Chapter 197. Melasma

A young Hispanic woman delivers a healthy baby boy. On the first postpartum day, she is sitting in the rocking chair after breastfeeding her son. Her doctor notes that she has melasma and asks her about it. She states that the hyperpigmented areas on her face have become darker during this pregnancy (Figure 197-1). She noted the dark spots started with her first pregnancy but they are worse this time. On physical examination, hyperpigmented patches are noted on the cheeks and upper lip (Figure 197-2). Although the patient hopes the pigment will fade, she does not want to treat the melasma at this time.

Melasma is an acquired hyperpigmentary disorder characterized by light- to dark-brown macules and patches occurring in the sun-exposed areas of the face and neck. It is most commonly caused by pregnancy or the use of sex steroid hormones, such as oral contraceptive pills.

Chloasma, mask of pregnancy.

• It is a relatively common disorder that affects sun-exposed areas of skin, most commonly the face. It is believed to affect up to 75% of pregnant women.1
• It affects predominantly women (Figures 197-1, 197-2, and 197-3), with men accounting for only 10% of all cases. It is particularly prevalent in women of Hispanic, East Asian, and Southeast Asian origin (skin types IV to VI) and who live in areas of intense UV radiation exposure.1
• Melasma caused by pregnancy usually regresses within a year, but areas of hyperpigmentation may never completely resolve.2 It may increase with each subsequent pregnancy becoming more obvious.

The major etiologic factors include genetic influences, exposure to UV radiation, and sex hormones.

• The precise cause of melasma has not been determined. Multiple factors have been implicated, including pregnancy, oral contraceptives, genetics, sun exposure, cosmetic use, thyroid dysfunction, and antiepileptic medications.3,4
• Women with melasma not related to pregnancy or oral contraceptive use may have hormonal alterations that are consistent with mild ovarian dysfunction.
• Melasma in men (Figure 197-4) shares the same clinical features as in women, but it is not known if hormonal factors play a role.5

Other factors associated with melasma include certain cosmetic ingredients (oxidized linoleic acid, salicylate, citral, preservatives) and certain antiepileptic drug. Some medications or topical preparations in combination with sun exposure worsen melasma.1

A recent global survey of 324 women with melasma demonstrated that a combination of the known triggers, including pregnancy, hormonal birth control, family history, and sun exposure, affects onset of melasma.6

Clinical Features

The diagnosis of melasma is based upon clinical appearance. Affected patients exhibit splotchy areas of hyperpigmented macules on the face (Figures 197-1, 197-2, 197-3, and 197-4). In natural light, epidermal melasma appears light to dark brown, and the dermal pattern is blue or gray.

Melasma is divided into four clinical types:

1. Epidermal type—The hyperpigmentation is usually light brown, and Wood's light enhances the color contrast between hyperpigmented areas and normal skin. It is the most common type, and it best responds to the use of depigmenting agents.

2. Dermal type—The hyperpigmentation is ashen or bluish-gray and exhibits no accentuation of color contrast under Wood's light. Depigmenting agents are generally not effective for this type.

3. Mixed type—The hyperpigmentation is usually dark brown, and Wood's light enhances the color contrast in some areas but not in others.

4. Indeterminate type—Presents in patients with darker complexions (skin types V to VI) and cannot be categorized under Wood's light.1

The lesion is found typically on sun-exposed areas. The three typical patterns of involvement are:

1. Centrofacial involving the cheeks, forehead, upper lip, nose, and chin.

2. Malar involving the cheeks and nose.

3. Mandibular involving the ramus of the mandible.

Imaging

A Wood's light may be used to determine the type of melasma.1 This does not change the choices of standard topical therapies.

Biopsy

Histologically, there are an increased number of melanocytes, with the deposition of additional melanin and a background of solar elastosis. The two main histologic patterns are epidermal and dermal, depending on the skin layers involved.

• The facial rash of systemic lupus may be confused with melasma as they both can have a butterfly pattern. Melasma is hyperpigmented, whereas the lupus facial rash is usually inflammatory. An antinuclear antibody (ANA) test should be positive in systemic lupus erythematosus (SLE) and negative in melasma. False-positive antinuclear antibodies are usually low titer and the patient does not have other criteria for lupus (see Chapter 180, Lupus Erythematosus).
• Discoid lupus or cutaneous lupus can occur across the face but is usually seen with scarring. In this condition, the ANA is often negative (see Chapter 180, Lupus: Systemic and Cutaneous).
• Contact dermatitis will be inflamed in the acute stage but the postinflammatory hyperpigmentation could be confused with melasma (see Chapter 146, Contact Dermatitis).

The treatment of melasma is challenging because treatment for melasma is generally unsatisfactory.7 Numerous less-than-adequate treatment options exist, including topical agents and chemical peels. Melasma treatment is started only when the patient is disturbed by the hyperpigmentation. All patients can benefit from sun protection and this is always a good place to start.

It is important to give the patient realistic treatment goals. The treatments that follow may lighten the hyperpigmentation but do not generally remove all the hyperpigmentation.

Side effects of all topical treatments include contact dermatitis, ­depigmentation of surrounding normal skin, and postinflammatory hyperpigmentation. Tretinoin should not be used during pregnancy. Discontinue oral contraceptives or other estrogen/progesterone agents, if possible.

Medications

• Hydroquinone is the main bleaching agent used to treat melasma.7 SOR A It is available over the counter in 2% or 3% formulations (some including sunscreens). The prescription strength is 4% and is available with or without a sunscreen. Generic 4% hydroquinone comes in many sizes and formulations, so write the prescription to be flexible to avoid hassles for you and the patient. Although hydroquinone with sunscreen may be somewhat better than ­hydroquinone alone, a combination product has not been shown to be better than using these two topical agents together as two separate products. SOR C
• Hydroquinone is applied twice daily for up to 3 months with subsequent tapering to once daily. If the patient has not noticed a benefit by 3 months, the treatment should be stopped. SOR C
• Ochronosis—If the skin becomes darker with treatment, then the hydroquinone should be discontinued as there is a known side effect of hydroquinone, called ochronosis, that causes hyperpigmentation. Ochronosis only occurs in the treated area, but the hyperpigmentation can be permanent.8
• Hydroquinone can also cause a contact dermatitis, so it is a good idea for the patient to try it on a small area of skin before applying it to large areas of the face. Hydroquinone should be avoided on inflamed skin to avoid additional postinflammatory hyperpigmentation.
• Tretinoin 0.1% (Retin-A) cream is applied once daily at bedtime to lighten melasma. In two studies where tretinoin was compared to placebo, participants rated their melasma as significantly improved in one but not the other. In both studies, by other objective ­measures, tretinoin treatment significantly reduced the severity of melasma.7 SOR A
• Combining tretinoin and hydroquinone is believed to potentiate their effects. SOR C
• There is a triple combination cream (Tri-Luma) containing 4% hydroquinone, retinoic acid, and fluocinolone (corticosteroid). It is used once daily before bed for a duration of 8 weeks. Studies show that it has a superior efficacy than hydroquinone monotherapy for melasma.9,10 SOR A However, the side effect of skin irritation is very common and it is not recommended for long-term use.9,10 Triple-combination cream was significantly more effective at lightening melasma than hydroquinone alone (relative risk [RR]1.58) or when compared to the dual combinations of tretinoin and hydroquinone (RR 2.75).7 SOR A
• Note that Tri-Luma is very expensive. Individual prescriptions for 4% hydroquinone, tretinoin cream, and a mild topical steroid cream can be given to keep the cost down. Desonide or 1% hydrocortisone are good options for the topical steroid. The steroid should not be used daily for longer than 8 weeks to avoid adverse effects.
• Azelaic acid (20%) was significantly more effective than 2% hydroquinone at lightening melasma but not better than 4% hydroquinone.7 SOR A
• Kojic acid formulations, and α-hydroxy acids (such as glycolic acid) also have been used in the treatment of melasma. SOR C
• The adverse events most commonly reported with topical agents were mild and transient such as skin irritation, itching, burning, and stinging.7 SOR A

Surgical Procedures

• Chemical peels are one option for patients with moderate to severe melasma that has not responded to bleaching agents and are seeking further treatment. SOR C
• Dermabrasion treatment is one aggressive option.11 SOR C
• Q-switched pigmentary lasers, intense pulsed light, and fractional laser treatments have some efficacy but can cause postinflammatory hyperpigmentation and relapses may occur so are usually not recommended.12 SOR C

Strict avoidance of sun exposure is important to prevent further hyperpigmentation. SOR C Broad-spectrum, high-protection-factor sunscreens (with UVB and UVA protection), such as titanium dioxide, micronized zinc oxide, Mexoryl, or avobenzone/Parsol, are essential.13

Follow-up is advisable when using bleaching agents. Long-term ­follow-up and reinforcement of limiting sun exposure can be ­accomplished during routine prevention visits.

• Provide the patient with realistic treatment goals.
• If the topical medications are irritating the skin, stop them and return for further evaluation.
• If after 3 months hydroquinone has not worked, stop it.
• If the skin is darkening rather than lightening, stop the medications and return for further evaluation.
• Bleaching agents are often not covered by insurance. The price of hydroquinone formulations can vary widely, so it helps to shop around when cost is a major concern.

Patient Resources

• WebMD. Skin Problems of Pregnancy—http://www.webmd.com/baby/skin-conditions-pregnancy.
• American Pregnancy Association. Skin Changes During Pregnancy— http://www.americanpregnancy.org/pregnancyhealth/skinchanges.html.
• WebMD. Cosmetic Procedures, Birthmarks, and Other Abnormal Skin Pigmentation—http://www.webmd.com/healthy-beauty/cosmetic-procedures-birthmarks.
• WebMD. Hyperpigmentation, Hypopigmentation, and Your Skin—http://www.webmd.com/skin-problems-and-treatments/guide/hyperpigmentation-hypopigmentation.

Provider Resources

• American Academy of Family Physicians. Common Hyperpigmentation Disorders in Adults: Part II—http://www.aafp.org/afp/20031115/1963.html.
• Kang HY, Ortonne JP. What should be considered in treatment of melasma. Ann Dermatol. 2010;22(4):373-378—http://pdf.medrang.co.kr/Aod/022/Aod022-04-01.pdf.