VITILIGO TREATMENT
GUIDELINES
Professor Andrija Stanimirović, MD, PhD
1Department
of Clinical Medicine, University of Applied
Health Sciences, Mlinarska 38, Zagreb, Croatia
2Private Dermatovenerology Office, Huga Badalića 26,
Zagreb, Croatia
3Croatian Vitiligo Association
Why guidelines in medicine?
• Systematically developed statements that assist
the clinician in choosing the most appropriate
therapy for a specific condition
• Tools to reduce inappropriate care
• Tools which control geographic variations in
practice patterns
• Tools which make the use of health care resources
more effective
• Recommendations linked directly to
scientific evidence of effectiveness
Guideline
Algorithm
Chronic plaquetype psoriasis
Calcineurin
inhibitors
Coaltar
basic
therapy
Corticosteroids
mild
BSA < 10%
PASI < 10 P
Topical
therapy
Dithranol
Laser
Tazarotene
Vitamin D3
moderate
BSA > 10%
PASI > 10 P
Combined:
Climate
balneotherapy
Calcineurin
inhibitors
Cyclosporine
Evidence-based (S3)
severe
Guidelines for the
Treatment of Psoriasis
Vulgaris
Nast et al., J Dtsch Dermatol
Ges 5 (Suppl. 3), 2007
Nast et al., Arch Dermatol Res
299.111-138, 2007 (short version)
Systemic
therapy
Fumaric
Acid Esters
Efalizumab
Methotrexate
Etanercept
Retinoids
UV
Infliximab
Adalimumab
Ustekinumab
RESULT OF:
Poor criteria (diagnosis and effectiveness) sharing
Poor outcomes sharing
Variable therapy duration
Home-made non-uniform trial designs
• Total of 96 studies with 4512 participants
state: 24/02/15
• 21/39 (54%) of the new studies assessed new
treatments, most of which involved the use of light
• NB-UVB light - used in 35/96 (36% of all included
studies), alone/in combination with other therapies the best results
• The majority of studies (53/96, 55%), most of which
were of combination treatments with light, assessed >
75% repigmentation
• 9/96 (9%)- the quality of life of participants
• The majority of all studies (65/96, 68%) reported
adverse effects, mainly for topical treatments
• Neither mometasone furoate nor hydrocortisone
produced adverse effects
• The majority of the studies reporting successful
repigmentation = combinations of various
interventions with light
Where do we stand in vitiligo?
• Lack of definitive and completely
effective therapies
• The most effective treatments:
phototherapy and combined
therapy
• THERAPEUTIC GOALS:
– Stopping the progression of the
disease
– Satisfactory repigmentation
– Maintenance of the pigment
GUIDELINES FOR VITILIGO – FIRST
STEPS
• TEAM (Njoo et al):
– 1 main investigator
– 2 staff members of the Department of
Dermatology
– Clinical epidemiologist
– Clinical librarian
– External expert on pigmentary disorders
• EVALUATION: questionnaire + structured
interview = 14 questionnaires/23 sent
• Meta-analysis of the literature (63 studies localized vitiligo,117 studies - generalized vitiligo)
GUIDELINES FOR VITILIGO – FIRST
STEPS
GUIDELINES FOR VITILIGO – FIRST
STEPS
GUIDELINES FOR VITILIGO – FIRST
STEPS
• The guidelines were
followed for most
adults
• Children with vitiligo 52% followed the
guidelines (no further
distinction was made
in the several clinical
types or the disease
activity)
Nordlund JJ
2008
Nordlund JJ
2008
PRESENT THERAPEUTIC
ALGORITHMS FOR VITILIGO
TREATMENT
• Gawkrodger DJ, Ormerod AD, Shaw L, et al.
Algorithm for the management of vitiligo in adults
and children by non-specialists in UK. Postgrad
Med J. 2010;86:466-71.
• Felsten LM, Alikhan A, Petronic-Rosic V. Vitiligo: a
comprehensive overview Part II: treatment options
and approach to treatment. J Am Acad
Dermatol. 2011;65:493-514.
• Taieb A, Alomar A, Böhm M, et al. VITILIGO
EUROPEAN TASK FORCE. Guidelines for the
management of vitiligo: the European Dermatology
Forum Consensus. Br J Dermatol. 2013;168:5-19.
PRESENT THERAPEUTIC
ALGORITHMS FOR VITILIGO
TREATMENT-ctd.
• Oiso N, Suzuki T, Wataya-Kaneda M, et al. Proposed
algorithm for the management of vitiligo in Japan. J
Dermatol. 2013;40:344-54.
• Stanimirović A, Šitum M, Kostović K, et al. Proposal
for Guidelines for the Treatment of Vitiligo in
Croatia. Global Journal of Dermatology and
Venereology 2014;2(1):19-26.
Algorithm for the management of vitiligo in adults and
children by non-specialists in UK. (Modified from:
Gawkrodger DJ et al. Source: Postgrad Med J. 2010;86:46671.)
Diagnosis of vitiligo:
- Classical presentation: primary care
- Atypical presentations: dermatologist
- Adults: thyroid blood tests
a) NO TREATMENT OPTION:
• ADULTS AND CHILDREN WITH SKIN TYPES I and II NO ACTIVE TREATMENT OTHER THAN CAMOUFLAGE
AND SUNSCREENS
Algorithm for the management of vitiligo in adults and
children by non-specialists in UK. (Modified from:
Gawkrodger DJ et al. Source: Postgrad Med J. 2010;86:46671.)
b) TOPICAL TREATMENT:
1. ADULTS WITH RECENT ONSET OF VITILIGO AND
CHILDREN: POTENT/VERY POTENT TOPICAL STEROIDS - no
more than 2 months (skin atrophy - common side effect)
2. ADULTS: TOPICAL PIMECROLIMUS (better safety profile)
3. CHILDREN: TOPICAL PIMECROLIMUS/TACROLIMUS (better
safety profile)
4. ADULTS SEVERELY AFFECTED BY VITILIGO:
DEPIGMENTATION (only by a specialist dermatology unit)
Algorithm for the management of vitiligo in adults and
children by non-specialists in UK. (Modified from:
Gawkrodger DJ et al. Source: Postgrad Med J. 2010;86:46671.)
c) PHOTOTHERAPY, SYSTEMIC THERAPY AND SURGICAL
TREATMENTS:
•Only in specialist units
•SURGICAL TREATMENTS- NOT RECOMMENDED IN CHILDREN
d)PSYCHOLOGICAL TREATMENT:
•Assessment of the psychological and QoL effects of vitiligo on
adults and children
•Psychological interventions
•Parents of children with vitiligo - psychological counseling
Felsten LM, Alikhan A, Petronic-Rosic V. Vitiligo: a
comprehensive overview Part II: treatment options and
approach to treatment. J Am Acad
Dermatol. 2011;65:493-514.
•TOPICAL STEROIDS
OR
•TOPICAL STEROIDS + TOPICAL VITAMIN D3 ANALOGS
1st line
therapy:
treatment of
naive vitiligo
ALTERNATIVE:
•TOPICAL CALCINEURIN INHIBITORS
•SYSTEMIC STEROIDS
•TOPICAL L-PHENYLALANINE
•TOPICAL ANTIOXYDANTS AND MITOCHONDRIAL
STIMULATING CREAM
•NATURAL SUNLIGHT WITH PO KHELLIN
RAPIDLY PROGRESSIVE
VITILIGO → SYSTEMIC
STEROIDS
RECALCITRANT LESIONS ON
EXTREMITIES→
TACROLIMUS NIGHTLY
UNDER OCCLUSION
Felsten LM, Alikhan A, Petronic-Rosic V. Vitiligo: a
comprehensive overview Part II: treatment options and
approach to treatment. J Am Acad
Dermatol. 2011;65:493-514.
•NBUVB + TOPICAL CALCINEURIN INHIBITORS
ALTERNATIVE:
•ADJUNCT NBUVB THERAPY WITH PO ANTIOXYDANTS
•SYSTEMIC STEROIDS /POLYPODIUM LEUCOTOMOS EXTRACT
•PUVA
•SYSTEMIC STEROIDS
•TOPICAL VITAMIN D3 ANALOGS
•PO KHELLIN
•PO L-PHENYLALANINE/TOPICAL L-PHENYLALANINE
2nd line
therapy:
vitiligo
recalcitrant
to first line
therapy
Felsten LM, Alikhan A, Petronic-Rosic V. Vitiligo: a
comprehensive overview Part II: treatment options and
approach to treatment. J Am Acad
Dermatol. 2011;65:493-514.
308 nm LASER + TOPICAL STEROIDS
ALTERNATIVE:
•ADJUNCT 308 nm LASER + TOPICAL CALCINEURIN
INHIBITORS
3rd line
therapy:
vitiligo
unsuccessfully
treated with
total body
phototherapy
Felsten LM, Alikhan A, Petronic-Rosic V. Vitiligo: a
comprehensive overview Part II: treatment options and
approach to treatment. J Am Acad
Dermatol. 2011;65:493-514.
•BLISTER GRAFT
•SPLIT THICKNESS SKIN GRAFT
•PUNCH GRAFT
•AUTOLOGOUS MELANOCYTE TRANSPLANT
SEGMENTAL VITILIGO:
TREATMENT AS ABOVE,
HE-NE LASER AS 3rd line
therapy
GENERALIZED VITILIGO:
TREATMENT AS ABOVE,
DEPIGMENTATION
AGENTS FOR
RECALCITRANT DISEASE
4th line
therapy:
vitiligo
recalcitrant
to 1st, 2nd
and 3rd line
therapy
CAMOUFLAGE
AND
PSYCHOTHERAPY
SHOULD BE
OFFERED TO
PATIENTS AT ALL
STAGES OF
TREATMENT
Guidelines for the management of vitiligo: the European Dermatology
Forum Consensus. (Modified from Taieb A et al. Source: Br J Dermatol.
2013;168:5-19.)
a)Simplified algorithm for NSV
Diagnosis of NSV:
 Avoidance of triggering factors
INITIAL RECOMMENDATION
 NB-UVB (3 months) + - /systemic/topical therapies (LOCAL
CS/TIM )
 Camouflage
STABILIZATION
STABILIZATION AND
REPIGMENTATION:
NB-UVB (9 months)
STABILIZATION AND
REPIGMENTATION CESSATION:
SURGICAL TREATMENT
Guidelines for the management of vitiligo: the European Dermatology
Forum Consensus. (Modified from Taieb A et al. Source: Br J Dermatol.
2013;168:5-19.)
a)Simplified algorithm for NSV
PROGRESSION
• CS MINIPULSE (3-4 months)
• OTHER IMMUNOSUPPRESSANTS
STABILIZATION AND REPIGMENTATION
AFTER PERIOD OF PROGRESSION: NBUVB (9 months)
NO REPIGMENTATION, KOEBNER
PHENOMENON +: DEPIGMENTATION
STABILIZATION WITH OR WITHOUT
REPIGMENTATION, KOEBNER
PHENOMENON -: SURGICAL
TREATMENT
Guidelines for the management of vitiligo: the European
Dermatology Forum Consensus. (Modified from Taieb A et al. Source:
Br J Dermatol. 2013;168:5-19.)
b) Algorithm for SV
Diagnosis of SV:
 Avoidance of triggering factors
INITIAL RECOMMENDATION: LOCAL CS/TIM
STABILIZATION AND
REPIGMENTATION: NO THERAPY
STABILIZATION
STABILIZATION WITH OR
WITHOUT REPIGMENTATION:
SURGICAL TREATMENT
Guidelines for the management of vitiligo: the European
Dermatology Forum Consensus. (Modified from Taieb A et al. Source:
Br J Dermatol. 2013;168:5-19.)
b) Algorithm for SV
PROGRESSION
 NB-UVB
 MEL
STABILIZATION AND
REPIGMENTATION AFTER PERIOD OF
PROGRESSION: NO THERAPY
NO REPIGMENTATION, KOEBNER
PHENOMENON +: CAMOUFLAGE
STABILIZATION WITH OR WITHOUT
REPIGMENTATION, KOEBNER
PHENOMENON -: SURGICAL
TREATMENT
Proposed algorithm for the management of vitiligo in Japan. (Modified
from Oiso N et al. Source: J Dermatol. 2013;40:344-54.)
Diagnosis of vitiligo:
• VASI score
• Age
• Affected duration
a) Complication (+) refer patient to specialist: Treatment of
vitiligo as shown in complication (-)
b) Complication (-)
Camouflage should be available for all patients
Proposed algorithm for the management of vitiligo in Japan. (Modified
from Oiso N et al. Source: J Dermatol. 2013;40:344-54.)
1st therapeutic option:
NB-UVB/PUVA +/- TOPICAL
CORTICOSTEROIDS/ TOPICAL
VITAMIN D3 ANALOGUES
2nd therapeutic option:
TOPICAL VITAMIN D3 ANALOGUES +
SUN EXPOSURE
3rd therapeutic option:
308-nm EXCIMER LASER/LIGHT
4th therapeutic option:
SKIN GRAFTING
STABLE (5
years or
more after
occurence)
Proposed algorithm for the management of vitiligo in Japan. (Modified
from Oiso N et al. Source: J Dermatol. 2013;40:344-54.)
1st therapeutic option:
TOPICAL VITAMIN D3 ANALOGUES
2nd therapeutic option:
TOPICAL CORTICOSTEROIDS
3rd therapeutic option:
SKIN GRAFTING
PROGRESSIVE
(5 ≤ years
after
occurence, or
variable in
size) on
patient 15 ≤
years old with
lesions on
face
Proposed algorithm for the management of vitiligo in Japan. (Modified
from Oiso N et al. Source: J Dermatol. 2013;40:344-54.)
1st therapeutic option:
TOPICAL CORTICOSTEROIDS
2nd therapeutic option:
TOPICAL TACROLIMUS
3rd therapeutic option:
TOPICAL VITAMIN D3 ANALOGUES +
SUN EXPOSURE
4th therapeutic option:
SKIN GRAFTING
PROGRESSIVE
(5 ≤ years or
after
occurence, or
variable in
size) on
patient 15 ≤
years old with
lesions on
trunk and
extremities
Proposed algorithm for the management of vitiligo in Japan. (Modified
from Oiso N et al. Source: J Dermatol. 2013;40:344-54.)
1st therapeutic option:
NB-UVB/PUVA +/- TOPICAL
CORTICOSTEROIDS/ TOPICAL
VITAMIN D3 ANALOGUES
2nd therapeutic option:
308-nm EXCIMER LASER/LIGHT
OR
TOPICAL VITAMIN D3 ANALOGUES +
SUN EXPOSURE
3rd therapeutic option:
ORAL CORTICOSTEROIDS /
IMMUNOSUPPRESSIVE AGENTS
4th therapeutic option:
SKIN GRAFTING
PROGRESSIVE
(5 ≤ years
after
occurence, or
variable in
size) on
patient 16 ≥
years old
Dear God
when will this
presentation
end!?
DEATH BY POWERPOINT!
Falabella R, Barona MI. Update on skin repigmentation
therapies in vitiligo. Pigment Cell Melanoma Res.
2009;22:42-65.
Falabella R, Barona MI. Update on skin
repigmentation therapies in vitiligo. Pigment Cell
Melanoma Res. 2009;22:42-65.
Falabella R, Barona MI. Update on skin
repigmentation therapies in vitiligo. Pigment Cell
Melanoma Res. 2009;22:42-65.
•
•
•
•
•
•
•
470 vitiligo patients, less than 10% affected skin
Tacrolimus 0.1% ointment
Pimecrolimus 1% cream
Betamethasone dipropionate 0.05% cream
Calcipotriol ointment 50mcg/g
10% L-phenylalanine cream
ALONE/IN COMBINATION WITH 311-nm NB-UVB
MICROPHOTOTHERAPY
Percentage of repigmentation in patients treated with 311-nm NBUVB
microphototherapy(BIOSKIN® ) alone or in combination, or with active topical
treatment alone
Treatment (n° of patients)
Excellent
(>75%)
Marked
(50-75%)
Moderate
(25-50%)
Minimal
(<25%)
Group 1: BIOSKIN® alone (100)
72%
19.8%
4.6%
3.6%
Group 2: 0.1% Tacrolimus + BIOSKIN® (59)
76.5%
18.2%
3.3%
2%
Group 3: 1% Pimecrolimus + BIOSKIN® (63)
76.1%
20.1%
2.7%
1.1%
Group 4: Betamethasone dipropionate 0.05%
+ BIOSKIN® (28)
90.2%
6.7%
2.2%
0.9%
Group 5: Calcipotriol ointment 50 mcg/g +
BIOSKIN® (60)
75.6%
14.1%
7.4%
2.9%
Group 6: 10% L-Phenylalanine + BIOSKIN®
(60)
74.8%
11.3%
10.1%
3.8%
Group 7: 0.1% Tacrolimus alone (22)
61%
16.1%
18.4%
4.5%
Group 8: 1% Pimecrolimus alone (19)
54.6%
18.4%
21.7%
5.3%
Group 9: Betamethasone dipropionate 0.05%
alone (23)
71.2%
25%
2.1%
1.7%
Group 10: Calcipotriol ointment 50 mcg/g
(18)
59.1%
10.6%
27.1%
3.2%
Group 11: 10% L-Phenylalanine alone (18)
29.3%
8.1%
55%
7.6%
Vitiligo Therapy 2014/15 General
Short Remarks
TOPICAL CORTICOSTEROIDS
• Limited, non-facial involvement: potent TCS, once daily
for 4 months or 15 days/month for 6 months
• First and safest choice: potent TCS rather than super
potent
• Suspicious systemic absorption: consider mometasone
furoate or methylprednisolone aceponate
• Facial involvement: consider topical calcineurin
inhibitors (TCI) rather than TCS
TOPICAL CALCINEURIN
INHIBITORS
• New and fast, actively spreading lesions and
involvement of face/neck areas
• Twice daily, initially for 6 months, both adults and
children
• Safety profile is better concerning the risk of skin
atrophy
• During the treatment: moderate but daily sun
exposure, without previous cream application
• If effective, consider prolonged treatment (↑12
months)
NBUVB AND TARGETED
PHOTOTHERAPIES
• Total body NB UVB for NSV- arrest and repigment
vitiligo
• Targeted phototherapies: localized vitiligo, recent
onset vitiligo & childhood vitiligo
• Maximum cycle duration- 1 year for adults and 6
months for children. One year interruption between
cycles!
• Halting of treatment: if no results in 3 months or if ↓
25% repigmentation in 6 months
• Maintenance treatment-not recommended
• Regular follow- ups necessary
PUVA AND
PHOTOCHEMOTHERAPY
• Oral PUVA-second or third line therapy in adults
• 12 to 24 months therapy
• Topical PUVA-very low dosage psoralens creams
• However, actually relatively opsolent
COMBINATION TREATMENTS
• Topical steroids and phototherapy
• In addition peroral antioxidants
• For difficult to treat areas such as bony prominences,
hands and feet
• Highly potent topical steroids once a day (3 weeks out
of 4) for the 3 first months of phototherapy
• Whole time peroral antioxidants
COMBINATION TREATMENTS-ctd
• Topical calcineurin inhibitors and phototherapy
• Effective and provides better results that the two
treatments separately alone
• Should be used with precautions due to
carcinogenicity ?
• Use of adequate photoprotection due to the lack of
data on long term safety (or not) of combination of TCI
and UV
COMBINATION TREATMENTS-ctd
Vitamin D analogues and phototherapy:
• Not recommended, data of efficacy lacking
Phototherapy and peroral therapy:
• Phototherapy+oral antioxidants possibly beneficial
Phototherapy after surgery:
• NB-UVB or PUVA should be used for 4 weeks after
melanocyte transplatation
ORAL STEROIDS/OTHER
IMMUNUNOSUPPRESSANTS
ORAL CORTICOSTEROIDS MINI PULSE:
• For stabilization of vitiligo - not useful as
repigmentating therapy
• For fast spreading vitiligo- weekend OMP (2.5
mg/day) of dexamethasone before phototherapyuseful as disease halting therapy
• Optimal duration of OMP to stop vitiligo progression is
3-6 months
OTHER
IMMUNUNOSUPPRESSANTS/
BIOLOGICS
Cyclophosphamide, Cyclosporine, MTX, Tetracyclines,
& Anti-TNF-α:
• Currently not yet recommended due to lack of data
and because of the possible side effects
Statins - promising
Low dose cytokines-promising
AFAMELATONIDE
• Simplified form of alpha-melanocyte stimulating
hormone (α-MSH) - stimulates melanocytes to grow
and produce melanin pigment
• Afamelatonide + NBUVB = faster repigmentation?
OTHER SYSTEMIC
INTERVENTIONS: ANTIOXYDANTS
•
•
•
•
•
•
Vitamin E
Vitamin C
Ubiquinone
Lipoic acid
Polypodium Leucotomos
Ginko biloba etc.
o Antioxidant supplementation could be useful during
UV therapy and reactivation phases
o Combination therapy with UVB and topical therapy is
recommended
SURGERY
• For NSV- patients with stable disease and negative
Koebner phenomenon
• Risk of relapse?
• For SV and other localized vitiligo forms-after failure
of medical interventions
• Only in specialized units
Stanimirović A, Šitum M, Kostović K, Bulat V, Kovačević M, Kaštelan
M, Puizina-Ivić N, Pustišek N, Čulav-Košćak I. Proposal for
Guidelines for the Treatment of Vitiligo in Croatia. Global Journal
of Dermatology and Venereology 2014;2(1):19-26.
POTENT TOPICAL CORTICOSTEROIDS
OR
TOPICAL CALCINEURIN INHIBITORS
(genital area and armpits in adults
and children)
OR
TOPICAL CORTICOSTEROIDS +
TOPICAL VITAMIN D ANALOGUES
OR
MINI ORAL PULSED
CORTICOSTEROID TREATMENT
(progressive, fast spreading vitiligo)
1st therapeutic
recommendation
Stanimirović A, Šitum M, Kostović K, Bulat V, Kovačević M, Kaštelan
M, Puizina-Ivić N, Pustišek N, Čulav-Košćak I. Proposal for
Guidelines for the Treatment of Vitiligo in Croatia. Global Journal
of Dermatology and Venereology 2014;2(1):19-26.
NB-UVB 311nm PHOTOTHERAPY
OR
NB-UVB 311nm PHOTOTHERAPY +
POTENT TOPICAL CORTICOSTEROIDS
OR
NB-UVB 311nm PHOTOTHERAPY +
TOPICAL CALCINEURIN INHIBITORS
OR
NB-UVB 311nm PHOTOTHERAPY +
PERORAL THERAPY:
CORTICOSTEROIDS, ANTIOXYDANTS,
Polypodium Leucotomos EXTRACT
2nd therapeutic
recommendation
Stanimirović A, Šitum M, Kostović K, Bulat V, Kovačević M, Kaštelan
M, Puizina-Ivić N, Pustišek N, Čulav-Košćak I. Proposal for
Guidelines for the Treatment of Vitiligo in Croatia. Global Journal
of Dermatology and Venereology 2014;2(1):19-26.
PUVA PHOTOTHERAPY (only in
specialist units)
3rd therapeutic
recommendation
Stanimirović A, Šitum M, Kostović K, Bulat V, Kovačević M, Kaštelan
M, Puizina-Ivić N, Pustišek N, Čulav-Košćak I. Proposal for
Guidelines for the Treatment of Vitiligo in Croatia. Global Journal
of Dermatology and Venereology 2014;2(1):19-26.
SURGICAL TREATMENT
(for inactive vitiligo on prominent
sites - i.e. face, hands):
• BLISTER GRAFT
• PUNCH GRAFT
• SPLIT THICKNESS SKIN GRAFT
• AUTOLOGOUS MELANOCYTE
SUSPENSION TRANSPLANT
4th therapeutic
recommendation
Camouflage and cognitive behavioral therapy should be
available for all patients.
Lotti T, Merkel A, Korobko I, Šitum M,
Keqiang Li, Stanimirović A, Putin V,
Valle J, Obama B, Hercogova J, Castro
F. World Consensus Guidelines for
the Treatment of Vitiligo. Space
Intergallactic Journal of
Dermatology and Venereology
2016;4(1):27-31.
croatia.vitiligo.org@gmail.com
http://vrfoundation.org/