Vitiligo

Pigmentary disorders of skin, leukoderma

1. Dr. Angelo Smith M.D
WHPL

3. •Melanocytes are special cells in our skin
that specialize in making a molecule
called melanin.
•What is Melanin?
•Melanin is something called a pigment,
which is the molecule that gives our skin
colour a darker shade.
MELANOCYTES AND MELANIN

4. What does melanin actually do?
Melanin protects our skin from the damaging
Ultraviolet (UV) rays from the sun.
Going sun tanning induces your body to
produce more melanin, which is why people
who return from tanning look darker.
More melanin in the skin is the reason why
people who are darker usually do not get
sunburned.

5. MELANOGENESIS
•Melanoblast
•Melanocyte
•Melanin
• Phenylalanine ® Tyrosine
•Color of the Race ® Rate of melanin
production.

7. In our skin, we all have around the same number
of melanocytes, which are the cells that produce
melanin.
However, the melanocytes in each of our bodies
produce different amounts of melanin.
The more melanin you have in your skin, the
darker your skin color will be.

8. FACTS

9. •It is a skin condition that can manifest after
birth at any point in someone’s life.
•It leads to death or loss of function of the
melanocytes in the body, which leads to the
inability to produce any more melanin in the
skin.
•Vitiligo is very visible on someone with a very
dark complexion due to the prevalence of white
splotches of skin.

10. •Chronic skin disease
•Other name = Leukoderma
•White spots occur when the skin no longer
forms melanin (pigment that determines the
color of your skin, hair, and eyes)
•The white patches of irregular shapes begin to
appear on your skin

11. •Any part of the body may be affected.
•Common sites are exposed areas (face,
neck, eyes, nostrils, nipples, navel,
genitalia), body folds (armpits, groin),
sites of injury (cuts, scrapes, burns)
and around pigmented moles (halo
naevi)

12. SYMPTOMS & SIGNS
•White patches of skin
•Whitening or graying of the hair on your scalp,
eyelashes, eyebrows or beard (leukotichia – seen in
segmental)
•Loss of color in the tissues that line the inside of your
mouth
•Loss or change in color of the inner layer of your eye

13. •The degree of pigment loss can vary within
each vitiligo patch which means that there
may be different shades of brown in a
vitiligo patch.
•This is called ‘trichrome’.
•A border of darker skin may circle an area
of light skin.

21. ASSOCIATIONS
•Premature graying of hairs in relatives.
•Koebner phenomenon.
•Emotional or Physical stress.
•Drugs ® Chloroquine and Clofazimine.

22. SYSTEMIC
ASSOCIATIONS
•
­ risk of Autoimmune diseases.
•  Thyroid dis. [Hashimoto’s, Grave’s]
•  Addison’s disease
•  Pernicious Anemia
•  Insulin dependent Diabetes
•  Alopecia Areata

23. SYSTEMIC ASSOCIATIONS
•Eye disorders
•  Uvietis
•  Depigmentation of Choroid.
• Ear disorders
•  Auditory problems

24. PSYCHOLOGICAL IMPACT
•Feelings of stress, embarrassment and self
consciousness.
•Perception of discrimination.
•Low self esteem.
•Disturbed sexual relationships.

25. ETIOLOGICAL THEORIES
•Familial Theory
•Auto-immune Theory
•Autocytotoxic Theory
•Neural Theory
•Self destruction Theory

26. FAMILIAL THEORY
•Epidemilogically, 25 - 33% have family
members with disease.
•Close biologic relatives ® 4 - 5 folds
increased risk.
•HLA studies have variable results.
•No specific genetic pattern.

27. AUTO-IMMUNE
THEORY
•Antibodies against melanocyte surface
antigens, correlate with the extent of
depigmentation.
•Antityrosinase ab., Antimelanin ab. and
melanin-sensitized lymphocytes.
•Leukocyte migration inhibition factor
levels and circulating immune complex
levels markedly elevated.

29. AUTOCYTOTOXIC
THEORY
•Increased melanocyte activity, leads to its own
demise.
•Inhibition of Thioredoxin reductase, by
Calcium.
•Higher Ca levels cause ­­ superoxide radicle
formation.
•Levels of Catalase, markedly decreased.

30. NEURAL THEORY
•Based on the following observations:
• Patients with nerve injury and vitiligo in
denervated areas .
• Clinical evidence of segmental dermatomal
vitiligo.
• Increased sweating and vasoconstriction in
vitiliginous areas.

31. NEURAL THEORY…
[CONT.]
•Depigmentation in animal models with severed
nerve fibres.
•Degenerative and regenerative autonomic
nerves in depigmented patches.
•Increased urinary excretion of VMA and HVA
in active vitiligo.

32. •It suggests that melanocytes are
destroyed by flaws in the protective
mechanism that removes the chemical
toxins that is generated in
melanogenesis.
SELF DESTRUCTION THEORY

35. MEDICAL SCREENINGS :
A family history of vitiligo
Look to see if there is a rash,
sunburn, or other skin trauma
that has occurred within 2 or
3 months after pigmentation
was discovered
Premature graying of the hair
(before age 35)
Stress or physical illness
Also they may ask for an eye
examination (inflammation of
your eye) and/or blood test
(autoimmune disease)

36. HISTOPATHOLOGY
•Uniform absence of Melanocytes.
•Periphery of depigmented patch show : signs of
cellular death.
•Dilatation of rough endoplasmic reticulum in
melanocytes.
•Inflammatory changes in dermis.

37. EVALUATION
•Total body Wood’s light examination.
•TSH levels [Thyroid disease].
•CBC [Pernicious anemia].
•Evaluation about Diabetes Mellitus.
•Ophthalmological examination.

38. TREATMENT
1. Cosmetic
2. PUVA
a. Topical
b. Systemic
3. Corticosteroids
4. Surgical Treatment
5. Monobenzyl ether of Hydroquinone

39. COSMETIC TREATMENT
•Patches on exposed parts can be concealed by:
Make up brands : Cover Mark, Derma blend, Derma color
etc.
Topical dyes : Clinique bronze gel, Vitadye, Dyoderm etc.
Tanning creams : Chromelin, self tanning milk etc.
Advantages:
Cost, ease of application, lack of side effects.
Disadvantages:
Vigorous physical activities and in extensive disease.

40. P U V A
•Historically, Egyptians in 13th century
The herb “Ammi majus linnaeus”
Ammoidin
8-MOP, 5-MOP and 8-isoamylene OP
•1904, Montgomery, Light therapy in vitiligo
•1948, Al-Moftey, First use of light therapy in
combination with psoralens.

41. MECHANISM OF ACTION [PUVA]
•Immunologically mediated action.
•Stimulation of tyrosinase activity.
• Inhibition of DNA and protein synthesis.
•Depletion of EGF expression.
•Depletion of vitiligo - associated melanocyte
antigens.

42. MELANOCYTE
REPIGMENTATION
•Activation of inactive cells [spared in vitiligo
process] in the middle and lower part of follicle
and in outer sheath.
•These inactive cells contain structural and
melanosomal proteins, but do not contain
enzymes, required for melanogenesis.

43. MELANOCYTE REPIGM. [CONT.]
•Migration of melanocyte from lower hair follicle to
epidermis, depends on :

a) Cytokine release, like FGF, IL-1,
b) Inflammatory mediators such as : TGF-a,
leukotriene C
4
, D
4
, and endothelin-1.

44. TOPICAL PSORALENS
•Patients with less than 20% of total body
surface.
•Initially 0.05% or 0.1% strength.
•Artificial UVA source for 30 seconds initially
and increasing exposure to up to10 minutes 2 - 3
times per week.
•At 10 minutes, higher strength (0.1% to 0.15%)
prescribed.

45. TOPICAL PSORALENS (CONT.)
•Shielding uninvolved skin and eyes.
•Wash off the topical solution immediately
after treatment.
•Sun blocks, Avoiding direct and filtered
sunlight for the rest of the day.
•Side effects ®® Blistering, Burning and
Perilesional hyperpigmentation.

46. •Most effective treatment available
• PUVA therapy is to repigment the
white patches
•time-consuming, and care must be
taken to avoid side effects
•Psoralen is a drug that contains
chemicals that react with ultraviolet
light to cause darkening of the
skin.
•Psoralen is injected orally or is
applied to the skin
•Then skin is carefully timed
exposure to sunlight or to
ultraviolet A (UVA) light that
comes from a special lamp.

47. ORAL PSORALEN / UVA
•Patients with extensive disease.
•0.5 mg / kg, 2 hours before treatment.
•Started at 1-2 j / cm
2
of light 2 - 3 times a week
.
•Darker pigmented patients and children
respond better to PUVA.

48. ORAL PSORALEN / UVA
•Trunk, proximal extremities and face respond
better to PUVA.
•Distal extremities, periorificial and dermatomal
lesions do not respond better.
•Side effects ®® burns, nausea, erythema,
pruritus, xerosis, fatigue, carcinogenecity,
pigmentation, cataracts and aging.

49. ORAL PSORALEN / UVA
•Contraindicated in ®
•Pregnant women, breast feeding, h/o skin cancer,
arsenic exposure, photosensitivity, radiotherapy,
and cataracts.
•Advised to ®
•Visit Ophthalmologist yearly, wear goggles, avoid
direct and filtered sunlight for 24 hours after
treatment.

50. CORTICOSTEROIDS
•First used in 1959 by Japanese.
•Both systemic and oral.
•Localized depigmented patches.
•High potency steroids for 1 - 2 months.
•Slowly tapered to lower strength.
•Usual side effects.

51. TOPICAL STEROID THERAPY
•The use of steroid creams may be helpful in returning the color to
the white patches
•A mild topical corticosteroid cream for children under 10 years
old and a stronger one for adults
•Cream must be applied to the white patches on the skin for at
least 3 months before seeing any results
•Corticosteroid creams are the simplest and safest treatment for
vitiligo, but are not as effective as psoralen photo chemotherapy
•SIDE EFFECTS occur in areas where the skin is thin, such as on
the face and armpits, or in the genital region
•They can be minimized by using weaker formulations of steroid
creams in these areas.

52. SURGICAL MODALITIES
•Localized non-progressive patch in a non- acral
location.
•Epidermal grafting
•Autologous minigrafting
•Transplantation of in vitro-cultured epidermis.
•Transplantation of non-cultured melanocytes.

53. EPIDERMAL GRAFTING
•Blisters at donor and recipient sites by suction or
liquid nitrogen.
•Roof of the blister is removed from both sites and
donor epidermis is placed on denuded recipient site.
•Reinforcement with biological dressing.
•Repigmentation seen in 2 weeks to 3 months.
•Pre-treating donor site with topical PUVA, to
stimulate melanogenesis, may enhance re-
pigmentation.
•Low incidence of scarring.

54. AUTOLOGOUS MINIGRAFTING
Multiple small punch biopsy specimens.
At Inconspicuous donor site, close together.
At recipient site, separated by 4 - 5 mm.
Test area chosen and 3 - 5 minigrafts are placed to
determine the ability.
After 2 months, if the pigment has spread, grafting
of the entire region continued.

55. IN VITRO CULTURED EPIDERMIS
Blisters at both donor and recipient sites.
Epidermis from donor site is treated with trypsin.
Melanocytes isolated and grown in cell culture for
3 weeks.
Melanocytes adhere to Vaseline gauze, which is
divided, and placed over the denuded recipient
site.

56. IN VITRO CULTURED EPIDERMIS
With this procedure, repigmented site can be as
large as 10 times the donor site.
Pitfalls of this technique :
1. Variegated color, due to variable
melanocyte concentration on the gauze.
2. Spotty graft failure

57. NON CULTURED MELANOCYTES
Non cultured melanocytes obtained with
dermatome from donor site.
Melanocytes treated with trypsin, EDTA, and
placed in a saline solution.
Injected as suspension into blisters in the recipient
site created by liquid nitrogen.
Repigmentation is faster than in vitro melanocytes.

58. HYDROQUINONES
Used in extensive disease where, remaining normal
skin is depigmented.
Inhibit tyrosinase, Decrease the number of
melanized melanosome, Alter melanosomal
configuration, and Cause melanocyte organelle
disuption and lysis.
Results may take from one month to one year, to
depigment completely.

59. •Vitiligo frequently begins with a rapid loss of
pigment which may be followed by a lengthy
period when the skin color does not change.
•Later, the pigment loss may begin again.
•The loss of color may continue until, for
unknown reasons, the process stops.
•Cycles of pigment loss followed by periods of
stability may continue indefinitely.
PROGNOSIS