Vitiligo - what’s New:Update in 2012

Torello Lotti

Professor and Chair of Dermatology and Venereology at Guglielmo Marconi University, Rome, Italy

The 58th Annual Howard Fox, MD Memorial LectureMarch 13, 2012

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.

Hypomelanoses

Normal

Albinism

Vitiligo

Functional defect in melanine synthesis

Localized loss / inactivation of melanocytes

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).

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.

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.

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.

Vitiligo: Epidemiology

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

Vitiligo: Clinical

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

Vitiligo: Favorite Sites

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.

Vitiligo: Differential Diagnosis

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

TUBEROUS SCLEROSIS

PIEBALDISM

IDIOPATHIC GUTTATE HYPOMELANOSIS

TINEA VERSICOLOR

LEPROSY

PINTA

NEVUS ANEMICUS

HALO NEVUS

MELANOMA ASSOCIATED LEUKODERMA

MELANOMA WITH REGRESSION

CHEMICAL INDUCED LEUKODERMA…

Ghosh S.cIndian J Dermatol. 2010;55(3):255-8.

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

Why? Loss of normal melanocytes Dopa

stain

ETIOPATHOGENESISETIOPATHOGENESIS

NEURAL HYPOTHESISNEURAL HYPOTHESIS AUTOIMMUNE HYPOTHESISAUTOIMMUNE HYPOTHESIS

AUTOCYTOTOXIC/AUTOCYTOTOXIC/RADICALIC HYPOTHESISRADICALIC HYPOTHESIS

GENETIC PREDISPOSITIONGENETIC PREDISPOSITIONAutoimmune Susceptibility Locus (AIS1)Autoimmune Susceptibility Locus (AIS1)

ECLECTIC HYPOTHESISECLECTIC HYPOTHESISMELANOCYTORRAGYMELANOCYTORRAGYSYNERGISTIC THEORYSYNERGISTIC THEORY

MELANOCYTEDESTRUCTION

Vitiligo: Etiopathogenesis GENETIC PREDISPOSITIONGENETIC PREDISPOSITION

Autoimmune Susceptibility Locus (AIS1)Autoimmune Susceptibility Locus (AIS1)

AUTOIMMUNEAUTOIMMUNE Umoral mechanism -AutoantibodiesUmoral mechanism -Autoantibodies Citotoxic mechanism – Cell mediatedCitotoxic mechanism – Cell mediated

METABOLICMETABOLIC Hydrogen peroxide accumulationHydrogen peroxide accumulation Abnormal expression of Tyrosine-Related Protein Abnormal expression of Tyrosine-Related Protein -1-1

OTHERSOTHERS Viral hypothesisViral hypothesis Neuronal toxicityNeuronal toxicity

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

Altered antioxidant and

scavenger mechanism

Increased activity of

superoxide 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

Metabolic Pathogenesis

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

Convergence Theory

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

Vitiligo: what’s new in 2012

Melanocytes are not completely absent in the depigmented epidermis

Massi D. Histopathological and ultrastructural features Massi D. Histopathological and ultrastructural features of vitiligo. In: Lotti T & Hercogova J (Eds.) Vitiligo – of vitiligo. In: Lotti T & Hercogova J (Eds.) Vitiligo – Problems and solutions. Marcel Dekker Inc, New York Problems and solutions. Marcel Dekker Inc, New York 20042004

Normal Skin Perilesional Skin Lesional Skin

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

VITILIGO: NOT ONLY A MELANOCYTIC

DISEASE?

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

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.

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

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

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

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

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

Functional alterations in Functional alterations in vitiligo skinvitiligo 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

Vitiligo in 2012: the importance of an

evidence-based approach1. 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?

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

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

Vitiligo: Disease Association

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

Is it everything about psychology?

The psychosomatic hypothesisThe psychosomatic hypothesis

The somatopsychic reboundThe somatopsychic rebound

Punishment and Leprosy complexPunishment 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

 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.

Vitiligo and Psychology

Should I suggest to buy a UV lamp?

Dermatologists no data availablePatient’s report 76% advised by

dermatologists

Short term side-effects: burning, ocular, viral infections

92%Long term side-effects: skin tumour, premature

ageing…???

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.

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.

Vitiligo: what’s new in treatment

Excimer laser / Monochromatic Excimer laser / Monochromatic excimer light (MEL) excimer light (MEL)

Focused microphototherapyFocused microphototherapy

Calcineurine inhibitors Calcineurine inhibitors with NB-UVB with NB-UVB

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.

BEFORE AFTER 20 TREATMENTS

J Korean Med Sci 2005; 20: 273-8

Narrow Band UVB Microphototherapy

UVB 311 nmUVB 311 nm Only the hypopigmented areas are treatedOnly the hypopigmented areas are treated No contrast between normal and affected No contrast between normal and affected

skinskin Low dose of radiationLow dose of radiation Reduced short-term and long-term adverse Reduced short-term and long-term adverse

eventsevents

BIOSKIN® emission spectrum

Intensity10-100 mW/cm2

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

treatment

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

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

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

Combination therapy in 2012

Combination therapy in 2012

Open studyOpen study Tacrolimus 0.1% ointment, Tacrolimus 0.1% ointment,

Pimecrolimus 1% cream, Pimecrolimus 1% cream, Betamethasone dipropionate Betamethasone dipropionate 0.05% cream, Calcipotriol 0.05% cream, Calcipotriol ointment 50mcg/g, 10% L-ointment 50mcg/g, 10% L-phenylalanine cream phenylalanine cream alone or alone or in combination with 311nm nb-in combination with 311nm nb-UVB microphototherapyUVB microphototherapy

470 patients affected by vitiligo 470 patients affected by vitiligo (<10% skin surface)(<10% skin surface)

Lotti T et al. Dermatol Ther 2008;21 Suppl 1:s20-Lotti T et al. Dermatol Ther 2008;21 Suppl 1:s20-66

Group 1Group 1 BIOSKINBIOSKIN® alone® alone

Group 2Group 2 0.1%Tacrolimus+ BIOSKIN0.1%Tacrolimus+ BIOSKIN® ®

Group 3Group 3 1% Pimecrolimus+BIOSKIN1% Pimecrolimus+BIOSKIN®®

Group 4Group 4 Betamethasone dipropionate 0.05%Betamethasone dipropionate 0.05%+BIOSKIN+BIOSKIN®®

Group 5Group 5 Calcipotriol ointment Calcipotriol ointment 50mcg/g+BIOSKIN50mcg/g+BIOSKIN®®

Group 6Group 6 10% L-phenylalanine+BIOSKIN10% L-phenylalanine+BIOSKIN®®

Group 7Group 7 0.1% Tacrolimus alone 0.1% Tacrolimus alone

Group 8Group 8 1% Pimecrolimus alone1% Pimecrolimus alone

Group 9Group 9 Betamethasone dipropionate 0.05%Betamethasone dipropionate 0.05%

Group 10Group 10 Calcipotriol ointment 50mcg/g aloneCalcipotriol ointment 50mcg/g alone

Group 11Group 11 10% L-Phenylalanine alone10% L-Phenylalanine alone

Repigmentation rates: beginning of repigmentation (weeks) as assessed by

clinical evaluation

0

2

4

6

8

10

12

14

Treatment Groups

Wee

ks

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

0

10

20

30

40

50

60

70

80

90

100

Time (Months)

Pe

rce

nta

ge

of

pa

tie

nts

re

ac

hin

g >

75

%

rep

igm

en

tati

on

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

Repigmentation rates and final repigmentation results: visual comparison of different treatment groups as assessed by

clinical evaluation

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.

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 .

PSEUDOCATALASE CREAM

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.

Pseudocatalase cream + NB-UVB vs NB-UVB alone

> 75% repigmentation (face, neck, trunk, and extremities)

70% disease progression

71 children with vitiligo

H2O2 H2O + O2

catalase

PROSTAGLANDN E

VITAMIN D ANALOGS•Possible role in melanocyte

differentiation ?

•Not effective alone.

•Possible combination therapy with UV and steroids.

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

Birlea SA et al. Med Res Rev. 2009; 29 (3): 514-546,

Vitamin D analogs

Calcipotriol and tacalcitol as topical therapeutic agents Calcipotriol and tacalcitol as topical therapeutic agents in vitiligoin vitiligo

Vitamin D ligands target T cell activation, mainly by Vitamin D ligands target T cell activation, mainly by inhibiting the transition of T cells from early to late G1 inhibiting the transition of T cells from early to late G1 phase and by inhibiting the expression of several pro-phase and by inhibiting the expression of several pro-inflammatory cytokines genes, such as those encoding inflammatory cytokines genes, such as those encoding TNF-alpha and IFN-gamma.TNF-alpha and IFN-gamma.

Vitamin D(3) compounds influence melanocyte Vitamin D(3) compounds influence melanocyte maturation and differentiation and up-regulate maturation and differentiation and up-regulate melanogenesis through pathways activated by specific melanogenesis through pathways activated by specific ligand receptors, such as endothelin receptor and c-kit.ligand receptors, such as endothelin receptor and c-kit.

Birlea SA, Costin GE, Norris DA. Curr Drug Targets. 2008 Apr;9(4):345-59.

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)

THERAPEUTIC ALGORITHM in CHILDREN

No recommendation for vitamin D anoalogues, PUVA, surgical treatments and systemic therapy

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 treatments5. Depigmentation with p-(benzyloxy)phenol

(> 50% depigmentation, extensive depigmentation on the face or hands)

No recommendation for vitamin D anoalogues and systemic therapy

Felsten LM, Alikhan A, Petronic-Rosic V. J Am Acad Dermatol. 2011 Sep;65(3):493-514.

Vitiligo: an evidence-based approach

Positive balance of active treatments of vitiligo patients*

Topical corticosteroids (max 6 months) Topical corticosteroids (max 6 months) 89% 89% PUVA treatment (max 12 months) PUVA treatment (max 12 months) 16% 16% PUVA treatment (max 9 months) PUVA treatment (max 9 months) 25% 25% UVB treatment (max 6 months) UVB treatment (max 6 months) 87% 87% (Broad + (Broad +

Narrow Band)Narrow Band) Surgical treatment (one shot + UVB) Surgical treatment (one shot + UVB) 68% 68%

*evaluation made by Dermatologists• Int J Dermatol 1999;38:866-872

• Arch Dermatol 1999;135:1514-1521

There is moderate evidence for the use oftopical corticosteroids, although long-term use is likely to lead to adverse effects.

Topical non-steroidal immunomodulators such astacrolimus 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).

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 effectivein combination with topical interventions such as hydrocortisone 17-butyrate, tacrolimus, or tacalcitol.

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

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

Positive effects of the supplementation of antioxidants

in cultured cells Total Antioxidant Capacity

(marker of cellular scavengingactivity)

Mitochondrial membrane depolarization (marker ofmitochondrial and cellularintegrity)

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 .

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

Before Immediately after surgery

Before After 2 months

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.

CONCLUSIONS

How to manage vitiligo

Correct diagnosis Correct diagnosis

ComorbiditiesComorbidities

Patient expectationsPatient expectations

Communication issueCommunication issue

in 2012 and further

OUR CONTRIBUTIONS

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.

VRF VRF Leadership TeamLeadership Team

Mr. Dmitry Aksenov MSc, MBA  VRF Founder and

President  

Mr. Dmitry Aksenov  established the Vitiligo Research Foundation as a  continuation of his medical-  research 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.

VRF VRF Leadership TeamLeadership Team

Prof. Robert A. Schwartz, MD, Professor and Head of Dermatology, New Jersey Medical School (US) 

One of the America's foremost dermatologists,

Robert Schwartz is Professor and Head of Dermatology at New Jersey Medical School, one of the eight medical schools in the New York City metropolitan area. He is also Professor of Medicine, Professor of Pediatrics, Professor of Pathology and Laboratory Medicine and Professor of Preventive Medicine and Community Health at the New Jersey Medical 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.

VRF VRF Leadership TeamLeadership Team

Torello Lotti, MD, Professor of DermatologyVRF Scientific Director and Chairman , Executive Scientific Committee

Full Professor of Dermatology, Dept of Dermatological Sciences, University of Florence, Italy. A world-renown expert on vitiligo, a key note lecturer at major dermatology meetings, visiting professor at several universities in 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

VRF VRF Leadership TeamLeadership Team

President-Elect of the

European Academy of Dermatology and Venereology, President of 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. 

• Jana Hercogova, MD,

PhDScientific

Director

VRF VRF Leadership TeamLeadership Team

Yan Valle, MSc, MBA

VRF Executive Director

Dr. Yan Valle specializes in commercial applications arising from advanced technologies for almost 20 years. He currently leads our Cloud Medical Research and Management project 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.

VRFVRF

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.

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.

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

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