Prof. Robert Schwartz
Vitiligo: Critical review of medical treatments
Presentation from the World Vitiligo Symposium 2011. Sponsored by the VR Foundation.
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Vitiligo - critical review of medical treatments by Prof. R. Schwartz
1. Vitiligo: Critical Review of
Medical Treatments
4th Russian Congress of Dermatovenereology
2nd Continental Congress of Dermatology
Saint Petersburg, July 6-9, 2011
Robert A. Schwartz MD, MPH, FACP
Professor and Head, Dermatology
Professor of Preventive Medicine
Professor of Pathology
Professor of Medicine
Professor of Pediatrics
UMDNJ-New Jersey Medical School
4. Vitiligo
Milk white splattering of patches
1-2% of the general population worldwide
Two types: nonsegmental and segmental
Loss of melanocytes in skin and rarely retina
Huggins RH, Janniger CK, Schwartz RA: Childhood vitiligo. Cutis 79: 277-280, 2007.
Lotti TM, Berti SF, Hercogová J, Huggins RH, Schwartz RA, Janniger CK: Vitiligo: recent
insights and new therapeutic approaches. Giornale Ital Dermatol Venereol (in press).
9. Vitiligo: Systemic Associations
• Other autoimmune diseases and syndromes
• Erythroderma
• Ocular pathologies
• Vogt-Koyangi-Harada (uveomeningitic) syndrome
• Alezzandini’s syndrome: uveitis, poliosis, retinitis
Huggins RH, Janusz CA, Schwartz RA: Vitiligo – a sign of systemic disease.
Indian J Dermatol Venereol Leprol 72: 68-71, 2006.
Janniger CK: Alezzandrini’s syndrome. eMedicine from WebMD. Updated
2011. http://emedicine.medscape.com/article/1117255-overview
10.
11.
12.
13. Tuberous Sclerosis
Autosomal dominant; 2/3 sporadic mutations
Characterized by widespread hamartomas of brain, eyes,
skin, kidney, liver, heart and lungs
Diagnostic triad: mental retardation, epilepsy, facial
angiofibromas (adenoma sebaceum)
Hypopigmented macules: earliest sign, best seen with
Wood’s lamp, called “Fitzpatrick patches”
Schwartz RA, Fernández G, Kotulska K, Józwiak S: Tuberous sclerosis complex:
advances in diagnosis, genetics, and management. J Am Acad Dermatol 57: 189-202,
2007.
Schwartz RA, Jozwiak S, Johnson CL, Pedersen R: Tuberous sclerosis. eMedicine
Pediatrics [Journal serial online]. 2011. http://emedicine.com/ped/topic2796.htm
14.
15. Hypomelanosis of Ito
Bizarre bilateral irregularly shaped patches
Neurologic and muscular abnormalities
3rd commonest phakomatosis: after TSC, NF 1
Janniger CK, Sotero de Menezes M: Hypomelanosis of Ito. eMedicine Pediatrics
[journal serial online]. 2011. http://emedicine.medscape.com/article/909996-overview
16. Vitiligo: To Treat or Not?
No treatment Treatment
Fair-skinned patients
Dark-skinned patients
Patients reassured only by
explaining the nature of their Serious impairment in
condition
Advice on use of
their quality of life
Camouflage products Patients regarded as
Sun-protection
social outcasts
17. Vitiligo Therapy
Best Candidates
Stable vitiligo
Vitiligo in children
Vitiligo on sun-exposed areas
Face and neck vitiligo
Perioral and periorbital vitiligo
18. Vitiligo Therapy
Less Desirable Candidates
Less effective on trunk and limbs
Least effective on acral extremities
Segmental vitiligo
23. Therapy for Vitiligo
57 trials, most with less than 50 participants
15 studies showed difference in > 75% repigmentation
Combinations + UV were most with significant differences
Topical steroids produced the most adverse effects
Some evidence supports existing therapies
No studies documented long-term benefit
Whitton ME et al: Interventions for vitiligo. Cochrane Review 2010, issue 7.
24. Therapy for Vitiligo
Low-quality RCT for many products
Moderate evidence for topical steroids
Calcineurin inhibitors promising, esp. + UV
Combinations + UV better than monotherapy
Eximer laser better with topicals than alone
No RCT on depigmentation for severe vitiligo
Whitton ME et al: Interventions for vitiligo. Cochrane Review 2010, issue 7.
25. Vitiligo: Current Treatments
Oral and topical PUVA
Oral phenylalanine + UVA
Oral and topical khellin + UVA
UVB narrowband or broadband
Oral, topical and intralesional steroids
Antioxidants and calcineuron inhibitors
Falabella R, Barona MI. Update on skin repigmentation therapies in vitiligo. Pigment Cell Melanoma Res
2009;22:42-65.
27. Topical Khellin for Vitiligo
Topical
Chemically resembles psoralen but less phototoxic
Used to treat in conjunction with sunlight or UVA
Best study is by Cestari and associates (2001)
She compared 2% khellin plus UVA v. PUVA
Burning sensation in 3 of 14 with 2% khellin
Cestari TF, Dias MCS, Fernandes EI, Albaneze R. Comparative study of two psoralens in topical
phototherapy for vitiligo [Estudo comparativo entre psoralenos na fototerapia topica do vitiligo]. Anais
Brasileiros de Dermatologia 2001;76:683–692.
28. Topical Steroids for Vitiligo
May arrest vitiligo and encourage repigment
Class 3 and 4 preferred: clobetasole 0.05%
Ultrapotent more effective, but limit is 2-4 mo
Follow with tacrolimus or pimecrolimus
Side effects: atrophy, striae, telangiectasia
29. Topical Steroids for Vitiligo
Ten studies
Quality of life
Percentage of repigmentation > 75%
Cessation of vitiligo spread
Adverse effects
30.
31. Calcineurin-Inhibitor Uses
Comparable to high-potency steroids
Should be rotated with topical
steroids/other agents
May be used with systemic therapies
33. Calcineurin-Inhibitor Uses
Skin burning is common adverse effect
Can be severe and long-lasting
Small amount of alcohol can produce
Aspirin 500 mg one hour before prevents
Can anticipate with ASA 2-3 days before
Mandelin J, Remitz A, Reitano S: Effect of oral aspirin on burning by tacrolimus. Arch Dermatol 146: 1178-1180, 2010.
34.
35.
36. Oxidative Stress in Vitiligo Skin
• 1991: Epidermis with vitiligo: consistent reduction in levels of
catalase compared to normal healthy controls (Schallreuter &
Wood)
1999: High levels of hydrogen peroxide (H2O2) confirmed in
epidermis of vitiligo (Schallreuter)
1999: Vacuolation was observed in vitro in melanocytes from
epidermis of patients with vitiligo, and was reversible upon
addition of catalase (Schallreuter et al.)
37. Oxidative Stress in Vitiligo Skin
2000: Melanocytes proven to remain present in the
depigmented epidermis of patients with vitiligo even after
stable disease of 25 years’ duration, and can recover their
functionality in vivo and in vitro upon the removal of
hydrogen peroxide (Tobin et al)
2002: Results support the necessity of epidermal H2O2
removal as well as the influence of solar UV-light in the
successful treatment of vitiligo
Tobin DJ et al: Melanocytes are not absent in lesional skin of long duration vitiligo. J Pathol
191: 406-416, 2000.
Schallreuter KU, Salem MM. Vitiligo. What is new. Hautarzt 61: 578-585, 2010.
38. Anti-oxidant Therapy for Vitiligo
Curcumin and capsaicin increase ERK
phosphorylation, thus inhibiting apoptosis
Antioxidants might represent an alternative
approach to protect against vitiligo progression
Vitiligo skin from 12 pts examined
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;13:1309-21.
39. Antioxidant Therapy for Vitiligo
Dietary curcumin may not be helpful in people
using topical pseudocatalase cream for vitiligo
Based on 15 Asian vitiligo patients
8 of these avoided curcumin, with 6 having
nearly complete facial repigmentation
Schallreuter KU, Rokos H. Turmeric (curcumin): a widely used curry
ingredient, can contribute to oxidative stress in Asian patients with acute
vitiligo. Ind J Dermatol Venereol Leprol. 72:57-59, 2006.
40. Topical Catalase/Dismutase Superoxide
Catalase/dismutase superoxide (DSO)
Topical 0.05% betamethasone vs. DSO + 15 min sun
25 patients, each with bilateral vitiligo
Skin repigmentation assessed: digital morphometry
After 10 months, 18% v 12% same statistically
Sanclemente G, Garcia JJ, Zuleta JJ, Diehl C, Correa C, Falabella R. A double-
blind, randomized trial of 0.05% betamethasone vs. topical catalase/dismutase
superoxide in vitiligo. J Eur Acad Dermatol Venereol. 2008;22:1359-64.
41. Topical Catalase/Dismutase Superoxide
Catalase is of vegetable origin
Catalase + dismutase superoxide in microsphere formation
Applied to one side of face/steroid to other + sun
15 min sun between 10:30 AM and 2 PM
52% on betamethasone v. 57% repigmented
Percentage of repigmentation, 18% v 12% same statistically
Objective skin assessment: digital morphometry
42. Topical Catalase/Dismutase Superoxide
High epidermal H2O2, low catalase levels in vivo and
in vitro
Topical pseudocatalase + UVB phototherapy: mixed
results
Catalase DMO combination is a topical antioxidant
Reduces oxidative stress
46. Oral Therapy for Vitiligo
Ginkgo biloba
Other anti-oxidants
Polypodium leucotomos (photoprotective fern)
Betamethasone and azathioprine
L-phenylalanine, vitamin B-12, folic acid
Systemic steroids
47. Oral Steroid Therapy for Vitiligo
Useful to retard rapid course of vitiligo
Low dose: prednisone 0.3 mg/kg may arrest
Undesirable in other circumstances
48. Oral Ginkgo biloba for Vitiligo
Ginko is immunomodulatory, antioxidant, etc.
Mechanism of action in vitiligo unknown
60 mg bid x 12 weeks in 12 patients
Small 2011 Canadian study favorable
Significant improved total VASI
60 mg capsules: 240 for $5.99
Szczurko O, Shear N, Taddio A, Boon H. Ginkgo biloba for the treatment of
vitiigo: an open label pilot clinical trial. BMC Complimentary Alternative
Medicine 2011: 11:21.
49. Ginkgo biloba
Distinctive non-flowering large tree, up to 164 feet tall
A living fossil, dating back 270 million years
Single surviving species, the ginkgo tree
Common in New York City
50.
51. Treatments of Localized Vitiligo: Study Data
Treatment N°of Random Trials N°
trials Trials included Patients
Methoxsalen+UVA 21 0 4 176
Trioxsalen+UVA 3 0 2 33
PS+UVA 5 0 2 40
Khellin 2-3%+UVA 5 2 3 81
Khellin 5% + UVA 4 2 3 64
Class 3 steroids 13 4 6 235
Class 4 steroids 7 2 7 277
Intralesional CTC 5 1 2 77
Catalase/dismutase 4 1 4 114
52. Treatments of Localized Vitiligo: Study Data
Reasons for exclusion:
Double publication
Combination treatment
Obsolete drug or scheme
Series <5 patients
Absence of placebo control
53. Treatments of Localized Vitiligo: Evaluation of results
Treatment Recommended RPG RPG RPG
duration 3m 6m 1year
Methoxsalen+UVA 1 year 2xweek >25% >50% >75%
Trioxsalen+UVA 1 year 2xweek >25% >50% >75%
PS+UVA 1 year 2xweek >25% >50% >75%
Khellin 2-3%+UVA 1 year 2xweek >25% >50% >75%
Khellin 5% + UVA 1 year 2xweek >25% >50% >75%
Class 3 steroid 6 month 1xday >50% >75% -
Class 4 steroid 6 month 1xday >50% >75% -
Intralesional CTC 6 month 1xday >50% >75% -
Catalase/dismutase 1 year 2dxday >25% >50% >75%
58. Timing for repigmentation
First results visible at 3 months of treatment
Sometimes, results visible at 1st month
Best results between 6 months-1 year
Stop treatment if no result visible after –6month
treatment
59. Broadband & Narrowband UVB
Treatment N° of N° of
Patients side-effects
Broad-B UVB 14 0
Narrow-B UVB 51 0