Treating Acne Vulgaris: Systemic, Local and Combination Therapy

Laura J Savage; Alison M Layton

Disclosures

Expert Rev Clin Pharmacol. 2010;13(4):563-580. 

In This Article

Adjunctive Therapies

A number of physical therapies are available for treating active acne, although their success is variable and some require considerable skill to perform.

Macrocomedones

Macrocomedones are usually closed comedones (whiteheads) but are occasionally open comedones (blackheads) up to 1.5 mm in diameter. Light cautery or hyfrecation after the application of local anesthetic cream (e.g., EMLA® [Bedfordshire, UK]) has been demonstrated to be successful in the treatment of multiple macrocomedones.[154] The topical anesthetic is applied for 60–90 min beneath an occlusive adhesive dressing, after which cautery is used to provide very low-grade thermal damage in order to stimulate the body's own defence mechanisms to induce resolution of the comedo. This takes seconds to perform and should be painless. There is very little associated scarring or postinflammatory hyperpigmentation and it is generally well tolerated. Hyfrecation is more effective than topical tretinoin in eradicating macrocomedones, although multiple treatments are frequently required.[166] The beneficial effects of acne surgery can be enhanced by the use of topical retinoids, which facilitate expulsion of the comedo and prevent the development of new lesions while existing comedones resolve.[15]

Glycolic acid and salicylic acid peels have also been reported to be beneficial in mild-to-moderate comedonal acne in women aged 13–40 years.[167–169] They promote desquamation, which reduces corneocyte adhesion and follicular plugging, enabling the extrusion of inflammatory contents.

Acne Nodules

Occasionally, persistent tender inflammatory nodules or cysts develop. A short course (7–10 days) of potent topical corticosteroids may be a useful initial strategy in severe inflammatory acne (especially acne conglobata or fulminans) to regain control, reduce pain and provide significant psychological benefit.[1,13] Topical steroids, such as clobetasol proprionate, applied twice-daily can also help resolve smaller persistent acne nodules in a matter of days. However, their long-term use is limited by the potential for delayed side effects, including skin atrophy, perioral dermatitis, steroid rosacea, papulopustular flares and rebound dermatitis.[1,13]

Larger inflammatory nodules and cysts respond well to intralesional injections with triamcinolone acetonide, with a rapid reduction in pain and swelling.[170,171] There is, however, the potential for atrophic scarring and, therefore, intralesional injections should only be performed on lesions that have been present for less than 7 days and have significant elevation over the surrounding skin.[171] A 30-gauge needle is used to inject 1–2 mg/ml triamcinolone acetonide into the center of the lesion until the erythema blanches. Injections can be repeated if necessary every 3 weeks. No more than 20 mg should be administered in any one sitting to avoid the adverse effects of adrenal suppression.[172] If large inflammatory lesions persist beyond 2 weeks, cryotherapy is the preferred option. Superficial freezing with liquid nitrogen will hasten the resolution of such lesions and is relatively painless. Two 15–30-s freeze–thaw cycles are recommended.[173]

Light Therapy

In recent years, light-based treatments for acne have gained popularity, and utilize light with different properties (i.e., wavelength, intensity and coherent/incoherent light). Lasers are the most common light sources utilized in acne therapy, which produce a high-energy beam of light of a precise wavelength range. A range of treatments are being investigated, including broad-spectrum continuous wave visible light sources (blue light and blue–red light), specific narrow-band light, intense pulsed light (IPL), pulsed dye lasers (PDL), potassium titanyl phosphate lasers, infrared diode lasers and photodynamic therapy (PDT) with or without photosensitizing agents (aminolevulinic acid or methyl-aminolevulinic acid). Early data suggest that these treatments offer greatest utility when used as an adjunct to medical therapy.[14] They may also play a role in patients who refuse or cannot tolerate medical therapy. Various delivery systems are available with timing controls for safety and cooling systems to reduce discomfort during treatment.

The mode of action for light therapy relates to the biological property of porphyrins as photosensitisers to induce destruction of P. acnes.[174] Light therapy exerts a selective cytotoxic effect on the proprionibacteria, which appear to be more susceptible to short-term damage from light therapies than keratinocytes. Comedonal and proinflammatory cytokines are also suppressed.[175] Porphyrins have peak absorption at blue-light wavelengths, so blue light is often used to treat acne.[176] However, although light in the 400–420 nM range requires the least energy for photosensitization, it does not penetrate the epidermis well. Longer red-light wavelengths allow for deeper penetration but carry an increased risk of adverse effects, including pain, erythema, crusting, edema, pigmentary changes and pustular eruptions.[177,178] Other light therapies attempt to selectively target and damage sebaceous glands directly, reducing their size and thus, sebum output.[179] These include infra-red lasers, low-energy PDL and radiofrequency devices.[180]

To date, the evidence in support of lasers and light therapies in acne is limited. Many of the outcomes of existing trials are contradictory. A 2008 evidence-based review of light therapies by Haedersdal et al., identified 27 potentially relevant studies, of which only 16 were RCTs and three were controlled trials.[181] Eight studies were excluded because of pilot studies or uncontrolled designs, and the randomization method was unclear in ten RCTs.[181] A total of 17 out of the 19 studies included assessed only a short-term efficacy (up to 12 weeks after treatment), limiting their relevance in the clinical setting. Patients often have great expectations for success and, as they are often self-funding, they will demand greater reassurance of benefit beyond 3 months. Patients should be advised that P. acnes do appear to regenerate rapidly and any perceivable benefit is usually short lived, necessitating repeated follow-up treatments.[14]

Haedersdal et al. found that the most substantial evidence for the efficacy of light therapies in acne exists for PDT.[181] Red-light-activated methyl-aminolevulinic acid-PDT and aminolevulinic acid-PDT document a beneficial efficacy on acne in approximately 50–60% of patients up to 20 weeks after one to three treatments.[182–186] One study (Wiegell et al.) demonstrated prolonged efficacy up to 1 year after treatment.[187] IPL-assisted PDT seems more efficacious than IPL alone, although some ambiguity exists within the three published RCTs.[188–190]

For PDL and infrared lasers, conflicting results are reported, with some studies reporting statistically significant efficacies on inflammatory lesions, while results of other studies are not significant when compared with untreated skin.[191,192] Only one RCT (n = 26) evaluated the efficacy of KTP (four treatments in 2 weeks) with a 35% (significant) and 21% (nonsignificant) improvement in total acne lesion scores at 1 and 4 weeks, respectively, but no longer-term data are available.[193]

The effect of broad-spectrum light sources has been evaluated in three RCTs and one controlled trial. Blue light (420 nm) twice-weekly for 4 weeks was significantly superior to untreated controls (50 vs 12% improvement in total acne lesion scores/counts; p < 0.05)[194] and reported to be superior to topical clindamycin (36 vs 14% improvement in total acne lesion scores/counts), although statistical analysis to support this observation was not provided.[195] Mixed blue–red light daily for 12 weeks improved inflammatory acne significantly more than topical BPO (76 vs 60% improvement in total acne lesion scores/counts; p < 0.006).[196] However, it should be noted that the lamp contained 7% of mainly UVA, and the cost–effectiveness, side effect profile and practicality of this approach over topical BPO should be considered.

Despite the limited evidence on the efficacy of light therapies in acne, consumer demand is increasing. Patients should be informed that currently available light treatments are not recommended amongst first-line treatments for acne vulgaris, and that long-term safety data in acne are as yet unknown. A Cochrane review is currently examining the evidence for the use of light treatment of different wavelengths for acne and it is likely that they will recommend that further research into this area is needed.[197]

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