Rethinking Chemical Peels: Must we ‘Burn’ our Patients?

John E. Kulesza

Does anyone remember the episode of "Sex and the City" where Samantha is talked into a chemical peel by her dermatologist and ends up looking like a boiled lobster? While some chemical peels in real life can do this, I worry the average TV viewer got the impression all chemical peels work this way and that's just not true. So to answer the title question scientifically, let’s first take a look at commonly used chemical peeling agents and categorize them by activity. There are actually three main types:

1. Corrosive Agents: Primarily acids used at a concentration sufficient to dissolve skin cells. Low pH (<2) Trichloroacetic acid and Salicylic acid at concentrations greater than 10% and alpha hydroxyacids (e.g. Glycolic and Lactic) greater than about 30%, are good examples of corrosive peeling agents.

2. Toxic Agents: Used for deep peels, toxic agents kill living cells. Phenol, Croton oil, (the combination of which are in the Baker-Gordon peel) and 5-FU are cytotoxic poisons that cause sheets of dermal cells to die, separate and slough off. Note that Phenol is only weakly acidic…a 10% aqueous dispersion has a pH of around 5. Croton oil, because it's not water soluble, isn't acidic at all. If that's not enough, 5-FU solutions are actually basic, with a pH of around 9! So who says you need a low pH to peel the skin?

3. Cell Adhesion Modifiers: These are compounds that peel the skin primarily by 'unsticking' skin cells from each other. Specifically, they chemically interact with cellular adhesion molecules, which include molecular complexes called desmosomes, along with special proteins and lipids that form chemical bonds on the surfaces of cells. They usually have low toxicity and corrosive properties, and thus don't really 'burn' or injure the skin.

The most widely used of these agents are low-concentration acids, such as TCA and Salicylic acid below around 10% and alpha hydroxyacids below approximately 30%. Here the acids don't dissolve cells; rather they just affect the adhesion molecules so that skin cells disengage and slough off.
Interestingly, some of these adhesion modifiers have additional biological properties of their own, in which case we sometimes get 'two things for the price of one!' Consider the polyhydric phenols, meaning phenol with an additional hydroxyl group (OH) attached to it:

As you can see, Phenol, Resorcinol and Hydroquinone are extremely similar molecules, the latter two differing from Phenol only via the addition of a single oxygen atom. This small addition, and its position on the carbon ring, radically reduces the toxicity of Phenol while conferring other biologicial properties such as keratolytic and  tyrosinase-inhibiting effects. While many practioners already make use of the keratolytic properties of Resorcinol (the Jessner's Peel contains 14%), few realize that at a similar level Hydroquinone will peel the skin and simultaneously inhibit melanogenesis. This property makes Hydroquinone an agent to consider for peeling high Fitzpatrick (dark) skin types, because it greatly reduces the risk of post-inflammatory hyperpigmentation (PIH).

Another important example of cellular adhesion modifiers are Vitamin A compounds such as Retinoic acid (Tretinoin) and Retinol. These are powerful keratolytic agents that also act on receptors in living cells to produce a variety of beneficial effects, such as upregulation of collagen production, dispersion of melanin granules and elimination of atypia and dysplasia. At relatively low levels (0.1% and below for Retinoic acid), vitamin A compounds can be applied at home for ongoing therapeutic purposes (anti-acne, anti-aging). However, at higher levels (0.5-1%), they begin to reduce the cohesion of sheets of cells deeper in the epidermis and act as a peel.

Other therapeutic compounds that can act as cellular adhesion modifiers include Ascorbic acid at concentrations greater than around 30%, and Phytic and Azelaic acids when properly solubilized at levels beyond about 10%. All three can provide anti-inflammatory, anti-oxidant and melanin-inhibiting effects while superficially peeling the epidermis, and are especially useful in treating high Fitz-type patients or those prone to PIH.

To better understand how the various peeling agents fall into this classification system, here is a graphical presentation that can be used as a quick reference:

So to answer my initial question, can we peel our patients without ‘burning’ them, the answer in many instances is yes. As we have discussed, some peel agents can even reduce side effects, such as inflammation and PIH, inherent in the peel process. That said, peeling agents that are toxic and/or corrosive also have their place in the treatment of deep lines and wrinkles associated with severe photodamage.

What remains unanswered is exactly how peels created using corrosive agents compare with cellular adhesion modifier-based peels. In other words, can a Tretinoin+Azelaic acid peel (which won’t hurt and has low PIH potential) deliver the same result as a TCA peel (which hurts and can cause PIH)? More study is required on that one.

And finally for dear Samantha, I have the following advice: Sometimes we have to endure the style-cramping side effects of chemical peels, but make sure your doctor knows about the full spectrum of agents that can keep you looking beautiful with much less drama!

John E. Kulesza is founder and president of Young Pharmaceuticals, Inc., a 32-year old firm based in Hartford, Conn. that develops and markets proprietary dermatology products to dispensing physicians. Kulesza, an industrial chemist by training, holds several US patents on dermatological technologies including drug delivery systems and prescription drugs. A graduate of Yale University, he is the principal formulator of one of the best known physician-promoted consumer product lines on the market today and scientific advisor to several multinational skincare product makers.

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