Decreased or absent melanin in the skin can lead to hypomelanosis
and can occur by two main mechanisms.
1. Melanocytopenic hypomelanosis: absent or decreased number
of melanocytes (e.g., vitiligo).
2. Melanopenic hypomelanosis: absent or decreased melanin production,
but normal number of melanocytes (e.g., oculocutaneous albinism).
Pityriasis alba is a common asymptomatic, sometimes scaly, hypopigmentation
of the face, neck, and body.
Pityriasis alba entails both mild dermatitis and pigment alteration;
generally, the former responds quickly while the latter continues
to be an issue for many months or years.
Age Young children, often between
the ages of 3 and 16 years.
Race All races, more noticeable
in darker skin types.
Etiology Likely a form of atopic
Thought to be an eczematous dermatosis, with hypomelanosis resulting
from postinflammatory changes and ultraviolet screening effects
of the hyperkeratotic and parakeratotic epidermis.
Hypopigmented areas are usually stable then gradually disappear
with age. Some lesions may persist into adulthood. The areas are
typically asymptomatic, but can sometimes burn or itch.
Type Macules, may have slight scale.
Number One to twenty lesions may
Color Pink, then off-white to tan-white.
Size and Shape 5 to 30 mm or larger.
Distribution Face (malar region),
neck, trunk, extremities.
Sites of Predilection Face, especially
the cheeks (Fig. 12-1), midforehead, and around the eyes and mouth.
Pityriasis alba Faint,
hypopigmented slight scaly macules located on the cheeks of a child.
May be associated with atopy (eczema, allergies, hay fever, asthma).
Pityriasis alba can be confused with other hypopigmented skin
disorders such as vitiligo, tinea versicolor, tinea corporis, pityriasis
lichenoides, and postinflammatory hypopigmentation.
Dermatopathology Histology reveals
hyperkeratosis, parakeratosis, moderately dilated vessels of the
superficial dermis, slight perivascular infiltrate, and edema of
the papillary dermis.
Electron Microscopy The number
of melanocytes is reduced and those present contain fewer and smaller
Wood’s Lamp Accentuates
hypopigmentation. Lesions are NOT depigmented.
Pityriasis alba is a benign condition and often is self-limited,
clearing at puberty. It is usually asymptomatic, but can be itchy
or have a burning sensation.
Treatment is unnecessary. The condition improves with age. For
cosmetic reasons, emollient creams (hydrated petrolatum, Vaseline,
mineral oil, moisturizers) may be useful to diminish the dry scales
and ambient UV exposure can help repigment the area. In severe cases
of pityriasis alba, a mild topical steroid can be used sparingly
in appropriate strengths for short durations (bid for 2 weeks).
A common cause of benign hypopigmentation characterized by decreased
melanin formation following cutaneous inflammation.
Synonym Postinflammatory hypomelanosis.
Etiology Usually follows involution
of any inflammatory skin disorders (e.g., eczematous or psoriatic lesions,
pityriasis rosea, burns, bullous disorders, infections, etc.).
Inflammatory conditions of the epidermis may result in transient
alterations in melanosome biosynthesis, melanin production, and
transport. Keratinocyte injury and may render them temporarily unable
to accept melanin from melanocytic dendrites. Severe inflammation
may even lead to a complete loss of melanocytes or melanocyte function.
Shape Linear, oval, round, punctate
depending on primary process (Fig. 12-2).
Postinflammatory hypopigmentation Residual
hypopigmented macules after resolution of tinea versicolor in a
Distribution Localized or diffused
depending on primary process.
A clinical history of an antecedent inflammatory dermatosis is
helpful to differentiate postinflammatory hypopigmentation from
tinea versicolor, tuberous sclerosis, vitiligo, albinism, or infectious
disease (leprosy etc.).
Dermatopathology Skin biopsy may
show decreased melanin in keratinocytes, inflammatory infiltrate
may or may not be present depending on the etiologic primary process.
Wood’s Lamp Accentuates
hypopigmentation. Lesions are NOT depigmented.
Hypopigmentation gradually self-resolves over a period of months
provided that the affected areas are kept disease-free. Common inflammatory
conditions that lead to postinflammatory hypopigmentation include
psoriasis, seborrheic dermatitis, atopic dermatitis, lichen sclerosus, lichen
striatus, and lupus.
Postinflammatory hypopigmentation is a benign reactive condition,
thus no treatment is necessary. Prevention would focus on eliminating
the primary inflammatory process, allowing the melanocytes to recover.
Then the hypopigmentation will slowly self-resolve. Patients should
be counseled that hypopigmentation may take weeks to months of inflammation-free
periods to improve. Ambient UV exposure may be helpful in repigmenting
Vitiligo is an acquired pigmentary disorder characterized clinically
by the development of completely depigmented macules, microscopically
by the absence of melanocytes, and medically by the increased risk
of autoimmune mediated disease (i.e., thyroid disorders).
Visible depigmentation carries deep cultural and religious stigma
for many and, while not life-threatening, vitiligo should be approached
with this understanding.
Age Any age, 50% begin
between ages 10 and 30 years.
Race All races. More noticeable
in darker skin types.
Incidence Common. Affects up to
2% of the population.
Genetics Up to 30% of
patients have a first-degree relative with vitiligo. Families with
thyroid disease, diabetes, and other autoimmune processes are at
increased risk of developing vitiligo. Several genetic loci have
been implicated: AIS1 (FOXD3), PTPN22, VIT1 (FBXO11), CTLA4, MITF, MHC
(HLA-DRB1, HLA-DRB4, HLA-DQB1), ESR1, AIS2, AIS3, MLB2, CAT, VDR,
MYG1, GCH1, NALP1 (SLEV1), ACE, AIRE, COMT.
Etiology Likely autoimmune mediated.
In lesions of vitiligo, there is a decrease or absence of functional
melanocytes in the skin. Numerous pathophysiologic mechanisms for
vitiligo have been proposed: an autoimmune destruction of melanocytes,
a defect in the structure and function of melanocytes, defective-free
radical defenses, decreased melanocyte survival, autocytotoxic metabolites,
faulty membrane lipid proteins in the melanocyte, defective melanocyte
growth factors, neurochemical destruction of melanocytes, viral
Both genetics and environment play a role in vitiligo. Many patients
attribute the onset of their vitiligo to trauma, as with cuts, suture
sites, etc. (Koebner or isomorphic phenomenon). Emotional stress
(e.g., grief over lost partner) is also mentioned by patients as
a cause. The depigmented areas gradually appear and 30% or
more can undergo spontaneous repigmentation.
Type of Lesion Macule, patch.
Size 1- to 5-mm confetti macules,
large several centimeter patches.
Color White depigmentation (Fig.
Vitiligo A. Areas of depigmentation
on the legs of a child with vitiligo. B. Area
of vitiligo with characteristic “islands of repigmentation” indicative
of follicular-based repigmentation.
Shape Oval, geographic patterns;
Distribution Face (periorificial),
dorsa of hands, nipple, axillae, umbilicus, sacrum, inguinal, anogenital
areas, extremities (elbows, knees, digits, wrists, ankles, shins),
Hair White hair and premature gray
hair, alopecia areata, and halo nevi.
Eye Iritis in 10%, but
may not be symptomatic; retinal changes consistent with healed chorioretinitis in
up to 30% of patients.
Perifollicular Repigmentation Repigmentation
occurs around hair follicles (Fig. 12-3B) with macules that enlarge
and eventually fuse to a confluent skin color.
Hyper- or hypothyroidism is present in up to 30% of
patients with vitiligo. Uncommon associations include diabetes mellitus,
pernicious anemia, Addison’s disease, gonadal failure,
polyendocrinopathy, halo nevi, alopecia areata, and lichen sclerosis.
The differential diagnosis of completely depigmented skin lesions
include lupus erythematosus, pityriasis alba, tinea versicolor,
piebaldism, chemical leukoderma, scleroderma, leprosy, nevus depigmentosus,
tuberous sclerosis, leukoderma with metastatic melanoma, and post-
Dermatopathology On skin biopsy,
melanocytes are completely absent in fully developed vitiligo macules,
but at the margin of the lesions, there may be melanocytes present
and a mild lymphocytic response.
Laboratory Examination of Blood Blood
tests for T4, TSH, glucose, CBC, and cortisol (in high-risk patients)
may be indicated to rule out concurrent autoimmune diseases.
Wood’s Lamp Depigmented
areas will light up brightly with the Wood’s lamp examination.
The course of vitiligo is unpredictable; lesions may remain stable
for years or progress rapidly. Approximately 30% of patients
have some degree of sun-induced or spontaneous repigmentation. Children
tend to have a better prognosis and have less associated endocrinopathies
as compared to adults.
Ambient sunlight with sunscreen can help repigmentation, especially
is cosmetically noticeable areas such as the face or hands. In older
children that are sunlight responsive and compliant, phototherapy
(narrowband UVB > PUVA) is useful. Limited use of topical steroids
to the affected areas has been successful, but should be discontinued
if there is no clinical improvement after 2 months. Topical tacrolimus
0.1% ointment has reported success without the adverse
effects of light or steroid therapy and can be tried alone or in
conjunction with other treatment modalities. In older refractory
adults, autologous small skin punch grafts from normal skin areas
can be grafted to depigmented areas, but scarring and dyspigmentation
Oculocutaneous albinism (OCA) is a rare group of inherited disorders
that present as a congenital absence of pigment in the skin, eyes,
and hair. The pigment deficiency is caused by decreased or absent
melanin, despite normal numbers of melanocytes in the skin.
OCA is primarily AR-inherited and can be categorized into four
1. OCA type 1: absent (OCA1A) or decreased (OCA1B)
2. OCA type 2: mutations in the P gene (? accumulation of glutathione).
3. OCA type 3: mutations in tyrosinase-related protein 1 (TRYP1)
4. OCA type 4: mutations in membrane-associated transported protein
Ocular albinism (OA) patients primarily have XLR-inherited retinal
depigmentation cause by a mutation in the ocular albinism type 1
Incidence 1:20000 in whites. 1:1500
in some African tribes.
Genetics OCA: AR (rare cases of
AD). OA: XLR (rare cases of AR).
OCA1 and OCA3 are endoplasmic reticulum (ER) retention diseases
where the mutated proteins (tyrosinase or TYRP1, respectively) cannot
leave the ER to become part of the melanosomes. OCA2 leads to a
dysfunctional P protein which leads to abnormal processing or transport
of tyrosinase. OCA4 leads to a defective transporter protein. OA
has a mutated membrane glycoprotein that is thought to influence
melanosomal growth and maturation.
Type Macular depigmentation of
entire body (Fig. 12-4).
Oculocutaneous Albinism An
infant with OCA1A type, see Table 12-1. Note the white-colored hair,
skin, and pink irises in an infant.
Color White or light tan (tyrosinase-negative).
Hair White or light brown (tyrosinase-positive),
Eyes Iris translucency, reduced
visual acuity, photophobia, strabismus, nystagmus, lack of binocular vision.
Light Microscopy Melanocytes are
present in normal numbers in the skin and hair bulb in all types
of albinism. The dopa reaction is markedly reduced or absent in
melanocytes of the skin and hair depending on the type of albinism.
Electron Microscopy Melanosomes
are present in melanocytes in all types of albinism but, depending
on the type of albinism, there is a reduction of the melanization
of melanosomes, with many being completely unmelanized.
Tyrosine Hair Bulb Test Hair bulbs
are incubated in tyrosine solutions for 12 to 24 hours and develop
new pigment formation from normal and tyrosinase-positive OCA patients,
but no new pigment formation is present in tyrosinase-negative OCA
The differential diagnosis would be whole-body vitiligo, but
iris translucency and the presence of other eye findings in the
fundus are reliable signs of albinism.
Depending upon the OCA type and degree of tyrosinase activity,
patients may vary in severity from complete loss of pigment to subtle
pigmentary dilution (Table 12-1). Patients with OCA learn early
in life to avoid the sun because of repeated sunburns, especially
as toddlers. They have a normal life span but can have problems
with vision, to the point of blindness, and skin cancers later in
life: squamous cell carcinomas (with metastases), basal cell carcinomas,
and melanomas (typically amelanotic).
Table 12-1 Classification
of Albinism ||Download (.pdf)
Table 12-1 Classification
|Type||Subtypes||Gene Locus||Includes||Clinical Findings|
|OCA1||OCA1A||TYR||Tyrosinase-negative OCA||White hair and skin, eyes (pink at birth → blue)|
|OCA1B||TYR||Minimal pigment OCA||White to near-normal skin and hair pigmentation|
|Platinum OCA||Platinum (pheomelanin) hair|
|Yellow OCA||Yellow (pheomelanin) hair, light red or brown hair|
|Temperature-sensitive OCA, tyrosinase loses activity at 35°C.||May have near-normal pigment but not in axillas|
|Autosomal recessive OA (some)|
|OCA2||P||Tyrosinase-positive||Yellow hair, “creamy” white (Africa)|
|Brown OCA||Light brown/tan skin (Africa)|
|OCA3||TRP1||Autosomal recessive OCA (some)|
|Rufous OCA||Red and red-brown skin and brown eyes (Africa)|
|OCA4||MATP||Generalized hypopigmentation (Japan)|
|OA1||OA1||X-linked OA||Normal pigmentation of skin, hair. Hypopigmented eyes|
Recognition of OCA early in life is important to begin early
patient education about rigorous protective skin care. Daily application
of topical, potent, broad-spectrum sunblocks, including lip protection
(SPF higher than 30) is necessary. Special UV protective clothing
and wide brim hats help to reduce sun exposure.
Avoidance of direct sun exposure between the hours of 10 am and
2 pm, especially in high-intensity seasons or climates is recommended.
OCA patients should have regular periodic skin examinations as they
help to detect skin cancers as early as possible. Patients should
also have UV protective eyewear and regular ophthalmologic care.
Nevus depigmentosus is a congenital hypomelanotic lesion characterized
by a single depigmented spot, a segmental absence of pigment, or
a Blaschkoid streak of hypopigmentation with a chronic persistent
Synonym Nevus achromicus, nevoid
Prevalence 1 in 75 people.
Proposed mechanism for nevus depigmentosus is chromosomal mosaicism.
Patients are born with the depigmented area of skin and the area
is asymptomatic but persists for life.
Color Depigmented white or light
tan (Fig. 12-5).
Nevus depigmentosus Depigmented
area on the arm of a child present since birth.
Size Few millimeters to several
Shape Isolate, segmental, or linear
following Blacshko’s lines.
Distribution Trunk, lower abdomen,
proximal extremities > face, neck.
An isolated nevus depigmentosus must be differentiated from vitiligo,
nevus anemicus, and lesions of tuberous sclerosis. Very extensive
lesions, multilinear Blaschkoid hypomelanosis should raise the possible
diagnosis of hypomelanosis of Ito in which the pigmentation is associated
with abnormalities of the hair, CNS, eyes, or musculoskeletal system.
Dermatopathology Lesions may show
normal or decreased melanocyte numbers.
Electron Microscopy Melanization
is decreased or normal.
Wood’s Lamp Accentuation
of depigmented areas.
Lesions persist for life, but remain asymptomatic.
A nevus depigmentosus is asymptomatic and for small lesions,
treatment is not necessary. Extensive lesions, or those on the face,
can be cosmetically upsetting to the patient. Since nevus depigmentosis
lesions do not tan as well as the surrounding skin, they become
more noticeable with UV exposure. Thus rigorous sun protection (SPF
30 of higher) would keep lesions less cosmetically detectable.
Nevus anemicus is a rare congenital area of pale skin that represents
localized, decreased perfusion.
Synonym Pharmacologic nevus.
It has been suggested that nevus anemicus arises from a focal
increased blood vessel sensitivity to vascular catecholamines and
thus are permanently vasoconstricted.
Lesions are present at birth and persist asymptomatically for
Type Macule or patch (Fig. 12-6).
Nevus anemicus Hypopigmented
macule in an adolescent present since birth. Stroking of the lesion
produces a normal erythematous response at the periphery (see arrow),
but not within the lesion, indicative of its avascularity.
Size Few millimeters to several
centimeters, average 5 to 10 cm.
Color Hypopigmented, avascular.
Distribution Chest > face and extremities.
The differential diagnosis includes nevus depigmentosus, tuberous
sclerosis, vitiligo, hypomelanosis of Ito, and incontinenti pigmenti.
Three factors may be helpful for differentiating a nevus anemicus
from a pigmentary problem: (1) a nevus anemicus does not accentuate
by Wood’s lamp; (2) pressure on the lesion by a glass slide
makes the lesion unapparent from surrounding normal skin; and (3)
stroking or heat application fails to induce erythema in the lesion
Dermatopathology A skin biopsy
reveals normal numbers of blood vessels and melanocytes. The biopsy
would most likely be interpreted as normal skin.
Wood’s Lamp Does not enhance
Nevus anemicus persists for life and is usually asymptomatic.
They are usually only noticeable when there is surrounding vasodilation
because of heat or stress.
No treatment is effective or necessary.