The precise mechanism which leads to generalised loss of skin pigmentation is still unknown. Patients with immunological disorders do have a higher prevalence of vitiligo. That is not to say that vitiligo patients necessarily suffer from immune disorders, since many of these patients have no other underlying disease. At the current state of clinical practice it is believed that in vitiligo pigment cells ( become dysregulated and susceptible to intracellular oxidative stress, and therefore lose the ability to produce melanin (due to increased activity of antigen specific T cells (immune cells). It is thought that the intracellular pathways through protein expressions and signalling via IFN γ STAT 1 CXCL 10 are part of the primary inflammatory pathway responsible for both progression and maintenance of the condition. ¹ ²
In some regions across Africa and Asia the social stigma of the disease is very high it is also often confused with leprosy Sweta Kushta white leprosy). 3
In North America, the disease is most prominent among African Americans and other individuals of darker skin types. In psychological assessment of vitiligo patients, some studies found that two thirds of the patients were embarrassed by vitiligo and over 50% of patients felt ill at ease, anxious, concerned and worried Patients report being stigmatised by their disease, as they often feel stared at, discriminated against, and subject to verbal abuse.


FITZPATRICK SKIN TYPES IV-V-VI
Various skin type classifications have been used over the years, but the most frequent one reported is the Fitzpatrick scale, categorised by one’s propensity to burn when exposed to ultraviolet light Figure 3 below summarises the classification.


LACK OF THERAPEUTIC SOLUTIONS
The standard NB UVB regimen globally is two to three weekly exposures for a duration of 12 to 18 months, depending on the clinical response of patients. In general, the clinical results are inconsistent and poor, with many patients relapsing within 12 months.
Other therapies such as local corticosteroids, mTor inhibitors, monoclonal antibodies, psoralen and skin grafting (transplants) have been tried without meaningful clinical results. Among the expert community of vitiligo physicians, there is a consensus that an effective repigmentation treatment is due and much desired.
The most resistant skin surface areas – those areas which show no response to any treatment – are the hands and feet.

Figure 4: Hair follicle and reservoir melanocytes
SIGNIFICANCE OF RESULTS CUV102 AND CUV103
Clinically important was the finding that patients who had received the combination therapy achieved earlier repigmentation than those on monotherapy (median time 43 days versus 68 days, p=0.086; 95% CI). In other words, the additional effects of the drug treatment became meaningful 43 days after starting the drug therapy. In assessing the highest therapeutic benefit, those vitiligo patients with skin types IV, V and VI showed a statistically superior degree of repigmentation following the combination drug treatment.
The analyses showed statistically significant decreases (improvement) in the VASI scores compared to baseline (Day 0) and at subsequent time points throughout the study; for the total body surface at Day 84 (p=0.001) through to Day 168 (p<0.001), for the head and neck, upper extremities and trunk at Days 112, 140, Day 168 (p-<0.05) and for the hands and lower extremities at Day 140 and Day 168 (p<0.05) . No differences in VASI over time were seen for the feet.
The studies individually showed that the SCENESSE® treatment led to follicular repigmentation and meaningful clinical results within six months. A cultural difference has become apparent in vitiligo patients and their ability to accept increases in pandermal (total skin surface) pigmentation.
For the first time, the patients of Asian descent expressed concerns at the overall temporary epidermal darkening induced by afamelanotide in combination with NB-UVB because skin darkening is culturally and socially unacceptable in Asian populations. This finding is significant compared to the willingness by African American patients who expressed having lost their colour and identity. Skin colour and vitiligo are in various regions of the world culturally charged and impact patients in various forms.
As required for the introduction of a new therapy – in our case a combination therapy – a pre-clinical study announced in 2016 demonstrated safety of SCENESSE® in combination with NB-UVB in a single species. The cumulative dose received ranged from 2,016-5,400 mJ/cm2 . In the CUV102 study the median cumulative dose was 28,031 mJ/cm2 and in the CUV103 study the median cumulative dose was 50,125 mJ/cm2 . From these three studies thus far it can be concluded that the introduction of a new combination therapy maintains a positive safety profile.
VITILIGO PATIENT ORGANISATIONS
These groups aim to provide support and resources to vitiligo patients beyond that provided by clinical care, ranging from communicating updates on research to the community through to advocating for treatment access and advising on camouflage techniques. Most often it is simply by providing vitiligo patients and their families with an outlet to be heard that provides the greatest support, particularly in the early stages of the disease.

REFERENCES
Richmond J. M. et al. Curr Opin Immunol. 2013 Dec; 25(6): 676-682. Innate immune mechanisms in
vitiligo: Danger from within.
Strassner J.P. et al. Curr Opin in Immunol Volume 43, Dec 2016, 81-88 Understanding mechanisms of
autoimmunity through translational research in vitiligo.
Onunu A.N. et al. Int J Derm. 2003 Oct;42(10):800-2. Vitiligo in the Nigerian African: a study of 351
patients in Benin City, Nigeria.
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