Segmental Phenol Croton Oil Peels for Brow Lifting, Eyelid Tightening, and Lip Eversion

Introduction

This special topic chapter explores a still pioneering aspect of deep chemical peeling using phenol–croton oil formulas. Although the basic concepts of safety, perioperative care, formulas, and the application of deep chemical peeling were well covered by Dr. Richard Bensimon, Dr. Marina Landau, and Dr. Peter Rullan in Chapter 12, Chapter 7, Chapter 8 , some extremely important phytochemical aspects are reinforced in this chapter for adequate understanding of the mechanisms of action involved in surface retraction and dermal neocollagenesis of such procedures.

Physicians who want to focus their expertise in deep peeling should further read about the shift of paradigms that occurred with the awareness of strength gradation by titration of the Croton tiglium oil concentration introduced by Dr. Hetter in an up-to-date, condensed review article recently published by the International Peeling Society (IPS) in the Journal of the American Academy of Dermatology continued medical education article, which also has videos.

Mechanism of Action

Dr. Adolph M. Brown, the plastic surgeon who first introduced to medical applications mixtures of phenol with croton oil, brought a premature rationale that phenol was the active ingredient of his formulas, which contained vegetable oils to “retard” its action, and that phenol penetrated deeper when it was more dilute. Brown’s original phenol–croton oil formula, shown as “Example 3” in his April 1959 US patent application entitled “Skin treating method and composition,” was the first mixture of phorbol esters with phenol in a chemical peel formula. It consisted of 0.5% croton oil in a mixture of water, 50% phenol, and 5% cresols (methylated phenol). To celebrate the 60th anniversary of Brown’s invention, let’s further elaborate on this formula and his efforts. Possibly because Brown apparently had no disciples to continue the application of his initial formula, and because of the patent, which would have commercial implications, his formula was never disseminated in the dermatology or plastic surgery practice. Also, Brown’s actual phenol–croton oil formula was never published in a medical journal. Brown and his wife, Dr. Marthe Erdos Brown, a dermatologist who trained in Paris, published the results of their technique in the British Journal of Plastic Surgery ; however, the formula omitted croton oil for unknown reasons. Two aspects of the 1960 publication were interesting: the sequential taping technique, which is performed as soon as each small area of the face is peeled, which is appropriate for occlusion of a volatile compound, and the “thick and stout applicator,” which allows better control of the surface spread of the formula.

Brownian dogmas about mechanisms of action were popularized among plastic surgeons and some dermatologists after the standard adoption of the Baker-Gordon classical formula, which was published shortly before Brown’s death in 1963, not leaving enough time for scientific discussions or further scientific elucidations.

Brown’s rationale at that time for the mechanisms of action of deep peeling was appropriate given that the field of dermatopathology was still in its infancy. Neither the Herovici stain nor immunohistochemistry methods existed to differentiate newer type III collagen from older type I collagen. “The principal concept … is to induce a controlled fibrosis of some of the inner layers of the skin to cause shrinkage by noticeable condensations of the collagenous fibers of the dermis and by lamination and flattening of some elements of the connective tissue parallel to the skin surface.”

Phorbol esters were initially discovered in croton oil itself in the late 1920s, and such molecules were since thought to explain the paradox of toxic and stimulative effects of croton oil for millennia in Eastern medicine and since the 1800s in Western medicine. Croton oil is still recognized as the richest matrix of these complex vegetable metabolites, which were later found in other species of Euphorbiaceae.

Probably, the interaction of these tetracyclic diterpenes of croton oil with follicular and dermal stem cells and other cells of the connective tissue create the observed rejuvenation, although science still seeks data to elucidate the direct and indirect mechanisms of action of phorbol esters in the connective tissue. Phorbol 12-myristate 13-acetate (PMA) and other phorbol esters trigger numerous biochemical functions in cells; the most well understood are related to the rapid and strong membrane activation of protein kinase C (PKC) isoforms. PMA, the most potent tumor-promoting agent known, is extracted from croton oil. Phorbol esters are not considered carcinogens, but when applied in combination with a carcinogen, they may promote tumor growth. PMA also has anticancer properties, causing differentiation of immature cell lines. The vast historical experience of phenol–croton oil peeling points to anticancer results by many authors, and no case of carcinogenesis was ever reported. Baker stated in 2003 that in thousands of facial peels performed during his career, he never observed a single case of skin cancer during decades of follow-up. The deep action of phorbol esters during a deep chemical peel might provide superior chemoprevention for field cancerization than any other known method; however, proper studies are still pending.

By current dermatopathology methods, after the application of phenol–croton oil formulas, the superficial layers of the skin clearly undergo coagulative necrosis. The deeper layers remain viable and undergo severe inflammation. The epidermal cells from follicles proliferate under the necrotic eschar, whereas type III collagen is formed below the newly formed epidermis. Once the eschar is detached, epithelization completes with a new, thicker epidermis. A thick neocollagenesis band continues to form for some weeks under the new epidermis. Thus skin tightening seems to occur by a deep, thick neocollagenesis band and longitudinal superficial surface shrinkage.

To better understand the effects of a deep chemical peel, one may think of the old skin as an old pillow that has a very loose, wrinkled cover over a flattened, nonelastic, old stuffing (deep dermis). The cover is completely removed, and the superficial part of the stuffing is scratched. Subsequently, in a few days, a new thicker and tightly fitted cover forms over the stuffing. After that, a new thicker and more elastic stuffing is formed between the cover and the scratched old stuffing, making the pillow more round and tight, with less cover surface area as well.

Strength and Effects

The current unequivocal ways to increase the penetration of a deep chemical peel are as follows:

• Increasing the concentration of croton oil

• Increasing friction and pressure (hand weight)

• Increasing the total volume applied: in each application or sets of applications/passes

• Priming the epidermal barrier: degreasing, topical retinoids, and abrasion

The belief that there is increased action by postoperative occlusion with petrolatum jelly or tape after complete absorption of the formula is still debatable, because animal models are extremely impractical and the evidence in patients is still limited to a single split-body case report with tape performed in an extra-facial area. Because postoperative occlusion for increasing the depth of wounding is still debatable, the physician should use the controlled environment in the office to apply the peel to the desired depth of penetration. The depth of penetration correlates to all the effects observed, including treatment goals: fading of deep wrinkles, superficial shrinkage, and collagen formation in the mid-dermis. However, along with deeper penetration, there is a trade-off with the risk of complications, including postoperative pain, edema, longer reepithelization time, longer periods of persistent erythema, skin dryness, postinflammatory hyperpigmentation in susceptible patients, and finally increased risks of pronounced hypopigmentation after full recovery.