Chapter 9: Pigmentary Disorders

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 ...