INTRODUCTION:

Pigment is a Colored substances in the organism or environment is known as pigment.these are classified in to two categories, they areendogenous and exogenous in nature. Endogenous again two types like autogenous and hemoproteins derived colours. Autogenous Pigments means the color substances formed in the organism as metabolic products. They are Melanin, Ceroid, Lipofuscin¹.

What are Melanocytes?

Melanocytes are special cells in our skin that specialize in making a molecule called melanin. The production of melanocytes is Oculocutaneous (origin from tyrosine in melanocytes) and neuromelanin - substantial nigra(origin from dopamin).

Melanin is something called a pigment, which is the molecule that gives our skin colour a darker shade². There are two different types of melanin like eumelanin – insoluble, brown-black another is phaeomelanin – soluble, yellow-red (high sulphur content). Melanin protects our skin from the damaging Ultraviolet (UV) rays from the sun.Melanin is Derived from the neural crest. Present in the basal layer of epidermis, dermis, hair folicles, mucose membranes, uveal tract of the eye, meninges, inner ear. Secretory in the contact with the epithelial cells – cytocrinia. The more melanin you have in your skin, the darker your skin colour will be³.

Functions of Melanin

· Cytoprotective

· light absorption & conversion of the photon energy into heat.

· uvea – absorption of the light retina protection of light overexposure.

· retina - visual acuity preventing light reflexion from the fundus.

· Ion exchanging capacity.

· Melanosomes can also act as detoxyfiing and excretory components accumulating great number of drugs and toxic component e.g. heavy metals. Melanins are colloidal pigments, known to have a high affinity for metal ions; therefore, certain metal ions such as copper, zinc and iron were found in high levels in pigmented tissues involved in melanin synthesis⁴.

Vitiligo is a melanin related condition of skin condition that can manifest after birth at any point in someone’s life. It leads to death or loss of function of the melanocytes in the body, which leads to the inability to produce any more melanin in the skin⁵. Vitiligo is very visible on someone with a very dark complexion due to the prevalence of white splotches of skin. It is a Chronic skin disease, the other name is leukoderma, white spots occur when the skin no longer forms melanin (pigment that determines the color of your skin, hair, and eyes). Finally the white patches of irregular shapes begin to appear on your skin⁶. Facts about vitiligo include can appear at any age, usually first appears between the ages of 20 and 30. White patches may begin on your face above your eyes or on your neck, armpits, elbows, genitals, hands or knees.1-200 of the world population develops. It affects both genders⁷.

Types of Vitiligo:

Segmental skin problem (SV):

Most frequently begins at associate degree early age and affects just one space, on one facet of the body, like one facet of the mouth, or neck. It typically spreads fairly quickly at the onset, then slows and remains stable once a year more or less, with over 0.5 conjointly developing patches of white hair. SV is never related to the autoimmune disorder⁸.

Non-segmental skin condition (NSV):

Associate in nursing disease and generally begins in areas like the hands, wrists, around the eyes or mouth, or on the feet, then spreads to areas like the neck, chest, knees, and legs. NSV is taken into account to be progressive, however, has cycles of spreading and cycles of stability. NSV includes every type of skin condition except segmental skin condition⁹.

Classes of non-segmental vitiligo include the following:

Generalized Vitiligo: the most common pattern, wide and randomly distributed areas of depigmentation. Widespread and mostly symmetrical distribution.

Universal Vitiligo: depigmentation encompasses most of the body. Complete or nearly complete coloration of skin¹⁰.

Focal Vitiligo: one or a few scattered macules in one area, most common in children. One or additional spaces of pigment loose in an exceedingly confined area.

Acrofacial Vitiligo: fingers and periorificial areas. Depigmented areas removed from the middle of the body like face, head, hands and feet¹¹.

Figure 1: Acrofacial Vitiligo: fingers and periorificial areas

Mucosal Vitiligo: depigmentation of only the mucous membranes and area unit affected.

Figure 2: Mucosal Vitiligo: depigmentation of only the mucous membranes

Mixed vitiligo (MV):Begins as segmental vitiligo and then later progresses into non segmental vitiligo, becoming "mixed vitiligo” ¹².

Symptoms and Signs:

· Chalk white patches of skin

· Whitening or graying of the hair on your scalp, eyelashes, eyebrows or beard

· Loss of color in the tissues that line the inside of your mouth

· Loss or change in color of the inner layer of your eye

· Convex margins on skin in 5mm to 5cm or more in diameter

· Round, oval, or elongated in shape^{13, 14}.

Patterns of vitiligo: 3 patterns

Focal pattern—the depigmentation is limited to one or only a few areas, one or a few scattered macules in one area, most common in children¹⁵.

Segmental pattern—depigmented patches develop on only one side of the body. It tends to affect areas of skin that are associated with dorsal roots from the spinal cord and is most often unilateral¹⁶.

Generalized pattern—(most common) depigmentation occurs symmetrically on both sides of the body. Generalized Vitiligo: the most common pattern, wide and randomly distributed areas of depigmentation. Focal and segmental patterns do not spread. The generalized pattern is hard to predict and can randomly stop^17,
18.

Figure 3: Localized vitiligo

Figure 4: Generalized vitiligo on entire face, Generalized vitiligo on body

Causes:

· Genetics reason

· A family history of vitiligo

· Look to see if there is a rash, sunburn, or other skin trauma that has occurred within 2 or 3 months after pigmentation was discovered

· Premature graying of the hair (before age 35)

· Stress or physical illness

· Also they may ask for an eye examination (inflammation of your eye) and/or blood test (autoimmune disease)

· When no melanin is produced, the involved patch of skin becomes white

· When a white patch grows or spreads the cause may be Vitiligo

· May be due to an immune disorder^{19, 20}.

Diagnosis of vitiligo:

Genetics:

Researchers from different areas of the world explored intensively the possible shared susceptibility genes involved in vitiligo and other autoimmune diseases and additional genes that may mediate the vitiligo itself. Four different approaches have been used to identify genes that mediate the susceptibility to vitiligo: gene expression analyses, candidate gene association studies, genome-wide linkage studies and genome wide association studies (GWASs). Gene expression studies in vitiligo were done to analyze the changes in the expression pattern of several genes associated with immune modulation, melanogenesis, and regulation of the development and survival of melanocytes.

In this context, IFN-g, TNF-a and several members of interleukin-10 family cytokines (IL-10, IL-22, IL-24) and their receptors (IL10RA, IL10RB) have previously been demonstrated to be associated with vitiligo pathogenesis. There was a significant increase in the expression of IFN-g, TNF-a and IL 10 in involved and adjacent uninvolved skin in vitiligo patients Medical Screenings.

Vitiligo Area Scoring Index (VASI):

Hamzavi have introduced a quantitative parametric score, named VASI for Vitiligo Area Scoring Index, which is conceptually derived from the PASI score widely used in psoriasis assessment. The total body VASI is calculated using a formula that includes contributions from all body regions (possible range, 0–100)

VASI = All Body Sites [Hand Units] × Residual Depigmentation. (1)

The body is divided into five separate and mutually exclusive regions: hands, upper extremities (excluding hands), trunk, lower extremities (excluding feet), and feet. The auxiliary region is included with the upper extremities while the buttocks and inguinal areas are included with the lower extremities. The extent of residual depigmentation is expressed by the following percentages: 0, 10 %, 25 %, 50 %, 75 %, 90 %, or 100 %. At 100 % depigmentation, no pigment is present; at 90 %, specks of pigment are present; at 75 %, the depigmented area exceeds the pigmented area; at 50%, the depigmented and pigmented areas are equal; at 25 %, the pigmented area exceeds the depigmented area; at 10 %, only specks of depigmentation are present.

Table 1: Vitiligo Area Scoring Index

Sl. No	VASI score	Condition
1	0 to -50	Very much worse
2	-50 to -25	Much worse
3	−25to−10	Worse
4	-10 to 0	Minimally worse
5	0 to 10	Minimally improved
6	+10 to 25	Improved
7	+25 to 50	Much improved
8	+50	Very much improved

Vitiligo European Task Force (VETF):

The VETF proposed a system that combines analysis of extent, stage of disease (staging), and disease progression (spreading) [2]. Staging is based on cutaneous and hair pigmentation in vitiligo patches, and the disease is staged 0–3 on the largest macule in each body region, except hands and feet, which are assessed separately and globally as one unique area. A proposal was made for simplifying the staging scale:

Stage 0: normal pigmentation (no depigmentation in area graded),

Stage 1: incomplete depigmentation (including spotty depigmentation, trichrome, and homogeneous lighter pigmentation)

Stage 2: complete depigmentation (may include hair whitening in a minority of hairs, <30 %), Stage 3: complete depigmentation plus significant hair whitening (>30 %). “Spreading” in VETF was introduced to include a dynamic dimension, since rapidly progressive vitiligo needs urgent intervention to stabilize the disease. The proposed grid allows scoring this dimension on a simple scale (+1: progressive; 0: stable; −1: regressive). Spreading is assessed by combining Wood’s lamp and electric light examinations in a dark room. Wood’s lamp includes a magnifying lens to assess hairs, especially vellus hairs²¹.

Treatment:

Traditional Treatment:

Red clays found by the river side or on hill slopes can also be used for the treatment of vitiligo. It can be given by mixing with ginger juice. Copper in the clay brings skin pigmentation back and ginger facilitates increased blood flow to the spot which helps into the repigmentation of the spots. Radish seeds powdered with the vinegar and paste is formed. This paste can be applied to treat the vitiligo. Mixture of turmeric and mustard oil which is prepared by heating two of them is also helpful in the treatment of white patches.

Yoga therapy:

Kapalbhati is helpful in the treatment of vitiligo. Because of inhalation and exhalation kapalbhati provides aeration to blood and purifies blood circulation. This is beneficial in different skin diseases like vitiligo, psoriasis and other allergies.

Homeopathic treatment:

Homeopathy is an alternative medicine originated in germany in 18^th century and it is adapted by many countries. Ars.ach, Bacillinum, Graphites, Mercasol, Nat mur, nuxvom, sil, sulph, thuja etc. medicines can be used under homeopathic treatment²².

Ayurvedic treatments:

In Ayurveda vitiligo is known as Switra and it is mainly caused due to the Pitta Dosha as aggravated Pitta leads to accumulation of toxins (ama) in deep layers of the sk in which leads to the condition of Vitiligo. Basic treatment of this disease includes Calming imbalanced body energies, cleansing blood and administering the herbs which restore the skin colour. Poor digestion cause build-up of toxins into the body thus it is a root cause for the disease. Therefore, restoring digestion is the essential part of the body (Jiva Ayurveda). Vitiligo involves four steps. First step is Purification therapies (Shodhana Karma), which includes use of herbal decoction of Psoralea Corylifolia and Eurphorbi anerifolia. Second step includes Oil massage, in which oil is selected on the basis of disease state (roga) and Patient Examination (rogi Pariksa). Third step is exposure of lesions to the sun rays depending on the tolerance of the patient (Soorya padasanthapam). And fourth and last step is delivery of decoction (kwatha) made of Ficushispida (malayu), Pterocarpus marsupium (asana), Calllicarpa macrophylla (priyangu), Peusedanumgraveolens (satapuspa), Coleus vettiveroides (ambhasa), and alkaline extract of Buteamonosperma (palasaksara), along with an alcoholic preparation of jaggery (the preparation is called phanitha in Ayurveda)to the patient. The diet should be salt-free and should contain buttermilk during the treatment of decoction²³.

Topical psoralen photo chemotherapy:

Used for children 2 years old and older who have small number white spots in a few areas. Treatments are done under an artificial UVA light once or twice a week. Psorglen is applied to your depigmented patches about 30 minutes before exposing you to enough UVA light to turn the affected area pink. The doctor usually increases the dose of UVA light slowly over many weeks. Eventually, the pink areas fade and a more normal skin color appears.

Side effects:

Severe sunburn and blistering, too much repigmentation or darkening (hyperpigmentation) of the treated patches or the normal skin surrounding the vitiligo.

Oral psoralen photochemotherapy:

For people with extensive vitiligo (affecting more than 20 percent of the body) or for people who do not respond to topical PUVA therapy. Not recommended for children under 10 years of age because it increases the risk of damage to the eyes caused by conditions such as cataracts. You take a prescribed dose of psoralen by mouth about 2 hours before exposure to artificial UVA light or sunlight. Treatments are usually given 2 or 3 times a week, but never 2 days in a row. For patients who cannot go to a facility to receive PUVA therapy, the doctor may prescribe psoralen that can be used with natural sunlight exposure.

Side effects:

Sunburn, nausea and vomiting, abnormal hair growth, and hyperpigmentation, itching. May also increase the risk of skin cancer, Phenylalanine, P-amino benzoic acid (PABA), Cantharidin, a blister beetle secretion²⁴.

Topical steroid therapy:

The use of steroid creams may be helpful in returning the color to the white patches. Doctors often prescribe a mild topical corticosteroid cream for children under 10 years old and a stronger one for adults. Cream must be applied to the white patches on the skin for at least 3 months before seeing any results. Corticosteriod creams are the simplest and safest treatment for vitiligo, but are not as effective as psoralen photochemotherapy.

Side effects:

occur in areas where the skin is thin, such as on the face and armpits, or in the genital region. They can be minimized by using weaker formulations of steroid creams in these areas. Ex: Topical Calcineurin Inhibitors- ELIDEL.

Figure 5: Marketed product- Topical Calcineurin Inhibitors- ELIDEL

Physical treatment options for Vitiligo:

· Tattooing (micropigmentation)

· Autologous skin grafts

· Skin grafting using blisters

· Autologous melanocyte transplantation

· Combination of Sun and Sunscreen

Surgical Therapies:

Autologous skin grafts:

Used for people with small patches of vitiligo. The doctor removes sections of the normal, pigmented skin and places them on the depigmented areas. Infections may occur at the donor or recipient sites. The recipient and donor sites may develop scarring, a cobblestone appearance, or a spotty pigmentation, or may fail to cure the white spot area. Takes time and is very costly²⁵.

Skin grafts using blisters:

Doctor creates blisters on your pigmented skin by using heat, suction, or freezing or cold, the tops of the blisters are then cut out and transplanted to a depigmented skin area.

Side effects:

scarring and lack of repigmentation, less risk of scarring with this procedure than with other types of grafting.

Micropigmentation (tattooing):

Implanting pigment into the skin with a special surgical instrument. Works best for the lip area, particularly in people with dark skin. Difficult to match perfectly the color of the skin of the surrounding area. The tattooed area will not change in color when exposed to sun, while the surrounding normal skin will. Tattooing tends to fade over time, also tattooing of the lips may lead to episodes of blister outbreaks caused by the herpes simplex virus.

Autologous melanocyte transplants:

Takes a sample of your normal pigmented skin and places it in a laboratory dish containing a special cell-culture solution to grow melanocytes. When the melanocytes in the culture solution have multiplied, the doctor transplants them to your depigmented skin patches. Currently experimental and is impractical for the routine care of people with vitiligo. Very expensive and its side effects are not known.

Sunscreen:

Helps protect the skin from sunburn and long-term damage. Minimizes tanning, which makes the contrast between normal and depigmented skin less noticeable.

Cosmetics:

Some vitiligo patients cover depigmented patches with stains, makeup, or self-tanning lotions. Dermablend, Lydia O’Leary, Clinique, Fashion Flair, Vitadye, and Chromelin offer makeup or dyes that you may find helpful for covering up depigmented patches. Self tanning lotions have an advantage over makeup in that the color will last for several days and will not come off with washing²⁶.

Figure 6: Marketed product- Topical Corrective leg and body makeup SPF 18 Cover Blend

Vitiligo associated disorders. Laboratory investigations

Due to the relatively high prevalence of associated autoimmune disorders especially in non-segmental vitiligo, investigations need to be performed including full blood cell count, TSH, T3, fT4, serum thyroid autoantibodies (Anti-Tg, Anti-Tpo) and antinuclear antibodies. (ANA) for detecting anaemia, thyroid disorder and ANA-positive photosensitivity respectively²⁷. The Hashimoto’s thyroiditis is 2.5 times more frequent among children and adolescents with vitiligo than in a healthy age- and sex-matched population and it usually follows the onset of vitiligo while 16 % of patients with non-segmental vitiligo had thyroid alterations. Several studies indicate a strong relationship between a positive family history of vitiligo and autoimmune/endocrine abnormalities (Autoimmune polyendocrinopathy- candidiasis-ectodermal dystrophy (APECED), leukotrichia and earlier disease onset.This may be the result of a mutation in the AIRE gene²⁸.

CONCLUSION:

Vitiligo is associated autoimmune skin disease in which destruction of melanocyte by different means occurs. The above discussed treatments are available to treat this disorder. Vitiligo is not contagious. Psychologically devastating, several patients feel isolated and desolate by its impact on their relationships and private and skilled lives. Various treatments, together with topical creams and light-weight medical care, will facilitate some patients. Some problems are also there with the treatment so some solutions to those problems are also discussed in above article. But as discussed above due to slow effect and longer duration and also due to some additional symptoms patients get frustrated and discontinue the treatment. This is a major problem with this treatment. So to avoid such things or to resolve this problem patient counselling should be carried out in which patients can be explained about the treatment and they can be taught to keep patience during the treatment to get effective results.

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Received on 01.11.2018 Modified on 01.12.2018

Asian J. Research Chem. 2019; 12(2):120-125.

DOI: 10.5958/0974-4150.2019.00026.9