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In Vitiligo research, vitiligo treatment

Vitiligo Treatment and Management

Vitiligo is a complex autoimmune disease that requires understanding and communication between clinician and patient. Nada Elbuluk, MD, dermatologist and clinical associate professor at the Keck School of Medicine of the University of Southern California, in Los Angeles, and David Rosmarin, MD, dermatologist and department chair at the Indiana University School of Medicine in Indianapolis, offered an overview of the condition, its prevalence, potential triggers, and treatment options in Updates in Vitiligo Management, a Dermatology Times® DermView series.

Elbuluk began by describing how she explains the disorder to patients. She tells them that because vitiligo is an autoimmune disease, their antibodies are attacking their melanocytes and when this happens, white patches appear on the skin. Elbuluk stresses that she tells patients that they did not cause their condition but rather are genetically predisposed to developing it.

“Some patients are worried they did something to cause the vitiligo,” Rosmarin said. “Maybe there were some instigating events, but we don’t want patients to blame themselves. Often, it’s idiopathic, and we don’t know why people get it. Maybe there’s a genetic predisposition, some environmental event that triggers it.”

Elbuluk and Rosmarin also discussed the common myth that vitiligo is a skin of color disease.

“It’s not,” Elbuluk noted. “It’s more visible in darker skin, so there’s a much greater contrast between vitiliginous patches in someone who has dark skin. People notice it more in darker skin. In my practice, I have patients of many different racial and ethnic backgrounds who have vitiligo.”

Elbuluk also tells patients with vitiligo that there is a 20% to 30% chance that they will develop some form of thyroid disease, and she checks thyroid-stimulating hormones (TSH) and vitamin D levels at the introductory visit. Rosmarin also screens for TSH at the first visit because 25% of patients with vitiligo go on to have an autoimmune thyroid disease.

Another topic they discuss with patients is genetic risk. According to Rosmarin, many of his patients who are in their 20s or 30s and thinking about having children tend to ask whether they will pass on vitiligo to their children and whether their parents passed it on to them.

“About 1% of the population, 0.5% to 2% in some estimates, will have vitiligo,” Rosmarin explained. “If you have a first-degree relative, then your risk is increased about 4%. It’s about sixfold higher. It’s complex, and there’s a genetic component, a predisposition.”

Wood’s lamp is a common tool used to identify vitiligo in patients with lighter Fitzpatrick skin types. According to Rosmarin, a Wood’s lamp is essential for seeing the true extent of vitiligo in fair-skinned patients. For many, the severity of disease and the extent of body surface it affects can cause emotional distress. To combat the fear of vitiligo, Rosmarin classifies patients as having either progressive or stable disease. If it is progressing, he tries to halt the process with 2-5 mg of dexamethasone, 2 days a week, for about 12 weeks.

Elbuluk always asks patients about their goals for vitiligo treatment. Many of her patients have been told that there is no way to treat vitiligo or they have been on previous treatments that failed. She tries to make each visit as educational as possible for patients.

“You hit the nail on the head,” said Rosmarin. “A lot of education takes place during these visits. I want to build on what you commented on, for quality of life. Our measures show that, when patients have [vitiligo] in exposed areas, that tends to affect their quality of life. Even more so…[with] progressive or unstable disease. They have anxiety…[about] not knowing when they’ll get a new spot. The unpredictability…[of] nonsegmental vitiligo can be quite bothersome to patients, more than even having the disease in the first place.”

In progressive vitiligo, Elbuluk and Rosmarin consider the percentage of body surface affected and the category of treatment that will work best. Combination therapy is typically more successful, especially in patients who have tried only 1 form of treatment for a brief period of time. Elbuluk also makes sure patients understand that success will not happen overnight. Phototherapy, for instance, can take at least 30 sessions or more to begin eliciting a response. Overall, Elbuluk tells her patients that with vitiligo there are 2 treatment goals: stabilization and repigmentation.

Ruxolitinib cream (Opzelura; Incyte Dermatology) is a favorite therapeutic option of both doctors. Elbuluk has transitioned many patients who failed traditional treatment to ruxolitnib cream and has seen success, and she has also seen early improvement with combination ruxolitnib and phototherapy.

“Usually, when I have a patient come in and I tell them what they should expect with the use of the [ruxolitnib] cream, I tell them it is better to use it twice a day, even though we…[know] that even once a day can help repigment patients,” Rosmarin said. “Twice a day certainly works better. I usually see patients back in 6 months, and I don’t do any lab work beforehand or as we’re using the ruxolitnib cream because from the phase 3 data, there weren’t significant changes in lab abnormalities.”

Elbuluk and Rosmarin ended their discussion by reminding colleagues to give patients hope, let them know that there are treatment options, and referring them to a vitiligo specialist if they don’t feel qualified to treat the condition. Rosmarin added that it’s crucial to educate all physicians about the different strategies available to personalize treatment.

Reference

  1. Elbuluk N, Rosmarin D. Updates in vitiligo management. DermView. November 22, 2022. Accessed November 30, 2022. https://www.dermatologytimes.com/dermview/updates-in-vitiligo-management

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VIPOC
In Vitiligo history, Vitiligo research

The History of Vitiligo Treatments

Vitiligo is a chronic skin disease that affects millions of people worldwide. It is characterized by the loss of pigment in the skin, resulting in white patches that can appear anywhere on the body. While the cause of vitiligo is not fully understood, it is believed to be an autoimmune disorder in which the body’s immune system attacks and destroys the melanocytes, the cells that produce skin pigment. Vitiligo affects about 1% of the world’s population, and there is currently no cure for the disease. However, there are several treatments available that can help control the spread of vitiligo and improve the appearance of the skin. Vitiligo can cause significant psychological distress and social stigma, especially in people with darker skin tones as it is more visible.

Historical Perspectives on Vitiligo Treatments:

Ancient texts from Egypt, India, and China describe various treatments for vitiligo, including the use of herbal remedies, sunlight exposure, and topical preparations made from animal products.

The earliest recorded treatments for vitiligo date back to ancient times. In ancient Egypt, for example, people with vitiligo were treated with a mixture of tar, honey, and oil. In India, vitiligo was treated with a combination of herbs, including psoralea corylifolia, which was believed to stimulate melanin production in the skin. In Ancient Greece, the physician Hippocrates recommended a mixture of ashes, wine, and honey to treat vitiligo.

However, it was not until the 20th century that more effective treatments for vitiligo were developed. In the early 1900s, doctors began experimenting with various topical treatments, such as corticosteroids and topical immunomodulators. In the 1950s, PUVA therapy was developed, which involves exposing the skin to a combination of psoralen and UVA light. This treatment can stimulate melanin production in the skin and is still used today. Other treatments for vitiligo included topical corticosteroids, topical calcineurin inhibitors, and phototherapy.

In the 1980s, a surgical procedure known as skin grafting was developed, which involves taking healthy skin cells from one part of the body and transplanting them to the affected area. This procedure can be effective but is expensive and can be associated with significant scarring.

In recent years, several new treatments for vitiligo have emerged, including targeted phototherapy, excimer laser therapy, and surgical treatments such as skin grafting and melanocyte transplantation. In 2019, the FDA approved a new treatment for vitiligo called Opzelura (ruxolitinib cream), which is a topical cream that works by inhibiting the Janus kinase (JAK) signalling pathway, a key pathway involved in the development of vitiligo. Opzelura was approved based on the results of two phase 3 clinical trials involving more than 500 patients with vitiligo. Read more about that here.

Opzelura is the first FDA-approved treatment specifically for non-segmental vitiligo, and it is also approved for use in the European Union. In clinical trials, Opzelura was shown to be effective in reducing the size and severity of vitiligo lesions, and it was well-tolerated by patients. However, like all medications, Opzelura may cause side effects, including skin irritation, itching, and redness.

While Opzelura represents a significant advance in the treatment of non-segmental vitiligo, it is not a cure for the disease. Vitiligo is a complex disease, and it is likely that a combination of treatments will be needed to effectively manage the spread of the disease. However, the approval of Opzelura is a promising development for people with vitiligo, and it is likely to be an important treatment option for many years to come.

 

Diverse Perspectives on Vitiligo Treatments:

Many people with vitiligo have tried multiple treatments with varying degrees of success. Some people report significant improvement with topical treatments, while others find them ineffective. PUVA therapy can be effective in some people, but it can also cause side effects, such as skin irritation and increased risk of skin cancer.

Many people with vitiligo also turn to alternative treatments, such as herbal remedies and dietary supplements. While some of these treatments may have anecdotal evidence of effectiveness, there is a lack of scientific evidence to support their use.

Vitiligo is a complex disease that can be challenging to manage. While there have been significant advances in the treatment of vitiligo over the years, there is still no cure for the disease. It is essential to consider diverse perspectives when evaluating the effectiveness of different treatments. What works for one person may not work for another, and it is important to work with a healthcare professional to find the most effective treatment for your individual needs.

VIPOC
In Vitiligo, Vitiligo research, Vitiligo Scientific Study, vitiligo treatment

Factors affecting quality of life in patients with vitiligo Part 2

Patients and methods

Participants and settings

A nationwide questionnaire-based study was conducted in 21 hospitals and clinics in Korea from July 2015 to June 2016. All patients aged ≥ 20 years diagnosed with vitiligo by dermatologists, and who provided written informed consent prior to the survey were enrolled. We restricted the participants to adult patients, because different questionnaires should be applied to children and adults. We explored demographic characteristics and vitiligo phenotypes and determined Skindex-29 scores. All patients first completed the questionnaires in paper-and-pencil format, and dermatologists then confirmed the clinical profiles after interviewing and examining the patients. The study protocol was designed in accordance with the Declaration of Helsinki and was approved by the institutional review board of each hospital.

Demographic characteristics

Demographic characteristics recorded included age, sex, marital status (single or married) and educational background (elementary school graduate, middle school graduate, high school graduate or college graduate).

Vitiligo phenotypes

The vitiligo phenotypes included subtype (segmental or nonsegmental), disease duration (< 1, 1–4, 5–9 or ≥ 10 years), affected body surface area (BSA; < 05, 05–09, 1–4, 5–9, 10–19 or ≥ 20%), involvement of visible body parts (yes or no) and the particular body parts involved (face and neck, scalp, upper extremities, lower extremities, trunk and genital area).

The Skindex-29 questionnaire

QoL was assessed using the Korean version of Skindex-29. This instrument is employed extensively to measure the effects of skin disease on a patient’s life;8,9 the Korean version was cross-culturally adapted by Ahn et al.10 The semantic equivalence of all back-translated items has been confirmed,10 and the Korean version has been validated by several previous studies.11–13 The questionnaire contains 29 items exploring the influence of skin disease on daily life using a five-point scale: 0 (never), 1 (rarely), 2 (sometimes), 3 (often) and 4 (all the time). The responses were transformed into linear scores varying from 0 (no effect) to 100 (effect always experienced). Each item belongs to one of three domains (symptoms, functioning and emotions); the scores of the three domains were calculated as the mean score of the items included in each domain.

The major items affecting patients with vitiligo

The proportions of patients affected by each item (sometimes, often and all the time) were calculated. The items of most concern were identified based on the answers.

Quality-of-life impairment

The outcomes of the study were mild or severe impairment of QoL, as determined by each domain (symptoms, functioning and emotions) of Skindex-29. Mild and severe QoL impairments were defined using the cut-off scores suggested by Prinsen et al.:14,15 ≥ 39 (mild) and ≥ 52 (severe) for symptoms, ≥ 21 (mild) and ≥ 37 (severe) for functioning, and ≥ 24 (mild) and ≥ 39 (severe) for emotions.

Statistical analyses

Absolute and percentage frequencies were determined for categorical variables, and position (mean and median) and scattering (SD, range) were described for continuous variables. Univariate and multivariate logistic regression analyses were sequentially performed to identify the factors independently associated with QoL impairment in each domain of Skindex29. All analyses were performed using R 3.3.1 (R Foundation for Statistical Computing, Vienna, Austria).

Results

In total, 1123 patients with vitiligo were recruited from 21 hospitals and clinics. Of the participants, 609 (542%) were male and 514 female (458%), with a mean age of 498  152 years (range 20–84). The median duration of disease was 30 years (range 0–60). The detailed clinical characteristics of the enrolled patients are summarized in Table 1.

The results of Skindex-29

The Skindex-29 items of most concern to patients with vitiligo were as follows: no. 13: I worry that my skin condition may get worse (746% of patients); no. 3: I worry that my skin condition may be serious (629%); no. 22: My skin condition is a problem for the people I love (556%); and no. 6: My skin condition makes me feel depressed (535%) (Table 2).

Impaired quality of life and associated factors in terms of the symptoms domain

Of the patients with vitiligo, 146% (164 of 1123) had mild and 52% (58 of 1123) had severe QoL impairment in terms of the symptoms domain (Fig. 1). On multivariate logistic

Table 1 The clinical characteristics of the 1123 patients with vitiligo included in the present study

 

 

 

 

 

 

regression modelling, the involvement of visible body parts (OR 153) and a larger affected BSA (compared with < 05%; 5–9%: OR 278, 10–19%: OR 284 and ≥ 20%: OR 469) were associated with mild symptom impairment (Table 3). A larger affected BSA was also associated with severe symptom impairment (compared with < 05%; ≥ 20%: OR 810).

Impaired quality of life and associated factors in terms of the functioning domain

Of the patients with vitiligo, 488% (548 of 1123) had mild and 282% (317 of 1123) had severe QoL impairment in terms of the functioning domain. The factors associated with

Table 2 The Skindex-29 items that affected > 25% of patients with vitiligo

Affected

Items (in order of frequency)                        patients     Domain

13. I worry that my skin condition may          746%         Emotions get worse

3. I worry that my skin condition may            629%         Emotions be serious

22. My skin condition is a problem for          556%                Functioning the people I love

6. My skin condition makes me feel               535%         Emotions depressed

9. I worry about getting scars from my           498%         Emotions skin condition

12. I am ashamed of my skin condition        497%       Emotions

28. I am annoyed by my skin condition        476%       Emotions

5. My skin condition affects my social           450%                Functioning life

15. I am angry about my skin condition        448%       Emotions

24. My skin is sensitive                                 433%          Symptoms

4. My skin condition makes it hard to            427%                Functioning work or do hobbies

21. I am embarrassed by my skin 410%         Emotions condition

19. My skin is irritated                                  379%          Symptoms

23. I am frustrated by my skin condition      356%       Emotions

20. My skin condition affects my 354%         Functioning interactions with others

11. My skin condition affects how close       328%       Functioning

I can be with those I love

17. My skin condition makes showing           305%                Functioning affection difficult

26. I am humiliated by my skin    296%         Emotions condition

10. My skin itches                                         291%          Symptoms

14. I tend to do things by myself  275%         Functioning because of my skin condition

30. My skin condition makes me tired          264%       Functioning

8. I tend to stay at home because of my          263%                Functioning skin condition

 

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VIPOC
In vitiligo treatment

Vitiligo treatment updates

Dr. John Harris discusses the current and future landscape for vitiligo treatment.

Vitiligo Treatment Updates – The Dermatology Digest (thedermdigest.com)

John E. Harris, MD, PhD, is Professor and Chair, Department of Dermatology, as well as Director of the Vitiligo Research Center at University of Massachusetts Medical School in Worcester, Mass.

“We’ve been using the same [vitiligo] treatments for about 3400 years: sunlight and light-activated chemicals, while now we use narrowband UVB, which is a small improvement,” said John E. Harris, MD, PhD, who discussed vitiligo treatment updates at the 4th Inflammatory Skin Disease Summit.

“We have good treatments for vitiligo, but they’re really cumbersome. They take a long time. Patients have to really commit to 12 to 14 months of treatment to get decent improvement.”

However, research over the past decade into what causes vitiligo has led to new treatment opportunities, said Dr. Harris. There are two signaling cytokine pathways that can be targeted for vitiligo: JAK inhibitors for interferon gamma signaling and biologics to target IL-15 signaling.

“A phase II and then phase III clinical trial have now been conducted using topical ruxolitinib [Opzelura] to treat vitiligo, and both showed that it was very effective….1 The FDA has approved it for atopic dermatitis and now we’re hoping in the next few months it will be approved for vitiligo. That would be the first FDA-approved treatment for vitiligo, ever.”

In terms of biologics, a clinical trial is currently recruiting patients to address disease relapse, which is about 40% within a year of stopping any treatment, said Dr. Harris.

“We wanted to know why—why does vitiligo come back? And importantly, why does it come back in exactly where it was before?”

According to Dr. Harris, they found that resident memory T cells form within vitiligo lesions.

“You can take a JAK inhibitor or any other treatment and turn off these cells, and everything gets better. But then if you stop the treatment, they’re still there. They wake back up and reinitiate everything.”

Those memory T cells require IL-15 signaling for long-term maintenance and survival, said Dr. Harris.

“When we blocked IL-15 signaling, not only did vitiligo get better in a mouse model, but those… memory T cells were erased from the skin. Short-term treatment gave us long-term effects. We’re hoping that blocking IL-15 with an antibody… will last not just for a short period of time but actually give a durable, long-term response.”

In their research, Dr. Harris and colleagues also have found hundreds of other activated pathways to potentially target for vitiligo treatment.2 

“We’re pursuing those. There’s some promise that that maybe someday we’ll have even better [treatments]. Could the cure for vitiligo be in that data somewhere? We’re hoping so.”

According to Dr. Harris, treatments under consideration include a bi-specific antibody and RNA interference (RNAi).

“We know we can treat psoriasis [and] atopic dermatitis with an antibody. We showed some data… [with] a bi-specific antibody, where one antibody targets two different things. We can bring the treatment into the skin, tether it there, and create a high local concentration that might be both safer and have higher efficacy for patients.”

RNAi may also be an option for treating vitiligo and other inflammatory skin diseases, said Dr. Harris.

“It’s a new way to turn off proteins in different tissues, and we found a way to deliver this specifically to the skin.”

Despite all these up-and-coming treatments, Dr. Harris has a key message for dermatologists who may believe they do not currently have viable treatment options for their vitiligo patients.

“There’s plenty you can do even now with the tools that we have, the drugs, the treatment approaches…. It’s just cumbersome and difficult and not everybody has access.”

Current off-label treatment options include tofacitinib (Xeljanz XR) and ruxolitinib, said Dr. Harris.

“Oral tofacitinib works for vitiligo. It’s tough to get because it’s not FDA approved for vitiligo. It’s very expensive. So, trying to get that approved for use in patients can be difficult, although not impossible.”

The oral JAK inhibitor also recently received a black box warning for safety concerns.

According to Dr. Harris, he has topical ruxolitinib compounded at a compounding pharmacy.

“I’ve used [ruxolitinib] over the last few years. But as soon as that gets FDA approved for vitiligo, we’ll have it from the pharmacy and be able to prescribe it on label which would be exciting.”

References

  1. Rosmarin D, Pandya AG, Lebwohl M, et al. Ruxolitinib cream for treatment of vitiligo: a randomised, controlled, phase 2 trial. Lancet. 2020 Jul 11;396(10244):110-120. doi: 10.1016/S0140-6736(20)30609-7. PMID: 32653055.
  2. Gellatly KJ, Strassner JP, Essien K, et al. scRNA-seq of human vitiligo reveals complex networks of subclinical immune activation and a role for CCR5 in Treg function. Sci Transl Med. 2021 Sep 8;13(610):eabd8995. doi: 10.1126/scitranslmed.abd8995. Epub 2021 Sep 8. PMID: 34516831; PMCID: PMC8686160.

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