NYAM Section on Dermatology Presents the 2012 Howard Fox, MD Memorial Lecture Date: March 13, 2012 to March 13, 2012 Time: 6:00 PM - 8:00 PM p.m., Lecture 7:00 p.m. – 8:00 p.m. Speaker(s): Torello Lotti, MD, Professor of the Dermatology and Venereology Division at Guglielmo Marconi University, Rome, Italy - Honorary Professor of Dermatology - China Medical University Shenyang, 18 Dec.2011 Chair, Executive Scientific Committee Vitiligo Research Foundation, New York , NY , USA. Sponsored by: NYAM Section on Dermatology Location: The New York Academy of Medicine, 1216 Fifth Avenue at 103rd Street, New York, NY 10029 "Vitiligo: What's New – Update in 2012" Vitiligo is a chronic acquired hypomelanotic disorder affecting 0.5-2% of the world's population. Different forms of vitiligo have been described, according to the distribution and the extent of the achromic lesion. Several hypotheses have been proposed to explain the pathogenesis of vitiligo. The two major pathogenetic hypotheses are focused on immune-mediated or toxic-mediated cell damage primarily directed at melanocytes. New data demonstrated an important involvement of the keratinocytes and dendritic cells in the pathogenesis of vitiligo. According to our progress in understanding Vitiligo pathogenesis, new and experimental therapies, such as narrow-band ultraviolet B microphototherapy (NB-UVB), narrow-band ultraviolet B excimer laser and monochromatic excimer light are available for the treatment of the disease. In addition, there are new topical treatments such as antioxidants, tacrolimus and pimecrolimus, prostaglandin E, and vitamin D derivatives. Excellent therapeutic results can be achieved through combination treatments. About the Speaker(s) Torello Lotti, MD, Prof. Lotti is Professor of the Dermatology and Venereology Division at Guglielmo Marconi University, Rome, Italy. Previously, he was Professor of the Dermatology and Venereology Division at University of Florence School of Medicine, Florence, Italy. The fields of his principal scientific investigations are focused on the study of neuropeptides in numerous skin diseases, of plasminogen activators in autoimmune dermatoses and in lichen planus, and the clinical aspects and treatment of psoriasis vulgaris with particular emphasis on new therapies with biological agents. Of particular relevance is his research on the pathogenesis and innovative treatments for vitiligo. Dr. Lotti is Visiting Professor and Director, International Centre for Balneology, Cell Biology, and Physiotherapy, Thomas Jefferson University, Philadelphia (PA, USA), Visiting Professor of Dermatology in six international universities, and Key Note Lecturer, Japanese Society of Cosmetic Dermatology. Past activities: Past-President of the Italian Society of Dermatology and Venereology, Past President of International Society of Dermatology.

1. Vitiligo - what’s New:
Update in 2012
The 58th Annual Howard Fox, MD
Memorial Lecture
March 13, 2012
Torello Lotti
Professor and Chair of Dermatology and
Venereology at Guglielmo Marconi

2. Hypomelanoses: Why ?
1. Loss or reduction of melanocytes;
2. Reduced melanine production from
melanocytes (altered tyrosinase
activity, altered structure/activity
of rough endoplasmic reticulum, lack
of specific melanocyte receptors…);
3. Decreased melanine transfer from
melanocytes to keratinocytes;
4. Primary disorder of keratinocytes.

3. Hypomelanoses
Normal
Albinism
Functional defect in melanine synthesis
Vitiligo
Localized loss / inactivation of melanocytes

4. Vitiligo: Definition
 Primitive acquired pigmentation disorder with
focal depigmentation of the skin;
 Characterized by well circumscribed milky
white cutaneous/mucous macules;
 Patches arise as a consequence of destruction
and/or functional inactivation of melanocytes
underlying a complex syndrome;
 Acquired (only in few cases congenital), often
familial (23% of the cases).

5. Vitiligo: Epidemiology
 Vitiligo affects 0.5-4% of the World
population.
 The disease generally begins between the ages
of 2 and 40.
 In a Dutch study, 50% of patients reported
the occurrence before the age of 20.

6. Vitiligo in 2012
Incidence ranges from 0,1% to 8,8%
in different country of the globe. The
highest incidence of the condition has
been recorded in India, Mexico and
Japan.

7. Vitiligo: Epidemiology
 Adults and children of both sex are equally
affected;
 No difference in races or skin type;
 The greater number of reports among females
is probably due to greater social consequence
to woman and girls affected by this condition;
 50% of patients  before the age of 20;
 25% of patients  before the age of 8.

8. Vitiligo: Clinical
Discrete, uniformly white
patches with convex borders
and surrounded by normal
skin, not painful and very
rarely itching.

9. Vitiligo: Favorite Sites
face (periorificial),
dorsal surface of the hands,
nipples,
axillae,
umbilicus,
sacrum,
inguinal/anogenital regions,
elbows,
knees,
digits,
flexor wrists.

10. Clinical Classification
 Localized
 Focal: one or more macules in one area but not clearly in a
segmental distribution;
 Unilateral/segmental: one or more macules involving a
unilateral segment of the body – lesions stop abruptely at
the midline;
 Mucosal: mucous membranes alone.
 Generalized
 Vulgaris – scattered patches that are widely distributed;
 Acrofacialis – distal extremities and face;
 Mixed – acrofacialis and vulgaris;
 Universalis
 Complete or nearly complete depigmentation.

11. Vitiligo: Differential Diagnosis
Alikhan A, Felsten LM, Daly M, Petronic-Rosic V.
J Am Acad Dermatol. 2011;65(3):473-91.

12. TUBEROUS
IDIOPATHIC SCLEROSIS
GUTTATE
HYPOMELAN
OSIS
PIEBALDISM

13. TINEA VERSICOLOR
PINTA
LEPROSY

14. HALO NEVUS
NEVUS ANEMICUS
MELANOMA
ASSOCIATED MELANOMA
LEUKODERMA WITH
REGRESSION

15. CHEMICAL INDUCED LEUKODERMA…
Ghosh S.cIndian J Dermatol. 2010;55(3):255-8.

16. Alikhan A, Felsten LM, Daly M, Petronic-Rosic V.
J Am Acad Dermatol. 2011;65(3):473-91.

17. Why?
Loss of normal melanocytes Dopa stain

18. ETIOPATHOGENESIS
GENETIC PREDISPOSITION
Autoimmune Susceptibility Locus (AIS1)
NEURAL HYPOTHESIS AUTOIMMUNE HYPOTHESIS
MELANOCYTE
DESTRUCTION
AUTOCYTOTOXIC/
RADICALIC HYPOTHESIS ECLECTIC HYPOTHESIS
MELANOCYTORRAGY
SYNERGISTIC THEORY

19. Vitiligo: Etiopathogenesis
 GENETIC PREDISPOSITION
 Autoimmune Susceptibility Locus (AIS1)
 AUTOIMMUNE
 Umoral mechanism -Autoantibodies
 Citotoxic mechanism – Cell mediated
 METABOLIC
 Hydrogen peroxide accumulation
 Abnormal expression of Tyrosine-Related Protein -1
 OTHERS
 Viral hypothesis
 Neuronal toxicity

20. Spritz RA. J Genet Genomics. 2011, 20;38(7):271-8

22. Metabolic
Pathogenesis
Altered antioxidant Increased activity
and scavenger of superoxide
mechanism dismutase
High levels of epidermic 7-BH4 and
H2O2
Inhibition of enzyme function (phenylalanine-hydroxilase
and tyrosinase) and abnormal expression of Tyrosinase
Related Protein-1 (TRP-1).
 impaired melanine synthesis

23. Convergence Theory
Westerhof, D’Ischia. Vitiligo puzzle: the pieces fall in place. Pigment Cell Res 2007 20; 345-359

24. Vitiligo: what’s new in 2012
Melanocytes are completely absent in the
depigmented epidermis
 Nordlund JJ and Lerner AB – Arch Dermatol, 1982;118:5-8
 Le Poole IC et Al. J Invest Dermatol, 1993;100:816-822
Vs.
Melanocytes are not completely absent in the
depigmented epidermis
 Bertosi KJ et Al. Eur J Dermatol 1998;8:95-97
 Tobin DJ et Al. J Pathol 2000;191:407-416
 Gottschalk GM, Kidson SH. Int J Dermatol. 2007;46(3):268-72

25. Vitiligo: what’s new in 2012
Melanocytes are not completely absent
in the depigmented epidermis
Normal Skin Perilesional Skin Lesional Skin
Massi D. Histopathological and ultrastructural features
of vitiligo. In: Lotti T & Hercogova J (Eds.) Vitiligo –
Problems and solutions. Marcel Dekker Inc, New York
2004

26. Vitiligo: what’s new in 2012
Melanocytes are not completely absent
in the depigmented epidermis
Comment:
– A subpopulation of “resistant” epidermal
melanocytes can persist independent of
disease duration
– Repigmentation can always
occur independent of
disease duration
and with
non-perifollicular pattern

27. VITILIGO:
NOT ONLY A MELANOCYTIC DISEASE?

28. Imokawa G. Autocrine and paracrine regulation of melanocytes in human skin and in
pigmentary disorders. Pigment Cell Res 2004

29. What’s new in 2012:
A focus on keratinocytes
 Impaired scavenging mechanisms can lead
to ROS increase and subsequent
melanocyte and keratinocyte damaging;
 Altered function of PAR-2 receptor can
impair calcium homeostasis in
keratinocytes and alter melanosome intake
and processing.

30. What’s new in 2012:
the focus on keratinocytes
 The importance in mitochondria in
keratinocytes from perilesional skin and
the role of oxidative stress.
Prignano F, et al. Ultrastructural and functional alterations of mitochondria in
perilesional vitiligo skin. J Derm Sci 2009;54:157–167

31. Mitochondrial alterations in
perilesional keratinocytes
 Mitochondrial activity plays a crucial role
in normal cell function
 Mitochondrial alterations observed in
perilesional keratinocytes appear to be
very similar to those described in the
same cell types during apoptosis
 The mitochondrial damage is associated
with an increase in ROS production and,
hence, oxidative stress.
Prignano F, et al. J Derm Sci 2009;54:157–167

32. Functional alterations in vitiligo
skin
 High levels of TNF-alpha and FasL in the
depigmented epidermis (role in increasing
apoptosis)
– Kim NH, et al. J Invest Dermatol 2007;127:2612–7.
 mRNA for TNF-α and IL-6, with an inhibitory
effect on pigmentation, was increased in the
epidermis from vitiligo biopsies.
 This could contribute to keratinocyte
apoptosis, which results in reduced release of
melanogenic cytokines and in melanocyte
disappearance.
– Moretti S, et al. Histol Histopathol 2009:24:849-857

33. Functional alterations in vitiligo
skin
 Apoptotic keratinocytes may cause a
decrease in SCF synthesis, which plays an
important role in melanocyte survival and
proliferation
 Keratinocyte apoptosis induces a decrease in
the synthesis of other melanocyte growth
factors, such as bFGF, resulting in
melanocyte disappearance.
– Lee AY, et al. Br J Dermatol
2004;151:995–1003.
– Moretti S, et al. Histol Histopathol
2009:24:849-857

34. Functional alterations in vitiligo
skin
 Endothelin-1 (ET-1) mRNA seems to be
significantly reduced in lesional as compared
to perilesional epidermis
 SCF and ET-1 may contribute to melanocyte
survival
– Moretti S, et al. Histol Histopathol 2009:24:849-857

35. Functional alterations in vitiligo
skin
 Protease-activated receptor (PARs) 2 is
abundantly expressed by keratinocytes, and
seems to contribute to the pigmentation
process
 PAR-2 impairment is seen in vitiligo, and may
contribute to the epidermal pigment deficit
through a reduced melanosome uptake in
keratinocytes.
 To date, a precise cause and effect
relationship between these two conditions
cannot be determined.
– Moretti S, et al. Pigment Cell Melanoma Res 2009;22:335–338

36. Vitiligo in 2012: the
importance of an evidence-
based approach
1. Is vitiligo an unmanageable disease?
2. Is systemic evaluation useful?
3. Is it everything about psychology?
4. Should I suggest to buy a UV lamp?

37. Is Vitiligo an unmanageable
disease?
 Only 16% of dermatologists in The Netherlands
are in favour of active treatment of vitiligo
– Njoo MD et Al, Int J Dermatol 1999;38:866-872
 84% of dermatologists in The Netherlands are
reluctant to start any active treatment in
vitiligo; 82% in the Mediterranean area either
prescribe placebos or treatments of cosmetic
relevance only
– Lotti T. La vitiligine: nuovi concetti e nuove terapie. UTET –
Torino, 2000

38. Is systemic evaluation useful?
 Vitiligo and tyroid disfunction: 8.7% to
38.5%
 Polyglandular syndrome (type I and II):
2.8%
 Diabetes mellitus type I: 1 to 7%
 Pernicious anaemia: 1.6% to 13%
 …
Llambrich A & Mascaro MJ. Vitiligo: Focusing on Clinical Association. In: Lotti T &
Hercogova J (eds.) Vitiligo: Problems and Solutions. Marcel Dekker Inc. – New York 2004,
pp. 179-184
El Mofti AM et Al. Disorders in healty relatives of vitiligo patients. In: Lotti T & Hercogova J
(eds.) Vitiligo: Problems and Solutions. Marcel Dekker Inc. – New York 2004, pp. 51-65

39. Vitiligo: Disease Association
Alikhan A, Felsten LM, Daly M, Petronic-Rosic V. J Am Acad Dermatol. 2011;65(3):473-91.

40. Is it everything about psychology?
The psychosomatic hypothesis
The somatopsychic rebound
Punishment and Leprosy complex
 33% cases of vitiligo are emotionally triggered,
with a biological incubation period of 2-3 weeks
between the stress event and the clinical
manifestation
– Griemser RD & Nadelson T, 1979
 80% of patients never tried any treatments
– Porter JR et Al, 1986
 The effect on sexual relationship
– Porter JR et Al, 1990

41. Vitiligo and Psychology
Vitiligo may impair quality of life
The dermatologist and the patient must openly discuss
this burden and react positively with quality of life
assessment.
Women are generally more psychologically affected by
the disorder than men
Observation of new pigmentation over the white
patches brings optimism to the vitiligo subject always
Psychotherapy can be of help in selected cases, but
only after careful consideration.

43. Should I suggest to buy a UV
lamp?
Dermatologists  no data available
Patient’s report  76% advised by dermatologists
Short term side-effects: burning, ocular, viral
infections
92%
Long term side-effects: skin tumour, premature
ageing…
???

44. VITILIGO TREATMENT: AN OVERVIEW
Lotti T, Gori A, Zanieri F, Colucci R, Moretti S. Vitiligo: new and emerging
treatments. Dermatol Ther 2008; 21:110-117.

45. VITILIGO TREATMENT: AN OVERVIEW
Lotti T, Gori A, Zanieri F, Colucci R, Moretti S. Vitiligo: new and emerging
treatments. Dermatol Ther 2008; 21:110-117.

46. Vitiligo: what’s new in
treatment
 Excimer laser / Monochromatic
excimer light (MEL)
 Focused microphototherapy
 Calcineurine inhibitors
with NB-UVB

47. Vitiligo: what’s new in
treatment
Narrow Band UVB Excimer Laser (XeCl) and
MEL (Monochromatic Excimer Light)
 UVB 308 nm;
 Only the hypopigmented areas are treated;
 No contrast between normal and
hypopigmented skin;
 Low dose of irradiation;
 Reduced short-term and long-term side
effects;
 Treatment of limited body areas.

49. BEFORE AFTER 20
TREATMENTS
J Korean Med Sci 2005; 20: 273-8

50. Narrow Band UVB
Microphototherapy
 UVB 311 nm
 Only the hypopigmented areas are treated
 No contrast between normal and affected skin
 Low dose of radiation
 Reduced short-term and long-term adverse
events

51. BIOSKIN® emission spectrum
Intensity
10-100 mW/cm2

52. Results of a study on
734 patients after 2
years of BIOSKIN®
treatment

53. Calcineurine inhibitors
 Tacrolimus ointment 0,03-0,1%
 Pimecrolimus cream 1%
 Alone or in association with XeCl
laser/MEL
 Best results in photoexposed areas (face
and neck)
 Inhibits T Lymphocyte activation and the
release of pro-inflammatory cytokines

54. Falbella R and Barone I. Update on skin repigmentation therapies in vitiligo.
Pigment Cell Melanoma Res. 2008: 22; 42–65

55. Calcineurine inhibitors:
are they really effective?
PROs
•0.1% tacrolimus is as effective as 0.05% clobetasol
propionate.
• Lepe V, Moncada B, Castanedo-Cazares JP, Torres-Alvarez MB, Ortiz CA, Torres-
Rubalcava AB. Arch Dermatol 2003;139:581-5
•Tacrolimus plus excimer laser is more effective than
excimer laser alone
• Kawalek AZ, Spences JM, Phelps RG. Dermatol Surg 2004;30(2 Pt 1):130-5
CONs
•The combination of NB-UVB and tacrolimus is no more
effective than NB-UVB alone.
• Mehrabi D, Pandya AG. Arch Dermatol 2006;142:927-9
•Pimecrolimus is no more effective than placebo in
achieving repigmentation.
• Dawid M, Veensalu M, Grassberger M, Wolff K. J Dtsch Dermatol Ges 2006;4:942-6

56. Combination therapy in
2012

57. Combination therapy in
2012
 Open study
 Tacrolimus 0.1% ointment,
Pimecrolimus 1% cream,
Betamethasone dipropionate 0.05%
cream, Calcipotriol ointment
50mcg/g, 10% L-phenylalanine cream
 alone or in combination with
311nm nb-UVB microphototherapy
 470 patients affected by vitiligo
(<10% skin surface)
Lotti T et al. Dermatol Ther 2008;21 Suppl 1:s20-6

58. Group 1 BIOSKIN® alone
Group 2 0.1%Tacrolimus+ BIOSKIN®
Group 3 1% Pimecrolimus+BIOSKIN®
Group 4 Betamethasone dipropionate 0.05%
+BIOSKIN®
Group 5 Calcipotriol ointment
50mcg/g+BIOSKIN®
Group 6 10% L-phenylalanine+BIOSKIN®
Group 7 0.1% Tacrolimus alone
Group 8 1% Pimecrolimus alone
Group 9 Betamethasone dipropionate 0.05%
Group 10 Calcipotriol ointment 50mcg/g alone
Group 11 10% L-Phenylalanine alone

59. Repigmentation rates: beginning of repigmentation
(weeks) as assessed by clinical evaluation
14
12
10
8
Weeks
6
4
2
0
Treatment Groups
Group I: Bioskin alone Group II: 0.1% Tacrolimus + Bioskin
Group III: 1% Pimecrolimus + Bioskin Group IV: 0.05% Betamethasone dipropionate + Bioskin
Group V: Calcipotriol ointment 50 mcg/g + Bioskin Group VI: 10% L-Phenylalanine + Bioskin
Group VII: 0.1% Tacrolimus alone Group VIII: 1% Pimecrolimus alone
Group IX: 0.05% Betamethasone dipropionate alone Group X: Calcipotriol ointment 50 mcg/g alone
Group XI: 10% L-Phenylalanine alone

60. Repigmentation rates and final repigmentation results: visual comparison
of different treatment groups as assessed by clinical evaluation
100
90
Percentage of patients reaching >75%
80
70
repigmentation
60
50
40
30
20
10
0
Time (Months)
Group I: Bioskin alone Group II: 0.1% Tacrolimus + Bioskin
Group III: 1% Pimecrolimus + Bioskin Group IV: 0.05% Betamethasone dipropionate + Bioskin
Group V: Calcipotriol ointment 50 mcg/g + Bioskin Group VI: 10% L-Phenylalanine + Bioskin
Group VII: 0.1% Tacrolimus alone Group VIII: 1% Pimecrolimus alone
Group IX: 0.05% Betamethasone dipropionate alone Group X: Calcipotriol ointment 50 mcg/g alone
Group XI: 10% L-Phenylalanine alone

61. General considerations:
how to treat vitiligo
 Dermatologists are prescribing less PUVA
in favour of UVB;
 Growing introduction of combined
treatments targeted UVB + “active”
topicals;
 Repigmentation rates show the
therapeutic success of phocused
microphototherapy which is more
remarkable when used in combination.

62. General considerations:
how to treat vitiligo
 Both BIOSKIN® and Potent topical
corticosterod preparations alone are the first
line treatment in vitiligo vulgaris affecting less
than 10% of the skin surface.
 Association of these 2 treatments gives
better results, with very high repigmentation
rate in more than 90% of patients.
 High repigmentation rates are observed also
for other combination treatments, while
Tacrolimus and Pimecrolimus but not
phenylalanine are relatively active when
applied without UVB irradiation .

63. PSEUDOCATALASE CREAM
catalase
H2O2 H2O + O2
71 children with vitiligo
Pseudocatalase cream + NB-UVB vs NB-UVB alone
> 75% repigmentation 70% disease progression
(face, neck, trunk, and extremities)
Schallreuter KU, Kru¨ ger C, Wu¨ rfel BA et al. From basic research to the bedside: efficacy of topical
treatment with pseudocatalase PC-KUS in 71 children with vitiligo. Int J Dermatol 2008;47:743–753.

64. PROSTAGLANDN E
PGE2 has stimulant and immunomodulatory effects on
melanocytes
Excellent response in neck scalp and trunk lesions.
Kapoor R et al. Br J Dermatol 2009; 160(4) 861-3
VITAMIN D ANALOGS
•Possible role in melanocyte
differentiation ?
•Not effective alone.
•Possible combination therapy
with UV and steroids.
Birlea SA et al. Med Res Rev. 2009; 29 (3): 514-546,

65. Vitamin D analogs
 Calcipotriol and tacalcitol as topical therapeutic agents in
vitiligo
 Vitamin D ligands target T cell activation, mainly by
inhibiting the transition of T cells from early to late G1
phase and by inhibiting the expression of several pro-
inflammatory cytokines genes, such as those encoding TNF-
alpha and IFN-gamma.
 Vitamin D(3) compounds influence melanocyte maturation
and differentiation and up-regulate melanogenesis through
pathways activated by specific ligand receptors, such as
endothelin receptor and c-kit.
 Birlea SA, Costin GE, Norris DA. Curr Drug Targets. 2008 Apr;9(4):345-59.

66. THERAPEUTIC ALGORITHM in CHILDREN
1. Potent/very potent topical steroid
(max 2 months)
2. Topical pimecrolimus/tacrolimus
(better short-term safety profile)
3. NB-UVB phototherapy
(max 200 treatments)
No recommendation for vitamin D anoalogues, PUVA,
surgical treatments and systemic therapy

67. THERAPEUTIC ALGORITHM in ADULTS
1. Potent/very potent topical steroid
(max 2 months)
2. Topical pimecrolimus (segmental vitiligo)
(better short-term safety profile)
3. NB-UVB (or PUVA) phototherapy
(max 200 treatments NB-UVB; 150 PUVA)
4. Surgical treatments
5. Depigmentation with p-(benzyloxy)phenol
(> 50% depigmentation, extensive depigmentation
on the face or hands)
No recommendation for vitamin D anoalogues and systemic
therapy

68. Felsten LM, Alikhan A, Petronic-Rosic V. J Am Acad Dermatol. 2011

69. Vitiligo: an evidence-based
approach
Positive balance of active treatments of vitiligo
patients*
 Topical corticosteroids (max 6 months)  89%
 PUVA treatment (max 12 months)  16%
 PUVA treatment (max 9 months)  25%
 UVB treatment (max 6 months)  87% (Broad +
Narrow Band)
 Surgical treatment (one shot + UVB)  68%
*evaluation made by Dermatologists
• Int J Dermatol 1999;38:866-872
• Arch Dermatol 1999;135:1514-1521

71. There is moderate evidence
for the use of
topical corticosteroids,
although long-term use is
likely to lead to adverse
effects.
Topical non-steroidal immunomodulators such as
tacrolimus as alternatives to corticosteroids are
a form of care that appear promising,
particularly in combination with light therapies
(caution when combining topical immunomodulators
with light:theoretical long term risk of skin
cancer).

72. The use of a light source,
either as monotherapy, or in
combination with oral or topical
photoactive chemical is the most
common method used in
practice.
There is some evidence that
excimer laser is more effective
in combination with topical
interventions such as
hydrocortisone 17-butyrate,
tacrolimus, or tacalcitol.

73. Surgical therapies can be effective for small
areas in peoplewith stable disease.
Suction blister grafts may result in adverse
effects, (precipitation of new areas of vitiligo
at donor sites, Koebner phenomenon).

74. In search for more evidence: the long road
 The importance of mitochondria in keratinocytes
from perilesional skin and the role of oxidative stress
 The possible role of antioxidant supplementation in
the treatment of vitiligo

75. Positive effects of the supplementation
of antioxidants in cultured cells
 Total Antioxidant Capacity
(marker of cellular scavenging
activity)
 Mitochondrial membrane
depolarization (marker of
mitochondrial and cellular
integrity)

76. Future perspectives
 Our study group is investigating on the
positive effects of the supplementation of
antioxidants in cultured cells form lesional,
perilesional and healthy skin of selected
vitiligo patients.
 The supplementation of curcumin and
capsaicin at peculiar concentrations can
dramatically improve the resistance of
cultured cells to oxidative stress.
 Focus on keratinocytes from perilesional skin
as the first actors in vitiligo pathogenesis .

77. What’s new in surgery
 Punch micrografting seems to be very
effective for the treatment of stable forms
of vitiligo.
Before Immediately after the surgery

78. Before Immediately after
surgery
Before After 2

79. CONCLUSIONS
 At the horizon of vitiligo therapy and cure we
see a complex puzzle with some essential bricks
already well positioned and installed in the right
place.
 The Vitiligo Research Foundation
(www.vrfoundation.org ; www.vitinomics.net ) is
committed to find the cure for vitiligo and to
bring the needing of the vitiligo subjects to the
attention of the National Health Sysems.

80. How to manage vitiligo
Correct diagnosis
Comorbidities
Patient expectations
Communication issue
in 2012
and further

81. OUR CONTRIBUTIONS

82. Vitiligo Research Foundation
 Firmly committed to curing Vitiligo, the VR
Foundation is a philanthropic organization
funding and fast-tracking medical research
globally.
 Creating Synergy for Expedited Research. The
world is now your R&D department. See
Vitinomics.net for more details.

83. VRF Leadership Team
Mr. Dmitry Aksenov established the
Mr. Dmitr y Aksenov 
 Vitiligo Research Foundation as a
MSc, MBA continuation of his medical- research
VRF Founder and President initiatives. He joined with leading
physicians and scientists in launching
the vitiligo research alliance to advance
progress against this annoying skin
disease. Recently, he formalized his
philanthropic activities by founding the
VR Foundation, which has become one
of leading supporters of vitiligo research
and treatment. As an entrepreneur, Mr.
Aksenov is often said to have
revolutionized Russian real estate
development market and created
thousands of jobs. He has introduced
the first energy-efficient and affordable
house to the local market in 2010. He
graduated with highest distinction and
earned his Master of Science degree in
1989.

84. VRF Leadership Team
One of the America's foremost dermatologists,
Robert Schwartz is Professor and Head of
 Prof. Rober t A .  Dermatology at New Jersey Medical School,
one of the eight medical schools in the New
Schwar tz, MD, Professor York City metropolitan area. He is also
and Head of Dermatology, Professor of Medicine, Professor of Pediatrics,
Professor of Pathology and Laboratory Medicine
New Jersey Medical School and Professor of Preventive Medicine and
Community Health at the New Jersey Medical
(US) School.
Professor Schwartz has authored several books, 10
monographs, and is the author of over 250 book
chapters, 500 articles, and 150 other
publications. Professor Schwartz has been
elected a Member Honoris Causa of 15 National
Dermatologic Societies in Europe. He has
lectured widely, including eighteen consecutive
years on the faculty of the annual meeting of the
American Academy of Dermatology, as a
featured speaker dozens of dermatological
congresses. He is a past President of the
Dermatology Section of the New York Academy
of Medicine, and in 2009 began a five-year term
on the Board of Directors of the International
Society of Dermatology.

85. VRF Leadership Team
 Torello Lotti, MD,  Full Professor of Dermatology, Dept
of Dermatological Sciences,
Professor of
University of Florence, Italy. A
Dermatology world-renown expert on vitiligo, a
VRF Scientific Director key note lecturer at major
and Chairman , Executive dermatology meetings, visiting
professor at several universities in
Scientific Committee homeland Italy and abroad,
chairman and director of
dermatology societies, a co-author ,
among many, of comprehensive
book “Vitiligo: Problems and
Solutions”, Professor Torello Lotti
provides top scientific advisory to
the VRF.
 www.torellolotti.it

86. VRF Leadership Team
•  Jana
Hercogova, MD,  President-Elect of the European
Academy of Dermatology and
PhD Venereology, President of
Scientific Director International Congress of
Dermatology, Chair of the
Communications Committee of
International Society of Dermatology,
Professor Jana Hercogova is best
known for her excellence in research,
education and training. A top
presenter at key professional events,
she is providing top scientific
advisory to the VRF.

87. VRF Leadership Team
 Yan Valle, MSc, MBA  Dr. Yan Valle specializes in
commercial applications
arising from advanced
VRF Executive technologies for almost 20
years. He currently leads our
Director Cloud Medical Research and Managem
and oversees all VRF
operations. Prior to joining
the VRF, he was a Director of
Business Development at a
leading technology company
in Toronto. Before 00’s, he co-
owned a consulting company
that served Fortune 500
companies, governments and
venture funds in emerging
markets of EEMEA and
LATAM.

88. VRF

89.  Berti S, Bellandi S, Bertelli A, Colucci R, Lotti T, Moretti S. Vitiligo
in an Italian outpatient center: a clinical and serologic study of 204
patients in Tuscany. Am J Clin Dermatol. 2011;12(1):43-9.
Prignano F, Ricceri F, Bianchi B, Guasti D, Bonciolini V, Lotti T,
Pimpinelli N. Dendritic cells: ultrastructural and
immunophenotypical changes upon nb-UVB in vitiligo skin. Arch
Dermatol Res. 2010
Arunachalam M, Sanzo M, Lotti T, Colucci R, Berti S, Moretti S.
Common variable immunodeficiency in vitiligo. G Ital Dermatol
Venereol. 2010;145(6):783-8.
Becatti M, Prignano F, Fiorillo C, Pescitelli L, Nassi P, Lotti T,
Taddei N. The involvement of Smac/DIABLO, p53, NF-kB, and
MAPK pathways in apoptosis of keratinocytes from perilesional
vitiligo skin: Protective effects of curcumin and capsaicin. Antioxid
Redox Signal. 2010, 1;13(9):1309-1321.

90.  Prignano F, Pescitelli L, Becatti M, Di Gennaro P, Fiorillo C,
Taddei N, Lotti T. Ultrastructural and functional alterations of
mitochondria in perilesional vitiligo skin. J Derm Sci 2009;54:157–
167;
Moretti S, Fabbri P, Baroni G, Berti S, Bani D, Berti E, Nassini R,
Lotti T and Massi D. Keratinocyte dysfunction in vitiligo epidermis:
cytokine microenvironment and correlation to keratinocyte
apoptosis. Histol Histopathol 2009;24:849-857;
 Moretti S, Nassini R, Prignano F, Pacini A, Materazzi S, Naldini A,
Simoni A, Baroni G, Pellerito S, Filippi I, Lotti T, Geppetti P and
Massi D. Protease-activated receptor-2 downregulation is associated
to vitiligo lesions. Pigment Cell Melanoma Res. 2009;22:335–338.
Lotti T, Berti S, Moretti S. Vitiligo therapy.Expert Opin
Pharmacother. 2009;10(17):2779-85.

91. Berti S, Buggiani G, Lotti T. Use of tacrolimus ointment in vitiligo alone
or in combination therapy. Skin Therapy Lett. 2009;14(4):5-7;
Lotti T, Buggiani G, Troiano M, Assad GB, Delescluse J, De Giorgi V,
Hercogova J. Targeted and combination treatments for vitiligo.
Comparative evaluation of different current modalities in 458 subjects.
Dermatol Ther 2008;21 Suppl 1:s20-6;
Prignano F, Pescitelli L, Ricceri F, Lotti T. The importance of genetical
link in immuno-mediated dermatoses: psoriasis and vitiligo. Int J Dermatol
2008;47:1060–1062;
Prignano F, Betts CM, Lotti T. Vogt-Koyanagi-Harada disease and
vitiligo: where does the illness begin? J Electron Microsc (Tokyo). 2008
 Lotti T, Prignano F, Buggiani G. New and experimental treatments of
vitiligo and other hypomelanoses. Dermatol Clin. 2007;24(3):393-400
 Hercogova J, Buggiani G, Prignano F, Lotti T. A rational approach to the
treatment of vitiligo and other hypomelanoses. Dermatol Clin.
2007;24(3):383-392

92. Thank you for your attention
www.torellolotti.it