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.