Dr Maryam Zamani highlights the different forms of melasma and the variety of treatment options currently available
Facial pigmentation is cosmetically important and can have considerable psychological impact. Melasma is a commonly acquired hypermelanosis of the skin characterised by brown-grey patches predominately found on sun-exposed areas of skin.1 Melasma is also the most common cause of facial pigmentation2 and is a cutaneous disorder affecting all races with particular prominence in darker skinned individuals (Fitzpatrick skin types IV to VI) such as Hispanic and Asian ethnicities.1,3 Women are predominately affected with a 90% predisposition to men, but the reason for this is currently unclear.27 While the pathogenesis of melasma is not known, there are multiple factors that can influence its presence such as hormones, genes and UV radiation; exacerbation of melasma is inevitable after prolonged sun exposure.2 Pregnancy, oral contraceptives, oestrogen/ progesterone therapies, photosensitising and anticonvulsant medication, thyroid dysfunction, cosmetics and some drugs can also influence melasma.1,2,4 Some studies have indicated that higher levels of oestrogen receptor expression were found in affected skin in women on the oral contraceptive pill.28 Melasma results from the increased deposition of melanin in the epidermis, in the dermis within melanophages, or both.5 One hypothesis is that a significant portion of melasma patients have an underlying hyper vascularity contributing to melanocyte dysfunction.6
There are three clinical patterns of melasma: centrofacial pattern, malar pattern and the mandibular pattern. The centrofacial pattern is the most common and affects the forehead, cheeks, upper lip, nose and chin. The malar pattern affects the cheeks and nose, and the mandibular pattern involves the ramus of the mandible.1 It is not known why these patterns occur.
Historically, the Wood’s lamp examination can be used to further differentiate melasma into four histological types depending on the depth of pigment deposition:1,7 The Wood’s lamp is a dermatologic tool whereby ultraviolet light is shone onto the skin in a dark room to observe fluorescence. It can be used for a number of skin problems including melasma.
Melasma may also be classified as transient and persistent types. The transient type disappears within one year of cessation of hormonal stimuli like pregnancy or oral contraceptive pills while the persistent type continues to persevere more than a year after the hormonal stimuli has been removed.5
Because of the dermal involvement of hypermelanosis, melasma is often difficult to treat and relapses after treatment is discontinued. This recurrence can happen immediately or over the course of a year. All patients with melasma should be counselled about the natural course of the disease and the necessity for long-term management.5 Careful history about precipitating factors should be taken with discontinuation of aggravating agents such as medications, contraceptives and UV exposure. Treatment goals for melasma are the suppression of melanogenesis and the removal of excess melanin present in the epidermis and dermis.10 The use of broad spectrum UVA and UVB sunscreen is imperative to melasma sufferers to help prevent further pigment stimulation. Epidermal pigmentation can often be removed with various chemical exfoliation techniques as long as melanin production is also simultaneously suppressed. The greater challenge is the treatment of dermal melanin.
Topical medications modify various stages of melanogenesis, with the most common mode of action being inhibition of the enzyme tyrosinase.5 Lightening agents such as hydroquinone, tretinoin, azelaic acid and corticosteroids can be used alone or in combination to have a synergistic efficacy on hyperpigmentation.11 Topical hydroquinone 2-4% in combination with tretinoin 0.05 to 0.1% has been an established treatment protocol.2 Despite controversies regarding hydroquinone-induced ochronosis, hydroquinone remains the most effective topically applied bleaching agent approved by the FDA.4 Depigmentation becomes evident only after five to seven weeks of therapy and should be continued for a minimum of three months, and often for up to one year.5 Irritation is the most common complication.
Tretinoin promotes the rapid loss of pigment through epidermopoiesis and increased epidermal turnover.12 However, clinically significant lightening only becomes apparent after 24 weeks and has common side effects like burning, dryness, scaling and erythema. Sunscreen is advised during treatment. Topical steroids in combination with other therapies has a synergistic effect and helps to reduce irritation from tretinoin.5 Topical azelaic acid 15-20% can be as effective, and one study indicated it was more successful than monotheraphy with hydroquinone but without the same irritation to the skin.13 Inhabitation of tyrosinase is key and topical azelaic acid has no depigmentation effect on normally pigmented skin because it selectively affects abnormal melanocytes.5,14
Kojic acid alone or in combination with glycolic acid or hydroquinone has also shown good results.2 Kojic acid, used in concentrations of 1-4%, is a potent antioxidant that also inhibits the production of freetyrosinase thereby inhibiting melanogenesis.15 Glycolic acid is an alpha hydroxy acid that has skin lightening properties when used in a 5 to 10% concentration. It directly reduces melanin formation by tyrosinase inhibition but should be used cautiously because of the risk of inducing hyperpigmentation from excessive skin irritation.10,16,17
Mequinol, N-acetyl-4-cysteaminylphenol, and arbutin are other hydoquinone deriviatives that have also been used successfully in the treatment of hyperpigmented disorders. Other new and experimental agents including ascorbic acid, niacinamide, liquorice derivatives, and flavonoids have been used to affect melanin pigmentation.5 Trichloroacetic acid, Jessner’s solution, alpha-hydroxy acid preparations, kojic acid alone or in combination also show good results by reducing hyperpigmentation and recurrences.2 Peels are best used in conjunction with a topical pigment suppressing preparation. Various combinations of topical agents have been studied. The most widely used and extensively studied combination therapy is a formulation with hydroquinone, retinoic acid and corticosteroids.18 Clinical studies indicate improved outcomes with triple combination therapy compared to 4% hydroquinone alone.10
Laser treatments and intense pulse light (IPL) therapy are other modalities that are used to help improve hyperpigmentation with varying success.2 Treatment with high energy pigment specific lasers, ablative laser resurfacing and fractional lasers can result in high rates of post inflammatory hyper and hypopigmentation with significant rebound melasma.10 Q-switched lasers can target melanosomes without damaging surrounding tissue structures. Its high pressure acoustic wave leads to melanocyte death but has a high incidence of hyperpigmentation, hypopigmentation and rebound melasma.10,19,20,21 IPL has also been used to treat melasma; however it is not possible to target dermal melanosomes with IPL. Consequently, IPL will produce transient improvement in epidermal pigmentation but not dermal pigmentation and may induce post inflammatory hyperpigmention.10,22,23 Similarly, ablative resurfacing lasers and fractional resurfacing lasers showed early promise in treating melasma but long-term follow-up studies have suggested that there is a high incidence of rebound melasma and post inflammatory hyperpigmentation.10 Kauvar studied combination microdermabrasion with low-fluence QS laser in conjunction with hydroquinone-based skincare with refractory melasma, with 80% of patients maintaining melasma clearance for up to 12 months.10, 24
Melasma is a common, chronic hyperpigmentation disorder with significant negative psychological consequences. While there is a plethora of therapeutic options, treatment is often challenging, requiring long-term therapy with no specific, effective, universal treatment.25 In my experience triple therapy using hydroquinone, tretinoin and topical steroids is most effective in improving melasma long term. However patients should be made aware that results are often unsatisfactory, with frequent remissions and rebound hyperpigmenation. One of the main obstacles to developing an effective therapy is the limited ability to destroy dermal melanosomes without producing inflammation that could exacerbate the melasma.4,10
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