Melanocyte Biology and Disorders of Pigmentation

Question 1

Melanocytes

Answer 1

cells responsible for making melanosomes

• melanoblast differentiate and migrate to epidermis, hair bulbs of skin, uveal tract of eye, cochlea, vestibular labyrinth, leptomeninges of brain (not retinal pigment)
• reside in basal layer of epidermis
• each melaocyte comes into contact with ~30-40 keratinocytes, allowing transporation of melanosomes

-UV exposure causes increase in size and increase in tyrosinase activity (TX of tyrosinase gene), increase in MC1-R

• UVA causes immediate darkening which fades (mostly in dark-skinned people who have rapid oxidation of existing melanin/precursor)
• delayed tanning within 48-72 hrs after UVA or UVB because of new pigment production following increased tyrosinase activity

Question 2

Melanosome

Answer 2

organelles that synthesize melanin

• keratinocytes continually phagocytose dendritic tip of melanocyte to take up melanosomes
• melanosomes either degraded by lysosomal enzymes or remain in cell until sloughed at surface of stratum corneum

Question 3

Melanin

Answer 3

pigment

• contained mostly by keratinocytes
• tyrosinase key in biosynthesis
• key melanogenesis proteins: MSH, endothelin-1, UV light
• formation of diff melanin influenced by binding of melanocyte-stimulating hormone to melanocortin-1 receptor on melanocytes

Eumelain - brown-black
-elevated aMSH, thyroid hormones, estrogen, progesterone, and ACTH levels

pheomelanin - yellow-red
-mutation in MC1-R (also inability to develop tan)

Question 4

Depigmentation

Answer 4

complete loss of pigment (milk white presentation)

Question 5

Hypopigmentation

Answer 5

reduced epidermal pigment due to decreased melanocytes or decreased melanin (off-white)

Question 6

Leukoderma

Answer 6

general term encompassing depigmentation and hypopigmentation

Question 7

Hyperpigmentation

Answer 7

Melanoderma = increase in melanin deposition

Question 8

Ceruloderma

Answer 8

gray, slate, blue discoloration arising from increase in number of melanocytes

Question 9

c-KIT gene

Answer 9

encodes receptor for steel factor

• binding to steel factor results in phosphorylation and cascade of signal transduction
• critical for melanocyte proliferation and migration

Question 10

Epidermal melanin unit

Answer 10

melanocyte + neighboring keratinocytes it is connected to

Question 11

Skin color

Answer 11

largely determined by activity of melanocytes and number of melanosomes

• dark skin: singly dispersed, oval shaped melanosomes
• light skin: fewer, smaller, clustered, spherical melanosomes

Question 12

Vitiligo

Answer 12

common autoimmune inflam –> destroy melanocytes

• depigmented patches, especially around mouth, eyes, nose, hands, and genitals
• possible Koebnerization (dev. disease in trauma area)
• diagnosed via clinical + histopathology
• treated via photoprotection +phototherapy

-also risk of other autoimmune disorders like alopecia areata (focal hair loss), hypothyroidism, and pernicious anemia

Question 13

Piebaldism

Answer 13

AD inherited melanocyte migration disorder

• white forelock 85-90%
• patterned areas of depigmentation @ midline
• pigment changes found at birth and persist unchanged as melanocytes fail to migrate
• due to mutation in c-KIT gene in group of cells
• c-KIT receptor inactivated = failure of pigmented cells to fully migrate to midline

Question 14

Pityriasis Alba

Answer 14

disorder of melanocyte downregulation

• ill-defined hypopigmented round patches, sometimes w/ scale
• common among pple with atopic dermatits
• no effective treatment
• apply moisturizer and sunscreen

Question 15

Oculocutaneous albinism

Answer 15

AR disorder of altered melanin production

• reduction or complete lack of pigment in hair, skin, eyes
• ocular signs: nystagmus, photophobia, bad visual acuity
• most often due to defect in tyrosinase gene
• complete absence of pigment
• risk skin cancer

Question 16

Melasma

Answer 16

“mask of pregnancy”
-patchy dark pigment deposition with ill-defined borders on photo-exposed areas like face, arms and chest

-due to stimulation of melaninogenesis by increased estrogen and progesterone

Question 17

Cafe-au-Lait Macules (CALMs)

Answer 17

disorder of increased epidermal melanin

• increased epidermal melanin with normal melanocytes
• uniformly pigmented ligh brown macules and patches with sharp borders
• 2% newborns, 33% black
• syndromes >6 (neurofibromatosis type 1)

-NF-1 = AD disorder with cutaneous, ocular, neurological and skeletal abnormalities

Question 18

Addison’s Disease

Answer 18

disorder of altered melanin synthesis by hormones

• diffused bronze pigment with adrenal insufficiency
• adrenal gland fail to respond to ACTH and MSH (pituitary)
• overproduce ACTH and MSH –> darker pigmentation

Question 19

Wood’s lamp

Answer 19

UV light source @ 365nm

• depigmented skin accentuates but hypopigmented doesn’t
• accentuates pigment in epidermis but not in dermis
• allows predict success of bleaching agent

Question 20

skin biopsy

Answer 20

identify whether pigment is endogenous or exogenous (drug-induced or foreign body)

Question 21

Treatments

Answer 21

de/hypopigmented skin

• stimulate melanocyte and melaninogenesis
• topical corticosteroids, calcinerin inhibitors and phototherapy
• surgical transfer of pigmented skin
• sunscreen to prevent surrounding skin darkening

hyperpigmentation

• destroy melanocytes or melanin
• topical bleaching agents (hydroquinone, azelaic acid)
• medical lasers