22 June 2022
Dark spots, blemishes, ‘pigmentation’, dark marks are some of the terms my patients in Singapore use to describe their hyperpigmentation. Hyperpigmentation refers to the patches of skin that are darker than the surrounding skin, such as freckles, melasma, lentigos, hori’s nevus…etc. Microscopically, these dark spots are collections of melanin, a type of pigment that looks dark brown or black.
Not all dark spots are equal- some can be more stubborn than others. It’s more important to understand the type or diagnosis of your hyperpigmentation so that skincare and treatments can be more directed. Hyperpigmentation is not a diagnosis per se; it is a description of any dark spot.
This review will cover why and how hyperpigmentation occurs, the common types of dark spots/ pigmentation and how you can treat and prevent hyperpigmentation from developing. I hope that you find this review on hyperpigmentation and darks spots useful.
1. Melanin is first formed in cells called melanocytes and one of the crucial steps involves an enzyme called Tyrosinase.
2. After melanin is formed in the melanocytes, melanin is then transferred to the skin cells called keratinocytes.
Melanin in the skin is responsible for the dark spots or hyperpigmentation in the skin. Melanin is produced mainly by cells called melanocytes. The key step in melanin formation is controlled by an enzyme called tyrosinase. Majority of pigment busters block tyrosinase and are known as tyrosinase inhibitors. Common examples of tyrosinase inhibitors are Kojic acid, azelaic acid, Cyspera and vitamin C (L-ascorbic acid)
In the last stage of pigmentation formation, the melanin synthesised by the melanocytes is transferred to the cells on the surface of the skin- i.e. melanin transfer.
Some of the causes that trigger melanin formation are:
• Genetic predisposition
• Sun exposure
• After injury or inflammation to the skin (e.g. pimples, cuts, burns)
‘Pigmentation’ or ‘hyperpigmentation’ is not a diagnosis; it is a description of a dark patch on the skin. Pigmentation or hyperpigmentation can be classified according to its causes and depths.
There is some overlap in these classifications; for example, some types of pigmentation are both superficial (i.e. epidermis) and deep (i.e. dermis)in depth. To add to the confusion, it is also possible to have more than one type of pigmentation- for example, post inflammatory hyperpigmentation and melasma can occur together in the same patient.
I’ll focus on 3 common types of hyperpigmentation in Singapore:
What is postinflammatory hyperpigmentation?
Postinflammatory hyperpigmentation refers to the dark patches that have developed after inflammation or injury to the skin. In other words, postinflammatory hyperpigmentation (PIH) is caused by another condition1,2.
Postinflammatory hyperpigmentation occurs because the injury (including surgery) or inflammation causes an increase in the formation and/or redistribution of melanin in the skin1. Patients with darker skin are more prone to postinflammatory hyperpigmentation3.
What causes postinflammatory hyperpigmentation?
Some of the causes of postinflammatory hyperpigmentation are1-3:
• Injury e.g. scratches, cuts, abrasions
• Infections: viral, bacterial and fungal
How does postinflammatory hyperpigmentation develop?
Postinflammatory hyperpigmentation can involve the epidermis and/or the dermis of the skin. In superficial (epidermal) form of postinflammatory hyperpigmentation, there is both increased formation of melanin as well as transfer of melanin to the keratinocytes in the epidermis4.
In dermal postinflammatory hyperpigmentation, melanin enters the dermis either through damaged basement membranes or special cells caused macrophages carry these melanin particles to the dermis5,6.
What is melasma?
Melasma commonly presents as brown-black patches that have irregular shapes on both sides of the face. It can appear on the cheeks, forehead and chin. Melasma mainly affects women. Melasma is particularly difficult to treat because of its propensity to recur and treatment is often protracted.
What causes melasma?
The causes of melasma are unclear. Some etiologic factors that have been identified are1,7:
• Sun exposure
• Genetic predisposition
• Hormone supplementation e.g. oral contraceptives
What does melasma look like?
Melasma typically occurs in females after pregnancy or beginning hormone replacement1,7. Both sides of the face tend to be affected. Melasma appears as brown blue-grey patches.
Is melasma a superficial or deep hyperpigmentation?
Melasma can involve both the superficial and deep layers of the skin. There are three types of melasma1:
• Epidermal melasma
• Dermal melasma
• Mixed melasma
Epidermal melasma, as its name suggests, is superficial in nature. It appears as brown patches. Dermal melasma involves the dermis and may also affect the fine blood vessels in the skin.
Dermal melasma appears as blue-grey or brown patches. Mixed melasma has features of both epidermal and dermal melasma. Mixed melasma is the most common type of melasma8.
What is the significance of correctly diagnosing melasma?
Melasma is complex and there may be recurrences of hyperpigmentation even after melasma has been treated, especially if you become pregnant or undergo hormone therapy.
The type of melasma that you have also matters- epidermal melasma responds well to treatment. Dermal melasma and mixed melasma are harder to treat than epidermal melasma9.
Some medications for lightening melasma may also not be useful in treating other types of pigmentation.
What are solar lentigo or solar lentigines?
Solar lentigo or solar lentigines are colloquially referred to as ‘age spots’ because they are frequently found in older patients1. Solar lentigos are harmless in nature.
What causes solar lentigines?
Sun exposure! Chronic sun exposure causes melanocytes and melanin content in the epidermis to increase1,10.
Can solar lentigines appear elsewhere besides the face?
Yes! Solar lentigenes can be found on sun exposed areas such as the hands.
The best way to treat any medical condition is… prevention. You’ll realise that sun exposure is one of the causes in the formation of hyperpigmentation; so always use sunscreen in the day! My post Sunscreen Beyond the Basics will explain how to choose a sunscreen and look at the data for oral sunscreens and sunscreen washes. My Sunscreen Reviews: the Best, the Worst and Unsafe Ones will share with you my sunscreen recommendations.
However, if hyperpigmentation has already developed, here’s what you can do with skincare, topical medications and clinic treatments. My practice is to encourage patient involvement with correct skincare options to sustain the results of treatments done in the clinic.
Skin care for lightening hyperpigmentation
Skin care for pigmentation removal targets the two steps in the development of pigmentation– (1) Tyrosinase Inhibition and (2) Inhibition of melanin transfer.
Topical treatments: Tyrosinase inhibitors
The most common active ingredients that get rid of unwanted pigmentation are the tyrosinase inhibitors. Tyrosinase inhibitors work by exactly how their names suggest- by blocking the activity of the key enzyme (tyrosinase) in the production of melanin.
Common examples of tyrosinase inhibitors are L-ascorbic acid (vitamin C), Cyspera (cysteamine cream), hydroquinone, kojic acid, arbutin and azelaic acid.
Hydroquinone is a tyrosinase inhibitor that is considered to be the gold standard for lightening melasma. Some of the side effects of hydroquinone are irritant contact dermatitis and a blue-black discolouration of the skin called ochronosis. In recent years, hydroquinone use has fallen out of favour as countries including Japan and the European Union have banned the use of hydroquinone. In Singapore, hydroquinone can be obtained only with a doctor’s prescription. Hydroquinone is commonly available in combination with a steroid and tretinoin as a medication called Tri-luma.
A safe tyrosinase inhibitor that is available in over the counter skincare products is topical vitamin C. There are several different types of vitamin C in skincare and the one that I recommend is L-ascorbic acid, which is the direct form of vitamin C that our skin utilises. You can read more about the different types of topical vitamin C and the differences between them in this blogpost All About Topical Vitamin C: One of the Best Ways to Protect Your Skin. Topical vitamin C also brightens the skin and reduces free radical damage from UV rays, so you can consider pairing it with sunscreen in the day.
The newest hyperpigmentation lightening cream to join the foray in Singapore is Cyspera cream. The active ingredient is Cyspera cream is Cysteamine, an antioxidant that lightens pigmentation through several pathways. Cyspera is an intensive pigment corrector that has shown results in lightening melasma. You can read about Cyspera as well as other skincare products for lightening dark spots in this blogpost How to Lighten Pigmentation and Dark Spots with Skincare.
Not all hyperpigmentation lightening skincare products are safe; some contain toxins like mercury. Some may also contain unsafe concentrations of steroids. Mercury and steroids are commonly found in skin bleaching creams and can cause brain damage, kidney failure and seizures.
You can read more about the ingredients of skin whitening creams and the dangers of these creams in Skin Bleaching and Whitening Drips. Please avoid buying lightening or bleaching cream online or from questionable retailers. The ingredients may not be fully declared in the ingredient lists and you may risk using these toxic chemicals.
Performing a chemical peel in my clinic for a patient with melasma.
If your dark spots still persist after your best efforts at home remedies; the next best thing you can do to remove unwanted pigmentation is to get professional help from your doctor. There are medications and treatments that can remove hyperpigmentation
1. Chemical peels for pigmentation removal
How do chemical peels remove pigmentation?
Chemical peels are generally effective and safe for most types of pigmentation including postinflammatory hyperpigmentation and melasma11. Chemical peels lighten hyperpigmentation by causing remodelling of the skin and increased cell turnover12,13. With sequential chemical peels, you can expect hyperpigmentation to get lighter.
What are the different types of acids used in chemical peels?
Two commonly used acids for chemical peels in Singapore are alpha-hydroxy acids (AHAs) and beta-hydroxy acids (BHAs). Most of the chemical peels performed in clinics in Singapore are superficial chemical peels i.e. only the epidermis is reached. This keeps the discomfort and downtime to a bare minimum.
You may have heard of another type of acid called polyhydroxy acids (PHA). PHAs are actually 2nd generation AHAs and are not a distinct type of acid. They do not reach the deeper layers of the skin as well as AHAs and BHAs. PHAs are more commonly found in over the counter skin care products rather than in medical grade chemical peels in the clinic. To see how I do chemical peels in my clinic, you can read this blogpost The Truth About Chemical Peels. The other benefits of chemical peels include smoother skin, brighter skin and improvement in acne.
Aftercare for chemical peels
With superficial chemical peels, there is almost no downtime at all. If you have sensitive or dry skin, you may experience very transient redness and dryness if at all. All you need are simply moisturiser and sunscreen. You can wear makeup immediately after the treatment if you would like to.
2. Lasers for pigmentation removal
Lasers are another modality of treatment for hyperpigmentation that are effective with durable results11,14. Laser for pigmentation removal is also a worthy option if topical therapy with skincare and lightening creams/ medications have failed.
One of the most commonly used lasers in Singapore is called the Q-switched Nd: Yag laser (or better known as Q-switched laser) as its wavelength allows the laser to target both the epidermis and dermis for pigmentation removal1. The Q-switched laser is also well absorbed by melanin in the skin for effective pigmentation removal1,14.
How does Q-switched laser remove hyperpigmentation?
Pigment lasers like the Q-switched laser are selectively absorbed by melanin in the skin. The laser energy causes the melanin or hyperpigmentation spots to break down into smaller particles to be naturally removed from the skin via lymphatic channels.
Melanin absorbs energy at a wide range of wavelength spectrum from 250nm to 1200nm1, 14. This is why lasers with wavelengths that fall within this spectrum are used for treating hyperpigmentation.
Q-switch laser is one of the lasers I find to be very effective and safe for treating most types of hyperpigmentation. As I’ve covered earlier, it is not uncommon that patients have more than one type of pigmentation- you can have melasma, sun damage and PIH from pimples. The Q-switched laser is a versatile laser that can lighten most types of pigmentation because its long wavelength allows the Q-switched laser to be absorbed by both the epidermis and dermis. This allows the Q-switched laser to reach pigmentation or melanin in both layers of the skin.
If you have acne/ pimples with postinflammatory hyperpigmentation, Q-switched laser and chemical peels are especially useful. Chemical peels and Q-switched laser can help to control the acne and exfoliate the skin on top of lightening the dark marks.
Some of the hyperpigmentation lightening skincare products that I’ve tried. I’ve reviewed some of them on the blog.
Now that we have reviewed established medical treatments and topical therapies for hyperpigmentation, let’s discuss something a little more interesting that seems to be very popular in Singapore and Asia: oral supplements for treating hyperpigmentation.
Lightening/ whitening supplements for hyperpigmentation can be easily obtained over the counter in drug stores and online retailers in Singapore. Most of them claim to lighten dark spots and provide additional benefits such as sun protection and anti-aging effects.
I’ll focus on two oral supplements for lightening hyperpigmentation (oral tranexamic acid and polypodium leucotomos extract) and the research findings behind them.
Oral tranexamic acid for lightening hyperpigmentation
What is tranexamic acid?
Tranexamic acid is a medication for stopping or preventing excessive bleeding. It is a relatively new treatment for hyperpigmentation, specifically melasma. Needless to say, oral tranexamic acid is not something you should try if you are prone to blood clots.
Tranexamic acid for treatment of melasma was first described in 1979. The discovery that oral tranexamic acid could lighten melasma was an accidental one while studying the effects of tranexamic acid for a different condition15. You can read more about this ingredient in Tranexamic Acid for Hyperpigmentation Explained.
How does tranexamic acid lightening hyperpigmentation
Tranexamic blocks the activity tyrosinase that is crucial in the formation of pigmentation16. Additionally, tranexamic reduces inflammation and blood vessel formation; all of which are factors in the formation of hyperpigmentation17,18.
What do the data and research show for oral tranexamic acid for treating hyperpigmentation?
A review of 17 studies that used oral tranexamic acid for melasma treatment showed that overall, oral tranexamic acid showed some improvement in melasma treatment- whether used alone or in conjunction with other treatments like Q-switched laser19. Patients who had other types of hyperpigmentation together with melasma did not see an improvement in these other types of pigmentation20.
Oral tranexamic acid for melasma is generally safe with few side effects19. The dosages of tranexamic acid for melasma treatment is less than the dosage for treating bleeding disorders.
Melasma also relapsed in some patients after cessation of oral tranexamic within 2-7 months in several studies18,20. More studies are needed to ascertain whether this relapse is due to the nature of melasma or related to stopping oral tranexamic acid therapy.
What should you know before trying oral tranexamic acid for pigmentation removal?
The role of tranexamic acid for treating melasma is still relatively new and we don’t know enough about it to recommend it widely. For now, oral tranexamic acid is not considered first line treatment for melasma.
If you would like to get started, try a low dose of 500mg a day; for short periods i.e. 8-12 weeks17. Please also note that oral tranexamic acid is not useful in lightening hyperpigmentation due to other causes except for melasma.
Oral Polypodium Leucotomos Extract
Polypodium leucotomos is a plant extract. You might find this familiar because polypodium leucotomos has been mentioned in my blogpost Controversies, Trends and FAQs About Sunscreens and fern leaf extracted can be found in some sunscreens.
What is Polypodium Leucotomos?
Polypodium Leucotomos is an antioxidant extracted from the fern species, Polypodiaceae. It has been marketed mainly as an oral sunscreen by some companies.
How does Polypodium Leucotomos lighten hyperpigmentation?
Some of the postulated mechanisms by which Polypodium Leucotomos lightens hyperpigmentation are through anti-inflammatory pathways and neutralisation of free radical damage from UV rays21.
What do the data and research say for Polypodium Leucotomos in lightening melasma?
Results have been equivocal regarding the efficacy of Polypodium Leucotomos in lightening melasma22-24. There is insufficient evidence to support the recommendation of consuming oral Polypodium Leucotomos for lightening of melasma22,23.
Hyperpigmentation is harmless albeit distracting dark spots on our skin. It’s more important that you get the diagnosis of your dark spot confirmed because that will affect your treatments and results.
To treat your hyperpigmentation, get started on the right skincare. My post How to Lighten Pigmentation with Skin Care will talk about the ingredients in great detail. Some of them are over the counter products that are very affordable. If that fails, then it’s time to call upon your doctor for her secret weapons- lasers and chemical peels.
Oral medications and supplements can be prescribed for treating hyperpigmentation. Tranexamic acid and Polypodium Leucotomos are two oral supplements that have been studied for melasma but the evidence is still preliminary. My recommendation would be to stick to proven and tested skincare products and treatments instead of using oral supplements alone.
I hope that you found this guide to pigmentation and treatments useful!
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22. A randomized double-blind placebo-controlled study evaluating the effective-ness and tolerability of oral Polypodium leucotomos in patients with melasma. Martin et al. American Academy of Dermatology Annual Meeting: 16–20 March 2012; San Diego.
23. A randomized, double-blinded, placebo-controlled trial of oral Polypodium leucotomos extract as an adjunct to sunscreen in the treatment of melasma. Ahmed et al. JAMA Dermatol. 2013;149(8):981–3.
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