Procedural treatments for acne
Simple physical modalities such as comedo extraction and intralesional steroid injections have been utilized in the treatment of acne for many years. Recently, new procedures including laser and light-based technologies have become available. Although many of these new modalities require more rigorous study to determine safety and efficacy, they provide a unique set of advantages for certain patient populations. These therapies provide alternative options for patients who find it difficult to adhere to traditional acne therapies, are concerned over adverse effects of systemic therapy, or for whom traditional therapies fall short in efficacy. In a climate where antibiotic resistance is increasing and isotretinoin therapy has become heavily regulated and scrutinized, such procedural treatment alternatives have become more and more desirable. This post will focus on procedural techniques for active acne lesions including extraction, intralesional injections, microdermabrasion, chemical peels, lasers, lights, and photodynamic therapy.
Physical removal of individual comedones not only has been popular among dermatologists but is also a technique commonly employed by many estheticians. Comedo extraction entails the application of simple mechanical pressure using a comedo extractor to express the contents of a blocked pilosebaceous follicle. For closed comedones, it may be necessary to pierce the top of the lesion with a needle or the tip of a number 11 blade scalpel to make the extrusion less traumatic. Although the technique is widely practiced, very little has been published to date regarding its efficacy and side effect profile (1). Advantages reported include a reduction in the number of future inflamed lesions and an immediate sense of improvement.
However, the procedure is known to carry a risk of tissue damage, making cystic lesions worse (1) and potentially inciting inflammation by rupturing the contents of a comedo through the base of the follicle into the dermis. Open comedones reappear clinically 20 to 40 days fol-lowing extraction, while closed comedones (whiteheads) reappear within 30 to 50 days. Biopsy specimens following extraction of open comedones demonstrate that it is occasionally possible to evulse the entire comedo epithelium and kernel in toto. In contrast, whiteheads, or closed comedones, cannot be completely removed with an extractor. When the entire open comedo epithelium is evulsed, new comedones do not reform. Consequently, extraction provides a temporary improvement for most noninflammatory lesions but has the potential to completely eradicate a very small percentage of open comedones (2). Care should be taken to use minimal force, as this will minimize inflammation and the risk of scarring.
INTRALESIONAL STEROID INJECTIONS
One of the most common procedures used to rapidly shrink inflammatory nodules is the use of intralesional corticosteroid injections. This modality is indicated for large, stubborn lesions or when a rapid response is desired. Concentrations of 5 mg/mL or less of triamcinolone acetonide are commonly used, and it has been demonstrated that concentrations as low as 0.63 mg/mL are just as effective as higher concentrations of 2.5 mg/mL (3). However, it is important to note that the quantity injected together with the concentration used is of paramount importance, rather than simply relying on a threshold concentration as a guide. The authors recommend injecting the smallest amount of a 2.5-mg/mL concentration with a 30-g needle directly into the lesion until the most subtle blanching is visualized. Although not studied, the authors believe that dilution with normal saline results in less stinging experienced by the patient as compared with dilution with sterile water. Following injection, nodules have been noted to flatten in 48 to 72 hours.
This procedure is not without risks and should be used judiciously in appropriate circumstances. Risks include atrophy, telangiectasias, and pig-mentary alterations (4), and hypothalamic-pituitary-adrenal axis suppression has been reported with repeated injections (5,6). Although studies are lacking, most obstetricians feel comfortable with the use of occasional intralesional injections during the second and third trimesters of pregnancy so long as the total dose and frequency of injections stay within reason.
Microdermabrasion is a superficial, minimally invasive technique of mechanical abrasion in which the stratum corneum is partially or completely removed. The technique is employed for mild acne scarring, aging, and pigmentary anomalies. Either a pressurized stream of abrasive particles such as aluminum oxide crystals or a roughened tip such as one made of diamond is used to physically exfoliate the skin surface. This superficial exfoliation of the stratum corneum appears to stimulate a dermal remodeling cascade similar to that seen following incisional wound healing (7). Limited data is available supporting the efficacy of micro-dermabrasion in acne (8), but it is generally well tolerated and requires no downtime. Proper eye protection must be worn to prevent corneal damage from stray crystals, and care must be taken to avoid aggressive treatment in areas of thin skin prone to purpura such as the eyelids. In contrast, multiple passes may be utilized over focal acne scars.
The desired end point is erythema, but one may also see edema following a microdermabrasion session. Although the procedure appears to have only a very modest effect on acne scarring, it does enhance the absorption of topically applied agents (9) and thereby may increase the efficacy of a concomitant topical acne regimen. Similarly, it will likely increase the side effects from these agents including photosensitivity and dry skin. Because of its ability to facilitate penetration of topical medications, it has been used as a pretreatment for photodynamic therapy (PDT) (10).
Chemical peeling involves the application of a chemical to induce an accelerated form of exfoliation. Light peeling agents result in sloughing of cells in the stratum corneum, while deeper peeling agents create necrosis and inflammation in the epidermis or even as deep as the reticular dermis. However, even very superficial peels that remove stratum corneum only can stimulate the epidermis to thicken and can ultimately even lead to increased deposition of collagen and glyco-saminoglycans in the dermis. Peeling has been used to treat active acne lesions, postinflammatory pigmentary changes from acne, as well as superficial acne scars.
Salicylic acid is a R-hydroxy acid safe to use in all Fitzpatrick skin types and ideally suited for acne because of its keratolytic and anti-inflammatory proper-ties (11). Even concentrations as low as 0.5% to 3% of salicylic acid have been demonstrated to speed the resolution of inflammatory acne lesions and decrease the formation of comedones (12). Salicylic acid is lipophilic and thus penetrates the pilosebaceous unit with ease.
When used in 20% to 30% concentrations as an in-office peeling agent, it is usually applied for a five-minute duration and is self-neutralizing. A pseudo-frost appears with application, and this frost becomes more apparent with more numerous passes. Side effects include erythema, dryness, burning, and crusting, which are all transient (11). Salicylism is a theoretical side effect if used over large surface areas, but this has never been reported with concentrations used to treat acne. It is contraindicated in pregnancy and in those with an aspirin allergy. Retinoids and benzoyl peroxide should be withheld one week prior to and one week following each peel to prevent uneven or erratic penetration.
Glycolic acid is an oc-hydroxy acid commonly used for conditions of abnormal keratinization (13). Reduction of comedones, papules, and pustules and overall improvement in skin texture (14) have been demonstrated in acne patients. Improvement in postinflammatory changes in black patients has also been observed (15). Furthermore, glycolic acid has been shown to increase epidermal and dermal thickness, with increased deposition of acid mucopolysaccharides, improved quality of elastic fibers, and increased density of collagen (16). Consequently, repeated peels might have a modest effect on mild acne scarring.
Glycolic acid peels produce no systemic toxicity, but disadvantages include a tendency for the acid to penetrate unevenly. There is significant variability from patient to patient with regard to reactivity and efficacy. Further complicating the standardization of this peeling agent, glycolic peels come in both free acid systems and partially neutralized systems. Consequently, a 70% free acid solution contains very close to 70% of bioavailable acid, while a 70% glycolic acid formulation from a company that uses a partially neutralized system might contain approximately 50% of biologically active acid. The depth of the peel is not related to the number of coats as is the case with salicylic acid. However, like salicylic acid peels, glycolic peels can penetrate more deeply or more unevenly in a patient who is using topical retinoids or benzoyl peroxide. Glycolic peels must be neu-tralized, which should be done when erythema is visualized.
LIGHT AND LASER THERAPY
The multiple pathogenic factors involved in acne provide many potential targets for light and laser therapy (17). Although well-designed studies including con-trols, blinding, and randomization are lacking, patients are drawn to laser and light-based technologies as a “cutting-edge” alternative to standard acne therapies.
Blue Light and Red Light
Propionibacterium acnes is an obvious target for visible light therapy as it produces photoactive compounds called porphyrins that absorb wavelengths in the visible light spectrum. Specifically, coproporphyrin III is the predominant porphyrin produced by P. acnes, while coproporphyrin I and protoporphyrin are produced at much lower concentrations (18). When exposed to visible light (with a maximum absorption peak at 403 nm), these photoactive compounds create reactive oxygen species that are toxic to P. acnes. Although the absorption of blue light is greatest, these shorter wavelengths do not penetrate as deeply into the skin as compared with red light. Thus, absorption efficiency is inversely correlated with depth of penetration. However, toxicity to P. acnes might not be the only mechanism of action when it comes to visible light. Blue light has been shown to reduce keratinocyte production of inflammatory cytokines including interleukin-1a, suggesting that blue light possesses anti-inflammatory properties as well as antimicrobial ones (19). Studies, although not rigorously performed, have shown benefit from both blue light therapy alone, as well as blue and red light combination therapy (20 22).
Pulsed Dye Laser
Controversial results regarding whether pulsed dye laser therapy has an effect on acne have been published (23 25). Two of the three studies fail to show a significant contribution from pulsed dye laser therapy, with one study examining the laser as monotherapy and the other as adjunctive treatment to topical therapy.
Potassium Titanyl Phosphate Laser
The use of the 532-nm potassium titanyl phosphate (KTP) laser in the treatment of acne has not been convincingly demonstrated. The largest study to date showed no significant difference between treated and control sides of the face at four weeks (26).
Theoretically, a mid-infrared laser device would be able to penetrate to the level of the sebaceous gland, thereby heating this gland and the associated follicle and thus improve acne. A light-based treatment that could destroy sebaceous glands would have the potential to cure acne (17). Protection of the epidermis is critical to the success of such a laser treatment. A 1450-nm laser device with a cryogen cooling system was shown to cause short-term thermal alteration of sebaceous glands while preserving the epidermis in an in vivo rabbit ear model (27). Three human clinical trials have all demonstrated statistically significant reduction in acne lesion counts following 1450-nm laser treatment (27 29). Side effects were limited and transient.
Although P. acnes is known to produce its own endogenous porphyrins in proportion to its population (30), the concept of introducing exogenous por-phyrins that can then be activated by light is known as photodynamic therapy. Aminolevulinic acid (ALA) is known to be preferentially taken up by the pilosebaceous units (31). As ALA penetrates the epidermis, it enters the heme biosynthetic pathway and is converted to PpIX (32). Methyl aminolevulinate (MAL) is a lipophilic derivative of ALA. The introduction of both molecules into the skin results in higher concentrations of porphyrins, which can then be activated by red or blue light.
In 2000, a landmark study was performed demonstrating the efficacy of ALA PDT using high-fluence red light to treat acne. On the basis of measure-ments of sebum excretion rates, autofluorescence from follicular bacteria, as well as histological evaluation of skin biopsies, it appeared as though topical ALA PDT acted by (i) inhibiting sebum secretion by damaging sebaceous glands, (ii) sterilizing sebaceous follicles by killing P. acnes, and (iii) reducing follicular obstruction by altering keratinocyte shedding and hyperkeratosis. With the protocol used, the patients experienced severe side effects. Although subsequent studies using PDT for acne have demonstrated good clinical outcomes, the mechanism proposed following the initial study described above has since been challenged.
Follow-up studies have shown clinical benefit from PDT for acne in the absence of significant changes in sebum secretion or P. acnes populations (33). Although PDT appears to have a clinical benefit in a number of studies (34 36), protocols have widely differed and the mechanism of action remains to be fully elucidated. The largest study to date was performed by DUSA Pharmaceuticals, Inc. but was unfortunately never published. This multicenter randomized, controlled, investigator-blinded study was conducted on 266 patients with moderate to severe acne. Levulan in vehicle or vehicle alone was applied to the full face of participants approximately 45 minutes prior to treatment with 5 to 10 J/cm2 of light with BLU-U (405 420 nm). Patients were treated once every three weeks for a maximum of four treatments. The results did not demonstrate a statistically significant difference between the Levulan PDT and the control group. However, both groups demonstrated a statistically significant reduction in the number of inflammatory lesions from baseline (37.5 41.7% reduction), providing further evidence that blue light alone has an effect on acne. Despite these results, there is no question that some experienced clinicians do indeed have reliably good results using PDT for acne.
The use of radiofrequency energy has recently been proposed as a nonablative treatment modality for acne. Radiofrequency currents directed at tissue cause thermal effects that depend on the electrical properties of the tissue. These thermal effects are speculated to affect sebaceous gland activity and thus have a potential effect on acne. Some preliminary studies show promise (37,38), but whether radiofrequency truly exerts a thermolytic effect on sebaceous glands remains to be determined.
A specialized device that combines negative pressure (suction) with the con-comitant delivery of broadband pulsed light (400 1200 nm) has been developed for the treatment of acne. This photopneumatic device is the only laser or light-based device cleared by the Food and Drug Administration (FDA) for the treatment of comedonal and inflammatory acne. The device applies a gentle vacuum to the skin surface, thereby mechanically evacuating trapped sebum and necrotic cells. This technology also stretches the skin within the treatment tip, thereby reducing the concentration of competing chromophores such as hemo-globin and melanin so that less painful fluences of the broadband light can be moved and the light can more directly target the porphyrins in P. acnes. Mechanical extrusion of comedo contents and thermally injured bacteria have been observed following treatment (39). Although a number of studies have demonstrated effect on subjects suffering from mild to severe acne (40 42), none of these studies included a control group for comparison. The authors (WPB and ARS) are currently conducting the first randomized controlled trial of this technology (study underway at date of publication).
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