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INTRODUCTION TO CHAPTER

Disorders of pigmentation, although not life-threatening, may cause significant psychosocial impairment in patients due to their visibility and associated stigma. Certain pigmentary disorders may also have associated symptoms. Management of pigmentary disorders requires accurate diagnosis and treatment in addition to careful assessment and monitoring of associated psychological conditions, such as depression and anxiety.

MELANOCYTE BIOLOGY

Melanocytes are neural crest-derived, pigment-producing cells located in the basal layer of the epidermis (stratum basale) as well as the middle layer of the eye (the uvea), the inner ear, vaginal epithelium, meninges, bones, and heart.1 Melanocytes typically migrate to the epidermis by the eighth week of life. Each melanocyte is attached to the basal layer via hemidesmosomes; however, there are no attachments between melanocytes and neighboring keratinocytes. Instead, they are connected through dendrites extending from each melanocyte to several keratinocytes. It is estimated that each melanocyte makes contact with roughly 36 keratinocytes in the suprabasal and basal layers.2 This contact between the two cell types is important in forming the epidermal-melanin unit,3 which allows for the transfer of packed pigmented granules called melanosomes.1,3

Melanosomes are the site for synthesis, storage, and transport of melanin. Melanin is formed via a four-step process (Figure 23-1). The first step involves the enzyme tyrosinase, which is formed in the rough endoplasmic reticulum and then processed in the Golgi apparatus of the melanocyte before accumulating in vesicles. Tyrosinase converts tyrosine into 3,4-dihydroxyphenylalanine (DOPA), which is then formed into polymers to create the different types of melanin, eumelanin, and pheomelanin.1

Figure 23-1.

Melanosome formation. Reproduced with permission from Mescher AL: Junqueira's Basic Histology: Text and Atlas, 16th ed. New York, NY: McGraw Hill; 2021.

Once formed, the melanosomes or melanin granules migrate to the tips of the melanocyte dendrites to be ingested by neighboring keratinocytes.3 Once in the keratinocyte, these melanin granules migrate toward the nucleus of the keratinocyte to aid in protection of the cell's DNA from ultraviolet light damage. This is referred to as a "supranuclear cap."1,3 As a result, keratinocytes contain more pigment than do melanocytes. Melanin pigment serves a protective function in melanocytes as well by protecting the membrane from ultraviolet A and B damage.1

The number of melanocytes does not determine differences in skin color. Rather, it is variation in melanosome number, size, and distribution that lead to the different skin phototypes.1 Individuals with darker skin have a greater number of melanosomes that are typically larger and more dispersed than those with lighter skin. The type of pigment produced by melanocytes may also contribute to differences in skin and hair color. Eumelanin is a black or brown pigment, while pheomelanin is a red or yellow pigment.1

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