Definition Differential Diagnosis Clinical Patterns of
Facial Melasma
Derived from the Greek word melas to mean
black, Melasma is one of the most common Most authors would generally state
causes of acquired symmetrical centrofacial (63%) predominating over the
hypermelanosis of the face characterized by malar (21%) and the mandibular (16%).
brown to gray brown macules and patches.
In Asia, however, the malar pattern is more
Predilection common than the centrofacial and the
mandibular.
It has predilection for sun exposed areas like
the cheeks, forehead, nose, cutaneous part of In the Philippines, in a study being conducted
upper lip, chin and forearms. at the Research Institute for Tropical Medicine,
centrofacial (59.5%) predominates followed
by malar (32%) and mandibular (8,5%)
Prevalence
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 cells within the dermis, and the production of
endothelin-1 by keratinocytes
Etiology still remains unclear.
Melasma as a Photocontact Dermatitis
Pathogenesis
Photoallergens are present in
The following factors in the pathogenesis of products used daily in much lower
melasma are concentrations than those used in
1. UV Exposure photo testing
2. Genetic Influence
3. Hormonal changes including Over time, cumulative exposure may
4. Cosmetics reach irradiance test doses.
Some authors do include drugs such as Development of photosensitivity
hydantoin. Ruling out everything, UV (asymptomatic suberythematous
exposure is still the number one factor to dermatitis), by about 30 to 40,
consider. followed by a post-inflammatory facial
hypermelanosis, called MELASMA
Pigmentation Formation Mechanism
B. IRRITATION OR DISEASES
1. UV Exposure
2. Irritation or Diseases The pathogenesis of this skin disorder
3. Hormonal includes at least two major processes. An
increase in melanocyte activity with increased
A. UV EXPOSURE melanogenesis and transfer of melanin
granules to surrounding keratinocytes may
UV Irradiation on Melanocytes occur. In addition, accumulation of
melanophages in the upper dermis as a result
Single exposure to UV of destruction of the basal cell layer in the
Increases size of melanocytes inflamed skin leads to hyperpigmentation
Increases Tyrosinase activity (Tomita, Maeda, & Tagami, 1989). This
Repeated exposure to UV distinction between epidermal versus dermal
Increases the number of Stage involvement is important when considering
IV Melanosome transfer to therapeutic options.
keratinocytes
Increases the number of active C. HORMONAL
melanocytes
Density of melanocytes 2x Hyperpigmentation induced by UVB at
greater in sun exposed sites. the application site of Estradiol
What causes increased melanin production? First report suggesting a direct
relationship between estrogen and
This results from activation of protein kinase melanogenesis in humans
A or C as well as exposure to growth factors
such as basic fibroblast growth factor or Pathogenesis of Melasma :
ultraviolet irradiation. Hypothesis
UV irradiation can lead to an increase in the 1. *GM-CSF ( Granulocyte
number and activity of Melanocortin 1- Macrophage Colony Stimulating
Receptor on melanocytes, the expression of Factor) is a growth factor for human
Propiomelanocortin and its derivative melanocytes involved in UVA- induced
peptides like MSH by keratinocytes and other hypermelanosis
Tyrosinase catalyzes three different reactions reside in the basal layer of the epidermis,
in the biosynthetic pathway of melanin: its dendrites coming in contact with
keratinocytes as far away as the mid stratum
spinosum, to which it transfer melanosomes.
Strategies
Melanin Biosynthetic Pathway
Dr. Thada Piamphongsant in his book
Practical Dermatology gave us simple
2. Increased expression of alpha strategies to treat melasma: To protect the
melanocyte-stimulating hormone in skin from sunlight, to reduce melanocyte
the lesional skin of melasma activity, to remove melanin, inhibit melanin
synthesis and to disrupt melanin granules.
3. Involvement of -MSH in Melasma
IDEAL DEPIGMENTING AGENT
Prognosis
1. Has a potent, rapid and selective bleaching
Idiopathic Melasma usually persists for effect on hyperactivated
several years. melanocytes
2. Carries no short or long-term side-effects
Pregnancy related Melasma persists for 3. Leads to a permanent removal of
several months after delivery undesired pigment.
Melasma related to hormonal changes can
persist for long periods after discontinuation INHIBITION OF MELANIN SYNTHESIS
of the oral contraceptive pills.
I. Before melanin synthesis
Recurrences
Common place after sun exposure. A. Tyrosinase transcription inhibitor
C2-ceramide Tretinoin
Diagnosis
B. Tyrosinase glycosylation inhibitor
Melasma is usually a clinical diagnosis. PaSSO3Ca
Tyrosinase
Tyrosinase, which is a metallo enzyme,
II. During melanin synthesis
requiring copper ions for its activity, is the
starting material and key regulatory enzyme A. Tyrosinase inhibition
that controls the initial chemical reaction Hydroquinone Kojic acid
4-hydroxy- Methyl Gentisate
1. the hydroxylation of tyrosine to 3,4- Anisole
dihydroxyphenylalanine (DOPA) 4-S-CAP & Ellagic Acid
2. the oxidation of DOPA to dopaquinone derivatives
3. the oxidation of 5,6- dihydroxyindole
Arbutin Resveratrol
(DHI) to indole quinin
Aloesin Oxyresveratrol
To understand the strategies of Azelaic acid Licorice
depigmentation it is of outmost importance to Lactic Acid
know the basic knowledge that melanocytes 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 Chamomile Inhibits UVB-induced
inhibition of melanization pigmentation, by avoiding
ET-1-induced DNA
Green Tea Epigallocatechin-3-gallate synthesis
(EGCG)- responsible for the Corticosteroids Suppression of cytokines
biochemical or through the inhibition of NF-
pharmacological effects kB activation, which may
explain their short-lived
Topical Acts like a steroid by non- effect with a transient loss
Indomethacin selectively suppressing of color
melanogenesis. Glabridin inhibit cyclooxygenase
activity and superoxide
PRODUCT REDUCTION & ROS anion production
SCAVENGERS
Tranexamic Acid Inhibits prostaglandins by
suppressing epidermal
Inhibits melanin production by pasmin activity
Ascorbic Acid
reducing o- quinones
Prevents UV-induced photo- TYROSINASE DEGRADATION
-Lipoic Acid
oxidative damage
Linoleic Acid Tyrosinase is selectively
targeted by linoleic acid, that
-tocopheryl ferulate inhibits act on the degradation of the
-Tocopherol tyrosinase hydroxylase activity enzyme
in an indirect manner.
A- Linolenic Unsaturated fatty acid
Glutathione cysteinyl reactive thiol group is acid suppress pigmentation;
responsible for many of the correlated with the degree of
antioxidant functions of GSH unsaturation
metabolism
Pycnogenol Several times more powerful
than vitamin E and vitamin C
INHIBITORS OF INFLAMMATION- Melanosome Transfer Inhibition
INDUCED MELANOGENIC Serine Protease inhibit PAR 2 cleavage
Inhibitors and reduce keratinocyte
RESPONSE 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
