Combination Therapy in Acne: Peels as Adjuvant Therapy

Introduction

Acne vulgaris is an exceedingly common inflammatory condition with a lifetime prevalence approaching 80%. Acne has been associated with depression, anxiety, and low self-esteem; untreated or poorly managed acne often has major effects on patient quality of life and has significant associated socioeconomic and healthcare costs. This underscores the importance of an effective and cost-conscious approach to acne treatment.

An accurate understanding of the disease process is essential to formulating a therapeutic plan for acne. The pathogenesis of acne is multifactorial and begins with corneocyte adhesion ( Box 10.1 ). As corneocytes collect and obstruct the pilosebaceous unit, sebum is simultaneously produced by sebaceous glands, in part because of hormonal stimulation. This combination of follicular obstruction and continued sebum production creates an environment that is conducive to the growth of bacteria, namely gram-positive Propionibacterium acnes (Cutibacterium acnes) . The resulting inflammatory response results in clinically visible acne: comedones, pustules, inflammatory papules, and cysts. If severe, this inflammatory process can result in significant and permanent scarring. There are several approaches to treating acne, and various treatments target specific steps in the disease process: decreasing corneocyte adhesion, minimizing sebum production, and lowering bacterial counts. Management is often approached in a stepwise fashion: topical retinoids and topical antibiotics for primarily comedonal acne, adjunctive systemic antibiotics and/or antiandrogens for inflammatory acne, and systemic retinoids for severe or recalcitrant cases. There are also several adjuvant therapies available for both active acne and acne scarring, including light-based therapies (photodynamic therapy, pulsed dye laser, CO ₂ laser) and mechanical-based therapies (microneedling, microdermabrasion). Chemical peels represent an additional effective, well-tolerated, and economical adjuvant treatment option for acne and acne scarring. As an often under utilized acne treatment modality, this chapter aims to reintroduce chemical peels as a valuable tool worthy of consideration when approaching the acne patient. Chemical peels are low cost, have minimal side effects, and are an effective method for treating acne and acne scarring. For patients with severe inflammatory acne, the adjuvant use of chemical peels should be considered only after first improving the condition with a systemic medication. Nonetheless, even these patients can frequently benefit from chemical peels.

Box 10.1

Pathogenesis of Acne Vulgaris: A Disease of the Pilosebaceous Unit

Abnormal follicular keratinization → microcomedo formation → comedo rupture → release of keratin and sebum → inflammatory papule/pustule → nodule/cyst

Acne: Why Chemical Peels?

Broadly speaking, chemical peels work by inducing controlled cutaneous damage and fostering dermal and epidermal regeneration. The mechanism of action and characteristics of many chemical peels make them well suited for the treatment of active acne and acne scarring. Many chemical peels exhibit keratolytic and comedolytic effects, especially helpful for noninflammatory comedonal acne. Chemical peels may also decrease sebum production and pore size, and many have antibacterial and antiinflammatory properties useful in decreasing bacterial counts on acne-prone skin. Additionally, the controlled cutaneous damage induced by chemical peels promotes the absorption of other topical acne medications, augmenting their pharmacological effect. By increasing the efficacy of topical medications, systemic medications and their associated health risks and economic costs may be avoided. Although chemical peeling can be an excellent adjuvant modality in the treatment of mild and moderate comedonal and inflammatory acne, chemical peels are not appropriate for the treatment of severe inflammatory or nodulocystic acne. Severe inflammatory or nodulocystic acne must first be improved with other medications before initiating a peeling regimen.

Peeling Agents and Patient Considerations

A variety of chemical peel formulations and treatment regimens exist. When treating active acne vulgaris, the most commonly used peels are superficial or light peels ( Table 10.1 ; see also Chapter 4 ). Peel depth depends on type of peel agent and concentration used, skin preparation technique, and skin contact time. Superficial chemical peels induce controlled cutaneous damage limited primarily to the epidermis. Their limited depth of penetration affords notable clinical improvement with minimal (if any) patient discomfort or downtime. Salicylic acid (SA) (5%–30%) and glycolic acid (GA) (20%–70%) are the most commonly used agents for the treatment of mild to moderate comedonal and inflammatory acne. Additional agents used include lactic acid (LA), mandelic acid (MA), trichloroacetic acid (TCA), and Jessner’s solution (JS). Unique qualities of each agent, coupled with practitioner confidence and patient characteristics, help guide chemical peel selection. Furthermore, the use of combination chemical peel treatments—treating patients in a sequential manner with one peeling agent followed by a different agent—can be considered when developing a treatment plan.

Table 10.1

Selected Peeling Regimens for Mild to Moderate Comedonal and Inflammatory Acne

Peel	Properties	Regimen	Contact Time	Considerations
Salicylic acid	Keratolytic, comedolytic, antibacterial, antiinflammatory	30% salicylic acid every 2–4 weeks for 3–6 sessions	∼6 minutes	Safer for darker skin types
Glycolic acid	Keratolytic, comedolytic, antibacterial, antiinflammatory	30%–70% glycolic acid every 2 weeks for 3–5 sessions	∼3–5 minutes	Requires neutralization Safe in pregnancy
Mandelic acid	Keratolytic, comedolytic, antibacterial, antiinflammatory	10% mandelic acid + 20% salicylic acid every 2 weeks for 6 sessions	∼3–5 minutes	Requires neutralization May help with skin lightening
Trichloroacetic acid (lower strength)	Desquamation induced via protein denaturation, antibacterial	25% trichloroacetic acid every 2 weeks for 4 sessions	N/A	Higher risk of procedure-related dyspigmentation
Jessner’s Solution	Keratolytic, comedolytic, antibacterial	Jessner’s every 2 weeks for 3–6 sessions	N/A	May help with skin lightening
Pyruvic acid	Keratolytic, comedolytic, antibacterial	50% pyruvic acid every 2 weeks for 5 sessions	∼3–5 minutes	Requires neutralization

Salicylic Acid

SA is a beta-hydroxy acid commonly used for the treatment of acne vulgaris. Its strong keratolytic and comedolytic properties make it particularly suitable as an acne treatment. SA promotes desquamation of the upper lipophilic layers of the stratum corneum, resulting in superficial desquamation and rejuvenation. SA also penetrates pores and has antibacterial and antiinflammatory properties. SA may also decrease sebum production in acne-prone patients. In clinical studies, SA peels have been shown to reduce the number of inflammatory and noninflammatory lesions in patients with active acne. Although several concentrations and treatment regimens exist, the most commonly utilized concentrations for treatment of acne is 30% SA. A common regimen includes 30% SA applied every 2 to 4 weeks for a total of three to six sessions ( Figs. 10.1–10.4 ). Lower concentrations can be used but typically require a greater number of treatment sessions to achieve an equivalent treatment effect. SA peels are self-neutralizing and generally very well tolerated. Patients occasionally note minimal procedural discomfort (i.e., tingling and burning) that is easily mitigated with the use of a handheld fan. Downtime is minimal, with postprocedural erythema and desquamation often resolving in 1 to 3 days and with reepithelialization complete in 7 to 10 days. SA peels represent a safe peeling agent even in darker-skinned patients, because postprocedural dyspigmentation is rare.

Fig. 10.2, Clinical endpoint for a 30% salicylic acid (SA) chemical peel. Application yields pseudofrosting as SA crystalizes. Typically, one to three layers are applied until a uniform pseudofrost is achieved. The face is then washed with water after approximately 6 minutes.

Fig. 10.3, Three days after 30% salicylic acid chemical peel. There is very minimal superficial peeling resulting in minimal to no downtime.

Fig. 10.4, One week after 30% salicylic acid chemical peel.

Glycolic Acid

GA is an alpha-hydroxy acid that shares many beneficial qualities with SA. In particular, GA reduces corneocyte adhesion and keratinocyte plugging. GA also has proven antibacterial efficacy against P. acnes . The only published randomized-controlled clinical trial comparing a chemical peel to placebo in the treatment of acne vulgaris demonstrated statistical improvement in both inflammatory and noninflammatory lesions with GA. GA acne treatment outcomes are largely comparable to outcomes with SA. One clinical study found a patient preference for GA over SA (41% versus 35%), but the underlying reason and clinical significance of this preference was unclear and has not been replicated in additional studies. GA does require neutralization with an alkaline solution to halt exfoliative effects, which should be considered when selecting this agent. A longer application time interval prior to neutralization results in increased penetration of the chemical peel. Treatment regimens typically use 30% to 50% GA every 2 weeks for 3 to 5 minutes for three to six sessions ( Figs. 10.5–10.8 ). Higher concentrations typically require shorter treatment times and fewer sessions but are likely to result in increased patient discomfort and carry a higher risk of complications. Generally, GA peels are safe and well tolerated, with common adverse effects limited to transient procedural burning and erythema and postprocedural desquamation. Although safety data are limited, GA is generally considered safe for pregnant patients given its limited dermal penetration.