Definition Differential Diagnosis Clinical Patterns of

Facial Melasma
Derived from the Greek word melas to mean
black, Melasma is one of the most common
causes of acquired symmetrical
hypermelanosis of the face characterized by
brown to gray brown macules and patches.
Predilection
It has predilection for sun exposed areas like
the cheeks, forehead, nose, cutaneous part of
upper lip, chin and forearms.
Prevalence
Most authors would generally state
centrofacial (63%) predominating over the
malar (21%) and the mandibular (16%).
In Asia, however, the malar pattern is more
common than the centrofacial and the
mandibular.
In the Philippines, in a study being conducted
at the Research Institute for Tropical Medicine,
centrofacial (59.5%) predominates followed
by malar (32%) and mandibular (8,5%)

As for prevalence, melasma is highest in

1. Drug-induced hyperpigmentation
patients
2. Postinflammatory hyperpigmentation due
to: cutaneous LE, skin infections,
Are of Hispanic & East Asian origin
photosensitivity rxns., atopic dermatitis or
Are of Fitzpatrick Skin Types IV-VI
contact dermatitis
Live in areas with intense UV Radiation
3. Exogenous ochronosis
4. Actinic lichen planus
Female: Male Ratio
5. Erythema dischronicum perstans
6. Poikiloderma of Civatte
In the Western hemisphere, Guevarra et al
7. Follicularis faciei et colli
puts a female to male ratio at 9:1.
8. Cutaneous mercury deposits
This is in contrast to the Asian Region as Prof
Types of melasma
Goh puts a higher predominance of women
vs. men having melasma at 21:1.
1. Epidermal Type
Patient Characteristics
suprabasal / and basal layers
of the epidermis
797 patients: 782 women (98.1%)
Most common and most
treatable form
Age
Mean: 44.2 years
2. Dermal Type
Range: 2176 years
milder epidermal
40 years: 287 (36%) hyperpigmentation
> 40 years: 510 (64%) dermal macrophages
Torok H et al. Long term safety and
efficacy of Tri-Luma in patients with less responsive to
melasma of the face. Submitted to J Drugs conventional therapy
Dermatol 2005
Torok H et al. A safe and efficacious 12
months treatment for melasma. Cutis 2005; 3. Mixed Type
75; 57-62 combination of 1 & 2
* Examine under Woods lamp
 Etiology
Etiology still remains unclear.
Pathogenesis
The following factors in the pathogenesis of
melasma are
1. UV Exposure
2. Genetic Influence
3. Hormonal changes including
4. Cosmetics
Some authors do include drugs such as
hydantoin. Ruling out everything, UV
exposure is still the number one factor to
consider.
Pigmentation Formation Mechanism
1. UV Exposure
2. Irritation or Diseases
3. Hormonal
A. UV EXPOSURE
UV Irradiation on Melanocytes
Single exposure to UV
Increases size of melanocytes
Increases Tyrosinase activity
Repeated exposure to UV
Increases the number of Stage
IV Melanosome transfer to
keratinocytes
Increases the number of active
melanocytes
Density of melanocytes 2x
greater in sun exposed sites.
What causes increased melanin production?
This results from activation of protein kinase
A or C as well as exposure to growth factors
such as basic fibroblast growth factor or
ultraviolet irradiation.
UV irradiation can lead to an increase in the
number and activity of Melanocortin 1-
Receptor on melanocytes, the expression of
Propiomelanocortin and its derivative
peptides like MSH by keratinocytes and other
cells within the dermis, and the production of
endothelin-1 by keratinocytes
Melasma as a Photocontact Dermatitis
Photoallergens are present in
products used daily in much lower
concentrations than those used in
photo testing
Over time, cumulative exposure may
reach irradiance test doses.
Development of photosensitivity
(asymptomatic suberythematous
dermatitis), by about 30 to 40,
followed by a post-inflammatory facial
hypermelanosis, called MELASMA
B. IRRITATION OR DISEASES
The pathogenesis of this skin disorder
includes at least two major processes. An
increase in melanocyte activity with increased
melanogenesis and transfer of melanin
granules to surrounding keratinocytes may
occur. In addition, accumulation of
melanophages in the upper dermis as a result
of destruction of the basal cell layer in the
inflamed skin leads to hyperpigmentation
(Tomita, Maeda, & Tagami, 1989). This
distinction between epidermal versus dermal
involvement is important when considering
therapeutic options.
C. HORMONAL
Hyperpigmentation induced by UVB at
the application site of Estradiol
First report suggesting a direct
relationship between estrogen and
melanogenesis in humans
Pathogenesis of Melasma :
Hypothesis
1. *GM-CSF ( Granulocyte
Macrophage Colony Stimulating
Factor) is a growth factor for human
melanocytes involved in UVA- induced
hypermelanosis
Tyrosinase catalyzes three different reactions
in the biosynthetic pathway of melanin:
Melanin Biosynthetic Pathway
2. Increased expression of alpha
melanocyte-stimulating hormone in
the lesional skin of melasma
3. Involvement of -MSH in Melasma
Prognosis
Idiopathic Melasma usually persists for
several years.
Pregnancy related Melasma persists for
several months after delivery
Melasma related to hormonal changes can
persist for long periods after discontinuation
of the oral contraceptive pills.
Recurrences
Common place after sun exposure.
Diagnosis
Melasma is usually a clinical diagnosis.
Tyrosinase
Tyrosinase, which is a metallo enzyme,
requiring copper ions for its activity, is the
starting material and key regulatory enzyme
that controls the initial chemical reaction
1. the hydroxylation of tyrosine to 3,4-
dihydroxyphenylalanine (DOPA)
2. the oxidation of DOPA to dopaquinone
3. the oxidation of 5,6- dihydroxyindole
(DHI) to indole quinin
To understand the strategies of
depigmentation it is of outmost importance to
know the basic knowledge that melanocytes
reside in the basal layer of the epidermis,
its dendrites coming in contact with
keratinocytes as far away as the mid stratum
spinosum, to which it transfer melanosomes.
Strategies
Dr. Thada Piamphongsant in his book
Practical Dermatology gave us simple
strategies to treat melasma: To protect the
skin from sunlight, to reduce melanocyte
activity, to remove melanin, inhibit melanin
synthesis and to disrupt melanin granules.
IDEAL DEPIGMENTING AGENT
1. Has a potent, rapid and selective bleaching
effect on hyperactivated
melanocytes
2. Carries no short or long-term side-effects
3. Leads to a permanent removal of
undesired pigment.
INHIBITION OF MELANIN SYNTHESIS
I. Before melanin synthesis
A. Tyrosinase transcription inhibitor
C2-ceramide Tretinoin
B. Tyrosinase glycosylation inhibitor
PaSSO3Ca
II. During melanin synthesis
A. Tyrosinase inhibition
Hydroquinone Kojic acid
4-hydroxy- Methyl Gentisate
Anisole
4-S-CAP & Ellagic Acid
derivatives
Arbutin Resveratrol
Aloesin Oxyresveratrol
Azelaic acid Licorice
Lactic Acid
B. Peroxidase inhibition
 Methimazole Phenols/Catechols Hydroquinone shown to decrease
Green Tea Topical Indomethacin tyrosinase activity by
90%.
C. Product reduction and ROS scavengers
4 hydroxy-anisole exhibits strong
Ascorbic -Toc melanocytotoxicity
acid 4-S-CAP & capable of reacting with
Ascorbic D, L- TF derivative crucial SH groups and
Acid forming thiol adducts, for
Palmitate example with GSH and
DNA polymerase
D. Inhibitors of Inflammation Induced
Melanogenic Response Arbutin reversible inhibition of
Chamomile melanosomal tyrosinase
Corticosteroids activity rather than
Glabridin suppression of the
Tranexamic Acid expression & synthesis of
tyrosinase
Aloesin a competitive inhibitor on
III. After melanin synthesis DOPA oxidation and as
A. Tyrosinase degradation an non-competitive on
Linoleic acid -Linolenic acid tyrosine hydroxylase
activity.
B. Melanosome transfer Inhibition Azelaic Acid due to its antiproliferative
Serine Niacinamide and cytotoxic effects. As
protease effective as topical
inhibitors hydroquinone
Soybean/milk extracts Kojic Acid more stable than
C. Skin turnover acceleration hydroquinone
Ellagic Acid induced a reversible
Lactic acid Retinoic acid inhibition of melanin
Glycolic acid Linoleic acid synthesis only in only in
UV-activated
melanocytes
Resveratrol anti-inflammatory effects
and inhibits
cyclooxygenase and
hydroperoxidase
functions
Oxyresveratrol A stronger inhibitor than
resveratrol
Licorice Extract Lowered the activities of
T1 & T3 tyrosinase
isoenzymes
Lactic Acid Inhibition of tyrosinase &
tyrosinase activity equal
to Kojic acid
TYROSINASE INHIBITORS
PEROXIDASE INHIBITORS
Methimazole induces mild to moderate
inhibition of melanization
Green Tea Epigallocatechin-3-gallate
(EGCG)- responsible for the
biochemical or
pharmacological effects
Topical Acts like a steroid by non-
Indomethacin selectively suppressing
melanogenesis.
PRODUCT REDUCTION & ROS
SCAVENGERS
Inhibits melanin production by
Ascorbic Acid
reducing o- quinones
Prevents UV-induced photo-
-Lipoic Acid
oxidative damage
-tocopheryl ferulate inhibits
-Tocopherol tyrosinase hydroxylase activity
in an indirect manner.
Glutathione cysteinyl reactive thiol group is
responsible for many of the
antioxidant functions of GSH
metabolism
Pycnogenol Several times more powerful
than vitamin E and vitamin C
INHIBITORS OF INFLAMMATION-
INDUCED MELANOGENIC
RESPONSE
Chamomile Inhibits UVB-induced
pigmentation, by avoiding
ET-1-induced DNA
synthesis
Corticosteroids Suppression of cytokines
through the inhibition of NF-
kB activation, which may
explain their short-lived
effect with a transient loss
of color
Glabridin inhibit cyclooxygenase
activity and superoxide
anion production
Tranexamic Acid Inhibits prostaglandins by
suppressing epidermal
pasmin activity
TYROSINASE DEGRADATION
Linoleic Acid Tyrosinase is selectively
targeted by linoleic acid, that
act on the degradation of the
enzyme
A- Linolenic Unsaturated fatty acid
acid suppress pigmentation;
correlated with the degree of
unsaturation
Melanosome Transfer Inhibition
Serine Protease inhibit PAR 2 cleavage
Inhibitors and reduce keratinocyte
phagocytosis
Soybean/ Milk soymilk and soymilk-
Extracts derived proteins are able
to inhibit PAR-2
activation and thus
induce skin
depigmentation
Lecithins & the transfer of
Neoglycoproteins melanosomes from
melanocytes to
keratinocytes include
plasma membrane
lectins and their
glycoconjugates.
Niacinamide Reduces cutaneous
pigmentation by
suppressing
melanosome transfer
from melanocytes to
keratinocytes

Depigmenting Agent Safety and

eficacy
Dermatology Update
Makassar 16 april 2017
Dr. Tandiono Hermanda SpKK