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Vitiligo
Digital Lecture Series : Chapter 15
Dr. Somesh Gupta, Additional Professor
Dr. Vishal Gupta, Senior Resident
Department of Dermatology & Venereology
All India Institute of Medical Sciences, New Delhi
CONTENTS
 Introduction
 Quality of life
 Epidemiology
 Non-surgical treatment
 Pathogenesis
 Prognostic factors
 Clinical features
 Surgical treatment
 Clinical classification
 MCQs
 Associations
 Photo Quiz
 Differential diagnosis
Introduction
 Vitiligo is an acquired disorder of the skin and mucous membranes
that is characterized by well circumscribed, depigmented macules.
 Lesional skin biopsy shows loss of melanocytes.
 Can have a severe negative impact on the quality of life, especially in
dark-skinned individuals.
Epidemiology
 One of the most common cutaneous disorders.
 Estimated overall world-wide prevalence of less than 0.5% in
population-based studies.
 In India, its incidence ranges of 0.25-2.5%, and varies geographically.
 Approximately half the patients present before the age of 20 years.
 No gender predilection noted.
Pathogenesis
 Exact cause unclear.
 Many theories have been proposed, none is mutually exclusive.
 Auto-immune hypothesis is the most widely accepted theory.
 Others : Neuro-humoral, auto-cytotoxic, oxidative stress,
melanocytorrhagy.
 Convergence theory : multiple factors contribute to the pathogenesis
of Vitiligo.
Pathogenesis
Genetics
 Non-Mendelian, polygenic, multifactorial inheritance, with
incomplete penetrance.

20% can have an affected relative.
 HLA associations: A2, DR4, DR7, DQB1*0303.
 Many susceptibility genes identified linking vitiligo with auto-immune
diseases.
Pathogenesis
Auto-immune hypothesis
 Immune-mediated destruction of melanocytes.
 Melanocytes are more sensitive to damage than keratinocytes.
 Humoral immunity : Auto-antibodies directed against melanocyte
antigens on the cell surface, intracellular pigment, and even the nonpigment cell antigens.
 Cell-mediated immunity : Melan-A specific CD8+ T cells, their number
in peripheral blood may correlate with disease extent.
Pathogenesis
Neuro-humoral hypothesis
 Both melanocytes and nerves arise from neural crest cells.
 Segmental Vitiligo may follow the nerve distribution.
 Increased levels of some neurotransmitters has been seen in lesional
Vitiligo skin e.g. Neuropeptide Y, norepinephrine.
 Increased neurotransmitters may directly or indirectly damage
melanocytes.
Pathogenesis
Autocytotoxic hypothesis
 Defective melanocyte receptor may lead to increased melanin
synthesis in melanocytes.
 Toxic by-products of melanin synthesis pathway may damage
melanocytes.
Pathogenesis
Biochemical theory
 Dysregulation of biopterin pathways can lead to melanocyte damage.
 Pteridines 6BH4 and 7BH4 are elevated in vitiligo.
 Increased 6BH4 leads to accumulation of 7BH4 and H2O2
•
7BH4 is a cofactor for enzyme phenylalanine hydroxylase, which
converts phenylalanine to tyrosine.
•
H2O2 can damage melanocytes by a no. of ways (see next slide).
Pathogenesis
Oxidative stress
 High levels of H2O2 in the epidermis of Vitiligo lesions.
 This can lead to
•
Inactivation of catalase enzyme, which further increases
concentration of H2O2.
•
Inactivation of tyrosinase enzyme (involved in melanogenesis).
•
Hydroxyl radicals can bleach the constitutional melanin, and
damage the cell membrane by lipid peroxidation.
Pathogenesis
Melanocytorrhagy
 Melanocytes are weakly anchored in the epidermis.
 Melanocytes are attached to extra-cellular matrix by fibronectin.
 Trauma can cause upward migration of melanocytes and
subsequently loss from the epidermis.
 This theory may explain the koebner phenomenon in Vitiligo.
Pathogenesis
Decreased melanocyte survival hypothesis
 Keratinocyte-derived stem cell factor binds to tyrosine kinase
receptor c-kit on melanocytes.
 Melanocyte survival may reduce if there is :
•
Decrease in the number of c-kit receptors in melanocytes
•
Or a lower expression of stem cell factor from surrounding
keratinocytes.
Clinical features of Vitiligo
Classical Vitiligo lesion has the following characteristics :
 Milky-white macules
 Round-oval shape
 Scalloped margin
 Overlying hair may be depigmented (leukotrichia)
Some variations in the lesional characteristics
 Raised red border in inflammatory Vitiligo.
 Multichrome Vitiligo- zones of hypopigmentation surrounding
depigmented macule.
Typical Vitiligo Macule
Koebner Phenomenon
Koebnerisation phenomenon in vitiligo : Note the linear streaks of depigmentation,
admixed with round-oval vitiligo lesions
Peri-follicular and perilesional pigmentation
Clinical Classification
 Non-segmental
• Acrofacial
• Mucosal
• Generalised
• Universal – 80 to 90% BSA
• Mixed – associated with segmental vitiligo
• Rare variants- punctata, minor, follicular
 Segmental
• Uni-, bi- or plurisegmental
 Unclassified
• Focal
• Mucosal
Bordeaux VGICC classification and consensus nomenclature 2011
Non-segmental vitiligo
“Generalized vitiligo or non-segmental vitiligo (NSV) is an acquired
chronic pigmentation disorder characterized by white patches, often
symmetrical, which usually increase in size with time, corresponding to a
substantial loss of functioning epidermal and sometimes hair follicle
melanocytes”.
.
Generalized Vitiligo
Segmental Vitiligo
“Segmental vitiligo is an acquired chronic
pigmentation disorder characterized by
white patches with a unilateral
distribution that may totally or partially
match a dermatome, but not necessarily.
Other distribution patterns can be
encountered that cross several
dermatomes, or correspond to large
areas delineated by Blaschko’s lines”.
.
Mucosal Vitiligo
Mixed-Segmental plus Non-Segmental Vitiligo
Punctate Vitiligo
Associations of Vitiligo
Association with auto-immune diseases
 Alopecia areata
Psoriasis
 Thyroid disease
Diabetes mellitus
 Pernicious anemia
Addison's disease
Association with syndromes
 Auto-immune polyendocrinopathy syndrome
 Vogt-Koyanagi-Harada disease
 Schmidt syndrome
Others
 Hearing loss in upto 20%
 Ocular abnormalities in upto 40%: choroidal abnormalities, uveitis,
fundal pigmentary disturbances
Differential diagnosis
 Piebaldism
 Nevus depigmentosus
 Halo nevus
 Pityriasis Alba
 Hansens disease
 Pityriasis Versicolor
 Lichen Sclerosus et Atrophicus
 Contact leucoderma
Nevus depigmentosus on the cheek of a
child : Note the feathery margins
Differential diagnosis
Lichen sclerosus et atrophicus
Contact leukoderma to footwear
Quality of life
 Vitiligo lesions on visible areas can lead to severe cosmetic
disfigurement.
 Source of considerable psychological distress, particularly in dark
skinned patients.
 Vitiligo is more than just a patch on the skin, it is a patch on the
mind.
Quality of life
 Psychosocial burden due to vitiligo needs to be measured separately
from the extent of its involvement.
 General and dermatology-specific quality-of-life instruments have
been used for this purpose.
 Recently, vitiligo-specific instruments have also been developed for
this purpose :
•
Vitiligo impact scale (VIS) - 22
•
Vitiqol
•
Vitiligo life quality index (VLQI)
Goals of treatment
Current treatment modalities are directed towards
 Stopping progression of the disease, and
 Achieving repigmentation
 To improve the quality of life of patients
Management of Vitiligo
 Non-surgical : Topical and systemic medications, phototherapy and
photochemotherapy, lasers.
 Surgical : Tissue grafts, cultured and non-cultured cellular transplants.
 Supportive : Camouflage, psychotherapy.
 Treatment approach needs to be individualised
 Combination of more than one modality is commonly used to hasten
response and prevent side-effects
Management of Vitiligo
Depends on
 Type of Vitiligo.
 Distribution, extent of involvement (BSA).
 Disease activity (stability / progression).
 Psychosocial, economic status & concern of patients towards disease.
 Easy availability, accessibility, acceptability of appropriate treatment
options.
Non-surgical treatment
Topical
Systemic
 Corticosteroids
 Corticosteroids
 Calcineurin inhibitors
 PUVA
 Vitamin D3 analogues
 NB-UVB
 Topical PUVA/PUVAsol
 Excimer laser
Used for localised Vitiligo
Used for progressive or generalised
Vitiligo
Topical corticosteroids
 Therapeutic mainstay, often the 1st line therapy
 Moderately potent to potent TCS
 Act by:
•
Modulating immune response
•
Melanocyte activation
 Best results on sun-exposed sites (upto 75% repigmentation)
 Requires prolonged treatment, often leading to side-effects
 Side-effects : atrophy, telangiectasias, folliculitis hypertrichosis, peri-
lesional hypopigmentation
Calcineurin Inhibitors
 Tacrolimus, pimecrolimus
 Mainly effective on head and neck
 Block the activity of calcineurin, which activates the expression of
many cytokines involved in vitiligo such as TNF-α and IFN-γ
 Comparable efficacy as TCS, especially for facial lesions
 Side-effects : lesional erythema, pruritus, burning, irritation
Vitamin D3 analogues
 Calcipotriene, calcpotriol, tacalcitol
 Mechanism of action is not entirely clear
•
Defective calcium transport has been shown in melanocytes and
keratinocytes harvested from patients with vitiligo
•
Vitamin D3 has been shown to activate melanin synthesis
 Conflicting reports on its efficacy
 Side-effects : lesional irritation, potential for hypercalcemia
Topical PUVA
 8-MOP cream or ointment used as photosensitiser.
 Apply for 30 min before UVA, on alternate days.
 Available as 0.75% ointment or 1% solution.
 Side-effects : Severe blistering reactions, perilesional
hyperpigmentation.
Topical PUVAsol
 Sun exposure = UVA source
 Drawbacks
•
Sunlight unpredictable – difficult to get correct dose
•
Difficulty in exposing all affected areas
 Increase exposure time by 2 min / 3rd exposure upto tolerance limit

Very low concentration (0.001%) should be used

At AIIMS : Diluted concentration of 0.025%, after diluting the solution with
propylene glycol (1:40 dil.)
Depigmenting agents
 Candidates : extensive and refractory vitiligo.
 Monobenzyl ether of hydroquinone almost always causes nearly
irreversible depigmentation.
 Available as 20% cream, applied 2-3 times a day.
 Depigmentation usually obtained in 1-4 months.
 Patients with skin phototypes V and VI are the best candidates.
 Avoid prolonged sun exposure.
Others
 Placental extract
•
PLACENTRIX gel 2-3 times a day
•
Seen to have a modest but insignificant additional effect on
efficacy of NB-UVB
 Basic fibroblast growth factor (decapeptide)
•
Used at bedtime followed by sunexposure x 10-15 min next day
•
Melgain lotion (2ml) 1mg/ml, now available as MELBILD
Emerging therapies
 Photocil cream
•
Topical drug used to filter nontherapeutic radiation from solar UV
•
The drug biases radiation from the sun toward a therapeutic
wavelength of 311 nm
•
Offers a convenient alternative to NB-UVB
 Pseudocatalase/Superoxide dismutase cream
•
Vitiligo patients have low catalase in epidermis
•
Only a few clinical studies so far
•
Conflicting results
Systemic Corticosteroids
 Usually used as pulse therapy in vitiligo.
 Oral minipulse of betamethasone / dexamethasone has been
pioneered in India by Pasricha et al.
 Given as a 5 mg on two consecutive days per week.
 The optimal duration of OMP therapy needed to stop Vitiligo
progression is between 3 and 6 months.
 Systemic steroids can arrest the activity of the disease.
Other Immunomodulators
 Azathioprine, CsA, cyclophosphamide.
 Current evidence does not support their routine use in vitiligo.
 Levamisole, minocycline may be of some benefit in slowly spreading
vitiligo.
PUVA
 Psoralens :
•
8-methoxypsoralen (8-MOP; 0.6–0.8 mg/kg)
•
5-methoxypsoralen (5-MOP; 1.2–1.8 mg/kg)
•
Trimethylpsoralen (0.6 mg/kg)
 Repigmentation in 70–80% of patients with PUVA, but complete
repigmentation is obtained in only 20% of patients.
 Relapse can occur in 75% of patients after 1 or 2 years.
 It is not recommended in children aged under 10–12 years because of
the risk of retinal toxicity.
AIIMS protocol – PUVA
 Starting dose
: 2 J/cm2 (type IV skin); 2.5 J/cm2 (type V)
Increments
: 0.5 J per 3rd sitting
Treatment frequency : 2 – 3 / wk
 Transient erythema (E) : no change
Trace asymptomatic E : rpt previous dose; then as per protocol
Well-defined E
: postpone 1; rpt previous dose; inc at 0.5J / wk
E + pain
: no further Rx till resolution; restart at 50% of
previous
dose; inc at 0.5 J / wk
E + pain + blistering
: stop Rx; review with treating Dr
 1 missed treatment
: rpt previous dose; then as per protocol
>1 missed treatment : decrease dose by 0.5 J / missed dose
 Maintenance dose
= last clearance dose
 Consider discontinuing if no response after 8 - 12 wks
PUVA Therapy : Side Effects
Acute
Chronic
Erythema
Chronic actinic damage
Pruritus
Carcinoma - rare
Nausea
Immunosuppression
Headache
Ophthalmic effect
Premature cataract
NB-UVB
 NB-UVB is considered superior to PUVA
•
Higher area of repigmentation
•
Better colour match
 Relapse rates of 21-44% within 1 year, and 55% within 2 years
AIIMS protocol – NbUVB
 Starting dose
Increments
Treatment frequency
 Transient erythema (E)
Trace asymptomatic E
Well-defined E
E + pain
: 280 mJ/cm2
: 20% of previous dose / wk
: 3/wk
: increase by 10% / wk
: rpt previous dose; then inc by 10% / wk
: postpone 1; rpt previous dose; inc at 10% / wk
: no further Rx till resolution; restart at 50% of
previous dose; inc at 10% / wk
E + pain + blistering
: stop Rx; review with treating Dr.
 1 missed treatment
: rpt previous dose; then as per protocol
>1 missed treatment
: decrease dose by 20% / missed dose
 Maintenance dose
= last clearance dose
 Consider discontinuing if no response after 8 – 12 wks
Targeted phototherapy
 Allows for selective treatment of lesional skin, avoiding unnecessary
irradiation of healthy skin.
 Quicker delivery of energy, shortened duration of treatment.
 Delivery of higher doses (super-erythemogenic doses) – enhancing
efficacy & faster response.
 Manoeuvrable hand piece – treatment of difficult areas, easy
administration for children.
 Disadvantage: cannot treat large areas.
Excimer laser
 The xenon chloride excimer laser emits a wavelength of 308 nm.
 Has the advantages and disadvantages of targeted phototherapy.
 Has been used with good results
•
Monotherapy.
•
in combination with topical steroids or calineurin inhibitors.
Prognostic factors
Cases resistant to medical line of treatment
 Acrofacial
 Patches on bony prominences
 Lesions on glans penis, palms, soles
 Patches with gray hair
 Patches around nipple
 Long standing cases
 Extensive depigmentation
Surgical treatment
 All surgical techniques have the same basic principle : to transplant
autologous melanocytes from pigmented donor skin to regions
without melanocytes.
 Suitable for stablised non-progressive Vitiligo, refractory to medical
treatment.
 No consensus on the definition of stability of disease.
 Various recommendations suggest stable Vitiligo for 6 months to 2
years.
Techniques in Vitiligo Surgery
Grafting Techniques
Tissue Grafts
Cellular Grafts
Minipunch grafting
Non cultured cell suspensions :
Epidermal and Follicular
Suction blister grafting
Cultured melanocytes /
keratinocytes grafts
Thin split thickness grafting
Smash grafting
Suction Blister Grafting
Smash Grafting
Epidermal cell suspension
(non- cultured)
MCQ’s
Q.1) Which of the following is not considered a poor prognostic factor
for medical treatment of vitiligo?
A. Leukotrichia
B. Vitiligo lesions on finger tips
C. Vitiligo lesions on the head and neck
D. Segmental Vitiligo
Q.2) Which of the following is considered to be the mainstay of
treatment in Vitiligo?
A. Systemic corticosteroids
B. Topical Vitamin D3 analogues
C. Topical corticosteroids
D. Minigrafting
MCQ’s
Q.3) Targeted phototherapy for Vitiligo suffers from the following
disadvantage
A. Can cause hyperpigmentation of normal skin
B. Not suitable for children
C. Cannot treat extensive areas
D. Longer duration of treatment
Q.4) Which of the following treatment modalities would be the best-suited
for generalised stable non-progressive Vitiligo in a 10-year-old boy?
A. NbUVB
B. PUVA
C. Oral mini pulse (systemic corticosteroids)
D. Targeted phototherapy
MCQ’s
Q.5) Which of the following tests would you order in an otherwise healthy
35-year-old man with acrofacial vitiligo of 2 years duration?
A. Thyroid auto-antibodies
B. Serum vitamin B12 levels
C. Skin biopsy
D. None of the above
Q.6)
A.
B.
C.
D.
20% monobenzyl ether of hydroquione is used in the treatment of
Segmental Vitiligo
Universal Vitiligo
Mucosal Vitiligo
Acrofacial Vitiligo
Photo Quiz
Q. 7) Identify the type of Vitiligo.
Q.8) Identify this differential diagnosis of
genital vitiligo
Thank You!