Facial Plast Surg Clin N Am 11 (2003) 209 – 217
Disorders of pigmentation
Elizabeth Arnold Spenceri, MD
Laser and Dermatologic Surgery Center, 14377 Woodlake Drive, Suite 111, Town and Country, MO 63017, USA
Disorders of pigmentation represent a wide vari-
ety of medically relevant and aesthetically significant
diseases for which physicians might be consulted.
The more common pigmentation disorders are
reviewed in this article to assist the clinician in
making accurate diagnoses and providing preferred
treatment options for patients.
Hyperpigmentation
Hyperpigmentation presents most commonly as
tan to brown macules or patches on otherwise nor-
mal-appearing skin. There is often no associated
surface change such as scale or thickened plaques.
Hyperpigmentation can occur as a single, isolated
lesion or as multiple or diffuse lesions in a variety of
geometric configurations. Many hyperpigmentation
disorders are acquired or idiopathic, although some
are linked with genetic diseases that might have
significant systemic associations.
Melasma
Melasma is one of the more frequently encoun-
tered disorders of hyperpigmentation. It occurs most
commonly in the setting of excess estrogen such as
during pregnancy or with estrogen supplementation
(including oral contraceptives and hormone replace-
ment therapy). Some cases of melasma are regarded
as idiopathic.
Melasma is benign but aesthetically displeasing. It
presents as mottled to solid, hyperpigmented patches
at the superior cutaneous lip, cheeks, and forehead
with varying degrees of intensity (Fig. 1). Ultraviolet
exposure exacerbates the disease. Melasma presents
histologically as increased melanocytes with
1064-7406/03/$ – see front matter D 2003, Elsevier Inc. All rights reserved.
doi:10.1016/S1064-7406(02)00026-3
increased melanin production and transfer to adjacent
keratinocytes. Not uncommonly, there is melaniza-
tion of the upper dermis, which might account for
recalcitrant cases.
Melasma can be managed in a variety of ways.
For affected pregnant patients, reassurance that the
condition often improves upon the end of pregnancy
might be sufficient. Nonpregnant patients might opt
for medical or surgical treatment options.
Sunscreen and sun protective measures minimize
the severity of the disorder. Additionally, hydro-
quinone and tretinoin are two commonly used topical
treatment modalities. Hydroquinone causes degrada-
tion of pigment and inhibits pigment production by
forming oxygen free radical species, which affect
existing melanin and tyrosinase activity, a key
enzyme in melanin synthesis [1]. Hydroquinone is
available in a variety of formulations and can be
applied once to twice daily. Over-the-counter con-
centrations are 2%, and most prescription hydro-
quinones are of 4% concentrations.
Tretinoin acts to normalize epidermal turnover
and disperse melanin granules within keratinocytes,
thereby reducing the appearance of pigmentation
[2,3]. Patients frequently experience mild irritation,
desquamation, and erythema during the initial phase
of treatment. Compliance is increased by counseling
patients on appropriate dosing recommendations:
small (pea-sized) doses applied to a dry face every
2 to 3 nights, gradually increasing to nightly as
tolerated. This schedule will minimize excess dryness
and irritation.
Two newer, naturally occurring acids have proven
skin-bleaching effects. Kojic acid, which is produced
by a variety of fungi including Asperigillus, Penicil-
lium, and Acetobacter, has inherent tyrosinase-inhib-
itory properties, which accounts for its therapeutic
210 E.A. Spenceri / Facial Plast Surg Clin N Am 11 (2003) 209–217

contact dermatitis. The etiology appears to be stimu-

lation of melanocytes secondary to inflammatory
mediators in the primary process [6]. The distribution
is variable yet dependent on the initial inflammatory
process (Fig. 2).
The disorder tends to resolve even without inter-
vention, but this might take many months. It is
imperative that the primary inflammatory process be
treated accordingly to prevent further hyperpigmen-
tation. Sun protection might hasten the resolution of
the hyperpigmentation.

Iatrogenic hyperpigmentation
Fig. 1. Melasma. Mottled hyperpigmented patches on the
forehead. (Courtesy of George J. Hruza, MD, St. Louis, MO.)
Hyperpigmentation might result from treatment
modalities such as post-laser resurfacing or post-
pulsed dye laser. This type of hyperpigmentation is
effects on hyperpigmentation [4]. Kojic acid is avail- essentially a postinflammatory response (see above)
able as a cosmeceutical through a physician’s office. and is limited to treatment areas, often presenting with
Formulations containing kojic acid often include a sharp geometric configuration. Ultraviolet exposure
other skin-lightening products such as hydroquinone might exacerbate or prolong the condition. Although
or alpha hydroxy acid (AHA). iatrogenic hyperpigmentation often improves over
Azelaic acid, a topical acne treatment, has a side time, the resolution phase can be accelerated by the
effect profile that includes skin-lightening effects. use of sunscreen and a combination of hydroquinone,
The yeast Pityrosporum ovale produces this naturally tretinoin, azelaic acid, or kojic acid.
occurring dicarboxylic acid. Azelaic acid inhibits
DNA synthesis and mitochondrial respiration, and Lentigines and ephelides
its cellular uptake is increased in hyperproliferative
disorders such as melasma [5]. It is available by Solar lentigines, also known as ‘‘sun spots’’ or
prescription only and can be used once or twice daily. ‘‘liver spots,’’ are ultraviolet-induced lesions on
Chemical peels and AHA products can improve exposed skin that occur most commonly with advan-
the appearance of melasma by decreasing keratinocyte cing age. They can occur on persons of any skin
adhesion, causing epidermolysis. Additionally, AHA- type and are most prevalent on the face, dorsal
containing peels and products can increase the bio- hands, and forearms, where they present as tan to
availability of other topical treatments for melasma. light brown macules and patches (Fig. 3). Histolog-
Laser therapy is a suitable treatment option for ically, solar lentigines reveal increased melanization
melasma, although results are not always predict-
able. The frequency-doubled Q-switched neodym-
ium-yttrium-aluminum-garnet (Nd:YAG, 532 nm),
ruby (694 nm), and alexandrite (755 nm) lasers tar-
get epidermal pigment. Side effects include slight
bruising or darkening of the treatment area and
crusting or scaling that can last 7 to 10 days. Un-
fortunately, recurrences are somewhat common as
long as the underlying hormonal excess remains.
Some lesions might actually darken following
Q-switched laser treatment. Consideration of a test
spot is recommended.

Postinflammatory hyperpigmentation

Nearly any inflammatory condition can result in Fig. 2. Postinflammatory hyperpigmentation. Coalescing, hy-
secondary hyperpigmentation. Examples include perpigmented macules within well-demarcated traumatic
eczema, psoriasis, traumatic injuries, and allergic scar. (Courtesy of George J. Hruza, MD, St. Louis, MO.)
 E.A. Spenceri / Facial Plast Surg Clin N Am 11 (2003) 209–217
Fig. 3. Solar lentigines. Multiple tan to brown, variably-
sized macules and patches on the cheek and forehead.
(Courtesy of George J. Hruza, MD, St. Louis, MO.)
of the basal layer with a normal number of mela-
nocytes and increased rete ridge elongation and
clubbing. Color variability is often minimal. Small
lesions are generally not clinically relevant, but
larger lentigines with notable border irregularity or
color variability might represent a malignant variant
such as lentigo maligna (melanoma in situ) or lenti-
go maligna melanoma (invasive melanoma). Biopsy
of such lesions is necessary to rule out atypia. Fur-
ther discussion of these malignant variants is beyond
the scope of this article.
Lentigo simplex is a tan to brown macule that
presents in childhood. It can occur on any part of the
body, including mucosa, and it is not influenced by sun
exposure. Clinically, lentigo simplex can be mistaken
for junctional nevi. Histology reveals proliferation of
melanocytes and rete ridge elongation. Fortunately,
lentigo simplex has no increased risk of malignancy.
Widespread lentigines in a young patient might
herald a genetic disorder such as Peutz-Jeghers syn-
drome, which has a high incidence of gastrointestinal
polyps, lentigines, atrial myxoma, and blue nevi
(LAMB) syndrome (which is associated with atrial
myxomas), or lentigenes, EKG abnormalities, ocular
hypertelorism, pulmonic stenosis, abnormal genitalia,
growth retardation, and deafness (LEOPARD) syn-
drome (which includes pulmonary stenosis and con-
duction abnormalities). In such cases, coordination of
care with the patient’s primary care physician is
211
necessary to monitor for systemic manifestations of
the disease.
Ephelides, or ‘‘freckles,’’ occur most commonly
on sun-exposed skin. They become darker with sun
exposure and lighter in tone with extended absence of
sun exposure. This fading can be so dramatic that the
ephelides nearly resolve during the winter season.
Ephelides present during childhood and adolescence
and are most common in persons with blonde or red
hair and Fitzpatrick skin types I or II. Histologic
findings include increased melanization of the basal
layer without an increased number of melanocytes.
The preferred treatment modality for benign-
appearing but aesthetically unacceptable lentigines
and ephelides is a Q-switched laser. Several types
of Q-switched lasers exist and are suitable options for
treating pigmented lesions, including Nd:YAG (fre-
quency-doubled 532 nm), ruby (694 nm), and alex-
andrite (755 nm). More than one laser session might
be required for complete resolution. In the case of
solar lentigines, patients should be informed that new
lesions might develop over time. Sun protection
measures will diminish future development of lenti-
gines and reduce the appearance of ephelides.
Café-au-lait macule
Café-au-lait macules (CALMs) are most com-
monly known for their association with neurofibroma-
tosis. CALMs present as uniformly tan macules or
patches that often have no specific distribution.
Lesions can be idiopathic, and several lesions can be
present without causing concern. If there are more than
five lesions of at least 0.5 cm diameter in a child less
than 5 years of age or at least six lesions of at least
1.5 cm diameter in an adult, the clinician should
strongly consider the diagnosis of neurofibromatosis.
Additionally, CALMs of notable size, quantity, or
distribution might signal one of a multitude of geno-
dermatoses. Histologically, CALMs reveal increased
melanocyte numbers with normal melanocyte activity.
Nevus spilus is a closely related lesion that
presents as a tan macule or patch with superimposed
dark brown macules in a ‘‘speckled’’ array. Histolog-
ically, nevus spilus is a CALM with coexistent
lentigines. Concerns over malignant transformation
might be raised because of the irregular pattern of
central pigmentation in a nevus spilus. Biopsy of a
representative area is indicated in such cases,
although these lesions have no inherent increased
risk of malignant transformation.
Q-switched lasers treat CALMs effectively. Mul-
tiple treatments might be necessary, and recurrences
are somewhat common.
212 E.A. Spenceri / Facial Plast Surg Clin N Am 11 (2003) 209–217
Hypopigmentation/depigmentation
Absence of normal pigment production and pig-
ment dilution can result from a variety of genoderma-
toses or can be acquired at a later age. In many cases
the clinical findings are dramatic, especially in patients
with darker skin types. Treatment options focus pri-
marily on photoprotection and camouflage techniques.
Vitiligo
Vitiligo is a disorder in which the skin loses
pigment, becoming white (leukoderma). It occurs
most commonly in adolescents and young adults.
Patients present with white patches, often in a sym-
metric distribution. Vitiligo can be focal, segmental,
or generalized. The lesions are often periorificial and
near joints, and they can develop in sites of trauma (a
process known as the ‘‘Koebner phenomenon’’).
These characteristic clinical findings are secondary
to loss of melanocytes within affected areas. The
often dramatic and potentially widespread nature of
vitiligo can be disfiguring, leading to significant
social stigma.
In many cases, there is a family history of vitiligo
or a personal or family history of endocrine disorders
such as thyroid disease, diabetes, pernicious anemia,
or Addison’s disease. The natural history of vitiligo is
unpredictable. Lesions can gradually progress over 1
to 2 years, at which time they often stabilize. Com-
plete spontaneous resolution is rare, but temporary
resolution can be achieved with treatment. The exact
etiology of vitiligo is uncertain; some possible mech-
anisms include autoimmune, autocytotoxic, and neu-
ral hypotheses [7].
Abnormalities in the review of systems might rep-
resent an underlying systemic disease as noted above.
Diagnostic workup for these patients should be coor-
dinated with the patient’s primary care physician.
There are several treatment options for vitiligo,
including corticosteroids and graduated ultraviolet
exposure. Topical corticosteroids of mid- to high-
potency might halt disease progression. Their use
should be managed by a clinician to minimize long-
term risks such as skin atrophy, telangiectasia forma-
tion, and adrenal suppression. Brief courses of sys-
temic corticosteroids should be reserved for rapidly
progressive vitiligo, keeping in mind that there might
be a rebound response upon taper of the medication.
Physician-directed phototherapy with topical or
systemic psoralen (PUVA) is one option, but patients
might find the frequent office visits inconvenient. A
more acceptable approach might include graduated
natural ultraviolet exposure. Patients undergoing this
treatment should use an ultraviolet B sunscreen (one
that has limited screening in the ultraviolet A range,
such as a zinc oxide-free or titanium dioxide-free
product) to prevent sunburn. Patients should begin
treatment during non-peak hours (before 10:00 AM
and after 4:00 PM). An exciting new treatment option
is treatment with a 308-nm excimer laser. Vitiligo
seems to respond to the laser with far fewer treat-
ments than is required with PUVA treatment, and the
ultraviolet dose is limited only to the vitiliginous
plaques. Regardless of the chosen treatment, all
patients with vitiligo should be counseled on appro-
priate sun protection measures because the lesional
skin is at risk of burning and disease progression by
way of Koebnerization (development of new lesions
in sites of trauma).
Camouflage techniques such as waterproof
makeup prepared in a matching skin tone can conceal
affected areas. Epidermal grafts and autologous mini-
grafts are suitable treatment options for stable, recal-
citrant lesions [8,9]. Patients with widespread,
unresponsive disease might be considered for ‘‘per-
manent’’ depigmentation with monobenzylether of
hydroquinone. Treatment duration might take many
months, and side effects include contact dermatitis,
depigmentation at distant sites, incomplete pigment
recurrence, and increased photosensitivity [10].
Albinism
Albinism is a genetic disorder characterized by the
absence of tyrosinase or its diminished activity.
Tyrosinase-negative albinism (oculocutaneous albi-
nism [OCA] 1) presents with a complete lack of
pigment in skin, hair, and irides. The result is
snow-white hair, pale white to pink skin, and gray –
blue irides. Because there is no loss of melanocytes,
tyrosinase-negative albinos often have nevi that are
pink or red in color.
Tyrosinase-positive albinism (OCA 2) results in
diminished melanocyte activity. Affected persons
typically have bright yellow – blonde hair, blue or
yellowish-brown irides, and a creamy pale skin color.
Nevi are generally pigmented.
Both OCA 1 and 2 are inherited in an autosomal
recessive manner. In addition to the previously noted
skin and hair phenotypes, both groups have a high
incidence of photophobia and nystagmus. All races are
affected, but there might be more severe psychosocial
implications for affected persons of darker races.
Management of albinism centers on sun protection.
Affected persons are at increased risk of sunburn and
early cutaneous malignancies. Squamous cell and
basal cell carcinomas are encountered most frequently.
 E.A. Spenceri / Facial Plast Surg Clin N Am 11 (2003) 209–217
Patients are also at risk of developing melanoma, but
diagnosis might be delayed because pigment abnor-
malities are not always readily apparent. Careful
surveillance of the skin is of utmost importance.
Ocular symptoms such as nystagmus should be eval-
uated by an ophthalmologist. Sunglasses with suitable
ultraviolet protection are recommended.
Tuberous sclerosis
Tuberous sclerosis is a hereditary disorder char-
acterized by hypopigmented macules and patches that
are clustered or located individually. Lesional sub-
types include ash leaf macules (the most character-
istic, early finding), polygonal macules, and confetti
macules (small lesions often clustered pre-tibially).
Patients might also have café-au-lait macules. Facial
angiofibromas (‘‘adenoma sebaceum’’) are frequent
findings that can be disfiguring. A shagreen patch is a
connective tissue nevus that presents as a shiny, skin-
colored, firm plaque on the trunk or extremities of
patients with tuberous sclerosis. Other associated
findings include periungal fibromas, retinal hamarto-
mas, cortical tubers, seizures, mental retardation, and
bony changes (including cysts and sclerosis).
A thorough physical examination and workup
for systemic disease by a primary care physician is
necessary. Treatment of adenoma sebaceum in-
cludes excision or laser resurfacing such as with
the erbium:YAG (2940 nm) or carbon dioxide
(10600 nm) lasers, though new lesions will con-
tinue to be developed.
Postinflammatory hypopigmentation
Hypopigmentation can result from a variety of
inflammatory processes. The mechanism is most likely
related to a destruction of melanocytes and an increase
in the number of inflammatory mediator-activated
melanophages [11], which can result in ill-defined,
hypopigmented macules and patches correlating to
areas of recent trauma or irritation. Although most
lesions resolve gradually over many months, some are
persistent. Sunscreen can protect these areas from
concomitant ultraviolet damage.
Idiopathic guttate hypomelanosis
Idiopathic guttate hypomelanosis is an acquired
disorder that presents with hypopigmented, round to
stellate macules on the forearms and anterior legs.
The disease affects all skin types and both genders.
The lesions are thought to arise from longstanding
ultraviolet exposure, which is confirmed by dimin-
213
ished melanocyte number, function, and structure
because the dendrites are often short and blunted.
Some cases appear to be familial.
Patients with darker skin types can have more
cosmetically significant findings. Unfortunately, there
are no ideal treatment options. For patients with lighter
skin, consistent use of sunscreen might help minimize
the appearance. For individuals with darker skin who
have significant involvement, camouflage makeup can
conceal the appearance. Punch grafts and intralesional
corticosteroids have also been successful [12].
Dyschromia
Drug-induced dyschromia
Dyschromia can result from systemic or topical
medication usage. Some of the more commonly
implicated medications include minocycline, amio-
darone, clofazimine, antimalarial agents, and pheno-
thiazine. Despite adequate therapeutic effects with
these agents, patient compliance is often diminished
in the presence of dyschromia.
Minocycline, which is commonly used in acne
treatment, can produce dyschromia by deposition of
the drug metabolite complexes in the dermis and
cartilage. Bone and thyroid tissue can be similarly
affected. There are three variants of minocycline-
induced dyschromia. The first is a blue – gray discolor-
ation in prior sites of trauma, scars, or inflammation.
This variant is idiosyncratic (not dependent on length
of treatment or total dose). The second variant pres-
ents as dusky, gray – blue macules that appear most
commonly on the anterior legs. Its incidence increases
as the length of treatment and total dose increase. The
pigment granules also distribute to bone, cartilage,
sclera, and dental pulp, contributing to a bluish
discoloration of the mid-portion of teeth (Fig. 4).
The dyschromia is secondary to minocycline oxida-
tion, which results in a color transformation from
yellow to dark brown. Additionally, minocycline
binds iron and iron-containing compounds, yielding
darkly pigmented complexes within macrophages and
adipocytes [13].
The third type of minocycline-induced dyschromia
presents as diffuse, dusky tan hyperpigmentation that
is accentuated on sun-exposed areas. It most likely
represents a low-grade photosensitivity reaction. As
with the second type, it occurs with greater frequency
as the total dose and length of treatment increase.
Minocycline-induced dyschromia often improves
upon discontinuation of the drug, but it might take
214 E.A. Spenceri / Facial Plast Surg Clin N Am 11 (2003) 209–217
Fig. 4. Minocycline-induced hyperpigmentation. (A) Blue sclera in patient with 1-year history of minocycline use. (B) Blue
helical cartilage in the same patient. (See also Color Plates 21 and 22.) (Courtesy of George J. Hruza, MD, St. Louis, MO.)
months to years. Q-switched laser therapy might
hasten resolution [14].
Amiodarone produces a generalized photosensi-
tivity reaction after just a few months of treatment.
These sites are prone to development of slate-blue
discoloration. Amiodarone-induced dyschromia
occurs in an estimated 1% to 10% of patients taking
the drug. Histologic examination reveals yellow –
brown pigment granules within dermal macrophages.
Endothelial cells are equally affected. The mech-
anism of amiodarone-induced dyschromia appears
to be related to a phototoxic insult in amiodarone-
containing cells. The dyschromia can take several
years to fully resolve (even after discontinuation of
the medication), which is most likely related to a
persistent photosensitivity reaction. Q-switched laser
therapy can be a suitable treatment option [15].
Antimalarials such as hydroxychloroquine and
chloroquine can produce a blue – gray to black dis-
coloration, most commonly on the anterior legs,
which is similar to minocycline-induced dyschromia.
It occurs in up to one third of patients receiving
antimalarial agents and often with at least 4 months of
treatment. In addition to the legs, antimalarial-asso-
ciated dyschromia can occur on the face, nail beds, or
palate [16]. Perivascular hemosiderin deposition and
dermal melanin are found upon histologic examina-
tion [17]. The lesions gradually resolve upon dis-
continuation of the offending drug.
Clofazimine, which is used in the treatment of
leprosy, causes a generalized pink discoloration that
progresses to a dusky red to brown dyschromia.
Histologically, lipofuscin pigment and clofazimine
particles are present within dermal macrophages and
there is increased basilar melanin. The dyschromia is
reversible upon discontinuation of the medication.
Phenothiazine therapy frequently leads to a diffuse
slate-gray dyschromia on sun-exposed skin. It devel-
ops gradually as the treatment duration and total dose
increases. Affected persons are also at risk of devel-
oping lenticular opacities. Upon histologic examina-
tion, yellow – brown deposits are seen within dermal
macrophages and there is increased dermal and epi-
dermal melanization. Resolution occurs gradually
upon discontinuation of the offending agent.
Dyschromia can also result from heavy metal
absorption. Systemic ingestion of silver or absorption
from ophthalmic use can result in argyria, a diffuse
slate-gray discoloration that occurs primarily in sun-
exposed areas. The silver is thought to stimulate
melanin production. Histologically, small, black gran-
ules are apparent within the epidermal basement
membrane and surrounding appendageal structures,
especially the eccrine sweat glands. The dyschromia
is permanent.
Chrysiasis results from accumulation of gold in
tissue following systemic gold therapy [18]. The
result is a dusky blue to slate gray pigmentation in
 E.A. Spenceri / Facial Plast Surg Clin N Am 11 (2003) 209–217
Fig. 5. Common blue nevus. A dark blue – gray macule on
cheek of a child. (Courtesy of George J. Hruza, MD, St.
Louis, MO.)
predominantly sun-exposed areas. Histologically,
there is no increased melanin production—rather,
the gold salts deposit perivascularly and around
eccrine glands. Localized chrysiasis can be precipi-
tated by Q-switched laser therapy, resulting from a
structural alteration in the gold deposits from prior
gold therapy. Fortunately, this pigmentation can be
faded with the long-pulse ruby laser.
Ochronosis
There are two variants of ochronosis: exogenous
and endogenous. Exogenous ochronosis occurs in the
setting of topical administration of hydroquinone or
other phenolic intermediates. Topical application of
these chemicals causes local accumulation of homo-
gentisic acid in the upper dermis secondary to inhibi-
tion of homogentisic acid oxidase. This accumulation
results in a blue – gray to dark brown discoloration on
the face or any other treated area. Exogenous ochro-
nosis occurs more commonly in darker-pigmented
individuals and it is idiopathic [19,20]. Homogentisic
acid appears histologically as yellow – brown
(‘‘ochronotic’’) globules. Exogenous ochronosis also
contains an abundance of dermal melanophages.
Treatment of exogenous ochronosis includes dis-
continuation of the responsible agent. Gradual res-
olution of the lesions is variable. Persistent lesions
can be considered for Q-switched laser therapy.
Endogenous ochronosis, or alkaptonuria, is an
inborn error of metabolism that is inherited in an
autosomal recessive manner. Affected individuals
have a deficiency of homogentisic acid oxidase that
results in a more diffuse dusky blue – gray dyschromia.
Homogentisic acid accumulates in the dermis and in
cartilage, bone, and other internal organs. Endogenous
ochronosis is associated with severe arthropathy. The
215
histologic findings are identical to exogenous ochro-
nosis. Unfortunately, there are no ideal treatment
options, but affected individuals should undergo phys-
ical therapy to maintain adequate joint mobility.
Blue nevus
A blue nevus is a collection of darkly pigmented,
spindle-shaped nevus cells in the mid-dermis. Clin-
ically, the lesion presents as a solitary dark blue to
black macule or domed papule (Fig. 5). There are
three subtypes of blue nevi: common, cellular, or
combined nevus. The common blue nevus has a
predilection for the face or extremities. It tends to
remain small and has a low risk for malignant
transformation. In contrast, the cellular blue nevus
is larger (f1 cm or more in diameter). It extends
more diffusely and deeply into the dermis. There are
reports of malignant transformation of cellular blue
nevi [21] and regional lymph node melanization [22].
The combined blue nevus is a common blue nevus
with a superimposed nevocellular nevus in the over-
lying epidermis. There is no increased risk of malig-
nancy with this variant.
The characteristic dark blue to black color might
raise suspicion of malignant melanoma. Biopsy of
any clinically suspicious, questionable pigmented
lesion is necessary to rule out atypia. Surgical
excision is the treatment of choice. Q-switched laser
treatment has also been successful for cosmetically
unacceptable lesions [23].
Nevus of Ota
Nevus of Ota presents as a gray – blue pigmented
patch in a unilateral, periocular distribution extending
to the temple, forehead, and upper cheek (corres-
ponding to a cranial nerve V1/V2 distribution; Fig. 6).
Onset is often at birth. Not uncommonly, the scleral
Fig. 6. Nevus of Ota. A periocular grey patch in an Asian
woman. (Courtesy of George J. Hruza, MD, St. Louis, MO.)
216 E.A. Spenceri / Facial Plast Surg Clin N Am 11 (2003) 209–217
conjunctiva is affected, revealing a bluish tint. There
is a racial predilection in patients of Asian descent.
Nevus of Ito is a similar lesion that presents on the
shoulder or upper trunk.
Histologically, the lesions exhibit spindle-shaped
melanocytes that extend diffusely into the dermis
parallel to the overlying epidermis. The spindle cells
might aggregate around appendageal structures. De-
spite the depth and intensity of pigment, nevus of Ota
responds well to Q-switched laser treatment [24,25].
Mongolian spot
A Mongolian spot, also known as ‘‘congenital
dermal melanocytosis,’’ presents as a gray – blue
patch overlying the lumbosacral region in newborns.
It occurs more frequently in patients of Asian or
African descent. Histologically, there are dendritic
melanocytes that are oriented parallel to the epidermis
and situated at the reticular dermis. Lesions tend to
resolve in childhood.
Tattoo
Tattoos result from the intentional or accidental
introduction of ink particles or foreign, pigmented
substance into the dermis. Professionally placed tat-
toos can have a variety of vibrant colors. The more
common pigments used include cadmium (yellow),
ferric chloride (red), cobalt (blue), and chromium
(green). Titanium dioxide is occasionally added to
brighten the hues. India ink is typically employed in
amateur tattoos as the pigment, which results in a
clinically apparent dark blue to black coloration.
Tattoos can result from traumatic injury such as a
motor vehicle accident, pencil puncture wounds, or
gunpowder, or they can be placed as guides for
radiation therapy. Histologic examination reveals
dermal macrophages with phagocytosed pigment
particles. Pigment is also found in the dermal extra-
cellular space.
The goal of tattoo removal is to effectively reduce
the pigment density while minimizing the risk of
dermal and epidermal injury. Q-switched laser ther-
apy selectively targets the ink or pigment particles,
causing a thermoaccoustic reaction. This reaction
results in decreased particle size within the affected
dermal macrophages with gradual removal to the
regional lymph nodes. Transepidermal elimination
of pigment particles following Q-switched laser ther-
apy allows for further resolution. Interestingly, biopsy
specimens from ‘‘fully’’ responsive tattoos reveal
persistent pigment within dermal macrophages.
Appropriate laser wavelengths must be chosen for
a given tattoo color. Red inks are best treated with the
frequency-doubled Nd:YAG (green light, 532 nm),
whereas greens are best treated by red light lasers, the
Q-switched alexandrite (755 nm) and Q-switched
ruby (645 nm). Black and blue pigments respond
well to the Q-switched ruby, alexandrite, and
Q-switched Nd:YAG (1064 nm) lasers. Multiple treat-
ments are required, but amateur and traumatic tattoos
and facial tattoos generally require fewer treatments
than professional tattoos because of a decreased
pigment load.
Potential side effects of laser tattoo removal
include transient hyperpigmentation, transient to per-
sistent hypopigmentation, and incomplete fading.
Bruising and focal exfoliation are anticipated compo-
nents of the normal, post-laser healing process.
Localized chrysiasis can be precipitated in patients
with a history of gold therapy. Tattoos can signifi-
cantly darken upon Q-switched laser therapy. This
reaction occurs most frequently in skin-toned, brown,
or white tattoos and likely results from the reduction
of ferric oxide (Fe2O3) to ferrous oxide (FeO) or
reduction of titanium dioxide. Cosmetic facial tattoos
such as lip tattoos will frequently turn irreversibly
black upon Q-switched laser irradiation. Further laser
treatment of these lesions can improve the residual
pigment [26].
Summary
Disorders of pigmentation can range from cosmet-
ically unacceptable to disfiguring. They can present
as a localized occurrence or represent a cutaneous
manifestation of a systemic condition. The approach
to managing patients with pigmentation disorders
requires a thorough history and physical examination.
The cornerstone of management often involves pho-
toprotection, with multiple medical and surgical
treatment modalities allowing for a variety of treat-
ment options for most patients.
References
[1] Jimbow K, Obatha H, Pathak M, et al. Mechanism of
depigmentation of hydroquinone. J Invest Dermatol
1974;62:436 – 49.
[2] Griffiths CE, Finkel LJ, Ditre CM, et al. Topical tre-
tinoin (retinoic acid) improves melasma. A vehicle
controlled clinical trial. Br J Dermatol 1993;1290:
415 – 21.
 E.A. Spenceri / Facial Plast Surg Clin N Am 11 (2003) 209–217
[3] Pathak MA, Fitzpatrick RB, Kraus EW. Usefulness of
retinoic acid in treatment of melasma. J Am Acad
Dermatol 1986;15:894 – 9.
[4] Garcia A, Fulton JE. The combination of glycolic acid
and hydroquinone or kojic acid for the treatment of
melasma and related conditions. Dermatol Surg
1996;22:443 – 7.
[5] Nguyen QH, Bui TP. Azelaic acid: pharmacokinetic
and pharmacodynamic properties and its therapeutic
role in hyperpigmentary disorders and acne. Int J Der-
matol 1995;34:75 – 84.
[6] Tomita Y, Maeda K, Tagami H. Melanocyte-stimulat-
ing properties of arachidonic acid metabolites: possible
role in post-inflammatory pigmentation. Pigment Cell
Res 1992;5(5Pt2):357 – 61.
[7] Kovacs SO. Vitiligo. J Am Acad Dermatol 1998;
38(5Pt1):647 – 66.
[8] Boersma BR, Westerhof W, Bos JD. Repigmentation
in vitiligo vulgaris by autologous minigrafting: results
in nineteen patients. J Am Acad Dermatol 1995;
38(5Pt1):647 – 66.
[9] Van Geel N, Ongenae K, DeMil M, et al. Modified
technique of autologous non-cultured epidermal cell
transplantation for repigmenting vitiligo: a pilot study.
Dermatol Surg 2001;27:873 – 6.
[10] Mosher DB, Parrish JA, Fitzpatrick TB. Monobenzy-
lether of hydroquinone. A retrospective study of treat-
ment of 18 vitiligo patients and a review of the
literature. Br J Dermatol 1977;97:669 – 79.
[11] Weiss JS, James WD, Cooper KD. Melanophages in
inflammatory skin disease demonstrate the surface phe-
notype of OKM5+ antigen-presenting cells and acti-
vated macrophages. J Am Acad Dermatol 1988;19:
633 – 41.
[12] Falabella R, Escobar C, Giraldo N, et al. On the patho-
genesis of idiopathic guttate hypomelanosis. J Am
Acad Dermatol 1987;16:35 – 44.
[13] Pepine M, Flowers FP, Ramos-Caro FA. Extensive cu-
taneous hyperpigmentation caused by minocycline.
J Am Acad Dermatol 1993;28:292 – 5.
[14] Wilde JL, English III JC, Finley EM. Minocycline-in-
217
duced hyperpigmentation. Treatment with the neodym-
ium:YAG laser. Arch Dermatol 1997;133:1344 – 6.
[15] Karrer S, Hohenleutner U, Szeimies RM, et al. Amio-
darone-induced hyperpigmentation resolves after treat-
ment with the Q-switched ruby laser. Arch Dermatol
1999;135:251 – 3.
[16] Granstein RD, Sober AJ. Drug- and heavy metal-
induced hyperpigmentation. J Am Acad Dermatol
1981;5:1 – 18.
[17] Wintroub BU, Stern R. Cutaneous drug reactions.
Pathogenesis and clinical classification. J Am Acad
Dermatol 1985;13:167 – 79.
[18] Trotter MJ, Tron VA, Hollingdale J, et al. Localized
chrysiasis induced by laser therapy. Arch Dermatol
1995;131:1411 – 4.
[19] Hardwick N, Van Gelder LW, Van der Merwe CA, et al.
Exogenous ochronosis: an epidemiologic study. Br J
Dermatol 1989;120:229 – 38.
[20] Lawrence N, Bligard CA, Reed R, et al. Exogenous
ochronosis in the United States. J Am Acad Dermatol
1988;18:1207 – 11.
[21] Temple-Camp CRE, Saxe N, King H. Benign and ma-
lignant cellular blue nevus: a clinicopathologic study
of 30 cases. Am J Dermatopath 1988;10:289 – 96.
[22] Bortolani A, Barisoni D, Scomazzoni G. Benign
‘‘metastatic’’ cellular blue nevus. Ann Plast Surg
1994;33:426 – 31.
[23] Milgraum SS, Cohen ME, Auletta MJ. Treatment of
blue nevi with the Q-switched ruby laser. J Am Acad
Dermatol 1995;32:307 – 10.
[24] Alster TS, Williams CS. Treatment of nevus of Ota by
the Q-switched alexandrite laser. Dermatol Surg
1995;21:592 – 6.
[25] Kono T, Nozaki M, Chan HH, et al. A retrospective
study looking at the long-term complications of
Q-switched ruby laser in the treatment of nevus of
Ota. Lasers Surg Med 2001;29:156 – 9.
[26] Anderson RR, Geronemus R, Kilmer SL, et al.
Cosmetic tattoo ink darkening. A complication of
Q-switched and pulsed-laser treatment. Arch Dermatol
1993;129:1010 – 4.