INTRODUCTION
Acne is one of the most common skin conditions estimated by the Global Burden of Disease Project to display a prevalence of 9.4%, ranking it as the eighth most common diseases worldwide.1 It predominantly affects adolescents and young adults affecting approximately 40-90% of this population, depending on the study methodology and definitions used. 2-7 Although the prevalence tends to decrease with age a substantial number of adults suffers from acne.8
Acne is defined as a chronic inflammatory skin disorder characterized by a prolonged course, a recurring pattern of flare-ups and remissions, and with a psychologic and social impact that affects patient’s quality of life.9 Thus, proper treatment is essential for the patients to avoid or reduce the risk of sequelae such as scarring, emotional and psychosocial distress, occupational consequences and potential psychiatric disturbances including depression and suicide.10 Although the underlying reasons for development of acne is uncertain, the disease associates with increased sebum production, colonization of hair follicles by Cutibacterium acnes (C. acnes formerly named Propionibacterium acnes ), and ongoing inflammation.11 These factors are reflected in treatment options for acne, that target bacterial growth via antibiotics (e.g. tetracycline), sebum production by isotretinoin therapy, and inflammation by corticosteroids 12-14 or by fluorescent light energy (FLE) that has reported efficacy against acne possibly in part through is recently described anti-inflammatory effects.12,13,15-19
In many cases of moderate to severe acne, antibiotics and retinoids as systemic therapies are well-established.14,20 However, some patients are not eligible to standard dose of isotretinoin treatment due to collateral effects, or do not reach a satisfying clearance with tetracycline or macrolides even when correctly combined with topical therapy. In these cases, low-dose regimens of oral retinoid recently demonstrated efficacy for treating acne, with superior patient satisfaction and fewer side-effects compared with standard doses.21,22 Moreover, studies suggest a preventing role of a low starting dose of isotretinoin on the acute inflammatory flares that may occur during the first 3–5 weeks of treatment.23,24 Additionally, systemic corticosteroids pose an adjunctive therapy option in cases of severe inflammation, to speed up clearing of lesions for approaches using low starting dose of retinoids.14,25,26 Finally, optical treatments including laser and light-based therapies (photodynamic therapy (PDT), light-emitting diode (LED), and intense pulsed light (IPL)) have gained increasing interest over the last years as acne treatments27-45 in an attempt to overcome the limitations associated with the standard established therapies for moderate to severe acne.46
Among these newer therapeutic approaches, the use and effectiveness of FLE therapy has been described in the treatment of acne.15,16,47,48 FLE is a biophotonic platform utilizing a chromophore-containing photoconverter gel activated by a blue LED light (440-460 nm) whereby longer wavelengths of visible light (500-700 nm) energy is relayed to the cells of the skin.17,19 Blue light alone has been suggested to have a cytotoxic effect on C. acnes likely acting on the porphyrins synthetized by the bacteria resulting in production of singlet oxygen and reactive radicals leading to membrane damage and bacterial death.49 Whereas, FLE generates a unique dynamic hyperpulsed multi-wavelengths of fluorescent energy shifting the light from shorter blue wavelengths to longer wavelengths within the blue, green, yellow, orange, and red spectrum creating a complex spectrum containing several wavelengths.17 This spectrum is facilitated by the Stoke’s shift phenomenon, describing fluorescence as chromophores absorbing photons from (blue) light and emitting them in a lower energy state of longer wavelengths, which compared with blue light penetrate and stimulate cells and structures in the deeper layers of the skin.17,50 FLE has reported efficacy on a number of (inflammatory) skin conditions, including rosacea,51,52 lentigines,53,54acneiforme eruption,55 acne conglobate, and hidradenitis suppurativa56 as well as skin rejuvenation57 and healing of acute and chronic wounds.19,58-61 In vitro findings has reported that FLE lowers production of essential pro-inflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) in cultures of human epidermal keratinocytes and human dermal fibroblasts.17-19 Finally, ongoing mechanistic studies suggest that FLE directly modify mitochondrial morphology and function.18,62
We hypothesize that targeting several aspects of acne by initially lowering sebum production by low-dose isotretinoin treatment63,64 or hampering bacterial growth by tetracycline in combination with the anti-inflammatory and homeostasis promoting properties of FLE will clear acne and normalize the skin longterm.15-17,19,62 This combination will initially target several pathways associated with acne and longer term FLE therapy will reprogram and balance skin cells and conditions ensuring no remission of disease. The combination of FLE treatment with systemic drugs has not yet been established. We recently complied the experiences of seven FLE-experienced doctors on their off label use of combining FLE and low-dose isotretinoin therapy suggesting new applications for treatment of acne.65 We suggest that the direct anti-inflammatory effects of FLE combined with administration of the well-described systemic anti-acne therapeutics, isotretinoin or tetracycline in low-dose will clear acne and normalize the skin ensuring longterm clearance without severe adverse effects. Our objective was to test and describe the efficacy and safety of the combination of FLE therapy with low-dose isotretinoin or tetracycline in cases of moderate to severe acne.