Introduction

As medical advancements have increased not only our life span but also our quality of life, it is natural to expect a greater public desire to undo the untoward effects of sunlight, aging, and genetics. This desire has spawned a myriad of unsubstantiated skin-care products and practitioners of “wonder” technologies promising unrealistic end results. Chemical peeling has withstood the harshest critics of both safety and results. Starting with “lay peelers” in the early 20^th century, chemexfoliation has provided not only a stalwart treatment for practitioners of skin rejuvenation, but also the standard by which other modalities are judged. The various formulations have provided treatment for rhytids, lentigines, dyschromias, and actinic damage. The goal of this chapter is to address some recent changes in our overall knowledge base regarding chemical peels; to uproot some old, outdated tenets; and to discuss the versatility of Hetter chemical peels.

Background: Basic Science of Procedure

The history of chemical peeling did not begin in the hands of physicians, but rather in those of the “lay peelers.” Hollywood, California, in the 1920s was fertile ground for these early practitioners because the stars of early motion pictures wished to maintain both a youthful appearance as well as career longevity. In the 1950s and 1960s that physicians began not only to learn these practices but also to “wrestle” them away from prominent “lay peelers” trained by Jean DeDesly and Antoinette LaGasse. Gregory Hetter, in his four-part series in 2000,1,2,3,5 eloquently laid out a detailed history of the passing of the chemical peeling art from the “lay peelers” to the plastic surgeons of the 1950s and 1960s.

With the entry of chemical peeling into the realm of medical science, many reports appeared in the literature regarding the experiences of plastic surgeons. Not all accounts were matched with scientific scrutiny. Instead, in some cases, dogma was written and adhered to for decades. Much of this dogma came from the use of the Baker-Gordon phenol-croton oil formulation ( Table 7.1 ), the earliest formula widely used by physician peelers.

Several insular suppositions were reported repeatedly, for years, in the literature regarding the phenol-croton oil peel. These assumptions date back to the late 1950s and early 1960s, when the phenol-croton oil formulas were introduced to the plastic surgery arena. It was from “lay peelers” in Hollywood in the 1920s and the Miami, Florida, area in the 1950s that plastic surgeons were able to “tease away” secret, long-used phenol-based peeling solutions.1 Most formulas contained similar concentrations of croton oil. Litton was the first to present one of these formulas to the American Society of Plastic and Reconstructive Surgeons (ASPRS) in the late 1950s. However, it was Baker who was credited for the formula he presented in November 1961 and then modified to his “classic” formula in 1962.2

Around the same time that Baker′s “classic” formula was described, Adolph Brown presented three doctrines of phenol peeling. First, increased concentrations of phenol (80 to 90%) prevented deeper peels by causing an immediate keratocoagulation that blocked its further penetration. Second, addition of saponin increased the depth of penetration of phenol. Third, croton oil′s role was simply to “buffer” the solution.3,4 The literature regarding chemexfoliation in the 1960s quickly adopted these assertions and created further claims (i.e., phenol was the one and only active ingredient within the Baker formulation; phenol in lower concentrations penetrated more deeply than in higher concentrations). It was believed, as a result of these pronouncements, that lower phenol concentrations were more dangerous due to their deeper penetration. It was supposed, as well, that Septisol (Steris, Mentor, OH) caused a deeper penetration and that croton oil had no physiological role in the peel. Since Brown′s assertions in the early 1960s, there had been neither animal nor human scientific studies that supported his postulates. Gregory Hetter questioned these claims in the late 1990s and, more importantly, questioned croton oil′s role, or supposed lack there of, in Baker′s formula.

Croton oil is pressed from the seeds of Croton tiglium, a small shrub found in India and Ceylon. The oil consists mainly of oleic, linoleic, myristic and arachidonic acids.5 Less than 5% of the oil is made up of a resin that has been known in scientific literature since 1895 to possess irritant and toxic properties. In 1935, Joseph R. Spies isolated this toxic resin and applied it to a volunteer′s arm, creating severe vesiculations of the skin and a resultant wound that took almost 3 weeks to heal.5 Spies also showed that croton oil was soluble in ethanol and benzene, and that it had poor solubility in a 50:50 phenol-to-water solution.5 Hetter theorized that this might create the need for the surfactant, Septisol, in the Baker formula.

To refute Brown′s postulates and to help elucidate the role of croton oil, Hetter found a patient who was willing to undergo multiple chemical peels at different concentrations of phenol and croton oil. His findings contradicted what had been previously assumed. At the lowest concentration of phenol, 18%, there was minimal postpeel effect. Mild keratolysis occurred with 35% phenol but there was no clear dermal effect. Hetter noted some desquamation with mild dermal effect after the 50% phenol peel. It was only with 88% phenol that Hetter saw an obvious upper dermal effect, which took 4 to 5 days to heal. A more profound dermal effect ensued with the addition of croton oil; and with different croton oil concentrations, there were varying healing times. A 0.7% croton oil concentration application required a 7-day healing time, whereas a 2.1% croton oil concentration—equivalent to that of the classic Baker formula—resulted in an 11-day healing period.5 From his experience with this one patient, Hetter deduced: phenol peels more deeply with increased solutions; higher concentrations of phenol (88%) without Septisol peel more deeply than lower mixtures (35% and 50%); and the resultant peel is deeper with increasing concentrations of croton oil.

Hetter used this case to guide his treatment of five additional patients with varying croton oil concentrations. The results from these five cases allowed him to arrive at some generalizations about phenol-croton oil peeling. First, the dilution of croton oil in a constant phenol solution shortens the healing time, suggesting a more shallow depth of penetration. Second, phenol concentration has little to do with depth of injury. He confirmed the observation of Stegman in 1980,6 reiterated by Stone in 2001,7 that multiple coats will increase the depth of injury. Obagi8 first described the need for different depths of peeling for individual subunits of the face. Hetter translated this to his use of varying concentrations of croton oil in diverse regions of the face. Although he found that the lower nose could tolerate croton oil concentrations up to 1.2%, the cheeks and forehead tolerated mixtures up to only 0.8%; and the upper nose, temple, and lateral brow could withstand concentrations up to only 0.4%—before the risk of complications rose. Last, Hetter believed 1% croton oil solutions were the upper threshold for safe use to avoid serious risk of hypopigmentation.

Initially, Hetter performed his preliminary work using phenol as a “vehicle” at 33% for the croton oil with 1-drop (0.35%), 2-drop (0.7%), and 3-drop (1.1%) formulations. Later, he believed it would be optimal to have a more standardized means of measuring the croton oil concentrations, rather than relying on inherently inconsistent droppers. He converted drops to cubic centimeters by having 25 drops equal 1 cubic centimeter. Using this conversion, he created a stock solution of 0.04 cc (now mL [milliliter] would be used) of croton oil per 1 cc of phenol. From this—needing only Septisol, phenol, and water—he could make varying croton oil concentrations of 0.4, 0.8, 1.2, and 1.6% in a constant phenol mixture. Using Hetter′s formulations, the practitioner can decide between a phenol concentration of 35 or 48.5%. Table 7.2 shows the formulas for the varying croton oil mixtures of the Hetter peels using a phenol concentration of 35%.

Hetter demonstrated that the depth of penetration is partially dictated not only by the components of the peeling solution, but also by the concentrations of the components. Stone emphasized the importance of how application of these different solutions must be controlled to create desired results. Stone tested Hetter′s postulations by performing peels on three sample patients. He used Hetter′s varying concentrations; the “classic” Baker formula with and without croton oil; and different phenol concentrations without croton oil.

In the first patient, Stone showed on successive biopsies that the “classic” Baker formula with and without croton oil created the same depth of penetration and injury with repeated rubbings and occlusive taping. In the second case, he peeled the patient with both alternating concentrations of phenol (50 and 88%) and solutions of croton oil (2.2 and 0.4%) on the thick forehead skin and the thinner nasojugal trough skin. Stone varied the number of rubs on the nasojugal trough as well, using wrung-out gauze. He found, on biopsy, that all formulas—when applied with 50 rubs—created equal histological results and similar fibrosis. However, by decreasing the number of rubs, Stone confirmed Hetter′s findings that the depth of penetration increases with increasing phenol concentration. These results suggest a threshold of injury that can be achieved with phenol and croton oil in varying concentrations, when enough applications are employed. This was confirmed in the third patient, on whom he used lower phenol concentrations with 2.2, 0.4, and 0% croton oil. He found that the injury threshold can be met with all three solutions, but with different numbers of applications. Stone concluded that croton oil serves to lower the threshold number of applications.7

Stone′s work emphasizes the important point addressed but not stressed in Hetter′s work—how the peeling solution is applied to the skin is as crucial as what active agents are present within the concentration. In the author′s opinion, this is where the experience of the peeler and the “art” of peeling become significant.