The biology driving hyperpigmentation.
Hyperpigmentation. The scourge of many melanated baddies. We can do everything right- from resisting the most difficult urge to pick at our acne, to mundane things like wearing sunscreen. And yet, we are faced with the inevitable. One pimple fades away and leaves a splotchy dark patch in its wake. Perfect.
The solutions are marketed to us as simple: buy an expensive serum, apply religiously, re-up when you run out, and repeat. Oh, how quickly achieving an even skin tone becomes a Sisyphean task! Worry not, my dearest muñeca. Hyperpigmentation is persistent, but then again, so are you. You have the wits, the resources, and hopefully, after reading this blog, the knowledge required to defeat your patchy foe. Pull up a chair and put your reading glasses on; class is in session!
Skin Anatomy
You might be aware that melanin is a skin pigment. It gets its namesake from the specialized cells that produce it- melanocytes. Melanocytes sit in the lowest layer of the epidermis and deposit their rich pigments into keratinocytes— another type of skin cell closer to the skin’s surface [1]. The interplay between melanocytes and their partner cells, keratinocytes, influences pigment creation, melanocyte growth and spread, and pigment deposit.
Figure 1. Adapted from [1]
Epidermis with component layers. The melanin unit comprised of the melanocyte and keratinocytes is shown on the right.
Melanogenesis
A specialized enzyme called tyrosinase in melanocytes converts tyrosine, an amino acid, into melanin. These enzymes create a reddish pigment, pheomelanin, when thiols ( sulfurous compounds) are around. Remove the sulfur from the equation, and a different product is formed— a brown-black eumelanin. Every human has a different ratio of eumelanin to pheomelanin. Ultimately, we’re left with a pigment that absorbs and scatters UV radiation and oxidizes free radicals [2][3]. This process is stimulated by UV radiation as well as chemical and hormonal signals secreted by neighboring cells.
Post-inflammatory Hyperpigmentation (it’s a mouthful, but when has that ever stopped you?)
As the name implies, post-inflammatory hyperpigmentation occurs after an inflammatory event: acne, contact dermatitis, or atopic dermatitis. Our bodies initiate the inflammation process to heal after an injury. Prostaglandins are one of many signaling molecules involved in the inflammatory process. Their role in the epidermis puts them at the front and center of this story.
Picture this. You step out on a sunny day and feel the warmth of the sun hit you. As you bask in its glory, keratinocytes recognize the influx of UV radiation and rapidly make prostaglandins [4][5]. Keratinocytes then secrete the prostaglandins. These molecules navigate to the neighboring melanocytes and communicate news of the solar assault. Once briefed on the presence of UV radiation, melanocytes spring into action. They begin to form more tentacle-like protrusions- called dendrites- which make contact with the keratinocytes. The increase in dendrites ends with more melanin concentrated in a patch of keratinocytes— underscoring the importance of sunscreen for hyperpigmentation [4][6][7]. While they are just one of many molecules involved in stimulating melanin production (like cytokines, hormones, and other factors), we can observe a correlation between inflammation and melanin production [reviewed in 1].
The biological process is complex. Your approach should be flexible
Take a look in your medicine cabinet or your beauty vanity and see if you can find any of the following ingredients in your skin potions: tranexamic acid, azelaic acid, vitamin C, kojic acid, arbutin, and hydroquinone. Got it? Good.
All of those ingredients block tyrosinase’s activity, reducing the amount of pigment that your melanocytes can produce. Some with more direct action than others. Vitamin C, for example, interacts with copper ions at the business end of tyrosinase, blocking its ability to convert tyrosine to melanin. Kojic acid does similar work to the copper ions in the tyrosinase active site [8]. Finding what works for you can be a process of trial and error, as some of these ingredients can be irritating, and not all are formulated equally. In fact, most of the products on the market have some blend of these ingredients designed to work together to fade your dark spots. Some products, like Topicals’s Faded serum, is made with known lightening actives like kojic acid and a superstar ingredient, niacinamide. This anti-inflammatory ingredient is usually well tolerated and hinders the transfer of melanin from the melanocytes to keratinocytes on your skin’s surface [8, 9]. Single active products, like The Ordinary’s Ascorbyl Glucoside, might be a better match for people with sensitive skin. That’s not to say anything about the quality of either product (although I do love them both), but the fewer ingredients in a product, the less likely it is that you’ll develop a sensitivity to it. And therein lies the problem: targeting multiple steps in the pigment pathway can provide synergistic effects for fading dark spots, but overloading on ingredients can cause irritation and worsen your problem.
Given the complexity of pigmentation, finding the right product, or combination of products, is going to take some trial and error. It’s a matter of trying something new, observing how your skin reacts, and trying again! My hope for you, my dearest muñeca, is that this knowledge empowers you to strut into the closest Sephora with confidence.
Cichorek M, Wachulska M, Stasiewicz A, Tymińska A. Skin melanocytes: biology and development. Postepy Dermatol Alergol. 2013 Feb;30(1):30-41. doi: 10.5114/pdia.2013.33376. Epub 2013 Feb 20. PMID: 24278043; PMCID: PMC3834696.
Costin GE, Hearing VJ. Human skin pigmentation: melanocytes modulate skin color in response to stress. FASEB J. 2007 Apr;21(4):976-94. doi: 10.1096/fj.06-6649rev. Epub 2007 Jan 22. PMID: 17242160.
Riley PA. Melanin. Int J Biochem Cell Biol. 1997 Nov;29(11):1235-9. doi: 10.1016/s1357-2725(97)00013-7. PMID: 9451820.
Cheng H, Huang H, Guo Z, Chang Y, Li Z. Role of prostaglandin E2 in tissue repair and regeneration. Theranostics. 2021 Aug 13;11(18):8836-8854. doi: 10.7150/thno.63396. PMID: 34522214; PMCID: PMC8419039.
Pentland AP, Mahoney M, Jacobs SC, Holtzman MJ. Enhanced prostaglandin synthesis after ultraviolet injury is mediated by endogenous histamine stimulation. A mechanism for irradiation erythema. J Clin Invest. 1990 Aug;86(2):566-74. doi: 10.1172/JCI114746. PMID: 1696589; PMCID: PMC296762.
Park HY, Kosmadaki M, Yaar M, Gilchrest BA. Cellular mechanisms regulating human melanogenesis. Cell Mol Life Sci. 2009 May;66(9):1493-506. doi: 10.1007/s00018-009-8703-8. PMID: 19153661.
Benito-Martínez S, Salavessa L, Raposo G, Marks MS, Delevoye C. Melanin Transfer and Fate within Keratinocytes in Human Skin Pigmentation. Integr Comp Biol. 2021 Oct 14;61(4):1546-1555. doi: 10.1093/icb/icab094. PMID: 34021340; PMCID: PMC8516110.
Gillbro, J.M. and Olsson, M.J. (2011), The melanogenesis and mechanisms of skin-lightening agents – existing and new approaches. International Journal of Cosmetic Science, 33: 210-221. https://doi.org/10.1111/j.1468-2494.2010.00616.
Sarkar R, Arora P, Garg KV. Cosmeceuticals for Hyperpigmentation: What is Available? J Cutan Aesthet Surg. 2013 Jan;6(1):4-11. doi: 10.4103/0974-2077.110089. PMID: 23723597; PMCID: PMC3663177.