Prof. Ossama Hussein Roshdy

It is a term given to a wide range of disorders all are characterized by cutaneous hypopigmentation.

Melanin is produced from Tyrosine.

Melanocytes in the skin, oral mucosa, and uvea derive from spinal portion of the neural crest.

Melanocytes originate from melanoblasts.

Density of Melanocytes in the skin is the same for all human races.

Tyrosine DOPA DOPA quinone

DOPAchrome

DHI + DHICA Melanin.

INFANCY ( Diffuse-CIRCUMSCRIBED).INFANCY ( Diffuse-CIRCUMSCRIBED).

CHILDHOOD (Diffuse/ CIRCUMSCRIBED).CHILDHOOD (Diffuse/ CIRCUMSCRIBED).

ADULTHOOD (Diffuse/ CIRCUMSCRIBED).ADULTHOOD (Diffuse/ CIRCUMSCRIBED).

INFANCY / DiffuseINFANCY / Diffuse

Eyes, skin & HairEyes, skin & Hair Skin &/or HairSkin &/or Hair

MenkesMenkes Griscelli ‘s – Griscelli ‘s – Elejalde Elejalde

syndromessyndromes

NutritionalNutritionalDeficiencies,Deficiencies,

e.g. Se, e.g. Se, CopperCopper

Sialic aSialic aStorageStorageDiseaseDisease

EECEEC

OCAOCAPhenylketonureaPhenylketonurea

(PKU)(PKU)

11 22 33 Hermansky PudlakHermansky PudlakChediak - HigashiChediak - Higashi

CrossCross

Prader – WilliPrader – WilliAngelmanAngelman

INFANCY / CIRCUMSCRIBEDINFANCY / CIRCUMSCRIBED

Lack of PigmentLack of Pigment Decreased Decreased PigmentPigment

PostPostInfectiousInfectious

Ash leafAsh leafspotsspots

Post-Post-InflammatoryInflammatory

WaardenburgWaardenburg WaardenburgWaardenburg++

HirshsprungHirshsprung

HypomelanosisHypomelanosisOf ItoOf ItoNevusNevus

DepigmentosusDepigmentosus

VitiligoVitiligo PiebaldismPiebaldism

CHILDHOOD / CIRCUMSCRIBEDCHILDHOOD / CIRCUMSCRIBED

PostPostInfectiousInfectious

ChemicalChemicalLeukodermaLeukoderma

Post-Post-TraumaticTraumatic

DiffuseDiffuse

VitiligoVitiligo

Melanoma-Melanoma-AssociatedAssociatedleukodermaleukoderma

VKHVKH

SclerodermaScleroderma

CircumscribedCircumscribed

Post-Post-InflammatoryInflammatory

Total BodyTotal BodyVitiligoVitiligo

ADULTHOODADULTHOOD

PostPostInfectiousInfectious

EczemaEczema

Post-Post-InflammatoryInflammatory

VitiligoVitiligo Post-Post-TraumaticTraumatic

PLC PLC LS & ALS & A

LichenLichenstriatusstriatusPsoriasisPsoriasisAtopic Atopic

dermatitisdermatitis

- White hairs.- Milky white skin.- Blue-grey eyes.

Oculocutaneous Albinism

- Rare syndrome.- Inherited as an autosomal recessive.

Chediak – Higashi SyndromeChediak – Higashi Syndrome

- Bleeding tendency.- Platelet dysfunction.- Progressive neurologic dysfunction.- Severe immunodeficiency.- Marked susceptibility to respiratory

and cutaneous infections.- Uusually fatal before the age of 10

years.- later on from a malignant

lymphoma.

- Autosomal dominant.- Mutatio n on

chromosome 4q11-12.- Since birth.- Mainly forehead,

trunk, and extrimities.- Triangular or diamond

shaped areas.

PiebaldismPiebaldism

- Usually on front of the body.

- Specially on midline distribution.

- Whit forelock.- May be poliosis of eyebrows and

eyelashes.- Treated mainly surgically.

- Rare, autosomal dominant or A. recessive.

- Achromia of hair and/or skin.

- Broad nasal root dystopia canthorum.

- Heterochromia irides.

Waardenburg SyndromeWaardenburg Syndrome

- Congenital deafness.

- Medial eyebrows hyperplasia.

- Superficial fungal infection. - Pityriasis versicolor.

- Unsaturated fatty acids oxidation

products inhibit tyrosinase activity.

Post Infectious lekodermaPost Infectious lekoderma

fungus

Azelaic acid

Others:- Leprosy.- Pinta.- Yaws.- Bejel.- Secondary stage Syphilis.

- It is a misnomer.- Usually present at birth.- Single but may be multiple,

circumscribed.- Rounded, dermatomal or in whorls

and streaks.

Naevus Naevus depigmentosusdepigmentosus

- It is an autosomal dominant disease.- Multiple, irregularly

scattered(ashleaf appearance).

Ash leaf spots (Ash leaf spots (tuberous tuberous sclerosis)sclerosis)

- A disease of unknown etiology.- It affects 4 organs in succession:

1- Meninges encephalitic or meningitic symptoms + lymphocytosis of CSF.

Vogt-Koyanagi syndrome (HARADA)

2- Eyes bilateral uveitis, choroiditis and optic neuritis(some recovery of visual acuity).

3- Inner ears deafness and/or tinnitus (over 50% of cases) completely restored.

4- Skin (permanent changes)

vitiligo (60% of cases), poliosis (80% of cases) and alopecia areata (in 50% of cases).

Positive family member affection in about 25-33% of cases.

No prove of autosomal (recessive-dominant) trait.

Multifactorial inheretance genetic pattern is postulated (on chromosomes 1-2-and 4).

Heterogenous-

Convergence theory

- Association with some auto-immune diseases.

- Antibody activity is more pronounced in active rather than stable disease.

I- Auto-immune theory:

- ↑ Antibodies against melanocyte surface antigens.

- ↑ Antibodies against common tissue antigens (thyroid, gastric parietal cells and adrenal tissue) in 80% of vitiligo cases.

- ↑ Level of anti-tyrosinase antibodies.

- T-cell profiles are abnormal in vitiligo with a decrease in T-helper cells.

- Melanocyte activity Melanocyte death.

II- Auto-cytotoxicity theory:

↑ Melanocyte susceptibility to the precursor molecule (Dopachrome) cell death.

• Inhibition of Thioredoxin reductase enzyme (a free-radical scavenger) ↑accumulation of free radicals.

• ↓Level of catalase (which reduces superoxides).

↑ Dopamine auto-oxidation.

Melanocyte death

• Depigmentation in animal models with injured nerve fibers.• Nerve injury associated absence of vitiligo lesions.

• Segmental dermatomal type of vitiligo.

• Increased adrenergic activity (sweating – vasoconstriction) in vitiligo areas.

III- Neural theory:

Evidenced by:

Elevated levels of in Melanocytes of

vitiligo lesions may suggest neurogenic control.

Neurotensin TNF-α

Vitiligo areas

Absent Melanocytes.

Normal skinVitiligo skin

Vitiligo. A melanocyte with a giant melanosome is present at the edge of the

depigmented area. (H&E)

• Cultured Melanocytes at lesion’s peripheries

Evidence of

Poor growth + premature death Degeneration: vacuolizationPyknosismelanosomes aggregation

Sometimes ?? Inflammatory changes at the borders of lesions.

Onset childhood or young adults. in ≈20% develops after severe

sunburn or severe emotional or physical stress.

Incidence ↓ with increasing age.

Gender preponderance in female patients (?? False preponderance).

Prevalence is variable from area to another:

USA → 1%. Denmark →

0.38%. India →

1.13%

According to the extent of involvement:

1- Generalized.2- Universal.3- Acrofacial (distal fingers + facial

orifices).4- Segmental (dermatomal-

asymmetric).5- Focal (localized non-dermatomal).

6- Vitiligo gradata (trichrome type).

7- Vitiligo with raised borders.

8- Drug induced vitiligo – rare type (Chloroquine- Clofazimine).

9- Chemical- induced leukoderma (occupational):

- Phenolic compounds (p-TBP)- monomethyl ether of hydroquinone)

- Sulfhydryls (Sulfanilic acid – Mercaptoethylamine MEA).

- Others: arsenic- corticosteroids – azelaic acid – mercurials.

10- Vitiligo with melanoma:

-Regression or slow progression of melanoma long survival time .-Halo nevus.-Diffuse depigmentation and/or hypo pigmentation (remote from the tumor)

A- Autoimmune diseasaes:- Addison’s disease.- Thyroid disease.- Diabetes.- Alopecia areata.B- Uveitis.C- Auditory problems.D- Vogt-Koyanagi-Harada Syndrome.

CLINICAL SYSTEMIC ASSOCIATIONS

EN

ALU

ATIO

N Wood’s light examinatiuon

TSH level

Complete blood picture

Ophthalmologic examination

Psychological evaluation

TREATMENT

Cosmetic camouflag

e

Topical and systemic steroids

Phototherapy•Psoralen UVA•Narrowband UVB

Surgical treatment

Type of dyes

Sites of application

On exposed areas (face, neck, and hands)

Cover mark- Dermablend – Dermacolor - Dermage

Drawbacks

Personal rejectionSevere reactionNot practical for extensive lesions

I- Cosmetic camouflage

P = Psoralens

UVA = Ultraviolet A

Topical

Systemic

360 nm waveleng

th

PUVA therapy

8 methoxy-psoralen 0.5 mg/kg. Used for extensive vitiligo.

Exposure:• 1.5-2 hours after ingestion of the drug.• 1-2 J/cm2 increments by 0.25 J/cm2 till erythema dose.• 2-3 times / week.

8 methoxy-psoralen 0.05- 0.1% solution.

Used in cases with less than 20% total surface area depigmentation.

Exposure:• Duration before exposure is not important.• 1-2 J/cm2 .• 30 seconds increments by 15-30 seconds up to 10 minutes. • 2-3 times /week.

PUVA increase the size but not the number of Melanosomes.

UV light Psoralen + DNA

photoadducts

(with thymine bases) DNA inhibition

RNA + protein synthesis.

1-photoadducts

Decreasing the antibodies directed against Melanocytes.

2- immunologic :

Cytokines release from keratinocytes:• Interleukin-1 Facilitates binding of α-MSH to keratinocytes.• Leukotriens C4, D4 Stimulate Melanocyte proliferation (in-vitro).• Endothelin-1 Proliferation and differentiation of Melanocytes.Leukotrien C4 + TGF-α Melanocyte migration (in-vitro).

SIDE EFFECTS

IMMEDIATE DELAYED

•Erythema.•Pigmentation.• Fatigue.• Xerosis.• Pruritus.

• Skin aging.•Malignancy (SCC).• Cataract

PUVASOL

Exposure:- We use 5 MOP or TMP.- Dose of 0.3 mg/kg.- 2-4 hours outdoor light exposure (10 AM – 3 PM).- 5-10 minutes increments by 5 minutes/ session for 4 exposures gradual increase up to 2 hours.

Usually 311-312 nm wavelength. Treatment of choice for adults and children

with generalized vitiligo. 250 mJ/ cm2 increments by

15% at each exposure erythema.

2-3 times /week.

1- Can be used in children.2- Can be used in lactating and pregnant

women.3- Can be used in hepatic or kidney dysfunction.

Narrowband UVB (NB-UVB)

Advantages

Repigmentation occurs from hair

follicles.

Upward migration of Melanocytes is influenced by cytokine release from

keratinocytes.

For localized lesions. Face and neck may respond better. High potency topical corticosteroid

preparations (0.1% betamethasone valerate -0.05% clobetasol propionate) are effective.

1-2 months tapering. IM corticotropins may also help.

Topical and systemic steroids

Segmental or localized vitiligo. Non progressive-inctive disease. In areas such as:- Dorsal aspect of fingers.- Forehead.- On hair lines.- Ankles.

Surgical treatment

INDICATIONS

A- Epidermal Grafting

B- Autologus Minigrafting

C- Transplantation of non-cultured Melanocytes

D- Transplantation of cultured Melanocytes

Surgical treatment modalities