Melasma, melanin, and mosaicism

While our facial skin’s cells all start out with the exact same DNA, they don’t all look alike. Skin, more than any other organ, reflects a genetic “mosaicism”, which is a fancy way to say they may be of an identical genotype but differ in terms of gene expression, or phenotype. Which itself is a fancy way of saying genes aren’t the only factor determining skin appearance. We won’t go too deep here, but will provide additional reading for those so inclined (we know some skin nerds read BFT). The main point to make is that skin is in some ways a patchwork quilt. Based on where it is on your facial anatomy, or physiognomy,  the amount of sun and chemical stress it is exposed to, and signals from elsewhere in the body, different regions of skin can start to look and feel quite, well,  different. Different colors, most certainly.  Other changes too, many of which are the signals of aging at key stress points. The analogy of a mosaic, where the final picture may be composed of many different bits of stone or glass, and yet adds up to a single unified image, really fits facial skin quite well.

Melasma

One major difference in how skin’s mosaic bits look in terms of coloration smoothness and consistency depends on how much melanin is being expressed in that bit, or that region. Melasma (sometimes called the “spattered suntan” creates a unique mosaic facial skin pattern.

Melasma is a disorder of pigmentation that affects women nearly ten times as often as it affects men. The word is from a Greek term that means “a black color”. It is seen more commonly in people with naturally darker skin tones. While mottled uneven pigmented spots and patches can affect any sun-exposed area, the face and neck predominate. The unwanted cosmetic effects can vary from slight to severe. The psychosocial impact can be significant.

The Fitzpatrick Skin Classification System differentiates skin on the basis of reaction to ultraviolet radiation.  There are six types based on progressive genetic predisposition to melanin production. Class I include skin types typically seen in northern regions such as Scandinavia and Ireland where fair skin is the norm. Class VI skin is the most darkly pigmented. The incidence of melasma is greater with types IV, V, and VI with type IV skin having the greatest predilection.  Hispanics and East Asians have melasma most frequently, but it is common in people of Middle Eastern, Indian, South American, and Ethiopian descent.

The Mask of Pregnancy

Aside from ultraviolet radiation which stimulates melanin production (think suntan), hormonal influences play a highly significant role in the etiology of melasma. It is sometimes referred to as “the mask of pregnancy” (called chloasma when caused by pregnancy) because fifty to seventy percent of pregnant women are affected. The use of oral contraceptives is associated with increased incidence and severity of melasma. Interestingly, post-menopausal women on treatment regimens for osteoporosis that utilize combined estrogen and progesterone therapy have increased incidence, while those taking estrogen only do not. Supporting the hormone association is the fact that men taking diethylstibesterol treatment for prostate cancer also have a higher incidence than other men. Other possible factors include thyroid and ovarian abnormalities, cosmetics, phototoxic reactions, anti-seizure drugs, liver disease and certain nutritional deficiencies.

Melanin – Where and How Much Is Key

The amount of melanin synthesized by the melanocytes and its distribution pattern in the surrounding keratinocytes determines the intensity and color of the skin. The increase may occur primarily in the epidermis, the dermis, or both. If the cause is principally increased production of melanin, it is referred to as melanotic hyperpigmentation. If caused by an increase in the number of melanocytes, it is termed melanocytic hyperpigmentation. The first type affects predominantly the epidermis, the second intradermal and peri-dermal tissues. Epidermal melasma appears light grown whereas dermal has ashen or bluish-grey coloration. Some may experience a mixed pattern with both dermal and epidermal involvement.

Ultraviolet radiation can cause peroxidation of lipids in cellular membranes, leading to the generation of free radicals, with consequential stimulation of melanocytes to produce excess melanin – hence the suntan. UV also stimulates MSH (melanocyte stimulating hormone) and ACTH (adrenocorticotropin hormone), both of which can in turn stimulate cellular receptors that lead to proliferation of melanocytes.

But the story gets even more complicated. In nine never-pregnant women with melasma, high levels of LH (luteinizing hormone) were measure along with lower than normal levels of estrogen. In men with melasma, higher than normal levels of LH were also seen, suggesting testicular dysfunction may be involved. It is an incompletely understood phenomenon.

Melanin is synthesized from the amino acid tyrosine by a series of oxidative reactions catalyzed by the enzyme tyrosinase. Normally, once formed, melanin is transported into nearby keratinocytes in the deepest layers of the epidermis. These cells progressively work their way towards the surface to become part of the stratum corneum where they are eventually sloughed off.  If a sunburn results in rapid peeling, the underlying skin will not have had sufficient time to incorporate similar amounts of melanin and is thus lighter in color.

Craniofascial

malar

mandibular

Melasma Treatments

Various methods are used to ameliorate the discoloration of melasma including hypopigmenting agents, chemical peels, lasers, and dermabrasion. No matter what modalilty is utilized, protection from ultraviolet radiation is essential in the treatment and prevention of melasma. Sunscreens that protect against UVA and UVB are recommended. Examples of broad-spectrum sunscreens are titanium oxide and micronized zinc oxide.

Hypopigmenting Agents

Inhibition of melanin synthesis through use of agents that reduce tyrosinase activity has been a mainstay in treating melasma for decades. The gold standard has been use of 2% to 4% hydroquinone. Although highly effective, high concentrations of this medication are associated with allergic contact dermatitis, hypopigmentation of the surrounding skin, and rarely hyperpigmentation that resolves only slowly after discontinuation of the drug. Its use is banned in the European Union and Japan. In 2006, the FDA revoked its previous approval of hydroquinone and proposed a ban on all OTC preparations. Its carcinogenetic potential is a concern following increased incidence of tumors in rats; additional testing is ongoing.

Other substances used include glycolic acid which is shown to thin the stratum corneum, disperse the melanin in the basal layer of the epidermis, and stimulate the lysis of epidermal cells. Kojic acid, a fungal metabolite, inhibits tyrosinase by chelating a necessary co-factor, copper, in melanin synthesis. Azeleic acid is a competitive inhibitor of tyrosinase. Tretinoin (aka Retin-A) stimulates keratinocyte proliferation and turnover. Liquirtin, a chemical found in licorice, disperses melanin in the skin. Ascorbic acid is believed to suppress melanin synthesis by tyrosinase inhibition.

Chemical, Abrasive, and Light Modalities

Chemical peels have been a mainstay treatment for years. Topically applied agents cause the skin to undergo exfoliation, thus creating revitalized skin. Glycolic acid peels are most commonly used. This is particularly valuable for epidermal melasma where pigmentation is superficial. Dermabrasion uses a rotary diamond fraise to cause physical disruption of the epidermis and superficial dermis. This treatment has good long term results with as many as 97% of patients in one series having no recurrence of their melasma. Light treatments include pulsed carbon dioxide, alexandrite, or YAG lasers, and IPL (intense pulsed light.) Light based treatments are preferred treatments for mixed or dermal type melasma where there melanin is in deeper layers of the skin.

before & after chemical peel

before & after laser

before & after IPL

When Budgets Are an Issue

Most medical insurance policies do not cover purely cosmetic procedures. While it is not the same as eliminating the problem, adept persons with limited resources can still manage to effectively camouflage melasma with appropriately applied makeup.