Melanin black polymers

Vitiligo, Depigmentation and
 Occurs worldwide about 1% of the population, mostly between the
age of 10-30
Chronic skin disease
Other name = Leukoderma
White spots occur when the skin no longer forms melanin (pigment
that determines the color of your skin, hair, and eyes)
The white patches of irregular shapes begin to appear on your skin
Total absence of melanocytes microscopically
 Associated with three other autoimmune diseases:
1. Addison’s Disease
2. Hyperthyroidism
3. Pernicious Anemia
A skin biopsy may be required to rule out the other causes
of pigment loss.
 Totally amelanotic macule (patch) surrounded by normal skin
 Vitiligo macules characteristically have fairly discrete margins
and they are round, oval or linear in shape
 Lesions enlarge centrifugally over time, but the rate may be slow
or rapid
 Vitiligo macule patches ranges from millimeter to centimeter in
•Normal skin is pigmented with melanin
that is produced by melanocytes
•Detection by Masson Silver Stain
•Therefore white spots are due to melanocyte
•a few isolated
• fingers and
around mouth
• total
Sub types of Vitiligo
Differ by anatomical location, and size of lesions
 Focal – A few isolated lesions, most common in children
 Segmental – unilateral distribution
 Acrofacial – fingers and periorificial areas
 Universal – almost total depigmentation
 Generalized – most common, symmetrical distribution,
occurs symmetrically on both sides of the body
 Mucosal – Depigmentation of only the mucous membrane
Causes of Vitiligo
 Autoimmune theory: Cell mediated immune process
 Biochemical Theory
 Oxidative Stress Theory
 Melanin is black pigment of skin, hair & eyes
 Synthesis occurs in melanosomes present in melanocytes.
 Tyrosine is the precursor of melanin and tyrosinase is the
enzyme involved in it’s formation
 Melanochromes formed from tyrosine polymerizes to form
melanin polymers
Melanin red polymers
Indole 5-6-quinone
Melanin black polymers
Chemical Melanocytotoxin:
1) Melanin synthesis can be triggered by:
 Sunburn, skin injury or exposure to cytotoxic compound stimulate melanin synthesis
 Melanocyte stimulating hormone induced by UV exposure
 Cytokines produced during emotional stress or physical trauma
2) Specific Quinones (Dopa Quinone) and Indoles (Dihydroxy indoles) are generated as
intermediates during melanin synthesis
3) Quinones & Indoles, if abundant in the cells, can readily oxidize either enzymatically or
spontaneously and produce reactive oxygen species and ultimately induce apoptosis.
Apoptosis in Vitiligo Melanocytes
1. Exposure of melanocytes to pigment
inducers via action of tyrosinase related protein
1 (Tyrp 1) results in generation of intracellular
2. Reactive oxygen species (ROS) forms
3. ROS stimulates the apoptotic pathway
4. Potentially could lead to cell death or
interact with endogenous or regulated
Essentials of Vitiligo Etiology in
Stress to the skin in form of wound,
burn, excessive sun exposure or contact
with bleching phenol
Differential gene expression among
Inflammatory infiltrate of T cells &
Further induce melanocyte apoptosis
Where Depigmentation Therapy
Generalized vitiligo
•Typical appearance of a man with
generalized vitiligo affecting the skin
around eyes, nose, mouth, and the chest
and hands
List of Depigmenting Agents
 Monobenzyl ether of hydroquinone (MBEH)
 Chemical Name: P- (Benzyloxy) - Phenol
 Oliver et al. discovered it on 1939
 Acts as a skin sensitizer
 Topical application increases the excretion of melanin from
melanocytes in animal
 Depigmentation spreads to distant sites unexposed to
Monobenzone, indicating that it induces a progressive
systemic reaction against melanocytes
Mechanism of Action
Many theories have been proposed:
 MBEH reacts with tyrosinase, the key enzyme in melanin synthesis, to form a reactive
quinone product. This quinone metabolite in turn binds covalently to cysteine residues in
tyrosinase proteins through the sulfhydryl (-SH) group to form hapten-carrier
complexes, i.e., generation of neo-antigens in the tyrosinase peptide chain occurs which
excites a systemic, melanocyte destructive, inflammatory response.
 MBEH induces cellular oxidative stress in exposed pigmented cells by producing reactive
oxygen species (ROS) such as peroxide. This induces lysosomal degradation of
melanosomes by autophagy, in addition to disruption of melanosomal membranes and
melanosome structure. This is followed by increased surface expression of melanosomal
antigens by both major histocompatibility complex (MHC) class I and II routes and
initiation of melanocyte Ag-specific T-cell responses.
 ROS generation also results in release of tyrosinase and MART-1
antigen containing exosomes which further contributes to
immune response.
 Rapid and persistent innate immune activation also occurs in
MBEH-exposed skin. MBEH is a contact-sensitizer inducing a type
IV delayed type hypersensitivity response against the quinone
hapten mentioned earlier. This depends on the production of proinflammatory cytokines such as interleukin (IL)-1b and IL-18 by
the Langerhans cells or keratinocytes.
Electron Microscopy
Necrotic changes consisting plasma membrane
and cytoplasmic disintegration
DNA fragmetation treated skin
within Monobenzyl Ether of Hydroquinone
Apoptosis is shown in
confocal microscopic images of
explant cultures exposed to 5 ml of
250mM MBEH (Monobenzyl Ether
of Hydroquinone) for 24 hours.
Side Effects of Monobenzone
 Mild burning,
 irritation,
 redness,
 cracking, or
 peeling of the treated skin may occur.
If any of these effects persist or worsen, doctor needs to be informed.
Note: Get emergency medical help if you have any of these signs of an
allergic reaction: hives; difficulty breathing; swelling of your face,
lips, tongue,or throat.
Why Monobenzone????
MBEH is the most widely used depigmenting agent
 Monomethyl ether of Hydroquinine / 4-Methoxy Phenol requires longer time
prior to the onset of visible depigmentation
 Application of 88% Phenol solution on large areas proved to be toxic to Liver
and Kidney. Cardiovascular shock, cardiac arrythmias, bradycardia as well as
metabolic acidosis with in 6 hours of skin peeling procedures with phenol.
 Different type of lasers are selectively destructive to melanocytes but technique
is painful and expensive. Moreover these are more efficient in patients with
Koebner Phenomenon (skin lesions which appear at the site of injury).
Moreover treatment is only available in the clinic. Patients with negetive
Koebner may relapse.
 Cyrotherapyrequires an experienced person hence treatment is hospital based.
It gives edema, pain and bulla formation as side effects.Moreover it is suitable
for small lesions since single sitting can not be utilized for extensive viiligo.
 Topical Imatinib, Imiquimod and Diphencyprone may be considered as potential
depigmenting agents, but require further investigation
Efficacy of Monobenzone Therapy
Residual patches of vitiligo affecting
more than 70% of her skin surface
Depigmentation after topical
application of 20% Monobenzone daily
during 8 months
Why Treatment is Important???
 Although vitiligo is usually not harmful medically and causes
no physical pain, its emotional and psychological effects can
be devastating.
In India, vitiligo patients, especially women, are sometimes
discriminated against in marriage.
Developing vitiligo after marriage can be grounds for
White patches of vitiligo can affect emotional and
psychological well-being and self-esteem.
People with vitiligo can experience emotional stress
 Most commonly acquired Hypomelanosis.
 Known as ‘‘ Ven kushtam’’ in India, means White Leprosy.
 Extremly disfiguring, leading to significant patient morbidity.
 Low self esteem, poor body image and poor quality of life has
been found in patients.
 Depigmentation is the only option when more than 70% of
the body covered with vitiligo.
 Monobenzone induce depigmentation that is clinically and
histologically indistinguishable from vitiligo vulgaris.
 Superiority of Monobenzone comes when it gives a uniform
white color
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Remember, A little Consideration, A
Little Thought for them makes all the
No wonder they are one amongst us.
And last, but not the least,
Monobenzone- a scientifically
established treatment for vitiligo.
Puneet Laboratories Pvt. Ltd.

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