Causes of Human Skin Hyperpigmentation

The color of human skin is due primarily to the production of melanin by specialized cells in the skin called melanocytes. Melanin produced by these cells both absorbs and scatters UV radiation and thus protects skin from the damaging and mutagenic effects of the solar radiation. Melanocytes can exist in either an activated or resting state.

Your skin is continually in and out of the sun, and thus, your melanocytes are always being turned on and off. During these years of sun exposure the resting state of the melanocyte slowly resets itself to one that is more active. Excessive exposure to sunlight can cause some melanocytes to multiply, producing an uneven distribution of active melanocytes in the skin. The high level of melanin production by some melanocytes and not by others results in a blotchy, uneven "freckle-like" appearance of melanin on the surface of the skin. These areas of hyperpigmentation are called lentigenes and are commonly referred to as age spots or liver spots.

Sun Exposure and Inflammation
How does long term exposure to sunlight cause the activation of melanocytes in the skin? The answer can be summed up in one word: inflammation. Exposure to the UV rays of the sun causes an inflammatory response in the skin and, as we all know, if this inflammatory response is severe, a sunburn results. However, exposure to solar radiation doesn't have to result in a sunburn before inflammation occurs. Very brief exposures to UV radiation can produce an inflammatory response in the skin. Simply walking outside to get in your car can cause subtle inflammatory processes to be initiated in your skin. This non-detectable but active level of inflammation may be thought of as smoldering inflammation.

How Inflammation Activates Melanocytes
If skin exposure to sunlight causes inflammation, what does inflammation have to do with activating melanocytes? When the sun hits the skin, it activates cells in your skin to produce hormone-like substances, commonly called inflammatory mediators. These hormones activate a wide variety of responses in the skin, including: increased vasodilation of blood vessels, which increases redness; increased vascular leakiness of fluid into the skin, which causes swelling; the activation of nerve endings, which causes pain; an increased release of histamine, which causes itching and irritation; and an activation of the melanocytes. In fact, during an inflammatory response, the skin may produce as many as eight to 10 different types of melanocyte activating hormones, which bind to specific receptors on the surface of melanocytes and, in doing so, trigger the activation of the cell from its resting state to a melanin-producing, active state. If the skin is continually exposed to solar radiation over many years, the constant production of inflammatory hormones ultimately results in a permanent activation of melanocytes.

Other Factors Contributing to Inflammation and Hyperpigmentation
Solar radiation isn't the only cause of skin inflammation and hyperpigmentation. Any external stimulus that damages the skin triggers the production of inflammatory mediators, which then activates melanocytes. There are many examples of this type of inflammation-induced pigmentation. Both topical and oral antibiotics (e.g., tetracycline) can induce phototoxic inflammation in the skin, resulting in hyperpigmentation. Accutane also increases the sensitivity of the skin to sunlight and can cause inflammation. Other inflammation triggers include topical retinoids, various fabric dyes, plant derived irritants (e.g., poison ivy), non-steroidal drugs, and chemotherapeutic drugs. Various forms of dermatitis, like eczema or chemically induced contact dermatitis, can cause hyperpigmentation. Acne (an inflammatory condition) and physical trauma to the skin (e.g., laser resurfacing procedures, cosmetic surgery, and temperature and chemical burns) can all increase skin pigmentation. Finally, in addition to inflammatory hormones, other hormones—primarily the sex steroids progesterone and estrogen—cause broad areas of hyperpigmentation, a condition referred to as melasma. This type of hyperpigmentation is quite common in pregnant women and those on birth control pills.

In conclusion, we can see that any insult to the skin can cause inflammation and trigger the onset of hyperpigmentation.

Bryan B. Fuller
Ph.D., Scientific Advisor

Dr. Fuller was integrally involved in the development of the Nu Skin® Tri-Phasic White™ System. His scientific expertise on the regulation of human skin pigmentation comes from more than 25 years of research and has led to 11 U.S. patents. As a molecular endocrinologist, Dr. Fuller has investigated numerous skin-derived hormones, and his research interests include inflammatory skin conditions. Dr. Fuller is currently an associate professor of biochemistry and molecular biology at the University of Oklahoma Health Sciences Center and an adjunct professor in the Department of Dermatology.