Download Treatment of Melasma

Melasma
Dr Z. Shahmoradi
Associate professor of dermatology
melanogenesis
 Melanin is produced in melanocytes and stored in
melanosomes within the keratinocytes.
1) The number,
2) melanin content,
3) and location of these melanized cells (along
with oxygenated and deoxygenated hemoglobin)
help determine the color of the skin.
 Melanocytes contain tyrosinase, a coppercontaining enzyme, that catalyzes the conversion
of L-tyrosine to L-dopa and
L-dopa to L-dopaquinone in melanin synthesis.
Melasma is a dysfunction of this pigmentary
system, resulting in an irregular brown or grayishbrown facial hypermelanosis.
Causes of acquired hyperpigmentation
 Skin disease and conditions:
Melasma, erythromelanosis follicularis, poikiloderma of
civatte, PIP, Riehl’s melanosis
 Exogenous causes:
cosmetics, drugs (estrogens, tetracyclines, amiodarone,
phenytoin, phenothiazines, sulfonamides, aldacton),
photosensitizing agents (bergamot oil, furocoumarins), UV
(melasma, freckle, solar lentigo)
 Other causes:
 Addison, hemochromatosis, liver disease, pituitary tumors,
pregnancy, hyperthyroidism
Melasma
 Acquired, brown hypermelanosis of the face that
develops slowly & symmetrically.
 Female (90%) , Male (10%)
 Etiology: Sunlight, pregnancy, genetic, racial,
endocrine (thyroid dysfunction,…)
 In men with melasma: higher LH & lower
testosterone
 Stress: release of MSH can be influenced by stress
 50-70% of pregnant women & 8-30% with OCP
..Melasma
 Centrofacial=63% in cheeks, forehead, upper lip,
nose, chin
 Malar=21% in cheeks & nose
 Mendibular=16% in ramous mendibular
Centrofacial localization of melasma(63%)
Malar localization of melasma(21%)
Mandibular localization of melasma(16%)
 Chloasma: can resolve within a few months after
delivery and treatment may not be necessary.
However, there are many cases in which the
disorder persists indefinitely.
Pregnancy-associated melasma may be caused by
an increase in placenta, ovarian, and pituitary
hormones.
Melasma has also been attributed to an elevation
of melanocyte-stimulating hormone (MSH),
estrogen, and progesterone leading to increased
melanogenesis.
Pathology
 In epidermal type:
increased number of melanocyte & melanocyte
activity
increased melanization
transport of melanosomes to epidermal cells
 In dermal type:
melanophage in dermis (papillary & reticular)
..Melasma
 Examination with Wood’s lamp:
1) Epidermal, enhancement of pig. [70%]
2) Dermal, no enhancement
3) Mixed, slightly enhancement
4) a type seen in type 5-6 skin in which the lesions
are not discernible under a wood’s light.
D.D
 Actinic lichen planus
 Drug-induced hyperpigmentation
 Riehl’s melanosis
 Poikiloderma of Civatte
 Exogenous ochronosis
 Erythema dyschromicum perstans
 PIP
Treatment of melasma
Treatment of Melasma
 Eliminate inciting agents: drugs, cosmetics
 HQ alone > 3%
 Tretinoin 0.05%-0.1%
 HQ with retinoic acid, Arbutin, Kojic acid (2-4%)
,Mandelic acid , Azelaic acid 20% , Steroid,...
 Broad-spectrum sunscreen
 4-isopropyl catechol (66%)
 N-acetyl-4-cysteine 3%
…Treatment of melasma
 Chemical peeling: glycolic acid 30-70% ,
 TCA 10-35% ,
 S.A 20-30%
 Dermabrasion, microdermabrasion
 Lasers: Erbium:YAG , Q-switched , CO2- laser
General management
 General management recommendations that
assist in the clearing of melasma include
discontinuation of birth control pills, scented
cosmetic products, and phototoxic drugs, coupled
with UV protection with use of broad spectrum
(UVA+UVB) sunscreens.
Solar exposure exacerbates melasma ,and its
avoidance is fundamental for the successful
management of the disease.
Hydroquinone:
 HQ remains one of the most prescribed agents for
melasma and is considered the gold standard of
therapy, especially for epidermal melasma.
The epidermal type generally has a good response
to topical therapy,
-Whereas skin with mainly dermal deposition of
Alternative therapies such as chemical peeling
agents or laser therapy are sometimes also used.
Hydroquinone:
 Mechanism of action:
HQ (1,4-dihydroxybenzene) is a hydroxyphenol,
which, in the presence of catalytic amounts of dopa,
will compete with tyrosine, the natural substrate of
tyrosinase.
 This process prevents the enzymatic oxidation of
tyrosine to dopa, thus, preventing the synthesis of
melanin. This is consistent with the selective mode of
action toward cells with active tyrosinase activity.
 HQ 3-5% concentration was determined to be the
optimal strength.
 Interestingly, their impression from clinical
observations was that many of the side effects
experienced may occur from misuse, excessive use, and
the application of multiple preparations.
It has also been suggested that patients may use
unsuitable cleansing agents, carry out vigorous
rubbing of the affected areas, and apply excessive
amounts of medication.
 Tri-Luma Cream: HQ 4% +fluocinolone 0.01% + tretinoin
0.05%
 Westerhof formula: HQ 2% + N-acetyl cysteine 3% +
hydrocortisone 1% .
- In 8 weeks: 77% improved the melasma
 HQ 4% + tretinoin 0.1% + lactic acid 7% in aqueous gel
 Kligman formula: HQ + tretinoin + dexamethasone
Ochronosis:
Erythema & pigmentation due to HQ
Colloid milium
Tretinoin:
 Mechanism of action (5)
Retinoids, such as vitamin A acid and retinoic acid
(RA) or tretinoin, were first used in combination with
HQ to
 1) enhance the penetration of HQ, but were later
recognized to have their own effect on the pigment.
2)Tretinoin's ability to depigment is based on its
ability
 3)to disperse keratinocyte pigment granules, interfere
with pigment transfer,
 4)and accelerate epidermal turnover and, therefore,
pigment loss.
 5) In addition, there is also evidence that it can inhibit
the induction of tyrosinase, DOPAchrome conversion
factor, and melanogenesis
 Tretinoin is available in 3 forms: gel, cream, and liquid,
at strengths ranging from 0.01% to 0.1% and
is approved for the treatment of acne vulgaris and
photoaging.
As a monotherapy it is not an approved treatment
for melasma; however, it is part of a combination HQ,
tretinoin, and fluocinolone acetonide cream (TriLuma) which is an approved treatment for melasma.
Safety and tolerability:
 The most common side effects of tretinoin include a
retinoid dermatitis characterized by burning or stinging,
erythema, scaling, and dry skin.
inflammation may cause hyperpigmentation, especially
in those with dark skin.
Fortunately, most adverse effects (AEs) are reversible on
discontinuation of therapy, although the
hyperpigmentation/hypopigmentation may persist for
many months.
 Topical tretinoin is not considered mutagenic or
carcinogenic, however, animal tests have
demonstrated evidence for teratogenicity.
 There have not been adequate and well-controlled
studies performed in pregnant women.(category C)
 In addition, the safety of tretinoin gel has not been
established in children younger than 12 years, neither
has the safety of the emollient cream in patients
younger than 18 years.
Corticosteroids:
 Mechanism of action(4)
Corticosteroids may directly affect the synthesis of
melanin, although the mechanism by which the skin is
lightened is 1) not completely known.
2) Melanocytes respond to a variety of chemical
mediators such as prostaglandins and leukotrienes
and, thus, it has been theorized that steroids might
alter melanocyte function by inhibition of
prostaglandin or cytokine production by various cells
of the epidermis.
 3) Corticosteroids may suppress secretory
metabolic products from melanocytes without
causing their destruction, and this could be the
reason for their short-lived effect on pigmentation
disorders.
 4)Topical steroids also inhibit tyrosinase activity &
affect endoplasmic reticulum secretory function of
melanocytes.
Efficacy:
 The use of corticosteroids in the treatment of melasma
is seen more often in conjunction with other topical
therapies (eg, tretinoin and HQ).
 As a monotherapy there has been little published
research
Unfortunately, the study failed to assess whether the
improvement caused by steroid treatment was a longterm benefit.
Azelaic acid
 A.A is a naturally occurring dicarboxilic acid derived
from P.ovale.
 It inhibits mitochondrial oxidoreductase activation &
DNA synthesis, as well as tyrosinase.
 Minimal effect on normal pig. and greatest
effect on heavily pigmented melanocytes.
…Azelaic acid:
 Useful in facial lentigo maligna (specificity for
abnormal melanocytes), rosacea, solar keratosis,
PIP due to herpes or burns.
 Effect comparable with HQ, 15-20% twice daily for
3-12 months, effective in dark skin
 Side effects: erythema, irritation
Azelaic acid:
 Mechanism of action:
Az.A has anti-inflammatory, antibacterial, and
antikeratinizing effects, which make it useful in a variety
of dermatologic conditions., acts on hyperactive and
abnormal melanocytes by competitively inhibiting
tyrosinase.
Safety and tolerability:
 Topical administration of 20% Az.A has produced
pruritus, burning, stinging, and tingling in 1% to 5% of
patients.
 Other adverse reactions, such as erythema, dryness,
rash, peeling, irritation, dermatitis, and contact
dermatitis, have been reported in less than 1% of
patients.
 Rarely asthma, vitiligo, small depigmented spots,
hypertrichosis, development of keratosis pilaris, and
exacerbation of recurrent herpes labialis may occur.
Kojic acid:
 5-hydroxymethyl-4H-pyrane-4-one is a
hydrophylic fungal derivative obtained from
Aspergillus & penicillium species.
 Some studies indicate kojic acid = HQ in skinlightening ability.
 The activity of kojic acid: prevent tyrosinase
activity by binding to copper.
Other topical agents
Kojic acid is not an approved treatment for melasma.
However, because both kojic acid and HQ are
tyrosinase inhibitors, the combination should be
expected to augment efficacy.
Thus, those who do not respond to HQ and GA may
benefit from the addition of kojic acid to the treatment
regimen
Licorice extract (glabridin):
 The principal active compound of licorice root extract is




glabridin : 10-40% in skin lightening
Depigmenting effect: 16 times greater than HQ
It is faster acting: after 7 days
0.4% licorice extract + 0.05% betamethasone + 0.05%
retinoic acid = 70% of patient reported excellent effects.
Licorice extracts are used as topical anti-inflammatory
agents to decrease skin redness & hyperpig.
..Licorice extracts:
 The active agents are known as liquiritin &
isoliquiritin, which are glycosides containing
flavonoids. Liquiritin induced skin lightening by
dispersing melanin.
Ascorbic acid
 Vit C interrupts the production of melanogenesis
by interacting with copper ions to reduce
dopaquinone & blocking dihydrochinindol-2carboxyl acid oxidation.
 Vit C, an antioxidant, is rapidly oxidized when
exposed to air and is of limited stability.
 High concentrations of Vit C must be used with
caution, as the low pH can be irritating to the skin.
 Cream 10% magnesium L-ascorbic acid-2phosphate (MAP), a stable derivative of vit
C=lighten pig.
 L-ascorbic-2-phosphate (magnesium-L-ascorbyl-2-
phosphate; VC-PMG) is a stable vitamin C derivative
that suppresses melanin production.
Applying VC-PMG cream 10% twice daily to the skin of
34 patients produced an improvement in 55% of those
treated, suggesting that it may be effective in reducing
hyperpigmentation
Arbutin:
 Arbutin (HQ-BETA-D- glucopyranoside) and
methyl-arbutin are skin-lightening glycosides
found in bearberry, a fruit enjoyed by bears but not
by humans.
 Arbutin is also present in certain herbs & pear tree
 Inhibiting melanosomal tyrosinase activity.
 A dose-dependent reduction in tyrosinase activity
& melanin content in melanocytes.
 Arbitin is nontoxic to melanocytes
 Efficacy is less than kojic acid
 3% is also applied.
 Higher concentrations=more effective but
paradoxically skin darkening may occur.
Glycolic acid:
 AHAs in low concentrations =rapid desquamation
of pigmented keratinocytes.
 High= epidermolysis
 30-70%, removal of superficial layers of epidermis,
can enhance the penetration of other topical skin
lighteners, such as HQ.
Aloesin:
 Aloesin is a natural derevative of aloe vera that
inhibits tyrosinase at noncytotoxic concentrations.
 In contrast to HQ, it shows no cell cytotoxicity;
however, its ability to penetrate the skin is limited
by its hydrophilic nature.
 Mixed with arbutin =enhance its skin-lightening
ability
 Aloesin is an experimental products.
Mequinol(4-Hydroxyanisol):
 5-20% for treatment of solar lentigines.
 Mequinol is a substrate to the enzyme tyrosinase
and acts as a competitive inhibitor of
melanogenesis.
 Mequinol 2% + retinoic acid 0.01% , LASER +
mequinol, reduced cessation of LASER therapy, as
well as prevent recurrences.
 In dark skin : prevent the postprocedural PIP
Niacinamide:
 Niacinamide, the amide form of Vit B3, inhibits
the transfer of melanosomes to the epidermal
keratinocytes.
 3.5% niacinamide + retinyl palmitate useful in
melasma
Chemical peels:
 The mechanism of action of chemical peeling agents is
the removal of melanin, rather than the inhibition of
melanocytes or melanogenesis.
Peels are usually well tolerated by individuals with
lighter complexion;
The risk of complications from chemical peels
increases proportionately with the depth of the
wound.
 Superficial peels carry the lowest risk of adverse
reactions, but have still been associated with
hyperpigmentation.
 Common adverse reactions to all types and
depths of peel are persistent postpeel erythema,
and the possibility of infection.
a, b. Malar melasma before and after combined peeling
with 25% salicylic acid and 10% TCA gel
Conclusions:

Melasma may be treated using monotherapy or with
combination therapy. HQ is a reliable treatment and
MKF is also effective.
 These therapies, coupled with regular application of a
UVA and UVB blocking sunscreen to avoid UVinduced recurrence, are the most common therapies
for epidermal melasma.
 AzA, currently only used as an off-label treatment, has
also shown notable efficacy.
 Alternative treatments to topical include chemical
peels, laser treatment, and dermabrasion.
The GA peel seems to have the most promise as an
alternative to bleaching creams.
 Laser treatments seem to show limited efficacy,
although in many cases the number of participants
with melasma in the studies are very small.
IPL has also shown potential, however, combining
topical agents such as HQ, tretinoin, and a
corticosteroid, in addition to patient education, sun
avoidance, and regular sunscreen use is the mainstay
of treatment in this difficult and frustrating condition.
:‫لیزر در ضایعات پیگمانته‬
1) Highly selective Q-switch lasers
2) Less pigmented selective, longer pulsed laser
3) Non-pigment specific ablative lasers
- highly: Q-switched frequency doubled Nd-YAG( 532 nm),
Q-S ruby (694 nm), Q-S alexandrite (755 nm), Q-S NdYAG (1064)
 532 nm: epidermal pigment
 694 & 755 nm: epidermal & dermal pigment
 1064 nm: dermal pigment
‫موفق باشید‬
‫دکتر شاهمرادی‬