Vitiligo & Disorders of

Hypopigmentation
Dalia Bassiouny, MD
Professor of Dermatology
Cairo University, Egypt
 Definitions
• Depigemtation: total loss of skin
colour
• Hypopigmentation: skin is lighter in
colour than uninvolved normal skin
• Pigmentary dilution: generalized
lightening of skin, hair & eyes
• Poliosis: white lock of scalp hair
• Canities: generalized
depigmentation of scalp hair
 Important Questions
• Age of onset
• Preceding inflammation
• Distribution pattern
• Degree of pigment loss
VITILIGO: Bordeaux VGICC classification

NSV
Generalized SV
Acrofacial Uni, Bi or
Universal Pluri-
Mucosal (>2) segmental
Rare variants
Unclassified/
Undetermined
Mixed Mucosal (1 site)
(NSV + SV) Focal

Ezzedine et al.; Pigment Cell Melanoma Res. 2012 May; 25(3): E1–13.
 NSV
• Generalized: 1% of world wide population
In 50% onset before 20 years
± Acrofacial
• Acrofacial: hands & feet and periorificial
around the eyes and mouth
• Universal: extensive involving >50% of the
body surface area
 Segmental Vitiligo

• Starts in childhood
• Dermatomal; Stabilizes in 1-2 years
• Commonly associated with leucotrichia
Pathogenesis of NSV
Innate
Immunity

Oxidative Adaptive
stress Immunity

Vitiligo
(NSV) Melanocyte
Melano-
Proliferation
cytorrhagy Migration &
Differentiation

Genetic
Factors
 Exogenous stimuli Endogenous stimuli
Chemicals Melanin Synthesis
Trauma Mitochondrial dysfunction
2. Oxidative
stress
1. Easier detachment of melanocyte 1. Melano-
cytorrhagy
IL6, IL8
Oxidative 2. ++ ROS: cell damage
stress markers TNFα

Tenascin

Anti-oxidative
Mechanisms E Cadherin
 3. Innate 1. Easier detachment of melanocyte
Immunity

2. ++ ROS: cell damage IL6,

TNFα

HSP70i, Mel Ag
Exosomes (DAMP)
melanocyte specific Ag 3. Release of DAMP > Cytokine release> DC maturation
HSP 70i IL1β, TNFα Melan A/MART1
IL6, L12, IFNα Gp100
TYR, TYR related ptns

DAMP
 4. Adaptive
1. Easier detachment of melanocyte Immunity
Cell Mediated
CXCL9
2. ++ ROS: cell damage IL6, CXCL10
Humoral
TNFα
JAK1,2
4. CD 8 cytotoxic TLC kill Melanocyte INFγ LN
CD8+
CD8+ cytotoxic
cytotoxic T cell
T cell

HSP70i, Mel Ag
3. Release of DAMP > DC maturation
IL1β, TNFα
IL6, L12, IFNα
Lymphatics
4. Antibodies

Mel specific CD8+

CLA + cytotoxic
T cell
Serum
CRXC3+
 SV
Mosaicism
Targeted
immune
response )
Innate
Immunity

Oxidative Adaptive
stress Immunity

Vitiligo
(NSV) Melanocyte
Melano-
Proliferation
cytorrhagy Migration &
Differentiation
Wnt Pathway
Genetic abnormality induced
Majority Factors by oxidative stress
Immunomoregulatory gene abnormalities
HLA gene
 Differential Diagnosis
A. Inherited or genetically induced
hypomelanoses (usually present at
birth)
• Piebaldism
• Waardenburg’s syndrome
• Tuberous sclerosis
• Ito’s hypomelanosis
 Piebaldism
(Autosomal Dominant)

White forelock 80-90% of cases

Leukoderma : central forehead,
anterior trunk, mid extremities
(with normally pigmented areas)
Family member involved AD
Surgical grafting
 Waardenburg’s syndrome
(Autosomal Dominant or Recessive)
• White forelock & skin
lesions similar to
piebaldism
• Partial or total
heterochromia iridis
• Deafness 10-40%
• Broad nasal root
• Medial eyebrow
hyperplasia
• Surgical grafting
 Ocul-ocutaneous Albinism
• Autosomal Recessive Genetic disorder with pigmentary dilution
• Melanocyte number is normal, absent melanin
• 1;1500 in Afric
• Strict photoprotection aggressive SCC may develop
OCA1 OCA2 OCA 3 OCA4
At birth (milky white skin At birth more At birth: Similar to
white hair, pink nevi, blue pigmentation Red-bronze skin type 2 with
eyes than type 1 Ginger red hair pigmentary
Type A: No pigmentation Blue or brown eyes variabiliy
over time Over time
Type B: some develop
pigmentation of skin & pigmented nevi
hair in 1st 2 decades & pigmented
Severe ocular lentigens in
abnormalities (type A) sunexposed
skin
90% of cases of OCA
 Tuberous Sclerosis
(Autosomal Dominant)

Hypomelanotic macules at birth

or during neonatal period
 Linear nevoid Hypopigmentation
• Follow blaschko lines
• Ito’s Hypomelanosis: if
associated with systemic
manifestation (CNS ,
eyes or muskuloskletal
abnormalities usually)
Hypopigmented Nevus

• Common: 1:50 children

• Classic form or Segmental form
• Black hair
 Halo nevus
• Usually around an acquired
melanocytic nevus
• T cell mediated response against
melanocytes
• Usually children, family history of
vitiligo. Adults onset exclude
melanoma
• Four stages: I: central pigmented
nevus, II: central pink nevus, III: no
central nevus, IV: repigmentation
• Treat as vitiligo, ? Removal debatable
 Differential Diagnosis
B. Post-inflammatory hypomelanoses

A. psoriasis
B. Seb dermatitis
C. PLC
D. Lichen stiatus
F Atopic dermatitis
G DLE
 Differential Diagnosis
B. Post-inflammatory hypomelanoses
- Pityriasis alba (children & adolescents, ill
defined, mild inflammation, topical hydrocortisone )
 Differential Diagnosis
• B. Post-inflammatory hypomelanoses
– Lichen sclerosis et atrophicus (genital & extragenital)
– Systemic sclerosis (salt & pepper appearance,
perifollicular retention of colour)
– Sclerosis of the skin, biopsy diagnostic
 C. Para-infectious hypopigmentation
Pityriasis versicolor Tuberculoid Leprosy
• Common, superficial • Well defined hypopigmented
fungal infection, patches with anhidrosis,
Malassezia furfur spp alopecia & loss of sensations.
• In seborrheic areas, fine • Diagnosed by slit smear &
scales biopsy
• Antifungal therapy • Long course of anti-leprotic
drugs till cure
 Differential Diagnosis
D.Para-Malignant Hypomelanoses
Hypopigmented Mycosis Melanoma-associated
fungoides
depigmentation
• Middle-aged dark-skinned
individuals • Immune reaction
• Young adults, against shared antigens
• Asymptomatic slowly on normal & malignant
progressive over years to melanocytes.
involve wide areas on trunk
and extremities. • Spontaneously: may
• Biopsy diagnostic: imply a better prognosis
epidermotropism • Following
• Good prognosis but high
recurrence rate immunotherapy
 Differential Diagnosis
E.Post-traumatic leucoderma
Post-burns
Post-scars
 Differential Diagnosis
F. Occupational and drug-induced
depigmentation
• Phenolic–catecholic derivatives (HQ, MBEH)
• Systemic drugs (chloroquine, fluphenazine,
physostigmine, imatinib)
• Topical drugs (imiquimod, DPC, long-term use of
topical corticosteroids)
 DD: Contact leucoderma

Rubber

Dyes (Henna)
 Differential Diagnosis
G. Miscellaneous
Idiopathic Guttate Hypomelanosis
 Differential Diagnosis
G. Miscellaneous
Progressive Macular Hypomelanosis of the Trunk

• Propionibacterium acnes bacteria living in hair follicles as a result

of production of a hypothetical depigmenting factor.
• 1% clindamycin lotion morning, 5% benzoyl peroxide gel at night,
and UVA light irradiation 3 sessions/week for 12 weeks.
 Differential Diagnosis
A. Inherited or genetically induced hypomelanoses
B. Post-inflammatory hypomelanoses
C. Para-infectious hypopigmentation
D. Para-Malignant Hypomelanoses
E. Post-traumatic leucoderma
F. Occupational, contact and drug-induced
depigmentation
G. Miscellaneous: IGH, PMH
 Differential Diagnosis
Milky White Hypomelanotic
• Piebaldism, Waardenberg • Hypopigmented nevus
• DLE • Tuberous sclerosis
• Systemic sclerosis • Postinflammatory
• Lichen sclerosus hypopigmentation
• Post-burn • Infections (TV, leprosy)
• Contact leucoderma • Hypopigmented MF
• Idiopathic guttate • Progressive macular
hypomelanosis hypomelanosis of the
trunk
Wood’s light Examination
 Wood’s light Examination

Takafuji, M. et al (2019) Non-Invasive Evaluation and Differential Diagnosis for

Pediatric Leukoderma in a Single Institute. Journal of Cosmetics, Dermatological
Sciences and Applications, 9, 313-320. doi: 10.4236/jcdsa.2019.94028.
 First Visit
• Patient education:
‫مش معدي‬
‫التعامل مع الشمس‬
‫تفادي االحتكاك الشديد‬
‫تفادي الحنة‬
• Explain the treatment plan clearly to ensure
Good Compliance
• Therapy takes a long period of time.
 Assessment
Disease features
Patient Features
Duration (patient’s opinion:
Phototype, Ethnic origin
progressive, regressive, stable
Age at onset
over the last 6 months)
Psychological profile
Previous repigmentation,
Halo naevus
Koebner phenomenon
History of autoimmune diseases
Genitals involvement
Global QoL assessment
photography

Interventions
Family
Type and duration of previous
Premature hair graying
treatments (useful ⁄ not useful)
Vitiligo & autoimmune
Current treatment(s)
disease
Treatments for other diseases
Taieb et al.; Br J Dermatol 2013 168: 5–19
 Patient Assessment
• Full history
• Full Examination
• Standardized
Photography
With & without
Wood’s light

Van Geel et al.; J Am Acad Dermatol 2020;83:1639-46

 Recommended Investigations
If Diagnosis is certain
Anti-thyroglobulin antibody, Anti-thyroid peroxidase
antibody ± TSH free T3 freeT4
ANA (for photosensitive patients)
CBC, Blood sugar, Liver & Kidney functions
ESR Vitiligo unit
Kasr Al-Ainy
If Diagnosis is uncertain School of Medicine

•Punch biopsy from lesional and non-lesional skin

•Other tests if needed (eg: mycology, molecular biology
to detect lymphoma cells )

Taieb et al.; Br J Dermatol 2013 168: 5–19

Prognosis=Patterns of Repigmentation
Perifollicular Repigmentation:
Vertical migration
From the hair follicles

Medical ttt +
Phototherapy

Marginal Repigmentation:
Horizontal migration
No or sparse hair, <2 cm

Sparse hair,>2 cm
Remote melanocytes are
needed= Surgery
Anbar et al; Experimental Dermatology, 2014, 23, 219–223
 Examination BSA hand
A. Body surface area Involvement units
VES/ VES
5-75%= Re-pigmentation (NSV or SV) plus score

https://www.vitiligo-calculator.com/
Active
Recent onset<6m
New lesions History
Expansion of old lesions Old standardized
Depigmentation of a
photos
Induce
repigmenting lesion Stabilization
New Koebner • Dexamethaone OMP (5-10 mg/w)
Confetti- like lesions Clinical signs on on 2 consecutive days1
Examination • Total body NbUVB2
Ill- defined edge • Others: MTX, Azathioprine3
Trichrome vitiligo 1. Pasricha et al; Indian J Dermatol Venereol Leprol 1989; 55:18–21
2. Esmat et al. Photodermatol photoimmunol photomedicine 2022 38(3):277-287
3. Searle et al. Clin Exp Dermatol 2021;46 (2):248-258
 Oral Minipulse Therapy
• Weekend OMP starting with low doses (2.5 mg
daily) of dexamethasone for fast-spreading
vitiligo. For an optimal duration of 3-6 m.
• OMP therapy is not considered useful for
repigmenting stable vitiligo.
• The benefit of adding OMP to phototherapy at
the onset of treatment in progressive vitiligo is
not proven and needs further assessment.
• Current data do not provide enough evidence to
recommend immunosuppressants or biologics.
Taieb et al.; Br J Dermatol 2013 168: 5–19
 Topical Corticosteroids:
Frequency, Site
• Once-daily application of potent TCS can be
advised for patients with limited, extrafacial
involvement
– Continuous treatment scheme: no longer than 3 m
– A discontinuous scheme :15 days/month for 6 m.
• Facial lesions can be treated as effectively and
with less side-effects by TCI

Taieb et al.; Br J Dermatol 2013 168: 5–19

 Topical Corticosteroids: Type

• As potent TCS appear to be at

least as effective as very
potent TCS, the first category
should be the first and safest
choice.
• TCS with negligible systemic
effects (such as mometasone
furoate) should be preferred
when large areas of skin,
regions with thin skin and
children are treated for a
prolonged time to avoid
systemic absorption.
Taieb et al.; Br J Dermatol 2013 168: 5–19
 Topical Calcineurin Inhibitors
• Can be considered in adults and children as an
alternative to TCS for new, actively spreading,
lesions on thin skin.
• Should be restricted to selected areas, in
particular the head and neck region.
• Twice-daily applications are recommended
initially for 6 months. During this period of
treatment, moderate but daily sun exposure
should be recommended. May extend longer if
effective as long-term Taieb
useetisal.;reassuring
Br J Dermatol 2013in AD.
168: 5–19
Esmat et al; Clinics in Dermatology (2016) 34, 594–602
 Phototherapies: Type
• 1st line: Total body NB-UVB indicated in
generalized NSV involving 15-20% of BSA.
Targeted phototherapies for localized vitiligo
and in particular for small lesions of recent
onset and childhood vitiligo and in all cases
where total body NB-UVB is contraindicated.
• 2nd line: oral PUVA in adults with generalized
NSV. Topical PUVA for localized lesions (very
low conc) or Topical KUVA/ sun.
Taieb et al.; Br J Dermatol 2013 168: 5–19
 Phototherapies: Duration
• There is as yet no consensus as to the optimum
treatment duration of phototherapies.
• Many therapists tend to stop irradiation if:
– no repigmentation within the first 3 months or
– < 25% repigmentation after 6 months of therapy.
• Continue as long as repigmentation is happening up
to 1-2 years. Recent evidence suggesting a negative
association between vitiligo and skin cancer.
• Maintenance is not recommended, regular follow-
up examinations to detect relapse.
Taieb et al.; Br J Dermatol 2013 168: 5–19
 Expert Recommendations:
Phototherapies: Duration
Phototherapy Unit at Kasr Al Ainy Hospital, Cairo University
Sunscreens to normal skin 3 sessions weekly ; Start dose:
Sunglasses during sessions SPT≥ III: 0.5J/cm2; SPT I, II : 0.3J/cm2
Patients wit acral & non acral Increase every session by 20% till faint erythema.
lesions should receive extra
exposure to acral sites 3/week= 4 months
Twice weekly= 6 months
70 sessions = 6 m (3 sessions /w) OR 9 m (2 sessions/w)

Esmat et al; Clinics in Dermatology (2016) 34, 594–602

 No erythema
Pink asymptomatic
erythema
Bright red
asymptomatic
erythema
Symptomatic erythema
Dose adjustment based on degree of erythema

NB-UVB Dose Adjustment

 Combination Treatments

• Combined treatments improve the overall

effectiveness and the time needed to achieve
repigmentation reducing the potential side-
effects.
• Combinations of phototherapies with
different topical or systemic drugs have been
evaluated as well as the combination of
surgical and medical treatments.
Taieb et al.; Br J Dermatol 2013 168: 5–19
 Expert Recommendations:
Combination Therapies
Beneficial Combinations
1. TCS and phototherapy: good evidence of efficacy especially in
recent active lesions. Potent TCS once/d for 1st 3 m of phototherapy
2. Phototherapy after surgery : good level of evidence that
phototherapy should be used after surgical procedures
3. TCI and phototherapy: Effective but long-term data on
carcinoginicity still lacking.
4. Phototherapy and antioxidants may be useful. But still needs
confirmation

Limited Benefit
Vitamin D analogues and phototherapy
Taieb et al.; Br J Dermatol 2013 168: 5–19
 Generalized NSV: 5-75% BSA
Avoidance of triggering factors
Surgical ttt
Medical ttt Phototherapy
STABLE>1 yr
Stabilization Tissue graft
OMP/NB-UVB Total Body NB-UVB Cellular graft
others Stabilization + Followed by Medical
Repigmentation ttt & Phototherapy
Topical therapy
Acral small lesions:
Corticosteroids: Combined with Periorificial
body topical PUVA or Over joints
Calcineurin Acral lesions
PUVA sol Leucotrichia
Inhibitors: H&N,
genitals Response:
Excellent>poor
Resistant Sites Type: SV>mixed>NSV
Antioxidants Site: H&N> Body> Joints>Acral
Ginkobiloba Camouflage Vitiligo unit
Kasr Al-Ainy School of Medicine
 Examination
A. Body surface area Involvement
>75%= De-pigmentation (Universal vitiligo)
Induce
Active
Depigmentation
New lesions
History
Expansion of old lesions Old standardized
Depigmentation of a photos
repigmenting lesion Induce
New Koebner
Clinical signs on
Stabilization
Confetti- like lesions
Examination
Trichrome vitiligo
Ill- defined edge
 Treatment Plan
Universal
Extensive
ExtensiveVitiligo
ACRAL
Acral
>75% of area affected with Prognosis
of Minimal Repigmentation
>75% of BSA affected Depigmentation
Monobenzyl ether of hydroquinone 20% Strict Use of sunscreen

Localized area depigmentation eg: hands

Monobenzyl Ether of Hydroquinone

Cryotherapy
Q-switched Laser

Photos courtesy Dr. ElMofty El Mofty et al, Dermatol Ther 2019;32 (5):e13052
 Segmental Vitiligo
Avoidance of triggering factors

Medical ttt Surgical ttt

Phototherapy
STABLE>1 yr
Stabilization
if active Black Hair
Tissue Grafting
Phototherapy
Topical ttt Cellular Grafting
Targeted NB-UVB,
(TCS,TCI) excimer light or Followed by
laser Medical ttt&
Antioxidants Phototherapy
Ginko-biloba
Leucotrichia
Dermoscopic In lesions >1 cm2 Response: Excellent>poor
Examination Type: SV>mixed>NSV
Site: H&N> Body> Joints>Acral
Camouflage
 Indications for Surgical ttt
• Lesion characteristics:
– lesions >1 cm with Leukotrichia (segmental
vitiligo usually) or sparse hair in (over hands,
feet, elbows or knees)
– Lesions refractory to medical treatment
• Stable vitiligo for a minimum of 12 months
– Stationary size of lesion
– No recent development of new lesions
– No signs of activity.
• No keloidal tendency
 Tissue grafts
Suction blister grafting: Technique:

Usually, the grafts fall off in 1 to 2

weeks; so essentially this is a
Khunger et al, Ind J Dermatol, 2009)
technique of melanocyte transfer.
 Tissue Grafts
Mini Punch Grafting: (1 or 1.5 mm punches)
 Melanocyte-Keratinocyte Transplantation
Procedure (MKTP)

Suspension Recipient site

Donor tissue
preparation preparation
 Camouflage
• Self-tanning agents in gel, cream, lotion or spray: give
the skin a brown colour that resembles a natural tan
and normally lasts from 3 to 5 days.
• Highly pigmented cover creams (+ fixing spray):
waterproof characteristics but on face daily application
is required. Make-up removers are necessary to clean
the skin, with gentle and delicate movements to avoid
koebnerization.
• Dermal pigmentation, cosmetic tattoos: may be
suitable for depigmented lips, especially in black
people, and for depigmented nipples. Not
recommended for other areas.Taieb et al.; Br J Dermatol 2013 168: 5–19
 Psychological interventions:
• Subjective assessment should be included as part of
the evaluation of disease severity (analogue scale or
Dermatology Life Quality Index).
• In the case of a recognized psychosocial impairment,
different types of psychological interventions can be
proposed. No specific psychological therapeutic
intervention prevails based on published evidence.
• Patients appreciate the opportunity to express
difficulties related to their disease and to be listened
to and understood (community interventions may be
necessary).
Taieb et al.; Br J Dermatol 2013 168: 5–19
 Camouflage

• Useful in any Visible site: SV & NSV

• Highly pigmented cover creams (+ fixing spray)
• Self-tanning agents in gel, cream, lotion or spray lasts 3-5 days
• cosmetic tattoos: Lips, nipples ONLY.
• Camouflage improves DLQI*
* Bassiouny et al, J Cosmet Dermatol 2021; 20:159-165
 Conclusion
• Vitiligo is classified mainly into NSV, SV
• Clinical diagnosis is usually easy
• Screening for associated autoimmune diseases is
recommended in GV.
• Examination with stress on extent and activity
• Management according to activity, type & extent:
– < 75%stabilization + repigmentation
– >75% depigmentation
– SV with leucotrichia or extensive acral lesions: surgical
grafting or camouflage
THANK YOU