Disorders of hypoigmentation

• They are general terms used to designate disorders
characterized by lightening of the skin. They may be:
- Melanin-related result of ↓ epidermal melanin
content.
- Hemoglobin-related secondary to ↓ blood
supply to the skin.

Is a more specific term that denotes an absence or reduction of melanin
within the skin;
Cutaneous hypomelanosis is often classified into two groups:
• MELANOCYTOPENIC HYPOMELANOSIS; caused by a
partial or total absence of epidermal &/or follicular melanocytes.
• MELANOPENIC HYPOMELANOSIS, in which the number
of epidermal and/or follicular melanocytes is normal but the
pigment cells fail to synthesize normal amounts of melanin
and/or transfer it to surrounding keratinocytes.

• Signifies the total absence of melanin.

• Usually implies a total loss of skin color, most commonly
due to disappearance of pre-existing melanin pigmentation,
as in vitiligo.

• This term is used to describe a generalized lightening of
the skin and hair, as in oculocutaneous albinism; this may
be apparent only if affected individuals are compared with
unaffected relatives.

Poliosis
• localized patch of white or gray hair.

Causes of Hypomelanosis
A. Genetic Hypomelanosis
B. Acquired Hypomelanosis

Genetic Hypomelanosis
1. Oculocutaneous albinism
(OCA)
2. Ocular albinism With
deafness
3. Albinoidism
4. Cross syndrome
5. Piebaldism
6. Waardenburg syndrome
7. Phenylketonuria (PKU)
8. Tuberous sclerosis (ash
leaf macules)
9. Naevus depigmentosus
10. Hypomelanosis of Ito

Acquired Hypomelanosis
I-Inflammatory
1. Eczema
2. Atopic eczema
3. Pityriasis alba
4. Pityriasis rosea
5. Pityriasis lichenoides
chronica (PLC)
6. Psoriasis
7. Parapsoriasis
8. Lupus erythematosus
9. Lichen planus
10. Lichen sclerosus
11. Lichen striatus
12. Scleroderma
13. Sarcoidosis
14. Bullous dermatoses

II- Infections
1. Pityriasis versicolor
2. Leprosy
3. Syphilis
4. Pinta (Treponematoses)
5. Yaws
6. Onchocerciasis
7. Post Kala-Azar dermal leishmaniasis

III-Chemical factors
(occupational and therapeutic)
1. Phenol derivatives e.g. Monobenzylether of
hydroquinone, Monomethylether of hydroquinone
2. Antimalarials: Chloroquine and hydroxychloroquine
3. Corticosteroids (topicals & intralesional)
4. Arsenic
5. Sulfhydryls
6. Azelaic acid

IV- Physical factors
1. Thermal burns
2. Freezing
3. Lasers
4. UV radiation
5. Ionizing radiation,
6. Dermabrasion

V-Endocrine factors
1. Hypopituitarism
2. Hypothyroidism
3. Addison’s disease

VI-Nutritional factors
1. Chronic protein deficiency
a) Kwashiorkor
b) Malabsorption
c) Nephrosis
2. Pernicious anaemia (vit. B12↓)

VII- Neoplasms
1. Halo naevus
2. Malignant melanoma
3. CTCL (hypopigmented MF & poikilodermatous
MF)

VIII- Miscellaneous
1. Poliosis
2. Canities
3. Idiopathic guttate hypomelanosis
4. Progressive Macular Hypomelanosis
5. Vitiligo
6. Vogt–Koyanagi–Harada syndrome
7. Vagabond’s Leukomelanoderma

Leukodermas without
Hypomelanosis
1. Woronoff ’s ring
2. Nevus anemicus
3. Cutaneous edema
4. Anemia
5. Angiospastic macules (Bier spots)

Definition
• Latin vitilīgō skin eruption, appar. akin to vitium fault,
defect.
• Vitiligo is an acquired pigmentary disorder of the
skin and mucous membranes characterized by
circumscribed depigmented macules and patches
that result from a progressive loss of functional
melanocytes that are selectively destroyed.

• Vitiligo affects 0.5-2% of the world population.
• The average age of onset is 20 years.
• The condition is frequently associated with disorders
of autoimmune origin, with thyroid
abnormalities being the most common.

INCIDENCE:
• Vitiligo is relatively common, with a rate of 0.5 -2% of
the general population worldwide.
• Approximately 30% of vitiligo cases occur with a familial
clustering of cases.
SEX:
• No statistically significant difference.
• The discrepancy has been attributed to an  in reporting
of cosmetic concerns by ♀ patients.

AGE:
• The onset is most commonly observed
in persons aged 10-30 years.
• The average age of onset for vitiligo is
approximately 20 years.
• Vitiligo rarely is seen in infancy or old
age. Nearly all cases of vitiligo are
acquired relatively early in life.
• The age of onset is unlikely to vary
between the sexes.

Pathophysiology
• Vitiligo is a multifactorial polygenic disorder with a
complex pathogenesis. It is related to both genetic
and nongenetic factors. Although several theories
have been proposed about the pathogenesis of
vitiligo, the precise cause remains unknown.
Generally agreed upon principles are
 An absence of functional melanocytes in vitiligo skin.
 A loss of histochemically recognized melanocytes,
owing to their destruction.

Pathophysiology
•  levels of SCF (stem cell factor) in lesional vitiligo skin
compared to non-lesional skin.
•  levels of TNF-α and IL-1 in lesional vitiligo skin
compared to non-lesional skin.
• In addition to the typical “absolute” type of vitiligo in
which there are no DOPA-positive melanocytes
“relative” types of vitiligo in which melanocytes remain
within the lesions but have  DOPA-positivity have
been observed. It is possible that relative types of vitiligo
are forerunners of the absolute type.

Pathophysiology
• There is increasing evidence that non-segmental
and segmental forms of vitiligo do not have the
same genetic influences and may be distinct entities.
For non-segmental vitiligo, accumulated data strongly
support an autoimmune etiology in genetically predisposed
individuals.
• Melanocytes may be present in depigmented skin
after years of onset & may still respond to therapy
under appropriate stimulation.

Pathophysiology
GENETICS OF VITILIGO:
• Both twin and family studies indicate the importance of genetic
factors in the development of vitiligo.
• Vitiligo is characterized by;
1. Incomplete penetrance (with environmental influences)
2. Multiple susceptibility loci.
3. Genetic heterogeneity.
• The inheritance of vitiligo may involve genes associated with;
1. Biosynthesis of melanin.
2. Response to oxidative stress.
3. Regulation of autoimmunity.
• An association with HLA-B13 in the presence of antithyroid Abs.

Pathophysiology
• THEORIES REGARDING DESTRUCTION OF
MELANOCYTES INCLUDE:
1. Autoimmune mechanisms.
2. Intrinsic defect of melanocytes mechanisms.
3. Oxidant-antioxidant mechanisms.
4. Neural mechanisms.
• “CONVERGENCE THEORY” has also been
proposed that vitiligo results from a combination of
several of the pathogenic mechanisms.

Pathophysiology
NEURAL THEORY
Based on the following observations:
• A neurochemical mediator released from nerve endings destroys
melanocytes or inhibits melanin production.
• Case reports describe patients afflicted with a nerve injury who also
have vitiligo have hypo- or depigmentation in denervated areas.
• Segmental vitiligo frequently occurs in a dermatomal pattern.
• Sweating and vasoconstriction are  in vitiliginous areas, implying an
 in adrenergic activity.
• Degenerative & regenerative autonomic nerves in depigmented patches.
•  urinary excretion of homovanillic acid (HVA) and vanilmandelic
acid (VMA) (neurometabolites) in active vitiligo has been documented
in patients with vitiligo. This may be a secondary or primary
phenomenon.
• Depigmentation in animal models with severed nerve fibres.

Clinical Features
• Usually asymptomatic.
• Onset: usually insidious.
• Color: The MC form of vitiligo is
totally amelanotic acquired chalk or
milk-white or hypopigmented
macules or patches surrounded by
healthy skin. The lesions are not
readily apparent in lightly
pigmented individuals; however,
they are easily distinguishable with
a Wood lamp examination.

Clinical Features
• Shape: Round, oval, irregular or
linear.
• Borders: Usually well demarcated
may be convex as if the
depigmenting process were
“invading” the surrounding
normally pigmented skin.
• Size: Range from mms to cms.
Lesions enlarge centrifugally over
time at an unpredictable rate (slow
or rapid).

Clinical Features
• Site: Interestingly, it has a predilection for sites that are normally
relatively hyperpigmented. Initial lesions occur most frequently on
the hands, forearms, feet, and face, favoring a perioral and periocular
(i.e. periorificial) distribution.
• The MC sites of vitiligo involvement are the face, neck, and scalp.
Many of the MC sites of occurrence are areas subjected to repeated
trauma pressure or friction esp. bony prominences, including the
following:
1. Elbows
2. Knees
3. Dorsal ankles
4. Shins
5. Extensor forearm
6. Ventral wrists
7. Dorsal hands
8. Digital phalanges
• Involvement of the mucous membranes is frequently observed in
the setting of generalized vitiligo.
• Vitiligo often occurs around body orifices such as the lips,
anogenital, gingiva, areolas, and nipples.

Clinical Features
• Vitiligo of the scalp usually
appears as poliosis, but scattered
white hairs due to involvement
of individual follicles or even total
depigmentation of all scalp
hair may occur. Scalp
involvement is the most frequent,
followed by involvement of the
eyebrows, pubic hair, and
axillary hair, respectively.

Clinical Features
LEUKOTRICHIA:
• Depigmented body hair in vitiliginous
macules.
• May indicate a poor prognosis in regard to
repigmentation.
• Spontaneous repigmentation of depigmented
hair in vitiligo does not occur as follicular
melanocytes are often spared in vitiligo.
• It’s occurrence does not correlate with disease
activity.
• Isolated early graying or whitening before 30 years
of age has been suggested to represent a form of
vitiligo.

Clinical Features
PSYCHOLOGICAL IMPACT
• Feelings of stress,
embarrassment and self
consciousness.
• Perception of discrimination.
• Low self steem.
• Disturbed sexual relationships.

Clinical Variants
1. Trichrome vitiligo: has an intermediate zone of hypochromia located between the achromic
center & the peripheral unaffected skin. The natural evolution of the hypopigmented areas is
progression to full depigmentation & number of melanocytes is also intermediate in this zone.
This results in 3 shades of color; brown, tan (fairly uniform hue), and white in the same patient.
2. Quadrichrome vitiligo: presence of 4th color (ie, dark brown) dt. perifollicular repigmentation.
3. Pentachrome vitiligo: with 5 shades of color (black, dark brown, medium brown [unaffected
skin], tan and white) has also been described.
4. (Marginal) inflammatory vitiligo: results in erythematous raised border which is present
from ‘onset of vitiligo (in rare cases) or which may appear several months or years after the initial
onset. Mild pruritus may be present.
5. Blue vitiligo: results in blue coloration of vitiligo macules. This type has been observed in a
patient with postinflammatory hyperpigmentation who then developed vitiligo.
6. Koebner phenomenon: is defined as the development of vitiligo in sites of specific trauma, such
as a cut, burn, or abrasion. Minimum threshold injury is required for Koebner phenomenon to
occur even friction from clothes. more common in progressive non-segmental vitiligo.
7. Vitiligo ponctué: “punctuated” an unusual clinical presentation of vitiligo, is characterized by
multiple small (confetti-like), discrete amelanotic macules, sometimes superimposed upon a
hyperpigmented macule.

Clinical Variants
1. Trichrome vitiligo: has an intermediate zone of hypochromia located between the achromic
center & the peripheral unaffected skin. The natural evolution of the hypopigmented areas is
progression to full depigmentation & number of melanocytes is also intermediate in this zone.
This results in 3 shades of color; brown, tan (fairly uniform hue), and white in the same patient.
2. Quadrichrome vitiligo: presence of 4th color
(ie, dark brown) dt. perifollicular repigmentation.
3. Pentachrome vitiligo: with 5 shades of color (black, dark brown, medium brown [unaffected
skin], tan and white) has also been described.
4. (Marginal) inflammatory vitiligo: results in erythematous raised border which is present
from ‘onset of vitiligo (in rare cases) or which may appear several months or years after the initial
onset. Mild pruritus may be present.
5. Blue vitiligo: results in blue coloration of vitiligo macules. This type has been observed in a
patient with postinflammatory hyperpigmentation who then developed vitiligo.
6. Koebner phenomenon: is defined as the development of vitiligo in sites of specific trauma, such
as a cut, burn, or abrasion. Minimum threshold injury is required for Koebner phenomenon to
occur even friction from clothes. more common in progressive non-segmental vitiligo.
7. Vitiligo ponctué: “punctuated” an unusual clinical presentation of vitiligo, is characterized by
multiple small (confetti-like), discrete amelanotic macules, sometimes superimposed upon a
hyperpigmented macule.

Classifications of Vitiligo “By
VITILIGO
Localized
Focal Segmental Mucosal
Generalized
Acrofacial Vulgaris Mixed
Universal
Distribution”

Classifications of Vitiligo “By
Distribution”
I. LOCALIZED VITILIGO “3”
1. Focal: characterized by one or more macules in one area but not clearly in a
segmental distribution, MC in the distribution of the trigeminal nerve.
2. Segmental/ Unilateral.
3. Mucosal: Mucous membranes alone are affected.
II. GENERALIZED VITILIGO “3”
• Generalized vitiligo implies more than one general area of involvement.
Macules are usually found on both sides of the trunk, either symmetrically
or asymmetrically arrayed. It represents 90% of vitiligo patients.
1. Acrofacial: distal extremities and face (periorificial areas).
2. Vulgaris: scattered patches that are widely distributed.
3. Mixed: Acrofacial and vulgaris vitiligo occur in combination, or segmental
and acrofacial vitiligo and/or vulgaris involvement are noted in
combination.
III. UNIVERSAL VITILIGO
• This is complete or nearly complete depigmentation. It is often associated with
multiple endocrinopathy syndrome.

Two distinct forms of vitiligo
SEGMENTAL:
• This type manifests as one or more macules in a dermatomal or quasidermatomal pattern.
• Onset early in life. occurs more commonly seen in children than adults (~30% versus ~10%).
• More than ½ the patients with segmental vitiligo have patches of white hair or poliosis.
• This type of vitiligo is not associated with thyroid or other autoimmune disorders.
• Lesions usually stop abruptly at midline doesn't cross it. rapidly spreads in affected area.
• The course of segmental vitiligo can arrest, & depigmented patches can persist unchanged
for the life of the patient (Stable).
NON-SEGMENTAL:
• This type includes all types of vitiligo, except segmental vitiligo.
• It is strongly associated with autoimmunity or inflammation such as halo naevi and
thyroid antibodies more than segmental vitiligo.
• Patients with non-segmental vitiligo were also more likely to have a family history of
vitiligo or autoimmunity.

Autoimmune diseases associated
with vitiligo
1. Thyroid disorders, most common &
usually occur after the onset of vitiligo.
Mainly in non-segmental vitiligo:
a. Hashimoto thyroiditis
b. Graves disease
2. Other endocrinopathies, such as
a. Addison disease
b. diabetes mellitus;
c. Autoimmune Polyglandular Syndrome
/ APECED (autoimmune
polyendocrinopathy–candidiasis–
ectodermal dystrophy) syndrome. In this
genetic, autoAb cause destruction of
endocrine cells.
3. Pernicious anemia;
4. Rheumatoid arthritis,
5. Inflammatory Bowel
Disease (IBD)
Dermatological disorders:
6. Halo nevus
7. Alopecia areata (AA)
8. Lupus erythematosus,
9. Psoriasis;
10. lichen sclerosus

• Unpredictable.
• It becomes more extensive by the appearance of new depigmented
macules, enlargement of pre-existing lesions, or both processes.
• The natural course of the disease is usually one of slow progression, but
it may stabilize for a long period of time or spread rapidly.
• Total body involvement that develops within a few weeks or even a few
days may occur.
• Some degree of
sun-induced or
spontaneous
repigmentation is
not uncommon in
vitiligo, but complete and stable spontaneous repigmentation is rare.

Investigations
• Diagnosis of vitiligo generally is made on the basis
of clinical findings.
• Vitiligo is diagnosed by means of inspection with a
Wood’s lamp.

Investigations
• If signs or symptoms of associated autoimmune diseases
occur, appropriate tests should be performed e.g.
1. Thyrotropin testing is the most cost-effective screening test
for thyroid disease.
2. Serum antithyroglobulin
3. Antithyroid peroxidase antibodies (Anti TPO) which
regarded as a sensitive and specific marker of autoimmune
thyroid antibodies.
4. Antinuclear antibody (ANA) screening is also helpful.
5. CBC with indices helps rule out anemia.
6. Fasting blood glucose (FBG) : for Screening for diabetes.
7. Glycosylated hemoglobin (HbA1c)

Vitiligo, 10x, stained for
melanin. Note that melanin
(tiny, dark spots) is absent on
the basal layer of the epidermis
although it is preserved around
the hair follicle.

Histopathology
• Biopsy is occasionally helpful for differentiating vitiligo from other
hypopigmentary disorders.
• Complete absence of melanocytes in association with a total loss of
epidermal pigmentation.
• Superficial perivascular and perifollicular lymphocytic infiltrates
may be observed at the margin of vitiliginous lesions, consistent with a
cell-mediated process destroying melanocytes.
• Degenerative changes have been documented in keratinocytes &
melanocytes in border lesions & adjacent skin.
• Other documented changes include increased numbers of
Langerhans cells, epidermal vacuolization, and thickening of the
basement membrane.
• Loss of pigment and melanocytes in the epidermis is highlighted by
Fontana-Masson staining and immunohistochemistry testing.

Treatment
• THE AIMS OF VITILIGO TREATMENT ARE;
1. Repigmentation.
2. Stabilization of the depigmentation process.
3. To prevent complications.
• No single therapy for vitiligo produces predictably good results in
all patients; the response to therapy is highly variable so treatment
must be individualized, and patients should be made aware of the
risks associated with therapy. The choice of therapy depends on
the extent, location, and activity of disease as well as the patient’s
age, skin type, and motivation to undergo treatment.
• Combination therapy may produce higher rates of
repigmentation compared to traditional monotherapies.

Treatment
• Period of at least 2–3 months is required to
determine whether a particular treatment is
effective.
• The areas of the body that typically have the
best response to medical therapy are the face,
neck, mid extremities and trunk, while the
distal extremities and lips are the most
resistant to treatment consider camouflage.
• Sunscreens (sun protection factor of 15 or higher is best) should be given to
all patients with vitiligo to minimize risk of sunburn or repeated solar damage to
depigmented skin.
• Tanning of surrounding normal skin exaggerates appearance of vitiligo this
is prevented by sun protection.

Treatment
• During medical therapy, pigment cells arise and
proliferate from the following 3 sources:
1. The pilosebaceous unit, which provides the
highest number of cells, migrating from the
ORS toward the epidermis (vertical migration)
When the hairs within an area of vitiligo are
depigmented, this pattern is not observed.
2. Spared epidermal melanocytes not affected
during depigmentation
3. The border of lesions, migrating up to 2-4
mm from the edge (horizontal migration)

Treatment
1. Phototherapy
2. Laser therapy
3. Corticosteroids
4. Topical calcineurin inhibitors (TCIs)
5. Vitamin D analogs
6. Depigmentation therapy
7. Surgical therapies
8. Micropigmentation
9. Pseudocatalase with narrowband UVB
10. Systemic antioxidant therapy
11. Dermabrasion followed by topical 5-fluorouracil and NB-UVB
12. Topical prostaglandins

1. Narrow-band UV-B phototherapy (NB-UVB).
2. Focused microphototherapy.
3. Psoralen photochemotherapy (PUVA).
4. Khellin plus UVA (KUVA).

1. NARROW-BAND UV-B
PHOTOTHERAPY (NB-UVB):
• Is widely used and produces good clinical results &
considered first choice of therapy for adults and children
with generalized vitiligo especially if it involves ≥20% of
the body surface area.
• Narrow-band fluorescent tubes with an emission spectrum
of 310-313 nm & a maximum wavelength of 311 nm.
• Initial assessment of the MED in a vitiliginous area that is
normally not sunexposed (e.g. buttocks, lower back or
abdomen) is recommended. Since intense erythema may
induce the Koebner phenomenon and worsening of the
disease.

NARROW-BAND UV-B PHOTOTHERAPY (NB-UVB):
• The UVB doses have to be  more carefully than in other disorders, because
of the  photosensitivity.
• The initial exposure is 70% of the MED in lesional skin, and subsequent
doses are chosen according to the response in vitiligo areas, i.e. the goal is to
induce a barely perceptible erythema. This minimal erythema is the only
useful parameter for determining dosage increments. The starting dose
ranges from 100 to 250 mJ/cm2, which is  in increments of 10–20% at
each subsequent exposure. The objective of the dose increments is to
achieve a minimally perceptible erythema within the lesions.
• Treatment frequency is 2-3 times weekly, but never on consecutive days
for sufficiently long period.
• Effective as monotherapy without the addition of exogenous
photosensitizers
• It is as effective as PUVA but had fewer side effects.

SHORT-TERM ADVERSE EFFECTS OF
NB-UVB
i) Intense Erythema
ii) Pruritus
iii) Xerosis
iv) Occasional Blistering
v)  frequency of recurrent HSV.
LONG-TERM SIDE EFFECTS OF NB-UVB
i) Photoaging
ii) Cutaneous carcinogenesis (carcinogenic
potential seems to be lower than that of
PUVA).

THE ADVANTAGES OF NARROW-BAND UV-B OVER
PUVA INCLUDE:
1. Shorter treatment times
2. No drug costs
3. No adverse GI effects (e.g. nausea)
4.  phototoxic reactions
5. No need for subsequent photoprotection.
6. Can be safely used in children, pregnant or lactating ♀,
individuals with hepatic or kidney dysfunction.
7. Produces less accentuation of the contrast between
depigmented and normally pigmented skin.

2. FOCUSED MICROPHOTOTHERAPY:
• Targeting only the specific small
lesions.
• A directed beam of broadband
or narrowband UVB is used
with a fiber optic system to direct
radiation to specific areas of skin.

3. PSORALEN PHOTOCHEMOTHERAPY (PUVA):
• Involves the use of photosensitizers
psoralens combined with UV-A light.
THE PSORALENS COMMONLY USED:
a. 8-methoxypsoralen (8-MOP,
methoxsalen) most commonly used.
b. 5-methoxypsoralen (5-MOP),
c. Trimethylpsoralen (TMP/
Trioxsalen).

• The best results from PUVA can be obtained on the face, trunk, and
proximal parts of the extremities.
• 2-3 treatments per week for many months or even years to achieve a
satisfactory result before repigmentation from perifollicular openings
merges to produce confluent repigmentation.
• If treatment is discontinued, reversal of acquired repigmentation may
occur unless the lesion has completely repigmented. Completely
repigmented areas can be stable for a decade or more without relapse
• The total number of PUVA treatments required is 50-300.
• Recommend that vitiligo patients receive a maximum cumulative UVA
dose of 1000 J/cm2 and a maximum number of 300 treatments.
• If there is no response after 4–5 months or approximately 30–40
treatments, PUVA should be terminated.

TOPICAL PUVA:
• Cream and solution of 8-
methoxypsoralen (0.1-0.3%
concentration).
• It is applied 30 minutes prior to UV-A
radiation (usually 0.1-0.3 J/cm2 UV-A)
exposure. It should be applied once or
twice a week.
• TMP and 5MOP can also be used for
topical PUVA but are more phototoxic
than 8MOP.

SYSTEMIC PUVA:
a) 8-MOP: 0.4–0.6 mg/kg. the initial dose of UVA is usually 0.5–1.0
J/cm2, which is gradually  until minimal asymptomatic erythema
of the involved skin occurs. To  the risk of the Koebner
phenomenon, significant erythema (phototoxicity) is avoided.
Inhibits mitosis by covalently binding to pyrimidine bases in DNA
when photoactivated by UV-A.
b) 5-MOP: has about the same response rate as 8-MOP in
repigmenting vitiligo, but a lower incidence of adverse effects,
including reduced phototoxicity as well as less nausea and vomiting.
c) TMP: Because of weaker phototoxicity, it is preferred to 8MOP
for treatment with sunlight as the radiation source.

SIDE EFFECTS OF PUVA:
1. PUVA-induced cutaneous carcinomas.
2. High risk of phototoxicity (e.g.
blistering, koebnerization) from topical
psoralen formulations.
3. Treatments stimulate the pigmentation of
normal skin, which will intensify the
contrast between normal and vitiliginous
skin. (Application of sunscreen to the
surrounding uninvolved skin prior to
application of the topical psoralen can
reduce hyperpigmented rims).

4. KHELLIN PLUS UVA (KUVA):
• Oral khellin as the photosensitizer [at a dose of 100 mg 2
hours before treatment] plus UVA or
• Topical khellin [4-5% ointment] plus UVA
ADVANTAGES:
a) Relatively low risk of phototoxicity.
b) Safe for home treatment or treatment with natural
sunlight.
c) lower mutagenic activity than psoralens.
DISADVANTAGES:
a) It requires a longer duration of treatment than oral
PUVA or monochromatic excimer light (MEL) 308 nm.
b) It requires a higher UVA doses than oral PUVA or
monochromatic excimer light (MEL) 308 nm.
c) Hepatic toxicity.

EXCIMER LASER
• It produces monochromatic rays at 308 nm close to that of NB-UVB to treat limited (<30%
BSA), localized stable patches of vitiligo.
• Twice weekly for an average of 24-48 sessions with the repigmentation rate depending on total
number of sessions, not frequency.
ADVANTAGES:
1. Efficacious,
2. Safe
3. Well-tolerated
DISADVANTAGES:
1. Expensive.
2. Erythema
3. (Rarely) blistering.
• Combination treatment with 0.1% tacrolimus ointment plus the 308-nm excimer laser is
superior to 308-nm excimer laser monotherapy for the treatment of UV-resistant cases.
• Segmental vitiligo has a better repigmentation response with excimer laser treatment used at earlier
stages of the disease.
Laser therapy

Corticosteroids
A. SYSTEMIC CORTICOSTEROIDS
B. TOPICAL CORTICOSTEROIDS
C. INTRALESIONAL CORTICOSTEROIDS

Corticosteroids
A. SYSTEMIC STEROIDS:
• Side-effects associated with long-term use of daily systemic
corticosteroids contraindicate their common use.
• Prednisone has been used esp. to arrest rapidly progressive
vitiligo, without inducing repigmentation.
• Steroids have been reported anecdotally to achieve success
when given in:
a. Oral mini-pulsed (OMP) therapy (2.5-5 mg of
dexamethasone on two consecutive days per week).
b. High-dose pulsed therapy
c. Low daily oral dose

Corticosteroids
B. TOPICAL STEROIDS:
• Is often chosen first to treat localized vitiligo because it is easy and
convenient for both doctors and patients to maintain the treatment.
• The results of therapy have been reported as moderately successful,
with either class 1 (superpotent) or class 2–3 (high-potency)
particularly in patients with localized vitiligo and/or an
inflammatory component to their vitiligo, even if the inflammation
is subclinical.
• To minimize side effects, class 1 corticosteroids can be used as
follow:
 In 6–8-week cycles.
 On a twice-weekly basis.
 Alternating with topical tacrolimus.
 Alternating with a less potent topical corticosteroid.

Corticosteroids
• Treatment should be discontinued if there’s no visible
improvement after 2 m.
• In addition, these agents modify the body's immune
response to diverse stimuli.
• These drugs’re used to stop spread of vitiligo &
accomplish repigmentation.
EXAMPLES FOR TOPICAL STEROID AGENTS:
1. Hydrocortisone topical: An adrenocorticosteroid
derivative suitable for application to skin or external
mucous membranes. Has mineralocorticoid and
glucocorticoid effects.
2. Triamcinolone topical: medium potency
topical steroid.
3. Clobetasol Propionate: Class I superpotent topical steroid.

Corticosteroids
C. INTRALESIONAL CORTICOSTEROIDS:
• Should be avoided because of the pain associated
with injection and the risk of cutaneous atrophy
that occurs in approximately one-third of vitiligo
patients.

Topical calcineurin inhibitors
(TCIs)
• Effective alternative therapy for vitiligo, particularly when the
disease involves the head and neck.
• Act as Immunomodulators that suppress the activity of the
immune system.
• Drugs of this class are more expensive than topical corticosteroids
• Combination treatment:  Better results superior to
monotherapy suggesting a synergistic effect
1. Sun exposure.
2. 308-nm excimer laser
3. Narrow-band UV-B
4. Corticosteroids
5. Microdermabrasion

Topical calcineurin
inhibitors (TCIs)
AGENTS:
1. Tacrolimus (0.03-0.1%
ointment)
Can be used in patients as young as 2
years old.
Applied twice daily.
2. Pimecrolimus (1% cream)
Originally approved for AD.
More Expensive than tacrolimus.

Vitamin D analogs
• Originally approved for psoriasis.
• They target the local immune response and act on specific T-cell
activation. They do this by inhibition of the transition of
T cells (early to late G1 phase) and inhibition of the expression
of various proinflammatory cytokines that encode TNFα and
IFγ.
• These vitamin D3 compounds influence melanocyte
maturation and differentiation, in addition to up-regulating
melanogenesis through pathways that are activated by specific
ligand receptors (eg, endothelin receptor and c-kit).
• The combination of topical calcipotriene and narrow-band
UV-B or PUVA results in improvement appreciably better than
that achieved with monotherapy.

Vitamin D analogs
AGENTS:
1. Calcipotriene (calcipotriol) 0.005%
Synthetic vitamin D-3 analog that
regulates skin cell production and
development.
Has immunosuppressive effects on
lymphoid cells.
2. Tacalcitol
 excessive skin cell turnover.

• In widespread & progressive vitiligo (BSA > 50%)
with only a few areas of normally pigmented skin
in exposed sites & repigmentation do not produce
satisfactory results.
• The patients must be carefully chosen, i.e. adults who
recognize that their appearance will be altered
significantly and who understand that procedure
generally results in permanent depigmentation &
requires lifelong strict photoprotection (e.g.
sunscreens, clothing, umbrellas).
• Depigmentation may be chemical or physical.
•
Depigmentation therapy

CHEMICAL DEPIGMENTATION:
1. Monobenzyl ether of hydroquinone
(MBEH) (20%), the only FDA approved
for depigmentation. The MC used agent is
applied once to twice daily to the affected
areas for 9–12 months or longer.
2. Monomethyl ether of hydroquinone
(20%)
cream can be used as an
alternative to MBEH.
S.E. include contact dermatitis,
exogenous ochronosis and
leukomelanoderma en confetti.

PHYSICAL DEPIGMENTATION:
1. Q-switched lasers:
Q-switched ruby laser therapy was
reported to achieve faster
depigmentation than that achieved
with a bleaching agent, and this laser
has also been used in combination
with topical 4-methoxyphenol to
induce depigmentation. Q-switched
alexandrite laser has also been described
2. Cryotherapy.

Surgical therapies
• Autologous transplantation.
• Surgical treatment for vitiligo can be considered in two
main categories:
A. Grafting of melanocyte-rich tissue (tissue grafting)
B. Grafting of melanocyte cells (cellular grafting).
• Limited to stable vitiligo.
• Segmental vitiligo has been shown as the most stable
form, responding well to surgical interventions.

Surgical therapies
SELECTION CRITERIA: “6”
1. Stable disease for at least 6-12 months (Spontaneous
repigmentation indicates vitiligo inactivity)
2. Unsatisfactory response to medical therapy
3. Absence of the Koebner phenomenon
4. A positive minigrafting test (retention/spread of pigment at
the recipient site and no koebnerization at the donor site after 2–
3 months), disclosing repigmentation at 4-5 minigrafts, which, to
date, is the most accurate evidence of vitiligo stability
5. No tendency for scar or keloid formation,
6. Age > 12 years

Surgical therapies
• Uppermost layer of affected skin is usually removed
under local anaesthesia in an outpatient setting.
Techniques to remove the skin include:
1. Cryotherapy
2. Dermabrasion
3. Shave biopsy
4. Punch biopsy
5. Laser therapy

Surgical therapies
BASIC METHODS FOR REPIGMENTATION
SURGERY HAVE BEEN DESCRIBED, AS FOLLOWS:
“6”
1. Punch Minigrafting
2. Noncultured epidermal cell suspensions
3. Thin dermoepidermal grafts
4. Suction epidermal grafting
5. Cultured epidermis with melanocytes or cultured
melanocyte suspensions
6. Grafting of individual hairs

Surgical therapies
1. Punch Minigrafting: the simplest
technique. Small Punch donor grafts
(1–2 mm) are inserted into the incision
of recipient sites separated from each
other by 5–8 mm and held in place by
a pressure dressing. The graft heals
readily and begins to show
repigmentation within 4-6 weeks.
The cosmetic result is excellent.

Surgical therapies
POTENTIAL IMMEDIATE COMPLICATIONS OF MINIATURE
PUNCH GRAFTING:
1. Loss of graft tissue
2. Infection
MID- TO LONG-TERM
COMPLICATIONS:
1. Persistent vitiligo
2. Hyperpigmentation
3. Colour matching
4. Graft rejection
5. Peripheral depigmentation (halo effect)
6. Keloid and hypertrophic scar at the donor or graft site (cosmetically
insensitive areas are chosen).
7. Cobblestone appearance (more common with larger punch biopsies)

Surgical therapies
2. Noncultured epidermal cell suspensions:
• After the achromic epidermis is removed, an
epidermal suspension with melanocytes and
keratinocytes previously prepared by
trypsinization of normally pigmented donor
skin is spread onto the denuded area and
immediately covered with nonadherent dressings.
• Using noncultured epidermal cellular grafts,
especially in segmental vitiligo, piebaldism, and
halo nevi.
• Color mismatches were common, and
generalized vitiligo did not repigment quite as
well.

Surgical therapies
3. Thin dermoepidermal grafts:
• The depigmented epidermis is
removed by superficial
dermabrasion, including the
papillary dermis, and very thin
dermoepidermal sheets harvested
with dermatome (skin graft knife)
are grafted onto the denuded skin.

Surgical therapies
4. Suction epidermal grafting:
• Epidermal grafts can be obtained by vacuum
suction, usually with -150 mm Hg.
• The recipient site can be prepared by suction,
freezing, or dermabrasion of the sites 24 hours
before grafting.
• The depigmented blister roof is discarded, and the
epidermal donor graft is placed on the vitiliginous
areas.
• Advantages of suction blister epidermal grafting are
the absence of scarring at the donor site and the
possibility of reusing this area. However, failure of
the graft to take and koebnerization may occur.

Surgical therapies
5. Cultured epidermis with melanocytes or cultured melanocyte
suspensions:
• Depigmented skin is removed using liquid nitrogen, superficial
dermabrasion, thermosurgery, or CO2 lasers.
• Very thin sheets of cultured epidermis are grafted or suspensions are
spread onto the denuded surface.
• Grafting of cultured autologous melanocytes
is an expensive technique that requires
specialized laboratory expertise; grafts
consist of pure melanocytes or
melanocytes admixed with keratinocytes.
• Involves mitogens to enhance cell growth.

Surgical therapies
6. Grafting of individual hairs

Micropigmentation
• Permanent dermal Micropigmentation to camouflage recalcitrant
areas of vitiligo.
• Tattooing can be used to repigment depigmented skin in dark-skinned
individuals.
• Non-allergenic iron oxide pigment / dihydroxyacetone preparations.
• In areas with poor rate of repigmentation e.g. the lips, nipples and
distal fingers.
• The color may not match perfectly with the normal surrounding
skin.
• The result is immediate and can represent a dramatic aesthetic
improvement.
• The color may fade slightly over a period of years.

Pseudocatalase with
narrowband UVB
• The rationale for this treatment is based on
the hypothesis that accumulation of
hydrogen peroxide leads to pathogenic
inactivation of catalase (Its functions include
catalyzing the decomposition of H2O2 to
H2Oand O2) in the skin of patients with
vitiligo.
• Topical pseudocatalase and calcium twice
daily plus UVB twice weekly, with may
induce repigmentation at 2–4 months.

Systemic antioxidant therapy
• The rationale for this approach rests on the hypothesis
that vitiligo results from a deficiency of natural
antioxidant mechanisms.
EXAMPLES:
1. Selenium
2. Methionine
3. Tocopherols (Vit. E)
4. Ascorbic acid (Vit. C)
5. Ubiquinone (Coenzyme Q)

Dermabrasion followed by
topical 5-FU & NB-UVB
• Erbium: YAG laser ablation of vitiligo lesions followed
by topical application of 5-fluorouracil and NB-UVB
therapy twice weekly for 4 months.

Topical prostaglandins
• Prostaglandin E2
• Prostaglandin analogues
eg. Latanoprost

Guidelines for the Management of Vitiligo
The European Dermatology Forum Consensus

References
• Dr. Angelo Smith M.D WHPL
• Mohammad Jafferany Ajyad general hospital Makkah.
• Bolognia 3rd ed.
• http://www.edoj.org
• http://www.e-ijd.org
• http://www.medscape.com

Disorders of hypoigmentation

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