structure of skin
DESCRIPTION
YE BHITRANSCRIPT
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 : [email protected]
Contact No. : +91-9557317321
CONTENTS
CHAPTER I STRUCTURE OF SKIN Introduction Development of skin Anatomical structure of skin Epidermis Dermis Hair follicles Nails
1-8
CHAPTER II SWEAT GLANDS Eccrine sweat glands Apocrine glands Sebaceous glands Composition of sebum Function of sebum Ceruminous glands Arrectores pilorum
9-12
CHAPTER III 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
13-17
CHAPTER IV COLOR OF THE SKIN Introduction Pigmentation in the human skin Melanin Melanoid Carotene Haemoglobin Oxyhaemoglobin
18-20
CHAPTER V 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
21-31
Pigment Production Inhibitors of melanin synthesis Importance of melanin pigmentations
CHAPTER VI BIOCHEMISTRY OF MELANIN PIGMENTATION Stages of Melanocytes Development Stages of Menanin Formation Dopaquinon Production Melanogenesis Biochemistry of Important Specialized
Product from Tyrosine Melanin Catecholamine
32-41
CHAPTER VII CLINICAL APPLICATION OF MELANIN Clinical applications of melanin Albinism Hypertyrosinemias Applied physiology of skin pigment
42-46
CHAPTER VIII
VITILIGO Introduction Historical aspect and vitiligo Synonyms Derivation Definitions Epidemiology Actiology Associated Aetiological factors
47-55
CHAPTER IX CLINICAL MANIFESTATIONS OF VITILIGO Distribution of vitiligo patches Koebner’s 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
56-59
CHAPTER X DIFFERENTIAL DIAGNOSIS OF VITILIGO Differential diagnosis Associated factors
60-65
CHAPTER XI MANAGEMENT OF VITILIGO General awareness Non surgical methods Surgical methods
66-86
Psychological and social counselingCHAPTER 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)
87-93
CHAPTER XIII
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
94-105
CHAPTER XIV
EXAMINATION OF SKIN AND ITS APPENDAGES
106-113
CHAPTER XV APPENDIX 114-125ABBREVIATIONS BIBLIOGRAPHY AND REFERENCES
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.
DEVELOPMENT OF SKIN :
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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. Stratum corneum
2. Stratum lucidum
3. Stratum granulosum
4. Stratum spinosum
5. 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. Stratum Description
1 Basale or Germinativam Deepest layer, composed of single row
of cubiodal or columnar keratinocytes
that contain scaltered tonofilaments
(intermediate filaments); stem cells
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.
DERMIS:
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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 are-
1. 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 the
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 the
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
cellular proteins. The shaft is the superficial portion of the hair, most of which
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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 like-
a. Axilla
b. Groin areolae of the breasts
c. Pubis
d. 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
of-
1. Triglyceride
2. Cholesterol
3. Proteins
4. Squalene
5. Sterols
6. Paraffin
7. Waxes
8. 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 krause’s end bulbs,
whereas ruffini’s ending are probably receptors for warmth. Meissner’s
corpuscles and market’s discs are implicated in the tactile sensation and the
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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. Melanin
2. Melanoid
3. Carotene
4. Hemoglobin
5. 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 TO DUCHON. J. FITZPATRIC, T.B. AND SEIJI M AND BREATHMACH
A.S.:
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
22 | P a g e
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
23 | P a g e
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. Total epidermal melanocyte population is about 2x109 cells.
2. The melanocyte mass forms a tissue 1.0 x 1.5 cm3.
3. The population density is high on face 2900 mm2.
4. Melanocyte density decreases by 6-8% per decade.
5. 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. Eumelanin
2. Pheomelanin
3. 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, appears-
bluish. 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 melanocyte-
stimulating 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
when cortisol secretion is low and low following administration of
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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 below-
STAGE : 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 O–dihydrophenyl 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 mµ.
TYROSINE
Irreversible oxidized Tyrosinase Oxygen
Dopa
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
Norepinephrin
e
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 Tyrosine hydroxylase
DOPA
(Dihydroxy phenylalanine)
DOPA decarboxylase
Dopamine
Cu++ Vit.CDopamine 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) Tyrosinemia (Type I) or Hepatorenal Tyrosinemias
(2) Tyrosinemia (Type II) or oculoocutaneous Tyrosinemias
(3) Neonatal Tyrosinemia
(1) 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
1 Leprosy It is a skin infection caused by Mycobacterium
leprae.
2 Vitiligo White patches in the skin, vitiligo caused by the
less of pigment producing cells melanocytes in
the skin.
3 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.
4 Pityriasis Alba Small circular spots on the child face usually the
cheeks, often noticeable in summer when the
skin is tanned.
5 Pigment loss after
skin damage
Sometimes after an ulcer, blister, burn or infection
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 Addision’s 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
bathing trunk nevi or
giant nevi
It is a round, brown and black, flat or slightly
raised and can be found anywhere on the skin. It
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.
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There is no complaint in vitiligo patient, except erthema and burning after sun
exposure in few. But psychologically it is very distressing.
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 person’s 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
vitiligo. But the etiology of vitiligo is still unknown, but genetic factors,
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:
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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
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 probably 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).
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Treatment of vitiligo or shweta kustha has been mentioned the Bakuchi seeds
for a long times.
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.
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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.
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 world’s 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’
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worsens a vitiligo and strict restriction on its intake and at least one half
effected person have a positive family history of vitiligo.
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.
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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
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 –
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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.
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.
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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
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. Grave’s disease
d. Toxic goiter
e. Thyroiditis
f. etc
2. Diabetes Mellitus
3. Hyper Parathyroidism
4. Additions disease
5. Pernicious anaemia
6. Halo Nevi
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7. Alopecia Areata
8. Myasthenia Gravis
9. Malignant melanoma
10. Cronic mucocutaneous candidiasis
11. Multiple endocrinopathy syndrome
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CHAPTER 9
CLINICAL MANIFESTATIONS OF VITILIGO
Distribution of vitiligo patches
Koebner’s 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
season, lesions become more conspicuous because of increased
pigmentation of the surrounding normal pigmented skin.
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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, bindi’s, gloves,
other rubber or plastic material, pressure to trauma and to remove
their influence as for as possible.
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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 agents – Sulphonylurea compounds,
phenothiazine derivatives, polypodium leukotomas,
psudocatalase with calcium
NON PHOTO CHEMOTHERAPEUTIC AGENTS:
These includes:
a. Corticosteroids
a. Topical
b. Oral
b. Placentral extract preparation
c. Nilamide
d. Levadopa
e. Canthaxanthin
f. Topical crude tar
g. Nitrogen mustard
h. Isoprinosine and pentoxifylline
i. Broad spectrum sunscreen
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j. Cosmetic camouflage
k. Fluorouracil
l. Dapsone
m. Quinoline Compounds
n. 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:
Exposure time (min . )=PrescribedUVA dose (J /Cm2)
0.86 x irradiance(wm /Cm2)
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 –
Psoralen originally obtains from the plant psoralea corylifolia (Bakuchi)
is India.
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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 : Psoralia corylifolia Linn.
English Name : Purple fleabane, psoralea seed
Family : Fabaceae (Papilionaceae)
Synonyms : Somaraji, Avalguja, Krishnaphala, Putiphali,
Kushthaghni (in Hindi and Sanskrit)
Part Used : Seed
Psoralia Corylifolia Linn Seed of Psoralia Corylifolia
PHYTOCHEMICAL COMPOSITIONS:
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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. Bavachinin ii. Bavachiniii. Isobavachin iv. 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.
4. CHALCONES :
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i. Isobavachalcone
ii. Isoneobavachalcone
iii. Bavachromanol
iv. 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.
Folk medicines in several cultures treated vitiligo with topical extracts of these
plants that contains Furocoumarins.
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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.
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 – Photosensitizing agents (orally or topically)UV – Ultra violet light irradiationA – Light source is artificialSOL – Light source is sun
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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
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.
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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.
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:
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Nausea
Epigastric discomfort
Pruritis
Insomnia
Nervousness
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.
NON PHOTO CHEMOTHERAPEUTIC AGENTS
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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.
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.
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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.
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.
QUINOLINE COMPOUNDS
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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. Punch grafting / autologous epidermal mini grafting.
2. Thin thiersch split skin grafting
3. Epidermal grafting
4. Melanocyte cuture and transplantation
5. Autologous grafting with non cultured melanocytes
6. Therapeutic spot and regional dermabrasion
7. 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
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.
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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 an
average of 180 - 300cm2 possible in one session.
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
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.
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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
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
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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
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:
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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 12AYURVEDIC 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
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.
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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).
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.
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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 Apatrapana
Brihana
Snehana
Stambhana
Langhana
Rukhana
Swedana
(A.H.Su. 14/1-3)
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
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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 once in 15 days
Virechana therapy once in 3 months
Shiroverchana once in 3 days
Raktamoshshana 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).
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.
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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) –
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 :
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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.
SATVAVAJAYA CHIKITSA (PSYCHOTHERAPY)
Satvavajaya Chikitsa is a type of Trividha Aushadhi in which physician try to
withdraw the mind of patients from harmful subjects1. 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
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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 13AYURVEDIC 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. Bakuchi (B.P. Batadi Varga 33)
b. Khadira (Cha. Su. 25/40)
c. Chitraka (A.H.U. 39/65)
d. Bhringaraja (A.H. Chi. 20/8)
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e. Bhallataka (A.H. Chi. 20/11)
f. Kakodumara (B.P. Batadi Varga 10)
g. Shinshapa (B.P. Batadi Varga 25)
h. Bakula (B.P. Pushpa Varga 33)
i. Endri (Cha. Chi 1/3/29)
j. Ashvagandha (B.P. Guduchyadi Varga 189)
k. Rasona (Cha. Su. 27/176)
l. 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. Lodhra – Symplocus race mosa
ii. Shyonaka – Oroxylum indicum
iii. Pathani Lodhra
iv. Ashoka – Saraca asoca
v. Palasha – Butea monosperma
vi. Bharangi – Clerodendrum serratum
vii. Kayaphala – Myrica esculenta
viii. Elabaluka – Prunus cerasus
ix. Shallaki – Boswellia serrata
x. Jingini – Odina woodier
xi. Sala – Shorea robusta
xii. Kadamba – Anthocephalus indicum
xiii. 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
ii. Ela – Elettaria Cardamomum
iii. Tagara – Valleriana Wallichii
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iv. Jatamansi – Nordostachyus Jatamansi
v. Dhayamaka
vi. Dalachini – Cinnamomum Zeylanicum
vii. Tejapatra – Cinnamomum Tamala
viii. Priyangu – Callicarpa Macrophylla
ix. Harenuka – Vitex negundo (Seeds)
x. Shukti – Margarita
xi. Vyaghranuka – Achantina fulica
xii. Chanda – Rauwolfia Serpentina
xiii. Sthauneyaka – Taxus baccata
xiv. Srivesthtaka – Pinus roxburghii
xv. Choraka – Angelia gluca
xvi. Guggulu – Commiphora mukul
xvii. Baluka – Mimosops elergi
xviii. Sarjarasa – Vateria indica
xix. Kunduru – Extract of Boswellia serrata
xx. Agaru – Aquilaria agalocha
xxi. Sprikka – Anisomeles malabarica
xxii. Ushira – Veteveria zizanoides
xxiii. Devadaru – Cedrus deodar
xxiv. Keshara – Crocus sativus
xxv. Punnagakeshara – colophyllum inophyllum
b. Asanadi Gana: According to Acharya Vagabhatta varnya medicines.
This includes (A.H.Su. 15-19/20)
i. Asana – Pterocarpus massupium
ii. Tinisha – Ougenia oojeinensis
iii. Bhojabatra – Betula utilis
iv. Arjuna – Terminalia arjuna
v. Puti Karanja – Holoptella integrifolia
vi. Khadira – Acacia catechu
vii. Shirisha – Albizzia lebbeck
viii. Shishapa – Dalbergia sissoo
ix. Meshashringi – Gymnema sylvestre
x. Trihima –
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xi. Tala – Borassus fdabbifer
xii. Palasha – Butea monosperma
xiii. Agaru – Aquilaria agalocha
xiv. Sagaun – Tectona grandis
xv. Sala – Shorea robusta
xvi. Supan
xvii. Dhava – Anogessus latifolia
xviii. Indrayana – Holarrhena antidysentrica
xix. Chhagakama
xx. 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.)
Kwatha (Decotion Preparation )
Dose : 20-40 ml
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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.)
3. Vidangadi Avaleha (A.H.)
4. Bhallatakavaleha (Y.R.)
Ghrita Preparations Dose : 10-20 gm.
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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
Saktu Preparations (Cha. Su. 23/19-24)
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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.)
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.)
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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).
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)
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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)
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)
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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)
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)
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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 14EXAMINATION OF SKIN AND ITS APPENDAGES
GENERAL SCHEME OF EXAMINATIONPatient registration DateName of Patient Father/Husband’s nameAge SexAddresDiagnosisChief ComplaintHistory of illnessExamination of the skin
(a) Inspection(b) Palpation(c) Microscopic examination
Examination of the hairExamination of the nailsDiagnosis
PROFORMA FOR THE STUDY OF THE SKIN DISEASE
HISTORY AND EXAMINATION
Chief complaints :
1. Eruptive skin lesions Year/month/day
2. Itchy skin lesions
3. Scaly skin lesions
4. Hyper pigmentation – skin lesions
5. Hypo pigmentation – skin lesions
6. Hemorrhagic skin lesions
7. Hair loss
8. Graying of hairs
9. Ulceration
10. Nail problems
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HISTORY OF THE PRESENT ILLNESS:Mode of onset : Sudden / Gradual
Acute / ChronicConstant / IntermittentLocalized / Spreading
COURSE AND PROGRESS:Family history of skin disease Yes / NoPrevious disease of the skin Yes / NoHistory of intake of drugs Yes / NoHistory of any local applications Yes / NoHistory of any allergy : Drug Yes / No
Food Yes / NoOthers Yes / No
If yes, specifyPredisposing factors : Food Yes / NoSpecify ________________________________________________________
Drugs Yes / NoSpecify ________________________________________________________
Seasons Yes / NoSpecify ________________________________________________________
Stress Yes / NoSpecify ________________________________________________________
Emotional/Psychological Yes / NoSpecify ________________________________________________________
Others Yes / NoSpecify ________________________________________________________History of previous medications Yes / NoIf yes –
AllopethicAyurvedicHomeopathicOthersPresent Medication ________________________________________________
OTHER ASSOCIATED COMPLAINTS
Hypothyroidism Yes / No
Grave’s disease Yes / No
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Addison’s disease Yes / No
Alopecia Areate Yes / No
Seleroderma Yes / No
Melanoma Yes / No
Uvetis Yes / No
Sarcoidosis Yes / No
Hirschsprungs disease Yes / No
Tuberous sclerosis Yes / No
Hypomelanosis Yes / No
Perniocious anaemia Yes / No
Herpes Zoster Yes / No
Halo nevi Yes / No
Tinea versicolor Yes / No
Lichen Sclerosis Yes / No
Piebaldism Yes / No
Nevus depigmentosus Yes / No
EXAMINATIONINSPECTION
Colour of the skin - Pale/Flushed/Cyanosed
Yellowish -Dusky Red/Slaty Grey/Brownish/Bronzed Pigmented /Depigmented
Skin lesions -Macular / Roseolar / Erythymatous / Popular / Pustular / Nodular / Lenticular / Vesicular / Bullous / Scales / Wheeles / Plaques / Haemorrhage Ulcer
Describe the skin lesionsDistributions Scalp/Face/Ears/Eyes/Lips/Neck/Trunk/Back/Hips/
Groins Genitals/Rt. Upper Limb/Lt. Upper Limb/
107 | P a g e
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
Type :
Symmetrical / Asymmetrical Generalised / Localized Exposed area / Non exposed area / both / medical aspect / lateral aspectItching Yes/NoItching Localised / Generalised/ Burning Yes / NoDischarge No / YesIf Yes (Blood/Pus/Watery/Serous)Smell Normal / Foul smellCrus Yes / No
Dermatographsium
Present/Absent
Hair on the affected part
Normal / Hair loss noted
Sensation of the affected skin
Normal / Lost
Reaction to sunlight
Present / Absent
Haemorrhagic skin lesions
Petechiae / Purpura / Ecchymoses Haematoma / Telangiectasis
Ulcerative skin lesionsDurationMode of OnsetAssociated PainSize and shapeNature of the floodCharacter of the edgeDischargeTendernessSurrounding skinLymph modes
Palpation Dry or moist
Texture Smooth / Rough / Thick / Thin / Elastic / Wrinkled / Pinched / Blanching or pressure
Tenderness Yes / No
Odema Localised / Generalized / Pitting / Non Pitting
Examination of the hair
108 | P a g e
Falling of the hairYes / NoSudden / 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 / NoFace / Forearm / Legs / Chest
Absence of the axillary, Pubic, Facial hair
Yes / No
Loss of eye brows Yes / No
Premature graying
Yes / No
Trichogram
Folioscope
SPECIAL EXAMINATION FOR ONLY VITILIGO :
1. Color of lesion
2. Surface of lesion
3. Itching
4. Burning Sensation
5. Sweating
6. Margin of lesions
109 | P a g e
7. Hair – Present / Absent
– Color
8. Pain in lesion
9. Size
10. Intolerance to heat
11. Pin point bleeding
12. Size of oldest lesions in mm
13. Size of newest lesions in mm
14. Size of biggest lesions in mm
15. Size of smallest lesions in mm
110 | P a g e
MICROSCOPIC EXAMINATION / SKIN BIOPSY
S.No. Name of Investigations
1. Hb gm%
2. TLC
3. ESR
4. DLC - Neutrophils
Lymphocytes
Eosinophils
Monocytes
Basophils
1. Serum Copper
2. Thyroid Function test - T3
T4
TSH
3. LFT SGOT
SGPT
S.Billrubin - Direct
Indirect
Total
4. Blood Sugar - Fasting
P.P.
5. Blood Urea
6. Serum Cretinine
7. Skin Biopsy
8. Others
9. Urine Examination
Routine
Microscopic
111 | P a g e
ABBREVIATIONS
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.Sha – Ashthang Samhita Sharir 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
112 | P a g e
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.) 353-
94 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, 447-
85.
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)
113 | P a g e
12. Fitzpatrick (1964)
13. El-Mofty AM - Vitiligo and psoralens Oxford England Pergamon.
14. Lerner AB, on the actiology and gray hair AMJ Med 1971, 51 : 141-
147.
15. Mc Burney E. Vitiligo clinical picture and pathogenesis. Arch Intern.
Med. 1979, 139 : 1295-1297.
16. Lerner AB - Vitiligo, J. Invest Dermatol 1959, 32, 285-310,
17. Lerner AB - Vitiligo, Progress in dermatology 1972, 6:1-6,
18. 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. Punshi S.K. 1977
21. Dutta 1988
22. 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. Lerner AB - Vitiligo, Progress in dermatology 1972, 6:1-6,
25. Lerner, A.B., Nordalund, J.J. Vitiligo, what is it ? Is it important ?
J.A.M.A. 239 : 1183-1187, 1978.
26. Lahiri KD, Leucoderma, Ind. J. Dermatol 1959, 4 : 78.
27. 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 : 141-
147.
114 | P a g e
32. Lerner AB, on the actiology and gray hair AMJ Med 1971, 51 : 141-
147.
33. Lerner AB, on the actiology and gray hair AMJ Med 1971, 51 : 141-
147.
34. Ortonne JP, Mosher DB and Fitzpatrik TB, Vitiligo and other
hypomelanosis of hair and skin new yound. 1983. Plenum Press, P-
257.
35. Ortonne JP, Mosher DB and Fitzpatrik TB, Vitiligo and other
hypomelanosis of hair and skin new yound. 1983. Plenum Press, P-
257.
36. Ortonne JP, Mosher DB and Fitzpatrik TB, Vitiligo and other
hypomelanosis of hair and skin new yound. 1983. Plenum Press, P-
257.
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. Lerner AB - Vitiligo, J. Invest Dermatol 1959, 32, 285
42. 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.
115 | 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. Lerner AB - Vitiligo, Progress in dermatology 1972, 6:1-6,
48. Ortonne JP, Mosher DB and Fitzpatrik TB, Vitiligo and other
hypomelanosis of hair and skin new yound. 1983. Plenum Press, P-
257.
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, P-
257.
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, 540-
542.
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. Arora PN, vitiligo : Current concepts, 210, 1990.
61. Nordlund JJ, Lener AB, Vitiligo it is important, Arch Dermatol 1981,
118-5.
116 | 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. 2nd all India
congrctyol genet 1975, P.173.
73. Indian Medicinal Plants (1-5 Vol.) P.S. Varier's Arya Vaidya Sala,
Kottakkal.
74. Wealth of India
75. Sanskrit-Hindi-English Dictionary, Suryakanta, First ed. 1975,
Orient Longman Ltd., New Delhi - 1
117 | 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. I.U.B. Engyme Nomenclature (1965).
89. Manual of Dermatologic Therapeutics, Kenneth A. Arnott, Little-
Brown and Co. Boston.
90. Clinical Tropical Dermatology, Ornaldo Canizares, Blackwell
Scientific Publication.
91. S. Rothman, Physiology and Biochemistry of the skin (1954).
92. A.J. Rook, D.S. Wilkinson, and F.T.G. Edeling (eds.) Text book of
Dermatology, 2nd Vol. (1968).
118 | 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. Indian Medicinal Plant. (I-III Vol.) Kirtikar & Basu (IInd ed.)
98. 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. T.B. Fitzpatrick, Dermatological differential diagnosis (1962).
108. 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.
119 | 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.
120 | P a g e
123. Charka Samhita – Satyanarayan Shastri
124. Charka Samhita – Dr. Brahma nand Tripati, Chaukhamba
Publication, Varanasi
125. Sushruta Samhita – Ambika Dutt Shastri, Chaukhamba Orientalia,
Varanasi
126. Harita Samhita – Govinda Shastri, Khemraj Shai krishandas,
Mumbai
127. Bhela Samhita – Grijadayalu Sukla, Chaukhamba vidhya bhawan,
Varanasi
128. Sushruta Sharir Sthan – Dr. Bhaskar Govind Ghanekhar Mehar
Chanda Laxmandas, Delhi – 6
129. Kasyap Samhita – Pandir Hemraj Sharma, Chaukhamba Sanskrit
Series Office, Varanasi
130. Vrahat Rasraj Sundar – Pandir Dut Ram Chaube, Chaukhamba
Orientalia, Varanasi
131. Rasendra Chaudamani – Dr. Sidhinandan Mishra, Chaukhamba
Orientalia, Varanasi
132. Ras Ratnakar – Dr. Indra Dev Tripathi, Chaukhamba Amar Bhartiya
Prakashana Varanasi
133. Ras Prakash Sudhakar - Dr. Indra Dev Tripathi, Chaukhamba Amar
Bhartiya Prakashana Varanasi
134. Yoga Trangini (Trimalla Bhatta) – Hari narayan Aapte, Ananda
Ashram, Mudranalaya
135. Rasa Ratna Samuchya – Prof. D. Anant Kulkarni, Meharchand
Laxman Das, New Delhi
136. Drvyaguna Vigyan – Acharya Priyavarat Sharma, Chaukhamba
Bharti Academy, Varanasi
137. Anand Kand – S.V. Radha Krishnan Shastri, Vilash Press, Shri
rangam
138. Siddh Bhaishyajya Manimala – Vd. Devendra Prasad Bhatta, Shri
Shankar Art Printers, Jaipur
139. Rasa Tarangini – Dharmanand Shastri, Motilal Banarasi das, Delhi
– 7
121 | P a g e
140. Ayurveda Prakash – Gul Raj Sharma Mishra, Chaukhamba Vidha
Bhawan, Varanasi
141. Rasendra Sara Sangraha – Sh. Jaydev Vidhaalankar Motilal,
Banarasi Das, Varanasi
142. Ashtang Sangraha – P.V. Sharma, Chaukhamba Orientalia
Varanasi
143. Ashtang Sangraha – Pandir Lal Chand Shastri, Shri Vaidhanath
Ayurveda Bhawan, Nagpur
144. Ashtang Sangraha – Dr. Ravidutt Tripathi
145. Ashtang Haridaya – Vd. Govardhan Sharma Changani,
Chaukhamba Sanskrit Series Varanasi
146. Ashtang Hridaya – Dr. Barhma Nand Tripathi
147. 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. Sushruta Samhita – Dr. Ambika Dutta Shastri I and II Vol.
156. Sidha Prayoga Samgraha
157. Brihat Nighantu Ratnakar
158. Ph.D. Thesis of Dr. P.S. Yadav
159. Ph.D. & M.D. Thesis of Dr. N.K. Dadhich
160. Twaka and Bhrajaka Pitta Vivechana – Dr. B.K. Panwar
122 | P a g e
161. Best and Taylor’s Physiology Basis of Medical Practices, Edited by
John B. West, Twelfth Edition, 1990, First Indian Edition, 1996.
162. Concise Medical Pysiology – By Sujit, K. Chaudhuri Forth Edition
2002.
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.
165. The fundamental principles of ayurveda by. D.C. Dwarkanath, Vol –
1 to 3, Reprint edition 2003.
166. The student Sanskrit English Dictionary by Vaman Shivram Apte,
Second edition, 1970
167. Essential of Medical physiology – K. Semutingam (Fifth Edition)
168. Text Book of Biochemistry for Medical Students Sixth Edition – D.M.
Vasudevan Steekumari’s and Kaman Vaidyan Athan
169. Human Physiology – C.C. Chatterjee
170. Principles of Anatomy and Physiology – Gerquard J. Tortosa and
Sandra Reynolds Grabowska
171. Priview of medcal Physiology – William F. Ganoyg
172. Practice of Dermatology, Bhel, P.N. 7th Ed. 1990 C.B.S. Publication
and Distributors, Shahdara, Delhi
173. S. Rothman – Physiology and Biochemistry of Skin (1954).
174. www.vitiligosociety.org uk/symposium.html
175. www.vitiligofoundation.org/approach.html
176. www.patholgy.ufl.edu./mccromac/abstracts/html
177. www.advarcement.uark.edu/pubs/reacherarch/fronters/tall2002/08-
Feature4.html
178. www.cancerres.aarjeornals.org/cgi/content/full/62/16/4836
179. www.americanbiologics.com/publication/monographs.html
180. www.womenshealth.com/library/bl_autoimmune 9.html
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