Acne phototherapy: a new evolution for the treatment of acne vulgaris

Acne therapy

Acne vulgaris is the most common dermatological disorder primarily affecting individuals during puberty and adolescence, decreasing their quality of life. Various modalities have been used for acne treatments, such as topical and oral therapies, phototherapies and chemical peeling. Topical therapy includes salicylic acid, benzoyl peroxide, azelaic acid, antibiotics, tretinoin, isotretinoin and adapalene. Oral therapy comprises antibiotics, isotretinoin and estrogen. Oral antibiotics have adverse effects, such as gastrointestinal, photosensitivity and hypersensitivity reactions. Antibiotic resistance in propionibacteria is an important issue for patients and prescribers. Systemic isotretinoin may cause teratogenicity and side effects, such as dry skin, dermatitis and liver dysfunction. These systemic drugs are expensive and are associated with potential adverse effects. Safer, more effective and less expensive therapies are, therefore, necessary. Novel apparatuses for acne phototherapy have recently been developed. This editorial focuses on the evolution of acne phototherapy.

Phototherapies for acne

Sun exposure is known to be beneficial for acne vulgaris. UV light, visible light and the combination of UVA plus visible light are reported to be effective for treating acne vulgaris, although the mechanisms have not yet been elucidated. In current phototherapies, blue light sources, photodynamic therapy (PDT) and lasers have been reported to have clinical effectiveness for acne vulgaris with substantial mechanisms.

Blue light therapy

Propionibacterium acnes is a major bacterium involved in the pathogenesis of acne. P. acnes produces porphyrins with absorption peaks in the near-UV and blue light spectrum. The major porphyrin produced by P. acnes is coproporphyrin III, with an absorption spectrum peak at 415 nm. Therefore, blue light ranging at wavelengths of 400–420 nm is a theoretically effective phototherapy, since exposure to blue visible light induces photoexcitation of bacterial porphyrins, singlet oxygen production and subsequent bacterial destruction. The visible light, with peaks at 405 and 420 nm [1], and the combination of blue (415 nm) and red (660 nm) light [2], both using low-intensity fluorescent lamps as a light source, are clinically effective in acne vulgaris. Recent reports demonstrate that a newly developed high-intensity, enhanced, narrow-band (407–420 nm) blue light source using metal halide lamps demonstrates the effectiveness and tolerability of such treatments [3–7]. Moreover, our study demonstrates in vitro reduction of P. acnes cultured from skin lesions of acne patients [4]. The blue light therapy with antibacterial activity against P. acnes is more effective for inflammatory papules and pustules than comedones, since inflammatory lesions are rich in porphyrins. Blue light has a wavelength of 400–420 nm, which does not penetrate into the deep dermis, suggesting that blue light is less effective for deeper acne lesions, such as nodules and cysts.

Photodynamic therapy

PDT using topical or systemic 5-aminolevulinic acid (ALA-PDT) has been used widely for the treatment of cancer. ALA-PDT using topical ALA has been reported to be effective for acne vulgaris [8–11]. ALA-PDT uses the visible light-induced phototoxic reaction of ALA-derived protoporphyrin IX (PpIX) accumulated in the target lesions of acne. This therapy uses red, blue or intense pulsed light, pulsed dye laser (PDL), diode laser or light-emitting diode sources. Phototoxic reaction causes the damage to sebaceous glands and hair follicles, resulting in improvement of acne lesions. ALA-PDT is effective for acne vulgaris with significant side effects, such as transient hyperpigmentation, superficial exfoliation and crusting. The techniques of topical ALA-PDT for skin disorders have not been optimally established owing to inhomogenous distribution or lack of selective accumulation of ALA-derived PpIX.

Indocyanine green (ICG), a photosensitizing dye used for the diagnosis of hepatic functions, cardiac outputs and blood volumes, is also used in PDT for acne. Topical ICG with an absorption peak at 805 nm is easily accumulated in the sebaceous glands. ICG-PDT using an 803- or 809-nm diode laser has demonstrated effectiveness for acne, as well as a reduction in P. acnes and sebum production [12]. A histological study demonstrates selective necrosis of the sebaceous glands in human skin after ICG-PDT [13].

Laser therapy

Recent reports demonstrate that laser therapies, including 532-nm potassium titanyl phosphate (KTP) laser, 585-nm PDL, 1450-nm diode laser and 1540-nm Erbium (Er):glass laser, are clinically effective in acne vulgaris.

The 532-nm KTP laser is usually used for the treatment of vascular lesions, such as telangiectasia and rosacea, since the target chromophore is oxyhemoglobin. This light can activate porphyrins from P. acnes and stimulate collagen production around the sebaceous gland, leading to the reduction of acne [14].

The 585-nm PDL, the target chromophore of which is oxyhemglobin, is used commonly for cutaneous vascular diseases, such as portwine stain, strawberry mark and telangiectasia. This laser mainly affects dilated vessels of reddish lesions of acne and partly activates porphyrins from P. acnes, thus indicating this laser to be effective for inflammatory lesions [15]. However, a randomized, single-blind, placebo-controlled trial revealed only a trend towards improvement of the laser-treated sites without significant differences [16].

The 1450-nm diode laser with a dynamic cooling device has received US FDA approval for the treatment of acne, atrophic acne scars and fine wrinkles. Studies using this diode laser were shown to be effective and well tolerated by acne patients [17,18]. Diode laser tretament is effective for nodules and cysts, as well as papules and pustules, with minimal adverse effects. Moreover, this laser therapy demonstrates significant long-term clinical remission after treatment [19]. The light at 1450 nm in the infrared spectrum corresponds to the peak of absorption spectrum of water in the dermis, indicating the target chromophore to be collagen and sebaceous glands in the mid-dermis. Histopathological studies reveal that this laser causes thermal damage to the collagen and sebaceous glands [17,20]. Clinically, this laser is also effective for atrophic acne scar [20] and sebaceous hyperplasia. Therefore, the 1450-nm diode laser may remodel the collagen, form new collagen and suppress the activity of sebaceous glands, following improvement of acne and acne scar. Interestingly, the combination therapy of PDL and diode laser has been effective for inflammatory facial acne, acne scarring and postinflammatory erythema [21].

The 1540-nm Er:glass laser also targets the intracellular water of collagen and sebaceous glands in the mid-dermis and is used for wrinkle reduction. Some reports demonstrate that the 1540-nm laser has reduced acne lesions with good tolerability [22,23].

Conclusion

Treatment of acne can be chosen in terms of major skin lesions, severity and the age of the patient. Skin lesions of acne include comedones, papules, pustules, cysts, nodules and scars. Acne vulgaris should be classified into mild, moderate and severe types. The indication for phototherapies should be determined considering these conditions. Blue light, KTP laser and PDL are effective for mild-to-moderate inflammatory acne. ALA-PDT and diode laser are indicated for the treatment of moderate-to-severe inflammatory acne. Acne scars could be treated with diode and Er:glass lasers. These phototherapies have substantial effects for specific lesions but also some adverse effects, indicating some limitations for the acne treatment. In the future, a combination of topical and systemic treatment and phototherapies should be investigated.