Hyperpigmentation 101

What is hyperpigmentation?

In the field of dermatology, hyperpigmentation is a general descriptor to refer to an increase or excess of natural pigment of the skin.¹ As you can imagine, this encompasses a vast variety of skin phenomena, with causes ranging from rare skin conditions such as acne to the most universal, like photoaging. For our purposes, we will be covering the most common forms of hyperpigmentation.

Before we get into the how’s and why’s of "excess" pigmentation, here’s a quick primer on the structure of our skin, and our skin’s pigment, melanin.  

Our skin can be considered to be two main layers sandwiched together: what we can see is the epidermis, made of smaller, functional layers of keratin to help us interact with the environment. Beneath the epidermis is the dermis, which is mostly follicles and glands.  They are separated by a thin wall called the basement membrane.² 

What is melanin?

Melanin is actually not a single compound, but a mixture of different biopolymers created inside melanocytes, or melanin-creating cells, mostly concentrated in the deepest bottom of the epidermis.²,³

The main creator of melanin in these cells is an enzyme named tyrosinase. Tyrosinase is who sets off the chain reaction that converts the amino acid called tyrosine into melanin.⁴

After the melanin is synthesized, it’s brought around to other places, like the keratin cells in the epidermis, where they pile up to protect the skin against UV rays, among other helpful functions.² You can also find melanocytes in the dermis, and even in hair follicles, giving color to our hair.²

It’s clear that melanin fulfills very important functions in our body. So what’s the problem? Well, just as our emotional defense mechanisms sometimes kick in at the wrong time, the melanin production in these cells can go into overdrive when they perceive a threat, as they try to protect us. Tyrosinase is activated by UV radiation, for example, and with enough UV, the tyrosinase is going to keep working at making more and more melanin!⁴

It’s important to remember that the body is a complex organism balancing an incredible array of moving parts. You have characters like estrogen, who are the ones producing tyrosinase.⁴ If you have extra estrogen, you’re going to have extra tyrosinase. So that’s a lot of extra melanin being made, and sometimes, it sticks around for much longer than we need or want it to. 

Common types & causes of hyperpigmentation, from age spots to dark spots

 

Solar lentigines

AKA age spots, liver spots, or sun spots (yes, all the same!) are like freckles, ranging from tan to dark brown, but larger, ranging from 3mm to 2cm.³ You’ll find pigmentation on hands, forearms, face, upper chest, and back –where the sun most often strikes. Like freckles, they’re more commonly found in skin on the lower end of the Fitzpatrick scale, with their likelihood directly correlating with age.³ They were found to be in 90% of the white population that is over the age of 60.³ 

Ephelides

AKA freckles, are small spots of hyperpigmentation, from 1-3mm, and mostly found in white skin lower on the Fitzpatrick scale.³ They’ll pop up in the areas most exposed to the sun, like the face, upper hands, and upper trunk. It’s a classic case of the sun’s UV spurring on the production of melanin, together with an increased movement of melanin to the visible surface area of the face. They can pop up all of a sudden, grow darker, and cluster together, but have the potential to naturally fade over time.³ 

Post-inflammatory hyperpigmentation (PIH) 

PIH is when the skin produces extra melanin, or irregularly distributed melanin, as a response to inflammation, whether from an internal skin condition such as acne or in response to external injury that results in scars.⁵ PIH is most prevalent in skin of color, which ranges from Fitzpatrick IV to VI.⁵

In certain cases, if the inflammation damages the basement membrane (the wall separating the epidermis from the dermis), the melanin can seep into the dermis.⁵ The process of breaking down this melanin in the dermis can take months to years to clear on its own.⁵ Epidermal PIH tends to be brown with clear borders, but dermal PIH has more diffuse borders, and is dark grey.⁵ The shape and size of pigment can vary greatly, as it depends on the previous inflammation.⁵

A most notable and frustrating part of PIH is that the inflammation is often caused by cosmetic procedures meant to improve the skin. Popular therapies like chemical peels, dermabrasion, and lasers can trigger long-lasting PIH. Fractional CO2 laser, in particular, caused 68-92% of Fitzpatrick skin type IV patients to develop PIH, which then lasted an average of 3.8 months!⁵ 

With these challenges in mind, it’s crucial to focus on prevention if you are predisposed to PIH. Take caution towards potential irritants, as we work towards finding more treatments and solutions!

Melasma or melasma gravidarum

AKA the “mask of pregnancy,” is – surprise! – not just for the pregnant.⁶ But indeed, 90% of those affected are women, mostly Fitzpatrick types III and IV.³ Melasma is characterized by symmetrical light to dark brown spots varying in size on the face, and usually in specific patterns – centered on the face, across the cheeks,nose and lips or on the lower jaw.⁷

Even though melasma is one of the most common forms of hyperpigmentation, affecting millions of people, research and knowledge regarding its causes has been unfortunately limited. It is generally believed that there is a genetic predisposition, which is then activated by chronic sun exposure and female hormonal changes like pregnancy or oral contraceptives.³

It definitely affects certain populations differently – a whopping 40% of women in Southeast Asia, for example – but it still remains unclear how and why.⁷ For instance, globally, 10% of melasma patients are men, but in India, it can be as high as 20%.⁷

As research on melasma has grown, it is now thought that melasma could be categorized  by inflammation, turning away from previous categorizations involving the depth of melanin through the layers of the skin, i.e. the dermis.⁷ We can only hope for more discoveries and knowledge!

It was found recently that in Fitzpatrick IV-VI skin types, visible light could trigger more intense hyperpigmentation than even UVA exposure. A physical sun block (like titanium dioxide or zinc oxide) would be helpful in this instance, in addition to broad spectrum UVA and UVB protection sunscreen.⁷ 

Maturational dyschromia

A diffuse hyperpigmentation of skin tone that affects mature skin on the deepest end of the Fitzpatrick scale.³ It presents as a general uneven skin tone across the forehead and cheekbone area. The causes of maturational dyschromia are uncertain, including whether extensive sun exposure is related.³ 

This is another case where the unevenness of research in the medical field becomes clear, as “one survey found that uneven skin tone was a chief complaint in more than one-third of black women”.³ Due to this lack of awareness, it may be misdiagnosed as melasma or PIH.³ 

Periorbital hyperpigmentation

Also known as idiopathic cutaneous hyperchromia of the orbital region (ICHOR) is perhaps most famously known as: dark circles.³ As universal it is, it is most frequently found in skin of color, and related to a variety of causes, such as genetics, allergies, sun exposure skin laxity, nutritional deficiencies, hormones, and so on.³ Studies have also confirmed that periorbital hyperpigmentation involves not only melanin deposits, but blood stasis.³

Most cases of persistent dark circles are resistant to most treatments, and this may have to do with the variety of causes. Like most long-lasting hyperpigmentation, it seems that melanin pigments in dark circles extend all the way down to the dermis.³

Pigmented contact dermatitis

Aka Riehl’s melanosis: When the skin is irritated by contact with something, usually a cosmetic – turns red, itchy, then assumes a diffuse or mesh-like brown-grey color. Avoid the allergen, SPF, skin lightening, chemical peels.

Hyperpigmentation treatment: Best skincare ingredients

The comforting part of looking into treatments for hyperpigmentation is that there are so many ways we can disrupt that melanin production line. We’ve got options. 

Topical treatments are skincare that incorporate ingredients that are known as “actives” – they’re not here to relax—they’ve got their own agendas, and they just might line up with yours in getting at that extra pigment. The different methods include: preventing the production of melanin, stopping the melanin from reaching that visible epidermis, speeding up skin and melanin turnover, and antioxidant properties.⁴

Niacinamide

A biologically active form of niacin (Vitamin B3). Niacinamide works by stopping the melanocytes in the bottom dermis from handing off that melanin to the upper epidermal keratin cells.⁵ It’s an incredible way to stop any hyperpigmentation in its tracks. 

Everybody from dermatologists and skincare enthusiasts are excited about niacinamide because the evidence is there, and it’s sound: a split-face trial by Hakozaki et al. showed that the application of a 5% niacinamide cream over 8 weeks significantly reduced hyperpigmentation and lightened the base skin color.⁷ Fun fact! OPTE's proprietary Optimizing Serum contains 5% niacinamide.

Hydroquinone 

Hydroquinone has been a gold standard for 50 years, and could be called the godfather of depigmentation … That is to say: he’s stubborn, he’s been asked to retire, but he still insists on showing up to work.  Key words here are veteran; workhorse; tyrosinase inhibitor; controversial; prescription-only. Hydroquinone is a wild destroyer that literally degrades melanosomes (melanin in its car) and destroys melanocytes (melanin in childhood home) by putting a stop to DNA and RNA synthesis.⁴ The proof is in the clinical study pudding, where a 4% Hydroquinone showed 40% of patients with melasma having complete improvement over the placebo’s 10%.⁴

If that’s not impressive enough, hydroquinone also plays very well with friends like tretinoin and fluocinolone acetonide, and the three of them synergize with the name triple-combination cream (TCC).⁴ It’s proven to be one of the best treatments for melasma, with one study showing complete clearance of melasma in 26% of patients after 8 weeks, and 90% of patients after 12 months.⁴ The FDA has even approved TCC as a proven treatment for melasma.⁷

So what’s the catch? Well, although hydroquinone can tackle stubborn PIH, it also can cause PIH that wasn’t there to begin with. The oxidative powers that stop tyrosinase equally apply to existing membrane lipids and proteins, that suffer from hydroquinone’s oxidative damage.⁷

At worst, long term use of hydroquinone can trigger a difficult-to-treat condition called exogenous ochronosis in deeply melanated skin – degenerating collagen, creating banana-shaped yellow-brown deposits in the dermis, that show up as grey-brown hyperpigmentation.³ And in animals with systemic absorption of hydroquinone, they’ve found nephrotoxicity, hepatic and renal adenomas and leukemia.⁴ With the possibilities of carcinogenic activity and exogenous ochronosis, the EU has prohibited hydroxyquinone in cosmetics.⁷

It remains controversial, though, because cancers have not been found in humans, and there have been only 22 cases of exogenous ochronosis reported in the US in the past 50 years.⁴

Arbutin

Hydroquinone’s friendly alter ego – Arbutin is a derivative form of hydroquinone found in cranberries, blueberries, wheat, and pears.⁴ Like hydroquinone, it inhibits tyrosinase but in a milder way, with a slower, controlled release. Arbutin can also be synthetically derived in the form of deoxyarbutin, and the two of them are considered as effective as hydroquinone, without too much risk at dosages below 3%.⁴

Azelaic Acid

Azelaic Acid is isolated from the fungus Malassezia furfur and is able to reduce pigment by inhibiting tyrosinase, DNA synthesis, and mitochondrial enzymes.5 It is commonly used at 20% concentration, but is also known to irritate skin with itching, redness, burning, and dryness.⁵

Kojic Acid

A tyrosinase inhibitor and an antibiotic produced from fungi like Acetobacter and Aspergillus.⁴ It was first used in Japan as a natural byproduct of food fermentation, where it is also added to food to prevent browning.⁴

Kojic Acid has been clinically shown to be extremely effective at reducing hyperpigmentation, especially in conjunction with other actives, like glycolic acid or hydroquinone.⁴ It is often used as a skin lightening agent, with most studies showing it most effective between 2% to 4%.⁴

Unfortunately, there is a concern of allergic contact dermatitis in concentrations above 1%, leading the Cosmetic Ingredient Review (CIR) expert panel recommending cosmetics cap concentrations at that level.⁴ Animal studies have also shown links to thyroid hyperplasia and carcinogenesis, though the risk of this in humans appears to be extremely low—it is safe at the levels normally found in food and cosmetic products.⁴

Retinoids

Retinoids reduce hyperpigmentation through pretty much every possible avenue. They’re thought to stop tyrosinase from making melanin. They interrupt any melanin currently being made. They increase keratin cell turnover, causing what melanin was there to be lost.3 And all available retinoids – retinoic acid, tretinoin, adapalene, tazarotene—have been found effective in treatments for melasma and PIH.³  The only tricky part is getting the dosage right. Higher concentrations are all the more effective, but come with increasing levels of irritation.³ 

Retinoids are available in face creams, oils, serums & more with varying potencies. Retinoids are also effective when combined with active ingredients like lactic acid, ascorbic acid, and hydroquinone. Keep an eye out for irritation, though, because that could backfire and add more hyperpigmentation.³

Ascorbic Acid

AKA Vitamin C, is the most abundant antioxidant in the human skin, and is much-celebrated for good reason. UV radiation’s oxidative effects are what activate tyrosinase to get to work making melanin. Ascorbic acid fights those oxidants, and chelates the copper ions in tyrosinase, rendering the tyrosinase impotent.⁴ As a robust antioxidant, ascorbic acid also reduces photo-oxidizing in any existing melanin.⁴ There are a very reassuring number of studies and trials to prove this. 

Ascorbic Acid’s only downside is that it is not the easiest for formulating cosmetics, as it oxidizes very quickly, and is extremely unstable in water solutions.³  To address this, its derivative cousins like the ester Magnesium ascorbyl phosphate (MAP) are sometimes used instead, as they have similar antioxidant properties. Although it doesn’t quite have ascorbic acid’s potency, MAP is nothing to laugh at – it was “found to reduce pigmentation significantly in 19 out of 34 patients with melasma and senile freckles but only one in three of 25 patients with normal skin.”³

Resveratrol

A natural antioxidant that has been shown to have considerable impact on melasma, with significant improvement seen in melanin index measurements.⁷

Professional hyperpigmentation treatment: Peels & lasers

Chemical Peels

Chemical peels are a second-line treatment for PIH, because they carry the risk of just making it worse. For this reason, chemical peels as a whole are avoided by most Asian patients, who are more prone to PIH.⁷ But they are an option if you’ve got a strong skin barrier and have been trying topical treatments for over 3 months but not seeing any results.⁵ If you have pale skin, they can be helpful for tackling melasma.⁷

If prone to PIH, chemical peels should only be undertaken with careful planning and preparation—but as always, consult with your dermatologist for the best plan for your skin. It’s recommended to start at least two weeks beforehand, prepping the skin with topical bleaching agents and avoiding sun exposure. This should be the regime for 6 weeks after the procedure as well. 

The benefit of chemical peels is really in how they can enhance other topical treatments. Glycolic acid (20-70%) and salicylic acid (20-30%) peels are often used together with topical actives like hydroquinone or tretinoin.⁵

Laser and light therapies

Intense pulsed light (IPL) can be a helpful therapeutic modality for melasma, it also has the paradox of risking triggering melasma-like hyperpigmentation due to inflammation.⁷

Fractional 1550-nm Non-ablative Laser Therapy works by selectively targeting dermal microphages with thermal injury via tiny microthermal zones, leaving the skin surrounding it to recover quickly.⁷ It happens to be the only FDA-approved laser device for melasma, but the results are inconsistent, with a high risk of PIH for Asian skin in particular.⁷ If you’re willing to take the risk, you can reduce your chances of PIH by pre-treating with a lightening active like hydroquinone and use lower fluences and variable pulses.⁷

Q-Switched Neodymium-Doped Yttrium Aluminum Garnet Laser Treatment also thankfully goes by the acronym 1064-nm QSNYL, and is referred to as “laser toning”.⁷ It is a first-line treatment for melasma in East Asian countries for its mysteriously effective way of selectively removing melanosomes without killing the melanocyte cells themselves.⁷ This “laser toning” cuts off communication lines for those melanocytes (again, without killing them), thus rendering them defunct.⁷ Trials and studies show impress improvement in lightness over hydroquinone, and attest to the growing popularity of the treatment.⁷  

Picosecond lasers are promising newcomers to the laser world. They are a step above nanosecond lasers, and manage to deliver less thermal damage yet more mechanical effect.⁵ They’ve gotten the green light for safely treating skin of color, but hang tight, because we’re still waiting to see studies demonstrating its efficacy for PIH.⁵ 

Protect your skin: prevent age spots, dark spots & more

It’s easy to get carried away in the skincare world, but it’s extra important to slow down when it comes to pigment-reducing activities. You’re dealing with powerful ingredients, and though it’s undeniably tempting to go full throttle, it’s all about the long game. 

Especially when it comes to strong activities, watch out for grandiose claims and promises. Ask to test your skin before jumping into full laser treatments and peels. 

Pre-and post-procedure care need to be custom-tailored for each individual and their needs. PIH is often the result of cosmetic procedures causing injuries to the skin, especially in skin of color. 

And lastly, you already know what’s coming…

Avoid the mid-day sun rays! Wear a generous layer of broad-spectrum sunscreen of at least 30 SPF, every single day! Wear sun protective clothing! Reapply every two hours, reapply. ☺ 

[Disclaimer: This information we have gathered here is no substitute for an in-person consultation with a dermatologist! Please make sure that any irregularities in your skin are examined by a licensed medical professional.]

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REFERENCES

¹ hyperpigmentation. In: Gale Encyclopedia of Medicine. The Gale Group, Inc; 2008. Accessed May 14, 2021. https://medical-dictionary.thefreedictionary.com/hyperpigmentation

² D’Orazio J, Jarrett S, Amaro-Ortiz A, Scott T. UV Radiation and the Skin. Int J Mol Sci. 2013;14(6):12222-12248. doi:10.3390/ijms140612222

³ Vashi NA, Kundu RV. Facial hyperpigmentation: causes and treatment. Br J Dermatol. 2013;169(s3):41-56. doi:https://doi.org/10.1111/bjd.12536

⁴ Galappatthy P, Rathnayake D. Depigmenting Agents. In: Kumarasinghe P, ed. Pigmentary Skin Disorders. Updates in Clinical Dermatology. Springer International Publishing; 2018:261-280. doi:10.1007/978-3-319-70419-7

⁵ Rodrigues M, Ayala-Cortés AS. Post-inflammatory Hyperpigmentation. In: Kumarasinghe P, ed. Pigmentary Skin Disorders. Updates in Clinical Dermatology. Springer International Publishing; 2018:197-208. doi:10.1007/978-3-319-70419-7

⁶ melasma. In: Miller-Keane Encyclopedia and Dictionary of Medicine, Nursing, and Allied Health. 7th ed. Saunders; 2003. Accessed May 14, 2021. https://medical-dictionary.thefreedictionary.com/melasma

⁷ Park K-C, Kang HY. Current Views on Melasma. In: Kumarasinghe P, ed. Pigmentary Skin Disorders. Updates in Clinical Dermatology. Springer International Publishing; 2018:167-181. doi:10.1007/978-3-319-70419-7