Melasma is a common disorder of pigmentation characterized by well-defined hyperpigmented patches on the face. There are three clinical patterns of melasma. The most common pattern is centrofacial and includes the forehead, cheeks, nose, upper lip and chin. The malar pattern involves the nose and cheeks. The mandibular pattern involves the ramus of the mandible. Melasma has also been reported on the forearms, although this presentation is less common.1

Wood’s light examination can be used to further classify melasma. Characteristic enhancement with the Wood’s light is used to pinpoint the location of the pigment in the epidermis or dermis.
Four types of melasma are described based on Wood’s light examination.
1. Epidermal melasma, which clinically is brown in color, appears darker and accentuated under the Wood’s light.
2. Dermal melasma, which clinically has a blue-gray appearance, is less visible under the Wood’s light.
3. A mixed epidermal/dermal pattern is also described.
4. Finally, in skin types V and VI, a fourth type of melasma is categorized. Due to the lack of contrast with surrounding skin in these patients, the lesions are not discernible on Wood’s light examination.2
Although the Wood’s light can help to classify melasma, one study found that Wood’s light examination was not useful in predicting response to treatment.3

A Closer Look
Melasma is most common in darker skinned patients and is prevalent in Asian, Hispanic and African- American populations. Women are affected most often, with men comprising only 10% of cases.
Histopathology reveals increased melanin in all layers of the epidermis, increased staining intensity of melanocytes, and increased number of melanocytes. Melanosomes are also increased and more widely dispersed in keratinocytes. In the dermis, there is prominent solar elastosis when compared to normal skin. With dermal melasma there are prominent melanophages in the superficial and mid dermis. Ultrastructurally, melanocytes have more mitochondria, Golgi apparatus, rough endoplasmic reticulum and ribosomes in the cytoplasm.4

What causes melasma?
The etiology of melasma is unknown. However, its strong association with pregnancy and birth control suggest hormonal influences.
Estrogen, progesterone, or both may be an initiating factor in predisposed patients. One study measured levels of luteinizing hormone (LH), follicular stimulating hormone (FSH), and testosterone in men with melasma and found elevated LH and low testosterone levels in affected men. The authors concluded that melasma in men represented testicular resistance.5
Increased levels of LH and lower levels of estradiol have also been demonstrated in women with idiopathic melasma, which may represent subclinical evidence of subtle ovarian dysfunction in these patients.6

Other endocrinologic abnormalities include an association with thyroid autoimmunity. This association is strongest in women who develop melasma during pregnancy or with oral contraceptive use.7
One of the most significant contributing factors in melasma is ultraviolet (UV) light. Melasma invariably worsens with UV exposure and this characteristic of melasma is what makes effective treatment challenging.
Genetic influences have also been implicated in patients with melasma. This theory has been entertained due to familial cases and the significant clustering of melasma in certain ethnic groups.
Cosmetics, heat exposure, phototoxic drugs, and antiseizure medications have also been implicated in this disease.8,9

Treatment
Effectively treating melasma is challenging. Conventional therapies include bleaching agents in combination with chemical peels. Epidermal melasma is more responsive to treatment than dermal melasma. Although clearance of lesions can be achieved, the condition tends to recur. Subsequently, there is a large body of literature on different therapies for melasma. Due to the resistant nature of this disease, many different treatment modalities have been tried.

Bleaching Agents. The following treatment methods are commonly used for melasma.
• Hydroquinone is the most widely used and most effective bleaching agent available for the treatment of melasma. Commercially available products range from 2% to -4%; however, in darker-skinned patients, concentrations of 6% to 10% are often required to effectively clear lesions. In the past, many dermatologists have avoided these stronger concentrations due the fear of ochronosis.
It’s important to note that the majority of ochronosis cases occurred in South Africa where variable high concentrations of hydroquinone were available without a prescription and used over decades without physician supervision.

However, in the United States, even with physicians who routinely prescribe higher concentrations of hydroquinone, ochronosis is rarely observed. Although hydroquinone is a highly effective bleaching agent, its effects plateau at 6 months. So it’s important to switch to alternative therapies after
6 months to maximize the future effectiveness of hydroquinone in your patient.

• Kojic acid is an alternate bleaching agent often used for melasma. Studies comparing 5% glycolic acid/2 % hydroquinone gel with 5% glycolic acid/2% kojic acid gel found the two treatments equally effective in treating melasma. However, in this study, the kojic acid preparation was more irritating.10

• Azelaic acid has also been used as a bleaching agent. In a double-blind placebo-controlled study azelaic acid was equally effective as 2% hydroquinone in twice-daily applications.11

• Arbutin, a tyrosinase inhibitor, is a less commonly used bleaching agent that may be effective in treating melasma.

Retinoids/Steroids. These agents have also proven effective.

• Tretinoin 0.1% has been demonstrated to be effective for melasma in vehicle-controlled studies.12 However, as monotherapy improvement is slow.

• Fluorinated steroids such as betamethasone valerate have also been shown to be effective in treating melasma.13

Combination therapies. This type of approach is being widely used.
Although hydroquinone, retinoids and steroids are all effective as monotherapies, the most widely used and highly successful therapy for melasma includes a combination of the three. The Kligman formula was first proposed in 1975 and consisted of 0.1% tretinoin, 5% hydroquinone, and 0.1% dexamethasone in a hydrophilic ointment.14 To date, variations of this formula continue to be the mainstay of melasma therapy.

• Chemical peels can play a significant role in melasma treatment. Melasma patients treated with topical therapies in combination with a series of glycolic peels showed a trend toward more rapid and greater improvement than patients treated with topical therapies alone.15 A 20% to 30% salicylic acid peel in conjunction with hydroquinone has proven to be safe and effective in treating melasma in skin types V and VI.16 Jessner, glycolic, and salicylic acid peels appear to be helpful adjuncts in the treatment of melasma.

• Dermabrasion has been utilized in melasma. One study of 410 Thai patients treated with dermabrasion demonstrated 97% clearance at a mean 5-year follow-up. Side effects included hypertrophic scars in two patients and hypopigmentation in one patient.17 Although these results are impressive, dermabrasion is always risky in skin types IV through VI and should be approached with caution.

• Multiple, different lasers have been used in melasma with variable success. The Q-switched alexandrite laser was effective in combination with the pulsed CO2 laser with minimal post-treatment sequela.18 One study of 10 female melasma patients treated with the Erbium:YAG described universal transient post inflammatory hyperpigmentation. The authors urged use of this laser therapy only for refractory cases.19

Melasma patients treated with intense pulsed light (IPL) and melasma patients treated with the Q-switched ruby laser have also demonstrated post-inflammatory hyperpigmentation.20,21 Based on these studies, neither IPL nor the Ruby laser appear to be effective in treating melasma.

Sun Protection
Sun avoidance and sun block are essential when approaching a patient with melasma. As discussed previously, only minimal exposure to ultraviolet light can reverse months of improvement in melasma patients. So you can’t stress enough the importance of sunblock and sun avoidance with your melasma patients. Physical blockers with zinc oxide or titanium dioxide are essential in patients with melasma. Novel treatments on the horizon include oral sunblocks as adjuncts to melasma therapy.22
Research in this area may prove to be most helpful in preventing the refractory nature of this often disfiguring condition.