in the past year, of which two were clinical trials. There were no notable regional differences in VitiQoL scores among studies, which were conducted in each of the seven geographic regions, with two in North America. Another instrument specific to vitiligo, the Vitiligo Impact Scale (VIS), was only used in three studies, with two published in the past year. One study used the original 27-item VIS [ 32 ], and two used the abbreviated 22-item scale (VIS-22) [ 36 , 100 ]; all studies were conducted in Southern Asian populations. Although the use of vitiligo-specific scales has increased recently, there remains an unmet need for a widely utilized, vitiligo-specific QoL instrument that has been validated in large interventional studies.

Psychosocial Comorbidities

Prevalence of psychosocial comorbidities.

A summary of studies that reported psychosocial comorbidities is presented in Table ​ Table2 2 (complete information presented in Table 1 of the ESM). Nine studies noted the presence of any (unspecified) psychosocial comorbidity in 32.6–90.0% of patients with vitiligo [ 22 , 23 , 34 , 39 , 42 – 44 , 138 , 145 , 173 ]. Depression and anxiety were the most commonly reported psychosocial comorbidities. Forty-one studies reported depression or depressive disorders (including major depressive disorder, bipolar disorder, and dysthymic disorder) in patients with vitiligo, with a prevalence range from 0.1–62.3% [ 15 , 17 , 22 , 23 , 28 , 30 , 32 , 34 , 35 , 39 , 40 , 43 , 44 , 46 , 48 , 50 , 57 , 68 , 69 , 71 , 92 , 100 , 104 , 113 – 115 , 131 , 137 , 138 , 142 , 143 , 145 , 146 , 150 , 154 , 155 , 158 – 160 , 163 , 177 ]. Twenty studies reported anxiety or anxiety-related disorders (including generalized anxiety disorder, agoraphobia, social phobia [not social avoidance], and panic disorder), with a prevalence of 1.9–67.9% [ 22 , 23 , 30 , 34 , 39 , 43 , 44 , 46 , 50 , 57 , 92 , 115 , 137 , 138 , 150 , 154 , 155 , 158 , 159 , 175 ]. Among studies that used the same rating scales for determining the prevalence of depression or anxiety, ranges were more narrow (Table ​ (Table2). 2 ). Concomitant depression and anxiety was reported in four studies (4.9–33.3%) [ 34 , 43 , 44 , 159 ].

Prevalence of psychosocial comorbidity in patients with vitiligo

ACS Adjustment to Chronic Skin Disorders Questionnaire, ADHD attention-deficit/hyperactivity disorder, ASEX Arizona Sexual Experience Scale, BAI Beck Anxiety Inventory, BDI Beck Depression Inventory, BHS Beck Hopelessness Scale, CES-D Center for Epidemiologic Studies Depression Scale, DLQI Dermatology Life Quality Index, ES-Q Emotional State Questionnaire, GAD generalized anxiety disorder, GHQ General Health Questionnaire, GHQ-H Hindi version of the General Health Questionnaire, HADS Hospital Anxiety and Depression Scale, HDRS Hamilton Depression Rating Scale, IPQ Illness Perception Questionnaire, K-SADS-PL Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime Version, MDD major depressive disorder, PAS Psychiatric Assessment Schedule, PHQ-9 Patient Health Questionnaire-9, PRIME-MD PHQ Primary Care Evaluation of Mental Disorders–Patient Health Questionnaire, QIDS-SR-16 Quick Inventory of Depressive Symptomatology-Self Report, RSES Rosenberg Self-Esteem Scale, SCID-I Structured Clinical Interview for DSM-IV Axis I Disorders, SDS Sheehan Disability Scale, SRE Schedule of Recent Experience, TAS-20 Toronto Alexithymia Scale-20, VIS Vitiligo Impact Scale, VIS-22 Vitiligo Impact Scale 22, VitiQoL Vitiligo-specific Quality of Life

a Reporting based on diagnosis or self-report, an unspecified tool, or a tool used in only 1 study for each comorbidity; if a comorbidity only included data from 1 study, the specific tool (including diagnosis or self-report) was listed. For “diagnosis on file” and “diagnosed during screening,” formal diagnosis or diagnostic criteria/codes (i.e., Diagnostic and Statistical Manual of Mental Disorders IV/V or International Classification of Diseases 9/10) suggestive of a formal diagnosis were provided in the article. Tools used in only 1 study per comorbidity include ACS (stigmatization, social and situational avoidance/restriction), ASEX (sexual dysfunction), DLQI (sleep disturbances), ES-Q (depression, anxiety, panic disorder, social phobia, sleep disturbances), Freiburger Personality Inventory (social and situational avoidance/restriction, low self-esteem, emotional impairment, anger), GHQ-H (sleep disturbances, somatoform disorder), HDRS (depression, MDD, suicidal ideation), Holmes and Rahe Social Readjustment Rating Scale (sleep disturbances, social and situational avoidance/restriction, sexual dysfunction), IPQ (depression, emotional impairment), K-SADS-PL (GAD, depression and anxiety), Participation Scale (stigmatization), PAS (MDD, anxiety, social phobia, depression and anxiety, sexual dysfunction), PRIME-MD PHQ (depression, MDD, anxiety, panic disorder, somatoform disorder, alcohol dependence or abuse), QIDS-SR-16 (depression, suicidal ideation), SCID-I (MDD, anxiety, GAD, social phobia, alcohol dependence or abuse), SDS (social and situational avoidance/restriction), Skindex-29 (depression, social phobia, worry about spread, embarrassment, emotional impairment, anger), Skindex-61 (depression, embarrassment, emotional impairment, anger), SRE (sleep disturbances, sexual dysfunction), VIS (depression, worry about spread, social and situational avoidance/restriction, embarrassment, relationship difficulties, suicidal ideation), VIS-22 (worry about spread, social and situational avoidance/restriction), and VitiQoL (social and situational avoidance/restriction). Additional details are available in Table 1 of the ESM

Other psychosocial comorbidities were also widely reported and included feelings of stigmatization (eight studies, 17.3–100%) [ 32 , 101 , 102 , 131 – 133 , 136 , 169 ], sleep disturbance (seven studies, 4.6–89.0%) [ 92 , 109 , 117 , 143 , 150 , 154 , 167 ], alexithymia (four studies, 23.8–46.7%) [ 72 , 108 , 129 , 142 ], anger (six studies, 14–36.9%) [ 40 , 46 , 141 , 142 , 145 , 158 ], and somatoform disorder (three studies, 6.3–9.4%) [ 22 , 137 , 150 ]. Various impairments were noted, including emotional impairment (11 studies, 6–65.0%) [ 13 , 23 , 32 , 40 , 46 , 56 , 131 – 133 , 141 , 145 ]; cognitive impairment (three studies, 0.3–50.8%) [ 23 , 137 , 145 ]; and behavioral impairments that included avoidance or restriction behavior (nine studies, 12.5–76%) [ 32 , 57 , 61 , 100 , 102 , 109 , 130 , 141 , 146 ], attention-deficit/hyperactivity disorder (one study, 20.0%) [ 34 ], obsessive disorders (five studies, 0.1–19.5%) [ 23 , 39 , 137 , 138 , 154 ], and binge-eating disorder (one study, 7.4%) [ 22 ]. Alcohol dependence or abuse was reported in three studies (2.4–7.6%) [ 22 , 57 , 137 ]. Patients were affected by adjustment disorders, such as stress associated with vitiligo and worry about spread (12 studies, 4–93.9%) [ 13 , 30 , 32 , 40 , 100 , 109 , 113 , 114 , 131 , 141 , 142 , 149 ], and also experienced aspects of self-consciousness, including embarrassment (eight studies, 24–66.7%) [ 13 , 32 , 131 – 133 , 135 , 142 , 145 ] and low self-esteem (four studies, 6.2–72.7%) [ 32 , 68 , 69 , 141 ]. Relationship difficulties including sexual dysfunction were reported over a wide range of patients (ten studies, 2.0–81.8%) [ 32 , 43 , 97 , 109 , 131 , 132 , 135 , 154 , 155 , 167 ]. Suicidality was reported among patients with vitiligo, including unspecified suicidality (one study, 28.3%) [ 138 ], suicidal ideation (six studies, 3–25.0%) [ 32 , 100 , 131 , 143 , 150 , 154 ], and suicide attempts (two studies, 3.3–3.7%) [ 150 , 154 ].

Degree of Psychosocial Burden

Compared with controls, psychosocial comorbidities noted to be significantly ( p ≤ 0.05) associated with vitiligo were depression (11 studies) [ 23 , 28 , 33 , 34 , 55 , 63 , 128 , 140 , 143 , 145 , 155 ], anxiety (ten studies) [ 23 , 30 , 33 , 34 , 55 , 63 , 119 , 128 , 140 , 155 ], emotional or behavioral impairment (six studies) [ 9 , 23 , 34 , 128 , 140 , 161 ], adjustment disorder (four studies) [ 15 , 30 , 37 , 128 ], low self-esteem (three studies) [ 57 , 65 , 134 ], relationship and sexual dysfunction (three studies) [ 33 , 155 , 161 ], sleep disturbance (two studies) [ 55 , 117 ], suicidality (one study) [ 128 ], self-consciousness (one study) [ 119 ], embarrassment (one study) [ 145 ], alexithymia (one study) [ 108 ], and alcohol abuse or addiction (one study) [ 128 ]. Five studies reported that depression [ 30 , 84 , 85 , 102 , 164 ] and/or anxiety [ 84 , 164 ] scores measured by Beck Inventory scales were not significantly different in patients with vitiligo vs controls.

The QoL and/or psychosocial burden of vitiligo was most frequently compared with psoriasis (26 articles) [ 4 , 9 , 27 , 58 , 60 , 76 , 83 , 84 , 87 , 92 , 110 , 111 , 113 , 118 , 123 , 130 , 134 , 136 , 137 , 150 , 154 , 159 , 162 , 173 , 174 ], alopecia areata (13 articles) [ 14 , 24 , 58 , 60 , 75 , 76 , 83 , 109 , 118 , 154 , 159 , 173 , 174 ], acne (11 articles) [ 14 , 58 , 76 , 117 , 118 , 137 , 140 , 154 , 159 , 174 , 175 ], atopic dermatitis (ten articles) [ 27 , 58 , 73 , 76 , 110 , 111 , 119 , 154 , 173 , 174 ], and urticaria (nine articles) [ 27 , 58 , 76 , 137 , 154 , 155 , 173 – 175 ]. Table ​ Table3 3 lists the prevalence of psychosocial comorbidity in vitiligo compared with other skin diseases. In general, psychosocial comorbidities were more prevalent in vitiligo compared with acne, alopecia areata, atopic dermatitis, and urticaria but less prevalent vs psoriasis. Regarding non-dermatologic diseases, one study reported comparable SF-36 mental component scores in patients with vitiligo vs chronic lung disease, arthritis, cancer, and congestive heart failure [ 9 ].

Psychosocial comorbidity burden in patients with vitiligo compared with other skin diseases

Bolded cells indicate a higher prevalence in vitiligo; italics cells indicate a lower prevalence in vitiligo

a Stress includes stressful events that stem from family, personal, work, and financial problems

Factors Associated with Psychosocial Burden

Factors that were significantly associated with higher psychosocial (Fig. ​ (Fig.3) 3 ) or overall QoL burden were female sex (30 studies) [ 15 , 21 , 25 , 28 , 30 , 45 , 46 , 49 , 51 , 57 , 62 , 66 – 68 , 70 , 88 , 90 , 99 , 104 , 107 , 109 , 112 , 113 , 120 , 123 , 132 , 143 , 146 , 154 , 158 ], lesion location in visible areas (e.g., face, hands [17 studies]) [ 4 , 25 , 35 , 37 , 49 , 62 , 70 , 80 , 89 , 90 , 92 , 101 , 122 , 123 , 138 , 143 , 151 ] or genitals (eight studies) [ 70 , 89 , 97 , 105 , 115 , 122 , 144 , 151 ], younger age (16 studies; particularly those aged <30 years and more so in adolescents) [ 17 , 25 , 30 , 48 , 49 , 62 , 67 , 68 , 70 , 88 , 100 , 113 , 119 , 132 , 151 , 160 ], and extensive body area involvement (13 studies) [ 4 , 25 , 63 , 65 , 70 , 89 , 92 , 96 , 98 , 107 , 151 , 152 , 166 ]. Unmarried and/or single relationship status (nine studies) [ 17 , 22 , 48 , 49 , 62 , 70 , 93 , 113 , 138 ], longer disease duration (nine studies; particularly duration >5 years) [ 4 , 25 , 30 , 62 , 65 , 68 , 88 , 107 , 119 ], progressive disease (seven studies) [ 22 , 25 , 35 , 89 , 92 , 107 , 143 ], Fitzpatrick skin phototype IV–VI (five studies) [ 21 , 35 , 37 , 77 , 107 ], lower education status (five studies; particularly high school or lower level of education) [ 17 , 48 , 49 , 108 , 136 ], non-segmental vitiligo (three studies; vs segmental or focal vitiligo) [ 97 , 115 , 143 ], non-Caucasian race (three studies) [ 93 , 96 , 133 ], positive family history of vitiligo (two studies) [ 98 , 101 ], being employed (one study; compared with being students, unemployed, or retired) [ 35 ], and higher socioeconomic level (one study) [ 25 ] were also significantly associated with increased burden. Four studies reported that comorbid depression significantly reduced overall QoL [ 35 , 92 , 100 , 115 ]. Management strategies [ 107 ] including camouflage [ 18 , 25 , 102 , 122 , 156 ], cognitive behavioral therapy [ 26 , 125 , 127 , 148 , 168 ], phototherapy [ 51 , 52 , 157 ], and depigmentation cream (in patients with extensive vitiligo) [ 19 ] were associated with decreased vitiligo-associated burden.

Heat map showing the references that report factors significantly associated with psychosocial comorbidity. Significance was conferred at p ≤ 0.05. Darker red shading indicates a larger number of studies reporting significant associations

Coping Strategies Among Patients with Vitiligo

The most commonly discussed coping strategies in studies included the use of concealing clothing (six studies, 8.3–78.3% of patients) [ 25 , 74 , 101 , 102 , 131 , 157 ], camouflage (four studies, 14.6–62.0% of patients) [ 25 , 74 , 102 , 131 ], and altered body movements (three studies, 5.9–8.1% of patients) [ 74 , 101 , 102 ]. Other coping strategies included vitiligo acceptance [ 42 , 132 , 170 ], avoidance behavior [ 101 , 102 , 170 ], and psychotherapy or support groups [ 42 , 61 , 170 ].

Perceptions Toward Vitiligo

Perceptions toward vitiligo were discussed in 13 articles; seven articles focused on perceptions of patients toward their vitiligo [ 32 , 46 , 79 , 126 , 158 , 165 , 172 ], and six focused on perceptions of others toward patients with vitiligo [ 31 , 47 , 54 , 78 , 91 , 171 ]. Several articles covered aspects of knowledge or beliefs about vitiligo, including attitudes and behaviors. Common misperceptions included thinking that vitiligo is contagious [ 31 , 47 , 54 , 91 , 172 ] and that vitiligo is caused by external forces (e.g., “evil eye,” witchcraft/sorcery, evil spirits/Jinn, chance/fate) [ 31 , 32 , 46 , 47 , 79 , 158 ], lack of hygiene [ 47 , 91 ], or infection with germs or viruses [ 47 , 54 , 79 , 158 ]. In three studies that investigated attitudes toward patients with vitiligo, participants with sufficient knowledge of vitiligo vs insufficient knowledge reported a lower prevalence of negative attitudes and a higher prevalence of positive attitudes [ 31 , 78 , 91 ]. In four studies that reported a willingness to have a relationship with or marry someone with vitiligo, 6.7–43.9% of participants responded in the affirmative [ 31 , 47 , 54 , 78 ]; reasons for refusing marriage included social reasons, the impact of vitiligo on appearance, and that vitiligo is believed to be inherited or contagious [ 31 , 47 ].

Caregiver Burden

Caregiver (e.g., parents, sibling, spouse) burden and associated factors were discussed in ten articles [ 20 , 24 , 53 , 64 , 86 , 103 , 111 , 121 , 139 , 172 ], although only four provided prevalence rates [ 64 , 86 , 103 , 111 ] for aspects of psychosocial burden. Overall QoL among caregivers was impaired, with depression, anxiety, emotional distress, and impaired social life commonly mentioned. There were no notable consistencies across studies regarding factors affecting caregiver burden. Two studies reported significant parental depression vs controls [ 24 , 121 ], and one study showed that caregiver depression and anxiety significantly reduced QoL among patients with vitiligo [ 111 ].

In the past decade, interest in and publication of the overall and psychosocial QoL of patients with vitiligo have increased tremendously, highlighting the QoL burden in vitiligo. Several recent studies have reported meta-analyses of depression and/or anxiety in patients with vitiligo [ 10 – 12 ], with less focus on other psychosocial comorbidities experienced by patients with vitiligo. We sought to comprehensively review the prevalence of any psychosocial comorbidity reported by patients in peer-reviewed scientific articles.

Studies in this systematic review reported wide ranges (likely owing to differing assessment tools and geographically heterogeneous populations) for the majority of psychosocial comorbidities. Psychosocial comorbidities reported in >50% of patients in any study were depression, major depressive disorder, anxiety, social phobia, feelings of stigmatization, adjustment disorders, sleep disturbances, avoidance and restriction behavior, self-consciousness, emotional impairment, relationship difficulties, and cognitive impairment. Psychosocial comorbidities reported in >25% of patients included coexistent depression and anxiety, sexual dysfunction, alexithymia, anger, suicidality (unspecified suicidality and suicidal ideation), and dysthymic disorders. The breadth and severity of these comorbidities and the resulting effect on QoL in patients with vitiligo extend beyond what has previously been dismissed as a cosmetic disease.

Factors that were most commonly associated with significantly higher psychosocial burden included female sex, visible or genital lesions, age < 30 years (particularly adolescents), and extensive body area involvement, among others. The implementation of facial vitiligo as a primary outcome measure in recent clinical studies [ 178 – 181 ] is supported by the gravity of the association between facial lesions and a higher psychosocial burden reported here. Some of the factors significantly associated with a higher psychosocial burden have been associated with a greater willingness to pay, although the association between willingness to pay and lesion location was not assessed [ 4 ].

In many cases, studies reported findings using broad QoL instruments that are not specific to vitiligo. Generic QoL instruments may not reflect the true burden of vitiligo, in part because of instrument design. For example, the DLQI includes an item for physical symptoms (i.e., itch, soreness, pain, or stinging) [ 182 ], which tend to be more pronounced in patients with atopic dermatitis or psoriasis, possibly leading to an underestimation of burden in vitiligo vs other dermatologic diseases [ 183 , 184 ]. In addition, the heterogeneity of studies included in this review may further complicate direct comparisons of general QoL in vitiligo with other dermatologic diseases. Interestingly, a recent study in South Korea showed that willingness to pay was highest in vitiligo compared with other dermatologic diseases including atopic dermatitis and psoriasis, despite lower median DLQI scores in patients with vitiligo [ 27 ]. The application of widely used generic QoL instruments in vitiligo may therefore be better suited for comparison across demographic or clinical characteristics. In our analysis, there were regional trends in DLQI scores, with a lower QoL burden among European and North American populations and a higher QoL burden noted among Middle Eastern and Asian populations, consistent with findings from another review [ 185 ]. Future studies should assess QoL instruments for cultural sensitivity/influence. Psychosocial morbidity should also be examined to further elucidate the effect of culture on vitiligo burden, which is an important consideration for dermatologists caring for diverse patients. During the past decade, the VitiQoL was developed specifically for measuring QoL in patients with vitiligo [ 184 ], although it does not differentiate between skin types (i.e., fair and dark skin), and its use has not been widespread. Our search criteria identified only eight studies that reported aspects of psychosocial comorbidity using the VitiQoL instrument [ 13 , 16 , 29 , 32 , 67 , 80 , 88 , 115 ], two of which were clinical trials published in the past year [ 16 , 29 ]. Further research using vitiligo-specific QoL instruments is warranted.

It is well recognized that more effective treatment strategies are needed for vitiligo. The results of this systematic review raise the urgency for strategies (including better treatments, counseling, and cognitive behavioral therapy) to improve the overall QoL and psychosocial health of patients. Although not directly assessed in this systematic review, the significant association of longer disease duration with poorer psychosocial and general QoL supports the possibility that delayed interventions could exacerbate disease burden. Furthermore, this review highlights the unmet need for a widely used vitiligo-specific instrument to assess psychosocial burden and reinforce that vitiligo is not a purely cosmetic disease. A cross-culturally validated, vitiligo-specific instrument, the 12-item short-form of the Vitiligo Impact Patients scale (VIPs-12), was recently developed to address QoL burden, including psychological effects on daily life and items specifically related to skin type; however, the instrument still awaits testing in prospective studies for responsiveness [ 186 ]. In addition to psychotherapy and/or counseling for patients, general education about vitiligo in the unaffected population may help lessen the stigma associated with vitiligo and assist in improving the psychosocial well-being of patients and their caregivers. In surveys among people without vitiligo, participants with sufficient knowledge of the disease were more likely to display positive attitudes toward patients with vitiligo compared with people who had insufficient disease knowledge [ 31 , 78 , 91 ]. The most commonly reported coping strategy among patients in our analysis was concealment of lesions through clothing choices, camouflage, and altered body movements. It may follow that if patients were made to feel more comfortable in their own skin and around others, and if nonpatients were educated to be more accepting, the psychosocial burden among patients with vitiligo and their caregivers could be lessened.

Limitations to this study include the heterogeneity of studies (together with differences in methods used to quantify the presence of psychosocial comorbidities), the paucity of details available in some publications, and restriction to English language in the search criteria. Additionally, inclusion of only peer-reviewed publications may be associated with publication bias [ 187 ].

Vitiligo has a significant and broad effect on psychosocial well-being, an aspect of QoL that may not be accurately or fully captured by currently available QoL instruments. The extent of the psychosocial comorbidities summarized in this systematic review indicates that multidisciplinary approaches to treatment strategies (including medical and psychological treatment) and education about vitiligo are needed to address the burden of this disease.

Below is the link to the electronic supplementary material.

Acknowledgements

Writing assistance was provided by Wendy van der Spuy, PhD, and Ken Wannemacher, PhD, of ICON (North Wales, PA, USA) and was funded by Incyte Corporation (Wilmington, DE, USA).

Declarations

The study was funded by Incyte Corporation, Wilmington, DE, USA.

KE is a consultant for AbbVie, Incyte Corporation, La Roche-Posay, Pfizer, Pierre Fabre, Sanofi, and Viela Bio. VE has nothing to disclose. HJ and FIK were employees and shareholders of Incyte Corporation when the study was conducted. KB and DS are employees and shareholders of Incyte Corporation. AGP has served as an investigator for Aclaris Therapeutics, Immune Tolerance Network, Incyte Corporation, and Pfizer; a consultant for Arcutis, Avita, Chromaderm, Immune Tolerance Network, Incyte Corporation, Pfizer, Viela Bio, and Villaris; and a board member who also holds stock options for Clarify Medical and Tara Medical.

Because data were collected from published articles, no ethical approval was required for the study.

Not applicable.

All data were collected from published articles available in the public domain.

KE, VE, HJ, KB, FIK, DS, and AGP contributed to the study design, including formulation of the search strategy, had access to extracted data, and contributed to data interpretation. KE, VE, HJ, KB, FIK, DS, and AGP were involved in drafting the manuscript. KE, VE, HJ, KB, FIK, DS, and AGP approved the final version for submission and agree to be accountable for all aspects of the work.

Data in this article were previously presented, in part, at the European Academy of Dermatology and Venereology 2020 Virtual Congress (29–31 October, 2020) and the Vitiligo International Symposium 2020 Virtual Conference (5–6 December, 2020).

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

The HPV vaccine prevents head and neck cancers in men, study suggests

The HPV vaccine is linked to a drastic reduction in head and neck cancers in adolescent boys and men, new research finds. 

HPV, or human papillomavirus, is a sexually transmitted infection responsible for virtually all cases of cervical cancer . But the virus is also linked to a number of other cancers , including penile, anal and vaginal cancers. 

It also accounts for the majority — up to 70% — of head and neck cancers , which affect the throat and mouth. Men are about twice as likely to develop these cancers than women, according to the National Cancer Institute.

The HPV vaccine, initially approved for adolescent girls, protects against strains of the virus linked to cervical cancer and has been found to significantly reduce rates of the cancer . But there’s growing evidence that the vaccine also protects against other HPV-related cancers.

“We want males to be thinking about HPV vaccination not just as something that protects female patients, but also male patients,” said Jefferson DeKloe, a research fellow in the department of otolaryngology at Thomas Jefferson University, who specializes in head and neck surgery and who co-authored the research.

The findings will be presented next week at the American Society of Clinical Oncology conference and have not yet been published in a peer-reviewed journal. 

Prior research showed a downward trend in oral infections with HPV strains known to cause cancer. That was a promising sign, said Dr. Glenn J. Hanna, a medical oncologist at the Dana-Farber Cancer Institute’s Center for Head and Neck Oncology, who was not involved in the new research.

“If we can lower the infection rate, we would hope that we would see what we are seeing now, a decline in cancer rates,” Hanna said. “This is an important evolution of the story.” 

The new study analyzed health records from a national database that included nearly 3.5 million people in the United States ages 9 to 39 who had received any vaccination — HPV or otherwise — from 2010 through 2023. About 1.5 million were male, half of whom had been vaccinated against cancer-causing strains of HPV. Nearly 1 million were females who had been vaccinated against HPV. 

The researchers compared the rates of HPV-linked cancers — including head and neck, anal, penile, and cervical cancers — in people who had received the HPV vaccine to those who hadn’t. They found being vaccinated reduced the overall risk of HPV-related cancers in males by 54%, a decrease driven primarily by a drop in head and neck cancers. Females were about 30% less likely to develop any type of HPV-related cancer, including cervical cancer. 

Most cases of head and neck cancer are in people older than 50. Since the U.S. is only about a decade into widespread HPV vaccination in both males and females, the vaccinated generation hasn’t reached this age yet. HPV typically infects younger people and takes decades for chronic infection to lead to cancer.

“These are the early results of a larger phenomenon we are going to watch play out over the next 20 or 30 years,” DeKloe said, noting that experts don’t expect to see the full effect HPV vaccination has on cancer rates until the largely vaccinated generation is older. 

A second study, which will also be presented at the ASCO conference next week and is not yet published in a peer-reviewed journal, found that HPV vaccination rates have been on the rise in the U.S. from 2011 through early 2020, including in all racial and ethnic groups.

HPV vaccination wasn’t recommended for males until 2011, five years after the Centers for Disease Control and Prevention recommended the vaccine series for girls. The HPV vaccine is now recommended for all adolescents starting as young as age 9, but can also be given to adults up to age 45. 

In the new study, which included children and young adults ages 9 to 26, the increase was largely driven by growing HPV vaccine uptake among males. Although overall HPV vaccination rates among males still lag behind females — about 36% compared to about 50% of those in the 9 to 26 age group — these rates are accelerating. 

“The gap is narrowing between males and females and eventually I would hope that they would meet up,” said Dr. Danh Nguyen, a resident physician at University of Texas Southwestern Medical Center, who led the research. 

Although vaccination efforts have focused on adolescents, adults should also consider getting vaccinated if they weren’t when they were younger, said Dr. Nancy Lee, service chief of head and neck radiation oncology at Memorial Sloan Kettering Cancer Center in New York City, who was not involved with either study. 

“If you are in your 20s or 30s, you can still get the vaccination. Even if you are 45, there is no reason you cannot get vaccinated because we have a population that lives a long time,” Lee said. 

Nguyen said it’s important that conversations about HPV vaccination continue to focus on the prevention of all cancers, including head and neck cancers that are more prevalent in men, rather than solely on cervical cancer prevention.

Hanna said stigma around HPV being a sexually transmitted infection has made discussions around vaccinating adolescents a sticky subject in the past, but that clear data showing the impact vaccination rates have on HPV-related cancers is shifting the narrative. 

“HPV vaccination is cancer prevention,” Hanna said. “The bottom line is that we are preventing cancers broadly by getting people vaccinated younger.”

Kaitlin Sullivan is a contributor for NBCNews.com who has worked with NBC News Investigations. She reports on health, science and the environment and is a graduate of the Craig Newmark Graduate School of Journalism at City University of New York.

Homoeopathy

How to recover fast from vitiligo, table of contents, homeopathic treatments.

Skin Disorders

Respiratory issues

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Infertility

Other Health Issues

• Dharma Homoeo Staff
• May 29, 2024

Introduction

What are the causes of vitiligo.

• Autoimmune Response: Many believe vitiligo is caused by the body mistakenly attacking its cells that make skin color, known as melanocytes. This attack leads to the white spots, characteristic of vitiligo.
• Genetic Factors: If you have family members with vitiligo or other autoimmune diseases, you might be more likely to develop vitiligo. Research shows a strong link to genetics.
• Oxidative Stress: This is when there’s an imbalance between antioxidants and harmful molecules in your body, damaging the melanocytes and contributing to vitiligo.
• Neurochemical Factors: Some scientists think that chemicals from nerve endings near the skin surface might harm melanocytes, causing vitiligo patches to form.
• Environmental Triggers: Things like sunburn, exposure to certain chemicals, and injuries to the skin might trigger vitiligo in some people.
• Hormonal Changes: Vitiligo can sometimes start after changes in the body’s hormones, such as during puberty, pregnancy, or with thyroid problems.
• Emotional Stress: Although not directly causing vitiligo, stress might worsen it in some individuals, possibly by affecting the immune system.

How Homeopathy’s Unique Approach Helps to Recover From Vitiligo?

• Special Care Just for You: Because everyone’s vitiligo is different, homeopathy makes a care plan just for you. It looks at the spots on your skin, your health history, how you feel inside, and how you live day-to-day.
• Whole Check-Up: To pick the right treatment, homeopathic doctors first have a big talk with the patient. They look at the physical symptoms of vitiligo and also think about how the patient feels inside, like if they are sad or worried.
• Helping the Body Fix Itself: The treatments help fight the root causes of vitiligo, like problems with the body’s defense system, feeling too much stress, or when hormones are out of balance. They help the body start to heal itself naturally.
• Tiny doses for safety: Homeopathic treatments are very watered down. This means they are very safe and you can use them for a long time without bad effects.
• Helpful changes in how you live and eat: Homeopathic doctors often tell you to eat better and change some of your daily habits to help your body heal. This could mean eating foods full of vitamins and minerals good for your skin and finding ways to feel less stressed.
• Emphasis on Mental and Emotional Health: Homeopathy acknowledges the psychological effects of vitiligo and strives to enhance the patient’s mental and emotional state of being, which is thought to be essential for comprehensive recovery.
• Preventive Approach: Homeopathy aims to stop the formation of new patches by treating the underlying causes and preserving the immune system’s equilibrium in addition to treating current patches.

How Dharma Homoeopathy Helps You to Recover From Vitiligo?

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NASA, IBM Research to Release New AI Model for Weather, Climate

By Jessica Barnett

Working together, NASA and IBM Research have developed a new artificial intelligence model to support a variety of weather and climate applications. The new model – known as the Prithvi-weather-climate foundational model – uses artificial intelligence (AI) in ways that could vastly improve the resolution we’ll be able to get, opening the door to better regional and local weather and climate models.  

Foundational models are large-scale, base models which are trained on large, unlabeled datasets and can be fine-tuned for a variety of applications. The Prithvi-weather-climate model is trained on a broad set of data – in this case NASA data from NASA’s Modern-Era Retrospective analysis for Research and Applications (MERRA-2)– and then makes use of AI learning abilities to apply patterns gleaned from the initial data across a broad range of additional scenarios.  

“Advancing NASA’s Earth science for the benefit of humanity means delivering actionable science in ways that are useful to people, organizations, and communities. The rapid changes we’re witnessing on our home planet demand this strategy to meet the urgency of the moment,” said Karen St. Germain, director of the Earth Science Division of NASA’s Science Mission Directorate. “The NASA foundation model will help us produce a tool that people can use: weather, seasonal and climate projections to help inform decisions on how to prepare, respond and mitigate.”  

With the Prithvi-weather-climate model, researchers will be able to support many different climate applications that can be used throughout the science community. These applications include detecting and predicting severe weather patterns or natural disasters, creating targeted forecasts based on localized observations, improving spatial resolution on global climate simulations down to regional levels, and improving the representation of how physical processes are included in weather and climate models.

“These transformative AI models are reshaping data accessibility by significantly lowering the barrier of entry to using NASA’s scientific data,” said Kevin Murphy, NASA’s chief science data officer, Science Mission Directorate at NASA Headquarters. “Our open approach to sharing these models invites the global community to explore and harness the capabilities we’ve cultivated, ensuring that NASA’s investment enriches and benefits all.” 

Prithvi-weather-climate was developed through an open collaboration with IBM Research, Oak Ridge National Laboratory, and NASA, including the agency’s Interagency Implementation and Advanced Concepts Team (IMPACT) at Marshall Space Flight Center in Huntsville, Alabama. 

Prithvi-weather-climate can capture the complex dynamics of atmospheric physics even when there is missing information thanks to the flexibility of the model’s architecture. This foundational model for weather and climate can scale to both global and regional areas without compromising resolution. 

“This model is part of our overall strategy to develop a family of AI foundation models to support NASA’s science mission goals,” said Rahul Ramachandran, who leads IMPACT at Marshall. “These models will augment our capabilities to draw insights from our vast archives of Earth observations.”  

Prithvi-weather-climate is part of a larger model family– the Prithvi family– which includes models trained on NASA’s Harmonized LandSat and Sentinel-2 data. The latest model serves as an open collaboration in line with NASA’s open science principles to make all data accessible and usable by communities everywhere. It will be released later this year on Hugging Face, a machine learning and data science platform that helps users build, deploy, and train machine learning models. 

“The development of the NASA foundation model for weather and climate is an important step towards the democratization of NASA’s science and observation mission,” said Tsendgar Lee, program manager for NASA’s Research and Analysis Weather Focus Area, High-End Computing Program, and Data for Operation and Assessment. “We will continue developing new technology for climate scenario analysis and decision making.” 

Along with IMPACT and IBM Research, development of Prithvi-weather-climate featured significant contributions from NASA’s Office of the Chief Science Data Officer, NASA’s Global Modeling and Assimilation Office at Goddard Space Flight Center, Oak Ridge National Laboratory, the University of Alabama in Huntsville, Colorado State University, and Stanford University. 

Learn more about Earth data and previous Prithvi models:  https://www.earthdata.nasa.gov/news/impact-ibm-hls-foundation-model

Jonathan Deal   Marshall Space Flight Center, Huntsville, Ala.    256.544.0034    [email protected]   

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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.

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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]

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