Photodynamic and photobiological effects of light-emitting diode (LED) therapy in dermatological disease: an update

Abstract

Benefit deriving from the use of light is known since ancient time, but, only in the last decades of twentieth century, we witnessed the rapid expansion of knowledge and techniques. Light-emitted diode (LED)-based devices represent the emerging and safest tool for the treatment of many conditions such as skin inflammatory conditions, aging, and disorders linked to hair growth. The present work reviews the current knowledge about LED-based therapeutic approaches in different skin and hair disorders. LED therapy represents the emerging and safest tool for the treatment of many conditions such as skin inflammatory conditions, aging, and disorders linked to hair growth. The use of LED in the treatment of such conditions has now entered common practice among dermatologists. Additional controlled studies are still needed to corroborate the efficacy of such kind of treatment.

Full text

REVIEW ARTICLE
Photodynamic and photobiological effects of light-emitting diode (LED)
therapy in dermatological disease: an update
Elisabetta Sorbellini
1,2
&Mariangela Rucco
1
&Fabio Rinaldi
1,2
Received: 16 April 2018 /Accepted: 5 July 2018 /Published online: 14 July 2018
#The Author(s) 2018
Abstract
Benefit deriving from the use of light is known since ancient time, but, only in the last decades oftwentieth century, we witnessed
the rapid expansion of knowledge and techniques. Light-emitted diode (LED)-based devices represent the emerging and safest
tool for the treatment of many conditions such as skin inflammatory conditions, aging, and disorders linked to hair growth. The
present work reviews the current knowledge about LED-based therapeutic approaches in different skin and hair disorders. LED
therapy represents the emerging and safest tool for the treatment of many conditions such as skin inflammatory conditions, aging,
and disorders linked to hair growth. The use of LED in the treatment of such conditions has now entered common practice among
dermatologists. Additional controlled studies are still needed to corroborate the efficacy of such kind of treatment.
Keywords LED .Photodynamic therapy .Acne .Aging .Androgenetic alopecia .Alopecia
Introduction
Use of light as therapeutic approach is one of the oldest known
methods to treat different health conditions, and its benefits
are known since the ancient Egyptians, Chinese, and Indian
populations [1–4]. Nevertheless, large use and well-known
benefits for more than thousands of years, the scientific basis
of phototherapy was laid at the beginning of twentieth century
when the term Bphotodynamic therapy^(PDT) was coined by
Oscar Raab and Herman von Tappeiner as referred to the
chemical reaction in which oxygen is consumed following
induction by a photosensitization process [5,6]. This was
followed in 1903 by the first reported use of artificial irradia-
tion in phototherapy by a Danish physician, Niels Ryberg
Finsen, winner of the Nobel Prize in Physiology or
Medicine. In the same year, von Tappeiner and Jesionek re-
ported the use of a combination of light and a topical sub-
stance, eosin, to treat skin tumors [1]. From its discovery till
now, PDT is growing fast and significant progress has been
made so far in light-based treatment of different disorders such
as lung disease [7,8], age-related degenerative processes of
macula [9], urology [10–12], periodontal diseases [13], and
different kinds of solid tumors [14]. Application of PDT in the
dermatological field is characterized by the greatest use, and
this is due not only to the easier accessibility of the skin for
light exposure and photosensitizing topical applications but
mainly to continuous advances in research.
Different kinds of PDT are currently available differing
themselves as regards light source or photosensitizers used
[15,16]. Light sources directly influence the efficacy of treat-
ment and include mainly low-level visible or near-infrared
light from lasers (low-level laser therapy, LLLT) and light-
emitted diodes (LEDs) [17]. Also, incandescent filament and
gas discharge lamps are currently available [17].
LLLT has been the prevailing PDT for a long time [18]
even if many limitations are reported for this approach: com-
plicated clinical setting, wavelengths used, or area that can be
covered by light. LEDs conveniently eliminate such limita-
tions and, on the contrary, reveal as cheaper and more com-
pact. Therefore, compared to lasers, LED power output is
significantly lower resulting as less invasive and less poten-
tially harmful to targeted tissues [19]. As many studies report-
ed [20], LEDs result non-ablative and non-thermal and, espe-
cially when no photosensitizers are used, not damaging to skin
and tissues. No common adverse side effects such as pain,
swelling, peeling reported with other laser therapies have been
reported from patients experiencing LED therapy.
*Elisabetta Sorbellini
elisabettasorbellinimd@gmail.com
1
International Hair Research Foundation (IHRF), Milan, Italy
2
Human Advanced Microbiome Project-HMAP, Milan, Italy
Lasers in Medical Science (2018) 33:1431–1439
https://doi.org/10.1007/s10103-018-2584-8
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Invented in 1962, LED was at the beginning unable to
produce a significant biological activity. First beneficial ef-
fects for human health have been found by the National
Aeronautics and Space Administration (NASA) with the de-
velopment of LEDs producing a narrow spectrum of light in a
non-coherent manner, able to deliver the appropriate wave-
length and intensity required for the process. In the past
15 years, LED technology was continuously ameliorated.
Red, blue, yellow, and near-infrared, also known as mono-
chromatic infrared energy (MIRE), lights are today available.
LED therapy is nowadays a US Food and Drug
Administration (FDA)-approved cosmetic procedure, in
which observed effects include increased ATP production,
modulation of intracellular oxidative stress, the induction of
transcription factors, alteration of collagen synthesis, stimula-
tion of angiogenesis, and increased blood flow [21]. LED
biological effects are strongly influenced by light parameters
as by clinical therapy [15].
The possibility to act on all ofthese parameters makes LED
therapy highly flexible and adaptable for the treatment of dif-
ferent skin disorders; each one implicates different biological
effects to be addressed.
Several studies reported effectiveness and safety of LED
therapy in photo-aged skin [22–26]. Therefore, narrowband
LED therapy using blue light reveals its efficacy and safety
as additional therapy for mild to moderate acne [27]. LED
therapy efficacy was also reported for instance in wound-
healing [28,29]asinpsoriasis[30–32] and rosacea [33–36].
Recent studies [37] also demonstrated the antimicrobial
effect of blue light. This antimicrobial effect is a non-
thermal photochemical reaction involving the simultaneous
presence of visible light, oxygen, and photosensitizer. Once
photosensitization has been activated by the proper light
source, chemical reactions are triggered leading to the produc-
tion of various reactive oxygen species (ROS) [38].
Antimicrobial efficacy of PDT has been verified against a
wide range of pathogens also in biofilm forms [39].
Therefore, use of blue light (405 nm) followed by treatment
with red light (603 nm) is under investigation in the treatment
of skin disorder involving microbial agents. Evidence on the
efficacy of LED therapy for antimicrobial purposes also sug-
gests its possible application in modulating skin microbiome.
This article will review the current LED-based therapeutic
approach in different skin and hair disorders.
Behind LED physiochemistry
and photobiomodulation
A typical LED system is based on a semiconductor chip upon
a reflective surface. When electricity runs through the system,
light is produced. From a radiometric point of view, LED
emission curve is in the form of a Lambertian pattern in which
all the light is emitted at angles less than 90°.
The knowledge and definition of physical parameters are
obligatory steps when setting-up PDT therapy. Maximization
of LED therapy is strictly related to optimization of treatment
parameters: (i) intensity and dosage, (ii) fluence rate, (iii)
wavelength, (iv) pulsing or continuous mode, and (v) treat-
ment duration [40]. Intensity or irradiance refers to the dose of
energy delivered by the LED system per surface area of skin
treated and is expressed in watts per square centimeter (W/
cm
2
). The optimal clinical intensity or irradiance is considered
to be around 50–100 mW/cm
2
.
Another key part of the process is the definition of the
optical properties of the tissues [15]. Once these have been
defined, the fluence rate at any position for a given source
specification can be calculated by mean of radiation transport
equation (RTE) (Fig. 1)[41]. This equation describes light
propagation to the site of treatment in a given direction per
unit solid angle per unit area perpendicular to that direction.
Since the resolution of this equation is not possible in almost
all cases, three alternative approaches have been introduced
[15]. Therefore, when setting up these kinds of physical eval-
uation, it is also important to consider the impact of the dif-
ferent geometries, such as the surface and the interstitial mo-
dality of irradiation, on the distribution of fluence rate [15].
Finding the appropriate combinations between the dose,
the irradiance and the intensity of treatment are another im-
portant parameters to be considered to achieve optimal effects
on the targeted tissues. Each skin conditions will require a
specific evaluation of these parameters.
Different wavelengths can be produced depending on the
composition of the semiconductor and LED system can deliv-
er light either in continuous or in pulsed mode.
Used wavelengths ranged from 400 to 1200 nm (Fig. 2);
longer wavelengths are able to go deeper into tissues [42,43].
Different cells and tissues absorb light at different wave-
lengths, and this is strictly related to the penetration that the
wavelengths have to achieve.
Red light (630–700 nm) is able to reach dermis activating
fibroblasts, increasing fibroblast growth factor expression as type
1 procollagen and matrix metalloproteinase-9 (MMP-9) [44].
Blue light (400–470 nm) has a lower potential for penetra-
tion and reveals useful for skin conditions in the epidermis
layer of the skin [45]. Yellow light (about 540 nm) is effective
in skin conditions involving redness, swelling, and other ef-
fects related to pigmentation [40]. Near-infrared light (700–
Fig. 1 Radiation transport equation (RTE). L(r,Ω)is the radiant power
transported at location rin a given direction Ωper unit solid angle per unit
area perpendicular to that direction; Ωand Ω′are the propagation
directions before and after elastic scattering; μ
s
(Ω→Ω′)isthe
differential scattering coefficient; S(r, Ω,t)refers to the light source
both internal and external
1432 Lasers Med Sci (2018) 33:1431–1439
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1200 nm) reaches the maximum penetration in the skin; in
vivo studies reveal its effectiveness in wound healing via an-
giogenesis stimulation [46].
Conflicting results are still reported as regards the best wave
transmission system [47] even though there is some reported
evidence showing a more favorable impact of pulsed mode on
collagen de novo production by fibroblasts and a greater stimu-
latory effect on cell proliferation and oxidation [48,49].
Establishing a time-dependent response and a precise
working distance are others but not less mandatory parameters
to ensure optimal results [40].
As a kind of PDT, LED acts on tissue and cells by photo-
biomodulation. This process typically involves three key ele-
ments: a light source, a photosensitizing agent, and oxygen.
The light sources have to be chosen according to the capacity
of the match both the activation spectrum of the photosensitizer
and to generate the adequate power at the selected wavelength
[17]. Once exposed to the chosen wavelengths, the photosensi-
tizer comes to an excitation stage following two types of reac-
tions, which led to free radical or singlet oxygen production
(1O2). The last is highly active in biological systems and able
to interfere with the mitochondrial electron transport chain in the
cells via cytochrome c oxidase enzyme. Consequently, cells of
the photostimulated tissue will increase the production of endog-
enous energy in the form of ATP and therefore will rapidly re-
store their integrity. By this process, LED therapy is able to
stimulate fibroblasts, lymphocytes, keratinocytes, and melano-
cytes [49] and macrophage proliferation [50,51].
Other observed effects include modulation of cell oxi-
dation [52], anti-inflammatory effects [53], stimulation of
angiogenesis and blood flow [54], the induction of tran-
scription factors [55], antibacterial activity [42], and the
alteration of collagen synthesis [43].
Photosensitizers in LED therapy
Different types of photosensitizers are available for PDT.
First-generation photosensitizers belong to the group of por-
phyrins. Porphyrin was approved by FDA in 1975 [55].
However, the use of this class of photosensitizers is limited
to superficial tumor since they get excited only in the visible
region. In order to overcome the above limitation, the second
generation of photosensitizers has been developed as modified
or substituted porphyrin. Among these, in 1999, FDA ap-
proved 5-aminolevulinic acid (ALA) and in 2004 its less polar
methyl ester aminolevulinate (MAL) for dermatological indi-
cations [56,57]. Both photosensitizers are prodrugs metabo-
lized, inside the cell, to protoporphyrin IX [58–60]. This leads
to endogenous porphyrin accumulation before light exposure.
Besides their use in the PDT, these photosensitizers are also
valuable markers for diagnosis of skin tumors [61]. In 1999,
we reported the use of topical application of ALA for the
identification of premalignant skin conditions, by means of
fluorescence images. At the same times, this approach also
reveals its utility in the clinical practice by reducing the num-
ber of biopsies required for the identification of malignant
lesions [62].
Further photosensitizers are under study: (i) temoporfin, be-
longing to the chlorine family, with a higher light absorption at a
longer wavelength (652 nm) in comparison with classic porphy-
rins [33] and (ii) indole-3-acetic acid (IAA) [63]. The third gen-
eration of photosensitizers is also under study. The development
of this new class includes both the conjugation of photosensi-
tizers with carrier bio-molecules and targeting peptides [16].
LED therapy in inflammatory and auto-immune skin
conditions
Acne vulgaris
Acne vulgaris is a multifactorial skin disorder associated with
pilosebaceous unit inflammation [16,64,65]. Both oral and
topical treatments are currently available even though they can
be ineffective or poorly tolerated in some patients [66]. Some
studies have suggested promising results for light therapies.
During metabolic and reproductive processes,
Propionibacterium acnes produces endogenous porphyrins,
responsible for light absorption [67]. Evidence of acne im-
provement after sunlight exposure suggested the development
of light-based therapy as a newer therapeutic approach.
Both red and blue lights reveal their efficacy for the treat-
ment of acne vulgaris. In particular, some in vitro studies
demonstrated a statistically significant inhibitory effect of
red light (630 nm) on sebum production [68,69].
Also, blue light (415 nm) showed a significant effect in
acne treatment acting in a dose-dependent manner in reducing
human sebocyte proliferation [67]. Many studies also reported
Fig. 2 How different wavelengths penetrate the skin
Lasers Med Sci (2018) 33:1431–1439 1433
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the beneficial effects of blue light treatments in acne vulgaris
via the alteration of skin microbiome [69–71]. PDT treatment
can act directly on microorganism’s density (e.g., P. acnes
density) [70] but also indirectly by modulating the immune
response [71]. Our new research is evaluating the real effect of
blue and red light (630 nm) on skin and scalp microbiome.
Other clinical trials also reported the efficacy of a combi-
nation of red and blue light in treating mild to moderate in-
flammatory acne lesions [72,73].
In another study, Barolet and Boucher [74] reported inflam-
matory lesion reduction following a combined treatment for
4 weeks with LED (970 nm) and ALA-PDT + LED (630 nm)
versus LED (630 nm) only. Combined treatment showed a
78% lesion reduction compared to 38% of LED only treat-
ment. A more recent study by Zhang and collaborators [75]
confirmed the efficacy of ALA-PDTand red light treatment in
acne vulgaris.
Rosacea
Rosacea is an inflammatory skin condition characterized by
flushing, facial erythema, dryness and burning of the skin,
telangiectasia, vascular inflammation, inflammatory papules,
andpustulesandredorwateryeyes[76]. Pathophysiology of
Rosacea is strictly related to the abnormal expression of
cathelicidins antimicrobial peptides, the elevated levels of
stratum corneum tryptic enzymes (SCTE), and the expression
of higher amounts of Toll-like receptor 2 (TLR2) in skin [73,
77]. Topical and oral therapies are currently available aimed at
controlling Rosacea symptoms [78]. Unfortunately, these
treatments do not carry a complete resolution and are not well
tolerated in all patients. There is new evidence as regards the
benefit of PDT and in particular LED therapies on Rosacea
[33], even if more clinical trials are required. Recently, Bryld
and Jemec showed the efficacy of MAL-PDT coupled with a
red light on papulopustular lesions in Rosacea patients [34].
Another study by Lee and collaborator [35] reported the in
vitro efficacy of LEDs at 630 and 940 nm on TLR2 and
kallikreins (KLKs) in keratinocytes and rosacea-like mouse
skin. Another in vitro study reported the efficacy of ALA-
PDT against biofilm of Staphylococcus aureus [36].
Eczema
Atopic eczema or atopic dermatitis or simply eczema is a
chronic, pruritic, inflammatory skin condition affecting up to
20% of children and 2–8% of adults [79], whom causes re-
main still unclear [80,81]. Treatment of eczema by PDT rep-
resents a valid second-line therapy after non-pharmacological
and topical measure failure.
Only one published randomized controlled trial has been
found related to the use of LED therapy [82]. Patients treated
with blue light (453 nm) for 4 weeks showed a 30%
improvement of clinical manifestations of atopic dermatitis.
Even if there is limited published evidence of LED efficacy
for eczema, its anti-inflammatory effect is generally accepted
and used in clinical practice as off-label treatment showing
varying degrees of beneficial effect treatment for both kids
and adults for moderate to severe conditions of eczema.
Psoriasis
Psoriasis is an immune-mediated inflammatory skin disorder
affecting 2–3% of the population [83]. Since protoporphyrin
IX (PpIX) is endogenously present in psoriatic conditions, it
represents a potential target for photodynamic treatment [84].
Currently, three double-blind controlled studies reported the
use of LED therapy in psoriatic subjects [85–87]. The first one
reported a plaque erythema reduction of 33.9 and 26.7%, re-
spectively, after comparing a 4-week treatment with blue light
(420 nm) and red light (630 nm), respectively, at 60 J/cm
2
,
50 mW/cm
2
, 20 min. Compared to daily salicylic acid, LED
therapy was less effective to reduce plaque desquamation,
while more effective against erythema [85]. Since PpIX has
a maximum absorption peak at 408 nm, it results more acti-
vated by blue light than red light and this reflects in the effi-
cacy of the treatment.
The other two studies reported improvement of local pso-
riasis after blue light LED therapy (420 and 453 nm, respec-
tively; 100 or 200 mW/cm
2
of irradiance) in 4 weeks of treat-
ment [86,87]. Despite reported efficacy, more studies are
currently needed for more precise recommendations about
irradiance to be used.
LED therapy as anti-aging and rejuvenation
treatment
Skin aging is the result of intrinsic and environmental factors
[88]. Aged and photo-damaged skin are characterized by a
reduction in the synthesis of collagen and the simultaneous
increase of matrix-metalloproteinase (MMP) expression. Skin
rejuvenation treatments involve the use of retinoic acid,
resurfacing by laser, chemical peels (trichloroacetic acid and
CO
2
)[89,90]. Other approaches include the use of injectable
skin rejuvenation and dermal fillers [90] and polypeptides that
have recently shown the ability to stimulate skin rejuvenation
when topically applied [91]. More recently, autologous
platelet-rich plasma (PRP) has attracted attention for skin re-
juvenation [92–95] although the molecular mechanism of skin
rejuvenation remains still largely unknown. Non-ablative skin
rejuvenation by PDT is recently becoming a rather common
therapeutic approach in skin rejuvenation thanks to its safety
and effectiveness. Many in vitro and in vivo studies showed
the ability of LED therapy to trigger skin collagen synthesis
and to reduce MMP expression [49,96,97]. Rejuvenation
effects have been reported followed by treatment with yellow
1434 Lasers Med Sci (2018) 33:1431–1439
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LED (590 nm) on 900 patients [98]. Red light (660 nm) effects
were also assessed in aged/photoaged individuals in a split-
face single-blinded study by Barolet and collaborators [99].
This study showed that LED therapy is able to reverse colla-
gen downregulation and MMP-1 upregulation, suggesting
that the use of LED at 660 nm could represent a safe and
effective collagen enhancement strategy. Evidence has been
also reported indicating the higher efficacy of the combination
of different wavelengths in LED therapy than monotherapy
[40,100]. Therefore, the use of blue light coupled with ALA-
PDT showed improved elasticity, texture, pigmentation, and
complexion of the skin [101–103]. In an in vivo study of 20
subjects [104], Zane and collaborators showed also a statisti-
cally significant improvement of skin rejuvenation following
treatment with MAL-PDT and red light. The efficacy of this
treatment has been also demonstrated in a larger study, involv-
ing 94 subjects [105]. LED therapy has also been successfully
coupled with LLLT as adjuvanttherapy for enhancing existing
result from photo rejuvenation treatments [106].
LED therapy in pre-cancerous and cancerous skin
lesions
Pre-cancerousskinlesionsrefertoskinlesionswithacertain
degree of risk of progression to squamous cell carcinoma of
the skin [107]. Actinic keratosis (AK) represents the most
common pre-cancerous lesion encountered in clinical practice,
developing after long-term exposure to the sun. Among dif-
ferently available therapies for AK [108], photodynamic ther-
apy is going to be an additional option. Therapy PDT has been
recognized as effective in the treatment of AK at sites of poor
healing or in case of poor response to other topical therapies
by therapy guidelines [109,110]. A randomized intra-
individual study of face/scalp AK in 119 patients published
by Morton and collaborators [111] compared LED therapy
using MAL as photosensitizer to conventional cryotherapy.
This study highlights a significantly higher rate of healing
after PDT treatment and an equivalent response in non-
responder-retreated subjects. Another study reported by
Piacquadio and collaborators [112] reported 75% clearance
of lesions in 77% of studied patients after treatment with a
formulation containing 20% of ALA and blue light. Another
randomized study showed the efficacy of narrowband red
LED source coupled to BF-200 nano-emulsion [113].
Recent studies compared red light LED-PDT to daylight-
PDT [114,115]. Both studies demonstrated slightly higher
clearance and recurrence rates with LED therapy.
PDT therapy is also considered a reasonable option for
treatment, even though not as first-line, for small and superfi-
cial basal cell carcinoma (BCC). Use of red narrowband LED
light has also been reported in the treatment of squamous cell
carcinoma (SCC) in situ [116].
LED therapy for hair loss disorders
The efficacy of PDT for the treatment of hair loss is reported in
several published studies [117]. Main reported evidence refers to
LLLT as the most used light source [118–120]. In the 2007, FDA
approved the first LLLT device (laser, 635 nm) for the treatment
of hair loss, in particular for androgenetic alopecia. Following, in
2009, FDA approved similar device (laser, 655 nm) for alopecia,
both in men and female. More recently also, LED therapy
showed a real efficacy in the field of hair loss, especially thera-
pies involving the use of red and infrared wavelengths [121,
122]. Today, both laser and LED devices have FDA approval
for hair loss. In two studies reported from Lanzafame and col-
laborator [121,122], 655 nm red light significantly improved hair
counts both in men and women with androgenetic alopecia
(Fig. 3). A more recent study [40] reported the effect of yellow
LED device both on patients with androgenetic alopecia and
alopecia areata. The efficacy of LED therapy by visible light
has also been recognized as a valid adjuvant therapy in the recal-
citrant form of alopecia areata [123].
Nowadays, no PDT studies are available for telogen efflu-
vium, although the use of LLLT and especially LED has now
entered common practice among dermatologists both in pre-
and post-surgical periods. Also, the role of PDT and LED
therapy in scarring alopecia should be further studied as a
potential adjuvant treatment in the clinical management of
cicatricial alopecia. ALA-PDT has been successfully used in
the treatment of cutaneous Lichen Planus, as reported by
many case reports [124]. PDT may act both on
hyperproliferation of cells [125] and also by an immunomod-
ulatory effect with increasing CD8+ reaction [126]. This evi-
dence coupled with the first data on LP treatment encourages
the use of LED therapy also in subjects with cicatricial alope-
ciasuchasLichenPlanopilaris.
Limitations section
Despite its increasing efficacy and use in medical practice,
knowledge on LED therapy remains still limited. Published
studies often addressed a small number of patients (n<20)
and are difficult to compare each other since diversity in pa-
rameters used.
Therefore, as explained above, wavelength, irradiation,
power density, and treatment time period can influence
clinical outcomes at several degrees. Different devices,
from different manufacturers, may present differences in
light output and power densities. These limitations pose
the need of future larger (patient sample n> 20) and more
controlled studies in order to define LED therapy efficacy
in different skin conditions, each of one presents specific
parameters to be set up.
Lasers Med Sci (2018) 33:1431–1439 1435
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Conclusion
PDT is an effective form of treatment for an increasing number
of human conditions, ranging from cancer to several skin con-
ditions. Benefit deriving from the use of light is known since
ancient time, but only in the last decades of twentieth century,
we witnessed the rapid expansion of knowledge and tech-
niques. Recent improvements of the therapy are related espe-
cially to photosensitizer’s development and delivery systems.
Nowadays, the use of LED-based devices represents the emerg-
ing and safest tool for the treatment of many conditions such as
skin inflammatory conditions, aging, and disorders linked to
hair growth. Although the use of LED in the treatment of hair
disorders has now entered common practice, better controlled
studies are still needed to corroborate its efficacy.
Acknowledgments No funding or sponsorship was received for this
study or publication of this article. All named authors meet the
International Committee of Medical Journal Editors (ICMJE) criteria
for authorship for this manuscript, take responsibility for the integrity of
the work as a whole, and have given final approval for the version to be
published.
Compliance with ethical standards
Conflict of interest The authors declare that they have no conflict of
interest.
Abbreviations LED, Light-emitted-diodes; PDT, Photodynamic thera-
py; LLLT, Low-level laser therapy; FDA, US Food and Drug
Administration; ALA, 5-aminolevulinic acid; MAL, Methyl ester
aminolevulinate; ROS, Reactive oxygen species; MMP,
Metalloproteinase; IAA, indole-3-acetic acid; PpIX, protoporphyrin IX;
AK, Actinic keratosis; BCC, Basal cell carcinoma; SCC, Squamous cell
carcinoma; LP, Lichen Planus; LPP , Lichen Planopilaris; FFA, Frontal
fibrosing alopecia; FAPD, Fibrosing alopecia in a pattern distribution;
VAS, Visual analog scale; AGA, Androgenic Alopecia
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appro-
priate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
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