Nonsegmental vitiligo is a common pigmentary disorder where the skin gradually loses its colour (melanin) in patches. It is unknown precisely what causes the condition, though it is generally thought to be a result of autoimmune damage to the pigment-producing cells, called melanocytes. Vitiligo is a complex, multifactorial disease, meaning that it occurs as a result of interactions between ones genes and their environment. The fact that vitiligo often presents in close relatives (10-30% of vitiligo patients report a family history of the disorder) indicates that, to some extent, it is a heritable condition. In other words, in some cases a person’s genetic make-up can predispose them to vitiligo.

In those susceptible to vitiligo, several environmental factors (commonly called ‘triggers’), may determine if, or the manner in which, the disease develops. Potential triggers, which have been implicated in the onset or spread of vitiligo, include: stress; pregnancy; physical trauma to the skin; and exposure to certain pathogens or industrial chemicals. Vitiligo is believed to be a combination of these environmental factors with genetics, though in some cases the instigating factor is unknown and the vitiligo is termed ‘idiopathic’.

The genes which predispose some people to vitiligo have been aptly named “susceptibility genes”. Having these genes does not guarantee that an individual will develop vitiligo, but rather that under certain environmental conditions they are more likely to develop the disease than others in the population. An assortment of multiple susceptibility genes determines ones risk of developing vitiligo.

Researchers have been looking at vitiligo susceptibility genes for some time in an attempt to better understand the disease and ideally find ways to improve management, treatment and even prevention of vitiligo. One of the ways this is done is called “Case/control association” where differences in particular genes are studied in patients with vitiligo compared with healthy subjects. Another conventional method is “Family-based association”, which looks at genetic changes common to parents and siblings of those with vitiligo.

Several vitiligo susceptibility genes have already been identified, including: AIS1 (1p31), PTPN22 (1p13) and SLEV1 (17p13); many more are still under investigation. Among other functions, genes which influence the development of vitiligo may be involved in regulating melanocytes or the immune system (affecting an autoimmune response).

Knowing the genes concerned may allow medical scientists to tailor specific vitiligo treatments to suit these genetic aberrations. It will also enable tests to be developed so that individuals who are prone to vitiligo can be made aware of this propensity and adjust their lifestyles to avoid triggers where possible. Finally, though still in its infancy, gene therapy – the manipulation of a person’s genetic information to treat a medical condition – is advancing. Hypothetically, in the future, this form of treatment may be able to benefit vitiligo patients whose genetic variations are known.

For those with vitiligo interested in participating in genetic studies, please see the following link http://www.vitiligosupport.org/treatments_and_research/clinical_trials.cfm, under the title, “Take Part in International Study to Find Vitiligo Genes”.

Further reading

Spritz, RA 2011, ‘Recent progress in the genetics of generalized vitiligo’, Journal of Genetics and Genomics, 38(7):271-8.

Image reference

‘DNA rendering’ uploaded to flickr.com by ’ynse’ on 12 June 2007, <http://www.flickr.com/photos/ynse/542370154/>.

Vitiligo is a common skin depigmentation disorder in which the melanocytes, the skin cells which produce melanin pigment, are progressively lost. Despite this, melanocyte stem cells, or immature melanocytes, are preserved in a special region within hair follicles called the bulge, or niche. Often these cells are able to be stimulated with narrowband ultraviolet B (NB-UVB) phototherapy to mature into fully functional melanocytes which migrate to the epidermis to replace the lost or damaged cells. Upon further exposure to UVB radiation, skin cells (keratinocytes) manufacture a hormone called alpha-melanocyte-stimulating hormone, or α-MSH. Alpha-MSH binds to receptors on the newly formed melanocytes and activates melanin production to repigment areas of skin affected by vitiligo.

Significant advances in the understanding of the factors which influence melanocytes and their stem cells have lead to improved clinical care for patients with vitiligo. The potential of α-MSH and its analogues to further stimulate these developing melanocytes following ultraviolet therapy, to aid in repigmentation of the vitiliginous skin, is an exciting prospect.

Patient responses to NB-UVB are hugely variable. It is impossible to predict whether vitiligo will improve as a result of the treatment, and if so, to what extent. Considerable time and resources are required to reach a clinical conclusion as to whether NB-UVB therapy is effective and there are potential long term risks associated with repeated exposure to UV radiation, a known carcinogen. Thus, there is a clear argument for the exploration of potential combination therapies with NB-UVB which could reduce the number of clinical visits required to achieve repigmentation.

Based on knowledge of the processes involved in repigmenting vitiliginous skin with NB-UVB, there are clear scientific grounds for the combined use of this light therapy with α-MSH analogues. Afamelanotide, the most clinically advanced α-MSH analogue, is thus a natural therapeutic candidate. It has a greater binding affinity with the receptor on melanocytes than natural α-MSH and is therefore able to more readily activate melanin to repigment skin. It is hoped that treatment with afamelanotide, in conjunction with NB-UVB therapy, will produce faster, more consistent repigmentation of vitiliginous skin.

This piece is adapted from Clinuvel’s latest Technology Update: Stem Cells and Repigmentation in Vitiligo.

This is the second of a two part series on vitiligo treatment from guest blogger Liz Tyler, to read the first part, click here. Liz runs @VitiligoProject and the Vitiligo Project blog, an initiative she founded to help others, like her, who are living with vitiligo.

I’ve had vitiligo since childhood and, like many others who have the disorder, I find it a challenge to live with. Whether you’re able to accept your vitiligo or not, it’s needless to say it takes a lot of getting used to. For me, I’ve never been completely comfortable with my skin and with a career in marketing and PR, where image is really important, I’ve always been willing to try new treatments and look for therapies that could help cure it.

Since being diagnosed, I’ve tried a number of treatments. I initially tried homeopathic therapy, which involved taking natrum marina (sea salt) and changing my diet, I then went on to protopic for just a couple of months, followed by steroid cream (clobetasone butyrate). Unfortunately I had no positive change with these treatments. I also saw the British Red Cross for a camouflage session but this was unsuccessful – I have freckles and the person I saw found it hard to find a make-up colour match.

Having put further treatment on hold for a year’s travel, I arrived back in the UK eager to continue with therapy. I went back to the doctor and was referred to a new dermatologist. He decided it was wise to escalate treatments if previous therapies proved ineffective and helped put together a new programme:

1) Protopic (three months)

2) Narrowband UVB light therapy (three months)

3) De-pigmentation (face only)

After trying Protopic for another three months, I moved on to narrowband UVB phototherapy and this has had fantastic results!

The first month of light therapy was challenging, it’s a very demanding course – I went to hospital twice a week for three months. Midway through the light therapy, the head of the phototherapy unit pulled me aside and told me that I should give up treatment as I was young and it didn’t appear to be working. It made me feel terrible as by now I had seen four different doctors and none of them had come up with a solution for me. I really did feel like chucking the towel in, but I chose to stick it out – what else did I have to lose? If I didn’t try, I’d never know – right?

I continued with treatment and I’m very glad I did. Over the next few weeks, tiny freckles began to appear in my smaller vitiligo patches. I was sure it was wishful thinking, but my nurse agreed that I was reacting to the treatment. A few more weeks passed and the repigmentation continued in all of the patches that were exposed to the light. It was amazing. After so long, something was working!

Unfortunately, three months of treatment was soon over and I had reached my dosage limit. I was starting to burn after the sessions and had to stop.

I had a follow-up meeting with yet another new dermatologist who agreed I had to stop NB-UVB therapy, but by no means stop treatment completely! He revisited the agreed programme and told me I shouldn’t start depigmentation treatment yet, as he felt I was too young. He asked me if I had ever had a blood test to see whether I had a thyroid problem (thyroid problems are apparently quite common in young females with vitiligo) and that he’d like me to go back onto a steroid cream – this time Eumovate (clobestsol propionate), a stronger variation. He is the first of five doctors to have mentioned a possible thyroid problem, so I was pretty amazed. I am currently still on the steroid treatment and am actually due back this week for the results!

If you’re like me and feel like you need to do something about your vitiligo, in my experience, there’s really no harm in trying and experimenting with different treatments. Just be aware of the risks and make sure you’re doing it the right way, through your doctor, and for the right reasons. Only do what you feel comfortable doing and don’t rush into it.

Additionally, if you feel your doctor isn’t prescribing you the treatment you had in mind – ask to discuss it and see what you can do about it. Every doctor is different; it took me a lot of visits before I felt I was being taken seriously – so don’t give up!

Most importantly, everyone reacts differently to treatments and what works for one person may not work for another – always go in knowing that it may not necessarily work. I’ve spent a long time trying different treatments and, although only one of them has shown a positive result, I don’t regret it in the slightest. If anything, I feel satisfied knowing I’ve tried the different options and that I’ve given it a go, instead of waiting down the line and wondering, “What if?”.

Image courtesy of Liz Tyler

We’re delighted to host guest blogger Liz Tyler. Liz runs @VitiligoProject and the Vitiligo Project blog, an initiative she founded to help others, like her, who are living with vitiligo. This is the first of a two part series on Liz’s personal treatment experience.

I’ve had vitiligo for thirteen years and like many, my journey of living with vitiligo hasn’t been an easy one. In this day and age when we’re all made to think we need to look like Kate Moss – it’s needless to say having patchy skin is a setback.

I have vitiligo in most areas of my body: around my eyes, on my cheek, hips, legs, ankles, elbows, hands, groin area and hair. I first began to contract it when I was about 11, in between my thighs – as I was so young I didn’t really know if patchy skin was normal or not, plus being in an intimate place I chose to keep it to myself.

It didn’t really bother me at first because my patches were hidden. My vitiligo began to spread progressively when I was 16 and throughout my time at University. It soon spread onto visible areas – my hands and face. That’s when living with vitiligo became a problem. I just couldn’t deal with it being in a place people would so blatantly see.

It’s really hard for me to admit it, but vitiligo impacts me every day. It’s the first thing I see when I look in the mirror and when I meet new people I can’t help but assume they’re looking at my skin. I know I shouldn’t, but I can’t help it because, other than the odd spot, their skin looks perfect – and I wonder if they see what I see.

Initially, I went to my doctors and saw a newly qualified doctor. I already knew it was vitiligo, but I needed to do something about it. To be honest I felt humiliated – she examined me, told me it was a disease and suggested I wore a hat and kept out the sun. Not the response I was looking for. She gave me a stack of information I had already found online and I felt very dissatisfied.

I looked into treatments by myself and joined many vitiligo forums on a hunt for as much information I could find. I eventually built up the courage to go back to the doctors and saw a lovely woman who recommended Protopic (tacrolimus). I told her how upset I was after my last visit and she referred me to a dermatologist.

Once I met with my dermatologist, I was taken off Protopic (which hadn’t shown any positive results) and was put straight onto steroid cream (Eumovate, clobetasone butrate) for three months. She also sent me to the British Red Cross for camouflage. The camouflage session didn’t go down very well as I have freckles and they couldn’t find a make-up colour match, but found my own alternative that seemed to work. After the three months I hadn’t seen any results with steroid cream so stopped the treatment. During that time, I went travelling so postponed further treatment for a year.

You can read the second part of Liz’s blog here. Additionally, you can read more about those living with vitiligo from guest bloggers Lee Thomas and Ogo Maduewesi.  

Image courtesy of Liz Tyler

Figures 1 & 2. A vitiligo patient before and after NB-UVB treatment. Images courtesy of Pearl E Grimes, MD.

Vitiligo is a common skin depigmentation disorder in which the melanocytes, the skin cells which produce melanin pigment, are progressively lost. Clinically, when vitiliginous lesions (the ‘patches’ of skin which have lost their pigment) are repeatedly exposed to an intensive dose of narrowband UVB radiation (308 or 311-313nm), it is common to see small spots, sometimes described as ‘freckles’ or  ‘islands’, of repigmentation forming within the lesion. This occurs because the melanocytes producing this melanin have developed from stem cells reserved in the bulge region of the hair follicle, known as the niche. Their development is stimulated by NB-UVB and they migrate to the skin directly surrounding the hair follicle from which they were derived. As the melanocytes continue to travel through the skin and produce melanin, these ‘islands’ begin to spread and merge, eventually creating broader, but seldom perfect, repigmentation in the treated area (see Figures 1 & 2).

The follicular repigmentation with NB-UVB therapy takes time (generally 2-3 weekly treatments for up to 18 months), but is believed to work through two distinct mechanisms within the skin. Firstly, UVB radiation activates the stem cells within the niche to mature to functional melanocytes and migrate into the epidermis, as previously mentioned. Secondly, UVB radiation impacts upon another type of skin cell, keratinocytes within the epidermis, stimulating them to produce the hormone α-MSH. This, in turn, binds to receptors on the melanocyte and activates melanin production (see Figure 3).

Unfortunately, this process is not guaranteed to repigment the skin of all patients; approximately 75% of patients see some degree of repigmentation, but the level is not consistent. There is no known time scale involved for repigmentation, nor is there a reliable method to evaluate which patients are suitable for treatment; frustrating factors given the time and financial investment required to undergo NB-UVB therapy. Further, while the wavelengths of light used in NB-UVB are recognised as being less carcinogenic than broadband UVB radiation, and the risks are considered minimal, the long term effects of this treatment are yet to be fully investigated.

Figure 3. The process of melanocyte migration and repigmentation in vitiliginous skin following NB-UVB therapy.

This piece is adapted from Clinuvel’s latest Technology Update: Stem Cells and Repigmentation in Vitiligo.

Human skin consists of a number of different cells. The majority of the top layer of the skin is made up of keratinocytes which are produced constantly and migrate to the surface of the skin where they ‘slough off’ as dead skin.

Melanocytes, the cells which produce pigment in the skin, lie below the keratinocytes at the base of the epidermis (see the figure, click to enlarge). Melanocytes also exist at the root of the hair follicle, in the matrix of the inner root sheath or shaft, and are responsible for giving hair its colour. The dermis, the layer of the skin beneath the epidermis, consists mostly of collagen, elastic tissue and reticulum fibres, along with some specialised nerves and glands. The bases of hair follicles are also embedded in this middle layer of skin.

Part of the outer root sheath of the hair follicle forms a bulge, a region called the ‘niche’. Contained within the niche are partially differentiated stem cells: immature cells which, given the right conditions, can be activated to develop into several cell types.

Based on modeling in animal studies, it is believed that melanocytes in the hair and skin develop early on in the lifecycle of a human embryo. At a later stage, the melanocyte stem cells are also formed and deposited within a specific region of the hair follicle. This ‘reservoir’ of stem cells (which sometimes contains only a single cell) is the aforementioned ‘niche’ or ‘bulge’ and is continuous with the epidermis.

Melanocyte stem cells can be activated and, given the correct stimulation, are able to mature into fully functioning melanocytes within the epidermis. Despite significant research efforts in recent years, the pathways and interactions responsible for the activation and migration of melanocyte stem cells are still not completely understood. What is known is that the expression of several genes, in response to ultraviolet light, leads to the production of various factors which play a critical role in activating stem cells. Initially, the stem cells divide and some begin to mature, forming melanoblasts; intermediate cells which are a precursor to adult melanocytes. With continued stimulation, melanoblasts further develop and differentiate, migrating to the epidermis where they become fully functioning, pigment producing melanocytes.

Under normal physiologic conditions, the maturation of melanocytes – from early stages of human embryonic development into the niche, then to fully grown melanocytes in the epidermis – is controlled by a variety of signaling pathways.  These pathways, including Ednrb and Kit, as well as the transcription factors PAX3, SOX10 and Mitf, play diverse roles in the stimulation, development, survival and migration of melanocyte stem cells.

Many of the processes described above are also influenced or enhanced when ultraviolet (UV) radiation impacts upon the skin. Therefore, in conditions where melanocytes are damaged, or completely lost from the skin, such as in the depigmentation disorder vitiligo, ultraviolet therapies can be employed to aid in their restoration.  This is is believed to be the underlying mechanism of action of current ultraviolet treatments in vitiligo patients where melanocyte migration can lead to the repigmentation of skin affected by vitiliginous lesions.

This piece is adapted from Clinuvel’s latest Technology Update: Stem Cells and Repigmentation in Vitiligo.

Each cell within the body has one or more receptors; molecules on or within the cell to which other molecules, called ligands, bind. This binding causes a series of chemical reactions within the cell, called a ‘signaling pathway’. Signaling pathways are responsible for cellular responses, allowing other cells and external elements to alter how a cell functions. There are two types of ligands which bind to receptors: agonists, which then promote a response in the pathway, and antagonists, which lead to an alternate response.

There are four significant signaling pathways that affect the function of melanocytes (pigment-producing cells) within the skin. Each pathway involves a receptor – melanocortin 1 (MC1R), Kit, Frizzled and EdnrB – to which specific ligands bind. When the appropriate ligand binds to a receptor, it creates a series of physical and chemical changes (signaling pathway), which affects change within the melanocyte and alters its function (see figure). MC1R is the key receptor involved in the signaling pathway which leads to the production of the brown pigment, melanin, in the skin.

To produce melanin naturally, the MC1R pathway must be activated by the ligand alpha-Melanocyte Stimulating Hormone (α-MSH) binding to the MC1R on the outside surface of the melanocyte. Approximately 1000 of these receptors exist on each healthy melanocyte.

In the skin α-MSH is produced by a specific type of cells (known a keratinocytes) in response to damage caused by ultraviolet radiation. α-MSH molecules then bind with the MC1R on the melanocyte to activate the MC1R pathway and produce melanin. Following this process, melanin granules are deposited in packages called melanosomes which are then transported to the ends of the melanocyte projections, called dendrites. The tips of these dendrites are then enveloped by nearby keratinocytes into which the melanin granules are released. These spread out to form a pigmented, protective barrier over the keratinocyte’s nucleus (see the figure below).

The process of α-MSH mediated melanin production in skin activated by ultraviolet light.

This piece is an abstract from Clinuvel’s latest Technology Update: Stem Cells and Repigmentation in Vitiligo.

This is the second blog in a two-part series by Ogo Maduewesi of the Vitiligo Support and Awareness Foundation (www.vitsaf.org); to view the first part, click here.  In this post Ogo continues her discussion about the types of difficulties West Africans with vitiligo confront on a daily basis.

Although people – particularly in my country, Nigeria – will always give you the impression that they don’t have an issue with vitiligo, many do segregate or ostracise those with the condition, especially in the rural areas. There is a social stigma attached to vitiligo, affecting the social well-being of patients. Especially in African countries, where the people are dark-skinned and the contrast to their natural skin tone is more obvious. 

Childhood

Parents and elders have not helped matters. You see them warning their children and charges not to go near other children or people with vitiligo, as if it were contagious or a ‘curse’ might befall them. This video is based on one such true story:

On another occasion, a parent shared with me how her daughter’s school called her to enquire about the white patches which had suddenly appeared on her daughter. Other parents were threatening to withdraw their children if her daughter was not removed from the school.

Rural Africa

Perhaps the worst stigmatisation of vitiligo occurs in rural and remote Africa. For people living in these areas and villages the social stigma and isolation is even greater. Most of them cannot join in meetings or activities and some are even ex-communicated, faced to live in oppression. They have no support from their families who believe that they bring shame. All of this has roots in supernatural beliefs because people refuse to see and understand life from its true and natural perspective. They think the wrath of the Gods is at work and want to avoid contracting vitiligo themselves.

The height of ignorance is such that people mistake vitiligo for a contagious disease. One man with vitiligo told me how a prophet warned him to stay away from his own family for the danger that he would infect them all. These people fail to understand that the person suffers, not only externally, but also experiences internal psychological trauma and depression.

Vitiligo is a non-contagious skin condition that occurs in all sexes and races equally. The myth about vitiligo being contagious is likely the result of a common fear: people stay away from anything different. This is typical, not only of Africans, but of the whole human race.

Editor’s note: The embedded video above is part of a series created by VITSAF to help combat the social stigma of vitiligo in West Africa. You can view all five videos in this series below:

http://www.youtube.com/watch?v=v_wBWmewlhE 
http://www.youtube.com/watch?v=HiwbYbHLnSA
http://www.youtube.com/watch?v=svYjaVMkHNw
http://www.youtube.com/watch?v=Ll9MA2Wefqo
http://www.youtube.com/watch?v=yLTOcCgET00 

VITSAF is also working on a documentary entitled More to Life – A Documentary on Vitiligo, keep an eye on the Youtube channel above for more information.

Image reference

‘The road ends here’ uploaded to flickr.com by ‘Barefoot In Florida’ on 25 December 2009, <http://www.flickr.com/photos/i_level_news/4668168146/in/photostream/>.

In the first of a two-part series, guest blogger Ogo Maduewesi, founder of the Vitiligo Support and Awareness Foundation (www.vitsaf.org), speaks candidly about the stigma associated with vitiligo and the challenges faced by sufferers in West Africa.

Vitiligo is a hugely stigmatised condition, especially in Africa. Facing not only a visible, disfiguring skin problem, many patients also endure psychological, psychosocial and emotional stress from the disease and its stigma. This usually results in increased susceptibility to vitiligo: the stress of stigmatisation can often lead to further progression of the disease.

Social, religious and tribal factors play a significant role in stigmatisation in Africa. The main contributing factor to social stigma is that vitiligo is considered by many as a wrath of the Gods upon an individual. Further, because little or nothing had been heard about vitiligo in West Africa before now, people were left to make assumptions or create fantasies about the condition.

Tribal beliefs

One particular tribe in Nigeria strongly believes that anyone who has vitiligo has offended the Gods by eating a particular food forbidden by his/her family and that until the Gods are appeased the vitiligo will not go away.

Another tribe believes that it’s a curse or nemesis: they practically see a person with vitiligo as someone who has committed an offence; the Gods are visiting with vitiligo vengeance. In one instance I know of, a husband left his wife and kids because she suddenly started turning white, he believed it was a nemesis from her family. To some, marriage has become a distant dream. Even when two people agree to wed, the family imposes and cancels their nuptials (VITSAF has tried to address this issue in one of its recent videos linked below).

The role of ‘magic’

This is a highly religious and superstitious part of the world and, as I’ve said in an earlier post, the words of local prophets and diabolical doctors (commonly called Dibia, Babalawo) weigh heavily. Their advice plays a large part in initial vitiligo treatment, until a certain stage of the condition’s progression, by which point so many resources have been wasted that could have been put to better use.

The most common vitiligo myth in Africa is that it’s inflicted by bad or evil people through magical powers. I have been told many times that such people brought vitiligo upon me to destroy my face so that I wouldn’t be able to find a husband.

I was called, at one point, to intervene between two families in a deep squabble: one was accusing the other of having inflicted vitiligo upon one of their members through magical powers. These beliefs are so strong that even when I meet some sufferers and try to counsel them, they look me straight in the face and tell me that their condition is different from mine: mine is a health condition, theirs is spiritual attack.

Editor’s note: Part two will be published shortly. VITSAF has created a series of videos to help combat the social stigma of vitiligo in West Africa, you can view all five videos in the series below:

http://www.youtube.com/watch?v=v_wBWmewlhE
http://www.youtube.com/watch?v=HiwbYbHLnSA
http://www.youtube.com/watch?v=svYjaVMkHNw
http://www.youtube.com/watch?v=Ll9MA2Wefqo
http://www.youtube.com/watch?v=yLTOcCgET00

Image reference:

“Africa Satellite Plan” By NASA, via Wikimedia Commons see http://commons.wikimedia.org/wiki/File:Africa_satellite_plane.jpg for license details.

Since our announcement last year that Clinuvel would commence a new program for SCENESSE® (afamelanotide) in nonsegmental vitiligo, the company has received vast interest in the application of the drug in this disease. Of the enquiries that best captured the essence of this program, one stood out: a US based analyst asked how the company intended to objectively measure the response to treatment, the repigmentation of vitiliginous lesions, in its trial.

Those acquainted with drug development will know this is the key question.

When evaluating a new therapy, one must be able to show the effects of that therapy first in isolation, then in comparison to the current standard of care (if it exists) and/or a placebo. The evaluation of the response to treatment must be objective and, importantly, should be done using a recognised method which allows third parties (initially regulators, but also the broader medical community) to compare the treatment to other therapies.

Vitiligo is a disorder where skin parts gradually lose pigment by the appearance of white lesions or ‘patches’. The pigment loss can be gradual or dramatic and can cease or recommence, spreading without warning. The medical community doesn’t quite yet know the reason for its onset. The goal of vitiligo therapy is to stop the spread of pigment loss and to return pigment to the lesions. One of the key issues in the evaluation of these therapies, however, has been how best to objectively measure the extent of repigmentation achieved and the time taken for the pigmentation to be restored.

Over the past decade, two methods of evaluation have been proposed and assessed in peer reviewed literature: the Vitiligo Area Scoring Index (VASI) and the Vitiligo European Task Force (VETF) system. Importantly, the two methods are recognised by the regulatory agencies EMA and FDA.

The VASI is a validated quantitative scale developed  by a North American team (Hamzavi et al, see references below) with the goals of quantifying the total extent of depigmentation, allowing physicians to measure de/repigmentation over time and evaluating the effect of treatment on various body sites. Based on the Psoriasis Area Severity Index (PASI; a system for objectively measuring psoriasis), the VASI was initially developed to measure the response of vitiligo to narrowband ultraviolet-B (NB-UVB) treatment, but has since been used to evaluate various vitiligo therapies.

In the VASI assessment, the body is separated into five sites: hands, upper extremities, trunk, lower extremities and feet (subsequent studies have added a sixth site: the head/neck). Each site is clinically evaluated by visual assessment for the percentage of vitiligo involvement (depigmented skin) and the degree of skin depigmentation (using a visual scale of 0, 10, 25, 50, 75, 90 or 100%). The VASI score is then derived by multiplying the values assessed for the vitiligo involvement by the percentage of affected skin for each body site and summing the surface of the lesions of all body sites together.

Clinical evaluations of vitiligo therapies now use the VASI to assess initial levels of depigmentation then to monitor the levels of repigmentation achieved over a period of time and will often provide a percentage improvement of VASI seen (overall and/or at individual body sites). While criticisms have been leveled at the subjectivity of the VASI, it is generally accepted that the VASI allows for a more practical clinical workup than more time or resource intensive methods.

Based on SCORAD, a clinical evaluation system for atopic dermatitis, the VETF system has been developed over several years by a European group (see full list of the VETF team in Taïeb & Picardo reference below). The VETF evaluation system seeks to add more specific parameters to the quantitative measurement of depigmentation. Indeed, the VETF assesses the three dimensions of the disease (extent, staging and spreading/progression), and so provides three different values. Similar to the VASI assessment, the body is also separated into five different sites, specifically the head/neck, trunk, arms, legs and hands/feet.

Each site is clinically evaluated by visual and photographic assessment for the extent or percentage of vitiligo involvement (depigmented skin), the staging and the spreading of vitiligo. The staging and the spreading of vitiligo are assessed on the largest lesion within each specific body site. A specific UV light (a Wood’s lamp which allows the dermatologist to view pigment which is impossible to determine with the naked eye) is then used to illuminate the skin. Staging is assessed using grades from 0 (normal pigmentation) to 4 (complete hair whitening). Spreading is assessed using the following scores: 0 (stable disease), -1 (regressive disease) and +1 (progressive disease).

A clinical assessment form can also accompany the scoring in the VETF system to determine various factors within the given patient population, including the sex, age, duration of disease, age of onset, episodes of repigmentation, impact of vitiligo on quality of life, family history, additional medical conditions and the Fitzpatrick skin type of the patients involved. This allows for a greater clinical workup and for physicians to compare treatments based on reported factors beyond depigmentation; the downside being that this is a very labour intensive approach.

While the two systems differ in their approach and outcomes, both are widely recognised as validated standards for the comparative evaluation of vitiligo and vitiligo treatments under clinical conditions. Importantly, they also allow independent reviewers to objectively evaluate the efficacy of a treatment on an internationally recognised scale.

For more information on Clinuvel’s vitiligo program, go to www.clinuvel.com/vitiligo

References

Hamzavi I, et al (2004). “Parametric modeling of narrowband UV-B phototherapy for vitiligo using a novel quantitative tool: the Vitiligo Area Scoring Index.” Arch Dermatol. 140(6):677-83. Abstract online

Taïeb A, Picardo M & VETF Members (2007). “The definition and assessment of vitiligo: a consensus report of the Vitiligo European Task Force.” Pigment Cell Res. 20(1):27-35. Abstract online

VETF, (2005). “Report on the 19^th IPCC Satellite Symposium on Vitiligo, Reston Virginia”. Online: http://www.espcr.org/docs/Report_VETF_IPCC2005.pdf.