Hyperpigmentation (stains, if you will) disorders of the skin are common. [Photo credit.] The most common are melasma and postinflammatory hyperpigmentation (PIH). These "stains" are the result of an increase in cutaneous melanin deposition either by increased melanin synthesis or, less commonly, by a greater number of melanocytes. The amount of color change will depend on the location of the melanin deposition. Epidermal involvement will appear as brown-grey discolorations. Epidermal deposition of melanin is enhanced with the use of a Wood's lamp (dermal is not). The mixed type hyperpigmentation will have enhancement in some areas, but not in others with the Wood's lamp. Dermal hyperpigmentation is much more challenging to treat.
Melasma occurs mainly in women (more than 90% of cases) of all racial and ethnic groups, but particularly in those with Fitzpatrick skin types IV-VI. The cause of melasma is unknown, but factors such as genetic predisposition, UV light exposure, and estrogen exposure play a large part. Estrogen is thought to induce melasma as it often develops during pregnancy, with oral contraceptive (OC) use, and hormone replacement therapy (HRT) in postmenopausal women. Melasma in pregnancy will often clear within a few months of delivery. Discontinuation of OC or HRT, along with adequate sun protection, may also result in melasma clearance. Melasma presents as brown to grey macules and patches with irregular / geographic borders. The pigmented patches are usually sharply demarcated and symmetrical. There is a predilection for sun-exposed areas. The three major patterns of distribution are:
Centrofacial--cheeks, forehead, upper lip, nose, and chin (66% of cases)
Malar--cheeks and nose (20% of cases)
Mandibular--rami of the mandible (15% of cases)
Differential diagnosis of melasma should include cutaneous mercury deposits, drug-induced hyperpigmentation, erythema dyschromicum perstans, mastocytosis, lichen planus actinicus, and postinflammatory hyperpigmentation.
Postinflammatory Hyperpigmentation (PIH) is a pathopysiologic response to any cutaneous inflammation, such as acne, atopic dermatitis, lichen planus, trauma (burns, abrasions, postsurgical), insect bites, and psoriasis. Similar to melasma, it is more obvious in patients with Fitpatrick skin type IV-VI. It has no gender or age predominance. The lesions are usually limited to the site of the preceding inflammation and have distinct, feathered borders. Melanocytes can either be stimulated by the inflammatory process to become hypertrophic (thereby secreting more melanin) or the number of melanocytes can increase. Epidermal hyperpigmentation (ie associated with acne) occurs when increased melanin is transferred to keratinocytes. Dermal hyperpigmentation (ie associated with lichen planus and cutaneous lupus erythematosus) occurs when the basement membrane is disrupted and melanin falls into the dermis, residing within the melanophages.
Treatment goals for hyperpigmentation include promoting melanosome degradation, inhibiting the formation of melanosomes, and retarding the proliferation of melanocytes. All patients should limit sun exposure and use a daily broad-spectrum high SPF sunscreen. Topical treatment is the mainstay. Combination therapy is more effective than single agents used alone. and includes:
Hydroquinone (HQ) 2-4%--It inhibits the conversion of dopa to melanin by inhibiting the activity of tyrosinase. It has been proposed that it may also interfere with DNA and RNA synthesis, degrade melanosomes, and destroy melanocytes. It is applied in a thin layer over the affected areas twice daily for up to 12 weeks. It should not be used longer than 12 weeks, as there are no studies regarding safety in long term use. Side-effects include irritant and allergic contact dermatitis, PIH, nail bleaching and rarely ochronosis-like pigmentation. Toxicity studies have shown HQ is capable of inducing renal adenoma in rats and is fetotoxic in animals. Because of these studies, HQ is banned in many countries including Japan, the European Union, South Africa, and Australia. In August of 2006, the FDA issued a proposal to remove it from any OTC products. Currently, the only FDA-approved prescription form of HQ is Tri-Luma (Galderma Laboratories).
Retinoids-- Tretinoin 0.05%-0.1% reduces pigmentation by inhibiting tyrosinase transcription and by interrupting melanin synthesis. It typically takes at least 24 weeks to see clinical improvement in melasma reduction using tretinoin. It may also increase pigmentation secondary to the irritation. It commonly causes erythema and peeling.
Azelaic acid (15%-20%) is a C9 dicarboxylic acid. It is a reversible inhibitor of tyrosinase. It may have cytotoxic and antiproliferative effects on melanocytes. It has been shown to be as effective as HQ 4% wibut without the side effects. Used in combination with 0.05% tretinoin or 15%-20% glycolic acid, it may produce earlier, more pronounced skin lightening. Adverse effects include pruritus, mild erythema, scaling, and burning.
Kojic Acid (KA) 2% is produced by the fungus Aspergilline oryzae. KA is a tyrosinase inhibitor. It is generally as effective as the other therapies, but may be more irritating. Generally, it is used in combination with GA 10% for 3 months.
Glycolic Acid (GA) 5%-10% is an alpha-hydroxy acid. It decreases pigment by thinning the stratum corneum, enhancing epidermolysis, dispersing melanin in the basal cell layer of the epidermis, and increasing collagen synthesis in the dermis. Mild irritation is a common adverse effect.
HQ 5% + tretinoin 0.1% + dexamethasone 0.1%--The addition of tretinoin to HQ eliminates pigment and increases keratinocyte proliferation by preventing the oxidation of HQ and improving the epidermal penetration. The addition of topical corticosteroids reduces the irritative effects of hypopigmenting agents, and inhibits melanin synthesis by decreasing cellular metabolism. This combination was first introduced in 1975 by Kligman.
HQ 4%,+ tretinoin 0.05% + fluocinolone acetonide 0.01% (Tri-Luma®, Galderma) --Clinically significant improvement may be noted as early as 4 weeks. The most common adverse effects are mild local irritation, erythema, and skin peeling. The mixture should be applied to the entire affected area to avoid blotchiness.
Over-the-Counter Products--There are many OTC products available. There is some evidence to support the use of Olay® Definity® (N-acetyl glucosamine (NAG) and niacinamide).
Treatment of melasma in pregnant women is routinely deferred until after delivery for multiple reasons: 1) treatment resistance while hormone trigger persists; 2) most women will show significant improvement without treatment after the pregnancy ends; and 3) drug therapy is contraindication during pregnancy.
Treatment of PIH should begin with management and control of the underlying skin condition. Most of the therapies used for hyperpigmentation have been studied in melasma and the same treatment principles hold for PIH.
Topical Treatments for Melasma and Postinflammatory Hyperpigmentation by C.B. Lynde; J.N. Kraft, MD; C.W. Lynde, MD, FRCPC--MedScape Article
Skin Lightening and Depigmenting Agents by Alaina James, MD--eMedicine Article
Melasma by Deborah Zell, MD--eMedicine Article