Vitiligo is a common skin disorder in which white spots appear on the skin usually occurring on both sides of the body in the same location. The disease has been around for thousands of years. Vitiligo occurs in 1-2% of the population. It affects both sexes, all races and all ages.

   Management of Vitiligo

Vitiligo is a relatively common pigmentary disorder (nearly 1-2% of population) of great socio-medical importance and one that has been observed since ancient times. Depigmentation of the skin, with loss of melanocytes on histology characterizes this disorder. It is defined as a circumscribed, acquired, idiopathic, progressive, hypomelanosis of skin and hair, often familial and characterised by total absence of melanocytes microscopically. This definition excludes post-inflammatory, chemically induced depigmentation, and those which are associated with melanoma secondary to various dermatoses and after burns.A range of clinical phenotypes lead to varying degrees of morbidity. The cause of vitiligo remains unknown, although an autoimmune pathogenesis seems most likely. Treatment also remains difficult. A number of new therapies show significant potential.                    

 

*HISTORICAL PERSPECTIVES

The term 'vitiligo' may have been derived from the Latin word 'Vitelius', meaning vale i.e. pale flesh of calf or another Latin word 'Vitium' meaning blemish.

The term vitiligo was first used by the Roman physician Celsus in the second century AD. It is interesting to note that the Rigved (1000 BC) called vitiligo as kilas, meaning a white spotted dear. The disease in known since time immemorial as its mention can be found in the ancient literature of Iran of 2200 BC in the period of Aushooryan "Tarkh-e-tibbl-e-Iran"

 Ebers Papyrus in 1550 BC mentioned about vitiligo

 In 1400 BC, the Indian classic Atherv ved mentioned about vitiligo as a variant of leprosy (shweta kusht)

 In the Buddhist sacred book "Vinay Pitah" (624-544 BC) this disease has been described as 'Kilas'.

In the Old Testament under the Hebrew word 'Zora' the white spots were decribed which, when translated from Greek meant Leprosy. However, vitiligo has nothing to do with leprosy and it is only a disorder of the pigment formation of the body. References to this disease are also found in the Bible

Vitiligo has also been referred to in the Quran10 (3:49, 5:113) as 'Bohak' and 'Baras'.

 

 

*CLINICAL MANIFESTATIONS

Vitiligo presents as sharply demarcated depigmented macules, that can appear anywhere on the skin. There is a predilection for orifices - eyes, nostrils, mouth, nipples, umbilicus, and genitalia. The natural history of the disorder is either that it spreads quite quickly (over months) and then is stable, or it relentlessly spreads over the body with time (over years). Sites of trauma (koebnerization), such as the elbows, may develop vitiligo. One percent of the population is affected by vitiligo. Twenty-three to twenty-six percent of these are children under the age of twelve. It is the most commonly acquired hypomelanosis. Vitiligo can be extremely disfiguring, leading to significant patient morbidity. A number of different studies have measured the quality of life for patients with vitiligo. Low self-esteem, poor body image and poor quality of life has been found in patients with vitiligo, including significant psychiatric morbidity (up to 25% in one study). The typical Vitiligo macules have a well defined light tan border and are chalky or snow white (trichrome Vitiligo), the fourth colour being the dark brown macules of repigmentation which are usually perifollicular (Quadrichrome Vitiligo) . Sometimes there may also be a hyperpigmented border or a red halo (Inflammatory Vitiligo). Segmental Vitiligo presents in dermatomal, multidermatomal, quasidermatomal forms which are arranged unilaterally. Most patients do not develop lesions elsewhere. Vitiligo of distant digits and the lips produces the lip-tip syndrome. Bilateral lesions may be symmetrical or asymmetrical. Palms and soles are commonly involved. Mucosal depigmentation, including gingiva, genitalia, lips and nipples, Leukotrichia -depigmented hair is common in Vitiligo patches. Classification Vitiligo is classified into focal, segmental, generalized and universal types, a conventional self-explanatory arrangement. However, Lerner 20 classified vitiligo into 3 groups namely:

a) segmental, localized, partial or focal vitiligo corresponding to a dermatome / adjacent dermatomes

b) vitiligo vulgaris generalized, involving the hands, face, axillae and limbs and

c) complete, total or universal vitiligo involving the entire or nearly entire body surface.

Aetiopathological Classification of Vitiligo

1 - Autoimmune Vitiligo or progressive Vitiligo, idiopathic Vitiligo

2 - Segmental or dermatomal Vitiligo

3 - Chemical or contact Vitiligo According to the patterns of distribution of lesions

(Dutta - 1988) , suggests the following three clinical types of Vitiligo.

1 Vitiligo vulgaris

2 Vitiligo Acro-orificialis

3 Vitiligo segmentalis ( Zosteriforms ) segmentalis

Table 5: Vitiligo: Suggested classification Segmental Vitiligo zosteriformis Macules distributed along a dermatome or a near dermatome or lines of body cleavage Non-segmental Vitiligo areata (localized, partial or focal)

Vitiligo acmfacialis Vitiligo vulgaris (generalized, universal)1591 Vitiligo mucosal 1 or 2 macules Macules affecting the face and tips of the hands and feet Generalize macules involving extensive body areas

An exclusive involvement of mucous membranes Childhood Vitiligo.The first study of childhood vitiligo was conducted by Halder et al. Previously, the observation had been made that vitiligo was an "acquired, sometimes familial depigmentary disorder of skin and hair" and that 50% of patients develop vitiligo before age 20. They concluded that childhood vitiligo is a distinct subset of vitiligo, with high incidence of segmental type, family history of autoimmune or endocrine disease, early or premature graying, increased autoantibodies, and poor response to topical PUVA.39 Interestingly, there has been a steady increase in the incidence of childhood vitiligo40 during the past 2 decades.

 

  

*DIAGNOSIS(LABORATORY EXAMINATION)

Skin biopsy with special staining for melanocytes is the only significant examination but usually is not necessary. Histology reveals the absence of melanocytes which appear to be replaced by Langherans' cells in the lesions. A lymphomonocytic infiltrate is sometimes present in the marginal areas. Differential diagnosis Wood's light examination should be part of the evaluation of every patient with vitiligo. It is most useful to differentiate the pure white appearance of the amelanotic vitiligo macules from the tan-white of grey-white colour of the relatively hypomelanotic disorders.

 The diagnosis of Vitiligo can normally readily be made on clinical examination of a patient with progressive, acquired chalk white macules in typical sites, with a hyperpigmented border. Few such conditions are patterned and symmetrical.

Wood's light examination accentuates the hypopigmented patches and is particularly useful for examining patients with light complexions. Generalized Vitiligo must be distinguished from piebaldism which is congenital, stable and spares the dorsal spine. Hyperpigmented macules are present in white patches and with a white furlock. Warden Gurg's syndrome and Woolf's syndrome include hearing, the former has characteristic eye features. Ziprkowski-Margolic syndrome is rare and occurs in males. It appears to be an X-linked recessive trait, characterized by deaf- mutism, heterochromic irides and piebald -like hypomelanosis of skin and hair. Segmental Vitiligo Naevus depigmentosus, tuberous sclerosis and incontinentia pigmenti achromians may require exclusion. Naevus depigmentosus is a rare, congenital, non-familial, stable quasidermatomal leukoderma. Unilateral macules are pale-white to tan colour with discrete, regular or serrated margins; most commonly present on trunk, lower abdomen, proximal extremities, but may involve the face and neck and are permanent. Rarely seizures and mental retardation are reported. Incontinentia pigmenti achromians is a bizarre, bilateral, irregularly shaped leukoderma of the trunk and extremities and usually manifests at birth. Lesions may be progressive or reverse before or after the age of one year. It is associated with eye, tooth, hair, musculoskeletal, neurologic and mental abnormalities. Disorders of keratinization and skin appendage malformations have also been observed. Depigmentation occurs later in incontinentia pigmenti and is an X-linked autosomal dominant trait. Tuberous Sclerosis Neurocutaneous syndrome is characterized by adenoma of sebaceum. Seizures and mental retardation are usually preceded by the appearance of white macules. Solitary Vitiligo Lesions Pityriasis versicolor usually affects the upper chest. Amelanotic fine scales with yellow fluorescence under Wood's Light, and a positive KOH confirms the diagnosis. Pityriasis alba is not amelanotic. Faint margins of white colour, erythema and slight scaling are diagnostic features. Idiopathic guttate hypomelanosis manifests as small, very sharp margins, usually on arms, legs or upper back. Post inflammatory hypomelanosis features white macules. There is a history of the characteristic lesions of psoriasis, eczema etc. in the same areas. Chemical leukoderma has a positive history of industrial exposure to phenolic compounds and germicides and it manifests as small white macules. Leprosy lesions are off-white in colour and are anaesthetic. Peripheral erythema may be seen in an endemic area. Lupus erythematosus lesions have atypical distribution. There is a positive immunofluorescence and serologic studies. Differential diagnosis of Vitiligo The hypopigmentation of Vitiligo must be differentiated from that of many other disorders of hypo-melanosis, e.g. oculocutaneous albinism, piebaldism, syphilis, Vogt-Koyanagi syndrome, severe ultraviolet and chemical burns (without scarring) contact with monobenzyl ether of hydroquinone, Addison's disease, hyperthyroidism, pernicious anaemia, leprosy, etc. Characteristic features of some disorders causing hypopigmentation or depigmentation to be differentiated from Vitiligo:

(i) Neavus anaemicus or achromicus: Birth marks are present from birth. On rubbing the lesions or affected areas, the surrounding normal skin will react by vasodilation and show erythema, while the affected area will not.

(ii) Leprosy (Leprotic leucoderma): Lesions of Vitiligo with incomplete loss of pigmentation may be mistaken for maculoanaesthetic leprosy, while leprous lesions with loss of pigmentation may at first sight be confused with Vitiligo.

Macules of indeterminate leprosy are transient and many either disappear or in the course of time, develop as tuberculoid or lepromatous leprosy. In such cases, macules, findings of bacteriological examination and lepromin test sensory impairment, vary from case to case. Lesions of maculo-anaesthetic leprosy are well defined, large and anaesthetic thermal sensations are impaired first, while pain sensations are lost last. In doubtful cases, sensations should be tested not with pins but with cotton wool and test tubes containing hot and cold water (Yawalkar S. J. and Punshi S. K.) Sometimes, a diagnostic aid to differentiate leprotic from non-leprotic leucoderma, "Nicotin acid" test is done (El Arini et al). Nicotinic acid, in a dose of 50 mg. injected intramuscularily is followed by intense marginal redness of the leprotic macules. This reaction is separate from the flush reaction known to be evoked by nicotinic acid, as it appears 30-45 seconds before the flush reaction occurs and persists for 11 minutes after it disappears. Tinea versicolor Lesions are scaly and microsporon can easily be demonstrated in the scrapping. Sensations in the lesions are normal.

 Phrynoderma Along with nutmeg-grater appearance of lesions, hypopigmented patches may be found on the knees and elbows.

 Pityriasis alba It is associated with atopic dermatitis - superficial scaly, ovoid itching lesions are formed on the face and extremities (Watkins).

 Achromia parasitica Slight depigmented lesions appear on the face and arms, mostly in children suffering from worm infestations.

In some cases, where the diagnosis is difficult, examination by Wood's light can be helpful. Under this light the pigmented epidermis is much less fluorescent that the non-pigmented epidermis. The normal skin gives a slight bluish fluorescence; the ephelides and pigmented patches appear black and the patches of Vitiligo appear milky white. Secondly, achromias take a greyish colour. Chemically Induced Leucoderma

(a) Occupation Leucoderma It includes depigmentation occurring on the hands of workers using rubber gloves containing monobenzyl ether of hydroquinone. It was first described by Liver E.A.

(b) Condom Leucoderma Predisposed persons using rubber condoms may get depigmented lesions on the glans of the penile shaft (Yawalkar S.J. and Punshi S.K. 1969) 27

(c) Nylon Leucoderma It has been described by Zawahry of Cairo (1956)

(d) Leucoderma Medicamentosa Prof K. Kitamura has reported leucoderma around the eyelids, with well defined hypopigmented lesions in cases being treated with eye lotion containing guanofuracin.

(e) Kumkum Leucoderma, Bindi Leucoderma, Brassiere Leucoderma, Purse Leucoderma, Watch Strap Leucoderma, Surgeons Gloves Leucoderma and Rubber Chappals Straps Leucoderma are commonly seen in day to day practice.

 

 

 

*ASSOCIATED CONDITIONS

with Vitiligo Premature graying of the hair, leukotrichia, halo nevus, lichen planus and alopecia areata are frequently reported associations.28-35 Of these, leukotrichia (poliois) is found in up to 45%, premature graying of the hair (canities) in 37%, followed by halo nevus in 35% and alopecia areata in up to 10% of cases.

1. Addison's Disease 2. Alopecia Areata 3. Diabetes Mellitus 4. Pernicious Anaemia 5. Thyroid Disease 6. Down's Syndrome 7. Halo Neavus (Sutton's Disease) 8. Melanoma 9. Psoriasis Course and Prognosis Vitiligo is a chronic disease process.

 

 

*THE COURSE

is highly variable but rapid onset followed by a period of stability or slow progress is most characteristic. Upto 30% may report some spontaneous repigmentation particularly in sun-exposed areas. Rapidly progressive or 'galloping' Vitiligo may lead to extensive depigmentation. Vitiligo zosteriformis / segmental, however, is the most stable form and may show a better prognosis.24,26Segmental Vitiligo is a special subset which usually develops precipitously in a region, which does not usually extend beyond quasidermatomal region, and is very stable once present. A few of the cases may once again start progressing at a rapid pace after a period of dormancy.Such an occurrence is not uncommon in nonsegmental vitiligo types namely vitiligo vulgaris, acrofacialis and areata. In addition, several other factors may assist in evaluating its prognosis

a) the younger the patient, the shorter the duration, the better is the prognosis,

b) the lesions located on the fleshy regions of the body may show better chance of recovery in contrast to that on bony / friction points and

c) the presence of leukotrichia or lesions on mucous membranes or mucocutaneous junctions may account for a poor prognosis.

Development or treatment of Vitiligo-associated disease appears to have no impact on the course of Vitiligo (and vice versa). The following factors available show poor prognosis;

1) Poor nutrition, digestion or use of broad spectrum antibiotics.

2) Presence of Vitiligo on resistant sites like hands, feet, front of wrists, elbows, waist, eyelids and lips.

3) Depigmentation of hair in vitileginous area.

4) Age above 45 years.

 

 

*INVESTIGATION FOR VITILIGO

a. Stool - Routine Examination

b. Hemogram

c. Urine - Routine Examination

d. Liver function tests

e. Investigations to pinpoint any endocrinal disorders.

f. Immunological studies with immuno-fluorescent Tests.

g. Skin scrapings, histopathology h.

Woods Lamp Examination Special Investigations

1. Histology

2. Electron microscopy

3. Immuno-fluorescence Melanocyte

The melanin pigments are formed within the specialised dendritic cells called melanocytes. They are present and resting:

(a) On the epidermal basal lamina at the dermo epidermal junction.

(b) Some are situated well within the basal layer.

( c) Also present in mucus membranes.

( d) Uveal Tract.

(e) Leptomeninges.  Squamous epithelium of nasal and oral cavities.

(g) In the hair follicles.

 

 

*EMBRYOLOGY

(1) The parent cells (Melanoblasts) originate from the embryonic neural crest and migrate into the epidermis during the 10th week of foetal life. Melanin pigmentation is under the influence of

a: Genetic factors

b: Hormonal factors

c: Ultraviolet radiation

d: Other factors

Factors influencing Melanogenesis in the Melanocytes

a: Not understood properly

b: Specific genes (Yet unidentified)

c: Gonadol, thyroid hormones, MSH, ACTH.

d: Vit. A, D, B.

e: Prostaglandins

f: Nutrition malnutrition

g: Some physical agents e.g. sunlight, artificial U V light rays, therapeutic agents.

h: Trace elements Copper, Zinc, etc.

 

Function of Melanocytes

1. Synthesis of pigment granules (Melanosomes)

2. Melanization of Melanosomes

3 Transfer of Melanosomes to adjacent keratinocytes

4. Maintenance of growth of dendrites.

Trace elements:

a. Zinc b. Iron c. Copper d. Manganese e. Nickel Trace elements play an important role in the process of Melanogenosis.

 

AGGRAVATING OR PRECIPITATING FACTORS in Vitiligo.

1. Pregnancy

2. Acute Severe illnessTyphoid, diabetes, hepatitis

3. Sudden Shock-Fall from height, accidents, death of near and dear ones.

Physical and Psychological trauma. Physical Trauma: Friction and pressure points like waistline in Indian women, tight wearing of sarees, bony prominences like knuckles, malleoli, chronic skin diseases, chemical irritation, burns and exposure to ionizing radiations .

 

Role of Genetic Predisposition There is no doubt that predisposition to Vitiligo is inherited.

a. The inheritance appears to be an autosomal dominant trait with variable penetrance

b. The patchiness of Vitiligo is probably due to activation of the mutant gene with indiscrete clones of cells which govern melonocyte behaviour at the site of pigment loss. Melanin Pigmentation Melanin is produced by melanocytes which appear at the eighth week of gestation in the foetus. These are specialized dendritic cells of neural crest origin except those which are found in the retinal pigment epithelium. Melanocytes are found in nearly every tissue but they are most common in the epidermis, hair follicles, dermis, eyes, around blood vessels, peripheral nerves and the sympathetic chain and are also present in the leptomeninges and the inner ear. It is estimated that the total epidermal melanocyte population in man is about 2x10' cells. There is a reduction in the number of cells with aging with a 6-8% decrease per decade. The melanosomes are formed in the melanocytes. They are transferred into the keralinocytes directly by phagocytosis of dendrites containing melanosomes of melanocyte. These are distributed throughout the epidermis by the outword movement of the keratinocytes and thus contribute to the colour among humans which are not due to quantitative differences in the number of melanocytes in the skin but apparently due to difference in the number of melanosomes, their size and distribution within the keratinocytes. For instance, the melanosomes in negroid skin are numerous,longer and wider than those in caucasoids. These differences are responsible for the negroid skin to be darker than the Caucasian skin. In man all the hues of skin colour are produced by melanin in the epidermis, haemoglobin in the veinules, and to a minor extent carotinoids. It is melanin that largely determines the tinctorial differences that exist in the hair and eyes of man. The pigment in human skin serves primarily as a barrier that shields the dermis from deleterious effects of solar radiation.