Materi kulit

2. NEWER & UPCOMING
THERAPY IN
HYPOPIGMENTATION
REIVA FARAH DWIYANA
Dept. Dermatology & Venereology, Faculty of Medicine,
Universitas Padjadjaran/Dr. Hasan Sadikin Hospital Bandung

3. Introduction
HYPO
PIGMENTA-
TiON
Inflammation-
noninflammation
Genetic-
nongenetic
Infection-
noninfection

4. ETIOPATHOGENESIS
None or less melanin pigment caused
by disorders in:
Melanocyte prekursor (melanoblast)
Melanosome transfer
Inflammation
Secondary effect after inflammation

5. Melanocyte formation, melanogenesis,
and melanosom transfer
! 27
!
Gambar 2.10 Ringkasan Tahapan Proses Pigmentasi Kulit
MELANOBLAST
SINYAL
- Wnt
- BMP
- ET
- SF
- HGF
- Cadherin
PROTEIN
MELANOGENIK
- Enzim
- Protein struktural
- Protein
melanogenik
tambahan
- Protein regulator
MELANOGENESIS
- Sintesis melanin
- Biogenesis
melanosom
- Sorting protein
- Biosintesis
melanosom
TRANSFER
MELANOSOM
" Ke dendrit
melanosit
" Ke keratinosit

6. MELANOGENESIS
•SINYAL
• PROTEIN
MELANOGENIK
• MELANOGENESIS
• TRANSFER
MELANOSOM
Wnt HGF
BMP ET
SF
Cadherin
Enzim
Prot. struktural
Prot. melanogenik
Prot. regulator
Sintesis melanin
Biogenesis mel.som
Sorting protein
Biosintesis mel.som
Ke dendritik
melanosit
Ke keratinosit
Melano-
blast

8. MELANIN
SYNTHESIS
PATHWAY

9. Classification of Hypopigmentation
inheritance acquire
Tabel'1.'Klasifikasi'kelainan'hipopigmentasi'kongenital'dan'akuisita'
'
'
'
Kongenital' Akuisita/didapat'
Genodermatosis:'
'
Non2genodermatosis:'
Infeksi:'
'
'
'
Non2
infeksi'
merupakan prekursor melanosit, yang akan berubah menjadi melanosit. Di
dalam melanosit terdapat serta organel tempat biosintesis melanin, yaitu
melanosom yang selanjutnya melalui ujung-ujung dendrit melanosit akan
terurai menjadi melanin dan tersebar di keratinosit.(9)
2.1.2.5.1 Sintesis Melanin
Melanin merupakan derivat indol dari 3,4-dihydroxyphenylalanine (DOPA),
yang terdiri dari dua jenis: eumelanin dan feomelanin. Melanin dibentuk di
melanosom melalui serangkaian tahap stres oksidatif. Suasana pH melanosom
menyebabkan terjadinya aktivitas enzimatik melanogenik dan memengaruhi
polimerisasi melanin.2-4

10. ILL DEFINE BORDER
WELL DEFINE BORDER

11. Classification of Hypopigmentation
inheritance acquire
Tabel'1.'Klasifikasi'kelainan'hipopigmentasi'kongenital'dan'akuisita'
'
'
'
Kongenital' Akuisita/didapat'
Genodermatosis:'
'
Non2genodermatosis:'
Infeksi:'
'
'
'
Non2
infeksi'
merupakan prekursor melanosit, yang akan berubah menjadi melanosit. Di
dalam melanosit terdapat serta organel tempat biosintesis melanin, yaitu
melanosom yang selanjutnya melalui ujung-ujung dendrit melanosit akan
terurai menjadi melanin dan tersebar di keratinosit.(9)
2.1.2.5.1 Sintesis Melanin
Melanin merupakan derivat indol dari 3,4-dihydroxyphenylalanine (DOPA),
yang terdiri dari dua jenis: eumelanin dan feomelanin. Melanin dibentuk di
melanosom melalui serangkaian tahap stres oksidatif. Suasana pH melanosom
menyebabkan terjadinya aktivitas enzimatik melanogenik dan memengaruhi
polimerisasi melanin.2-4

12. segmental
generalized
(non-segmental)
Acral Localized Vulgaris Universalis
Classification of Vitiligo

13. DIAGNOSIS
• Very easy based on clinical
appearance
• Hypopigmented macule 
Wood’s lamp
At first diagnosis and follow up (at least
every 6 months): examination
VASI (Vitiligo Area Severity Index) is better
than VETF (Vitiligo European Task Force)
(Pasadena et al, 2013)

14. Etiology & pathogenesis
• Like a PUZZLE
• 3 hypothesis:
• Autoimmune
• Imbalance of
oxidative stress
• Neuro-
chemical
• Predisposing:
• Genetic non-
Mendelian
• Precipitating:
• Chemical
• Sun exposure
• Viral: HSV (?)

15. Shajil, E. M., S. Chatterjee, et al. (2006). Vitiligo: Pathomechanisms and genetic polymorphism of
susceptible genes. Ind J Exp Biol 44: 526-539.

16. Phenol and cathecol
TRP-1
Keratinocyt
e
TNF-α
H2O2
Minor trauma
SCF <<
Melanocyte damage
Presentation to Langerhans cell
Activation T-cell effector
T-cell migration to epidermis
ICAM 1, IL-8
IgG
Melanocyte destruction
Oxidative stress
Oxidative stress
Ortoquinone ↑
L-phenilalanin L-tirosin
Asetilkolin ↑
Tyrosinas
eee
Hydroxilase tyrosin
6BH4
Norephinephrinerin
MAO ↑
6BH4 7BH4
H2O2
H2O2
Dopamine
DOPA
Hydorxylase
phenilalanin
Melanin
GTP
PNMT ↓
COMT
NPY
6BH4 + H2O2 → 6 biopterin
Epinefrin
AUTOIMMUNE
hypothesis
OXIDATIVE
STRESS &
NEURO-
CHEMICAL
hypothesis

17. Convergence
Theory
Autoimmunization
Growth factors
deficiency
Defective
adhesion
Catecholamines, ROS,
Neuropeptides
Loss of
dendricity
Weakening of
melanocyte
attachment
Detachment
Apoptosis
Trans-epidermal
elimination
Genetically
supported
Zinc-α2-
glycoprotein
deficiency
Virus
Clinical
vitiligo
Subclinical
vitiligo
Cell-
mediated
Humoral
Cytokines
Friction
Chronic
melanocytorrhagy

18. VASI Score:
Vitiligo Area
Scoring Index
1 hand unit = 1%

19. VASI score with Dubois Palm Hand

20. VASI score with Dubois Palm Hand
Pasadena et al, 2014

21. Therapy
 < 10% BSA:
 Topical
 Combinantion
> 10%:
Photherapy
Surgical

22. Bethametasone only
Initial 2 months 7 months

23. Kombination
bethametasone + calcipotriol
2 months
baseline 7 months, side effect (-)

24. Applied 30 minute
prior to sunbath
 sunbath for 10 min
28 days
VASELINE ALBUM + 2% LCD
Repigmentation
(+)

25. PHOTOTHERAPY
UVA
UVB
Narrow band
311 nm
Excimer 308 nm
CHAMBER UVB 311 nm

26. Narrow Band 311 nm
After 48
treatments

27. UVB 308 nm EXCIMER LAMP
3rd treatment 12th
treatment
8th treatment

28. 5 sessions
Initial 150mJ, total 25 sessions Max dose 550mJ
Dr.K Maeda Otaru dermatological office
Base Line
5 sessions
(290mJ)
15 sessions
(550mJ)
24 sessions
(550mJ)J)

29. Initial 150mJ, total 17 sessions Max dose 300mJ
Dr.K Maeda Otaru dermatological office
Base
Line
6 sessions
(300mJ)
9 sessions
(300mJ)
12 sessions
(300mJ)
17 sessions
(300mJ)

30. Side effect: IRRITATION
• Stop treatment
• Topical corticosteroid
• After healed: start with
lower dose
• Often become
hyperpigmentation
at the border

31. SURGERY
INDICATION:
-Stable vitiligo: > 6 months not enlarge (all
lesions) and no new lesion
-Technique: blistering, grafting, punching,
“stem cell”
-Combine with phototherapy after surgery
 good result
HALO NEVI:
Must excision at the nevi (not halo), because the
nevi has antigen to destroy melanocyte around the
nevi  depigmented halo

32. Geel, N. v., B. K. GOh, et al. (2011). A Review of
Non-Cultured Epidermal Cellular Grafting in
Vitiligo. J Cut and Aest Surg 4(1): 17-22.

33. Blister technique

34. Punch graft

35. Epidermal graft

36. Better combination of
graft and phototherapy

37. Newer and Upcoming?
Gen therapy
Stem cell
Vitamin D
Unknown:
Prostaglandin analog
Tofacinitib citrate
Anecdotal: tincture iodine

38. Immune cells
Monocytes, macrophages,
dendritic cells, B&T lympocytes
Skin cells:
Keratinocytes, melanocytes,
fibroblasts, Langerhans cells,
endothelial cells, sebaceous
glands
VITAMIN D

39. Role of Vitamin D in Skin Immunity

40. Repigmentation
Stimulation
Role of Vitamin D in Vitiligo

41. UVB pada sinar matahari
(290 -320 nm)
Provitamin D3
(7-dehidrokolesterol)
Previtamin D3
Vitamin D Synthesis
Mediator (partial)
→ melanogenesis ↑
25(OH)D ↑
Combinantion of NB-UVB - Vitamin D

42. 25-(OH)D before and after NB-UVB 311 nm
phototherapy
0%
20%
80%
Normal
Insufisiensi
Defisiensi
After phototherapy
X: 13,48, SB: 6,08
Median: 13,05
Rentang 3-28,05
Pasaribu et al, 2012

43. Larasati et al, 2017

44. Larasati et al, 2017

45. Combination of excimer light 308 nm
& vitamin D3 5000 IU oral for 8 weeks at
pediatric vitiligo
Before After

46. Excimer light 308 nm single therapy
for 8 weeks at pediatric vitiligo
Before After

47. VASI Score in Combination Treatment of
Narrow Band 311-nm and Vit D 5000 IU in adult
vitiligo

48. VASI Score in Single Treatment of
Narrow Band 311-nm in adult vitiligo

49. Combinantion of NB UVB 311 -nm
and Vitamin D 5000 IU

50. Monotherapy of NB UVB 311-nm

51. Bimatoprost (Prostaglandin
Analog)
- Glaucoma
treatment
- Eye lash
- Hypopigmentation?
Dose:
Bimatoprost 0,03% one
drop/cm2, twice
daily for four
months

53. Bimatoprost mechanism in alopecia

54. Tofacinitib citrate

56. Tincture Iodine + UVA light
American Journal of Dermatology and Venereology 2014, 3(4): 75-79
DOI: 10.5923/j.ajdv.20140304.03
Treatment of Vitiligo with Topical 5% Tincture Iodine
and UVA Light
Khalifa E. Sharquie1,*
, Hayder R. Al-Hamamy2
, Adil A. Noaimi1
, Mosa H. Al-Obeidy3
1
Department of Dermatology, College of Medicine, University of Baghdad, Iraqi and Arab Board for Dermatology and Venereology,
Baghdad Teaching Hospital, Medical City, Baghdad, Iraq
2
Chairman of Scientific Council of Dermatology & Venereology-Iraqi Board for Medical Specializations, Baghdad, Iraq
3
Department of Dermatology & Venereology, Baghdad Teaching Hospital, Baghdad, Iraq
Abstract Background: There are many therapies for vitiligo like PUVA Sole, steroid, Narrow band UVB, 15 % lactic
acid and 5%tincture iodine. Objective: To re-evaluate topical 5% tincture iodine action in vitiligo alone and in combination
with UVA exposure in comparison with UVA exposure alone and tap water as placebo controlled in treatment of localized
vitiligo. Patients and Methods: This single blind placebo controlled therapeutic trial where 20 patients with 80 patches of
localized vitiligo were included. Patches were divided into 4 groups according to type of treatment: Group I: 20 patches
treated with topical 5% tincture iodine solution alone. Group II: 20 patches treated with UVA exposure alone. Group III: 20
patches treated with topical 5% tincture iodine solution with UVA exposure. Group IV: 20 patches treated with application
of tap water as a placebo control. All treatments were given on a twice weekly base. Patients were evaluated according to the
grade of response to treatment. Results: After 6 months of treatment with 2 months follow up for each patient, the results
were as follow: Group I: 85% (17 patches) patients showed re-pigmentation more than 75%of size of patches. Group II:
78 Khalifa E. Sharquie et al.: Treatment of Vitiligo with Topical 5% Tincture Iodine and UVA Light
Table 4. Showing the response to the different modes of therapy after 6 months of treatment
Iodine + UVA
No. %
UVA
No. %
Iodine
No. %
Group
-
-
-
-
-
-
Grade 0
-
-
25%
5
5%
1
Grade I
-
-
35%
7
_
_
Grade II
5%
1
25%
5
10%
2
Grade III
95%
19
15%
3
85%
17
Grade IV
100%
20
100%
20
100%
20
Total

57. Conclusion
 Mechanism of hypopigmentation is complex
and unrelated yet each other
 New therapies are still in clinical studies
 Further pathogenesis study must be done in
order to find new hypopigmentation therapy

58. THANK YOU