Chapter 36

Disturbances of
Pigmentation
JoAnne M. LaRow. D.O.

Melanin

= primary pigment producing brown

coloration
Tyrosine tyrosinase melanin- this occurs in
the melanosomes of melanocytes
Then the melanosomes are transferred from
the melanocyte to a group of keratinocytes
called the epidermal melanin unit
Variations in skin color is related to the
number of melanosomes, the degree of
melanization, and the distribution of the
epidermal melanin unit

Pigmentary Demarcation
Lines
Can be divided into five categories:

Group A- lines along the outer upper arms with

variable extension across the chest
Group B-lines along the posteromedial aspect
of the lower limb
Group C-Paired median or paramedian lines on
the chest, with midline abdominal extension
Group D-medial, over the spine
Group E-bilaterally symmetrical, obliquely
oriented, hypopigmented macules on the chest

Pigmentary Demarcation
Lines
More

than 70% of blacks have one

or more lines
These are much less common in
whites
Type B lines often appear for the
first time during pregnancy

Normal Pigmentation
Normal

skin pigmentation is
influenced by:
-the degree of vascularity
-the amount & location of melanin
-the presence of carotene
-the thickness of the horny layer

Melanin Production

The amount produced is dependent on:

-genetics
-the amount and the wavelengths of
ultraviolet light received
-the amount of melanocyte-stimulating
hormone(MSH) secreted
- the effect of melanoccytestimulatingg
chemicals like furocoumarins (psoralens)

Hemosiderin
Hyperpigmnetation
Pigmentation due to deposits of
hemosiderin occurs in:
-purpura
-hemochromatosis
-hemorrhagic diseases
-stasis ulcers
** difficult to distinguish from
postinflammatory dermal melanosis
clinically

Postinflammatory
Hyperpigmentation
Any inflammatory condition can cause either
hypopigmentation or hyperpigmentation
Also may be a complication of chemical
peels, dermabrasion, laser therapy, or
liposuction
Histologically, there is melanin in the upper
dermis and around upper dermal vessels,
located primarily in macrophages
(melanophages)

Postinflammatory
hyperpigmenation

Postinflammatory
hyperpigmentatio
n following
resolution of
lymphocytoma
cutis on the cheek
of a black child

Industrial
Hyperpigmentation
Occurs

in coal miners, anthracene

workers, pitch workers, etc
Pigmentation of the face may occur
from the incorporation in
cosmetics of derivatives of coal tar,
petrolatum, or picric acid, mercury,
lead, bismuth, or furocoumarins
(psoralens)

Systemic Diseases

Syphilis, malaria, pellagra, and diabetes

Addisons disease- diffuse melanosis
pronounced in the axillae and palmar
creases, and nipples and genitals, and
buccal mucosa
Diabetes produces diffuse bronzing of
the skin
** patients with virilizing adrenal tumors
usually develop hyperpigmentation and
hypertrichosis

Systemic Diseases

Nelsons syndrome (a
pituitary MSHproducing tumor)
Pheochromocytoma
Hemochromatosis
Amyloidosis
Scurvy
Pregnancy
Menopause
Porphyria cutanea
tarda

Vitamin B12
deficiency
Kwashiorkor
Vitamin A
deficiency
Primary biliary
cirrhosis (triad=
hyperpigmentation,
pruritis, xanthomas)

Hemochromatosis
Characterized by:
Gray-brown
mucocutaneous
hyperpigmentatio
n
Diabetes mellitus
hepatomegaly

Usually are present:

Cirrhoisis
Hypogonadism
Liver cirrhosis

Hemochromatosis

Skin pigmentaion is
usually generalized
But, more pronounced on
face, extensor aspect of
the forearms, backs of
the hands, and the
geniocrural area
Iron is deposited in the
skin
Iron is present as
granules around blood
vessels and sweat glands
and within macrophages

The actual
pigmentation is
caused by increased
basal-layer melanin
Mucous memebranes
are pigmented in up to
20% of patients
Koilonychia is present
in 50%
Localized ichthyosis in
40%
Alopecia is common

Hemochromatosi Dx:
Elevated plasma iron and IBP
s Occurs mostly in men in
High serum ferritin without

their sixties
Women who have genetic
hemochromatosis can have
full phenotypic expression
Extremely rare in the young
Neonatal hemochromatosis
has been associated with
intrauterine infections ie
cytomegalovirus
Adults with
hemochromatosis are
susceptible to Yersinia
enterocolitica

an obvious cause should

prompt investigation for both
hemochromatosis and PCT
Etiology is either an inborn
error of metabolism or
excessive number of blood
transfusions
AR gene for heredity
hemochromatosis is linked to
the HLA-A locus on
chromosome 6p

Hemochromatosis-tx

Phlebotomy until
satisfactory iron levels
are found
Extracorporeal
chelation has also
been used successfully
Associated DM
requires medical tx
Long-term
complications are
cirrhosis and then
hepatomas

Melasma

Brown patches, sharply

demarcated, typically
on the malar
prominences and
forehead
The three clinical
patterns are:
centrofacial, malar,
mandibular
Increased pigment may
simultaneously occur
around the nipples and
external genitalia

Tends to affect the

darker-complected
It may also be found on
the forearms
Occurs at pregnancy and
at menopause
It may also be seen in
ovarian disorders and
other endocrine disorders
Most frequently 90% of
the time seen in women,
10% in men

Melasma

Strong association with

the use of birth control
pills or dilantin
Discontinuing the
contraceptives rarely
clears the
pigmentation, and it
may last for years after
discontinuing them.
Melasma of pregnancy
usually clears within a
few months of delivery

Tx- avoid sunlight, and a

complete sun block with
broad-spectrum UVA coverage
should be used daily
Kligmans formula (Triluma)
> then 4% hydroquinone may
be needed
Side effects of this is
ochronosis and satellite
pigmentation
Jessners solution, glycolic
acid peels,azelaic acid, kojic
acid, and cystamine and
buthionine sulfoximine are
other options

Melasma

Melasma

Melasma

Acromelanosis Progressiva

AKA acropigmentation
A progressive
pigmentary disorder first
described in a Japanese
infant
Characterized by diffuse
black pigmentation on
the dorsum of all the
fingers and toes
Pigmentation became
progressively more
widespread and more
pigmented

By age 4 or 5 the
perineum,
extremities, and
areas of the head
and neck were
involved
Epileptiform
seizures occurred
History revealed
consanguinity

Pigmented Anomalies of
the Extremities

Acropigmentation of
Dohi
Found to affect
individuals from Europe,
India, Caribbean
First described in Japan
in 12 patients
AKA dyschromatosis
symmetrica hereditaria
or symmetrical
dyschromatosis of the
extremities

Patients develop
progressive
pigmented &
depigmented macules
Often mixed in is a
reticulate pattern
Many believe this to
be a variation of
acropigmentation of
Kitamura

Reticular Pigmented
Clinically it looks smooth
Pigmententation is
Anomaly of the Flexures
reticular; at the periphery,

A rare pigmentary
adult-onset disorder
AKA Dowling-Degos
disease or dark dot
disease
Should be considered
whenever acanthosis
nigricans is in the
differential & pt is not
obese and is known
not to have any
internal malignancy

discrete, brownish black

macules surround the
partly confluent central
pigmented area
Typically, axillae,
inframmary folds, and
intercrural folds are
involved
There are frequently pits,
sometimes pigmented ,
about the mouth

Reticular Pigmented
Anomaly of the Flexures

It begins age 20
to 30 yrs and
progresses
gradually
Unknown etiology
AD with variable
penetrance and
expressivity, and
delayed onset

Many authors believe

it is a spectrum of
reticulate
acropigmentation of
Kitamura
Another manifestation
of this disorder is
familial-rocacea-like
dermatitis with warty
keratotic plaques on
the trunk and limbs
There is no treatment

Histology

Distinctive
elongation, tufting,
and deep
hyperpigmentation
of therete ridges,
with protrusion of
similar tufts even
from the sides of
the follicles

Reticulate
Acropigmentation of
One report of a pt
AD
Kitamura
with bony

Characterized by
linear palmar pits
and pigmented
macules 1-4 mm
in diameter on the
volar and dorsal
aspects of the
hands and feet

abnormalities
consisting of absence
of terminal phalanges
of the second, third,
and fourth toes
Some tx success has
been reported using
axelaic acid ointment

Dermatopathia
Pigmentosa Reticularis

Consists of a triad of
generalized reticulate
hyperpigmentation,
noncicatricial alopecia,
and onychodystrophy
Other associations:
adermatoglyphia,
hypohidrosis or
hyperhidrosis,
palmoplantar
hyperkeratosis, and
nonscarring blisters on
dorsa of hands and feet.

An autosomal
dominant
inheritance
pattern has been
reported.

Dermatopathia
Pigmentosa Reticularis

Transient Neonatal
Histologically, there are
Pustular Melanosis
intracorneal or

Infants develop 23mm macules,

pustules, and
ruptured pustules
at birth,
predominantly
involving the face
Pigmentation may
last for weeks or
months after the
pustules are healed

subcorneal aggregates of
predominantly
neutrophils, but
eosinophils may also be
found
Dermal inflammation is
composed of an
admixture of neuts and
eos
Differential dx: ETN,
neonatal acne, &
acropustulosis of infancy

Transient Pustular
Neonatal Melanosis

Transient Neonatal
Pustular Melanosis

Peutz-Jeghers

Characterized by
hyperpigmented macules
on the lips and oral
mucosa and polyposis of
the small intestine
Dark brown or black
macules appear typically
on the lips, especially the
lower lip, in infancy or
childhood
Similar lesions may
appear on buccal
mucosa, tongue, gingiva,
and genital mucosa

Macules may also occur around

the mouth, on the central face,
backs of the hands, especially
the fingers, and on the toes
and tops of the feet.
Associated polyposis involves
the small intestine preferencely
But, hamartomatous polyps of
the stomach and colon may
occur
Symptoms of hamhartomas of
the small intestine may cause
repeated bouts of abdominal
pain and vomiting, and
intussusception

Peutz-Jeghers Syndrome

Cosmetic tx of labial
macules has been
accomplished with the
use of a 694-mm ruby
laser
incidence of malignancy
within the polyps is 2-3%
Incidence of GI
malignancy is low, but
increased incidence of
other kinds of cancerbreast, and gynecologic
malignancies in women

Syndrome is inherited
and transmitted as a
simple mendelian
dominant trait
Sporadic noninherited
cases may occur
The gene (STK11) has
been localized to
19p13.3
19p13.3 is believed to
be a tumor suppressor
gene

Peutz-Jeghers
Cronkhite-Canada
syndrome should be
Syndrome
considered in dx

Characterized by melanotic
macules on the fingers and
gastrointestinal polyposis
Also generalized , uniform
darkening of the skin,
extensive alopecia, and
onychodystrophy
The polys that occur are
usually benign adenomas
and may involve the whole
GI tract

A protein-losing
enteropathy may develop
and is associated with the
degree of intestinal
polyposis
Onset is after age 30 yrs
Sporaically occurring,
benign condition
Hypogeusia is the
dominant initial symptom
Diarrhea and ectodermal
changes may follow
75% of cases have been
reported in Japan

Peutz-Jeghers syndrome

Lip lentigenes in
an adolescent
with PeutzJeghers syndrome

P-J syndrome

Pathology

Reihls Melanosis

Photosensitivity,
phototoxic dermatitis
Begins with pruritis,
erythema, and
pigmentation,
gradually spreads,
then becomes
stationary
Melanosis occurs
mostly in women and
develops over months

Characteristic feature
is spotty light to dark
brown pigmentation
Most intense on the
forehead, malar
regions, behind the
ears, on the sides of
the neck, on other
sun-exposed areas
Also circumscribed
telangiectasia and
temporary hyperemia

pathogenesis

Sun exposure
following perfume
or cream
A photocontact
dermatitis
One report of a
positive patch test
results to lemon
oil, geraniol, and
hydroxycitronellal

Has been reported in

patients with AIDS and
Sjogrens syndrome
No good treatments
The cause of the
sensitivity needs to be
determeined
Hyperkeratosis and
pigmentation
disappear
spontaneously

Tar Melanosis

An occupational
dermatosis occurring
among tar handlers
after years of exposure
Severe, widespread
itching develops,
followed by reticular
pigmentation,
telangiectases, and a
shiny appearance of the
skin
There is a tendency for
hyperhidrosis

Small, dark, lichenoid,

follicular papules
become profuse on
the extremities,
namely the forearms
Bullae are sometimes
observed
Represents a
photosensitivity or
phototoxicity induced
by tar

Familial
Characterized by patches
Progressive
of hyperpigmentation,
present at birth,
Hyperpigmentatio
increasing in size and
number with age
n Hyperpigmentation
appears in the

conjunctivae and the

buccal mucosa over time
Eventually large portions
of skin and mucous
membranes become
involved

AD inheritance
Histologically- increase in
melanin in the basal cell
layer, especially at the tips
of the rete ridges
Pigmented granules are
scattered diffusely
throughout the epidermal
layers
Differentiated from other
hyperpigmentations by
presence of bizarre, sharply
marginated patterns of
hyperpigmented skin

Universal Acquired
Melanosis(Carbon Baby)

Ruiz-Maldonado
reported a case of a
Mexican child, born
white, who
progressively
became black
Developed
pigmentation of the
palms, soles,
mucous
membranes

EM showed a
negroid pattern in
the melanosomes
of the epidermal
melanocytes and
keratinocytes
Melanocytes were
not increased in
number

Zebralike
Hyperpigmentation

Alimurung et al
reported an unusual
pattern of
hyperpigmentation in
a black male infant
with congenital
defects (ASD,
dextrocardia,
auricualr atresia,
deafness. And
growth retardation)

Hyperpigmenation was
linear and symmetrical,
involving the trunk and
extremities
Increased number of
melanocytes in the
bands of
hyperpigmentation
Pigmentary anomaly
fades with time
spontaneously
May be a varient of
incontinentia pigmenti

Periorbital
Hyperpigmentation
1.) Familial
periorbital
melanosis (AD)
Usually involves
all four eyelids,
may extend to
involve the
eyebrows and
cheeks

2.) Erythema
dyschromicum
perstans is a rare
cause
3.) Familial dark
circles around the
eyes, frequently
seen in individuals
of Mediterranean
ancestry

Metallic Discolorations
Pigmentation

from deposition of
fine metallic particles in the skin
Metal may be carried to skin from
the blood stream or may permeate
into it from surface applications

Argyria

Localized or widespread
slate-colored
pigmentation
Due to silver in the skin
Most noticeable in parts
exposed to sunlight
Tissue silver may
stimulate melanocytes
Initially discoloration is
hardly perceptible,
having only a faint blue
color, but a slate-gray
color develops with time

Local tx with a silvercontaining product may

produce argyria
Examples: conjunctivae, from
eye drops; a wound from
sulfadiazine cream, earlobes
from silver earings; and from
silver acupuncture needles
Can also occur from
occupational exposure, usually
siversmiths
In localized exposures, the
appearance may be separated
by many years from the
exposure

Histology
Systemic and localized argria have the
same features
Normal appearing skin under low power
Fine black granules in the basement zone
of the sweat glands,blood vessel walls, de junction, and arrector pili muscles
Unstained biopsy section by darkfield
illumination demonstrates silver granules
outlining basement membrane of the
epidermis and the eccrine sweat glands

Bismuth

Rarely associated with deposition of metallic

particles in gums when used IM or orally
Also known as the bismuth line
Presence of stomatitis or peridontitis
increased the risk
Generalized cutaneous discoloration, in
addition to oral mucous membrane and
conjunctival pigmentation resembling
argyria has occurred but has not be
reported in the last 50 years

Lead
Chronic

lead poisoning can

produce a lead hue with lividity
and pallor
Deposit of lead in the gums may
occur and is known as the lead
line

Iron
In

the past, soluble iron compounds

were used in the treatment of allergic
contact dermatitides
In eroded areas iron was sometimes
deposited in the skin, like a tattoo
Use of Monsels solution can produce
similar tattooing

Gold

Chrysiasis may be induced by parenteral administration

of gold salts, usually for the treatment of rheumatoid
arthritis
More commonly recognized in white patients
A mauve, blue, or slate/gray pigmentation develops
initially on the eyelids, spreading to the face, dorsal
hands, and other areas
Severity is related to the total dose received, rare < a
dose of 20 mg/kg of elemental gold
Pigment is accentuated in light-exposed areas, and sun
protected areas do not demonstrate gold
Localized chrysiasis has been induced by the Q-switched
ruby laser tx in a patient on parental gold therapy

Mercury
Mercurial pigmentation in the skin is
rare, especially since the use of
mercurials has been strictly controlled
Most common presentation is
subcutaneous nodules that result from
accidental implantation of elemental
mercury from a thermometer into skin

Canthaxanthin

Orange-red pigment canthaxanthin is

present in many plants ( notably algae and
mushrooms) and in bacteria. Crustaceans,
sea trout, and feathers
When ingested for the purpose of simulating
a tan, its deposition in the panniculus
imparts a golden orange hue to the skin
Stools become brick red and the plasma
orange, and golden deposits appear in the
retina

Dye Discoloration
Blue hands from accidental dyeing
were reported by Albert in 1976
A mans hands were dyed as a
result of warming them in his
armpits while wearing a new blue
flannel shirt
The dye was insoluble in water, but
soluble in sweat

Rubeosis
A

rosy coloration of the face

occurring in young people with
uncontrolled diabetes mellitus
May be associated with
xanthochromia to produce a
peaches and cream complexion

Vitiligo

Usually begins in childhood or young

adulthood
50% of cases begin before age 20
Prevalence ranges from 0.5% to 1%
Females are disproportionately
represented among patients seeking
medical care, it is not known if it is
actually more common in females or
simply because they more often bring it
to their physicians attention

Clinical Features

An acquired pigmentary anomaly of the skin

Manifested by depigmented white patches
surrounded by a normal or a hyperpigmented
border
There may be intermediate tan zones or lesions ,
halfway between the normal skin color and
depigmentaton-so-called trichrome vitiligo
Hairs in vitiliginous areas usually become white also
Rarely, the patches may have a red, inflammatory
border
Patches are of various sizes and configurations

Types
Localized

or focal(including
segmental)
Generalized
Universal
Acrofacial

Vitiligo

Generalized is the most common

Involvement is symmetrical
Most commonly involving the face, upper
chest, dorsal aspects of the hands, axillae,
and groin
Tendency for skin around orifices to be
affected (eyes,nose, mouth, ears, nipples,
umbilicus, penis, vulva, anus)
Lesions also favor areas of trauma (elbows
and knees)

Generalized Vitiligo

Involvement of
perineal and
inguinal skin
Note the distinct
borders

Acral Vitiligo

Symmetric, Acral Vitiligo

Left:

pre-PUVA treatment
Right:same pt shows perifollicular
pattern of repigmentation during
PUVA therapy

Segmental Vitiligo

Rapidly
progressing
segmental vitiligo

Segmental Vitiligo

Segmental vitiligo
of the eyebrow
and eyelashes

Segmental Vitiligo

Segmental vitiligo on
the arm , neck, and
chest
Note areas of
spontaneous follicular
repigmentation
Left upper back with
partial spontaneous
repigmentation

Universal Vitiligo

Applies to cases
where the entire
body surface is
depigmented

Focal Vitiligo

May affect one

nondermatomal site
Or asymmetrically affect a
single dermatome
This form is treatment
resistant, has an earlier
onset, and is frequently
associated with other
autoimmune phenomena
It represents 5% of adult
vitiligo and 20% of
childood vitiligo
Trigeminal area is most
commonly affected

Acrofacial Vitiligo

Type affecting the

distal fingers and
the facial orifices

Vitiligo

Local loss of pigment may occur around nevi and

melanomas, the so-called halo phenomenon
Vitiligo-like leukoderma occurs in 1% of melanoma
patients
In those previously dx with melanoma, it suggests
metastatic disease
Paradoxically, patients who develop leukoderma
have a better prognosis than patients without it
Halo nevi are more common in patients with vitiligo
Lesions are hypersensitive to UV light and burn
easily when exposed to the sun

Ocular abnormalities are

increased in patients with
vitiligo
Iritis and retinal pigmentary
abnormalities
8% of pts with idiopathic
uveitis have vitiligo or
poliosis
Most frequent associations
are with other
autoimmune
diseases((IDDM, pernicious
anemia, Hashimotos
thyroiditis, Graves disease,
Addisons disease, and AA)

Vitiligo occurs in 13% of

pts with the autoimmune
polyendocrinopathycandidiasis-ectodermal
dystrophy (APECED)
Familial aggregation is
seen- up to 30% of
vitiligo pts have an
affected relative-it is not
inherited as AD or AR
trait, but has a
multifactorial genetic
basis

Childhood Vitiligo
Shows an increase
in segmental
presentation
More frequent
autoimmune or
endocrine
anomalies
High incidence of
premature graying
in females

Poor response to
PUVA therapy

Vitiligo

Completely
depigmented oval
ivory white areas
with convex
hyperpigmentate
d borders

Vitiligo

Vitiligo with
depigmentation of
the lips

Henne Induced Vitiligo

Occupational Vitiligo
All the intermediates in the
biosynthesis of melanin
are phenolic compounds,
therefore postulated that
accumulation of these
within the melanocyte
may damage or kill the
cell.
Clinical pattern may be
similarto vitiligo, but
lesions tend to be
concentrated in areas of
contact with the
incriminated substance

Thiols, phenolic
compounds, catechol,
derivatives of catechol,
mercaptoamines, and
several quinones
produce
depigmentation
Seen in pts who work in
rubber garments or
wear gloves containing
an antioxidant,
monobenzyl ether of
hydroquinone

Occupational
Vitiligo
Many phenolic compounds can produce leukoderma, with or

without antecedent dermatitis

Examples: paratertiary sulfhydryls; monobenzyl ether of
hydroquinone
One source is phenolic antiseptic detergents used in hospitals
Adhesives and glues containing them may be found in shoes,
wristbands, and adhesive tape, and rubber products used in
brassieres, girdles, panties, or condoms may also be at fault
Self-sticking bindis (the cosmetic used by many Indian woman
on the forehead) has been reported to induce leukoderma
from the adhesive material
Electrocardiograph electrodes may cause similar
hypopigmented spots

Chemical Depigmentation
Chemical
depigmentation
due to a germicidal
detergent
Pts usually
improve with
discontinuation of
the offending
agent

Pathogenesis
Three

possible mechanisms have

been proposed as inducing vitiligo
are autoimmunity, neurohumoral
factors, and autocytotoxicity
No mechanism has been
conclusively proven

Histology

There is complete
loss of
melanocytes
Usually there is
no inflammatory
component

Differential
Morphea
Lichen

sclerosis
Pityriasis alba
Tinea versicolor tertiary pinta

Treatment

Spontaneous
repigmentation occurs
in no more than 15% to
25% of cases
Response is slow
PUVA may actually
worsen the appearance
initially by pigmenting
surrounding skin
Cover-up
strategies(topical dyes,
make-up, self-tanning
creams)

Fair-skinned pts may manage

their disease with sunblock
Sun protection is mandatory
in all pts with vitiligo because
of the loss of protection from
UV radiation in the
depigmented skin
Topical steroids may be
useful on focal or limited
lesions
Mid to super high-potency
steroids are often required on
trunk and acral lesions with
the strength tapered as the
lesions respond

Systemic steroids lead to

temporary repigmentation, this
is usually lost as the steroidal
agents are tapered
PUVA therapy is the most
common treatment for
generalized vitiligo
Topical application of 8methoxypsoralen at a
concentration of 0.05% to
0.01%, followed by UVA
exposure
Topical PUVA is used for focal or
limited lesions
Inadverrtent burns with
blistering are frequent during tx

Treatment
Trioxsalen, at a dose of
up to 20-40mg, is taken
a few hours before
natural sun exposure
Risk of phototoxicity is
low,so this can be done
at home
Ocular protection must
be worn from the
ingestion of the drug
through the whole tx
day

Most commonly, 8methoxyporalen is used

Initially tx is QOD(because of
the delayed erythema of
PUVA), increased to QD once
dose is defined
1hr to 30 mins before UVA
exposure , 8-methoxypsoralen
0.5mg/kg is ingested
Initial UVA dose is 1 or 2 J/cm
squared, which is gradually
increased; 5-MOP has an
aefficccacy equal to that of 8MOP and less risk of
phototoxicity

Two-three txs/week are done

20% of pts total
repigmentation occurs;30%
to 40% have partial response
Acral, periorificial, and
segmental lesions respond
less well
Darker-skinned pts have a
better response, since they
tolerate higher UV doses
Repigmentation may begin
after 15-25 txs;significant
improvement may take 100300 txs

If there is no follicular
repigmentation after 3-6
months or approx 50 txs
PUVA should be abated
CI to PUVA: photosensitivity,
porphyria, liver disease, SLE
Surgical txs can be applied
to limited lesions if all other
tx modalities have been
exhausted
Epidermal grafting,
autologous minigrafts, and
transplantation of cultured
and noncultured
melanocytes

Phenylalanine/UVA(PAUVA)
is much less effective than
PUVA
UVB tx alone with 311-nm
irradiation is associated
with a higher rate of acute
phototoxicity but may be
successful
UVA plus topical steroids is
superior to either agent
alone, but is successful
only 24-36% of the time
after 9 months

If > 50% of the body surface area is

affected by vitiligo, the pt can consider
depigmentation
This tx is permanent
Monobenzone 20% is applied BID for 3-6
months to residual pigmented areas
Up to 10 months may be required
One in six pts will experience acute
dermatitis, usually confined to the stillpigmented areas

Vitiligo

Partial
repigmentation of
lesions of vitiligo
on the leg of a 14year-old child at
the end of the
summer of sun
exposure

Vitiligo

Partial
repigmenation of
vitiligo following
psorralenultraviolet light
(PUVA) therapy

Vitiligo

Permanent
repigmentation
after 2 years of
photochemothera
py (tripsoralen
followed by
sunlight
exposure)

Vogt-Koyanagi-Harada
Syndrome

Characterized by bilateral uveitis, symmetrical

vitiligo, alopecia, white scalp hair, eyelashes
and brows(poliosis, and dysacousia(diminished
hearing)
Occurs in thirties
Initial or meningoencephalitic phase occurs
with prodromata of fever, malaise, headache,
nausea, and vomiting
Also may have psychosis, paraplegia,
hemiparesis, aphagia, and nuchal rididity
Recovery is usually complete

VKHS
Second

phase(ophthalmic-auditory
stage) is characterized by uveitis,
dreased visual acuity, photopobia,
and decreased hearing(50%)
The convalescent phase begins
3weeks to 3 months after it begins
to improve

Alezzandrinis Syndrome
Extremely

rare syndrome
characterized by a unilateral
degenerative retinits
This is followed several months
later by ipsilateral vitiligo on the
face and ipsilateral poliosis
Deafness may also be present

Alezzandrinis Syndrome

Leukoderma

Postinflammatory leukoderma may result

from inflammatory dermatoses ie:
Pityriasis rosea, psoriasis, herpes zoster,
secondary syphilis, and morphea,
sarcoidosis, tinea versicolor, mycosis
fungoides, scleroderma, and pityriasis
lichenoides chronica, and leprosy
Other causes: burns, scars,
postdermabrasion, and intralesioal
steroid injections

Leukoderma

Postinflammatory
hypopigmentation
in a 4-month-old
black child with
atopic dermatitis

Leukoderma

Postinflammatory
hypopigmentation
following
resolution of
guttate psoriasis

Pityriasis alba

Ill-defined
hypopigmented oval
patches are generally
seen on the face,
upper arms, neck, and
shoulders of affected
persons
It can be differentiated
from vitiligo by its fine
adherent scale, partial
hypopigmentation,
and distribution

Pityriasis alba

White, slightly
scaly patches
with indistinct
borders on a
childs cheek

Postinflammatory
hypopigmentation

Albinism

A partial or complete congential absence of

pigment in the skin, hair, and eyes
(oculocutaneous albinism), or the eyes alone
(ocular albinism)
Cutaneous phenotype of the various forms is
broad, but the ocular phenotype is
reasonably constant in most forms
The ocular phenotype includes decreased
visual acuity, nystagmus, pale irides that
transilluminate, hypopigmented fundi,
hypoplastic foveae, and lack of stereopsis

Albinism

This pt has light

skin, yellowish
white hair, and a
lack of
pigmentation in
nevi

Oculocutaneous
Albinism
OCA 1 results from mutations in the tyrosinase gene
Affected pts are homozygous for the mutant gene or are
1compound heterozygotes for different mutations in the

tyrosinase gene
AR
Two forms: 1) OCA 1A & OCA 1B (indistinguishable at birth)
OCA 1 is most severe with complete absence of tyrosinase
activity and complete absence of melanin in the skin and
eyes
Visual acuity is decreased to 20/400
OVA 1B tyrosinase activity is reduced but not absent. Pts
may show increase in skin,hair, eye color with age and can
tan

OCA 1

OCA 1B was originally called yellow

mutant albinism
Temperature sensitive OCA (OCA 1-TS)
results from mutations in the tyrosinase
gene that produce an enzyme with
limited activity < 35 degrees C and no
activity below this temp. pts have white
hair, skin, andeyes at birth, at puberty
dark hair develops in cooler acral areas

Top:albinism with
white hair, pale skin,
and translucent irides
Bottom:ophthalmosco
pic view of a pt with
albinism demonstrates
a pale fundus, poor
macular development,
and prominent
choroidal vasculature

Oculocutaneous Albinism
2Prevalence of 1:15,000

Pts were named tyrosinase-positive albinos

AR and mutations occur in the P gene
P gene codes a membrane transport protein that is
present in the melanosome membrane
Cutaneous phenotype of OCA 2 pts is broad, ranging
from nearly normal pigmentation to virtually no
pigmentation
Pigmentation increases with age, and visual acuity
improves with age
Prader-Willi and Angelman syndromes are caused by
deletions in the P gene; 1% of pts with these syndromes
also have OCA 2

Oculocutaneous Albinism
3

AR-caused by mutations in the tyrosinerelated protein 1 (TRP-1), located on

chromosome 9
OCA 3 has been described only in black
pts and is characterized by light brown
hair, light brown skin, blue/brown irrides,
nystagmus, and decreased visual activity
Brown rather than black melanin is formed

Ocular Albinism

There are multiple forms of ocular albinism

OA 1 may be present with lighter than
expected skin
It is X-linked
Female carriers have mud-splattered
fundi
Macromelanosomes are found in the skin,
so skin bx may be a helpful tool
Many cases of AR ocular albinism have
been reclassified as OCA 1 or OCA 2

Syndromes Associated
with Albinism
Chediak-Higashsi

Syndrome
Hermansky-Pudlak Syndrome
Griscelli Syndrome(partial albinism
with immunodeficiency)
Elejalde Syndrome
Cross-McKusick-Breen Syndrome
Cuna Moon Children

Classification of
Oculocutaneous Albinism

Selenium Deficiency
Selenium

deficiency in the setting

of total parental nutrition can lead
to pseudoalbinism
Skin and hair pigmentation return
to normal with supplementation

Waardenburgs Syndrome
Four genotypic variants
exist:
Types 1 & 3 are caused
by mutations in the PAX
gene on chromosome 2
Type 2 is caused by
mutations in the MITF
gene on chromosome
3, and type 4 due to
mutations in the
ENDRB gene on
chromosome 13

Pts have features of

piebaldism, with white
forelock,
hypopigmentation,
premature graying,
synophrys, congenital
deafness, a broad nasal
root, and ocular changes
including heterochromia
irides
Apparently, melanoblasts
fail to reach the target
sites during
embryogenesis

Piebaldism

Rare, AD with variable

phenotype, presenting at
birth
White forelock, patchy
absence of skin pigmenation
Depigmented lesions are
static and occur on the
anterior and posteroir trunk,
mid upper arm to wrist, midthigh to mid-calf, and shins
A characteristic feature is the
presence of hyperpigmented
macules within the areas of
lack of pigmentation and on
normal skin

Piebaldism

Piebaldism

Segmental white
patch on the neck
with a tuft of
white hair present
from birth

Piebaldism

White forelock
and patch of
unpigmented skin
in a young girl
with piebaldism

Piebladism

The white forelock arises from a triangular or

diamond-shaped midline white macule on the
frontal scalp or forehead
The medial portions of the eyebrows, and
eyelashes may be white
Histologically, melanocytes are completely absent
in the white macules
Etiology is a mutation in the c-kit protooncogene
Phenotypic differences seen in families is caused
by different locations of mutations in the gene
The white lesions may respond to surgical excision

Idiopathic Guttate
Hypomelanosis
AKA leukopathica symmetrica progressiva

Very common aquired disorder affecting

women more frequently than men
Usually occurs after age 40
Lesions occur on the shins and forearms; are
small (6 or 8mm), rarely become very
numerous ( a dozen or two at most), and never
occur on the face or trunk
Lesions are irregularly shaped and very sharply
defined, like depigmented ephelides, and are
only of cosmetic significance

Idiopathic Guttate
Hypomelanosis