Written by Dr. Katie Wang
Edited by Dr. Paul M. Graham
Post-inflammatory hyperpigmentation (PIH) is a common source of frustration particularly among darker-skinned individuals. Those most susceptible to developing PIH include African Americans, Hispanics, Asians, Native Americans, Pacific Islanders, and those of Middle Eastern decent. Many common dermatologic conditions such as acne, eczema, allergic dermatitis, and physical injury can leave pigmented marks long after the skin lesions have resolved. In this two-part series, we will discuss the mechanism behind these stubborn dark spots and what you can do to treat them. Stay tuned for an upcoming article discussing pigmented spots caused by sun exposure and aging.
PIH can be caused by a variety of factors, including fungal and viral infections, bug bites, and allergic reactions. However, the most common causes that often affect darker-skinned individuals tend to be acne, eczema, and a superficial skin infection called impetigo. PIH can result from overproduction of skin pigment 
(melanin) in response to inflammation or to damage of the melanocytes (skin pigment cells) within the epidermis. Inflammatory mediators such as prostanoids, cytokines, chemokines, and reactive oxygen species (ROS) have all been found to play a role in stimulating melanocytes (pigment cells) to produce too much melanin or demonstrate irregular dispersion of pigment. If this inflammation is confined to the epidermis (top layer of the skin), there can be an increase in the production or transfer of pigment to surrounding skin cells (keratinocytes) in the affected area. However, if the PIH occurs in the dermis, the excess pigment can become entrapped within cells known as melanophages. Accumulation of melanophages often results in a bluish-gray color left at the site of inflammation. Some researchers suggest that pigment may remain in these melanophages for years before slowly resolving.
Because PIH can be so difficult to treat, the most important step to prevention is to address the underlying causes of inflammation and avoidance of inciting factors. Furthermore, these 
hyperpigmented skin lesions can significantly darken with ultraviolet (UV) light exposure even after the inflammation has resolved. Therefore, it is paramount to prevent UV light exposure in the affected area with diligent application of SPF 30+ sunscreens and sun-protective clothing. Unfortunately, without any treatment, PIH can take months to years to resolve. In addition to proper sun-protection, there are several other treatment options that lead to promising results.
Topical depigmenting agents (bleaching creams) are the most common first line treatments for PIH. Hydroquinone, azelaic acid, kojic acid, licorice extract, and retinoids can be used alone or in combination. Hydroquinone is a phenolic compound that inhibits tyrosinase (pigment producing enzyme), which subsequently blocks the conversion of dihydroxyphenylalanine (DOPA) to melanin. Hydroquinone is commonly available in a cream base at concentrations of 2-4%. A study investigating the effectiveness of combined agents did find better results in patients that used a mixture of hydroquinone, retinol/retinoid, and antioxidants.
Are there any side effects to using hydroquinone?
Unfortunately, yes. If the topical agent causes skin irritation, it may lead to inflammation and subsequently a worsening of the PIH. Using topical steroids could decrease the amount of irritation and help prevent worsening of PIH. However, because of the side effects of topical steroids and hydroquinone use, it is important to be monitored by a dermatologist when using these products. Prolonged use of hydroquinone increases the risk of developing deposition of the medication within the skin with long term use, known as onchronosis. Although rare, it is highly recommended to limit the use of hydroquinone to less than three months. Another common side effect of prolonged hydroquinone use is hypopigmentation of the surrounding skin, especially to the unaffected skin around the dark spot.
In summary, there are a lot of factors that play a role in the development of dark spots. Fortunately, PIH does eventually fade. Without treatment, it typically takes 6-12 months to return to the skin natural appearance. Keep in mind that prolonged use of depigmenting medications do have their side effects, but are generally safe and effective when used as prescribed.
In our next PIH article, we will highlight some newer, less well-known treatment options that are currently on the horizon.
Photo Credit: Idiva.com, LaserMelbourne.com, Qsota.com
References:
- Davis E, Callender V. Postinflammatory hyperpigmentation: a review of the epidemiology, clinical features, and treatment options in skin of color. J Clin Aesthet Dermatol 2010;3:20.
- http://www.uptodate.com
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