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Clinical Updates

Roopal V. Kundu, MD

Evaluation and treatment of post-inflammatory hyperpigmentation

Roopal Kundu

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 effective. 

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 igne.

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:

  1. Treat the underlying skin condition effectively.
  2. Simplify the skin-care regimen and avoid any potential irritants that could lead to further inflammation and PIH.
  3. Abide by strict sun-protective behaviors daily (including sun-protective clothing with wide-brimmed hats).
  4. Treat the hyperpigmentation with the wide array of treatment options currently available.
  5. Educate the patient that the treatment of PIH requires time and patience.

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 topical corticosteroids.

Table 1. Treatment modalities for post-inflammatory hyperpigmentation.

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:

  1. Use a repeat open application test on a small area for several days to test for potential irritation.
  2. Apply hydroquinone-based bleaching agents to the hyperpigmented areas, using a precise technique to minimize halo hypopigmentation of the surrounding normal skin.

Special considerations

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.

Future considerations

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 patients.


  1. Nordlund JJ. Postinflammatory hyperpigmentation. Dermatol Clin 1988;6:185-192.
  2. TomitaY, K. Maeda, Tagami H. Melanocyte-stimulating properties of arachidonic acid metabolites: possible role in postinflammatory pigmentation. Pigment Cell Res 1992;5:357-361.
  3. 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.
  4. 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 1993;328:1438-1443.
  5. Humphreys F, Spencer J, Mclaren K, Tidman MJ. An histological and ultrastructural study of the 'dirty neck' appearance in atopic eczema. Clin Exp Dermatol 1996;21:17-19.
  6. Merola JF, Meehan S, Walters RF, Brown L. Exogenous ochronosis. Dermatol Online J 2008;15:6.
  7. Levitt, J. The safety of hydroquinone: a dermatologist's response to the 2006 Federal Register. J Am Acad Dermatol 2007;57:854-872.