SKIN DISORDER VITILIGO & ITS MANAGEMENT

BY DR. NAND KISHOR DADHICH M.D. [AY.] Ph.D. ASSISTANT PROFESSOR S.K.D. GOVT. AYURVEDIC COLLEGE RAMPUR, MUZAFFARNAGAR (U.P.) 251001 E-mail : dadhichnand@yahoo.com Contact No. : +91-9557317321

CONTENTS
CHAPTER I STRUCTURE OF SKIN Introduction Development of skin Anatomical structure of skin Epidermis Dermis Hair follicles Nails SWEAT GLANDS Eccrine sweat glands Apocrine glands Sebaceous glands Composition of sebum Function of sebum Ceruminous glands Arrectores pilorum FUNCTIONS OF SKIN Circulation and vascular reactions Sensory functions Radiation Conductions Evaporation Vasodialation Decrease in heat production Increase in heat production Synthesis of Vitamin D Sweat secretion Thermoregulation Skin as a immunologic organ Protection COLOR OF THE SKIN Introduction Pigmentation in the human skin Melanin Melanoid Carotene Haemoglobin Oxyhaemoglobin THE MELANOCYTE Derivation of the word melanin Historical aspects of melanin Embryology of melanin Epidermal melanin unit Distribution of melanocytes 1-8

CHAPTER II

9-12

CHAPTER III

13-17

CHAPTER IV

18-20

CHAPTER V

21-31

CHAPTER VI

CHAPTER VII

CHAPTER VIII

CHAPTER IX

CHAPTER X

Ultra structure of melanocytes Classification of melanin pigments Pigment Production Inhibitors of melanin synthesis Importance of melanin pigmentations BIOCHEMISTRY OF MELANIN PIGMENTATION Stages of Melanocytes Development Stages of Menanin Formation Dopaquinon Production Melanogenesis Biochemistry of Important Specialized Product from Tyrosine Melanin Catecholamine CLINICAL APPLICATION OF MELANIN Clinical applications of melanin Albinism Hypertyrosinemias Applied physiology of skin pigment VITILIGO Introduction Historical aspect and vitiligo Synonyms Derivation Definitions Epidemiology Actiology Associated Aetiological factors CLINICAL MANIFESTATIONS OF VITILIGO Distribution of vitiligo patches Koebners Phenomenon Onset of the Disease Border of the patches Trichome Sensation and blood vessels in vitiligenous skin Location of patches Punshi sign Sweat reaction in Vitiligo Reaction to sunlight Rate of the Pigment Loss Nature of Development of disease Common Pattern of Vitiligo Psychological Symptoms Others DIFFERENTIAL DIAGNOSIS OF VITILIGO Differential diagnosis Associated factors

32-41

42-46

47-55

56-59

60-65

CHAPTER XI

MANAGEMENT OF VITILIGO General awareness Non surgical methods Surgical methods Psychological and social counseling CHAPTER XII AYURVEDIC MANAGEMENT OF SHWITRA (VITILIGO) Principal of Ayurvedic management Divavyapashraya Chikitsa (spiritual therapy) Yuktivyapashraya chikitsa (Rational therapy) Antaha parimarjana chikitsa (Internal purification) Bahi parimarjana chikitsa (External purification) Shastrapranidhana (Surgical measures) Satvavajaya Chikitsa (Psychotherapy) CHAPTER AYURVEDIC MEDICINES OF VITILIGO XIII Single Drugs Chruna (Powder) Preparations Kwatha (Decotion Preparation ) Asava /Arishta Preparations Avaleha (Paste) Preparations Ghrita Preparations Taila Preparations Guggulu Preparations Peya Preparations Guda (Jaggery) Preparations Urines (Mutras) Saktu Preparations Loha Preparations Rasayana Preparations Rasa / Bhasma / Pisti (Metalic Preparations) Vati (Tablets) Preparations Lepa Preparations (Ointments) Or Topical Applications Abhyanga Preparations CHAPTER EXAMINATION OF SKIN AND ITS XIV APPENDAGES CHAPTER XV APPENDIX ABBREVIATIONS BIBLIOGRAPHY AND REFERENCES

66-86

87-93

94-105

106-113 114-125

CHAPTER 1
STRUCTURE OF SKIN
Introduction Development of Skin Anatomical Structure of Skin Epidermis Dermis Hair Follicles Nails

INTRODUCTION : Skin is the largest organ of the integumeutory system made up of multiple layers of epithelial tissues that guard underlying muscles and organs. It is important role in protecting the body against pathogens. The skin being sensitive to pain, pressure, touch, hot, cold, trauma is indeed a unique sense organ more then it skin is the protective boundary between the organism and the environment. According to clinical practice dermatological problems account and about 12% of total medical problems. Among skin disorders, disorders of pigmentation cover a big spectrum. They not only interfere with the normal skin functioning but also hamper the internal environment of the body ever. In pigmentary disorder, disorders related to the hypopigmentation needs attention, where a long with soma, psyche is involved much more. It is important to know about skin i.e. affected part by the disease. Skin can be examined by naked eye and can furnish a lot of information about the person and the disease. In certain cases the changes are not clear. Hence, the study of the skin structure and its physiology is essential for proper assessment.

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DEVELOPMENT OF SKIN : The skin or cutaneous membrane covers the external surface of the body. It is the largest organ of the body in surface area and weight. The weight of the skin about 8% of the body weight and its 4.8 kg in an average man and about 3.2 kg in an average woman. The eight of the subcutaneous fat is about 12 kg in an average man and 15 kg is an average woman. The area of the skin of an average adult is 2784.4 sq. inches. To this ends it has become highly specialized and some knowledge of its normal state and behavior is necessary before its abnormalities can be adequately studies. The epidermis and its specialized appendages are derivatives of the ectoderm, while the corneum is formed from the somatic layer of the mesoderm with some contribution from dorsal lateral aspects of the mesodermal somites. The ectoderm at first consists of a single stratum of cuboidal cells but by the sixth week these have proliferated to form a double layer - a superficial periderm or epitrichium of flattened cells, and a subjacent stratum germinativum. By the six month most of the periderm, which becomes keratinized, has disappeared and the strata granulosum, lucidumand corneum of the epidermis are established. The superficial cornified cells, together with sebaceous secretion and the remains of periderm, from a chessy or caseous material, the vernix caseosa, which may exercise the function of protecting the underlying epidermis from maceration by amniotic fluid. Formation of daughter cells by the deeper layer leads eventually to the production of the definitive epidermis of the skin. Towards the end of the third month the mesoderm next to the epidermis begins to condense and define the dermis, deep to which areolar connective tissue appears. A month later dermal papillae can be identified and the characteristic patterns of ridges on the ventral hairless skin of the extremities best seen and most familiar as fingerprints are quickly established and remain substantially unchanged in the individual apart from growth in size.

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Structure of Skin ANATOMICAL STRUCTURE OF SKIN: It is divided anatomically into two layers, the epidermis and the dermis. The superficial thinner portion, which is composed of epithelial tissue in the Epidermis and the deeper, thicker connective tissue part, is the Dermis. The glands, hair and nails are epidermal structures, although they arise in the dermis. EPIDERMIS: The epidermis is the most superficial layer of the skin and it is composed of stratified epithelium which varies in thickness in different part of the body. It is thickest on palms of the hands and soles of the feet. There are no blood vessels or nerve endings in the epidermis but its deeper layers are bathed in interstitial fluid which is drained away as lymph. Epidermis it is formed by Stratified epithelium, which consist of 5 layers.
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1. 2. 3. 4. 5.

Stratum corneum Stratum lucidum Stratum granulosum Stratum spinosum Stratus germinativum

1.

STRATUM CORNEUM : It is also known as horny layer. It is the outermost layer. The cell on the surface are flat, thin, non nucleated, dead cells in which the protoplasm has been replaced by Keratin.

2.

STRATUM LUCIDUM : Lucid means clear. It is made up of flattened epithelial cells. Many cells have degenerated nucleus and in some cells the nucleus is absent. As these cells exhibit shiny character the layer looks like a homogenous translucent zone.

3.

STRATUM GRANULOSUM : It is a thin layer with 3-5 rows of flattered Kertinocytes. In which organelles are beginning to degenerate cells, contain the protein keratohyalin, which converts tonofilaments into keratin and lamellar granules, which release lipid rich water repellent secretion.

4.

STRATUM SPINOSUM : It is also known as prickle cell layer because the cells of this layer possess some spine like protoplasmic projections. By these

projections, the cells are connected to one another. 5. STRATUM GERMINATIVUM : It is the deepest layer. It is a thick layer made up of polygonal cells superficially and columnar or cuboidal epithelial cells in the deeper parts. Stem cells undergo cell division to produce new keratinocystes. Another type of cell called melanocytes are scattered between the keratinocytes. The melanocytes produce the pigment called melanin. The color of the skin depends upon melanin. Langerhan cells and merkel cells associated with tactile discs are scattered among the keratinocytes.

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SUMMARY

S.No. 1

Stratum Basale or Germinativam

Description Deepest layer, composed of single row of cubiodal or columnar keratinocytes that contain scaltered filaments); tonofilaments stem cells

(intermediate

undergo cell division to produce new keratinocystesl melanocytes, langerhan cells and merkel cells associated with tactile discs are scattered among the keratinocytes. 2 Spinosum 8-10 rows of many sided keratinocytes with bundles of tonofilaments; includes projections of melanocytes and

langerhans cells. 3 Granulosum 3-5 row of flattered keratinocytes, in which organelles are beginning to

degenerate cells; contain the protein keratohyalin, which converts

tonofilaments into keratin, and lamellar granules, which release lipid rich water repellent secreation. 4 Lucidum Present only in skin of fingertips, palms and soles; consists of 3-5 of clear, flat dead keratinocytes with large amount of keratin. 5 Corneum Twenty five to thirty (25-30) rows of dead, flat keratinocytes that contain mostly keratin. These cells are

continuously shed and replaced by cells from the deeper strata.

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DERMIS: Dermis is the inner layer of the skin. It is the second, deeper part of the skin. The dermis is composed mainly of connective tissue layer made up of dense and stout collagen fibers, fibroblast and histiocytes. The collagen fibers exhibit elastic property and are capable of storing or holding water. The collagen fibers contain the enzyme collagenase. The structures in the dermis are1. BLOOD VESSELS: Arterioles form a line network with capillary branches supplying sweat glands. Sebaceous glands, hairfollicles and the dermis. The epidermis has no blood supply. It obtains nutrition and oxygen from interstitial fluid derived from blood vessels in the papillae of the dermis. 2. LYMPHS VESSELS: These form a network throughout the dermis and the deeper layer of the epidermis. 3. SENSORY NERVE ENDINGS: Nerve ending which are sensitive to touch, change in temperature, pressure and pain are widely distributed in the dermis. The skin is an important sensory organ through which individuals are aware of their environment. Nerve impulses that originate in the nerve endings in the dermis are conveyed to the spinal cord by sensory somatic cutaneous nerves, then to the sensory area of the cerebrum where t he sensations are perceived.

HAIR FOLLICLES:

Hairs of pilli are present on most skin surfaces except the palms, palmer, surface of the fingers, soles and planter surfaces of the feet. In adults hair usually is most heavily distributed across the scalp in the eye brows, axillae and around the external genetalia. Hair follicles consist of a down growth of epidermal cells into the dermis or subcutanecus tissue. At the base of the follicle there is a cluster of cells called the bulb. The hair is formed by th e multiplication of cell of the bulb and as they are pushed upwards, away from their source of nutrition. The cells die and are converted to keratin. The part of the hair above the skin is the shaft and the remainder, the root . Each hair is composed of columns of dead, keratinized cells bounded together by extra
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cellular proteins. The shaft is the superficial portion of the hair, most of which projects from the surface of the skin. The root is the portion of the hair deep to the shafts that penetrates into the dermis and sometimes into subcutaneous layer.

The shaft and the root both consist of three concentric layers. The inner medulla is composed of two or three rows of irregularly shaped cells containing pigments granules and air spaces. The middle cortex consists of elongated cells that contain pigments granules in dark hair but mostly in gray or white hair.

The cuticle of the hair, the outermost layers, consist of a single layer cuticle of the hair are nucleated. In upper part of the root and in the shaft they are scale like and lack nuclei cuticles cells on the shaft are arranged like shingles on the side of the house.

Surrounding the root of the hair is the hair follicle, which is made up an ext. root sheath and an internal root sheath, the ext. root sheath is a downward, continuation of the epidermal layer. At the base of the hair follicle, the ext. root sheath contain only the stratum basale. The Inter root sheath is produced by the matrix and forms a cellular tubular sheath of epithelium between the external root sheath and the hair.

The color of hair due to primarily to the amount and type of melanin in its keratinized cells. Melanin is synthesized by the melanocytes scattered in the matriz of the bulb and passes into cells of the bulb and passes into cells of the cortex and medulla.

Dark color hair contains mostly true melanin, where as blond and red hair contain variants of melanin in which there is iron and more sulphur.

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NAILS:

Nails are plates of tightly packed, hard, keratinized epidermal cells. The nails develop from the epidermis. They begin to grow at the third month of intrauterine life. Continuous to grow throughout the life, although the rates of growth slow down at old age. The finger nails grow at the rate of 0.1 mm per day. Taking about five month to be restored after removal.

The keratinized epidermal cells from a clear solid covering over the dorsal surface of the distal portion of the digits. Each nail consist of a nail body. A free edge and a nail root. The nail body is the portion of the nail that is visible. The free edge is the part that may extend past the distal end of the didit and the nail root in the portion that is buried in a fold of a skin.

Most of nail body appears pink because of the blood following through underlying capillaries. The nails are horny translucent plates of approximately rectangular shape lying on the extensor surface of the distal segment of each digit. The thickness of mature nails varies from 0.5 to 0.75 mm. The nail includes three major regions. The proximal root, the exposed body of nail and the free distal border. The root is inserted in a deep, curved cleft about 5 mm long with an overlaying proximal nail fold whose stratum cornium is prolonged distally on the body of the nail as the thin cuticle or aponychium.

The aponnychium or cuticle is a narrow band of epidermis that extends from and adheres to the margin Lateral boider of the nail wall. It occupied the proximal border of the nail and consists of stratum corneum. The epithelium deep to the nail root is the nail matix where cell divide by mitosis to produce growth.

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CHAPTER 2
SWEET GLANDS
Eccrine Sweat Glands Apocrine Glands Sebaceous Glands Composition of Sebum Function of Sebum Ceruminous Glands Arrectores Pilorum

SWEAT GLANDS: These are found widely distributed throughout the skin and are most numerous in the palms of the hand, soles of the feet, axillae and groins. There are 3 4 million sweat glands. The cells of sweat glands release their secretion by exocytosis and empty them into hair follicles or into the skin surface through pores. They are divided into two main types Eccrine and Apocrine, based on their structure, location and type of the secreations. ECCRINE SWEAT GLAND there are simple, coited lobular gland and are much more common than the apocrine sweat gland. There are many eccrine gland over thick skin. They are distributed throughout the body, except the margin of the lips, nail leads, glans penis, glans clitoris, labia minora and eardrums. These are numerous in the skin of the forehead, palms, and soles. The secretory portion of the eccrine gland is located mostly in the deep dermis. A duct portion which passes though dermis and epidermis. The eccrine sweat gland opens out through the sweat pore. They are composed of epithelial cells. The bodies of the glands lie coiled in the subcutaneous tissue. Some ducts open on to the skin surface at tiny depressions or pores and other open into hair follicles.

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Glands opening into hair follicles do not become active until puberty. In the axilla they secrete an odourless milky fluid which, if decomposed by surface microbes, causes an unpleasant odour. The function of this secretion is unknown. These glands secrete a clear watery sweat. The secretion increases during increase in temperature and emotional conditions. The sweat produced by eccrine sweat gland (about 600 ml/day) consists of water, sodium chloride, urea, uric acid, ammonia, amino acids, glucose and lactic acid. The main functions of eccrine glands is to help regulate body temperature through evaporation and also play a small role in eliminating waste such as urea, uric acid and ammonia. Eccrine glands are under nervous control and nerve supplied by sympathetic cholinergic fibres, which secrete acetylcholine. Stimulation of these nerves causes secretion of sweat. APOCRINE SWEAT GLANDS are also simple. Coiled tubular glands they are situated only in certain area of the body likea. b. c. d. Axilla Groin areolae of the breasts Pubis Umbillicus

And bearded regions of the face in adult male and release their secreations through exocytosis manner. The secretory portion of these sweat glands is located mostly in the subcutaneous layer. The coiled portion lies in deep dermis but the duct opens into the hair follicle above the opening of sebaceous gland. These glands are nonfunctional till puberty and start functioning only at the time of puberty. The secretion of the apocrine gland is thick and milky at the time of secretion. It is odorless. When micro organism grows in this secretion a characteristic odor develops in the regions where apocrine glands are present.

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Apocrine sweat glands are stimulated during emotional conditions, emotional stress and sexual excitement. These secreations are commonly known as cold sweat their onset of function at puberty. These glands do not play any role in temperature regulation. These are innervated by sympathetic a drenergic nerve fibers. But the secretory activity is not under nervous control. SEBACEOUS GLANDS : These glands are simple or branched alveolar glands situated in dermis. These glands are ovoid or spherical in shape and these are situated at the side of the hair follicle. These glands develop from hair follicles. These consist of secretory epithelial cells derived from the same tissue as the hair follicles. They pour their secretion sebum into the hair follicles so they are present in skin of all parts of the body except the palms of the hands and the soles of the feet. They are most numerous in the skin of the scalp, face, axillae and groins. In regions of transition from one type of superficial epithelium to another, such as lips, eyelids, nipple, labia minora and glans penis, there are sebaceous glands that are independent of hair follicles secreting sebum directly on the surface. COMPOSITION OF SEBUM: Sebaceous glands secrete an oily substance called sebum, which is a mixture of1. 2. 3. 4. 5. 6. 7. 8. Triglyceride Cholesterol Proteins Squalene Sterols Paraffin Waxes Inorganic salts

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FUNCTIONS OF SEBUM : 1. Sebum coats the surface the hair and help keep them from drying and becoming brittle. It keeps the skin smooth and oily. It protects the skin from unnecessary desquamation and injury caused by dryness. 2. Free fatty acid content of the sebum has antibacterial and antifungal actions. Thus it prevents the infection of skin by bacteria or fungi. 3. The lipid of the sebum prevents heat loss from the body. It is also useful in cold climate. CERUMINOUS GLANDS: Modified sweat glands in the external ear, called ceruminous glands, produce waxy secretion. The secretory portions of ceruminous glands lie in the subcutaneous layer, deep to sebaceous glands. Their excretory duct opens either directly on the surface ducts of sebaceous glands. The combined secretion of the ceruminous and sebaceous glands is called cerumen or ear wax, provides a sticky barrier that impedes the entrance of foreign bodies. ARRECTORES PILORUM: These are little bundles of involuntary muscles fibres attached to the hair follicles contraction makes the hair stand erect and raises the skin around the hair, causing gooseflesh. The muscles are stimulated by sympathetic nerve fibers in response to fear and cold. Although each muscle is very small the contraction of a large number generates an appreciable amount of heat, especially when accompanied by shivering i.e. involuntary contraction of skeletal muscles.

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CHAPTER 3
FUNCTIONS OF SKIN
Circulation & Vascular Reactions Sensory Functions Radiation Conductions Evaporation Vasodialation Decrease In Heat Production Increase In Heat Production Synthesis of Vitamin D Sweat Secretion Thermoregulation Skin as a Immunologic Organ Protection

CIRCULATION AND VASCULAR REACTIONS: The cutaneous vascular system is extremely complex and contributes significantly to the general circular and vascular reactions. Direct visualization of flow in minute vessels can be carried out by observing the capillary circulation of the base of the nail. The color of the skin, which is related to melanin and carotene pigments is also dependent upon the quantity of blood in the subpapillary plexus of vessels, particularly in the Caucasian. Arteriovenous anastomoses of digital skin play an important role in temperature regulation and are implicated in the formation of the glomus tumor. SENSORY FUNCTIONS: Skin is largest sense organ in the body. It has many nerve endings, which form the specialized cutaneous receptors. Sensory functions pertain to the modalities of pain, itching, touch, presser, temperature. Skin consists of a mosaic of multiple sensitive spots, the relative density of which varies with the region of body. Cold sensitivity is probably mediated by krauses end bulbs, whereas ruffinis ending are probably receptors for warmth. Meissners
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corpuscles and markets discs are implicated in the tactile sensation and the pacinial corpuscles are involved in the sensation of pressure. Pain is mediated by free nonmyelinated endings, which are in a plexiform arrangement. Following injury to the skin, there is a wide spread area of hyperalgesia that radiates from the point of injury. A striking condition of increased pain and sensitivity accompanied by cutaneous vasodilation may occur after nerve injury. RADIATION : Loss of heat of radiation means loss in the form of infrared that rays in type of EM waves. Most infrared heat rays that radiate from the body have wave length of 5-20 micrometers. The human body radiate heat in all direction. If body temperature is greater than temperature of surroundings, a greater quantity of heat is radiated from the body than is radiated to the body. CONDUCTION: Only minute quantities of heat, about 3% normally lost from the body by direct conduction from the surface of the body to solid objects, such as chair or a bed. Loss of heat represents a sizable proportion of the body heat loss about 15% even under normal conditions. EVAPORATION: When water evaporate from the body surface 0.58 calorie of heat is lost for each gram of water that evaporates even when a person is not sweating, water still about 450 to 600 ml/day. This causes continual heat loss at the rate of 12-16 calories per hour. VASODIALATION: In almost all areas of the body, the skin blood vessels become intensely dilated. This is caused by inhibition of the sympathetic centres in the posterior hypothalamus that cause vasoconstriction.

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Full vasodialation can increase the rate of heat transfer to the skin as much as eight fold. DECREASE IN HEAT PRODUCTION: The mechanisms that causes excess heat production, such as shivering and chemical theromogenis are strongly it inhibited. INCREASE IN THE HEAT PRODUCTION: Heat production by metabolic, system is increased by promoting shivering sympthatic excitation of heat production and thyroxine secretion. SYNTHESIS OF VITAMIN D: Vitamin D has a potent effect to increase calcium absorption from the intestinal tract, It also has important effects on both bone deposition and bone absorption. Synthesis of Vitamin D require activation of precursor molecule in the skin, by UV rays in sunlight. Cholecalciferol (Vita-D3) is formed in the skin as a result of irradiation of 7-dehydro-cholesterol a substance normally in the skin, by ultraviolet rays from the sun. Consequently appropriate exposure to the sun prevents vitamin D deficiency. Further cholecalciferol is converted to 25 hydroxycholecalciferol into 1, 25 dihydrocholecalciferol in the proximal tubules of the kidneys controlled by parathyroid normone this latter substance is by far the most active form of vita D. SWEAT SECRETION: The skin contains two types of a sweat glands, eccring glands, which are small gnalds, and apocrine or large sweat glands. The eccrine glands are distributed all over the body and are the true secoretory glands that produce clear, aqueous sweat responsible for heat regulation. The apocrie glands in the human being are almost rudimentary structures.

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Nitrogen compounds are also lost transdermally, and the concentration of urea in sweat is twice as high as that in the blood. Creatinine is present in sweat in only a minute amount, and amino acids have also been noted. Ammonia is a primary constituent of sweat, and it can be concentrated by the sweat gland with nearly the same efficiency as the renal excreting unit. Large amount of lactic acid and lactate have been demonstrated in sweat particularly during heavy muscular exercise and in association with thermogenic sweat. THERMOREGULATION: The skin play an important role in the regulation of body temperature. Heat is lost though the skin under process of radiation convection, conduction and evaporation. Sweating is a useful process only when the sweat can evaporate. It is therefore very efficient as a regulatory mechanism in a dry, hot environment but with increased humidity the efficiency decreases markedly. Humidity begins to be of importance between 30 and 310C (86 to 880F) air temperature, at which point the difference between 50 and 100 percent relative humidity decides whether the persons will be comfortable or hyperthemic. If heat production is raised or atmospheric temperature is raised, there is a shift to blood flow from the interior to the skin. The converse is also true and this process is carried out reflexly. SKIN AS AN IMMUNOLOGIC ORGAN: Another important function of the skin is that of an immunologic organ. Since harmful substances or infectious organism are likely to encounter the skin as the host first. It is reasonable to expect the skin to initiate are immune response. The Langerhans cells, keratinocytes, lymphocytes and even melanocytes make up the skin associated lymphoid tissues (salt) are critical in antigen recognition and immune surveillance. PROTECTION:

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Skin is a barrier, against harmful bacteria or chemicals. The skin harbors many bacteria which are beneficial to the body as they destroy many harmful bacteria of the environment. Ultraviolet (UV) rays of the sun are absorbed by the melanin and melanin pigment provides some protection against the damaging effect of UV light. UV exposure can cause UV rays injury which includes skin cancer, notably basal cell carcinoma (Previously called rodent ulcer). In person who are white and live under hot sun in a smoke free environment. Skin cancers are common (seen in Australia) But in the black south African hardly develop basal cell carcinoma or rodent ulcer. The acidic pH of perspiration retards the growth of some microbes. The oily sebum from the sebaceous glands also protect the skin and hairs from drying out and contain bactericidal chemicals that kill surface bacteria. Water balance Stratum corneum is impermeable to water that is water cannot pass in or out through stratum corneum. Two types of cells carryout protective functions that are immunological in nature. Epidermal langerhans cells alert. The immune system to the presence of potentially harmful microbial invaders by recognizing and processing them and microphages in the dermis phagocytic bacteria and virusis that manage to penetrate the skin surface.

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CHAPTER 4
COLOR OF THE SKIN
Introduction Pigmentation in the human skin Melanin Melanoid Carotene Haemoglobin Oxyhaemoglobin

INTRODUCTION:

The pigment carotene, heamoglobin and melanin are responsible for color in skin. Melanin is produced by melanocytes and is transferred to the surrounding epidermal keratinocytes.

Two types of melanin pigmentation occur in humans. The first is constitutive that is genetically determined melanin pigmentation in the absence of sun exposure and other influence.

The next is facultative which results from sun exposure. Other factor like endocrine influence, pregnancy, nutritution status and some autoimmune disorders also influence the skin color.

PIGMENTATION IN THE HUMAN SKIN:

The skin of human beings is variously coloured with remarkable individual variations occurring even within members of the same race. The fine color of the skin is determined by the presence of at least five pigments at various levels and places in the integument.

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These are :

1. 2. 3. 4. 5.

Melanin Melanoid Carotene Hemoglobin Oxyhaemoglobin

MELANIN: Primary determinant of variability in human skin color is the amount density and distribution of the pigment melanin. It has a dark brown and black color.

MELANOID: A substance, similar to melanin, present diffusely throughout the epidermis.

CAROTENE: The least common skin pigment result in yellowing of skin. Yellow to orange, in the stratum corneum and the adipose cells of the dermis and superficial fascia, results preliminary from over consumption of carotene containing foods like carrots.

HAEMOGLOBIN: It is a complex molecule responsible for transport of oxygen throughout our bodies. Oxygenated haemoglobin has a reddish blue, produce a pinkish tint to lightly pigment skin. Deoxygenated haemoglobin has a purplish color, produce a bluish tint to lightly pigmented skin that in characteristic of oxygen deprivation and suffocation.

OXYHAEMOGLOBIN: Contained in the vascular supply of the skin particularly the superficial venous plexuses. Oxyhaemoglobin gives reddish blue to the skin can be well seen in high altitude and also in areas where arterial supply is rich i.e. face, neck, palm and nipples. Reduced haemoglobin gives bluish tinge to the skin.
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The amount of the first of three pigments, vary topographically throughout the body, chronologically with the age of the individual and genetically between individuals. Their relative contributions determine the characteristic racial pigmentation. Although considerable genetically determined differences may occur within a single ethnic group.

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CHAPTER 5
THE MELANOCYTE
Derivation of the word melanin Historical aspects of melanin Embryology of melanin Epidermal melanin unit Distribution of melanocytes Ultra structure of melanocytes Classification of melanin pigments Pigment Production Inhibitors of melanin synthesis Importance of melanin pigmentations

Melanocytes are pigment producing cells derived from the neural crest. These specialized exocrine cells produce melanin.

The number of melanocytes per surface area in any part of the body is roughly the same within and between races and the blondest Europeans may have as many melanocytes as the darkest negros. This means that the quality rather than the quantity of these cells determines the intensity of pigmentation in the skin. When on exposure to sunlight the skin becomes tanned. The resident melanocytes have not increased in number only but their activity has also increased.

DERIVATION OF THE WORD MELANIN:

Melanin has derived its name from the Greek word melas, meaning black. The melanin is responsible for the normal colour of the skin. It is a dark brown pigment.

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HISTORICAL ASPECTS OF MELANIN:

The term melanin was first used to described a set of pigments ranging from yellow to black by Robin in 1873.

Melanin are found both in plant and animal kingdom and the oxidizing enzymes which from the intermediate products are also very wide spread.

ACCORDING TO BARNES, R.B, 1963:

The functions of melanin pigmentation in mammals is less clear, but in hairy mammals it is probably that it is largely concerned with camouflage and with sexual display and other suggestion is that pigmentation is important in temperature regulation. But infrared photography has shown that this radiation is of little importance, because the heat emission from body is not significantly affected by the degree of pigmentation.

ACCORDING TO MITCHELL, R.E., 1963, 1967:

It seems nevertheless that pigmentation of epithelium has some evolutionary advantage in hairless primates, since their lack of hair protection of skin against solar radiation render them more liable to solar radiation injury.

ACCORDING A.S.:

TO

DUCHON. J. FITZPATRIC, T.B.

AND

SEIJI M

AND

BREATHMACH

The melanin is responsible for the normal color of the skin it is a dark brown pigment. Chemically a protein like polymer of the amino acid tyrosin and possibly of related catecholamine also.

It is found in skin, hair, feathers, scales and some internal membranes. It is also in peritoneum of many animals (ex. Frog) but its role there is not
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understood. Formed as an end product during metabolism of the amino acid tyrosin and related compounds, melanin and conspicuous in dark skin moles of man, in black dermal melanocytes of most dark skinned peoples, as brown, diffuse sports in the epidermis, and in black tumorous growths of many vertebrates such as melanomas in man, fishes and reptiles.

EMBRYOLOGY OF MELANIN: ACCORDING TO BOYD.J.D., 1960 : Melanocytes arise from the neural crest. This is a region of embryonic ectoderm that originates from the margin of the neural plate. Sagebiel have shown the presence of melanocyte in the epidermis by the 8 th week of gestation and that by 10th week, these cell contain melanosome showing early melanization then later on metanocyte in the skin continue to reproduce them by cell division.

Rodahl 1978 shows that this mitosis was stimulated by ultraviolet radiation. The mitotic index of the melanocyte is quite lower than keratinocytes.

Okum and Coworker studied morphological, enzymatic and histological correlationship between mast cell and melanocytes.

According to Hunter JAA opines that langerhance cell might related to melanocytes.

EPIDERMAL MELANIN UNIT: Melanin pigmentations in the skin also depend upon the distribution and transfer of pigmented granules to surrounding epidermal keratinocytes. Each melanocyte in epidermis is surrounded by few keratinocyte, which is functionally known as "Epidermal Melanin Unit" (Fitzparid 1967), likewise the nephrons of the kidney. The concept of epidermal melanin unit is structural
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and functional. Frenk E 1969 says this active unit is vary in number of different region of human body but the number of keratinocytes served by melanocytes is constant. A single metanocyte supplied melanosome to a group of keratinocytes. According to Hadly, in the animal like frog, this unit can produce melanin as well as it also rearranges melanin, so that they can adopt skin colour as per the background. Three different mechanisms may be involved in the control of the colour changes, that are individual, humoral and nervous, third mechanism said that the activity of the pigment cell might be under humoral control (Montaga W. & Hu.F. Advance in biology of skin voll VIII, Oxford Pergamon, 1967). Pituitary hormones cause expansion of melanophores or promote the formation of melanin in epidermis.

DISTRIBUTION OF MELANOCYTES:

Melanocytes are most commonly founds in epidermis and less frequently in hair bulb, eyes, around blood vessels, peripheral nerves, sympathetic chain and lining of coelomic cavity, leptomenenges and inner ear.

Some important facts related to distribution of metanocytes is given below-

1. 2. 3. 4. 5.

Total epidermal melanocyte population is about 2x109 cells. The melanocyte mass forms a tissue 1.0 x 1.5 cm 3. The population density is high on face 2900 mm2. Melanocyte density decreases by 6-8% per decade. The number of melanocyte is about two fold higher in exposed skin.

ULTRA STRUCTURE OF MELANOCYTE: Melanocytes are dendritic cell in the basal layer of the skin. They behave as a unicellular glands producing melanosome which are transferred to

surrounding epidermal keratinocyte, a cytocrine activity. These are known as secretory variety. Non secretary melanocytes are melanophore. Studies have shown that melanocytes are rather inactive and non mobile and become
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dendritic in relation to keratinocyte. The tip of the dendrite of the melanosome becomes embedded in the cytoplasm of the keratinocyte. Melanosomes are packaged according to the size, the larger ones as single unit and the smaller unit as complex of two or more. The action of melanocyte transfers to keratinocyte is like phagocyte.

Structure of Melanocyte

The characteristic feature of cell is the presence of special cytoplasmic organells, the melanosome, on which melanin is formed by the action of the enzyme tyrosinase. On electron microscopy, the malanocyte is readily distinguishable from the keratinocyte by the lack of desmosomes and tonofibrils and by more lucent cytoplasm. Melanosomes are the site of melanogenesis and shown tyrosinase activity. The developing melanosome shows varying degree of electron density, the more fully melanised being very dense melanocyte are fine, cytoplasmic filaments about 100 nm in diameter.

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CLASSIFICATION OF MELANIN PIGMENTS: Melanin is a dark brown pigment of skin and hair in animals particularly in vertebrates, derived from amino acid tyrosine. Melanin pigments can be categorised as 1. 2. 3. Eumelanin Pheomelanin Neuromelanin

1. EUMELANIN - Eumelanin is nitrogenous pigment having black or reddish brown colour. It is formed by oxidative polymerization of phenolic amino acid tyrosine. It is insoluble in all solvent. In the presence of metal ion, eumelanin oxidized chemically or photo chemically to a soluble form. 2. PHEOMELANIN - Pheomelanin is alkali soluble pigment ranging from yellow to reddish brown colour and containing sulphur and nitrogen. It arises by oxidative polymerization of cysteinyl group. Pheomelanins are found in hairs and are the pigment in human red hair. 3. NEUROMELANIN - Cytoplasmic organell are contained in the pigmented nuclei in the brain stem and dorsal root ganglia. These organells decreases or increases in case of Parkinson's disease. Eumelanins are insoluble heterogeneous, high molecular-weight, black to brown heteropolymers of 5, 6 dihydroxyindole and several of its biosynthetic precursors. Phenomelanins are yellow to reddish-brown polymers but, while also of high mo lecular weight, are soluble is dilute alkali. The low molecular weight trichochromes are related to pheomelanins both are derived from crysteine and dopa-quinone. Pheomelanins and trichochromes are present primarily in hair and feathers.

Each epithelial melanoblasts possesses many slender branches terminating in flattened expansion applied to the surface of neighbouring keratinocytes. The melanin granules formed in the perikaryal region of the melanoblast pass along the dendritic branches, and are either secreted at their tips, being subsequently engulfed by keratinocyte cell processes and incorporated into
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their cytoplasm, or else phagocytosed within dendritic fragments by these cells.

The melanin pigment, when present is found not only in the melanocytes but also in the more deeply situated epithelial cells. It is considered that the melanin granules in the latter have been transferred from the former. Certainly the melanocytes are the only established seats of pigmentary activity in the epidermis. Indeed pigmentary activity is the only special function known to be possessed by the melanocytes. Epithelia which lack melanocytes - such as those of the throat or tongue of man are never pigmented with melanin. If the melanocytes do not enter the epidermis the pigment they produce, owing to the depth of the overlying tissue through which light must pass, appearsbluish. This appearance is frequently seen in pigmentary abnormalities.

Black melanin recovered from the wool of hybrid downs - Dorset sheep was originally assigned the empirical formula C105H173N23SO38. But there are variation in the elementary composition of melanins from different sources; They are polymers (compounds consisting of repeating units) of variable mass and complexicity. Extractable in very dilute alkali, melanins are also soluble when fresh and undried in very dilute acid solutions; they are bleached by hydrogen peroxide, which is sometimes applied to growing hair to create a blond effect, and by chlorine, chromate and permangnate.

Melains are conspicuous in dark skin moles of man, in the black dermal melanocytes (pigment cells) of most dark-skinned races, as brown, diffuse spots (melanoproteins) in the epidermis, and in black tumorous growths of many vertebrates, such as melanomas in man, fishes and reptiles. The melanins are end products of metabolism involving the amino acid tyrosine and similar compounds. The progressive oxidating of tyrosine by atmospheric oxygen is catalyzed by the copper-containing enzyme, tyrosinase. In the oxidation of tyrosine the chemically reversible yellow, orange and red intermediate compounds are followed by an intensely black end product, which is a true melanin.
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The degree of natural melanization depends upon relative concentrations of copper and of the copper-containing enzyme tyrosinase. Dark hairs contain higher traces of copper than do pale ones. In human hair the cortex, which lies beneath the outer layer of cuticular cells, surrounds the central medullary column, or pith, very small ellipsoidal or spherical granules of melanin are randomly distributed within the dried cortical cells, imparting pale-puff, brown, or black colours, the colour depends upon relative numbers, sizes and depth of hue of the individual granules. Melanin occurring within the medulla may appear as a colloidally dispersed stain rather than as microscopically discernible particles. Human red hair, unlike all other hair, human and non human yields a unique, iron-rich red pigment.

PIGMENT PRODUCTION:

Pigment production by melanocyte cells is a complex biological process. The copper-containing, metalloenzyme-tryrosinase system is influenced not only by metabolic and harmonal changes in the body but also by local disease in the skin, especially inflammation. The normal stimulus to the enzyme is ultraviolet light of wavelengths 290 to 315 nanometres (billionths of a metre), producting suntan. The response is greatly increased by the ingestion or local application of a group of chemicals called psoralens, which are found in many plant products and are now made synthetically.

Inflammatory disease in the skin, such as eczema, psoriasis lichen planus, and infections, as well as trauma to the epidermis, will often induce a temporary increase or decrease of pigmentation. The general control of melanocyte function is by the melanocyte-stimulating hormone secreated by the pituitary gland, and skin-lightening factor (melatonin) secreted by the pineal gland. Disease of these and other endocrine gland (e.g. Addison's disease and Thyrotoxicosis) cause increased or decreased pigmentation by disturbing the normal balance of these harmones, protein, and therefore tyrosine, deficiency as in kwashiarkar or appropriate enzyme deficiency (as in phenylketonuria) will cause decreased melanin formation.
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The intermediate part of the pituitary gland produces the melanocytestimulating hormone (MSH), which causes expansion of the pigmented melanophores (cells) in the skin of frogs and other batrachians. Two hormones, called - MSH and -MSH, have been prepared from hog pituitary glands. -MSH consists of 12 amino acids, Its N terminal serine is acetylated (i.e., the acetyl group. CH3CO-, of acetic acid is attached), and its C terminal valine residue is present as valinamide. -MSH contains is its 18 amino acids many of those occurring in -MSH.

(CH3CO)

S.Y.S.M.E.H.F.R.W.G.K.P.V. (CONH2) Porcine -MSH,

D.S.G.P.Y.K.M.E.H.F.R.W.G.S.P.P.K.D Procine -MSH A.E.K.K.D.E.G.P. Y.K.M.E.H.F.R.W.G.S.P.P.K.D Human -MSH S.Y.S.M.E.H.F.R.W.G.K.P.V G.K.K.R.R.P.V.K.V.Y.P.D.G.A.E.D.Q.LA.E.A.F.P.L.E.F. Procine -Corticotropin

The amino acid sequences of hormones produced by the intermediate part of the pituitary gland. The amino acid sequence, M.E.H.F.R.G.W. occurs in all melanocyte stimulating hormone and in adrenocorticotropic hormones.

-MSH is found in human blood, but -MSH has not been detected in any of the body fluids. Little is known about the metabolism and excretion of these compounds.

MSH can produce some darkening of the human skin increasing the formation of dark pigments, but this does not occur under normal conditions, many other functions have been hypothesized for and -MSH in humans but there is insufficient evidence to consider any of them as established. It is known that the p-MSH level in the circulation tends to parallel that of ACTH being high
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when cortisol secretion is low and low following administration of adrenocortical hormones. ACTH has some MSH activity because it contains a sequence of amino acids that is also found in the latter. In certain disease high levels of -MSH is the blood are associated with increased pigmentation of skin. These are also disease in which the rate of ACTH secretion is high, but the ACTH is not present in sufficient quantities to produce the pigmentation by itself.

In some animal species, the intermediate lobe appears to be under direct neural control via nerve fibres from the hypothalamus that inhibits its secretion. The existence in the hypothalamus of two factors that influence MSH secretion has been claimed one as MSH inhibiting factor (MIF) and the other as MSH-releasing factor (MRF), but the role that these factors play, if any, in the regulation of MSH secretion is uncertain.

INHIBITORS OF MELANIN SYNTHESIS Following factors act as inhibitors of melanin synthesis Vitamin C, copper is essential for tyrosinase enzyme. Copper binding agents like ascorbic acid (Vitamin C) are capable of retarding various oxidative reactions in the melanogenesis pathway. Thus vitamim C act as a reducing agents. Role of the metabolites of melanin synthesis. Lerner, A.B. (1972) postulated that a precursor or metabolite of precursor in melanin synthesis inhibits or destroys melanocytes (self destruction theory). IMPORTANCE OF MELANIN PIGMENTATION Melanin is a substance that is responsible for variety of appearances in human beings. The some important work of melanin is described below: 1. PROTECTION OF SKIN Pigmentation protects the skin from sun induced skin cancer, solar keratosis and sun burns etc. Sun induced skin cancer on the exposed parts of the body like face and other extremities is very rare in black
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people living in geographic region with high ultra violet radiation, while black albinos living in these area are very susceptible to skin cancer.

2.

ACT AS DENSITY FILTER Melanin decreases the transmission of ultraviolet radiation (UVR) through Skin and hence provides defence against biological damage viz. sunburn, reaction, damage of skin etc. Melanin in the uveal tract and in the retinal pigment protects the eyes from visible and longer wave length radiation energy which is largely filtered by the cornea. In albino there is a progressive deterioration of sight due to the absence of protective pigment.

3.

PREVENT PREMATURE AGING All the skin related pathological conditions described above, in the absence of pigmentation are involved in skin aging. Melanin provides protection against environmentally induced premature aging. It seems clear that melanin pigmentation has protective role to play in geographical regions where there is high solar radiation. Conversely it could be argued that in the regions where solar ultraviolet radation is low, it may be disadvantageous to be highly pigmented, because, rickets may develop due to the reduced natural synthesis of vitamin "D" in the skin (Loomis, W.F.I 967).

4.

ACT AS FREE RADICAL One of the most important properties of the melanin is its free radical character. Electron spine resonance study reveals that melanin is stable free radical. Skin irradiated by ultraviolet radiation shows increase in free radical (Mangus IA). Melanin acts as optical fashion by diffusing and absorbing light. It also acts as a trap for electron and possibly free radical.

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CHAPTER 6
BIOCHEMISTRY OF MELANIN PIGMENTATION

Stages of Melanocytes Development Stages of Menanin Formation Dopaquinon Production Melanogenesis Biochemistry of Important Specialized Product from Tyrosine Melanin Catecholamine

The melanocytes melanocyte is a pigment producting specialized cell which are located in the skin. These specialized exocrine cells produce melanin, which in packaged and dispersed to neighboring keratinocytes in organelles called melanosomes.

STAGES OF MELANOCTYE DEVELOPMENT STAGE : I In this stage a spherical vesicle derived from golgi apparatus. It shows tyrosinase activity and contains melanofilament having length of 7 nm. How tyrosin is available in vesicle is uncertain. Tyrosinase is produced on membren bound ribosome and transferred via the endoplasmic recticulum to the golgi apparatus where it accumulates in vesicles that were derived from the golgi.

STAGE : II Here melanosome are in shape and it contains numerous melanofilamrnt. STAGE : III In this stage melanin are deposited in melanosome. STAGE : IV
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Now they become electron dense. Studies have shown they are partially amorphous in nature. It also contain micro vesicle called vesico globular bodies. These bodies are key unit for the development of macro melanosome. STAGE OF MELANIN FORMATION The stage of melanin formation are explained as given belowSTAGE : I Tyrosine is converted into DOPA. This process is very slow at start but becomes very fast after an inducting period. This reacting being accelerated by Odihydrophenyl compounds. DOPA further converted into dopaquinon and 2-3 dihydrow 5, 6 dhydroxy indole-2 carboxylic acid. It is rapidly oxidized to quinone. It is red pigment and is characterized by the absorption at 305-310 m. TYROSINE Irreversible oxidized Dopa Tyrosinase Oxygen

Dopa quinone Irreversible intramolecular change

2, 3- dihydro 5,6 dihydroxyindole -2 carboxylic acid

Quinon (Hallachrome)

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STAGE : II

At the 5.6 6.8 Hallachorome undergoes aromatization with or with out decarboxylation to afford two colorless compounds.

These steps are not clearly oxidative and are found to proceed in nitrogen atmosphere.

Indole 5, 6 Quinone is characterized by purple color.

DOPAQUINON PRODUCTION

Uinon (Hallachrome) PH 5.6-6.8 Aromatization with or without decarboxylation

5, 6- dinhydroxyindole -2- carboxylic acid Require nitozen atmosphere

5,6 dinhydroxyindole Oxidization

Indole 5, 6 Quinone

5, 6 dihydroxyindole is likely intermediate in a pathway of tyrosine to melanin. Indole 5, 6 quinone is has been recognized as a bifunctional monomer capable of undergoing itself. The mechanism of above reaction is obscure.

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STAGE : III

In this stage, Quinone is polymerized to melanin with the consumption of approximately one atom of oxygen.

Indole 5,6 quinone

Quinone Polymerization Consumption of one or atom Malanin MELANOGENESIS: With the melanocyte, tyrosine is converted to DOPA and then dopaquinone via the bifunctional enzyme tyrosinase dopaquinone is oxidized further to form the pigment melanin. This process is called melanogenesis. Melanogenesis and melanin pigmentation of skin is related to 10 these biologic process. There are 1. Migration of melanoblasts to epidermis 2. Differentiation of melanoblasts into melanocytes 3. Mitotic division of melanocytes 4. Tyrosinase Synthesis in the melanocytes 5. Melanosome matrix Synthesis in melanocytes 6. Tyrosinase Transport to melanosome matrix 7. Melanosome formation 8. Melanosome melanisation 9. Melanosome transfer to keratinocytes 10. Melanin removal with loss of stratum corneum. This whole length of the process of melanogenesis and melanin pigmentation is controlled or affected by a number of factors, they are
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1. Genes 2. Hormones 3. Ultraviolet radiation 4. Chalones and glycopeptides GENES: This study is based on various skin colors in American blacks and their progeny. It has been estimated that between three to six pairs of genes may account for black white colour gradient. These genes pairs are responsible for genetic colour (Constitutive colors) only, genetic or constitutive color of unexposed color (color which arises from sum induced tanning reaction or increased MSH) is not yet known. HORMONES : MSH (Melanocyte) stimulating hormone appear to act by a direct effect on adenylate cyclase, which results in increased cyclic AMP leading to increased tyrosinase and melanosome synthyesis. Aggregation and dispersion of melanosomes probably play a little part in the pigmentary anomalies of human. Such movement has been observed in specialized cells called melanophores, which are only present in invertebrates below mammals. This movement of melanosome is under neural and hormonal control in these animals. Diffuse Brown hypermelanosis is the main feature of adrenocortical insufficiency (Addisons disease). The same type of hypermelanosis is also seen in patients having cushing disease other adrenalectomy. The same type of melanosis is seen in patients with pancreatic and lung tumors. In all conditions hypermelanosis is due to the over production of melanocyte stimulating hormone (MSH). These two hormone share common

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amino acid sequences. Both MSH and ACTH are increased in addisons disease due to decreased out put of cortisol by adrenal. Melasma (Mark of pregnancy) is found in pregnant woman. Woman an oral contraceptives and in some other wise normal woman and men which also indicates same role of sex hormones. Hypopituitarism and hyperthyrodism produces hyparmelanosis (leucoderma). Hydrocartisone, Cartisone, Epineprine and nor epinephrine inhibit the action of MSH. The gathering of melanosome is stimulated by melatonin a hormone form the pineal body. III ULTRA VOILET RADIATION Melanocyte by producting and transferring the melanin provide defense against the biological damage of skin by ultra voilet radiation (UVR). In human this defens against UVR is highly developed. Exposure of skin to UVR. Causes the activation of an integrated mechanism (tanning) for the formation of dense organelles containing choromoprotein melanosome. With in the epidermal cells, melanosomes seatter and absorb ultraviolet radiation and remove the damaging free radicals that are generated in the skin after UVR exposure (UVR is dealt in detail under treatment) CHALONES AND GLYCOPEPTIDES Specific chalones and glycopeptides may markedly affect melanogenogenesis and melanin pigmentation by exerting negative feedback control and regulating the mitotic activity of melanocytes and keratinocytes. The rate of transfer of melanocytes to keratinocytes regulate the amount of melanosome synthesis. Chalones may regulate adenyle cyclase activity as well as melanocyte and keratinocyte division.

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BIOCHEMISTRY OF IMPORTANT SPECIALIZED PRODUCT FROM TYROSINE

1. Melanin 2. Catecholamines (Epinephrine) 3. Thyroxine Synthesis of melanin Melanocytes in the deeper layer of epidermis synthesis melanin in granular from in melanosone. Melanin pigment gives the black color of the hair and skin. There is only one enzyme involved, which catalyzes the first two steps. The remaining reactions are non enzymatic and occur spontaneously. (1) Formation of DOPA The first step is hydroxylation of tyrosine by tyrosinage. It is a mono oxygenase containing copper. (2) Formation of DOPA quinine Tyrosinage again acts on DOPA to form dopaquinone. (3) Formation of Indolequinone DOPA quinine convert to indolequinone through a series of reaction involving decarboxylation and oxidation of the side chain. The indoquinone is polymerized to form melanin.

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TYROSINE METABOLISM
(Hydroxy Phenyl Pyruvic Acid)

Phenylalanine

Tyrosine

HPPA

Homogentistic Acid

DOPA

DOPA

Thyroxine

Maleylaceto acetate

Dopamine

Dopaqinone

Fumaryl acetoacetate

Norepinephrine

Melanin

Fumarate

Epinephrine

Acetoacetate

VMA

CATECHOLAMINES:

Catecholamines are derived from tyrosine. They are named because of the presence of catechol nucleus.

They include metanephrine epinephrine, non-epinephirne and dopamine. They are produced by the sympathetic ganglia and adrenal medulla.

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Tyrosine +O2 DOPA (Dihydroxy phenylalanine) DOPA decarboxylase Dopamine Cu++ Vit.C Dopamine hydroxylase Tyrosine hydroxylase

Norepine Phrine N-methyl transferase Epinephrine Catechol-O-methyl Transferase Metanephrine Mono Amino oxidase Vanillyl mandelic acid

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Metabolism of Catecholamine Tyrosine +O2 DOPA (Dihydroxy phenylalanine)

Dopa quinine

Indolequinone

Melanin

Melanin Synthesis

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CHAPTER 7
CLINICAL APPLICATION OF MELANIN
Clinical applications of melanin Albinism Hypertyrosinemias Applied physiology of skin pigment

CLINICAL APPLICATIONS OF MELANIN: (i) Leukoderma When tyrosinase or melanin forming cells are absent from epidermis leukoderma appears. (ii) Graying of hair Graying of hair is also due to the disappearance of melanocytes from the hair root. (iii) Malignant melanoma Melanoblasts, especially in junctional naevi may multiply give to rise to malignant melanoma. Melanogen may be excreted through urine in such conditions.

COPPER DEFICIENCY: Tyrosinase is a copper containing enzyme, there may be disturbances in pigmentation during copper deficiency. If copper deficiency is intermittent, skin is white and black and which regions may be seen in the hair.

ALBINISM: Leukoderma and albinism are different. In albinism tyrosinase is completely absent in melanocytes over all the body. Leading to defective synthesis of melanin.

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In albinism the ocular fundus is hypopigmented and iris may be red or grey. There will be associated photophobia, nystagmus and decreased visual acuity.

Skin is sensitive to UV rays because skin has low pigmentation. The skin may show presence of naevi and melanomas. Hair is also white.

Causes of albinism may be produced:

1. Failre of melanocytes to form melanosomes. 2. Failure of melanosomes to form melanin. 3. Failure of melanosomes to store melanin. 4. Failure of melanosomes to transport melanin to keratinocytes. 5. Destruction of functional melanosomes (in excessive conditions) 6. Melanocyte deficiency secondary to a failture of melanoblasts to colonize the skin.

HYPERTYROSINEMIAS : There are three types of hypertyrosinemias-

(1) (2) (3) (1)

Tyrosinemia (Type I) or Hepatorenal Tyrosinemias Tyrosinemia (Type II) or oculoocutaneous Tyrosinemias Neonatal Tyrosinemia HEPATORENAL TYROSINEMIAS: DEFINITION: It is due to a deficiency of enzyme fumaryl acetoacetate hydrolase. It is also called tyrosinosis. SYMPTOMS: Symptoms of in this disease the first 6 months of life and death occurs rapidly. Cabbage like odor and hypoglycemia and liver failure are seen. There may be mild mental retardation are seen in this disorder. TREATMENT: Tyrosine and phenylalanine restricted diet is advised.

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(2)

OCULOOCUTANEOUS TYROSINEMIAS: DEFINITION: It is due to deficiency of tyrosine amino transferase (tyrosine transaminase). It is also known as Richner Hanhart syndrome. SYMPTOMS: Symptoms in this disorder are : Mental retardation Painful corneal lesions Keratosis of palmar surface Photophobia Increased excretion of tyrosine and tyramine in urine.

TREATMENT: A low protein diet is advised. (3) NEONATAL TYROSINEMIA: DEFINITION: It is due to deficiency of enzyme para hydroxyl phenyl pyruvate hydroxylase. Due to this deficiency hypertyrosinemia may occur in new born. TREATMENT: Ascorbic acid and low protein diet is advised.

APPLIED PHYSIOLOGY OF SKIN PIGMENT:

A melanocyte is a specialized cell located in the skin which produces melanin. Melanin is cause skin coloration.

An amino acid, tyrosine is converted to melanin through a series of complex chemical steps in the skin cells.

This process may be affected by heredity, heat trauma solar or ionizing raliation heavy metals and other factors. Pigment production and distributions in the body is regulated in part by harmones.

Change in any of these factors can result in hyper pigmentation, hypopigmentation or both. The changes may be permanent or temporarily. Pigment changes can be primary (existing as separate disorder) or secondary (resulting from) to other disorders.
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Some common skin pigment disorders

HYPOPIGMENTATION

S.No.

Hypopigmentation disorders

Characteristics

Leprosy

It is a skin infection caused by Mycobacterium leprae.

Vitiligo

White patches in the skin, vitiligo caused by the less of pigment producing cells melanocytes in the skin.

Albinism

This in inherited disorder is characterized by the total lack of melanin in the skin. In this condition Iris may be grey or red. The skin is low pigmentation and so skin may sensitive to UV rays.

Pityriasis Alba

Small circular spots on the child face usually the cheeks, often noticeable in summer when the skin is tanned.

Pigment loss after Sometimes after an ulcer, blister, burn or infection skin damage heals, the skin losses some of it pigment in that area.

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Hyper Pigmentation 1 Melasma Dark brown symmetric patches of pigment on the face. During pregnancy this is called the mark of pregnancy. 2 Scleroderma A rare progressive connective tissue disorder involving thickening and hardening of skin and connective tissue involving hyper pigmentation of the skin. 3 Addisions disease A glandular disorder caused by failure of functions of the cortex of the adrenal gland marked by aneamia and prostration with

brownish skin. 4 Moles(nevi) and It is a round, brown and black, flat or slightly

bathing trunk nevi or raised and can be found anywhere on the skin. It giant nevi is benign proliferation of cells with melanocytic differentiation. 5 Malignant melanoma Melanoma is increased concern of nevi.

Melanoma usually has a more irregular, notched or scalloped border. Raised lesions and lesions with increase marking as viewed by tangential lighting are the increased risk for malignant transformation.

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CHAPTER 8
VITIIGO
Introduction Historical aspect and vitiligo Synonyms Derivation Definitions Epidemiology Actiology Associated Aetiological factors

INTRODUCTION:

Vitiligo is a pigmentary disorder presenting as depigmented macules or patches over skin or mucosa appear after birth and characterized histologically by marked reduction of DOPA positive melanocytes in the lesion.

Vitiligo is an acquired, idiopathic, hypomelanotic disease characterized by circumscribed depigmented macules often familial and total absence of melanocytes.

It is a common acquired heritable, melanocytopenic disorder which is progressive, well circumscribed, cutaneous white macules, ocular

abnormalities, autoantibody and a high incidence of associated disorders, particularly thyroiditis, diabetes mellitus and premature leucotrichia.

The lesions of vitiligo may develop at any age, however in many cases the onset is reported at the second decade of life.

There is no complaint in vitiligo patient, except erthema and burning after sun exposure in few. But psychologically it is very distressing.
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In India there is a stigma associated with vitiligo and affected person and their families particularly girls are socially ostracized for marital purpose. It is very distressing particularly in females. A common man may confuse it with leprosy and in some communities it is regarded as social stigma.

The cosmetics disfigurement has a substantial impact on persons social and professional relationship that often leads social embarrassment and psychological turmoil. The affected person gets mentally depressed because it is also a common erroneous belief among that this is a variety of leprosy.

The distribution of epidermal melanocytes in different part of the body. There being a greater population density in the face and genital area than the trunk. In addition to epidermis, dermis and hair follicles. Melanocytes are present in eyes amount blood vessels, peripheral nerves, sympathetic chain and lining of the coelomic cavity, inner ear and leptomeninges. The characteristic feature of the vitiligo lesions is absence or marked reduction of DOPA positive melanocytes in the epidermis. There are some inactive (DOPA negative) melanocytes in the outer root sheaths of hair follicles and form the melanocytes reservoir for melanocytes. In the epidermis of the areas around the margins of vitiligo are abnormalities of the keratinocytes and melanocytes.

Various theories have been suggested for the etiology and

treatment of factors,

vitiligo. But the etiology of vitiligo is still unknown, but genetic

oxidative stress, auto immunity, neurological factors, toxic metabolites and lack of melanocytes growth factors might contribute for precipitating the disease in susceptible people and treatment of vitiligo none of them can singly account for all types of vitiligo. There is no universally effective treatment for vitiligo, various therapeutic modalities available with variable beneficial result.

HISTORICAL ASPECT OF VITILIGO:

Vitiligo is a disease known since ancient times. In the India sacred Rigveda (2500B.C.). It is described as term Kilasa. Sacred book Atharvaveda it is
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described as Shweta Kustha (White leprosy). In south India where Tamil is spoken, condition is known as Venkustham white leprosy.

The term vitiligo was first used by Roman Physician Celsus in 2nd Century A.D. This term is probably derived from Latin Word Vitium and the suffix igo vitium means veal or calf i.e. pale pink flesh and probab ly refers to the typical whitish macules or patches of disease which resemble white sports of the calf.

The disease vitiligo is also found in the period a Aushooryan (2200 B.C.) as described in Tarikh e Tibb Iran. Information concern to vitiligo comes from pharahic medicine in the Ebers Papyrus (1550 B.C.), where two types of disease affecting color of the skin are mentioned. One with tumours and mutations. Probably leprosy and other probably vitiligo which according to Ebers-Papyrus was treatable.

The reference to the vitiligo is also found in the Bible (Laviticus Chapter XII). Vitiligo has also been referred to in the Quran (3:49, 5:113) as Bohak and Baras.

Ancient Chinese literature mention about the use of Pu-Ku-C, which is similar to the Bakuchi (Psoralia Corylifolia).

In the Buddhist sacred book Vinay Pitaka (624-544 B.C.) the word kilasa is mentioned which means white spots on the skin.

In the thirteen century Ibn-EL Bitar in Egypt treated vitiligo with the extract from the fruit of the plant known as Ammi Majus (Aastrillal).

Treatment of vitiligo or shweta kustha has been mentioned the Bakuchi seeds for a long times.

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DERIVATION: The derivation of term vitiligo is described below:

Vitellus (Latin word) = Veal; that is pale pink flesh. Vitium (French) = means white color Vitilenam ageo (Latin word) translated rather freely means I wish to see the madam of thio bordello The word vitiligo is derived from Latin word vitillius which means calf. The characteristic white patches of the disease resembles with the white patches of spotted calf.

DEFINITION: It is an idiopathic, acquired and circumscribed hypomelanosis characterized by progressively enlarging amelanotic macules.

1.

Fitzpatrick defined vitiligo as a specific, common, often heritable acquired disorder Characterized by well circumscribed milky white cutaneous macules devoid of identifiable melanocytes.

2.

Vitiligo is defined by J.A. Kenney (1988) as a common, acquired heritable, melanocytopenic disorder characterized by progressive, well circumscribed, cutaneous white macules, ocular abnormalities, auto antibodies and high incidence of associated disorder particularly thyroid disease, diabtesmellitus and premature leucotrichia.

3.

K. pavithran (1991) defined vitiligo as an acquired pigmentary disorder of the skin characterized by the development of circumscribed depigmented mucule of variable sizes.

4.

Arora (1990) described vitiligo as a circumscribed idiopathic progressive hypomelanosis of skin and hair which is often familial and is characterized microscopically by total absence of melanocytes.

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SYNONYM: Most physicians use the two terms, leucoderma and vitiligo. Synonymously but a little bit difference exits between these two terminologies.

Leucoderma- the word leucoderma is composed of two words 'leuco' and 'derma'. Leuco menas whiteness of the skin. But this whiteness of skin is due to burns or found after healing wounds. This term is commonly used for the acquired localized loss of pigmentation of skin of unknown etiology.

EPIDEMIOLOGY: Vitiligo is common seen in at least 1%-2% of worlds population. The highest incidence has recorded in India and maxico. In Egypt it is about 1%, in Japan it is 1.64%, in India it appears to be 3% in Russia it is 0.34% and approximately 1% people in United States reported.

In India, the Gujarat and Rajasthan state have the highest prevalence i.e. around 8.8%. In India the prevalence of vitiligo is varying from 0.46 to 8.8%.

Frequency is higher in the land of the sun. It is more apparent here because of fact that sun exposure magnifies the difference between normal skin and that involved by the vitiligo. People belong to different religions, different races, different socioeconomic groups and different dietary habits do not show an significant variation in proclivity towards the disease. Prolong consumption of a diet poor in protein and curpominerals was thought to be contributory. In India there is popular but erroneous that dietary or drug intake of vitamin C worsens a vitiligo and strict restriction on its intake and at least one half effected person have a positive family history of vitiligo.

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AGE INCIDENCE: Vitiligo may start at any age. Onset of the unilateral dermatomal type is usually in childhood within 10 years of age. Onset has been reported form birth to 81 year of age. Peak age of onset is 10-30 years. Where all most cases with bilateral non dermatomal lesions (Vitiligo vulgaris type) begin in the second to fourth decade of life. A few instances of vitiligo lesions present at birth have been reported as cases of congenital vitiligo.

SEX INCIDENCE: Both sexes are affected more or less equally. In few studies there is slight female preponderance, which is likely because female are more sensitive to cosmetic disfigurement and more likely that males to present themselves for treatment.

INCIDENCE AND HEREDOFAMILIAL ASPECTS: Some patients give a family history, which possibly indicates a role of genetic factor in its pathogenesis.

1. Vitiligo seems to be a complex hereditary disease governed by a set of recessive alleles situated at several unlinked autosomal loci which may be involved in the generation of oxidative stress, melanin synthesis, autoimmunity etc. that could collectively confer the vitiligo phenotype. 2. Increased HLA DR4 in black colored people, HLA-B13 in morocean Jews and HLA-BW 35 in Yemenite Jews with vitiligo has been reported. 3. Atopy is another familial association. An atopic diathesis (Bronchial asthma, allergic rhinitis, atopic dermatitis) is reported to be often (nearly 40% in one Indian study) in patients presenting with vitiligo. 4. Elevated levels of auto antibodies have been found in the sera of patients with vitiligo and their first and second degree relatives. These

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relative also have on increased incidence of vitiligo and autoimmune endocrine disorders. 5. Vitiligo and alopecia areata also appears to be linked. Patient with scleroderma or morphea have an increased incidence of vitiligo, approximately 50% of patients with vitiligo have halo navi, and perhaps most significant of all, there appears to be link between vitiligo and melanoma. (20% of patients with melanoma have vitiligo.)

Skin Disorder Vitiligo ETIOLOGY There are many causative factors of vitiligo. The relative importance and significance of each one varies and is difficult to evaluate. Vitiligo is a multifactor disease by all accounts. But many possible precipitating / predisposing factors are

Nutritional Deficiency of B-Complex factors, (Thiamine, Riboflavin, pyridoxin, pantothenic acid) folic acid and biotin, deficiency of proteins, minerals, copper, zinc and other dietic factors and digestive upset like amoebiasis, helminthes, chronic diarrhea, dysentery etc.

Trophonurosis and Autonomic imbalance.

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 Copper deficiency Serum copper studies in vitiligo by different workers show conflicting results. However theoretically at least copper deficiency can cause vitiligo. Infections and toxins (septic foci) Sun burn Drugs Many drugs like Quinones, Amylophenoles, Chlorthiazide, Broad spectrum antibiotics, Chloroquine, Guanofuracin etc. Acute sever illnesses Typhoid, diabetes, hepatitis Gastrointestinal and hepatic disturbances Pregnancy Food adulterants Modern food habits Ultraviolet radiation deficiency may have some etiological role. Blood Groups B and AB Hypochlorhydria and Achlorhydria Psychosomatic troubles Physical trauma (Koebner's phenomenon) Synthetic garments Foot wears - In some cases vitiligo lesions are located on the dorso of the feet in pattern corresponding to the straps of the slippers or shoes. Rubber and plastic gloves and nylon articles. Cosmetics e.g. 'Bindi' fore head in the region where the plastic 'Bindi' is applied. Rubber padded or purse Vitiligo may develop on the breast if the patient uses rubber padded brassieres or keep a purse in this region may cause. Tight wearing In some other cases vitiligo lesions are located on the Hanks of ladies who were a tight petticoat string. It is due to prolonged pressure. Photographic developing solutions may cause vitiligo Lack of melanin stimulating hormone from pituitary gland. Increase in melatonin like substances at nerve endings. Stress and emotional trauma e.g. death in family, economical loss, loss of job etc. play important role in the development of the disease
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 Ecology is significant as there are certain belts of the disease especially where there is water and air pollution; near textile industry etc. role of food adulterants industrial chemical and dyes contaminating water and food may guess work at this stage but may prove to be the ultimate cause.

Genetic Predisposition is important 30% patients give positive family history. SOME ASSOCIATED ETIOLOGICAL FACTORS: Vitiligo patient are clinically well but some disease are usually associated with the vitiligo. Some abnormalities are found with significant frequency and some disease increasing tendency of vitiligo. There are

1.

Thyroid Disease a. Hypothyroidism b. Hyperthyroidism c. Graves disease d. Toxic goiter e. Thyroiditis f. etc

2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

Diabetes Mellitus Hyper Parathyroidism Additions disease Pernicious anaemia Halo Nevi Alopecia Areata Myasthenia Gravis Malignant melanoma Cronic mucocutaneous candidiasis Multiple endocrinopathy syndrome

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CHAPTER 9
CLINICAL MANIFESTATIONS OF VITILIGO

Distribution of vitiligo patches Koebners Phenomenon Onset of the Disease Border of the patches Trichome Sensation and blood vessels in vitiligenous skin Location of patches Punshi sign Sweat reaction in Vitiligo Reaction to sunlight Rate of the Pigment Loss Nature of Development of disease Common Pattern of Vitiligo Psychological Symptoms Others

Vitiligo is a worldwide disease and all races are affected between 1-3%. In India the incidence is higher varying between 0.39% to 8.8%. Both sexes are likely affected equally. The clinical manifestation of the disease is described as following

1.

DISTRIBUTION OF VITILIGO PATCHES Distribution may include the dorsa of hands, the face and the body folds including axillae and genitalia. Lesions are common around body openings such as the eyes, nostrils, mouth, nipples, umbilicus and anus. The distribution of the lesion is usually symmetrical, some times unilateral or may have dermatomal arrangement. There is rarely complete Vitiligo is seen.
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2.

KOEBNER'S PHENOMENON Vitiligo lesions also accurs at site of trauma, such as around elbows, knees and digits and an amelanotic lesion confirming to the area of injury, bums, excoriations and friction sites such as shoulder strap areas, waist band and collar region, may be seen after 2 to 4 weeks, being delayed from 6 to 96 months.

3.

ONSET OF THE DISEASE Vitiligo may develop at any age. Onset has been reported from birth to 81 years of age. Congenital Vitiligo is very rare, however in 50% of cases. the age of onset fell within the first "two decades of life. Family history is positive in about 30% of cases. The disease usually starts with a small, faint, hazy, localized discolouration of skin. Sometime, it begins with a rapid pigment loss. As the spots enlarge they merge with each other and in due course of time, form a broad patch. In some cases, most of skin may be covered with white patches.

4.

BORDER OF THE PATCHES The macules have convex outlines. The margin of the patches are mostly hyperpigmented. They increase in size and fused with neighbouring patches to form complex lesion.

5.

TRICHOME Generally the hairs of the patches are normally pigmented, but in chronic cases they also tend to white in colour.

6.

SENSATION AND BLOOD VESSELS IN VITILIGENOUS SKIN Some authors feel that there is vasoconstriction in the vitiligenous patch and hypoaesthesia in the affected skin.

7.

LOCATION OF PATCHES No any fixed part of the body where Vitiligo patches arise firstly. But following the more common sites of Vitiligo patches Exposed body areas : Face, Upper part of the chest, hands and feet. Around body openings : Eyes, nostrils, mouth, nipples, umbilicus, genitalia Body folds : Arm pits (Axilla), groin region.
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 Sites of injury, cuts, scrapes, burns etc. Hair: Early graying of the scalp, beard or other areas. 8. PUNSHI SIGN In young girl during the menstrual cycle, the white colour of the Vtiligo patches turn to pink red and after the menstrual period over, they return to the original white colour every month. 9. SWEAT REACTION IN VITILIGO It is reported increased sweating in the Vitiligo affected skin as evidenced by electrical resistance tests (Lerner). 10. REACTION TO SUNLIGHT Vitiligenous macules are less tolerant to sun than normal skin. 11. RATE OF THE PIGMENT LOSS The beginning of Vitiligo and the severity of pigment loss differ with each patient. The degree of pigment loss also can vary with each white spot. It is very difficult to assess what would be-the rate of pigment loss. In some patients it is observed that if the patient consume high amount of vitamin "C" rich meals the rate of pigment loss increases and if stop to intake the ascorbic acid containing food material its vise versa. The loss of colour may continue until for unknown reasons, the process stop. The vicious cycle of pigment loss and stability period of lesion is not predictable and may continue. 12. NATURE OF DEVELOPMENT OF DISEASE The condition of white patches is gradually progressive in nature. Sometimes it spreads very rapidly within few month and can cover the entire body, while some time one or two patches appears and remain constant for a long periods. Spontaneous repigmentation may occur in 10 - 20% of the patients and the site of repigmentation is mostly the sun exposed area. This type of development and regress of patches mostly observed in younger patients.

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13.

COMMON PATTERN OF VITILIGO Developmental pattern of Vitiligo patches vary in cases. Segmental Vitiligo presents in dermatomal, multidermatomal, quasidermatomal forms which are arranged unilaterally. Most patients do not develop lesions elsewhere. Vitiligo of distant digits and lips produces lip - tip syndrome. Bilateral lesions may be symmetrical or asymmetrical. Palms and soles are commonly involved. Achromotrichia has been reported in 9-45% of Vitiligo patients. Depigmentation of scalp hairs occurs with or without on underlying Vitiligo patch and may have poorer repigmentation response.

14.

PSYCHOLOGICAL SYMPTOMS Though Vitiligo is not a lethal disorder except depigmented skin, burn early when exposed to the sun. But the psychological features are very important these are It is cosmetically and psychologically devastating (Lerner). Resulting in a lower self esteem (Papadopoulas 1999). Poor body image and difficulties in sexual relationship (Porter).

15.

OTHERS Rarely the patches shows slight erythema, but as a rule, they show only depigmentation and sensitivity to light e.g. in the summer become more conspicuous because of increased surrounding normal pigmented skin.

season, lesions pigmentation of the

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CHAPTER 10
DIFFERENTIAL DIAGNOSIS OF VITILIGO
Differential diagnosis Associated factors

The hypopigmentation of Vitiligo must be differentiated from that of many other disorders of hypomelanosis, characteristic features of some disorders causing hypopigmentation or depigmentation to be differentiated from Vitiligo.

1.

CHEMICAL LEUCODERMA Chemical leucoderma has positive history of industrial exposure to phenolic compounds and germicides and it manifests as small white macules. Monobenzylether of hydroquinone, however causes

permanent Vitiligo like patches, even remote from the site of application. Chemicals used in leather industry and photography can produce Vitiligo type picture. 2. ALBINISM Albinism is an autosomal recessive trait characterized by congenital, uniform hypomelanosis of skin and hair. Albinism involving the skin alone has not been reported, but ocular albinism with minimal or no cutaneous involvement has been observed. In occulocutanous albinism, marked hypomelanosis or amelanosis of skin, white or faintly blondish hair, photophobia, nystagmus, hypopigmented fundus oculi are found. Occulocutaneous albinism can be classified into two types on the basis tyrosinase presence in the hair follicles i.e. tyrosinase positive occulocutaeous albinism and tyrosinase negative occulocutaneous albinism. Both these types are known to have different gene loci.

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3.

LEPROSY( LEPROTIC LEUCODERMA ) Tuberculoid and lepromatous leprosy have hypomelanotic macules and papules that are anaesthetic. The colour unlike Vitiligo is not pure white rather off white and margins of these macules are characteristically indiscrete.

4.

PSORIASIS White halos surrounding psoriatic plaques are result of abnormal prostaglandin synthesis and are not an abnormality of melanin synthesis.

5.

PITYRIASIS ALBA It is also called Pityriasis simplex. In this disease well defined patches with fine scaling, may be erythematous or skin coloured or depigmented, usually seen in children. Usually occur on face, particularly on cheeks and chin, may be seen on upper arms. Condition lasts remittently or intermittently for a few years. Clear up usually before puberty.

6.

WARDEN BURG SYNDROME It is dominantly inherited dermatologic disorder in which the individual is asymptomatic heterozygotes. Physical findings in this syndrome are wide bridge of nose, frontal white blaze of hair, heterochromia iridis, white eyelashes and deafness. Therapeutic advantage of early diagnosis is to clarify the deafness.

7.

TUBEROUS SCLEROSIS It is a autosomal dominant disease which manifest itself by the presence of congenital, circumscribed white macules in up to 98 percent of cases and classically by the development of seizures, mental retardations and adenoma sebaceum. Macules are located on trunk, buttocks are hypomelanotic, size and colour of these do not change with time. Histologically melanocyte present but with decreased melanosomes.

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The presence of three or more macules in a patient with above symptoms is strongly suggestive of tuberous sclerosis. All patients with unexplained seizures or mental retardation should be screened with woods lamp examination for white spots to exclude tuberous sclerosis. 8. TINEA VERSICOLOR A hypomelanotic but not amelanotic scaling, circumscribed eruption of upper anterior and posterior chest in young people, results from the presence of pityrosporum orbiculare, which contains an enzyme that form azelaic acid, a melanocyte toxin and result HI decreased melanin pigmentation. Sun exposure with appropriate antifungal regime proves helpful. 9. ATAXIA TELANGIECTASIS It is autosomal recessive genetic disorder characterized by cerebellar ataxia, acute cutaneous telangiectasis i.e. small red, focal lesions due to the dilations of capillaries, arterioles or venules and

immunodeficiency. Onset of truncal ataxia occurs in the infancy and progressive, recurrent and chronic pulmonary infections leads to bronchiectasis. Cause of death is chronic pulmonary disease or malignancy. Persistent high serum' levels of oncofetal proteins, including alpha, fetoprotein and carcinoembryonic antigen,may be of diagnostic value. 10. ECZEMA When some external agents inflames the skin, a series of highly characteristic changes develop in epidermis, term eczema is applied. Sometimes eczema may present a white patch like spot. It can be differentiated from characteristic history and association of the lesions. 11. PIEBALDISM Piebaldism is a congenital autosomal, dominant, stable, circumscribed hypomelanosjs which resembles Vitiligo except that it has a characteristic distribution pattern different from Vitiligo, does not usually

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progress or resolve. In this disease patches appear in circumscribed area on the extremities and anterior surface of thorax. 12. NEOPLASTIC DISORDERS ASSOCIATED WITH HYPOMALANOSIS Hyponmelanosis has been found around benign halo nevi in healthy patients but may also be found in or around malignant melanoma. Vitiligo like hypomelanotic macules remote from the melanoma may

also occur. Histopathological studies confirm the diagnosis. 13. VAGABOND'S LEUCODERMA Long standing infestation with pediculus corporis leads to

depigmentation, igmentation or excoriations. Demonstration of parasite confirm the diagnosis. 14. NEAVUS ANAEMICUS OR ACHROMICUS Birth marks are present from birth. On rubbing the lesion or affected areas, the surrounding normal skin will react by vasodilation and show erythema, while affected area will not. 15. PHRYNODERMA Along with nutmeg grater appearance of lesions, hypopigmented patches may be found on the knees and elbows. 16. SARCOIDOSIS It is a chronic, multisystem disorder of unknown etiology characterized by accumulation of lymphocytes and mononuclear phagocytes and derangement of normal tissue architecture. Plaques are purple, often raised and usually on face, buttocks and extremities. 17. POST KALA AZAR HYPOMELANOSIS After proper treatment of Kalazar three percent of African cases and 10 percent of the Indian cases develop post Kala Azar dermal leishmaniasis (PKDL) characterized by lesions ranging from

depigmented macules to wart like nodules over the face and extensor surfaces of the limbs. In Indian cases PKDL appears after a latent period of 1 to 2 years and may last for years.
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18.

VOGT KOYANGI HARDA SYNDROME This syndrome is produced after B.C.G. (Bacillus Calmette Guerin) therapy of melanoma in which skin colour clinically appears as blue. It is due to large amount of conjugative derivative of 5,6 dihydroxyindole, intermediate of tyrosine to melanin pathway, its oxidation takes place in the absence of tyrosinase even, dermal pigmentation is brown to blue.

19.

ACHROMIA PARASITICA Slight depigmented lesions appear on the face and arm, mostly in children suffering from warm infestations.

20.

PINTA It is an infectious disease caused by Treponema carateum. It has three stages. First stage of small papules appears after 7 to 21 days of exposure and lymphadenopathy occurs. Secondary eruptions not associated with lymphadenopathy appears after one month to one year of the initial lesions. These are called Pintides. Initially they are red and pigmented. In the third stage within three month-to one year most of the Pintides show varying degree of depigmentation becoming brown and finally white. Treponema carateum can be demonstrated in the transudate of the lesions. Anti treponemal antibodies test is positive, but takes four times more time to become positive in Pinta than in veneral syphilis.

21.

SYPHILIS Post syphilitic white patches can be differentiated from a typical history and specific serological tests, depigmentary lesions scattered on the trunk & extremities.

22.

SCLERODERMA Sometimes hypopigmented macules with perifollicular

hyperpigmented macules are seen in scleroderma.

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23.

LDIOPATHIC GUTTATE HYPOMELANOSIS

When white spots resembling a drop like size are scattered in the body and cause is not known.

ASSOCIATED FACTORS WITH VITILIGO

Some disorders are usually associated with the Vitiligo. It means increasing tendency of Vitiligo is seen in the following disorders-

Alopecia areata Addition's disease Autoimmune Disorders Chronic Mucocutaneous Candidiasis Diabetes Mellitus Down's Syndrome Halo Naevi (Sutton's disease) Hypothyroidism and Hyperthyroidism, Thyroiditis Melanoma Non Toxic Goitre. Psoriasis Pernicious Anaemia

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CHAPTER 11
MANAGEMENT OF VITILIGO
General awareness Non surgical methods Surgical methods Psychological and social counseling

INTRODUCTION

Vitiligo is a harmless, non infection disease. Except for the cosmetic defect, vitiligo is an absolutely harmless disease. A patient having vitiligo can be as efficient physically, mentally and sexually as any other individuals. Patient and their relative should be assured about this disease and it has no relationship to leprosy. This gives immense moral strength. Thus the patient may decide not to take any treatment and accept to live with his/her vitiligo.

At present, there is no universally effective drug for vitiligo therapy, there are however, various therapeutic modalities available with variable beneficial result.

The selection of patient for therapy should take into consideration the patients motivations, the psychological impact of the disease and the clinical presentation of vitiligo and should weight the risks and benefits of prolonged therapy.

On the other hand contrary to the common belief, the spread of the disease can be arrested and even considerable degree of re-pigmentation of the skin

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can be achieved in all most patient. Provided the patient takes an appropriate treatment.

Various treatment modalities are present and medical fraternity is using them. The treatment of vitiligo can be categorized in the following sections.

1. General awareness 2. Non surgical methods 3. Surgical methods 4. Psychological and social counseling

Photograph of Vitiligo during treatment

GENERAL AWARENESS

General awareness and preventive aspects are :

1. Counseling of personal, social and familial health 2. Diet 3. Vitamin 4. Personal habits and others

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1.

COUNSELING OF PERSONAL, SOCIAL AND FAMILIAL HEALTH : Care of personal, social and familial health and try to concentrate their mind in own work not to the disease. Avoid stress Avoid alcohol Avoid smoking Avoid junk food like pizza, burger, chawmin and other placked food item.

2.

DIET : Educating the patient regarding the need of good general health and balanced diet. Nutritious diet Enriched diet Adequate good quality of protein diet

3.

VITAMINS : Vitamin C and other substance known for causative factor of vitiligo should be availed. Educating the patient regarding to need of vitamin B complex, Vitamin E, minerals such as copper, zinc and iron etc.

4.

PERSONAL HABITS AND OTHERS: If patient suffering from hypothyroidism, hyperthyroidism, diabetes mellitus, pernicious anaemia and other endocrinological disturbance then that should be treated accordingly. If any chemical exposure is there that should be removed. If any nutritional deficiency or other condition precipitating the disease is there then should be treated, should be first. Photoprotection of amelanotic areas with topic sunscreens to decrease the acute and chronic damaging effects of solar radiation and to reduce the color contrast between the normal and vitiligo areas. Patients need to be instructed in every case is to evaluate if any of the factor known to cause vitiligo such as shoes, bindis, gloves,

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other rubber or plastic material, pressure to trauma and to remove their influence as for as possible.

NON SURGICAL METHODS

Following non surgical methods are commonly used in the management of vitiligo: 1. Phototherapy a. UVR and Visible light rays 2. Chemotherapy a. Oral photosensitivity drug and topical photosensitive ointments. 3. Photo chemotherapeutic agents a. Psoralen photo chemotherapy i. Topical photo chemotherapy ii. Oral photo chemotherapy b. Khellin and UVA c. Phenylalanine and UVA d. Miscellaneous phenothiazine agents Sulphonylurea polypodium compounds, leukotomas,

derivatives,

psudocatalase with calcium

NON PHOTO CHEMOTHERAPEUTIC AGENTS:

These includes: a. Corticosteroids a. Topical b. Oral b. c. d. e. f. Placentral extract preparation Nilamide Levadopa Canthaxanthin Topical crude tar
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g. h. i. j. k. l. m. n.

Nitrogen mustard Isoprinosine and pentoxifylline Broad spectrum sunscreen Cosmetic camouflage Fluorouracil Dapsone Quinoline Compounds Cyclophosphamide

NON SURGICAL METHODS: 1. Phoeotherapy UVR and visible light rays. Ultra violet radiation rays are used for this purpose. UVR The biggest natural source of UVR is the sun, which can be obtained naturally be exposure of affected areas to raising and setting the sun. The terrestrial sun light the UVR region extends from 290 to 490 nm. The visible spectrum from 400 to 760 nm (Nano meter) and near infrared spectrum, from wavelengths longer than 760 nm. Except sun various artificial sources like UV lamps, UV tubes etc. can be used as UV radiation source. After the determination of minimal phototoxic dose (MPD) by photo testing, the exposure time is calculated which the help of following formula: ( ) ( ( ) )

Prescribed UVA dose is 0.5 to 5 (J/cm2), which is more than MPD.

2.

CHEMO THERAPY: A number of drugs used for this purpose. Some important drug are as follows: Psoralen
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Psoralen originally obtains from the plant psoralea corylifolia (Bakuchi) is India. Natural psoralens have been isolated from four major plants families in more than 30 plants. Umbelliferae (Parsdey, Parship, celery) Rutaceae (bergamot fruits, lime gesplant, cloves) Leguminasae (Psoralen corylifolia) Moraceae (Figs)

PSORALIA CORYLIFOLIA LINN (BAKUCHI): PHARMACOGNOSTIC DESCRIPTIONS Botanical Name English Name Family Synonyms : : : : Psoralia corylifolia Linn. Purple fleabane, psoralea seed Fabaceae (Papilionaceae) Somaraji, Avalguja, Krishnaphala, Putiphali, Kushthaghni (in Hindi and Sanskrit)

Part Used

Seed

Psoralia Corylifolia Linn

Seed of Psoralia Corylifolia

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PHYTOCHEMICAL COMPOSITIONS:

Psoralia is a very useful drug in Ayurveda as well as in modern medicine for the management of leucoderma, psoriasis and other skin disease. The activity of the drug is mainly due to presence of two furocoumarin psoralen and isopsoralen. A large number of other compounds are also isolated from Bakuchi. There is following main constituents-

1.

COURMARINS:

i.

Proralin (C11H6O3)

ii.

Isopsoralen

iii.

Methoxysoralen

iv.

Trimethyl psoralen

Psoralin was isolated by Jois (1934) from petroleum ether extract. Chopra and Chaterjee have reported 0.27% to 1.1% of psoralen from dried fruits.

Isopsoralen was reported by Khastagir et. Al. from ether extract and it was found same effective as psoralen in the treatment of vitiligo.

2.

COUMESTAN: i. Corylidin ii. Psoralidin

3.

FLAVONOIDS: i. iii. Bavachinin Isobavachin ii. iv. Bavachin Bakuchiol

Bhalla et. Al (1974) isolated above three flavonoids from Bakuchi and Bakuchiol was isolated by Mehata et. al (1973). Bakuchiol protected human R.B.C. against oxidative haemolysis.
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4.

CHALCONES : i. ii. Isobavachalcone Isoneobavachalcone iii. iv. Bavachromanol Bakuchalcone

AMINO ACIDS: Alanine, Arginine, Glycine, Histidin, Isoleucine and lycine, phenylealanine, Tryptophan MINERALS: It also contains trace minerals like Mangesium, Calcium, Iron, Phosphorus and Potassium TYROSINASE: The root of Psoralia corylifolia contain very trace amount of enzyme tyrosinase, which is very important in the pathway of melanin formation.

SYSTEMIC ROLE OF PSORALEA: According to Indian system of Medicine Ayurveda the powdered babachi or bakuchi (Psoralea seed) by the mouth the beneficial effect may be due to: 1. Absorption and excretion of oil through the skin where it produce it specific action. 2. Stimulate action on the intestinal mucosa which may cause increased absorption of amino acids concerned in pigment formation. 3. Antiseptic action in the gastrointestinal tract.

So far as in know psorlea corlifolia in the only drug that has action on the rougets and melanoblastic cells of the skin (Chopra).

Psoralens have been the main stay of treatment of vitiligo. Historically, photochemotherapy of vitiligo can be traced back as far as 200 to 1500 B.C. in India and Egypt. These agents were originally obtained from the plant psoralea corylifolia in India and Ammi Majus in Egypt.

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Folk medicines in several cultures treated vitiligo with topical extracts of these plants that contains Furocoumarins.

Psoralen were useful in the treatment of vitiligo. They used various preparation of psoralen orally, topically and in combination and exposed the patient to natural sunlight and conventional ultraviolet lamp.

In 1947 (Fahmy and Shady) isolated several photosensitizing agents such as ammoidin ammidin, majudin, known as fuocoumarins from the fruit extract of the Ammi Majus plant. These were identical with the active principal of the oil Bakuchi (Psoralen corylifolia)

Numerous psoralens have been identified only few have clinical use.

Following main compounds are available for this purpose. For this purpose no much different in their therapeutic effects or toxicity and can be used inter changeably.

Psoralen 8- methoxypsoralen (8 mop, methoxsalen) 4, 5 8 trimethyl psoralen (TMP, Trioxalen) 5- methoxy psoralen (5- mop, bergapten)

PHOTO CHEMO THERAPY AGENTS: The most common recommended treatment involves the ingestion of either 8 mop or TMP followed by exposure to solar radiation (PUVASOL) or UVA radiation from artificial light sources. The biologic action spectrum for psoralen induced stimulation of melanin pigmentation is in the 320 to 360 nm range.

The skin is most sensitive to UVA at 1 to 3 hours after the ingestion of psoralen.

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The dose usually recommended is 0.6 mg/kg body weight biweekly. In PUVASOL an initial sun exposure of 5 minutes are recommended 2 hours after ingestion.

PUVASOL THERAPY : When psoralens are combined with sunlight exposure. It is called PUVASOL.

P UV A

Photosensitizing agents (orally or topically) Ultra violet light irradiation Light source is artificial Light source is sun

SOL

UVA lamps are quite costly and the patient has to come to the clinic for this therapy but PUVA has the advantage of administering measured doses of UVA.

TOPICAL PHOTO CHEMO THERAPY: It should be used in vitiligo patients with less than 20% involvement of body surface area. It can be used both of children over two years of age and for the adult. It may be used the treatment give in once and twice in a month. It may be used in concentration of 0.01% to 1.0% which may be applied to the body surface area 30 minutes before exposure to UVA. The initial UVA dose is 0.12 to 0.25 Jule/cm2, usually according to the patient skin type. The treatment area should be washed with soap and covered with a broad spectrum sun screen. Side effects may be includes : Pruritus
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Edema Blistering Hyper pigmentation Hyperkeratos of the treated area or lesions.

ORAL PHOTO CHEMOTHERAPY: Oral photo chemotherapy usually is safe but the following important points kept in mind.

It should be avoid in less than 12 years of age. Avoid during pregnancy Avoid during lactation Avoid in the patient who have past history of photo sensitizing. During PUVA therapy concurrent treatment with potential

photosensitizing drug e.g. phenothiazines. Oral anti-diabetes should be avoided. Following pathological and clinical examination should be done during the PUVA therapy. Opthalmological checkup including slit lamp examination should be done initially during the therapy. Contraindication includes abnormal liver function tests and ocular defects including cataracts presence of photosensitivity. Haemotological status, renal and hepatic functions are to be assessed initially during the therapy.

ADMINISTRATION OF DRUG: TMP (Trymethylpsoralen) oral psoralen therapy should be prefer with long term. 4-5-8 Trymethylpsoralen are used in the vitiligo patients.

It started with 0.6 mg/kg body weight of TMP ingested with food and two hour before exposure to the UV radiation.
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The exposure should be for 5 minutes availing approximately 3 joule per squire cm of UVA.

The does of TMP is increased to 0.9 mg/kg of body weight and 45 minutes respectively. Till the wanted result are obtained.

8 Mop (8, Methoxypsoralin)- is started when there no response seen TMP drug after 20-30 treatment sessions. 8 Mop is started with 0.3 mg/kg body weight along with an artificial UVA light source.

It still no response in 0.3 mg/kg b.w. and 8 Mop plus 0.6 mg/kg b.w. of TMP may be tried. It still no response in 30-50 more treatment abandon the treatment as a failure. The treatment therapy usually need to be continued for 9-19 months and about 150-300 exposures. The danger of a sever burn is much greater with 8 mop than the mop.

During the treatment patient should be instructed to wear UVA blocking sunglasses before and after the exposure on the day. Because the UVA rays passes though ordinary glasses.

Repigmentation occurs more readily on the face, neck, hairy and muscular regions than on the dorsa of hands, elbow, and ankles. It treatment is interrupted before an area gets completely repigmented the area once again becomes depigmented, usually within a short time.

SHORT TIME SIDE EFFECTS:

Nausea Epigastric discomfort Pruritis Insomnia Nervousness

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Erythema Blistring reactions

LONG TERM SIDE EFFECTS:

Cataract in eyes Skin Cancer Damage the skin

KHELLIN AND UVA:

Khellin is a furanochrome isolated from the seeds of ammi visnaga. It has been found to be as effective with UVA and has been effective with PUVA therapy. It is free from phototoxic side effect and it is very well tolerated. The oral dose of khellin is 50-100 mg given 2 hours before UVA exposure.

PHENYLALANINE

AND

UVA 5% Concentration Solution of L phenylalanine is

used in 50-100 mg/kg body weight and it is given orally one hour before UVA exposure (2-12 joule/cm2). If no response over this period of treatment. Supplemented with 10% topical cream over the acromic areas before 20 minutes of the exposure. There is no side effects and even children can be treated by this method.

MISCELLANEOUS AGENTS:

Sulphonylurea

compounds

(tolbutamide),

phenothiazine

derivatives

promethazine hydrochloride, chlorpromazine hydro chloride) and griseofulvin have been tried orally excepting phenothiazine which is used locally. Pseudocatalase and calcium chloride have been used as short term sub erythemogenic by twice daily application. Extract of algae polypodium leukotomas along with solar radiation may also be useful.

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NON PHOTO CHEMOTHERAPEUTIC AGENTS CORTICOSTEROIDS: The use of corticosteroids preparations in different form that is oral, topical and intra lesional giving encouraging results.

The side effects of topical corticosteroids such as acne, dermal atrophy, telengiectesia local hypertrichosis, ecchymosis may developed with long term local and oral used. If the disease is still active for patients in whom the disease is spreading very fast, systemic corticosteroids are the best choice to stop the progression of the vitiligo and then to initiate the process of repigmentation while others prefers alternate day schedule and combine corticosteroids with PUVA and PUVA SOL given on the days when corticosteroids are not given.

PLACENTRAL EXTRACT PREPARATIONS: Human placental extract, both aqueous and alcoholic has been considered as a biogenous stimulator and it used in vitiligo patients.

Placental extract contains tyrosine, a precursor of melanin, copper which act as a catalyst in the formation of melanin, copper which act as a catalyst in the formation of melanin pigment. It contains vitamins and trace elements which act as important supportive therapy in vitiligo.

It can be also used as lotion topically and intra dermal injection in small isolated patches.

It act as biogenous stimulator directly stimulating the exhausted or tired melanocyte.

The does of placental extract is 2 cc.Im. alternate days systemically.

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NILAMIDE: It is a mono amino oxidize inhibitor, suppressing the metabolism of catecholamine in a sympathetic nerve ending, which is responsible for segmental vitiligo in a dose of 150 mg. per day. It shows no improvement of all in non dermatomal type cases.

LEVADOPA It can be also used as both orally and topically. It is useful drug to treat the disease Parkinsonism. But in the vitiligo this method is not widely used.

CANTHAXANTHIN It is a naturally carotenoid. Present in some plants e.g. cantherellus cinnabarinus an edible mushroom, crayfish.

Sea trout, bird and marine algae. But now it can also be synthesized. It is used in 60-80 mg per day for 10-20 days. In 10-20 days to achieve yellow brown color. But the color fades in about 2 weeks and hence a maintains dose is always needed. This medicine is practically not useful in Indian skin. It also used as a food coloring agent, and sun tanning agent. In acural vitiligo of white female. It may produce good cosmetic result

TOPICAL CRUDE TAR It is used with corticosteroid topical medicine. But result did not appear satisfactory.

NITROGEN MUSTARD (MECHLORETHAMINE) It is used topically. In few patients unresponsive to PUVA therapy in whom it produce a parital response with speckled repigmentation.

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ISOPRINOSINE AND PENTOXIFYLLINE Vitiligo foundation (USA) has suggests that prostag landing inhibitor action in vitiligo, and in few cases of vitiligo unresponsive to PUVA and corticosteroid therapy but no encourgaging result was observed.

BROAD SPECTRUM SUNSCREEN They prevent the hyper pigmentation of normal skin during photo chemotherapy. Broad spectrum sunscreen decrease the short term and long term effects of UVA and UVB radiation and to decrease the contract between normal and vitiligenons skin.

COSMETIC CAMOUFLAGE These mask the acromic macule available in different color for different complexions includes make ups, dyes, quick tanning preparations. These are resistant to washing with soap and water and lasts for several days.

The color achieved with the use of 3-5% dihydroxyacetone preparations, silver nitrate or potassium permanganate solutions are used for this purpose.

FLUOROURACIL: It has been used in non dermatomal vitiligo. Topically used after abrasion resulting into epithelialization within 7 days and semalanization starts within the next 1-2 weeks.

DAPSONE: It is used as an immune modulator in the does of 100 mg daily for prolonged period.

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QUINOLINE COMPOUNDS Chloroquine and hydroxy chloroquine also suppress lymphocyte

transformation and reduce the number of T-cells and prostaglandin synthesis and establish lysosomal enzymes.

Does of chloroquine is 250mg/day and Hydroxycholoquine is 400mg/day.

CYCLOPHOSPHAMIDE It is an anticancer drug but due to side effect it use is not recommended. It useful in combination with oral corticosteroid.

Does of cyclophosphamide is 50mg/BD or twice daily

SURGICAL METHODS: 1. 2. 3. 4. 5. 6. 7. Punch grafting / autologous epidermal mini grafting. Thin thiersch split skin grafting Epidermal grafting Melanocyte cuture and transplantation Autologous grafting with non cultured melanocytes Therapeutic spot and regional dermabrasion Tattoing

PUNCH GRAFTING / AUTOLOGOUS EPIDERMAL MINIGRAFTING: It is a relatively simple technique and has been reported to be effective in focal and segmental Vitiligo, post burn depigmentation, chemical leucodermas, piebaldism and post dermabrasion leucoderma. It was first used by Orentriech and Selmanowitz in 1972 for a patient with postburn leucoderma. It was also used by Falabella in 1978 and then in 1983 in cases of segmental Vitiligo. He used punches of the size 1-2 mm. He noted that it showed 95% to almost total recovery in patients with segmental Vitiligo of stable nature but was unsuccessful in the
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Vitiligo of progressive nature. It has been noted pigment cells proliferate and migrate from the minigrafts into adjacent achromic skin.

THIN THIERSCH SPLIT SKIN GRAFTING: It involves the free transfer of epidermis along with a portion of dermis from one site to another. Behl (1964) was the first to report the use of thin thiersch's graft for treatment of Vitiligo. Success depends on proper selection of cases and use of a very thin graft obtained under local anaesthesia with the help of a dermatome and is spread on the dermabraded patch of stable Vitiligo and further sealed with pressure and local immobilization. They initially turn hyperpigmented with uneven borders. Gradually the colours lightens and the border merge with the surrounding skin. The complications include graft rejection, stuck on tyre appearance, curling of borders, colour mismatch, thick raised grafts, perigraft halo of depigmentation, reactivation of Vitiligo on grafted and perigraft area and Vitiligo on donor site. Thin thiersch grafts are useful for larger areas with average of 180 - 300cm2 possible in one session. an

EPIDERMAL GRAFTING (SUCTION BLISTER TECHNIQUE): A complete physiological dermo epidermal split is possible with the formation of a suction blister (Kiistula 1968). Falabella in 1971 used a negative pressure of 200 - 300 mm of Hg for 2-4 hours to obtain epidermal sheets to replace depigmented epidermis of the vitiligenous areas. It is used both as a carrier of melanocytes and an epithelial graft to cover depigmented area that has be denuded of epidermis with liquid nitrogen. Successful results have been obtained in Vitiligo, piebaldism and in post burn eucoderma. In Vitiligo epidermal grafting has been useful in the segments, Vitiligo. This procedure does not cause any scaring, but is more time consuming and require especial equipment for preparation of the recipient and obtaining the graft. Complications have included allergic dermatitis caused by antibiotic ointment and a care of photo allergic contact dermatitis due to

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mthoxsalen application. There may also be secondary infection, pigmentary changes, graft rejection and depigmented perilesional halo.

THERAPEUTIC SPOT AND REGIONAL DERMABRASION: Savant (1996) defined stable Vitiligo for cases which fail to respond or respond partially to medical line of treatment and in addition, the disease is inactive and no new patch has developed in past 2 years. In this method superficial layer of skin is dermabraded either with electric or manually till pin point bleeding occurred. They were further deep dermabraded to an appropriate depth manually. On healing they were treated with PUVA or PUVASOL. After therapy most of the area showed total pigmentation and some showed partial pigmentation. Side effect were superficial scaring, hypopigmentation which improve over six months, secondary infections etc.

MELANOCYTE CULTURE AND TRANSPLANTATION: Lerner et.al. (1987) first of all used cultured melanocytes to repigment cases of Vitiligo and piebaldism. Another new method of treating Vitiligo is melanocyte culture and transplantation which comprises of transplantation of autologous melanocytes into area of skin that are hypopigmented. Split skin thickness sample of size 2-4 sq. cm. is obtained from the patients usually from the thigh region and is then transported to the laboratory in special transport media. Then the section is trypsinized and disintegrated to obtain single cell suspension containing both keratinocyte and melanocytes which are then placed on a specialized medium supplemented with fetal bovine serum no-era toxin and hydrocortisone in a culture dish containing murine fibroblast. Then nutrients like epidermal growth factor may be added to obtain sheets containing both keratinocytes and melanoctyes. For obtaining a pure culture of melanocytes certain growth promoting factors such as TPA (Tetradecanoyl phorbol 13 acetate), IBMX (Isobutyl Methylxanthine), placental extracts and fibroblast growth factors are first added. Then selective growth inhibition of keratinocytes (By maintaining a high pH of

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7.2 of media), fibroblasts and langerhans cells (By addition of cholera toxin to media), is carried out. This treatment is used when medical treatment is failed and in non progressive or stable form of Vitiligo. AUTOLGOUS GRAFTING WITH NON CULTURED MELANOCYTES: Gauthier and Bazeille (1991) used this method as an alternative to use of cultured melanocytes as the technique involving is difficult. They produced blisters on depigmented skin by freezing with liquid nitrogen and injected into each blister a suspension of epidermal cells consisting mainly of keratinocytes and melanocytes which was obtained from sample of skin of the hair scalp after trypsinization. In this treatment 75 - 100% repigmentation was seen in cases of segmental Vitiligo. TATTOING: It is the process involving uniform implantation of minute, metabolically inert, pigment granules into the dermis, so as to create a cosmetic camouflage using manual or electrically driven needles. The different tattoo pigments include titanium oxide (white), cinnabar (red), cadmium sulphate (yellow) , iron oxide (camel yellow, light brown). Its advantage include that it gives instant results with good cosmetic results There are minimal or no chances of rejection and that it can be done on any anatomical site. It can be repeated if required. Its limitations includes it cannot be used for large areas, chances of colour mismatch exist and that it may be difficult to perform at certain sites with thick skin like the palms and soles. Therefore it can be concluded that with the use of appropriate medical or surgical procedure the Vitiligo can be managed.

PSYCHOLOGICAL AND SOCIAL COUNSELING:

Vitiligo is only a cosmetic problem. It is an absolutely harmless disease. There is a no complaints in vitiligo patients except erythema and during after sun
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exposure in few, but psychological it is very distressing particularly in females. A common man may confuse it with leprosy and in some communities it is regarded as social stigma.

A patient having vitiligo can be as efficient physically, mentally and socially, sexually as any other individual. Even family, friends, spouse are prone to reject the involved in subtle way. Patient experience personal unhappiness, social discrimination at work, at school, marital discard and other reverse psychosocial disasters.

The patients are advised about:

The nature of disease Difference between vitiligo and leprosy Try to develop positive attitude towards the conditions Carry out various public awareness programme about the disease and suffering patients. It is also important to carry out various awareness programmed at public places, through Television, Pamphlets, Radio programme, school and other method about the disease.

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CHAPTER 12
AYURVEDIC MANAGEMENT OF SHWITRA (VITILIGO)
Principal of Ayurvedic management Divavyapashraya Chikitsa (spiritual therapy) Yuktivyapashraya chikitsa (Rational therapy) Antaha parimarjana chikitsa (Internal purification) Bahi parimarjana chikitsa (External purification) Shastrapranidhana (Surgical measures) Satvavajaya Chikitsa (Psychotherapy)

According to Ayurveda (Indian System of Medicine) the treatment of shwitra (vitiligo) are described in vedic period with successful result but not in detailed. Acharya Charka, sushruta and vagbhatta have indicated some specific procedures in the treatment of shwitra (vitiligo).

PRINCIPAL OF AYURVEDIC MANAGEMENT

According to acharya charka has also enumerated that all the measure by which the aggravated and vitiated Doshas, Dhatus and Malas are brough back to their state of normally and disease is cured, they constitute the therapeutics or management (Chikitsa).

Further explained by acharya charka the scope of chikitsa (Management) more removal of the causative factors may not always result in the total removal of the disease as such, because the effects of disease may still continue to be operative. This aim is radial removal of the causative factors of the disease and the restoration of Doshika equilibrium.

Skin disease vitiligo or shwitra Roga causes both somatic and mental trauma. This disease are always very difficult to cure and are time consuming. In this disease process of returning skin color towards normally is very slow and rate

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of improvement arises greatly from case to case. They are to be required external medication with internal medication.

According to Ayurveda the basic of pathogenesis and etiology switra (vitiligo) is a Raktaja Roga (Cha. Su. 9/4, 5). Its etilogical factors are very much similar to kustharoga. Rakta dusti and pitta dusti and its management is very similar to these ailments.

Therefore following line of treatment mention and can be successfully applied for the management of switra roga (vitiligo).

a. Divavyapashraya Chikitsa (spiritual therapy) b. Yuktivyapashraya chikitsa (Rational therapy) Antaha parimarjana chikitsa (Internal purification) Bahi parimarjana chikitsa (External purification) Shastrapranidhana (Surgical measures) c. Satvavajaya Chikitsa (Psychotherapy)

Daivavyapashraya Chikitsa (spiritual therapy)

According to ayurveda the disease which is produced by the sinful acts of previous birth which already described under the heading of nidana (etiology).

In this therapy includes recitation of mantras, wearing of medicinal root and gems, auspicious acts, offering gifts, oblations, following religious precepts, atonement, fasting, invoking blessings, falling on the feet of God and pilgrimage etc. (Cha.Su. 11/54).

These methods may reduce the effects of sinful acts. According to Ayurveda these type of method produce mental fitness of patient which are helpful to cure the disease switra (vitiligo).

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Yuktivyapashraya chikitsa (Rational therapy)

It is divided into three parts : a. Nidan parivarjana (Avoidance of causative factors) b. Samshodhana Chikitsa (Bio-purification) 1. Vamana Karma (Therapeutic emesis) 2. Virchana Karma (Purgation Therapy) 3. Shiro Virchana Karma (Errhine Therapy) c. Sanshmana Chikitsa (Palliative therapy)

All three therapy are based on reporting physical conditions in which proper dietary and medicinal regime is followed.

Antahparimarjan Chikitsa (Internal Purification)

In this therapy those drugs, medicines are included which are given to the patients internally to eradicate the vitiated doshas by internal cleansing.

According to acharya Charka described six types of chikitsa i.e. Langhana, Brihana, Rukshana, Shehana, Swedana and Stambhana (ch.su. 22/4).

According to Acharya Vagabhatta has above six types into two parts namely santarpana and apatrapana.

Santarpana Brihana Snehana Stambhana

Apatrapana Langhana Rukhana Swedana (A.H.Su. 14/1-3)

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According to Acharya Charka Shwitra (vitiligo) is Santarpana Janya Roga. (Cha.Su 23/6). Hence in Shwitra (vitiligo) Apatarpana Chikitsa (Therapy) is indicated which includes Langhana, Rukhana and Swedana (Cha.Su. 22/18).

1.

NIDAN PARIVARJANA (AVOIDANCE OF CAUSATIVE FACTORS) : It is related to the patients discipline and attitude, therefore the Doctor may instruct the patients about the dietic and medicinal regime. It is a fact that mithya Ahara and vihar are main cause of the Shwitra (vitiligo) roga. It is the first line of treatment. So the first step to avoid the ailment is to avoid the Nidan. These Nidans are: i. Virudda Ahara ii. Mithya Ahara iii. Mithya Vihar iv. Papa Karma v. Vishamasana vi. Disobeying of elderly persons etc.

2.

SAMSHODHANA CHIKITSA (BIO PURIFICATION) Acharya sushruta has indicated the repeated samshodhana chikitsa in skin disorders. (Su.Chi. 9/42) It is divided into four parts: Vamana therapy Virechana therapy Shiroverchana Raktamoshshana once in 15 days once in 3 months once in 3 days once in 6 months interval

Samshodhana chikitsa (bio purification) is radial removal of the causative morbid factors of the disease. Removal of aggravated and vitiated doshas from the body through their hearer route is called samshodhana (bio purification). If the causative morbid factor of the disease is not done properly due in time then vitiated doshas spread in the body and skin disease become incurable (Su.Chi. 9/42).

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VAMANA KARMA (THERAPEUTIC EMESIS) Vamana Karma (Therapeutic Emesis) should be advised in shwitra roga. It is useful in: Kapa Dosha Dominant Pitta and Vata Dosha in Kaphasthana According to Acharya Sushruta advised to repeat this therapy after every fifteen days in skin disorders.

Virechana Karma (Purgation Therapy): Virechana Karma (Purgation therapy) is also useful in Shwitra Roga (Vitiligo) and other skin patients. According to Acharya Charka has mentioned that the patient of Shwitra (Vitiligo) roga should be subjected to routine samshodhana therapy first and after proper internal cleaning use this therapy. In the patient of (vitiligo) shwitra roga subjected to specific virechana with guda (jaggery) and Kakodumbra swarsa. After that patients should take sun bath for three days and take peya if he become thirsty. If the blisters appears on shwitra patients they should be pricked and discharged. (Cha.Chi. 7/162). According to Acharya Sushruta mention the virechana in Shwitra and other skin disorders. He has advised to take drugs in such a dosage that five to eight motions may be induced per days. (Su.Chi. 9/68). This therapy in shwitra and other skin disorder mentioned should be repeated after one month interval. (Su.Chi. 9/43). So virechana is most useful in the shwitra roga (vitiligo) and other skin disorders.

SHIROVIRECHANA KARMA (ERRHINE THERAPY): In (vitiligo) shwitra roga patients if white patches developed mainly above neck region nasya or shirovirechana therapy should be administered. According to Acharya Charka, in the management of Shwitra Roga (vitiligo) or other skin disorder drugs which are commonly used for Nasya or Shiroverchana are (Cha. Chi. 7/48)
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Pipali Maricha Dantimoola Karanja Phala

Tulsi Bheeja Saindhva Vidanga

Dhoompana is given after shirovirechana for alleviation of remaining kapha dosha (Cha.Su.5/20-24).

SHAMANA CHIKITSA : According to Acharya Sushruta in the management of shwitra roga (vitiligo) and other skin disorders have given a very important note that doctor using their intellect can prepare a number beneficial preparation. According to patient Age, symptoms, prakriti, Sara, dosha and other principals. For this treatment by giving due consideration to the basic compound of drugs and other fundamental properties.

RAKATA MOKSHANA (BLOODLETTING): The art of healing is one of the oldest intellectual properties of human being originated out of constraint, need, self protection and urge to help. According to ayurveda persons Let the noxious blood be let out. It will cure the disease or otherwise it will make a clear pathway towards further treatment modalities among bloodletting procedures. Leech therapy is vividly practiced in ayurveda. The use of leeches in ayurveda medicinal practices in India is very ancient. Medicinal leech therapy got a big boost by plastic surgeons that used leeches in transplant surgery.

LEKHAN KARMA (SCRAPING): The scraping should be in the direction of hair follicles and if such is not followed when the excessive bleeding and pain will be resulted. The scraping is to be advocated in skin lesions.

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SATVAVAJAYA CHIKITSA (PSYCHOTHERAPY)

Satvavajaya Chikitsa is a type of Trividha Aushadhi in which physician try to withdraw the mind of patients from harmful subjects 1. This therapy includes the restrain of mind from the unwholesome objects. It is advisable to attend course of conduct as described in various Ayurvedic texts. Various measures like administration of Satvika diet, practicing meditation and Yoga will increase the Satva of patients. As mentioned earlier in etiology some factors responsible for Manasika involvement also paly an important role in complicating the disease. Hence it is essential to increase the Satva Guna of patients. Psychologically patients should be treated and make him assure that it has no relation to any sinful acts. It may occur to anyone. According to Acharya Vagabhatta the actual dependable treatment for various

psychosomatic disorders is by improving Dhi, Dhriti and Smriti, which ultimately improve the Satva of patients and cure the disease.

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Chapter 13
AYURVEDIC MEDICINES OF VITILIGO
Single Drugs Chruna (Powder) Preparations Kwatha (Decotion Preparation ) Asava /Arishta Preparations Avaleha (Paste) Preparations Ghrita Preparations Taila Preparations Guggulu Preparations Peya Preparations Guda (Jaggery) Preparations Urines (Mutras) Saktu Preparations Loha Preparations Rasayana Preparations Rasa / Bhasma / Pisti (Metalic Preparations) Vati (Tablets) Preparations Lepa Preparations (Ointments) Or Topical Applications Abhyanga Preparations

According to Ayurveda (Indian System of medicine) various types of medicines like single drug, churna, rasa, bhasma, pisti (metallic preparation), paka, grita, avaleha, ashawa, aritha etc. Described widely which are useful in the management of vitiligo (shwitra roga)

SINGLE DRUGS a. b. c. Bakuchi (B.P. Batadi Varga 33) Khadira (Cha. Su. 25/40) Chitraka (A.H.U. 39/65)
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d. e. f. g. h. i. j. k. l.

Bhringaraja (A.H. Chi. 20/8) Bhallataka (A.H. Chi. 20/11) Kakodumara (B.P. Batadi Varga 10) Shinshapa (B.P. Batadi Varga 25) Bakula (B.P. Pushpa Varga 33) Endri (Cha. Chi 1/3/29) Ashvagandha (B.P. Guduchyadi Varga 189) Rasona (Cha. Su. 27/176) Other important medicines

According to Acharya Sushruta various groups of medicines which can be used successfully in the treatment of shwitra roga (vitiligo) like:

Lodhradi Gana, Eladi gana, Asanadi Gana etc.

a. Lodhradi Gana: Acharya sushruta has described as a Varnya (Color and complexion promoter medicine). This gana includes (Su.Su. 38/14) i. ii. iii. iv. v. vi. vii. viii. ix. x. xi. xii. xiii. Lodhra Symplocus race mosa Shyonaka Oroxylum indicum Pathani Lodhra Ashoka Saraca asoca Palasha Butea monosperma Bharangi Clerodendrum serratum Kayaphala Myrica esculenta Elabaluka Prunus cerasus Shallaki Boswellia serrata Jingini Odina woodier Sala Shorea robusta Kadamba Anthocephalus indicum Kadali Musa sapientum

b. Eladi Gana: Acharya sushruta has also describe as a complexion promoter (varnya) medicine. This gana includes (Su.Su. 38/24) i. Kushtha Saussarea lappa
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ii. iii. iv. v. vi. vii. viii. ix. x. xi. xii. xiii. xiv. xv. xvi. xvii. xviii. xix. xx. xxi. xxii. xxiii. xxiv. xxv.

Ela Elettaria Cardamomum Tagara Valleriana Wallichii Jatamansi Nordostachyus Jatamansi Dhayamaka Dalachini Cinnamomum Zeylanicum Tejapatra Cinnamomum Tamala Priyangu Callicarpa Macrophylla Harenuka Vitex negundo (Seeds) Shukti Margarita Vyaghranuka Achantina fulica Chanda Rauwolfia Serpentina Sthauneyaka Taxus baccata Srivesthtaka Pinus roxburghii Choraka Angelia gluca Guggulu Commiphora mukul Baluka Mimosops elergi Sarjarasa Vateria indica Kunduru Extract of Boswellia serrata Agaru Aquilaria agalocha Sprikka Anisomeles malabarica Ushira Veteveria zizanoides Devadaru Cedrus deodar Keshara Crocus sativus Punnagakeshara colophyllum inophyllum

b. Asanadi Gana: According to Acharya Vagabhatta varnya medicines. This includes (A.H.Su. 15-19/20) i. ii. iii. iv. v. vi. vii. viii. Asana Pterocarpus massupium Tinisha Ougenia oojeinensis Bhojabatra Betula utilis Arjuna Terminalia arjuna Puti Karanja Holoptella integrifolia Khadira Acacia catechu Shirisha Albizzia lebbeck Shishapa Dalbergia sissoo
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ix. x. xi. xii. xiii. xiv. xv. xvi. xvii. xviii. xix. xx.

Meshashringi Gymnema sylvestre Trihima Tala Borassus fdabbifer Palasha Butea monosperma Agaru Aquilaria agalocha Sagaun Tectona grandis Sala Shorea robusta Supan Dhava Anogessus latifolia Indrayana Holarrhena antidysentrica Chhagakama Ashvakama Shorea robusta

CHRUNA (POWDER) PREPARATIONS Dose : 3-6 gram.

1. Somaraji Churna (Cha.D.) 2. Avalguja Beeja Churna (Cha.D.) 3. Nimbadi Churna (R.R.S) 4. Shwitrari Yoga Churna (R.R.S.) 5. Udumbaradi Churna (R.R.S.) 6. Panchanimba Churna (B.P.) 7. Kathoomara Bakuchi Churna (B.P.) 8. Bakuchi Churna (B.P.) 9. Bakuchyadi Churna (G.Ni) 10. Somaraji Churna (G.Ni ) 11. Bakuchyadya Churna (G.Ni) 12. Manjisthadi Churna (R.T.S. & S.P.S.) 13. Narasingha Churna (R.T.S. & S.P.S.) 14. Mustadi Churna (Cha.Sa.) 15. Vidangadi Churna (Y.R.)

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Kwatha (Decotion Preparation ) Dose : 20-40 ml

1. Dhatri-Khadira Kwatha (B.R.) 2. Bibhitakadi Kwatha (B.P.) 3. Triphaladi Kwatha (Cha.Sa.) 4. Mustadi Kwatha (Cha.Sa.) 5. Malayuvadi Kwatha (Cha.Sa.) 6. Khadira Kwatha (Cha.Sa.) 7. Dhatryadi Kwatha (Cha.D.) 8. Udumbara Mula Kwatha (Su.Sa.) 9. Patola Muladi Kwatha. (A.H.Chi.)

Asava /Arishta Preparations Dose : 20-40 ml

1. Rodhrasava (A.H.) 2. Abhayarishta (Cha.Sa.) 3. Madhwasava (Cha.Sa.) 4. Kanakabindwarishta (Cha.Sa.) 5. Madhukasava (Cha.Sa.) 6. Lodhrasava (Cha.Sa.) 7. Punarnavadyarishta (Cha.Sa.) 8. Khadirarishta (Sha.Sa.)

Avaleha (Paste) Preparations

Dose

10-20 gm

1. Mahabhallatakavaleha (B.P.) 2. Panchanimbakavaleha (B.P.)

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3. Vidangadi Avaleha (A.H.) 4. Bhallatakavaleha (Y.R.)

Ghrita Preparations Dose : 10-20 gm.

1. Tiktaka Ghrita (A.H.Chi.) 2. Dantyadi Ghrita (A.H.Chi.) 3. Mahatiktaka Ghrita (A.H.Chi.) 4. Mahavajraka Ghrita (A.H.) 5. Neeli Ghrita (Ga.Ni.) 6. Somaraji Ghrita (B.R.) 7. Mahaneela Ghrita (Su.Sa)

Taila Preparations

Dose

2-5 ml

1. Bakuchi Taila 2. Bhallataka Taila (A.H.) 3. Tuvaraka Taila (A.H.) 4. Sarshapa Taila (A.H.)

Guggulu Preparations

Dose

250-500 mg

1. Swayambhuva Guggulu (B.P.)

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Peya Preparations

1. Vijayasara Siddha Milka (A.H.Chi. 20/8). 2. Gavya Mutradi Peya (Su.Chi. 9/39). 3. Khadirajala Pana (Cha.Chi. 7/166).

Guda (Jaggery) Preparations

Dose

250-500 mg.

1. Vidangadi Guda (A.H.Chi. 19/45) 2. Pathyadi Guda (A.H.Chi. 19/47) 3. Manibhadra Guda (A.H.Chi. 19/31-32) 4. Chandra Shakaladi Guda (A.H.Chi. 19/44)

Urines (Mutras)

All the Ayurvedic texts especially Charaka Sushruta and Astang indicates eight types of urine in the management of Shwitra Roga (vitiligo) [A.H.Su. (5/82, 83), A.S.SU. (6/141 142), Cha.Su. 1/96 100, Su. Su. 45/226].

1. Cow Urine. 2. She buffalo urine. 3. Sheep Urine 4. She goat urine 5. Elephant urine 6. Horse urine 7. Ass urine 8. Camel urine
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Saktu Preparations (Cha. Su. 23/19-24)

1. Vyoshadya Saktu (Cha.Su.)

Loha Preparations

Dose 250-500 mg

1. Ashtadashanga Loha (B.P.)

Rasayana Preparations

1. Bhallataka Rasayana (Cha.Sa.) 2. Shilajatu Rasayana (Cha.Sa.) 3. Endra Rasayana (Cha.Sa.Chi. 1/3/29) 4. Pittala Rasayana (R.R.S.) 5. Bakuchi, Rasayana (A.H.U.) 6. Chitraka Rasayana (A.H.U. 39/65) 7. Brahmi Rasayana (A.H.U.39/50-53)

RASA / BHASMA / PISTI (METALIC PREPARATIONS)

Dose

125-250 mg.

1. Shwetari Rasa (B.R) 2. Kushtha Haritaleshwara Rasa (B.R.) 3. Galatkushthari Rasa (B.P.) 4. Khageshwara Rasa (R.R.S.) 5. Medinisara Rasa (R.R.S.) 6. Kashisha Baddha Rasa (R.R.S.) 7. Udayaditya Rasa (R.R.S.) 8. Shwitrantaka Rasa (R.R.S.)
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9. Shwitrari Rasa (R.R.S.) 10. Shwitra Kushthari Rasa (R.R.S.) 11. Tamralipta Kajjali Rasa (R.R.S.) 12. Veera Chandeshwara Rasa (R.R.S.) 13. Vijayanand Rasa (R.Sa.Sa.) 14. Rajataleshwara Rasa (R.Sa.Sa.) 15. Chandrakanti Rasa (R.Sa.Sa.) 16. Mahataleshwara Rasa (Sha. Sa.) 17. Vijayeshwara Rasa (Y.R.) 18. Udayadi Rasa (Sha. Sa.Ma.Kha)

VATI (TABLETS) PREPARATIONS

Dose

250-500 mg

1. Arogyavardhini Vati (R.R.S.) 2. Shwitrahara Vati (R.Chi.Ma.) 3. Chandraprabha Vati (Rasa Kamdhenu) 4. Triphaladi Gutika (Y.R.) 5. Kshara Gutika (Cha. Sa.) 6. Shashilekha Vati (Y.R.)

Lepa Preparations (Ointments) or Topical Applications

According to Acharya Charaka if the Lepa Chikitsa applied after proper Sanshodhana Karma, they produce much beneficial effect in skin disorders (Cha.Chi. 7/53)

While applying these lepas it should be kept in mind that for their better and immediate effect they should be applied from downward to upward direction i.e. Romabhimukha (Sha.sa. Utt. 11/73-74).

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In Ayurvedic classics a large number of Lepas are described in the management of Shwitra Roga. The important Lepas useful in Shwitra Roga are following-

1. Kadaliksharadi Lepa 2. Manahshiladi Lepa (Cha.Chi. 7/167) 3. Malatyadi Lepa (Cha.chi. 7/168) 4. Moolakadi Lepa (Cha.Chi. 7/169) 5. Manahshila Barhipittadi Lepa (Cha.Chi. 7/170) 6. Neelotpaladi Lepa (Cha.Chi. 7/169) 7. Kakodumbaradi Lepa (Cha.Chi. 7/170) 8. Avalgujadi lepa (Cha.Chi. 7/171) 9. Krishna Sarpa Masi 10. Lakshadi Lepa (Su.Chi. 9/12) 11. Saindhavadi Lepa (Su.Chi. 9/13) 12. Rajabrikshadi Lepa (Su.Chi. 9/16) 13. Prapunnadi Lepa (Su.Chi. 9/19) 14. Tutthadi Lepa (Su.Chi. 9/27) 15. Tilvakadi Lepa (Su.Chi. 9/28) 16. Putikadi Lepa (Su.Chi. 9/40) 17. Gajalendajadi Lepa (Su.chi. 9/21-22) 18. Amra Haritakadi Lepa (Su.Chi. 9/23-24) 19. Hreeberadi Lepa (Su.Chi. 9/26) 20. Bhallataka Taila and Gramyaanoopa Pashu Khura Kshara (Su.Chi. 4/92). 21. Vibhitaka Taila and Gramyanoopa Pushu khura kshara (Su.Chi. 1/93). 22. Avalguja Beeja (A.H.Chi. 20/13) 23. Bhallatakadi Lepa (A.H.Chi. 20/16-17) 24. Phanijjhakadi Lepa (Cha.Su. 3/4) 25. Vachadi Lepa (Cha.Su. 3/5) 26. Manahshiladi Lepa (Cha.Su. 3/5) 27. Aragvadhadi Lepa (Cha.Su. 3/3) 28. Shrayahavadi Lepa (Cha.Su. 3/3)
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29. Bhojapatradi Lepa (Cha. Su.3/4) 30. Girikarnyadi Lepa (B.P. 54/153) 31. Shiladi Lepa (R.R.S. 20/195) 32. Akoladi Lepa (R.R.S. 20/196) 33. Krishnikarana Yoga Lepa (R.R,.S. 20/203-204) 34. Vishaladi Lepa (R.R.S. 28/85) 35. Kukubhadi Lepa (R.R.S. 29/86) 36. Gunjaphalagni Lepa (Sha. Sa. Ma. Kha. 12/192) 37. Shila Apamarga Lepa (Sha.Sa.Ma. Kha. 12/193) 38. Pratisaraniya Kshara Lepa (A.H.Su. 30/3, Su.Su. 11/7) 39. Shwitra Dadru Patala Lepa (R.Sa.Sa. Kushtha Chikitsa 113/115) 40. Shwitrahara lepa (R.Sa.Sa. Kustha Chi./ 116) 41. Balyadi Lepa (Y.R.Kushtha Chikitsa/5) 42. Triphaladi Lepa (Y.R.Shwitra Chikitsa/6) 43. Ayorajadi Lepa (Y.R.Shwitra Chikitsa/7) 44. Pootikadi Lepa (Brinda Madhava) 45. Balyadi Lepa (Brihat Nighantu Ratnakara) 46. Bhringarajadilepa (B.N.R.) 47. Savarna Karta Lepa (Yoga Tarangini Tarang/ 62) 48. Snuka Lepa (Bangasena) 49. Hayadi Lepa (B.N.R.) 50. Grihadhoomadi Lepa (G.Ni.) 51. Jalapippalyadi Lepa (Su.Chi. 9/21-22) 52. Lepa with Ash of Sugandhabala with Bibhitakha Taila. (A.H.Chi. 20/12). 53. Lepa of the Ash of tiger skin with oil (Su.Chi. 9/16) 54. Lepa of the Ash of elephant skin with oil (Su.Chi. 9/16) 55. Lepa with Ash of Peocock Bile with Bibhitaka Taila (A.H.Chi. 20/12).

Abhyanga Preparations a) Ghrita Preparations 1. Kashishadi Ghrita (Sha. Sa. Ma.Kha. 9/51-57) 2. Neela Ghrita (Su.Chi. 9/29-33)
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3. Maha Neela Ghrita (Su.Chi. 9/34-38)

Taila Preparations

1. Bhallataka Taila (Su.Chi. 30/5) 2. Madanaphala Taila (Su.Chi. 31/5) 3. Vajraka Taila (Su.Chi. 9/5) 4. Vibhitaka Taila (Su.Chi. 31/5) 5. Visha Taila (B.R.54/321-324) 6. Kandarpa Sara Taila (B.R. 54/348-363) 7. Kushtha Rakshasa Taila (B.R. 54/294-288) 8. Aragvadhadya Taila (B.R.54/275) 9. Panchanana Taila (B.R. 54/272-274) 10. Ankoladi Taila (R.R.S. 20/110) 11. Laghu Marichyadi Taila (B.P. 54/107-111) 12. Maha Vajraka Taila (A.H.Chi. 19/81-82) 13. Marichyadi Taila (Sha. Sa.Ma.Kha. 9/149-152) 14. Kushthari Taila (R.R.S. 20/211-212) 15. Lakshadi Taila (R.R.S. 29/89-91) 16. Shwitra Gaja Singh Taila (Ra.Chi. Sta. 4) 17. Kushthadi Taila (Cha.Chi. 7/117-118) 18. Chitraka Taila (Rasa Kamadhenu) 19. Jyotishmati Taila (A.H.Chi. 19/75-76) 20. Shwitra Hara Taila (Ra.Chi. Sta. 4)

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CHAPTER 14
EXAMINATION OF SKIN AND ITS APPENDAGES

GENERAL SCHEME OF EXAMINATION

Patient registration Name of Patient Age Addres Diagnosis Chief Complaint History of illness Examination of the skin (a) (b) (c) Inspection Palpation Microscopic examination Date Father/Husbands name Sex

Examination of the hair Examination of the nails Diagnosis

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PROFORMA FOR THE STUDY OF THE SKIN DISEASE

HISTORY AND EXAMINATION

Chief complaints : 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Eruptive skin lesions Itchy skin lesions Scaly skin lesions Hyper pigmentation skin lesions Hypo pigmentation skin lesions Hemorrhagic skin lesions Hair loss Graying of hairs Ulceration Nail problems Year/month/day

HISTORY OF THE PRESENT ILLNESS: Mode of onset : Sudden / Gradual Acute / Chronic Constant / Intermittent Localized / Spreading COURSE AND PROGRESS: Family history of skin disease Previous disease of the skin History of intake of drugs History of any local applications Yes / No Yes / No Yes / No Yes / No
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History of any allergy :

Drug Food Others

Yes / No Yes / No Yes / No

If yes, specify Predisposing factors : Food Yes / No

Specify ________________________________________________________ Drugs Yes / No

Specify ________________________________________________________ Seasons Yes / No

Specify ________________________________________________________ Stress Yes / No

Specify ________________________________________________________ Emotional/Psychological Yes / No

Specify ________________________________________________________ Others Yes / No

Specify ________________________________________________________ History of previous medications If yes Allopethic Ayurvedic Homeopathic Others Present ________________________________________________ Medication Yes / No

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OTHER ASSOCIATED COMPLAINTS Hypothyroidism Graves disease Addisons disease Alopecia Areate Seleroderma Melanoma Uvetis Sarcoidosis Hirschsprungs disease Tuberous sclerosis Hypomelanosis Perniocious anaemia Herpes Zoster Halo nevi Tinea versicolor Lichen Sclerosis Piebaldism Nevus depigmentosus Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No Yes / No

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EXAMINATION INSPECTION Colour of the skin

- Pale/Flushed/Cyanosed Dusky Red/Slaty Grey/Brownish/Bronzed Pigmented Yellowish /Depigmented Macular / Roseolar / Erythymatous / Popular / Pustular Skin lesions - / Nodular / Lenticular / Vesicular / Bullous / Scales / Wheeles / Plaques / Haemorrhage Ulcer Describe the skin lesions Scalp/Face/Ears/Eyes/Lips/Neck/Trunk/Back/Hips/Groi ns Genitals/Rt. Upper Limb/Lt. Upper Limb/ Distributions Rt/Lt/Both/Rt. Lower Limb/Rt. Knee/Rt.Ankle/Rt. Sole/Lt. Upper Limb/Lt.Knee/Lt. Ankle/Lt. Sole/Whole Body Colour of the skin lesion Symmetrical / Asymmetrical Generalised / Localized Exposed area / Non exposed area / both / medical aspect / lateral aspect Itching Yes/No Type : Itching Localised / Generalised/ Burning Yes / No Discharge No / Yes If Yes (Blood/Pus/Watery/Serous) Smell Normal / Foul smell Crus Yes / No Dermatographsiu Present/Absent m Hair on the Normal / Hair loss noted affected part Sensation of the Normal / Lost affected skin Reaction to Present / Absent sunlight Haemorrhagic Petechiae / Purpura / Ecchymoses Haematoma / skin lesions Telangiectasis Ulcerative skin lesions Duration Mode of Onset Associated Pain Size and shape Nature of the flood Character of the edge Discharge Tenderness Surrounding skin Lymph modes Palpation Dry or moist

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Texture

Smooth / Rough / Thick / Thin / Elastic / Wrinkled / Pinched / Blanching or pressure Yes / No Localised / Generalized / Pitting / Non Pitting

Tenderness Odema Examination of the hair

Falling of the hair

Yes / No Sudden / Gradual / Patchy / Generalized

Nature and distribution Thick / Coarse / Scanty / Greasy / Abundant / Silky / Soft / Split / Curly / Straight Color Black / Blond / White / Grey / Red

Excessive growth of the hair Yes / No Face / Forearm / Legs / Chest Absence of the axillary, Pubic, Facial hair Yes / No Loss of eye brows Premature graying Trichogram Folioscope Yes / No Yes / No

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SPECIAL EXAMINATION FOR ONLY VITILIGO :

1. 2. 3. 4. 5. 6. 7.

Color of lesion Surface of lesion Itching Burning Sensation Sweating Margin of lesions Hair Present / Absent Color

8. 9. 10. 11. 12. 13. 14. 15.

Pain in lesion Size Intolerance to heat Pin point bleeding Size of oldest lesions in mm Size of newest lesions in mm Size of biggest lesions in mm Size of smallest lesions in mm

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MICROSCOPIC EXAMINATION / SKIN BIOPSY

S.No. 1. 2. 3. 4.

Name of Investigations Hb gm% TLC ESR DLC Neutrophils Lymphocytes Eosinophils Monocytes Basophils

1. 2.

Serum Copper Thyroid Function test T3 T4 TSH

3.

LFT

SGOT SGPT S.Billrubin - Direct Indirect Total

4.

Blood Sugar

Fasting P.P.

5. 6. 7. 8. 9.

Blood Urea Serum Cretinine Skin Biopsy Others Urine Examination Routine Microscopic

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ABBREVIATIONS
A.H.Sha Ashthang Samhita Sharir Sthan Cha. Su Charak Sutra Sthan Cha. Ni Charak Nidan Sthan Cha. Vi Charak Viman Sthan Cha. Sha Charak Sharira Sthan Cha. Chi Charak Chikitsa Sthan Cha. In Charak Indriya Sthan Cha. Ka Charak Kalpa Sthan Cha. Sa Charak Samhita Su.Su Sushruta Sutra Sthan Su. Sa. U Sushruta Samhita Uttar Tantra Su. Sa. Su Sushruta Samhita Sutra Sthan Su. Sa. Ni Sushruta Samhita Nidan Sthan Su. Sa. Sha Sushruta Samhita Sharir Sthan Su. Sa. Chi Sushruta Samhita Chikitsa Sthan Su. Sa. Kal Sushruta Samhita Kalpa Sthan Kas. Sa. Su Kasyapa Samhita Sutra Sthan Kas. Sa. Khi - Kasyapa Samhita Khil Sthan A.H.Su Ashthang Samhita Sutra Sthan A.H.Ni Ashthang Samhita Nidan Sthan A.H.Chi Ashthang Samhita Chikitsa Sthan A.H.Ka. Si Ashthang Samhita Kalpa Sthan A.H.U Ashthang Samhita Uttar Sthan R.R.S. Ras Ratna Samuchaya B.P. Bhav Prakash G.Ni. Gada Nigraha Cha. D Chakra Dutta R.T.S. Rasa Tantra Sara S.P.S. Sidha Prayoga Samgraha Y.R. Yoga Ratanakar B.R. Bhaishajya Ratnawali A.H. Ashtang Hridaya R.Sa.Sa Rasendra Sara Samgraha Sha.Sa Saranghar Samhita Sha. Sa. Ma. Kha - Saranghar Samhita Madhyam Khanda B.N.R. Brihat Nighantu Ratanakar Ra. Chi. Sta Rasendra Chintamani Ra.Ta Rasa Tarangini A.Sa Ashtang Samagraha

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REFERENCES

1.

Duchon J. Fitzpatric. T.B.and Seiji M. (1968) Melanin (1968) Some definitions and problems. In 1967-68 year book of Dermetology (Kopf A.W. and Andrade R. (eds) 1-33, Chicago year book publishing company, chicago.

2.

Breathmach

A.S.

(1969)

Normal

and

Abnormal

melanin

pigmentation of skin. In pigments in pathology (wolman M.Ed.) 35394 Academic press Newyork, London. 3. Fitzpatrick T.B. and Quevedo W.C.Jr (1971) Biological processes underlying melanin pigmentation and pigmentary disorders. In Modern Trends in dermatology (Borrie P.ed) volume 4, 122-149 Butterworth, London. 4. Cruickshank C.N.D. and Harcourt S.A. (1964). Pigment donation in Vitro, J.Invest. Derm, 42, 183-84. 5. Cohen J, Szabo G. 1968, Study in pigment donation in vitro Expl. cell. Res., 50, 418-434. 6. Rosdanl. I, Rosman H, an estimate of the melanocytes mass in humans, J. Invest. Dermatol, 1983, 81 : 278-81. 7. Szabo G. Regional andtomy of the human integument with special reference to the distribution of hair follicles, sweat glands and melanocytes. Phil Trams Roy Soc. London (Biol) 1967, 252, 44785. 8. Goldgeir Mark H, The distribution of melanocytes in the leptomeninges of the human brain, J. Invest. Dermatol, 1984, 82, 235-238. 9. Cui, J. et al Role of Hair follicles in the repigmentation of vitiligo J. Invest Dermatol, 1991, 97 : 410. 10. Cui, J. et al Role of Hair follicles in the repigmentation of vitiligo J. Invest Dermatol, 1991, 97 : 410. 11. Disease of Skin (Book)

115 | P a g e

12. 13. 14.

Fitzpatrick (1964) El-Mofty AM - Vitiligo and psoralens Oxford England Pergamon. Lerner AB, on the actiology and gray hair AMJ Med 1971, 51 : 141147.

15.

Mc Burney E. Vitiligo clinical picture and pathogenesis. Arch Intern. Med. 1979, 139 : 1295-1297.

16. 17. 18.

Lerner AB - Vitiligo, J. Invest Dermatol 1959, 32, 285-310, Lerner AB - Vitiligo, Progress in dermatology 1972, 6:1-6, Nordlund JJ, Lerer AB, Vitiligo its relationship to systemic disease. In maschella SL (Ed.) : Dermatology update. Review for Physician, 1979, 411-432.

19.

Iyengar B. Pathology and pathogenesis of vitiligo and correlates. ICMR Bulletin 1990.

20. 21. 22.

Punshi S.K. 1977 Dutta 1988 Fitzpatrick TB, Elsen Az, Wolff K, et al, Dermatology in general medicine 4th edition Vol-1, New York, McGraw Hill, 1993, 923-933.

23.

Iyengar B. Pathology and pathogenesis of vitiligo and correlates. ICMR Bulletin 1990.

24. 25.

Lerner AB - Vitiligo, Progress in dermatology 1972, 6:1-6, Lerner, A.B., Nordalund, J.J. Vitiligo, what is it ? Is it important ? J.A.M.A. 239 : 1183-1187, 1978.

26. 27.

Lahiri KD, Leucoderma, Ind. J. Dermatol 1959, 4 : 78. Behl PN, Kapur TR, Majumdar M., epidermological study of vitiligo. Dermatology times Feb. 1988, Vol.-IX, No.-1.

28.

Montes LF et al : Folic acid and vitamin B12 in vitiligo a natural approach, cutis, 1992, 50 (1), 39-40.

29.

Lobitz WC, Jr. The Hla system in dematology in recent advance in dermatology. 5th ed. Edinburgh. Ed. rook A savin. J. Churchill. Livingstone, 1980, 51-52.

30.

Behl PN, Kapur TR, Majumdar M., epidermological study of vitiligo. Dermatology times Feb. 1988, Vol.-IX, No.-1.

31.

Lerner AB, on the actiology and gray hair AMJ Med 1971, 51 : 141147.
116 | P a g e

32.

Lerner AB, on the actiology and gray hair AMJ Med 1971, 51 : 141147.

33.

Lerner AB, on the actiology and gray hair AMJ Med 1971, 51 : 141147.

34.

Ortonne JP, Mosher DB and Fitzpatrik TB, Vitiligo and other hypomelanosis of hair and skin new yound. 1983. Plenum Press, P257.

35.

Ortonne JP, Mosher DB and Fitzpatrik TB, Vitiligo and other hypomelanosis of hair and skin new yound. 1983. Plenum Press, P257.

36.

Ortonne JP, Mosher DB and Fitzpatrik TB, Vitiligo and other hypomelanosis of hair and skin new yound. 1983. Plenum Press, P257.

37.

Lobitz WC, Jr. The Hla system in dematology in recent advance in dermatology. 5th ed. Edinburgh. Ed. rook A savin. J. Churchill. Livingstone, 1980, 51-52.

38.

Cui, J. et al Role of Hair follicles in the repigmentation of vitiligo J. Invest Dermatol, 1991, 97 : 410.

39.

Mosher DB et al, Abnormalities of pigmentation, in Dermatology in General medicine, Fitzpatrik TB, Eisen Az et al, Editord 3rd ed. Newyork, McGraw Hill, 1986, 794-876.

40.

Banerjee BN and Pal SK, Len Koderma, Ind. J. Dermatol, 1956, 2 : 1-10.

41. 42.

Lerner AB - Vitiligo, J. Invest Dermatol 1959, 32, 285 Dutta A.K. Vitiligo - Neural and immulogical linkges Ed. Indira Publications, Calcutta, 1988.

43.

Sehgal VN, A clinical evaluation of 202 case of vitiligo, Cutis, 1974, 14, 440-445.

44.

Sarin RC and Kumar AJ, A clinical study of vitiligo. Ind. J. Dermatol venereol Leprol, 1977, 43, 311-314.

45.

Koranee RV and Sachdeve KG. Vitiligo J. Invest Dermatol, 1988, 27, 676-681.
117 | P a g e

46.

Sharma SC. Autoimmune and cutaneous association of various types of vitiligo, Ind. J. Dermatol venerol Laprol, 1991, 57, 107-108.

47. 48.

Lerner AB - Vitiligo, Progress in dermatology 1972, 6:1-6, Ortonne JP, Mosher DB and Fitzpatrik TB, Vitiligo and other hypomelanosis of hair and skin new yound. 1983. Plenum Press, P257.

49.

Brostoff J, Bor S and Feiwel M, autopantibodies in patients with vitiligo, Lancet, 1969, 2 : 177-178.

50.

Sharma SC. Autoimmune and cutaneous association of various types of vitiligo, Ind. J. Dermatol venerol Laprol, 1991, 57, 107-108.

51.

Ortonne JP, Mosher DB and Fitzpatrik TB, Vitiligo and other hypomelanosis of hair and skin new yound. 1983. Plenum Press, P257.

52.

Brostoff J, Bor S and Feiwel M, autopantibodies in patients with vitiligo, Lancet, 1969, 2 : 177-178.

53.

Betterle C, Del Prete GF, Pescerico et al, autoantibodies in vitiligo Arch, Dermatol, 1976, 112, 1328.

54.

Bor S et al. Vitiligo and its etiologic relationship to organ specific autoimmune disease. Br J Dermotol, 1969, 81, 83.

55.

Naughton GK et al. Detection of antibodies to melanocytes in vitiligo by specific immunoprecipitation. J. Invest Dermatol, 1983, 81, 540542.

56.

Naughton GK et al. Expression of vitiligo antigen on a revertant line of hamster melanoma cell. J. Invest Dermatol, 1984-83, 317.

57.

Grimes PE et al. T-cell profiles in vitiligo J AM Acad Dermatol, 1986, 14, 196-201.

58.

D Amelio R et al. Peripheral T-cell subset imballence in patient with vitiligo and in their apparetly healthy first degree relatives. An Alleggy, 1990, 65, 143.

59.

Mozzanica N et al, T-cell population in vitiligo, a chronobiologic study J. Am Acad Dermatol, 1990, 22, 223-230.

60. 61.

Arora PN, vitiligo : Current concepts, 210, 1990. Nordlund JJ, Lener AB, Vitiligo it is important, Arch Dermatol 1981, 118-5.
118 | P a g e

62.

Gokhale BB, Mehta LN, Histopathology of Vitilligenous Skin. Int. J. Dermatol, 1983, 22; 477-480.

63.

Bhel, PN, Pradan BK : Histopathological spectrum of change in three clinical stages of vitiligo Ind. S. Dermatol Venereol Leprol, 1977, 43; 304-308.

64.

Bhawan J, Bhutani LK, Possible Lymphocyte mediated melanocyte and keratinocyte damage in vitiligo. Proceeding of the XIth International pigment cell conference, Sendia, Japan, 1980, Tokyo, 1982, Tokyo Univ. Press, P. 173.

65.

Koach, YuHS : Depletion and repopulation of Lungerhans cells in nonsegmental vitiligo, I, Dermatol (Tokeyo), 1990, 17; 287.

66.

Bleechen,

S.S.;

Pathak,

M.A.,Hori.V.;

Fitzpatrick

T.B.

Depigmentation of skin with 4-isopropyl catechol mercaptoamines and other compounds, J.Invest. Derm. 50:103 (1968). 67. Oliver, E.A. ; Schwartz, L.; Warren , L:occupational leucoderma preliminary report J.AM.Med. Ass. 113:929 (1939). 68. Malten, K.E.; seuter, E.Hama, I; et.al. Occupational vitiligo due to paratertiary butylphenol and nomologues. Trans. St. John's Hosp. derm. Soc. 5:115-134 (1971). 69. Colman, C.D.; Cooke, M.A., Leukoderma in industry. J.Soc. Occ. Med. 24:59 (1974). 70. Bajaj A.K., Govil, D.C.; Contact depigmentation in India. J.derm. Vener.Lepr. 48:112-115 (1982). 71. Pandit R.K., Kumar A.S., Contact Leukoderma due to Bindi and footwear, Darmatologic, 170:260-262 (1985). 72. Shah VC, Majamdar M.V., Sharma KS, some genetic biochemical and physiological aspects of leucodermia / vitiligo, Proc. 2 nd all India congrctyol genet 1975, P.173. 73. Indian Medicinal Plants (1-5 Vol.) P.S. Varier's Arya Vaidya Sala, Kottakkal. 74. 75. Wealth of India Sanskrit-Hindi-English Dictionary, Suryakanta, First ed. 1975, Orient Longman Ltd., New Delhi - 1

119 | P a g e

76.

Dorland's Illustrated Medical Dictionary, 23rd ed., 1961 W.B. Saunders Co., Philadelphia & London.

77.

Webster's New Twentieth Century Dictionary, 2nd ed., William Colling and World Publishing Co., U.S.A.

78.

Encyclopaedia Britannica, Warren E. Preece, Philip W. Geotz, Donald E. Stewart, Christopher H.W. Kent, 15th ed. 1979, Helen Hemingway Benton, Publisher, U.S.A.

79.

Kirtikar, K.B., Basu, B.D. : Indian Medicinal Plants, Bishen Singh M.P. Singh. Periodical Experts, Delhi, 1975.

80.

Medicinal Plants of India, C.V. Satyavati and A.K. Gupta, 1987, Indian Council of Medical Research, New Delhi.

81.

Hooker, J.D. The flora of British India, L Reeve and Co., London (1897), 2nd Indian Reprit. 1978.

82.

Phytochemical Investigations of Certain Medicinal Plants used in ayurveda, First ed. 1990, C C R A S, Delhi.

83.

Indian Materia Medica, Nadkarni, K., 3rd ed. Popular Book Depot Bombay and Dhootpapeswar Prak. Ltd. Panvel.

84.

Flora of British India - J.D. Hooker, C.B. K.C. S.F. (I-VI Vol.) International Book Distributors, Deharadun.

85.

A Niederwieser and G. Pataki (eds.), New Techniques in amino acid, Peptide and protien analysis (1971).

86.

M.O. Dayhoff (ed.), Atlas of Protien sequence and structure (1969, Published in Intervals of 1 or 2 years).

87.

Felix Haurowitz, The Chemistry and Function of Protiens, 2nd ed. 1963.

88. 89.

I.U.B. Engyme Nomenclature (1965). Manual of Dermatologic Therapeutics, Kenneth A. Arnott, LittleBrown and Co. Boston.

90.

Clinical Tropical Dermatology, Ornaldo Canizares, Blackwell Scientific Publication.

91. 92.

S. Rothman, Physiology and Biochemistry of the skin (1954). A.J. Rook, D.S. Wilkinson, and F.T.G. Edeling (eds.) Text book of Dermatology, 2nd Vol. (1968).

120 | P a g e

93.

A.L. Lorincz, Physiological and pathological changes in skin from Sunburn and Suntan, J.A.M.A. 173 (1960).

94.

W.M. Leach, Biological Aspects of ultraviolet Radiation, Tech. Rep. U.S. Bur. Radiol. Hlth.(1970).

95.

Rothman S., Physiology and Biochemistry of the skin, 1954, The University of Chicago Press, Chicago.

96.

Jefrey P. Callen, Mark V. Dahl. Loren E. Golitz, Lawrence A. Schachner, Samual. J Stegman : Advances in dermatology, Vol. 4. 1989.

97. 98.

Indian Medicinal Plant. (I-III Vol.) Kirtikar & Basu (IInd ed.) Waring, Edward, John, 1968, Pharmocoepia of India, W.H. Allen and Co., London.

99.

Sidney Hurwitz, Clinical pediatric Dermatology, W.B. Saunders Company, Philadelphia and London.

100.

Roxburgh's Common skin disease, John D. Kirby, 15th ed. 1980, H.K. Lewis and Co. Ltd., London.

101.

Practice of Dermatology, Bhel, P.N., 7th ed. 1990, C.B.S. Publishers and Distributors, Shahdara, Delhi.

102.

Manual of skin diseases, Gordon C. Sauer, 3rd ed., J.B. Lippincott Company.

103.

A Treatise on Tropical skin disease, K.B.D. Lahiri Thacker, Spink and Co. Pvt. Ltd.

104.

Dermatology in General practise, Sigmund S. Greenbaum, F.A. Davis Company.

105.

Principal and practise of Dermatology, W.E. De. Launey, W.A. Land, Butter Worths, London.

106.

Harrison's Principles of internal medicine, 12th ed., 1991, Jean D. Wilson, Eugene Braunwald, Kurt J. Isselbacher, Robert G. Petersdorf, Joseph B. Martin, Anthony S. Fauci, Richard K. root, McGraw-Hill, Inc.

107. 108.

T.B. Fitzpatrick, Dermatological differential diagnosis (1962). L. Schwartz, L. Tulipan and D.J. Birmingham, Occupational Disease of the skin, 3rd ed. 1957.

109.

W.F. Lever Histopathology of the skin, 4th ed., 1967.

121 | P a g e

110.

H.E. Schultze and J.F. Heremans, Molecular Biology of Human Proteins, 2 Vol. 1966.

111.

Parrish, J.A. Fitzpattrick, T.B. Shea, Photochemotherapy of vitiligo. Use of orally administered proralen and high - Intensity Longwave ultraviolet system Arch, Dermatol. 112; 1531-1534, 1976.

112.

Hale, A.R. (1952) Morphogenesis of volar skin in human fetus, Am. J. Anat, 91,147-81.

113.

Ellis H., Morgan M.N. : Surgical treatment of severe hyperhidrosis, proc. Roy. Soc. Med. 64 : 768, 1971.

114.

Hartfall W.G., Jochimsen P.R.: Hyperhidrosis of upper extremity and its treatment, Surg. Gynecol. Obstet., 135 : 586,1972.

115.

Elias P.M.: Plastic wrap revisited: The stratum corneum two compartment model and its clinical implications, Arch. Dermatol 1987,123:1405-6.

116.

Nordlund J.J., Abdel - Maiek Z.A. Mecanisms for post-inflammatory hyperpigmentation and hypopigmentation, proc. XIII Int. Pig. Cell. Conf.

117.

Streliein J.W.: Skin associated lymphoid tissues (SALT): Origins and functions, J. Invest. Dermatol. 1983, 80 :12s-16s.

118.

Duchon J. Fitzpatric T.B. and Seiji M. (1968). Melanin (1968): Some definitions and problems. In : 1967-68 Year book of Dermetology (Kopf A.W. and Andrade R. (eds), 1-33, Chicago year book publishing company, Chicago.

119.

Breathmach

A.S.

(1969)

Normal

and

Abnormal

melanin

pigmentation of the skin. In pigments in pathology (Wolman M.Ed.) 353-94, Academic press : Newyork, London. 120. Fitzpatrick T.B. and Quevedo W.C. Jr. (1971), Biological processes underlying melanin pigmentation and pigmentary disorders. In. Modern Trends in dermatology (Borne P.ed.) Volume 4, 122- 149, Butterworth: London. 121. Cruickshank C.N.D. and Harcourt S.A. (1964). Pigment donation in vitro, J. Invest. Derm, 42,183-84. 122. Cohen J. Szabo G. 1968, Study in pigment donation in vitro Expl. Cell. Res., 50, 418-434.
122 | P a g e

123. 124.

Charka Samhita Satyanarayan Shastri Charka Samhita Dr. Brahma nand Tripati, Chaukhamba Publication, Varanasi Sushruta Samhita Ambika Dutt Shastri, Chaukhamba Orientalia, Varanasi Harita Samhita Govinda Shastri, Khemraj Shai krishandas, Mumbai Bhela Samhita Grijadayalu Sukla, Chaukhamba vidhya bhawan, Varanasi Sushruta Sharir Sthan Dr. Bhaskar Govind Ghanekhar Mehar Chanda Laxmandas, Delhi 6 Kasyap Samhita Pandir Hemraj Sharma, Chaukhamba Sanskrit Series Office, Varanasi Vrahat Rasraj Sundar Pandir Dut Ram Chaube, Chaukhamba Orientalia, Varanasi Rasendra Chaudamani Dr. Sidhinandan Mishra, Chaukhamba Orientalia, Varanasi Ras Ratnakar Dr. Indra Dev Tripathi, Chaukhamba Amar Bhartiya Prakashana Varanasi

125.

126.

127.

128.

129.

130.

131.

132.

133.

Ras Prakash Sudhakar - Dr. Indra Dev Tripathi, Chaukhamba Amar Bhartiya Prakashana Varanasi Yoga Trangini (Trimalla Bhatta) Hari narayan Aapte, Ananda Ashram, Mudranalaya Rasa Ratna Samuchya Prof. D. Anant Kulkarni, Meharchand Laxman Das, New Delhi Drvyaguna Vigyan Acharya Priyavarat Sharma, Chaukhamba Bharti Academy, Varanasi Anand Kand S.V. Radha Krishnan Shastri, Vilash Press, Shri rangam Siddh Bhaishyajya Manimala Vd. Devendra Prasad Bhatta, Shri Shankar Art Printers, Jaipur Rasa Tarangini Dharmanand Shastri, Motilal Banarasi das, Delhi 7

134.

135.

136.

137.

138.

139.

123 | P a g e

140.

Ayurveda Prakash Gul Raj Sharma Mishra, Chaukhamba Vidha Bhawan, Varanasi Rasendra Sara Sangraha Sh. Jaydev Vidhaalankar Motilal, Banarasi Das, Varanasi Ashtang Sangraha P.V. Sharma, Chaukhamba Orientalia Varanasi Ashtang Sangraha Pandir Lal Chand Shastri, Shri Vaidhanath Ayurveda Bhawan, Nagpur Ashtang Sangraha Dr. Ravidutt Tripathi Ashtang Haridaya Vd. Govardhan Sharma Changani,

141.

142.

143.

144. 145.

Chaukhamba Sanskrit Series Varanasi 146. 147. Ashtang Hridaya Dr. Barhma Nand Tripathi Vanga Sen Samhit Ram Kumar Rai, Prachya Prakashan, Varanasi 148. Chakaradutt Jagdishwar Prasad Tripathi, Chaukhamba Sanskrit Series, Varanasi 149. Sharngadhar Samhita Dr. Brahma Nand Tripathi, Chaukhamba Subharti Prakashan, Varanasi 150. Bhaishajya Ratnawali Rajeshwar Dutt Shastri, Chaukhamba Sanskrit Sansthan, Varanasi 151. Gada Nigraha Dr. Indra Dev Tripathi, Chaukhamba Sanskrit Office, Varanasi 152. Bhav Prakash Brahama Shankar Shastri, Chaukhamba Sanskrit Series Office, Varanasi 153. Yoga Ratanakar Brahama Shankar Shastri, Chaukhamba Sanskrit Series Office, Varanasi 154. Yoga Chintamani Pandit Sitaram Sharma, Bhargava Pustkalaya, Varanasi 155. 156. 157. 158. 159. 160. Sushruta Samhita Dr. Ambika Dutta Shastri I and II Vol. Sidha Prayoga Samgraha Brihat Nighantu Ratnakar Ph.D. Thesis of Dr. P.S. Yadav Ph.D. & M.D. Thesis of Dr. N.K. Dadhich Twaka and Bhrajaka Pitta Vivechana Dr. B.K. Panwar
124 | P a g e

161.

Best and Taylors Physiology Basis of Medical Practices, Edited by John B. West, Twelfth Edition, 1990, First Indian Edition, 1996. Concise Medical Pysiology By Sujit, K. Chaudhuri Forth Edition 2002.

162.

163.

Text Book of Medical Biochemistry, By. M.N. Chatterjee and Rana Shinde, Third Edition, 1998.

164.

Text Book of Medical Physiology, By. Guyton and Hall, Ninth Edition 1999. The fundamental principles of ayurveda by. D.C. Dwarkanath, Vol 1 to 3, Reprint edition 2003.

165.

166.

The student Sanskrit English Dictionary by Vaman Shivram Apte, Second edition, 1970 Essential of Medical physiology K. Semutingam (Fifth Edition) Text Book of Biochemistry for Medical Students Sixth Edition D.M. Vasudevan Steekumaris and Kaman Vaidyan Athan Human Physiology C.C. Chatterjee Principles of Anatomy and Physiology Gerquard J. Tortosa and Sandra Reynolds Grabowska Priview of medcal Physiology William F. Ganoyg Practice of Dermatology, Bhel, P.N. 7th Ed. 1990 C.B.S. Publication and Distributors, Shahdara, Delhi S. Rothman Physiology and Biochemistry of Skin (1954). www.vitiligosociety.org uk/symposium.html www.vitiligofoundation.org/approach.html www.patholgy.ufl.edu./mccromac/abstracts/html www.advarcement.uark.edu/pubs/reacherarch/fronters/tall2002/08Feature4.html

167. 168.

169. 170.

171. 172.

173. 174. 175. 176. 177.

178. 179. 180.

www.cancerres.aarjeornals.org/cgi/content/full/62/16/4836 www.americanbiologics.com/publication/monographs.html www.womenshealth.com/library/bl_autoimmune 9.html

125 | P a g e