Evaluation and treatment of post-inflammatory hyperpigmentation
Wednesday, October 13, 2010
Post-inflammatory hyperpigmentation (PIH) primarily affects
people with richly pigmented skin (Fitzpatrick skin phototype
III-VI) or lighter-skinned individuals with dark hair and dark
irides. There is no age or gender predilection. As an example, in
the US, the skin of color population (currently defined as
Black/African American, Hispanic/Latino, Asian, Pacific Islander,
and Native American) is growing rapidly, with a projection that
this collective minority will overtake the current Caucasian
majority by 2050. Consequently, PIH will be a dermatologic sequela
that will be encountered more frequently.
PIH often leads to psychosocial distress, which can be more
anxiety-provoking than the triggering condition itself. This
anxiety is often heightened, as there is no quick and effective
treatment other than cosmetic cover-up. PIH is defined simply as
darkening of the skin secondary to a prior source of inflammation,
as seen in acne, contact dermatitis, insect bites, infections,
burns, or eczema (Figure 1). PIH may also be referred to as
post-inflammatory melanoderma; however, this differential diagnosis
is limited and may include melasma, solar lentigo, and drug-induced
hyperpigmentation. Usually, PIH follows the shape and distribution
of the preceding inflammation and is easily diagnosed by clinical
history and examination.
This article highlights the etiology, clinical evaluation and
special considerations for the treatment of PIH.
Figure 1. Post-inflammatory
hyperpigmentation from acne vulgaris on the forehead.
Etiology and pathophysiology
There are structural and functional differences in skin of
color, as well as cultural traditions, that influence clinical
disease presentation and treatment. It is unclear why inflammatory
processes cause hyperpigmentation, but a complex interaction has
been proposed between inflammatory cells and
melanocytes.1 Moreover, inflammatory mediators, such as
leukotriene (LT)C4, LTD4 and thromboxane
B2, have been specifically mentioned as key
contributors.2 It is possible that the degree of
hyperpigmentation parallels the severity of inflammation, as seen
in UVB-induced PIH.3
PIH can be epidermal, dermal or a combination of the two. A
light-brown appearance suggests superficial pigmentation with
melanin within the epidermis, where there is typically an increase
in melanogenesis and an increased transfer of melanin granules to
the surrounding keratinocytes. In contrast, a deep brown-gray tone
represents dermal pigmentation, in which there is often disruption
and/or destruction of the basal cell layer, phagocytosis of the
resultant debris by macrophages, and residual persistent
melanophages in the dermis.
More specifically, PIH associated with acne, folliculitis, or
eczema typically leads to increased melanin in the basal layer of
the epidermis but not the dermis.4 In contrast, when the
basement membrane is disrupted, eg, in atopic dermatitis or lichen
planus, pigmentary incontinence can occur, with subsequent dermal
deposition of melanin.5 Furthermore, cultural practices
performed among the skin of color population, such as moxibustion,
coin rubbing, and cupping, may lead to burns, ecchymoses and
secondary epidermal and/or dermal post-inflammatory
hyperpigmentation. The location of melanin deposition helps to
select the treatment modalities that will potentially be
Patient history and clinical examination
Identifying the primary disease process through patient history
and clinical examination is the most critical step in diagnosis and
development of a treatment plan. It is essential to explain to the
patient why the cause must first be addressed in order to allow for
long-term improvement in PIH. It is often easy to identify the
primary dermatologic disease leading to PIH; however, some disease
entities pose a more challenging differential diagnosis such as
phytophotodermatitis, fixed drug eruption, and erythema ab
Clinical examination begins with an assessment of the borders,
color and distribution of pigmentation. A Wood's lamp helps to
identify the depth of pigmentation in epidermal lesions, which have
accentuated pigmentation; dermal lesions lack this trait. Mixed
lesions, characterized by both epidermal and dermal pigmentation,
show partial accentuation.
There is no simple treatment for PIH; however, some basic
principles for treating PIH are:
- Treat the underlying skin condition effectively.
- Simplify the skin-care regimen and avoid any potential
irritants that could lead to further inflammation and PIH.
- Abide by strict sun-protective behaviors daily (including
sun-protective clothing with wide-brimmed hats).
- Treat the hyperpigmentation with the wide array of treatment
options currently available.
- Educate the patient that the treatment of PIH requires time and
It is important to set the stage that PIH is difficult to treat.
An initial candid discussion with the patient regarding realistic
clinical expectations allows for a more satisfactory long-term
physician-patient relationship. The next step is to discuss the
various treatment options, along with the risks and benefits of
each. Several topical therapies for PIH, along with their
mechanisms of action, are listed in Table 1. One of the most
commonly used treatment regimens includes topical
hydroquinone-containing agents, together with strict
photoprotection. Likewise, combination therapies have been used
effectively; these include variants of the original Kligman's
formula (tretinoin 0.1% + hydroquinone 5% + dexamethasone 0.1%)
with differing amounts of topical retinoids, hydroquinone, and
Table 1. Treatment modalities for post-inflammatory
It generally takes 2-3 months of topical treatment to see partial
lightening of the hyperpigmentation, and more notable improvement
(near resolution of PIH) may take many more months to a year. All
topical therapies for PIH have the potential to cause irritant or
allergic contact dermatitis; therefore, some basic recommendations
include the following:
- Use a repeat open application test on a small area for several
days to test for potential irritation.
- Apply hydroquinone-based bleaching agents to the hyperpigmented
areas, using a precise technique to minimize halo hypopigmentation
of the surrounding normal skin.
Hydroquinone has been the standard treatment for
hyperpigmentation for several years. Yet, in 2006, the Food and
Drug Administration (FDA) proposed a ban for over-the-counter
hydroquinone. They cited reports of exogenous ochronosis and
development of murine hepatic adenomas, renal adenomas, and
leukemia in rats who were given large systemic doses of
hydroquinone over extended periods of time.6,7 Such
carcinogenicity has not been shown or established in humans.
Furthermore, in the US, only a limited number of cases of exogenous
ochronosis has been reported in the medical
literature.6,7 There has been no final decision on the
proposed ban; however, in March 2010, the FDA announced the
nomination of hydroquinone for further studies. These studies are
to be conducted by the National Toxicology Program and include
comparative metabolism studies in rats and mice by the oral and
dermal routes, a reproductive toxicity study by the oral route in
rats and mice, and dermal carcinogenicity studies of hydroquinone
in mice and rats.
Unfortunately, with the increasing frequency of PIH amongst the
growing skin of color population, and despite some advances in
clinical research, there is still no simple treatment for PIH. It
is imperative to emphasize the inherent difficulty in treating
hyperpigmentation, and to stress the importance of patience to our
- Nordlund JJ. Postinflammatory hyperpigmentation. Dermatol
- TomitaY, K. Maeda, Tagami H. Melanocyte-stimulating properties
of arachidonic acid metabolites: possible role in postinflammatory
pigmentation. Pigment Cell Res
- Takiwaki H, Shirai S, Kohno H, et al.The degrees of
UVB-induced erythema and pigmentation correlate linearly and are
reduced in a parallel manner by topical anti-inflammatory agents.
J Invest Dermatol 1994;103:642-646.
- Bulengo-Ransby SM, Griffiths CE, Kimbrough-Green CK, et
al. Topical tretinoin (retinoic acid) therapy for
hyperpigmented lesions caused by inflammation of the skin in black
patients. N Engl J Med
- Humphreys F, Spencer J, Mclaren K, Tidman MJ. An histological
and ultrastructural study of the 'dirty neck' appearance in atopic
eczema. Clin Exp Dermatol
- Merola JF, Meehan S, Walters RF, Brown L. Exogenous ochronosis.
Dermatol Online J 2008;15:6.
- Levitt, J. The safety of hydroquinone: a dermatologist's
response to the 2006 Federal Register. J Am Acad Dermatol