pathogenesis vitiligo

Question 1

Vitiligo and melanocytes

“absolute” /“relative”

immunohistochemical

Answer 1

-destruction.of functional
immunohistochemically recognizable melanocytes -“absolute” type
no DOPA-positive melanocytes
“relative” melanocytes remain but decreased DOPA-positivity
-absent antibodies to melanocyte markers
putative melanocyte precursors -KIT receptor,protein expressed early in melanocyte differentiation

Question 2

• vitiliigo affects the entire keratinocyte–Langerhans cell–melanocyte unit
• epidermal milieu

Answer 2

decreased Keratinocyte-derived cytokines(SCF; KIT ligand)
increased TNF-α, (IL)-1 tacrolimus decreases

Langerhans cell changes-density, functional degenerative

Question 3

Pathogenic hypotheses convergence theory for vitiligo.“

Answer 3

1. Autoimmune destruction of melanocytes
2. intrinsic defect in melanocytes, their adhesive properties and/or factors critical to their survival
3. Defective defense against oxidative stress leading to destruction of melanocytes

Question 4

evidence for  
Autoimmune destruction of melanocytes
1. GENES & AB 
2. MICE
3. CELL CYTOTOXICITY

Answer 4

1. GENES & AB
   Epidemiologic association with autoimmune
   immunoregulatory genes variants linked
   Detection of sera melanocyte proteins antibodies TYR, TYRP1, DCT, MCHR1, SOX10

2.MICE
engrafted human skin nude mice, vitiligo patient sera melanocyte destruction
T-cell receptor transgenic mice recognizetyrosinase epitope develop vitiligo

3. CELL CYTOTOXICITY
   CD8+ T cells Infiltration perilesional
   Skin-homing, melanocyte-specific cytotoxic T cells against Melan-A/MART-1 blood
   generalized vitiligo following BMT vitiligo donors

Question 5

evidence for

intrinsic defect in melanocytes, adhesive properties and/or critical survival factors

Answer 5

1. abnormalities of cultured vitiligo melanocytes:
   Dilated RER
   Abnormal TYRP1 synthesis
   Increased sensitivity to oxidative stress (UVB)
2. transepidermal melanocytorrhagy
   defective melanocyte adhesion:
   mechanical stress, Koebner phenomenon
3. reduced melanocyte survival/dysregulation melanocyte apoptosis
   a) bcl-2–/– mice progressive loss of hair follicle melanocytes
   b) melanocyte maintenance factors deficiency SCF, KIT, MITF
   c) depigmentation tyrosine kinase inhibitors treatment target KIT

Question 6

Defective defense against oxidative stress leading to destruction of melanocytes

Answer 6

1.high in vivo epidermal H2O2 (oxidized pteridines, 6-biopterin); catecholamine biosynthesis/MAO A activity
2. defective calcium transfer/homeostasis
Inhibition of thioredoxin/thioredoxin reductase
3. low levels catalase(protective)-Oxidative