The optimal management of melasma

Melasma is a psychologically distressing condition that is influenced by many factors including genetics, environment and medications. The Melasma market is huge, so developing a good programme for your clients will keep your clinic busy.
When managing this condition, it is important to remember some specific points. These relate to managing client expectations, not missing an underlying medical problem, helping the client to prevent their own melasma problem worsening at their own hands, and optimising your ability to help control and manage this condition over the long term, without making them worse yourself.
Melasma is indeed very common. 50-70 percent of pregnant women develop it during the second or third trimester. Up to 29 percent of women on the contraceptive pill develop it. Asian women with type 3-4 skin have a 40 percent prevalence of melasma and their male counterparts have 20 percent prevalence. Latin women have up to 80 percent prevalence. 
Melasma involves irregular brown or greyish brown facial pigmentation, more commonly affecting women.  Although the precise causes are unknown, it is related to melanin production by melanocytes within keratinocytes. It is often difficult to treat, particularly if there is a dermal component and there is a tendency for this condition to relapse.
Pigmentation can vary according to influences like race, Fitzpatrick skin type, sun exposure, internal disease or inflammation, drugs including the contraceptive pill, pregnancy, hormone dysfunction or treatments thereof, skin injury or inflammation, stress, and even whether a mole or rash is present.
When approaching a case of melasma it is important to include a general health and drug questionnaire as part of your screening process in case there could be an underlying medical condition contributing to the pigmentation. These conditions can include inherited conditions, metabolic or hormonal conditions, inflammatory disorders, chemical or drug-induced disorders, nutritional problems or even cancer.
Not all pigmentation is melasma. Common diseases that could be mistaken for melasma include Addison’s disease, which is the failure of the adrenal glands that cause dark pigmentation of the skin.  Haemochromatosis is as common as one in two hundred people in the community and can cause dark pigmentation of the skin. Polycystic ovarian syndrome is fairly common amongst women of childbearing age and often involves excessive hairiness and acne as well. 
Other less-common diseases may include Lupus (Systemic Lupus Erythematosis), Cushing’s disease, systemic sclerosis, etc, so it is important to always ask about general health problems and drugs in your clients so that you don’t end up assuming that their problem is only localised in the skin.
Remember that you see your aesthetic clients far more often than they would see a doctor. They will show you things on their skin that have changed or may concern them. If you suspect that the pattern or colour of the pigmentation is not what you are used to, you should refer your client to their doctor. 
Drug-induced pigmentation can account for 10-20  percent of new cases of pigmentation. Commonly taken drugs that can contribute to pigmentation include non-steroidal anti-inflammatory drugs (for example; Noreen®, Voltaren®) – they can cause a single, sharply defined, red area which then resolves quickly and develops into a local brown area.
Phenytoin is used for epilepsy and 10 percent of people on this drug develop a similar look to melasma on their face and neck – it will fade a few months after stopping the drug. Chloroquine is used for autoimmune diseases and 25 percent of these people can develop a bluish-grey pigmentation on their face, neck and sometimes legs and arms. Cytotoxic drugs used for cancer and anti organ rejection can cause general hyperpigmentation including banding of the nails. Tetracycline antibiotics that are often used in acne can also cause pigmentation. Too much iron or even heavy metal poisoning can also cause pigmentation. Because of this, a list of drugs or medications should be included in your health questionnaire. You should be suspicious if the abnormal area of pigmentation also involves the fingernails.
There are three histological (microscopic) types of melasma – dermal, epidermal and mixed. 
There are three clinical patterns of melasma:
1. Centro-facial – this is the most common and involves the cheeks, forehead, upper lip, nose and chin.
2. Malar – this involves the cheek and the nose.
3. Mandibular – this involves the jawline. Other sites can involve forearm and neck.

The number, melanin content and location of the melanised cells (along with oxygenated and de-oxygenated haemoglobin) help determine the colour of the skin. Melanosomes contain tyrosinase, a copper containing enzyme that catalyses the conversion of L-tyrosine to L-dopa and then L-dopa to L-dopa-quinone in melanin synthesis. Melasma is a dysfunction of this pigmentary system. As mentioned before, it is more commonly seen in women with darker skins – mainly Fitzpatrick type 4 and 5 in Latin and Asian women. The Fitzpatrick skin types are as follows:

itzpatrick’s scale of sun reactive skin types
Type I  Always burn,
never tan
Type II  Tan only with difficulty and usually burn
Type III Tan, but sometimes burn
Type IV Rarely burn and tan with ease
Type V Tan very easily and very rarely burn
Type VI Tan very easily and never burn

Melasma develops slowly and symmetrically and can last for many years with worsening in the summer and improvement in the winter. Factors that contribute to and aggravate this condition include a significant family history and sun aggravation. Internal causes of increased pigmentation can involve abnormal hormone conditions.
A very important point about this condition is that you need to prepare your patient for realistic expectations and prepare them for a maintenance programme rather than a cure.
Post-inflammatory pigmentation can contribute to pigmentation and can often be involved in melasma. Underlying conditions that contribute to inflammation can include skin infections, allergic reactions, reactions to medications, and trauma-like burns. It can also involve inflammatory reactions like acne, dermatitis and a medical condition called lichen planus.
It is important when dealing with hyperpigmentation to determine any contributing factors that have already been mentioned above and consider eradicating them before moving onto your definitive treatments which are going to be skin care and clinic treatment based.
Your general management protocol, in addition to removing any aggravating factors, will include the following:
• A broad-spectrum UVA and UVB sun block
• Skin cream therapy
• Microdermabrasion
• Chemical peels
• Laser and light therapies.

Your ultimate goal is to reduce the area affected, improve the cosmetic defect, reduce any recurrence, and keep side effects of your treatment to a minimum.

Detailed principles of therapy are as follows:
• Manage expectations – it is important to emphasise that this is a condition that needs to be managed and often cannot be cured. Your client’s expectations need to be clarified and managed, and they should be encouraged to undertake a programme that you have designed for them in the clinic that will improve and then maintain their skin.
• Deal with any internal health issues like stress, hormone problems, etc. This may require a referral.
• Avoid inflammation by picking up whether your client is irritating or inflaming the skin, either themselves by picking or by any practices that they are using, like scrubbing, using perfumes etc.
• Broad spectrum UV light protection that is reapplied more than once during the day.
• Antioxidant therapy that can be on the skin and even oral antioxidants can be useful.
• Inhibit melanocytes activity and melanin synthesis by using tyrosinase inhibiting creams.
• Add other creams, like retinoids, that help with pigment management.
• Disrupt and remove melanin granules – this can include retinoids and possibly peels.
• In-clinic treatments can include microdermabrasion, peels, iontophoresis, intense pulse light, non-ablative laser and ablative laser.
• Be careful that your clinic treatments do not aggravate the condition by unnecessarily irritating or inflaming the skin.
Managing expectations involves informing your client from the beginning that melasma is a dynamic, ongoing, multifactorial process. If your client is contributing to its production they must cooperate with you in helping it. Warn your client that this condition is difficult to treat and has a tendency to recur, and give them education about its long-term management and suppression. Your goals are to reduce and control this condition but not cure it. Never promise a cure.
Before you embark on any sort of skin cream, cosmeceutical or in-clinic treatment, it is very useful to perform a Woods light analysis. This will identify the depth of pigment and its position – either epidermal, dermal or both. This will help you determine how successful you are likely to be and also what sorts of treatments you will need. Dermal melanin is harder to eradicate. Woods light examination helps you manage your client’s expectations from the beginning and have them on board with you throughout their programme.
In 2010, the gold standard Cochrane Organisation reviewed melasma treatments and made comments about the best components available. They stated that the treatment should include sunscreens, bleaching creams like hydroquinone, and could also include acne creams like adapalene, retinoids and facial peels.  Some success has been gained by placing a triple combination into a cream which included a steroid, tretinoin and hydroquinone; however, this is not available in New Zealand at present. The Cochrane review team commented that there is still inadequate information about the best scientific approach, because most studies went no longer than six months. They asked for more quality scientific studies to be done to help us understand more.
Nevertheless, the mainstay of melasma treatment amongst dermatologists has been tretinoin and hydroquinone as a start. Although beauty therapists cannot access these components, it is important for you to know about them and how they work, and also because some of your clients will have already tried them or still be using them when they come to see you.
Hydroquinone (HQ) – this is regarded as a gold standard treatment and can actually be effective when used alone. It has been available as a 2 percent cream over the counter and with higher concentrations available on prescription. It has mostly been used for epidermal melasma which responds well and other treatments have been added to it. It acts as a tyrosinase inhibitor – this prevents the enzymatic oxidation of tyrosine to dopa, thus preventing the production of melanin. When used twice a day, it may take up to six months to show the benefit. 


 In one trial, the 4 percent hydroquinone cream was used with a broad-spectrum sunscreen and by the end of twelve weeks, those with moderate pigmentation had a reduction from 56 percent to 0.1 percent. Those with severe pigmentation reduced from 44 percent to 8.4 percent. Side effects of hydroquinone can be worse if using higher concentrations and can include mild irritation like itching, burning and stinging. Higher concentrations can cause allergic dermatitis. Long-term use is discouraged because of further side effects and the concern that it could contribute to cancer, although there is no proof in humans.
Tretinoin is a retinoid like vitamin A and retinoic acid. It is available as a gel, cream and liquid at strengths of between 0.01 and 0.1 percent. It was first used with hydroquinone to enhance its penetration and then later it was realised it had its own effect.
Tretinoin acts as a tyrosinase inhibitor and also disperses keratinocytes pigment granules by interfering with pigment transfer. It also accelerates epidermal turnover, therefore pigment loss.
In a study of 1 percent tretinoin cream used for 40 weeks, the group using tretinoin as compared with the base cream had significantly lightened skin. Microscopy in these subjects showed a 36 percent reduction of epidermal pigment.
Tretinoin side effects include retinoid dermatitis, which involves burning, stinging, redness, scaling and dryness. This is usually remedied by reducing the dose or application. There is a theoretical risk of sunburn with this cream and it has not been established as being safe in pregnancy because animal studies have shown foetal abnormalities. It is not safe in children under 12.
Corticosteroids have often been used to reduce melanin production by reducing inflammation – they reduce inflammatory messengers in the body. Alternatively, corticosteroids can also directly reduce melanin production. There has been no significant research on corticosteroids used alone. They are usually used in combination with other creams. When they are used excessively they can cause a rosacea-type rash, contact dermatitis, and thinning of the skin.
A brand of triple therapy that was available in New Zealand for a time was called Tri-Luma. This contained tretinoin 0.05 percent 4 percent hydroquinone and a steroid called fluocinolone 0.01 percent marketed by Galderma. An eight week scientific trial showed 77 percent of subjects experienced complete, or near complete clearing of their melasma when using this.
Azelaic acid works as an anti-inflammatory, anti-bacterial and anti-keratinising agent. It acts on hyperactive and abnormal keratinocytes by competitively inhibiting tyrosinase. Side effects include, in 1-5 percent of subjects, itching, burning, stinging. In 1 percent of subjects, redness, dryness, rash, peeling, irritation and dermatitis. Rarely it can cause asthma, vitiligo (under pigmentation of skin), small depigmented spots, hair growth, keratoses polaris (elephant skin or goose bumps) and exacerbation of cold sores.
In a study of azelaic acid 20 percent versus a cream base, there was a significant reduction of pigmentation in 55 percent of total subjects versus 12 percent of those using the base.
Kojic acid has not been approved for use and there are no scientific trials available. It is thought to work in a similar way and is thought to be at work as a tyrosinase inhibitor. Most subjects get burning and peeling, and this product is generally more irritating.
Adapalene cream 0.1 percent is marketed as Differin® and is available on prescription for acne. It controls cell proliferation and differentiation and some of the trials have had similar results to tretinoin.
Attention has also been given to other cream based treatments that included liquorice extracts, vitamin C and other botanicals. A liquorice botanical called Liquirtin cream 2 percent showed an excellent response in 80 percent of subjects but with mild irritation and burning in 20 percent of them.
Ascorbic acid 10 percent applied twice a day showed an improvement in 55 percent of subjects.
Oral therapy for melasma has included the Mediterranean diet with soy and green tea, all of which give a collective UV SPF factor or four. This diet contains plant chemicals called flavonoids, polyphenols, and antioxidants like lycopene etc, all which protect the skin and prevent pigmentation.
Another oral therapy is Pycnogenol® which is pinus pinaster bark extract. This contains flavonoids and other compounds that act as antioxidants and anti inflammatories.
There has also been research on oral transexamic acid marketed as Cyclokapron® which is actually used to reduce heavy periods in women. It acts on inflammatory messengers in the body.
We are starting to see a theme that inflammation and oxidation can be improved internally with diet, lifestyle, stress management and oral supplementation which can then affect skin pigmentation. Similarly, stress in some people can allow more oxidation and inflammation and thus cause more pigmentation. So this makes a very good case for stress management being part of treatment of melasma.
Many cosmeceutical companies have anti-inflammatory and antioxidant ingredients that could theoretically help with melasma.
In-clinic procedures for melasma include the following:
• Microdermabrasion
• Chemical peels
• Non ablative laser – 1064 nm Nd:Yag
• Intense pulsed light
• Fractionated or ablative laser.
• Photodynamic therapy – medical only.

Before embarking on any in-clinic procedures, skin preparation needs to be thorough to prevent any post-treatment inflammatory hypo or hyper pigmentation. In any case, you will have included these ingredients as part of your melasma treatment anyway. They should include some form of retinoid, some exfoliation as well as a tyrosinase inhibitor. Your other skin care ingredients would include any anti-inflammatory or antioxidant ingredients. Many cosmeceutical companies have available botanical and other ingredients in their skin care that act as anti-inflammatories and antioxidants. These will help inflammation and melasma.
Microdermabrasion for melasma can provide you with an in-clinic exfoliation of the epidermis which would be most useful in epidermal melasma. It is also useful for collagen stimulation, acne and sun damage. Microdermabrasion can be used as part of a melasma programme, along with skin care. It is important to avoid over-aggressive treatment to prevent inflammatory hyperpigmentation. This treatment can possibly be followed by some sort of sonophoresis or infusion of antioxidants to assist your treatment.
Chemical peels for melasma are designed to remove or break up melanin. They are well tolerated by light skins but care needs to be taken in darker skins. A worsening of melasma is a risk if there is inflammation. The most popular peels include tretinoin, glycolic acid and even lactic acid.
The non ablative laser 1064 nm Nd:Yag is a single laser wavelength that reaches the epidermis and mid dermis. Its target is red pigment. It can be used as a complementary treatment to eradicate any deep redness that contributes to the discolouration of melasma, which is actually found in 40-60 percent of subjects. This treatment reduces microvascularities and superficial and deep redness with no downtime. It also reduces inflammation, stimulates collagen and enhances the immune system of cells. It is not a stand-alone treatment and would be a part of a total programme.
Intense pulse light (IPL) for melasma: The wavelength of this light therapy ranges from 500 to 1200nm and it can be used for red and brown discoloration of the skin, collagen sis and hair removal on different settings. IPL can treat:
• Diffuse superficial redness.
• Rosacea.
• Poikiloderma which is mixed red and brown discoloration, often on the neck and chest of sun-damaged clients
• Facial veins
• Brown blotches
• Sun damage and photo ageing
• Acne and very fine wrinkles.

It will not treat deep melasma and is not safe in skins darker than Fitzpatrick type III. Pre-treatment preparation is very important to prevent post-inflammatory hyperpigmentation, especially in type III skins.
Laser resurfacing with fractional or even ablative lasers available. These modalities are mainly used for texture, collagen sis and pigmentation. Generally, pain has to be managed for these procedures. When it is fractionated, anything between 10-30 percent of the skin can be treated by one or more treatments are used. This treatment cannot be used in Fitzpatrick type four or darker. This treatment carries with it five to seven days of down time. Depending on the depth, it may be able to get some of the dermal component of the pigment.
In summary, correct diagnosis of whether you are dealing with melasma or some internal or other condition is important. Preparing your client for a long-term relationship with you in the clinic to get control of this condition and manage it long term is important. You are the most common person your client sees for skin issues and so if something looks unusual to you, you can refer them to their doctor for a further opinion. You can also refer when your client has not responded to your treatment or has actually worsened, or if you suspect something internal is going on.
When you manage melasma optimally, you gain a satisfying long-term relationship with a client who will visit the clinic regularly.



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