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DOI: 10.1111/jdv.

12048 JEADV


Hyperpigmentation: types, diagnostics and targeted

treatment options
L. Nieuweboer-Krobotova*
Woerden, The Netherlands
*Correspondence: L. Nieuweboer-Krobotova. E-mail:

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 taining pigment are ingested by the keratinocytes, and the melanin
The tone of human skin can vary from a dark brown to nearly a is shed with the stratum corneum cells. Melanin production and
colourless pigmentation, which may appear reddish because of the skin colour are affected not only by keratinocytes but also by Lan-
blood in the skin. Skin colour is determined primarily by the gerhans cells, mast cells and probably by lymphocytes. The effec-
amount and type of melanin, the pigment in the skin. Variation in tive treatment of pigment disorders is characterized by influence
skin colour is largely because of genetics. of melanin formation, but must be always targeted to the other
Virtually, every society tends to assign some valuation to skin histopathological processes in the skin.
colour differences, especially when these have corresponded to The therapy of hyperpigmentation is based on accelerate epider-
existing political and economic differentiations. Social isolation of mal turnover with removal of pigment in superficial layer (glycolic
individuals with discoloration in some countries such as India acid, salicylic acid and lactic acid), increase in melanosome
does happen because of the easy association with diseases like lep- transfer and downregulation of tyrosinase (Tretinoin), retard
rosy. melanocyte proliferation, melanocyte secretory function and inhi-
Differences in skin tone are the most readily perceptible pheno- bition of inflammation (corticosteroids) and inhibition of enzyme
types of human populations, and hence have historically lent itself tyrosinase with decrease melanogenesis (hydroquinone).
to colour terminology for race. Classification of pigmentation based on histology (or Woods
For practical purposes, such as exposure time for sun tanning, six light examination 320–400 nm).
skin types are distinguished according to Fitzpatrick, listed in
decreasing lightness. Epidermal melanosis
Pigment formation is highly complex. It is involved in inflam- The hyperpigmented skin shows only excessive quantities of mela-
mation, sun protection and many other processes. Melanocytes in nin, but a normal number of melanocytes. Clinical examples
cooperation with enzyme tyrosinase are responsible for the pro- include café-au-lait spots and urticaria pigmentosa. The borders
duction and conversion of dopa to melanin; melanosomes con- 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 3

examination and have dark brown colour. A drawing of normal and melanoma form the base of differential diagnosis of palmar
skin is provided for comparison. This hyperpigmentation is most and plantar hyperpigmentation.
responsive to local treatment.
Familiar periorbital hyperpigmentation
Dermal melanosis Periorbital hyperpigmentation is a generally benign, extremely
This type of hyperpigmentation is caused by melanin within the common condition which is characterized by dark circles around
dermis, between bundles of collagen, or within melanophages the eyes, often familial, and frequently found in individuals with
(clear cells). The epidermal melanin is normal. Clinical examples dark pigmentation or Mediterranean ancestry. Usually, hyperpig-
include fixed drug eruption, incontinentia pigmenti, lichen planus mentation starts in the lower eyelid during childhood and pro-
and many forms of post-inflammatory hyperpigmentation. The gresses with age.2 A topic patients may also exhibit per orbital
Woods light does not show any sharp demarcations of the lesions; pigmentation (allergic shiners) thus none of the topical bleaching
the colour of the lesions is brown-grey. A drawing of normal skin therapies will be effective.
is provided for comparison. This melanin incontinence and
phagocytosis of melanosomes by macrophages is less responsive to Mongolian spot
local therapy such as bleaching creams containing for example Mongolian spots represent areas of dermal melanocytosis as result
hydroquinone. of arrest in migration of melanocytes from the neural crest to the
epidermis. Approximately 80–100% of the Asian and black new-
Mixed type born have them.1 The grey-black macular lesions may be solitary
This hyperpigmentation is characterized with increased melanin in or multiple. The sacrum, buttocks and back are the most common
epidermis and melanophages in dermis. The most common locations. These symptoms tent to fade in time.
example is post-inflammatory hyperpigmentation after traumati-
zation (peeling, laser treatment) or inflammatory dermatoses Abnormal hyperpigmentation
(acne). The Woods light inspection shows clinical aspect of both
pigmentation types. The local bleaching is effective only in epider- Post-inflammatory hyperpigmentation
mal component of hyperpigmentation. Post-inflammatory hyperpigmentation is one of the most common
In the following section, we will give an overview of normal pig- and rather persistent in dark-skinned people. The different skin
mentation, the most often common pigment abnormalities and conditions like inflammatory dermatoses, trauma and medical
the targeted treatment options of epidermal ⁄ dermal hyperpigmen- interventions (such as laser therapy) are in dark people often the
tation. aetiology of remaining hyperpigmentation. Sunlight, some medica-
tion and chemicals often worsen the spots. The dyschromia follows
Normal variations the pattern and distribution of the original dermatoses, but its
intensity is not necessarily related to the degree of previous inflam-
Futcher’s or Voigt’s lines mation. Epidermal pigmentation is mostly brown and fades out in
These lines are normal colour patterns seen in pigmented individu- several months. Dermal pigmentation has a grey-brown colour
als, especially in Asian people. This demarcation between darker and is generally permanent for years.3 Treatment of post-inflam-
and normal pigmented skin can be found on the upper arm antero- matory hyperpigmentation is difficult. The primary goal of therapy
medially, the posterior portion of the lower limb, the pre-sternal is treating the aetiology. Most significant clinical improvement for
area, the post-eromedial area of the spine and the bilateral aspect of the lesions is directly correlated with different topical therapies
the chest. There are no symptoms. The contact dermatitis and other such as depigmenting agents. Particularly important is the combi-
inflammatory dermatoses can create similar lines of demarcation. nation of these therapies with the frequented use of sunscreens.

Hyperpigmentation at the extensor side of the joints Melasma ⁄ Chloasma

Stretching of the skin at the joints can possibly be a mechanical Most melasma develops on the faces of some women who are
trigger for the melanocytes.1 Next causation of striking skin hyper- pregnant or taking birth control pills. Other aetiological factors
pigmentation over the joints can be an episode of inflammatory include genetic influence, exposure to UV-radiation, phototoxic
arthritis. The phenomenon may be related to increased vascularity drugs, cosmetics and anti-convulsants. The usually symmetrical
over areas of subcutaneous cellulitis. hyperpigmented spots are most prominent on the forehead, malar
eminence and cheeks anterior to the ears. Sometimes it affects the
Palmar and plantar hyperpigmentation upper lip and the chin. The goal of therapy is to decrease the pro-
Macular hyperpigmentation usually involves palms and soles of duction of melanin without killing melanocytes. Current treat-
healthy black people and is characterized by linear hyperpigment- ment options include bleaching agents, chemical peels and the
ed macules. The lesions of Addison’s disease, lues, ephelides, nevi frequented use of sunscreens.

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
4 Nieuweboer-Krobotova

Ashy dermatosis The targeted treatment options of epidermal

Ashy dermatosis or erythema dyschromicum perstans is a progres- ⁄ dermal pigmentation
sive pigmented disorder. The pathogenesis of this discoloration Epidermal pigmentation responds to many treatments, but con-
remains unclear. Most cases have been in blacks, especially those comitant dermal pigment is often present in the lesions.
from Latin America and Asia. The disease has been called ashy The dermal pigmentation is less ⁄ not responsive to local therapy
dermatosis because of its peculiar slate like grey coloration occa- such as bleaching creams. The laser therapy is in many cases of
sionally demonstrated, in its beginning stages, by an erythematous dermal melanin not effective too. The post-inflammatory hyper-
raised border.4 The disorder is usually asymptomatic. Multiple pigmentation after laser treatment is frequently occurring.
brown-grey macules and patches develop over the trunk and For the epidermal pigmentation still is hydroquinone one of the
extremities. The face and neck, palms, soles and mucous mem- most effective depigmenting agents.
branes are usually not affected. The differential diagnosis should Bleaching agents with phenolic compounds are: hydroquinone
include lichen planus pigmentosus, fixed drug reaction, Addison’s (2–5%), monobenzon (20%), 4-methoxy-phenol (20%), isopro-
disease, argyria, photodermatoses or leprosy. None of the therapies pylcatechol and N-acetyl-4-S-cystaminylphenol.
is presently effective.5 Patients, especially those suffering from With non-phenolic compounds are: N-acetylcystein, 4-N-
hyperpigmentation on visible places such as the face, hands and butylresorcinol, tretinoin – (0.05–0.1%), azealic acid (20%), kojic
neck, can camouflage these areas using skin-coloured cosmetics. acid, ascorbic acid and corticosteroids. Combinations: Kligman
formula (tretinoin, hydroquinone and dexamethasone).
Nevus of Ota and nevus of Ito The often used hydroquinone containing bleaching formula is
These nevi are seen in all races, but affect mostly Asian people. mostly effective, but has the following disadvantages: high
Nevus of Ota (nevus fuscocoeruleus ophthalmomaxillaris) is a recurrence rate, first effect after 3–4 months applications, high
blue to grey-brown pigmented patch located on the face, usually concentration required and not effective in all cases. The following
within the distribution of the ophthalmic and maxillary branches side-effects after prolonged use may occur: contact dermatitis ⁄ irri-
of the trigeminal nerve with involving of the sclera in some cases. tation, dermatosis ‘en confetti’ and risk of exogenous ochronosis.
The nevus of Ito is located unilaterally on the shoulder and neck. The indication for 4-N-butylresorcinol is the role of keeping up
The macules are present at birth or soon thereafter. The start of the bleaching result after ending therapy with hydroquinone. The
puberty is likewise possible. The lesions look like Mongolian spots application of this agents by a mild form of epidermal
but are not self-limiting. Malignant transformation has been hyperpigmentation can be effective too. The 4-N-butylresorcinol is
observed in rare instances. The therapy with pigment laser, has optimal indicated for long-term use because of absence of the
been in the literature reported as an effective treatment.6 side-effects as appear by the use of hydroquinone and other phe-
nol containing creams.
Lentigo solaris
These lesions are characterized by increased numbers of epidermal References
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dermal hypermelanosis accompanied by epidermal hyperplasia. melanoses and hypermelanoses. In Fitzpatrick’s Dermatology in General
Histologically, they are characterized by an increased number of Medicine, 6th ed. Mc Graw-Hill; Vol. 1, 2003: 836–881.
3 Lacz NL, Vafaie J, Kihicza NI, Schwartz RA. Postinflammatory hyper-
melanocytes producing an excessive amount of melanin in the epi-
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man found that lentigines solares were resistant to topical treat- of Cinderella or Ashy dermatosis. Int J Dermatol 2004; 43: 230–232.
5 Kupres K, Meffert JJ. Ashy dermatosis. Am Fam Physician 2003; 68:
ment with a combination of tretinoin, hydroquinone and
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ablative lasers.

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JEADV 2013, 27 (Suppl.1), 2–4 Journal of the European Academy of Dermatology and Venereology ª 2012 European Academy of Dermatology and Venereology