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MELANOCYTES

  • Epidermal melanocytes are dendritic cells derived from neural crest cells

  • Their migration and differentiation is influenced by a number of signaling molecules: steel factor (stem cell factor, c-Kit ligand), Wnt, bone morphogenic proteins (BMPs), and hepatocytes growth factor

  • Provide melanin for 36 neighboring basal and spinous layer keratinocytes = one epidermal melanin unit

  • Number and distribution are the same in all skin types and ethnicities

  • Concentration and distribution/retention of melanosomes in keratinocytes cause different skin colors

  • Types of melanin:

    • Pheomelanin: red-yellow

    • Eumelanin: brown-black

  • Melanosomes

    • Membrane-bound organelles, site of melanin synthesis and storage

    • Found in melanocytes; they move from melanocytes to keratinocytes

  • Types of melanosomes:

    • Eumelanosomes: large, elliptical in shape and contain organized fibrillar glycoprotein matrix needed for eumelanin synthesis

    • Pheomelanosomes: smaller, spherical in shape, loose fibrillar glycoprotein matrix

    • Four stages of melanosome maturation:

      • – Stage I melanosomes (premelanosomes)

        • ▴ Found in the cytoplasm of melanocytes

        • ▴ Amorphous matrix; contain unprocessed glycoprotein known as Pmel17 (gp100)

      • – Stage II melanosomes

        • ▴ Found in the cytoplasm of melanocytes

        • ▴ Fully formed melanosome matrix, fibrils elongate and assemble into parallel sheets

        • ▴ Contain tyrosinase

        • ▴ No active melanin synthesis in eumelanosomes; melanin synthesis (not melanogenesis) in pheomelanosomes

      • – Stage III melanosomes

        • ▴ Found in the cytoplasm or dendrites of melanocytes

        • ▴ Tyrosinase activity becomes positive and round or oval, electron dense, deposits of melanin found on the internal filament network

        • ▴ Melanization begins at this stage

      • – Stage IV melanosomes

        • ▴ Found in the cytoplasm or dendrites of melanocytes

        • ▴ Round or oval, electron opaque

        • ▴ Fully melanized

        • ▴ Possess melanin, no enzymatic activity

  • Tyrosinase

    • Cofactor: copper (Cu2+)

    • Catalyzes two reactions

      • – Hydroxylation of tyrosine to DOPA (dihydroxyphenylalanine)—this is the rate limiting step

      • – Oxidation of DOPA to DOPAquinone

PIGMENTED LESIONS

Melasma

  • Melasma may be caused by the presence of more biologically active melanocytes in the affected skin rather than increase in melanocytes (Fig. 9-1)

  • Predominantly affects Fitzpatrick skin types III and IV. Genetic and hormonal influences in combination with UV radiation

  • May be precipitated by the following: oral contraceptive pills, pregnancy, thyroid dysfunction, cosmetics, and phototoxic or photoallergic medication reaction

  • Clinical findings

    • Brown reticulated hyperpigmented macules and patches, can be confluent or punctate

  • Clinical subtypes

    • Centrofacial: forehead, cheeks, upper lip, nose, and chin

    • Malar: symmetrical involvement of the upper cheek area

    • Mandibular: ramus of the mandible

    • Depth may be epidermal, dermal, or mixed

  • Diagnosis

    • Wood's light (wavelength, 340–400 nm): identifies depth of pigment; epidermal pigment enhanced, dermal pigment is not

  • Treatment

    • Topical: broad spectrum sunscreen is cornerstone of therapy. Topical therapy with a triple combination agent appears to be the most clinically effective: hydroquinone, tretinoin, and topical steroid. Other commonly used, but less studied agents: azelaic acid, kojic acid, ascorbic acid, and arbutin

    • Chemical peels: glycolic acid may be the most efficacious α-hydroxy peeling agent. Should be used in combination with daily use of depigmenting agent

    • Device-based: carbon dioxide fractional ablative laser appears to be the ...

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