1. Melasma

2. Biology of melanocyte Dendritic cell at basal layer of epidermis Dendritic cell at basal layer of epidermis Produce melanin and send to surrounding keratinocyte Produce melanin and send to surrounding keratinocyte Epidermal melanin unit (melanocyte:keratinocyte) = 1:36 Epidermal melanin unit (melanocyte:keratinocyte) = 1:36

3. Biology of melanin Synthesis from melanosome Synthesis from melanosome Transport to keratinocyte via dendritic process of melanocyte Transport to keratinocyte via dendritic process of melanocyte 2 type 2 type : eumelanin : pheomelanin

4. Melanin synthesis Binding Melanocyte Melanocortin 1 stimulating hormone receptor adenylase cyclase adenylase cyclase Tyrosinase cAMP

5. Melanin synthesis Tyrosine tyrosinase tyrosinaseDopa Dopa quinone Eumelanin Pheomelanin

6. Melanin synthesis MSH MC1R mutation of MC1R Eumelanin Pheomelanin

7. Melanin transfer Phagocytosis Phagocytosis : melanin transfer to dermis : phagocytose by melanophage Endocytosis Endocytosis : melanin transfer to keratinocyte via intercellular space

8. Melasma Acquired bilateral symmetrical hypermelonosis Acquired bilateral symmetrical hypermelonosis Irregular light to gray brown macule and patch Irregular light to gray brown macule and patch Ill defined margin Ill defined margin Involved sun exposure area Involved sun exposure area Most common in women Most common in women

9. Melasma is a common acquired pigmentary disorder that occurs mainly in women (more than 90% of cases) of all racial and ethnic groups, but particularly affects those with Fitzpatrick skin types IV–VI Melasma is a common acquired pigmentary disorder that occurs mainly in women (more than 90% of cases) of all racial and ethnic groups, but particularly affects those with Fitzpatrick skin types IV–VI

15. Distribution of melasma Central facial pattern (63%) : cheek, forehead, nose, chin Central facial pattern (63%) : cheek, forehead, nose, chin Malar pattern (21%) : cheek, nose Malar pattern (21%) : cheek, nose Mandibular pattern (16%) :chin Mandibular pattern (16%) :chin

16. Cause of melasma Light : UVA, UVB, visible light Light : UVA, UVB, visible light Hormone : pregnancy, contraceptive pill Hormone : pregnancy, contraceptive pill Drug : dilantin, anti-malarial drug, tetracycline, minocycline Drug : dilantin, anti-malarial drug, tetracycline, minocycline Cosmetic : perfume, color Cosmetic : perfume, color Genetic Genetic Malnutrition : liver dysfunction, B12 def. Malnutrition : liver dysfunction, B12 def.

17. Types of melasma Epidermal melasma Epidermal melasma Dermal melasma Dermal melasma Mixed epidermal dermal melasma Mixed epidermal dermal melasma

18. The use of a Wood’s lamp can often be very beneficial in determining the location of melanin deposition showing enhancement of color contrast in lesional skin for the epidermal type, but not the dermal types. The mixed type has enhancement in some areas of lesional skin, but not in other areas. The use of a Wood’s lamp can often be very beneficial in determining the location of melanin deposition showing enhancement of color contrast in lesional skin for the epidermal type, but not the dermal types. The mixed type has enhancement in some areas of lesional skin, but not in other areas.

19. Estrogen may play a role in melasma induction(OCP,HRT,pregnancy) Estrogen may play a role in melasma induction(OCP,HRT,pregnancy) Pregnancy induced melasma will recover after some months (but not completely). Pregnancy induced melasma will recover after some months (but not completely).

20. Epidermal melasma Light or dark brown color Light or dark brown color Melanin deposition in basal, suprabasal layer of epidermis Melanin deposition in basal, suprabasal layer of epidermis Larger melanocyte with more noticeable dendritic process Larger melanocyte with more noticeable dendritic process

21. Dermal melasma Blue gray color Blue gray color Perivascular melanophage at superficial and middermis Perivascular melanophage at superficial and middermis Melanin granule in dermis Melanin granule in dermis

22. Whether the melanin is deposited in the epidermis or dermis is important therapeutically because dermal hyperpigmentation is much more challenging to treat Whether the melanin is deposited in the epidermis or dermis is important therapeutically because dermal hyperpigmentation is much more challenging to treat

23. Topical Treatments for Melasma In those patients with epidermal type melasma, there are multiple treatments available (see Table 2).6 Topical agents include phenols, e.g., hydroquinone (HQ); retinoids, e.g., tretinoin; azelaic acid; kojic acid (KA); and glycolic acid (GA). In those patients with epidermal type melasma, there are multiple treatments available (see Table 2).6 Topical agents include phenols, e.g., hydroquinone (HQ); retinoids, e.g., tretinoin; azelaic acid; kojic acid (KA); and glycolic acid (GA).

24. Hydroquinon 2%–4% has been widely used for melasma therapy. 2%–4% has been widely used for melasma therapy. inhibits the conversion of dopa to melanin by inhibitin theactivity of tyrosinase. inhibits the conversion of dopa to melanin by inhibitin theactivity of tyrosinase. may interfere with DNA and RNA synthesis, degrade melanosomes, and destroy melanocytes. may interfere with DNA and RNA synthesis, degrade melanosomes, and destroy melanocytes.

25. Reports of contact dermatitis in up to 25% Reports of contact dermatitis in up to 25% As an itchy eruption it is best to be tested in a hidden part before use it is best to be tested in a hidden part before use Side-effects included irritant and allergic contact dermatitis, PIH, nail bleaching and rarely, ochronosis-like pigmentation.

26. retinoids 0.05-0.1% 0.05-0.1% inhibiting tyrosinase transcription,interrupting melanin synthesis. inhibiting tyrosinase transcription,interrupting melanin synthesis. While tretinoin may be effective in reducing melasma, it typically takes at least 24 weeks to see clinical improvement. While tretinoin may be effective in reducing melasma, it typically takes at least 24 weeks to see clinical improvement.

27. azelaic acid 1) 15%–20% a dicarboxylic acid, is a reversible inhibitor of tyrosinase 2) shown to be as effective as HQ 4% but without its side effects. 3) The combination of azelaic acid with 0.05% tretinoin or 15%–20% glycolic acid may produce earlier, more pronounced skin lightening. Adverse effects include pruritus, mild erythema, scaling, and burning.

28. KOJIC ACID KA 2% is generally equivalent to other therapies but may be more irritating. KA 2% is generally equivalent to other therapies but may be more irritating.

29. Glycolic acid GA 5%–10% is an alpha-hydroxy acid GA 5%–10% is an alpha-hydroxy acid It decreases pigment by many mechanisms including thinning the stratum corneum, enhancing epidermolysis, dispersing melanin in the basal layer of the epidermis, and increasing collagen synthesis in the dermis. It decreases pigment by many mechanisms including thinning the stratum corneum, enhancing epidermolysis, dispersing melanin in the basal layer of the epidermis, and increasing collagen synthesis in the dermis.

30. HQ 5%, tretinoin 0.1%, and dexamethasone 0.1%, was first introduced in 1975 and termed the Kligman formula HQ 5%, tretinoin 0.1%, and dexamethasone 0.1%, was first introduced in 1975 and termed the Kligman formula combination of HQ 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% (Tri- Luma®, Galderma) proved better than any combination of two of the above agents, with 77% of patients showing complete or nearly complete clearing. combination of HQ 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% (Tri- Luma®, Galderma) proved better than any combination of two of the above agents, with 77% of patients showing complete or nearly complete clearing.

31. Laser treatment for melasma Target chromophore is melanin Target chromophore is melanin Should destroy melanocyte in hair follicle Should destroy melanocyte in hair follicle Good in dermal and mix melasma Good in dermal and mix melasma Epidermal melanin removal : lPL Epidermal melanin removal : lPL Dermal melanin removal : Q-switched Ruby, Q-switched Alexandrite, Q-switched Nd:YAG Dermal melanin removal : Q-switched Ruby, Q-switched Alexandrite, Q-switched Nd:YAG