Light-based, adjunctive, and other therapies for acne vulgaris

INTRODUCTION — Acne vulgaris is a common condition, and there is significant demand for effective acne therapies. Many over-the-counter products are marketed. In addition, a number of procedural therapies are utilized for the treatment of acne vulgaris with variable effectiveness.

The use of over-the-counter and light-based therapies as well as several adjunctive therapies (office-based chemical peels, microdermabrasion, comedo extraction, intralesional glucocorticoids, and heat therapy) will be reviewed here. Conventional therapies, hormonal therapy, and isotretinoin therapy for acne vulgaris are discussed separately. (See "Acne vulgaris: Overview of management" and "Oral isotretinoin therapy for acne vulgaris" and "Acne vulgaris: Management of moderate to severe acne in adolescents and adults".)

OTHER TOPICAL MEDICATIONS — For many people with acne, treatment begins with nonprescription regimens. Numerous products are available, and nonprescription treatments are effective for some individuals. Some of the most common ingredients found in nonprescription acne products include salicylic acid, benzoyl peroxide, sulfur, and alpha hydroxy acids. Tea tree oil has also been used for treatment of acne. In July 2016, the US Food and Drug Administration (FDA) approved adapalene 0.1% gel for over-the-counter use, making it the first topical retinoid approved for distribution directly to consumers. (See "Acne vulgaris: Overview of management".)

Patients with mild to moderate acne who do not respond to nonprescription products after three months of treatment should be clinically evaluated. Patients with more severe acne should be evaluated earlier, to consider the use of the most effective treatment regimens to prevent or minimize scarring.

Topical nonprescription acne therapies are generally well tolerated. However, rare but serious and potentially life-threatening hypersensitivity reactions to nonprescription topical acne products containing salicylic acid or benzoyl peroxide have been reported [1]. Whether these active ingredients or inactive ingredients are responsible for the reactions is unclear. Symptoms may occur within minutes to one day or longer after product use and may include severe skin reactions, throat tightness, difficulty breathing, feeling faint, or swelling of the eyes, face, lips, or tongue. The US FDA recommends limiting application of these products to one or two small affected areas during the initial three days of use to test for hypersensitivity [1].

Salicylic acid — Salicylic acid (0.5 to 2%) is a beta hydroxy acid available in a number of nonprescription gels, lotions, solutions, cleansers, pads, and masks. It is a desquamating agent, and its lipophilic properties enable it to penetrate the pilosebaceous follicle, producing a comedolytic effect [2]. Topical salicylic acid also possesses mild anti-inflammatory properties. Salicylic acid is usually applied once daily and subsequently increased to two or three times per day if needed [3]. The frequency of application can be reduced to once daily or every other day if the patient develops skin dryness or peeling [3].

In three placebo-controlled studies, salicylic acid was an effective treatment for acne [4]. It is a treatment option for patients who cannot tolerate topical retinoids or benzoyl peroxide [5,6]. Salicylic acid can also be used in combination with benzoyl peroxide, as the mechanisms of action of these drugs complement each other in the treatment of acne. (See "Acne vulgaris: Overview of management", section on 'Benzoyl peroxide'.)

Higher concentrations of salicylic acid may be used in the office to perform superficial chemical peels. (See 'Office-based superficial chemical peels' below.)

Benzoyl peroxide — Benzoyl peroxide is a commonly used antimicrobial acne treatment that also possesses comedolytic properties. The drug is an effective treatment for inflammatory and comedonal acne. It is available in both nonprescription and prescription formulations. (See "Acne vulgaris: Overview of management", section on 'Benzoyl peroxide'.)

The combination of benzoyl peroxide and salicylic acid may be useful for patients who desire a nonprescription regimen [2,7].

Sulfur — Topical sulfur has been used for the treatment of acne for many years, although there are few data supporting its efficacy [8]. The mechanism of action remains unknown. It is thought that sulfur interacts with cysteine in keratinocytes, resulting in the production of hydrogen sulfide, which has a keratolytic effect [9]. Sulfur also inhibits the proliferation of Cutibacterium (formerly Propionibacterium) acnes [8]. Older formulations of sulfur were sometimes offensive to patients due to an unpleasant, rotten egg-like odor. This odor is minimized in newer formulations.

Sulfur is often combined with salicylic acid in nonprescription products. In addition, sulfur has been studied in combination with benzoyl peroxide. In a case series of 113 patients with acne, a combination of 2.5 to 5% sulfur and 10% benzoyl peroxide was efficacious for the majority of patients [10].

Prescription products that combine sulfur with sulfacetamide, an ingredient with antibacterial properties, are available and have been effective in open-label studies [11,12].

Alpha hydroxy acids — The most commonly used alpha hydroxy acids are glycolic acid and lactic acid. Alpha hydroxy acids are weak organic acids that cause desquamation and diminish corneocyte cohesion, thereby normalizing follicular keratinization [13]. These agents may also promote dispersing of basal layer melanin, which can help to improve postinflammatory hyperpigmentation.

Alpha hydroxy acids in low concentrations and buffered alpha hydroxy acids in higher concentrations are available as over the counter washes, lotions, creams, and at-home peel systems. High concentrations with more free acid are used in the office to perform superficial chemical peels. (See 'Office-based superficial chemical peels' below.)

Only low-quality evidence is available regarding the use of low concentrations of alpha hydroxy acids for the treatment of acne. Alpha hydroxy acids may be most effective as components of a treatment regimen containing other acne medications [14]. Glycolic acid is generally considered to be less effective than topical tretinoin, when used as monotherapy. However, a synergistic effect has been observed when the two medications are combined [13].

Alpha hydroxy acids also diminish the signs of aging skin, and are marketed for use in antiaging skin care regimens.

Tea tree oil — Tea tree oil is a product derived from the Australian Melaleuca alternifolia tree that possesses antimicrobial and anti-inflammatory properties. Two randomized controlled trials have investigated this agent for the management of acne vulgaris. In a 45-day trial of 60 patients with mild to moderate acne vulgaris, patients treated with 5% tea tree oil exhibited a 44 percent reduction in total lesion counts, compared with a 12 percent reduction in the placebo group [15]. In another trial comparing treatment with 5% tea tree oil or 5% benzoyl peroxide (n = 124), patients in both groups showed a significant reduction in inflammatory and noninflammatory acne lesions, but a slower onset of action occurred with tea tree oil therapy [16].

LIGHT/LASER THERAPIES — Clinician-administered light sources are used for the treatment of acne, though well-designed clinical trials supporting the benefit of these treatments are limited, and there is uncertainty about the efficacy of these interventions [17]. Examples of light-based therapies include [18]:

●Broad-spectrum continuous-wave visible light sources (blue light, red light)

●Intense pulsed light

●Laser sources including the potassium titanyl phosphate (KTP) laser, pulsed dye laser (PDL), and infrared lasers

●Photodynamic therapy

●Photopneumatic technology

Photodynamic therapy involves the application of a photosensitizing agent such as aminolevulinic acid (ALA) or methyl aminolevulinic acid (MAL) prior to exposure to blue or red light, lasers, pulsed light sources, or nonpulsed broad spectrum light. It is hypothesized that once applied to the skin, ALA and MAL are preferentially taken up by the pilosebaceous unit and augment the response to light therapy [19]. Additional topical photosensitizers that have been less extensively studied in photodynamic therapy for acne include indocyanine green and indole-3-acetic acid [20,21].

Photopneumatic technology is a newer therapeutic modality. It has been less extensively studied for the treatment of acne than other light treatments. Photopneumatic devices combine gentle negative pressure with broadband pulsed light (400 to 1200 nm). The suction pressure helps to open follicular ostia through the evacuation of sebum and brings pilosebaceous units closer to the treatment tip. The broadband light exerts antibacterial and anti-inflammatory effects [22-24].

Mechanism of action — The mechanisms of action for light-based therapies in the treatment of acne are not completely understood. Proposed theories regarding the mechanisms through which these modalities work include the following:

●Blue and red light therapy for acne are thought to work via the absorption of light by porphyrins produced by C. acnes [25,26]. The porphyrins absorb light wavelengths between 400 and 700 nm, and absorb most effectively at wavelengths around 410 nm, which is within the absorption spectrum of blue light. As a result of light exposure, the porphyrins become activated, leading to the production of free oxygen radicals and bacterial death. Red light activates porphyrins less intensely than blue light, but penetrates more deeply into the skin.

●Infrared lasers (1320 nm, 1450 nm), radiofrequency devices, and photodynamic therapy are thought to inflict thermal damage to sebaceous glands and decrease sebum production. Photodynamic therapy also reduces obstruction of follicles, hyperkeratosis, and inflammation within acne lesions [27].

●Intense pulsed light (400 to 1200 nm), pulsed dye lasers (585 to 595 nm), and KTP lasers (532 nm) may function through inhibition of C. acnes and/or damage to the sebaceous glands [28].

Efficacy — The efficacy of light-based therapies for the treatment of acne vulgaris remains under investigation. High-quality data to support a recommendation for routine use of light-based therapies are lacking [17].

Although many articles on the use of photodynamic therapy in acne have been published, as with other light-based interventions, the efficacy of this intervention remains unclear. There is a lack of consensus regarding the optimal treatment protocol: the best photosensitizer, the best photosensitizer delivery method, the ideal contact time, the preferred light source and light dose, and the optimal treatment interval remain to be determined [29]. Photodynamic therapy is also associated with side effects that are unacceptable for some patients (eg, erythema, crusting, pain, and postinflammatory dyspigmentation) [19,30].

Only a few studies have compared light-based treatments with traditional acne therapies [17]. As an example, a small randomized controlled trial found blue-red light more effective than 5% benzoyl peroxide for treatment of inflammatory lesions, with a 17.6 percent difference in mean percentage improvement [31]. No difference in treatment efficacy was noted in small randomized controlled trials of blue light therapy versus clindamycin 1% solution (n = 34) [32], intense pulsed light plus benzoyl peroxide versus benzoyl peroxide alone (n = 30) [33], or pulsed-dye laser treatment plus topical clindamycin/benzoyl peroxide versus topical clindamycin/benzoyl peroxide alone [34]. In another small randomized trial, improvement in inflammatory lesions with photodynamic therapy was found to be less than that with adapalene 0.1% gel [35].

Additional randomized controlled trials and comparative treatment studies are necessary to clarify the role for laser and other light-based therapies in the treatment of acne. Continued research may also be useful for identifying new light-based therapies that will be useful for acne. An in vitro study found that laser wavelengths of 1720 nm were able to selectively target sebaceous glands without damaging adjacent skin structures [36]. If laser treatments at this wavelength are determined to be safe and effective, this may present a future treatment option for acne.

Emerging therapy — The findings of two small randomized trials suggest that topical application of light-absorbing gold microparticles followed by exposure to an 800 nm diode laser may improve inflammatory acne [37]. The treatment causes selective photothermolysis of sebaceous glands.

Home-use devices — The use of home-use, handheld devices for acne, particularly those using light-emitting diode, is gaining popularity. Although there have been small studies published supporting its efficacy and safety, high-quality, peer-reviewed data are lacking [38].

ADJUNCTIVE THERAPIES

Office-based superficial chemical peels — Superficial chemical peels are most appropriate for patients with primarily comedonal acne, and work to quicken the process of comedone resolution [39]. Of note, multiple treatments are required, results are temporary, and improvement may be mild [3]. Glycolic acid (an alpha hydroxy acid) and salicylic acid (a beta hydroxy acid) are the most common agents utilized. Resorcinol, lactic acid, trichloroacetic acid, and pyruvic acid may also be used.

High-quality, placebo-controlled efficacy trials are lacking. A randomized trial and several case series have supported the efficacy of glycolic acid and salicylic acid chemical peels [40-43]. The split-face randomized trial (n = 20) compared the treatment of facial acne with glycolic acid peels versus salicylic acid peels [40]. After 12 weeks, the treatments were similarly effective for the reduction of acne lesions. However, at two months post treatment, only the salicylic acid-treated areas maintained a significant decrease in the number of acne lesions.

Patients on oral retinoids should not be treated with chemical peels due to the potential for significant irritation. It is also recommended that patients on topical retinoids discontinue treatment for several days prior to treatment with chemical peels. Patients with skin phototypes IV to VI (table 1) are at increased risk of postinflammatory hypo- or hyperpigmentation, and care must be taken to minimize this risk.

Microdermabrasion — Microdermabrasion is a noninvasive procedure in which abrasive crystals (eg, aluminum oxide) are propelled onto the skin within a controlled vacuum suction system, leading to exfoliation of the stratum corneum. Microdermabrasion was reported to show benefit in a nonrandomized pilot study (n = 24) comparing severity of acne in photographs before and after treatment [44]. Patients continued to adjust acne medications throughout the study period, and the severity assessment was not quantitative. Thus, the effectiveness of microdermabrasion has been called into question [45].

Microdermabrasion may have benefit as a pretreatment for photodynamic therapy to decrease incubation time of the topical photosensitizer [39,46].

Comedo extraction — Mechanical removal of comedones can be a useful adjunct to topical therapy in patients with resistant comedones [3]. Pretreatment with tretinoin cream for four to six weeks often facilitates the procedure [47].

To perform the extraction, gently excise the roof or enlarge the opening of the comedo with an 18-gauge needle, sterile lancet, or no. 11 blade. Gently but firmly apply pressure with a comedo extractor to the skin to remove the keratin plug or milial cyst through the opening of the extractor. Lidocaine/prilocaine cream (EMLA) may be applied under an occlusive dressing for 1.5 to 2 hours prior to the procedure for anesthesia. Scarring is a potential risk.

Intralesional glucocorticoids — Intralesional glucocorticoids are a treatment option for nodular acne lesions that might otherwise take weeks to resolve. Treated lesions typically flatten in 48 to 72 hours, improving appearance and discomfort [48]. Triamcinolone acetonide, in concentrations of 1.25 to 2.5 mg/mL, is typically injected using a 30-gauge needle.

There is no high-quality evidence demonstrating the efficacy of such injections, but extensive clinical experience supports their use. Lower concentrations of triamcinolone may be as effective as higher concentrations and may reduce the risk of adverse effects; in one small randomized trial, lesions treated with 0.63, 1.25, or 2.5 mg/mL of triamcinolone acetonide exhibited similar improvement scores [48].

Patients should be cautioned regarding potential side effects including cutaneous atrophy, hypopigmentation, and telangiectasias. (See "Intralesional corticosteroid injection".)

Heat — The US Food and Drug Administration approved a home device (ThermaClear) that provides a pulse of heat for acne treatment. An unpublished five-day trial of the device compared heat treatment on one side of the face with no treatment on the other side [49]. A blinded analysis of photographs found that a greater percentage of treated lesions (44 versus 11 percent of untreated lesions) completely cleared. Other available devices include Zeno and the Radiancy Clear Touch Lite Acne Clearance System [50]. The latter uses a combination of heat and pulsed light.

Because of the lack of published studies supporting their efficacy and safety, heat sources are not recommended as first-line treatments for acne.

Diet — The relationship between diet and acne is controversial, but several studies published in the last decade suggest that dietary modifications may affect acne severity. The data on diet and acne are reviewed elsewhere. (See "Pathogenesis, clinical manifestations, and diagnosis of acne vulgaris", section on 'Diet'.)

Additional study is needed prior to a recommendation for dietary changes in the treatment of acne [3].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Acne vulgaris".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Acne (The Basics)")

●Beyond the Basics topics (see "Patient education: Acne (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Numerous nonprescription products are available for the treatment of acne. Common ingredients in nonprescription products include salicylic acid, benzoyl peroxide, sulfur, and alpha hydroxy acids.

●For patients with mild to moderate acne who do not want to initiate prescription medications, we suggest a trial of benzoyl peroxide and/or salicylic acid (Grade 2B). For patients with inflammatory lesions, benzoyl peroxide is preferred due to the drug's antimicrobial properties. Combination therapy with both drugs may lead to additional benefit. Patients with mild to moderate acne who do not respond to nonprescription products after three months of treatment should be clinically evaluated. Patients with more severe acne should be evaluated earlier, to consider use of more effective treatments to prevent or minimize irreversible scarring. (See 'Other topical medications' above and "Acne vulgaris: Overview of management".)

●The role of laser and other light-based therapies in the treatment of acne is not clearly defined. We suggest that light-based therapies should not be used as first-line treatment for acne vulgaris (Grade 2B). These therapies may be utilized as an adjunct to medical acne therapy or as an option for patients who decline medical therapy although further studies are necessary to clarify their role. (See 'Light/laser therapies' above.)

●In patients with primarily comedonal acne who desire an accelerated treatment response, we suggest superficial chemical peels (Grade 2B). However, peels should be avoided in patients taking oral isotretinoin and should be used with caution in patients with dark skin pigmentation. (See 'Office-based superficial chemical peels' above.)

●Until further evidence is available, we suggest not using microdermabrasion for the treatment of acne (Grade 2C). However, this procedure may be useful as a pretreatment for photodynamic therapy. (See 'Microdermabrasion' above.)

●We suggest intralesional glucocorticoids for selected nodular inflammatory acne lesions in order to accelerate their resolution (Grade 2C). Patients should be warned of the potential side effects of cutaneous atrophy, hypopigmentation, and telangiectasias prior to treatment. (See 'Intralesional glucocorticoids' above.)