Pigmentation is the natural colour of a person’s skin and it is related to melanin production. Melanin protects skin cells and their DNA by absorbing the sun’s ultraviolet rays (UVR).
Hyperpigmentation occurs when excess melanin causes a darkened appearance to the skin in either small or large areas.
Darker skin types, in general, are more susceptible to hyperpigmentation than lighter skin types because their skin naturally contains more melanin.
There are 3 common types of hyperpigmentation:
1) UV ray induced: From the sun or tanning beds. This type of hyperpigmentation shows in the form of freckles, age spots and uneven skin tone.
2) Post-Inflammatory Hyperpigmentation (PIH): PIH is found in areas of the skin that have been subjected to inflammation due to trauma, acne or irritation (eg. fragrances or laser side effects). Inflammation stimulates Langerhans cells (immune cells), which alter the activity of melanocytes (skin cells), causing increased pigment production.
3) Melasma (AKA chloasma): This appears as patches most often on the cheeks, chin, upper lip and forehead. It can be related to hormones eg pregnancy, the contraceptive pill, or menopause.
The hyperpigmentation process:
1) Hyperpigmentation trigger (Inflammation, UV rays, or hormones)
2) Melanin production is stimulated within melanocytes. Tyrosinase is one of the key enzymes in this process.
3) Melanin is transferred from melanocytes to skin cells.
4) Skin cells are in a constant state of upward motion to the surface.
5) Skin develops dark spots or areas on the surface, or is uniformly darker (as in a tan).
Hyperpigmentation can become darker as the skin cells move closer to the surface. This point is important because, with many treatments, hyperpigmentation can darken in appearance before fading.
Melasma (from the Greek word, “melas” meaning black) is a common, acquired, patchy hypermelanosis (hyperpigmentation) of sun-exposed skin.
The most common locations are the cheeks, upper lips, the chin, and the forehead, but other sun-exposed areas may also occasionally be involved.
Causes of melasma:
Environmental and genetic causes:
Melasma occurs in all skin types and in people of all racial and ethnic groups, but is more common in those with darker complexions living in areas of intense UV radiation.
There is a family history of melasma in up to 30% of cases.
Oestrogen/progesterone contraception or HRT: The incidence of melasma increases with the length of time for which the hormonal treatment has been taken.
The incidence associated with the oral contraceptive pill is unknown but varies from 9% to 37%, with the higher incidence associated with sunnier climates.
Pregnancy: Melasma caused by pregnancy is called Cholasma, or the“mask of pregnancy”.
Most pregnant women have increased skin pigmentation, and around 5% get chloasma.
The probability of chloasma depends on sunlight exposure, genetic predisposition, and skin type.
It usually resolves after the pregnancy.
Phototoxic (sun-sensitizing) drugs, especially phenytoin for epilepsy, can increase the risk of melasma.
Dermal or epidermal Melasma:
Melasma can be in the epidermal (top layer of the skin) layer or dermal (deeper) layer.
A Woods lamp (blacklight) can help to distinguish between these forms of melasma in people with fair skin.
This distinction is important as the epidermal form is much more responsive to treatment.
Treatment of Melasma:
The pigmentation often fades spontaneously, particularly after the end of pregnancy, or on stopping oral contraceptives, although this is not always the case.
If it persists, melasma can be difficult to treat.
Limiting exposure to UV rays is the most important treatment: People with melasma should use a sunscreen effective against both UVA and UVB with sun protection factor of 30 or greater, and should avoid the midday sun.
Intense pulsed light therapy has been used to treat melasma, and Laser treatment is often tried. However, neither seem to be particularly effective.
Topical (cream) treatments:
Hydroquinone – 2, 4, or 5%. This It is a depigmenting agent; it inhibits tyrosinase, an enzyme needed for melanin synthesis. It also affects the membranes of melanocytes and causes their apoptosis (cell destruction).
Side effects can include redness, dryness, and even cracking of the skin. In rare cases, it can cause a condition called ochronosis, which is a bluish-black pigmentation of the skin.
Tretinoin – this works very slowly – the lightening of the melasma is often not apparent until after 24 weeks of treatment, if Tretinoin alone is used.It works better if used in combination with hydroquinone.
Tretinoin acts in 3 ways: it helps speed the removal of pigment by accelerating the keratinocytes’ (epidermal cells) turnover, it enhances hydroquinone penetration into the skin, and it protects hydroquinone from oxidation.
Tretinoin can be irritating to the skin in some people.
Steroid creams – mometasone, fluocinolone or hydrocortisone – The addition of a corticosteroid cream can reduce inflammation which can be a side effect of both hydroquinone and tretinoin. Steroids also inhibit melanocyte metabolism.
Azelaic acid 20% –this has been shown to be an effective treatment for melasma and also post-inflammatory hyperpigmentation – it is the easiest formulation to use and best tolerated. The effect of azelaic acid can be attributed to its ability to inhibit the energy production and/or DNA synthesis of hyperactive melanocytes. It also has antityrosinase activity.
Often, therapy with other creams can only be used for a limited time, and azelaic acid is used after this course has finished to maintain results.
Glycolic acid peels – There have been reports of chemical peels alone improving melasma, however they are more likely to be effective when used in conjunction with regular topical treatments of hydroquinone, tretinoin, and steroid.
Melasma can be treated with 1,2,3, or 4 of these treatments in combination, depending on severity of the condition, personal preference, and tolerance/side effects.
Azelaic acid, hydroquinone, tretinoin, or glycolic acid peels can be used alone.
Hydroquinone 4% alone is a commonly used first line treatment for mild melasma.
Azelaic acid and tretinoin:
If hydroquinone and steroid creams are unsuitable, the other 2 effective creams for melasma can be used together.
One study showed Azelaic acid with tretinoin caused more skin lightening after three months than azelaic acid alone, and a higher proportion of excellent responders at the end of treatment
Azelaic acid and hydroquinone:
If tretinoin is unsuitable, azelaic acid and hydroquinone can be used together, with better results shown than single therapy.
Tretinoin and hydroquinone:
These can be used together without a steroid.
Triple therapy formulations:
The gold standard of treatment is to use both of the best treatments for melasma – hydroquinone and tretinoin – and also a steroid to reduce the inflammation from these and further reduce melanocyte action.
“Tri-luma” cream is a stable combination of fluocinolone acetonide 0.01%, hydroquinone 4%, and tretinoin 0.05%. This formulation is FDA approved.
“Pigmanorm” is a combination of hydroquinone 5%, hydrocortisone 1%, and tretinoin 0.1%.
The steroid cream Mometasone furoate can also be used – It can be added to hydroquinone and tretinoin creams to make up a triple therapy.
Having the creams separately has the benefit of being able to use the steroid component less frequently than the other ingredients – for example every second or third day.
Long term use of steroid creams can cause redness, thread veins, and thinning of the skin.
Therefore, triple therapy formulations should never be used long term – they are usually limited to 2-3 months use at a time.
Chemical peels in conjunction with triple therapy:
Serial chemical peels, when used as well as triple therapy, can create a more rapid initial response and more overall lightening of skin.
3-4 weekly peels can be given. A course of 6 is usually required.
A 50 – 70% Glycolic acid has proven to be effective and safe to be used in this way.
Other options are other alpha-hydroxy acids, salicylic acid, Jessner’s peel, and trichloroacetic acid.
Duration of treatment:
Triple therapy always has a limited duration of use, due to the steroid component. Results can then be maintained with the non-steroid creams.
It is recommended to cease triple therapy including mometasone after 4-8 weeks.
If the triple therapy contains fluocinolone as the steroid component (eg “Tri-Luma”), it is usually given for 8 – 12 weeks.
Triple therapy containing hydrocortisone as the steroid component (eg “Pigmanorm”) should be used for no more than 8-12 weeks at a time.
Hydroquinone should not be used for more than 6 months at a time
Tretinoin is often used long term – in some cases for years.
Azelaic acid can be used for months or years.
These creams are all best applied at night.
Other, rarely used treatments:
This is a tablet that promotes blood clotting. It is most commonly used to control heavy periods.
At 250mg dose, twice a day, this has been shown to help melasma. However, once stopped, relapse generally occurs.
There are risks of causing blood clots with this medication.
Topical forms of tranexamic acid, or micro-injections of this into the skin – have been used with success.
Other possible oral treatments:
- Polypodium leucotomoa
Skin lighteners other than hydroquinone:
Other skin lighteners, alone or in combinations, can be used in people who do not tolerate hydroquinone.
There is some evidence for:
- Kojic acid
- Cysteamine hydrochloride
- Undecylenoyl phenylalanine
Summary of melasma treatment:
- The most effective treatment regime for melasma is triple therapy – a cream containing hydroquinone, tretinoin and a steroid (hydrocortisone, fluocinolone or mometasone)
- If combined with monthly glycolic acid peels, this treatment is more effective
- These “triple therapy” creams can only be used temporarily, for 2-3 months at a time, as the steroid component of these creams can cause side effects with prolonged use.
- Hydroquinone and tretinoin can also be used without steroids, together or as single therapy.
- Azelaic acid is a gentler (but less effective) alternative if triple therapy is not tolerated. It can be used in combination with tretinoin or hydroquinone. Alternatively, it can be used in between courses of triple therapy.
- A high SPF sunblock is essential
- Melasma is challenging to treat and will unfortunately frequently recur after being treated.