Hyperpigmentation is a medical term used to describe patches of skin that are darker than surrounding skin. Types of hyperpigmentation include freckles, lentigos, melasma, post-inflammatory hyperpigmentation etc. These dark patches result from excess melanin production, which can be triggered by
- Genetic predisposition
- Sun exposure
- Post inflammation or injury to skin (e.g. pimples)
- Hormonal fluctuations
Now, let us examine the steps involved in melanin formation (melanogenesis). Melanin is a black/brown pigment responsible for human skin color.
- They are synthesized in specialized cells called melanocytes in the basal layer of epidermis, through a series of steps catalyzed by an enzyme called tyrosinase.
- Melanin are then transferred from melanocytes to the surrounding skin cells called keratinocytes.
Today, we will be focusing our discussion on melasma – which is a type of hyperpigmentation.
Melasma is a common, acquired skin condition in adults. It presents as brownish or grayish irregular patches on sun exposed areas – commonly over the face, such as the cheeks, nose, forehead and chin. While melasma can occur in anyone, there are a few groups who are at higher risk, such as those with
- Positive family history – but it is not an inherited condition
- Darker skin phototypes (Fitzpatrick skin types III-VI)
- Living in areas with high ultraviolet radiation
- Women, particularly oral contraceptive pill users, or during pregnancy (hence known as “the mask of pregnancy”). This is because estrogen strongly influence melasma.
Recent studies have shown more complex mechanisms behind melasma, such as,
- Inflammation and oxidative stress (free radicals)
- Increase in new blood vessels in the dermis
- Impaired skin barrier
This multifactorial nature makes melasma difficult to treat and highly prone to recurrence.
Melasma can involve both superficial and deep layers of the skin, with three histologic variants: epidermal, dermal, and mixed melasma. Epidermal melasma are more superficial and appear as brown patches. Dermal melasma involves the dermis and are deeper, and they may appear brown or bluish-grey. Mixed melasma are the most common, sharing features of both. Generally, epidermal melasma are easier to treat as opposed to dermal and mixed melasma.
Combination of therapies with skincare/topicals, oral medications, and in-clinic treatments are generally more effective than monotherapy, for this therapeutically-challenging condition.
Here is an overview of treatment modalities for hyperpigmentation.
from UV radiation with Broad- Spectrum Sunscreen with UVA/B protection
|Prevent new dark spots with Antioxidants e.g. Vitamin C, E, Niacinamide, Green Tea (EGCG)||Correct existing dark spots that have formed|
|Before melanin synthesis – Tyrosinase transcription regulators||Retinoids|
|During melanin synthesis – Tyrosinase inhibitors||Hydroquinone, Azelaic Acid, Arbutin, Cysteamine, Kojic Acid, L-ascorbic acid (vitamin C)|
|After melanin synthesis –
Melanin Transfer inhibitors
|In-clinic procedures||Destroy melanocytes||Q-switched Nd:Yag Lasers|
|Increased keratinocyte turnover||Chemical peels|
|Oral medications||Inhibits plasminogen/ plasmin pathway à Inhibit melanin synthesis||Tranexamic Acid|
|Inhibit reactive oxygen species||Polypodium leucotomos, Glutathione|
Armed with the knowledge of how melanin is synthesized as discussed earlier, we can tackle these unwanted dark spots via different stages of their formation using different pathways.
Hydroquinone is a tyrosinase inhibitor that is considered to be the gold standard for lightening melasma. Some of its side effects include irritant contact dermatitis and rarely ochronosis (bluish-black discoloration of the skin). It is classified by FDA as pregnancy risk category C , and is not recommended for use in breastfeeding females due to its unknown safety profile. Its use has been banned by countries such as Australia, Japan and European Union. In Singapore, it can be obtained only with a doctor’s prescription, and is commonly given as a medication called Tri-luma combined with a steroid and tretinoin (which is found to be more effective than hydroquinone alone). They are typically given for a short-term only.
For pregnant and lactating mothers, it would be prudent to consider safer actives such as vitamin C, niacinamide and azelaic acid.
For those who suffer from severe/ non-responsive melasma despite topical treatments, there are oral medications and in-clinic treatments that can help with removing hyperpigmentation.
Chemical peels using alpha-hydroxy acids (AHAs) and beta-hydroxy acids (BHAs) can lighten hyperpigmentation by increasing skin cell turnover. Superficial chemical peels are generally well-tolerated. Some possible side effects include burns, peeling and post-inflammatory pigment alteration.
Lasers utilize thermal energy to selectively target various chromophores in the skin. Non-ablative lasers are preferred over ablative lasers in the treatment of melasma due to its reduced tendency for inflammation and hence reduced post-inflammatory pigment alteration. Lasers should be used judiciously, as they can cause post inflammatory hyperpigmentation in individuals with darker skin types.
- Non-ablative Q-switched lasers are selectively absorbed by the chromophore melanin. The laser energy causes melanin to break down into smaller particles to be naturally removed from the skin. The wavelength of Q-switched Nd:Yag laser allows the laser to target both the epidermis and dermis for pigmentation removal.
- Non-ablative fractional lasers have also been used with varying success to treat melasma, via fractional photothermolysis for melanin extrusion.
Oral supplements for hyperpigmentation are increasingly popular, such as tranexamic acid, Polypodium leucotomos and Glutathione. They work via different mechanisms as illustrated in the table above. In the next article, let us explore the science behind tranexamic acid and its use in treating hyperpigmentation.
It is important to keep in mind that what works for someone’s melasma may not necessarily work for you, as there are many factors such as skin phototype, genetics, gender etc. that influence treatment efficacy. If skincare alone does not help to completely eradicate your pigmentation, consider consulting your doctor for in-clinic treatments. It is also vital to get the right diagnosis for your pigmentation, so as to formulate the right treatment plan.
Here’s a reminder to stay patient in this journey of spot-eradication – just as pigmentation took time to build up, it will take time for them to fade. We’re all in this together.
 Muriel W. Lambert, Spandana Maddukuri, Katrice M. Karanfilian, Marcus L. Elias, W. Clark Lambert, The physiology of melanin deposition in health and disease, Clinics in Dermatology, Volume 37, Issue 5, 2019, Pages 402-417, ISSN 0738-081X, https://doi.org/10.1016/j.clindermatol.2019.07.013.
 Rajanala S, Maymone M, Vashi NA. Melasma pathogenesis: a review of the latest research, pathological findings, and investigational therapies. Dermatol Online J. 2019;25(10):13030. doi:10.5070/D32510045810
 Sanchez NP, Pathak MA, Sato S, Fitzpatrick TB, Sanchez JL, Mihm MC., Jr Melasma: a clinical, light microscopic, ultrastructural, and immunofluorescence study. J Am Acad Dermatol. 1981;4(6):698–710. doi: 10.1016/S0190-9622(81)70071-9
 Ogbechie-Godec, Oluwatobi A, and Nada Elbuluk. “Melasma: an Up-to-Date Comprehensive Review.” Dermatology and therapyvol. 7,3 (2017): 305-318. doi:10.1007/s13555-017-0194-1
 Schwartz C, Jan A, Zito PM. Hydroquinone. [Updated 2021 May 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK539693/
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