DOI: 10.1111/jdv.

12048 JEADV

ORIGINAL ARTICLE

Hyperpigmentation: types, diagnostics and targeted

treatment options
L. Nieuweboer-Krobotova*
Woerden, The Netherlands
*Correspondence: L. Nieuweboer-Krobotova. E-mail: lnieuweboer-krobotova@zuwehofpoort.nl

Abstract
Background Pigment formation is highly complex. It is involved in inflammation, sun protection and many other
processes. For practical purposes, such as exposure time for sun tanning, six skin types are distinguished
according to Fitzpatrick, listed in decreasing lightness. The hyperpigmentation commonly occurs in Fitzpatrick skin
types III to VI and can have a considerable impact on quality of life.
Material & Methods In this article we will give an overview of normal variations of pigmentation and the most
often common pigment abnormalities. It also reviews diagnostics and the current targeted treatment options of
epidermal and dermal pigmentation.
Results There are multiple hyperpigmented skin lesions, classification of pigmentation is based on histology or
Woods light examination. Bleaching agents with phenolic compounds with non-phenolic agens as follow-up therapy
appears to be the most beneficial treatment options for the hyperpigmentation.
Conclusions The effective treatment of pigment disorders is characterized by influence of melanin formation, but
the therapy should be based on a the correct diagnosis and always targeted to the other histopathological
processes in the skin. The Woods light examination shows clinical aspect of the lesions and may be helpful in the
determination of the diagnosis.

Conflict of Interest
None declared.

Introduction
The tone of human skin can vary from a dark brown to nearly a
colourless pigmentation, which may appear reddish because of the
blood in the skin. Skin colour is determined primarily by the
amount and type of melanin, the pigment in the skin. Variation in
skin colour is largely because of genetics.
Virtually, every society tends to assign some valuation to skin
colour differences, especially when these have corresponded to
existing political and economic differentiations. Social isolation of
individuals with discoloration in some countries such as India
does happen because of the easy association with diseases like lep-
rosy.
Differences in skin tone are the most readily perceptible pheno-
types of human populations, and hence have historically lent itself
to colour terminology for race.
For practical purposes, such as exposure time for sun tanning, six
skin types are distinguished according to Fitzpatrick, listed in
decreasing lightness.
Pigment formation is highly complex. It is involved in inflam-
mation, sun protection and many other processes. Melanocytes in
cooperation with enzyme tyrosinase are responsible for the pro-
duction and conversion of dopa to melanin; melanosomes con-
taining pigment are ingested by the keratinocytes, and the melanin
is shed with the stratum corneum cells. Melanin production and
skin colour are affected not only by keratinocytes but also by Lan-
gerhans cells, mast cells and probably by lymphocytes. The effec-
tive treatment of pigment disorders is characterized by influence
of melanin formation, but must be always targeted to the other
histopathological processes in the skin.
The therapy of hyperpigmentation is based on accelerate epider-
mal turnover with removal of pigment in superficial layer (glycolic
acid, salicylic acid and lactic acid), increase in melanosome
transfer and downregulation of tyrosinase (Tretinoin), retard
melanocyte proliferation, melanocyte secretory function and inhi-
bition of inflammation (corticosteroids) and inhibition of enzyme
tyrosinase with decrease melanogenesis (hydroquinone).
Classification of pigmentation based on histology (or Woods
light examination 320–400 nm).
Epidermal melanosis
The hyperpigmented skin shows only excessive quantities of mela-
nin, but a normal number of melanocytes. Clinical examples
include café-au-lait spots and urticaria pigmentosa. The borders
of these spots are sharply demarcated during Woods light

ª 2012 The Author

JEADV 2013, 27 (Suppl.1), 2–4 Journal of the European Academy of Dermatology and Venereology ª 2012 European Academy of Dermatology and Venereology
Hyperpigmentation
examination and have dark brown colour. A drawing of normal
skin is provided for comparison. This hyperpigmentation is most
responsive to local treatment.
Dermal melanosis
This type of hyperpigmentation is caused by melanin within the
dermis, between bundles of collagen, or within melanophages
(clear cells). The epidermal melanin is normal. Clinical examples
include fixed drug eruption, incontinentia pigmenti, lichen planus
and many forms of post-inflammatory hyperpigmentation. The
Woods light does not show any sharp demarcations of the lesions;
the colour of the lesions is brown-grey. A drawing of normal skin
is provided for comparison. This melanin incontinence and
phagocytosis of melanosomes by macrophages is less responsive to
local therapy such as bleaching creams containing for example
hydroquinone.
Mixed type
This hyperpigmentation is characterized with increased melanin in
epidermis and melanophages in dermis. The most common
example is post-inflammatory hyperpigmentation after traumati-
zation (peeling, laser treatment) or inflammatory dermatoses
(acne). The Woods light inspection shows clinical aspect of both
pigmentation types. The local bleaching is effective only in epider-
mal component of hyperpigmentation.
In the following section, we will give an overview of normal pig-
mentation, the most often common pigment abnormalities and
the targeted treatment options of epidermal ⁄ dermal hyperpigmen-
tation.
Normal variations
Futcher’s or Voigt’s lines
These lines are normal colour patterns seen in pigmented individu-
als, especially in Asian people. This demarcation between darker
and normal pigmented skin can be found on the upper arm antero-
medially, the posterior portion of the lower limb, the pre-sternal
area, the post-eromedial area of the spine and the bilateral aspect of
the chest. There are no symptoms. The contact dermatitis and other
inflammatory dermatoses can create similar lines of demarcation.
Hyperpigmentation at the extensor side of the joints
Stretching of the skin at the joints can possibly be a mechanical
trigger for the melanocytes.1 Next causation of striking skin hyper-
pigmentation over the joints can be an episode of inflammatory
arthritis. The phenomenon may be related to increased vascularity
over areas of subcutaneous cellulitis.
Palmar and plantar hyperpigmentation
Macular hyperpigmentation usually involves palms and soles of
healthy black people and is characterized by linear hyperpigment-
ed macules. The lesions of Addison’s disease, lues, ephelides, nevi
JEADV 2013, 27 (Suppl.1), 2–4 Journal of the European Academy of Dermatology and Venereology ª 2012 European Academy of Dermatology and Venereology
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and melanoma form the base of differential diagnosis of palmar
and plantar hyperpigmentation.
Familiar periorbital hyperpigmentation
Periorbital hyperpigmentation is a generally benign, extremely
common condition which is characterized by dark circles around
the eyes, often familial, and frequently found in individuals with
dark pigmentation or Mediterranean ancestry. Usually, hyperpig-
mentation starts in the lower eyelid during childhood and pro-
gresses with age.2 A topic patients may also exhibit per orbital
pigmentation (allergic shiners) thus none of the topical bleaching
therapies will be effective.
Mongolian spot
Mongolian spots represent areas of dermal melanocytosis as result
of arrest in migration of melanocytes from the neural crest to the
epidermis. Approximately 80–100% of the Asian and black new-
born have them.1 The grey-black macular lesions may be solitary
or multiple. The sacrum, buttocks and back are the most common
locations. These symptoms tent to fade in time.
Abnormal hyperpigmentation
Post-inflammatory hyperpigmentation
Post-inflammatory hyperpigmentation is one of the most common
and rather persistent in dark-skinned people. The different skin
conditions like inflammatory dermatoses, trauma and medical
interventions (such as laser therapy) are in dark people often the
aetiology of remaining hyperpigmentation. Sunlight, some medica-
tion and chemicals often worsen the spots. The dyschromia follows
the pattern and distribution of the original dermatoses, but its
intensity is not necessarily related to the degree of previous inflam-
mation. Epidermal pigmentation is mostly brown and fades out in
several months. Dermal pigmentation has a grey-brown colour
and is generally permanent for years.3 Treatment of post-inflam-
matory hyperpigmentation is difficult. The primary goal of therapy
is treating the aetiology. Most significant clinical improvement for
the lesions is directly correlated with different topical therapies
such as depigmenting agents. Particularly important is the combi-
nation of these therapies with the frequented use of sunscreens.
Melasma ⁄ Chloasma
Most melasma develops on the faces of some women who are
pregnant or taking birth control pills. Other aetiological factors
include genetic influence, exposure to UV-radiation, phototoxic
drugs, cosmetics and anti-convulsants. The usually symmetrical
hyperpigmented spots are most prominent on the forehead, malar
eminence and cheeks anterior to the ears. Sometimes it affects the
upper lip and the chin. The goal of therapy is to decrease the pro-
duction of melanin without killing melanocytes. Current treat-
ment options include bleaching agents, chemical peels and the
frequented use of sunscreens.
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4 Nieuweboer-Krobotova
Ashy dermatosis
Ashy dermatosis or erythema dyschromicum perstans is a progres-
sive pigmented disorder. The pathogenesis of this discoloration
remains unclear. Most cases have been in blacks, especially those
from Latin America and Asia. The disease has been called ashy
dermatosis because of its peculiar slate like grey coloration occa-
sionally demonstrated, in its beginning stages, by an erythematous
raised border.4 The disorder is usually asymptomatic. Multiple
brown-grey macules and patches develop over the trunk and
extremities. The face and neck, palms, soles and mucous mem-
branes are usually not affected. The differential diagnosis should
include lichen planus pigmentosus, fixed drug reaction, Addison’s
disease, argyria, photodermatoses or leprosy. None of the therapies
is presently effective.5 Patients, especially those suffering from
hyperpigmentation on visible places such as the face, hands and
neck, can camouflage these areas using skin-coloured cosmetics.
Nevus of Ota and nevus of Ito
These nevi are seen in all races, but affect mostly Asian people.
Nevus of Ota (nevus fuscocoeruleus ophthalmomaxillaris) is a
blue to grey-brown pigmented patch located on the face, usually
within the distribution of the ophthalmic and maxillary branches
of the trigeminal nerve with involving of the sclera in some cases.
The nevus of Ito is located unilaterally on the shoulder and neck.
The macules are present at birth or soon thereafter. The start of
puberty is likewise possible. The lesions look like Mongolian spots
but are not self-limiting. Malignant transformation has been
observed in rare instances. The therapy with pigment laser, has
been in the literature reported as an effective treatment.6
Lentigo solaris
These lesions are characterized by increased numbers of epidermal
melanocytes that are producing excessive quantities of melanin
within the epidermis. Commonly, the epidermal morphology is
also hyperplastic. Lentigines are the prototype of melanocytic epi-
dermal hypermelanosis accompanied by epidermal hyperplasia.
Histologically, they are characterized by an increased number of
melanocytes producing an excessive amount of melanin in the epi-
dermis and prolongation of the epidermal rete pegs. Bleaching
creams containing hydroquinone are not usually effective. Klig-
man found that lentigines solares were resistant to topical treat-
ment with a combination of tretinoin, hydroquinone and
dexamethasone in a hydrophilic ointment. Solar lentigo is actually
being treated with an increasing variety of ablative and non-
ablative lasers.
JEADV 2013, 27 (Suppl.1), 2–4 Journal of the European Academy of Dermatology and Venereology ª 2012 European Academy of Dermatology and Venereology
The targeted treatment options of epidermal
⁄ dermal pigmentation
Epidermal pigmentation responds to many treatments, but con-
comitant dermal pigment is often present in the lesions.
The dermal pigmentation is less ⁄ not responsive to local therapy
such as bleaching creams. The laser therapy is in many cases of
dermal melanin not effective too. The post-inflammatory hyper-
pigmentation after laser treatment is frequently occurring.
For the epidermal pigmentation still is hydroquinone one of the
most effective depigmenting agents.
Bleaching agents with phenolic compounds are: hydroquinone
(2–5%), monobenzon (20%), 4-methoxy-phenol (20%), isopro-
pylcatechol and N-acetyl-4-S-cystaminylphenol.
With non-phenolic compounds are: N-acetylcystein, 4-N-
butylresorcinol, tretinoin – (0.05–0.1%), azealic acid (20%), kojic
acid, ascorbic acid and corticosteroids. Combinations: Kligman
formula (tretinoin, hydroquinone and dexamethasone).
The often used hydroquinone containing bleaching formula is
mostly effective, but has the following disadvantages: high
recurrence rate, first effect after 3–4 months applications, high
concentration required and not effective in all cases. The following
side-effects after prolonged use may occur: contact dermatitis ⁄ irri-
tation, dermatosis ‘en confetti’ and risk of exogenous ochronosis.
The indication for 4-N-butylresorcinol is the role of keeping up
the bleaching result after ending therapy with hydroquinone. The
application of this agents by a mild form of epidermal
hyperpigmentation can be effective too. The 4-N-butylresorcinol is
optimal indicated for long-term use because of absence of the
side-effects as appear by the use of hydroquinone and other phe-
nol containing creams.
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