Professional Documents
Culture Documents
LLLT in Alopecia Areata . . . . . . . . . . . . . . . . . . . . . . . . . . 240 MPHL, and AA. In the next paragraphs, experi-
Authors Experience: Case Studies . . . . . . . . . . . . . . . . 241 mental and clinical studies conducted with the use
of LLLT in these conditions will be discussed.
Take Home Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
Historical Data
Introduction In 1996, a team of researchers from Kuopio
University, Finland, conducted a single-blind pla-
The use of laser in dermatology was firstly cebo-controlled study to assess and compare the
assessed in the treatment of benign vascular effects produced by three different types of laser/
tumors. However, it gained ground while proving light (He-Ne, As-Ga-Al diode, noncoherent LED
clinical effectiveness and safety in the treatment light) on hair blood flow. The study involved ten
of other dermatological conditions such as healthy male individuals. Two sessions were held,
removal of pigmented lesions, tattoos, scars, and and the placebo (noncoherent LED light) was
undesirable hairs and in photoaging treatment. compared to other two laser sources (He-Ne and
Laser therapy has become popular over the last As-Ga-Al diode). Measurements were carried out
years. The first report of the use of the laser for by laser Doppler flowmetry. Results demonstrated
hair growth was carried out by Professor Endre that coherent laser sources were the only light
Mester et al. in 1967, during an experimental sources able to produce vasodilation (Pöntinen
observation. Investigators reported the hair regrowth et al. 1996).
in the epilated area exposed to low-potency ruby In 2000, a study carried out by researchers
laser, evaluated to demonstrate the potential car- from Harvard Medical University showed that
cinogenic effect on the shaved backs of guinea volunteers exposed to ruby laser (694 nm) for
pigs (Mester et al. 1968). This finding triggered hair removal and diode (800 nm), responders or
the interest not only in identifying which laser nonresponders, presented some level of hair
apparatus could give efficient clinical responses growth, thinner and without pigment, sometime
without risk but also in verifying which therapeu- after the procedure. The authors concluded that
tic mechanisms would be involved in those changes observed depend on the type of laser and
responses. individual response (Lin et al. 2000).
To understand the mechanism of action of laser Gerardo Moreno-Arias et al. (2002) reported a
in hair regrowth process, mainly in the scalp, laser phenomenon called paradoxical hypertrichosis or
medicine experts have developed different lines of terminalization or induction of terminal hair
research in low-level laser therapy (LLLT) and growth. The clinical finding was described as a
hair loss disorders with available data to date rare but significant secondary effect present in
demonstrating efficacy. patients with hirsutism who undertook intense
The LLLT could be distinguished from other pulsed light (IPL) treatment during a period
forms of laser therapy using low power and low from 3 to 6 months. As the authors argue, intense
density. Most low-level laser therapy devices pulsed light would have the property of inducing
operate at wavelength intervals between 600 and latent hair follicle in non-treated areas located
1000 nm and use much less power than the around treated areas (Moreno-Arias et al. 2002;
amount requested to warm tissue (10 mW/cm, Desai et al. 2010).
2–5 W/cm2) (Bouzari and Firooz 2006). In recent literature’s review made by Sophia
Recently, the use of low-level laser therapy Rangwala, paradoxical hypertrichosis rates range
(LLLT) has been proposed as an alternative from 0.6% to 10% after low-energy laser therapies
therapy (mono or in combination) for hair loss to with almost all types of laser: XeCL excimer
stimulate hair regrowth in alopecia: FPHL, 308 nm, helium-neon (He-Ne), and fractional
Laser on Hair Regrowth 235
Erbium glass fiber 1550 nm. The event is more 1989; Karu and Kolyakov 2005; Hawkins-Evans
frequent over the face and the neck of volunteers and Abrahamse 2008a, b).
with darker skin color (prototypes III–IV), dark When laser therapy is used in the visible elec-
hair, and/or with coexisting hormone imbalance tromagnetic spectrum, there is an initial photo-
(Rangwala 2012). biostimulation in mitochondria, which activates
The appearance of pilli bigeminy in four cases a chain of biological events. When the irradiation
after alexandrite or ruby laser treatments due to is in the infrared spectrum, there is stimulation of
suboptimal fluencies insufficiently low to induce the plasmatic membrane channels, resulting in
thermolysis, but high enough to stimulate changes in membrane permeability, temperature,
follicular growth. Although the face and neck and pressure gradient (Lubart et al. 1992; Oliveira
seem to be the areas which are most sensitive et al. 2008; Mognato et al. 2004; Karu 1987).
to hair growth induction effect, sensitivity and Both visible and infrared light can be absorbed
response of scalp under these conditions are not by different components of the cellular respiratory
recognized (Ye et al. 1999). chain such as chromophores in cytochrome C
Under some researchers’ perspective, laser oxidase or porphyrins, which results in the pro-
phototherapy prolongs the duration of anagen duction of reactive oxygen species or superoxide
phase, stimulates the anagen reentry in telogen radicals. It has been commented that reactive oxy-
hair follicles, increases the proliferation rates of gen species have a fundamental role in increasing
the anagen hair follicles, and prevents the pre- the proliferation of keratinocytes (Lubart et al.
mature catagen development (Chung et al. 1992; Oliveira et al. 2008; Mognato et al. 2004;
2004). There are many theories to explain the Karu 1987).
LLLT’s mechanism of action in hair loss, but it According to Mognato et al., the oxidation
has not yet been fully elucidated (Karu 1989; reaction seems to be associated with stimulation
Karu and Kolyakov 2005; Hawkins-Evans and and proliferation, whereas the reduction reaction
Abrahamse 2008a, b; Lubart et al. 1992; seems to be associated with inhibition of cell
Oliveira et al. 2008; Mognato et al. 2004; Karu growth (Mognato et al. 2004).
1987). Kreisler et al. (2003) emphasized that there is a
Although medical guidelines make special stimulation of photoreceptors in the mitochondrial
reference to LLLT clinical benefits in alopecia, it respiratory chain. After the laser light has been
is important to reinforce the need for clinical absorbed, photophysical and photochemical
studies of a better quality, randomized with an effects, isolated or combined, stimulate the
adequate number of volunteers (Kreisler et al. mitochondrial membrane, increasing the mem-
2003; Kim et al. 2015; Avram and Rogers 2010; brane potential and, consequently, changing the
Stillman 2010). mitochondria’s properties. LLLT acts on
the mitochondria and may alter cell metabolism
through photodissociation of inhibitory nitric
Proposed Mechanisms: LLLT on Hair oxide (NO) from cytochrome C oxidase (CCO),
Growth resulting in an increased production of molecular
oxygen and ATP, which stimulates the activity of
The LLLT has biomodulating effects on cells DNA and RNA to synthesize regulatory proteins
and tissues. These effects activate or inhibit of the cell cycle, and thus the speed of mitosis can
physiological, biochemical, metabolic processes be increased (Kim et al. 2015; Avram and Rogers
through photophysical or photochemical effects 2010; Stillman 2010). Moreover, NO is known
and promote morpho-differentiation, cellular pro- to be a potent vasodilator via its effect on
liferation, tissue neoformation, revascularization, cyclic guanine monophosphate production, and
reduction of edema, increased cellular regeneration, it can be speculated that LLLT may cause photo-
microcirculation, and vascular permeability (Karu dissociation of NO not only from CCO but also
236 J.R. Antonio et al.
INCREASES COLAGEN
DECREASES
INFLAMMATION
GENE UP
REGULATION
PROMOTES HEALING
MITOCHONDRIA
ADAPTED FROM SAJJAD KHAN 2016
ILHT.COM
Results showed that low-level laser treatment Kobielak et al. 2003, 2007; Lee et al. 2011) (see
accelerated significantly hair growth after CIA, Table 1).
without affecting chemotherapy efficiency, con- The HairMax LaserComb# (Lexington Int-
cerning the guinea pig model used for that study ernational, Florida), a 3R class laser (safety level),
(Wikramanayake et al. 2013). was evaluated in androgenetic alopecia in multi-
center, double-blind controlled study (against a
non-active device). The clinical trial was per-
LLLT in Androgenetic Alopecia (AGA) formed in four centers and assessed 110 men
with male AGA (Norwood-Hamilton: IIa-V,
Androgenetic alopecia (AGA) is one of the most Fitzpatrick: I a IV) aged between 30 and 60 years
common chronic problems seen by dermatolo- (Jimenez et al. 2014).
gists worldwide, characterized by progressive The study subjects were instructed to use the
hair loss, especially of scalp hair. It has distinc- device three times a week, during 15 min, over
tive patterns of loss in women versus men, but in 26 weeks. The sites for application were marked
both genders the central scalp is most severely with a circular tattoo, 2.96 cm in diameter, which
affected. was assessed after haircut. By means of comput-
It often begins around puberty and is known to erized countdown, the scalp was evaluated via
effect self-esteem and the individual’s quality of macroimage.
life. In contrast to the high prevalence of AGA, The study subjects treated with laser comb
approved therapeutic options are limited. In addi- (655 nm) showed an increase in density of around
tion to the scarce pharmacologic treatments, there 19.8 hairs/cm2 in comparison to 7.6 hairs/cm2
are numerous nonprescription products claimed presented by the control group (P < 0,0001). No
to be effective in restoring hair in androgenetic statistical improvement was observed in the inves-
alopecia. tigator’s overall evaluation.
Low-intensity laser therapy or photobio- In 2014, another group of researchers published
modulation or photobiostimulation was approved a double-blind, randomized, controlled, multicenter
by US Food and Drug Administration (FDA) in study which had been performed to assess the clin-
2007 with a safe approach to the treatment of male ical efficacy and safety of the same device in
and female androgenetic alopecia. From then on, a women and men with androgenetic alopecia.
series of devices designed for domestic use (daily A hundred and forty-one female volunteers
or many times a week) became available on the (n = 141) and a hundred and twenty-eight male
market, relatively cheap if compared to medical volunteers (n = 128) were randomized to receive
treatment and hair transplant surgery. the active device LaserComb or sham device
Although the mechanism of action of this (control) according to the following design: #1
device is still not clear about androgenetic alope- with beams 9 X control, #2 with beams 12 X
cia treatments, some controlled clinical studies control, #3 with beams 7 X control, and #4 with
show visible hair growth. beams 12 X control.
Different types of laser have been studied dur- The application all over the scalp was
ing the assessment of hair growth in androgenetic performed three times a week throughout
alopecia, including XeCL excimer 308 nm, 26 weeks. Terminal hair density in the targeted
helium-neon (He-Ne), and fractional Erbium area was assessed at the beginning and in the 16th
glass fiber 1550 nm (Blumeyer et al. 2011; Tsuboi and 26th weeks of the follow-up.
et al. 2012; van Zuuren et al. 2012; Zarei et al. Both investigators and study subjects remained
2016; Jimenez et al. 2014; Leavitt et al. 2009; blind to the type of device used during the test.
Wikramanayake et al. 2009; Avram et al. 2007; The specialist responsible for evaluating the dig-
Kim et al. 2011; Kobielak et al. 2013; Kandyba ital pictures taken along the trial also remained
and Kobielak 2013; Kandyba et al. 2013; blind to each branch of the study.
238 J.R. Antonio et al.
At the end of study, the investigators observed mechanism by which LLLT convert telogen into
an increase statistically significant in terminal hair anagen follicles remains unknown.
density for subjects treated with active device Avram and Rogers conducted the first indepen-
against those treated with the sham device dent blinded study of LLLT and hair growth with
(control). seven volunteers and found that on average, there
No serious adverse events have been reported. was a decrease in the number of vellus hairs, an
According to the authors, these results suggest increase in the number of terminal hairs, and an
that LLLT might be an efficient option for hair increase in shaft diameter. Nevertheless, these
loss regarding both male and female patterns. data were not considered statistically significant
However, the researchers recognized that the (Avram et al. 2007).
Laser on Hair Regrowth 239
The first study involving a fractional Erbium Twenty-eight South Korean volunteers took part
glass fiber 1550 nm (Mosaic# Lutronic Co., Ltd., into the study. The volunteers received laser appli-
Seoul, South Korea) published is a non-clinic cation with intervals of 15 min, following the
essay carried out in 2011. The investigators eval- same parameters of the study conducted with
uated the effect of the device on hair cycle in a male volunteers. Phototrichograms and global
form of alopecia in rats. The radiation was applied photos were taken at the beginning and at the
over the shaved skin of C3H/HeN rats using var- end of the treatment. Changes in density and in
ious power and density configurations in different the hair shaft diameter were analyzed. The global
radiation intervals. Stimulation effects on hair were photos were evaluated by three independent der-
observed due to the level of power employed, matologists using a scale of seven points.
density, and radiation interval. Histologic findings Volunteers involved also answered an efficacy
reveal the conversion of hair in telogen phase into self-evaluation questionnaire. All adverse events
anagen phase. The conversion into anagen hair and were reported during 5 months of treatment.
the increase of 5a Wnt, β-catenin were regarded as After 5 months of study, the results demonstrated
signs of therapeutic response. an increase in hair density of 157 28/cm2
Later, to assess the clinical effects of that same (P < 0.0001) and in shaft thickness of 75
sort of laser, a study was performed involving 13 μm (P < 0.001).
20 males with AGA (Kim et al. 2011). In the According to the global photos, out of the
study involving humans, 20 male volunteers remaining 27 volunteers, 24 (87.5%) showed an
were treated in five sessions and in 2-week inter- improvement in their conditions. Two volunteers
vals. It was employed with 5 mJ power with a total (7.4%) reported moderate pruritus after laser appli-
density of 300 spots/cm2. cation, which was spontaneously solved 2 h later.
According to the investigators, fractional laser In 2013, a multicenter, double-blind, random-
can cause thermal injury or photothermolysis for ized, controlled study was performed to evaluate
each thermal microzone (TMZ), which induces col- the efficacy and safety of LLLT in volunteers with
lagen regeneration and thermal shock over proteins. androgenetic alopecia against a sham device, over
Both events lead to the expression of growth fac- 24 weeks, against sham device (control).
tors, including vascular endothelium growth factor The study involved 40 volunteers with andro-
(VEGF), which induces neoangiogenesis. Other genetic alopecia. One group of volunteers was
possible mechanisms are cytokine biomodulation exposed to a helmet-like apparatus, which pro-
and growth factors such as PDGF, KGF, and IGF. duces radiation in wavelengths of 630, 650, and
Nowadays, it is known that there is a complex 660 nm, and the other group was exposed to sham
net of genes involved in the control of hair growth device (control) during 18 min per day.
cycle and connected to Wnt and BMP signaling A phototrichogram and overall evaluations
pathways, especially Wnt7 gene, which cause inad- were carried out. After 24 weeks, the results
equate hair growth, if inactivated. Research data showed a significant increase in hair density in
have already proved that, if BMP signaling path- group of volunteers exposed to the active appara-
ways are reduced and Wnt pathways are increased, tus (LLLT) against the other group (sham device).
a hair growth phase is activated (Kobielak et al. The average diameter of hair shaft also increased
2013; Kandyba and Kobielak 2013; Kandyba et al. significantly in the volunteers submitted to the
2013; Kobielak et al. 2003, 2007). intervention compared to sham device group.
During the study, incremental improvements in According to the investigator’s evaluation, a
hair density and hair growth rate were observed, significant clinical improvement was observed in
which suggested that fractional Erbium glass fiber the group of volunteers exposed to the active
1550 nm might induce hair growth. apparatus. No adverse event was reported. In
In that same year (2011), the investigators the investigators’ opinion, LLLT was considered
evaluated fractional Erbium glass fiber 1550 nm effective and safe concerning AGA treatment
effect on female pattern alopecia (Lee et al. 2011). (Kim et al. 2013).
240 J.R. Antonio et al.
LLLT in Alopecia Areata (904 nm), pulse rate of 40/s. Photos were taken of
each patient before and after the treatment, being
Alopecia areata is an autoimmune disease which 11 males (68.75%) and 5 females (31.25%).
is characterized by rapid and complete hair loss in Concerning the volunteers’ age, there was a range
one or many sites in the form of patches, generally between 4 and 50 years of age with an average of
located on the scalp. Available treatments are 26.6 +/ SD of +/ m 13.8. The disease duration
employed with variable success. These include varied between 12 months and 6 years with an
pulsed high doses of oral or intravenous steroids, average of 13.43 +/ SD of +/ 18.34.
topical high-potency steroids under occlusion, Results showed that hair regrowth was
photochemotherapy, and topical immunotherapy. observed in 32 areas of alopecia (94%), whereas
Efficacy of treatments in patients with alopecia only two areas of alopecia did not show any
totalis and alopecia universalis is poor, with response. On the alopecic patches, considered
long-term complete regrowth in less than 20% of control, hair regrowth was not verified. On
patients (Tosti et al. 2006). 29 patches (90.6%), terminal hair could be veri-
In 1984, Trelles and collaborators investigated fied. Less pigmented vellus have been observed
He-Ne laser action in alopecia areata (Trelles et al. on three patches (Waiz et al. 2006).
1984), and, from 2002 on, a series of studies were In responders, the effect was earlier detected:
undertaken to evaluate the role played by different 24 volunteers(75%) a week after the first session.
forms of light/laser as an alternative therapy to the At the end of the study, the researchers concluded
types of alopecia (particularly alopecia areata) that pulsed infrared diode laser is an efficient
(Shukla et al. 2010; Touma and Rohrer 2004). therapy with a high success rate in volunteers
In 2003, a study assessed the effects of polar- with alopecia areata (patches) refractory to vari-
ized linear infrared radiation produced by a com- ous modalities of treatment.
mercial device denominated Super Lizer# in In 2009, a group of researchers from the
volunteers with alopecia areata. Fifteen volunteers Department of Dermatology of Chung-Ang
over 18 years old diagnosed with alopecia areata University College of Medicine, Seoul, SK,
and with multiple patches were engaged in this report the case of a 35-year-old man with several
trial. Results showed that, out of 15 volunteers large-sized alopecia areata patches on frontal
(46.7%), 7 presented hair growth in the radiated region of the scalp refractory to different
areas around 1.6 months earlier than those not methods/drugs (minoxidil topical solution 5%,
radiated. Regarding the adverse events, only one topical steroids, and intralesional corticosteroid
patient complained about heat sensation over the injections). Non-ablative laser (fractional Erbium
radiated area (Yamazaki et al. 2003). glass fiber 1550 nm) applications were made once
The most explored laser in the treatment of alo- a week, during 24 weeks. A pulse energy of
pecia areata is the XeCL excimer 308 nm, better 10–15 mJ, with a density of 300MTZ/cm2, was
established by a vast number of studies conducted used in each application. Two applications were
even in children, proposing as its mechanism of made in each session (Yoo et al. 2009).
action apoptotic effect over T cells (Gundogan The treatment was well tolerated, without any
et al. 2004; Raulin et al. 2005; Al-Mutairi 2007, side effect reported. Firstly, hair growth was
2009; Ohtsuki et al. 2010, 2013; Byun et al. 2015). observed 1 month after the treatment was started.
In 2006, a study evaluated the efficacy of After 3 months, lesions were covered with termi-
superpulsed Ga-As, 904 nm diode laser, in the nal hair, mostly pigmented, in an average of
treatment of alopecia areata. For this purpose, 30–40%. Six months after the therapy began,
16 volunteers with 34 alopecia areata patches new hair grew over all lesions. No relapse was
refractory to other forms of therapy were selected. reported during a 6-month clinical follow-up.
In each patient, there was a remaining patch with- Regarding the LLLT’s mechanism of action on
out treatment as control lesion. Four sessions were AA, researchers assumed that one or more factors
held, one per week, with pulsed infrared diode laser among improved microvascular circulation,
Laser on Hair Regrowth 241
reduced inflammation, and increased cell energy consistent protocols requires the conduction of
in the form of ATP, working together, could randomized, double-blind, sham-device-con-
explain the clinical benefits of LLLT on AA. trolled trial with an adequate number of volun-
In conclusion, a LLLT offers a safe and effec- teers and longer follow-up.
tive option as monotherapy or in combination
with other conventional therapy for non-scarring
alopecia, such as male and female pattern hair Authors Experience: Case Studies
loss, chemotherapy-induced alopecia, and alope-
cia areata, with available data to date demonstrat- Our case studies (Figs. 2, 3, and 4) involving two
ing efficacy. We must consider that, regardless of patients with androgenetic alopecia using Erbium
these good results, the establishment of more glass laser 1550 nm, energy of 8 mJ, density of
a b
Lateral view
Vertex view
Fig. 2 Patient 1: Before (a) and 6 months after (b) 6 sessions, 1 month apart. Erbium glass laser 1550 nm; energy, 8 mJ;
density, 9%
Parietal view
242 J.R. Antonio et al.
Vertex view
9%, and making 6 applications over the areas Avram MR, Rogers NE. The use of low-level light for hair
affected by alopecia. One-month interval between growth: part I. J Cosmet Laser Ther. 2010;12(2):116.
Avram MR, Leonard Jr RT, Epstein ES, Williams JL,
sessions. Bauman AJ. The current role of laser/light sources in
the treatment of male and female pattern hair loss.
J Cosmet Laser Ther. 2007;9(1):27–8.
Take Home Messages Blumeyer A, Tosti A, Messenger A, Reygagne P, del
Marmo V, et al. Evidence-based (S3) guideline for the
treatment of androgenetic alopecia in women and in
1. LLL therapy offers a safe therapeutic option as men. JDDG. 2011;9(Suppl.6):S1–S57.
monotherapy or in combination with other Bouzari N, Firooz AR. Lasers may induce terminal hair
conventional therapies for non-scarring alope- growth. Dermatol Surg. 2006;32:460.
Byun JW, Moon JH, Bang CY, Shin J, Choi GS. Effective-
cia, taking into consideration the data available ness of 308-nm excimer laser therapy in treating alope-
demonstrating efficacy up to date. cia areata, determined by examining the treated sides
2. The interaction of laser light with tissues of selected alopecic patches. Dermatology. 2015;
can lead to different results (stimulation or 231(1):70–6.
Chung PS, Kim YC, Chung MS, Jung SO, Ree CK.
inhibition) depending on several factors, wave- The effect of low-power laser on the murine hair
length, dose, power, time, number of irradia- growth. J Korean Soc Plastic Reconstruct Surg. 2004;
tions, optical properties of tissues, and type of 31:1–8.
irradiated cell, besides the physiological char- Chung H, Dai T, Sharma SK, Huang YY, Carroll JD,
Hamblin MR. The nuts and bolts of low level laser
acteristics of the cells at the time of irradiation. (light) therapy. Ann Biomed Eng. 2012;40(2):516–33.
3. There has been a rapid increase in market Desai S, Mahmoud BH, Bhatia AC, Hamzavi IH. Paradox-
availability of devices each with differing char- ical hypertrichosis after laser therapy: a review.
acteristics making both physician and patient/ Dermatol Surg. 2010;36(3):291–8.
Gundogan C, Greve B, Raulin C. Treatment of alopecia
consumer navigation difficult. areata with the 308-nm xenon chloride excimer
4. Further investigation is needed to compare laser: case report of two successful treatments with
efficacy of LLLT devices to be able to address the excimer laser. Lasers Surg Med. 2004;34
patient needs and expectations. (2):86–90.
Hawkins-Evans D, Abrahamse H. Efficacy of three laser
wavelengths for in vitro wound healing. Photodermatol
Photoimunol Photomed. 2008a;24(4):199–210.
References Hawkins-Evans D, Abrahamse H. Efficacy of three laser
wavelengths for in vitro wound healing. Photodermatol
Al-Mutairi N. 308-nm excimer laser for the treatment of Photoimunol Photomed. 2008b;24(4):199–210.
alopecia areata. Dermatol Surg. 2007;33(12):1483–7. Jimenez JJ, Wikramanayake TC, Bergfeld W, Maria
Al-Mutairi N. 308-nm excimer laser for the treatment of Hordinsky M, Hickman JG, Hamblin MR,
alopecia areata in children. Pediatr Dermatol. 2009; Lawrence A, Schachner LA. Efficacy and safety of a
26(5):547–50. low-level laser device in the treatment of male and
Laser on Hair Regrowth 243
female pattern hair loss: a multicenter, randomized, on cell cultures. J Photochem Photobiol B Biol.
sham device-controlled double-blind study. Am J Clin 1992;12(3):305–10.
Dermatol. 2014;15:115–27. McElwee KJ. Shapiro JS. Promising therapies for treating
Kandyba E, Kobielak K. Wnt7b is an important intrinsic and/or preventing androgenic alopecia Skin Therapy
regulator of hair follicle stem cell homeostasis Lett. 2012;17(6):1–4.
and hair follicle cycling. Stem Cells. 2013;32 Mester E, Szende B, Gartner P. The effect of laser beams on
(4):886–901. the growth of hair in mice. Radiobiol Radiother. 1968;
Kandyba E, Hazen VM, Kobielak A, Butler SJ, 9(5):621–6.
Kobielak K. Smad1&5 but not Smad8 establish stem Mognato M, Squizato F, Facchin F, Zaghetto L, Corti L.
cell quiescence which is critical to transform the pre- Cell growth modulation of human cells irradiated
mature hair follicle during morphogenesis towards the in vitro with Low-level laser therapy. Photomed Laser
postnatal state. Stem Cells. 2013;32(2):534–47. Surg. 2004;22(6):523–6.
Karu TI. Photobiological fundamentals of low-power laser Moreno-Arias G, Castelo-Branco C, Ferrando J. Paradox-
therapy. J Quantum Electron. 1987;23(10):1703–17. ical effect after IPL photoepilation. Dermatol Surg.
Karu TI. Molecular mechanisms of therapeutic effect of 2002;28(11):1013–6.
low intensity laser irradiation. Laser Life Sci. 1988; Ohtsuki A, Hasegawa T, Ikeda S. Treatment of alopecia
2(1):53–74. areata with 308-nm excimer lamp. J Dermatol. 2010;
Karu T. Photobiology of low-power laser effects. Health 37(12):1032–5.
Phys. 1989;56(5):691–704. Ohtsuki A, Hasegawa T, Komiyama E, Takagi A,
Karu TI, Kolyakov SF. Exact action spectra for cellular Kawasaki J, Ikeda S. 308-nm excimer lamp for the
responses relevant to phototherapy. Photomed Laser treatment of alopecia areata: clinical trial on 16 cases.
Surg. 2005;23(4):355–61. Indian J Dermatol. 2013;58(4):326.
Kim WS, et al. Fractional photothermolysis laser treatment Oliveira DAAP, Oliveira RF, Zangaro RA, Soares CP.
of MPHL. Dermatol Surg. 2011;37:41–51. Evaluation of low-level laser therapy of osteoblastic
Kim H, Choi JW, Kim JY, Shin JW, Lee SJ, Huh CH. cell. Photomed Laser Surg. 2008;26(4):401–4.
Dermatol Surg. 2013;39(8):1177–83. Pöntinen PJ, Aaltokallio T, Kolari PJ. Comparative effects
Kim TH, Kim NJ, Youn JI. Evaluation of wavelength- of exposure to different light sources (He-Ne laser,
dependent hair growth effects on low-level laser ther- InGaAl diode laser, a specific type of noncoherent
apy: an experimental animal study. Lasers Med Sci. LED) on skin blood flow for the head. Acupunct
2015;30(6):1703–9. Electrother Res. 1996;21(2):105–18.
Kobielak K, Pasolli HA, Alonso L, Polak L, Fuchs Rangwala S, Rashid RM. Alopecia: a review of laser and light
E. Defining BMP functions in the hair follicle by con- therapies. Dermatology Online Journal. 2012; 18(2):3.
ditional ablation of BMP receptor IA. J Cell Biol. Raulin C, Gündogan C, Greve B, Gebert S. Excimer laser
2003;163(3):609–23. therapy of alopecia areata–side-by-side evaluation of a
Kobielak K, et al. Loss of a quiescent niche but not follicle representative area. J Dtsch Dermatol Ges. 2005;
stem cells in the absence of bone morphogenetic pro- 3(7):524–6.
tein signaling. PNAS. 2007;104(24):10063–8. Shukla S, Sahu K, Verma Y, Rao KD, Dube A, Gupta PK.
Kobielak K, et al. Competitive balance of intrabulge Effect of helium-neon laser irradiation on hair follicle
BMP/Wnt signaling reveals a robust gene network growth cycle of Swiss albino mice. Skin Pharmacol and
ruling stem cell homeostasis and cyclic activation. Physiol. 2010;23:79–85.
PNAS. 2013;110(4):1351–6. Stein A, Benayahu D, Maltz L, Oron U. Low-level laser
Kreisler M, Christoffers AB, Willershausen B, d'Hoedt B. irradiation promotes proliferation and differentiation of
Low-level 809nm GaAlAs laser irradiation increases human osteoblasts in vitro. Photomed Laser Surg.
the proliferation rate of human laryngeal carcinoma 2005;23(2):161–6.
cells in vitro. Lasers Med Sci. 2003;18(2):100–3. Stillman L. Reply to: the use of low-level light for hair
Leavitt M, Charles G, Heyman E, Michaels D. HairMax growth: part I. J. Cosmet. Laser Ther. 2010;12(2):116.
LaserComb laser phototherapy device in the treatment Tosti A, Bellavista S, Iorizzo M. Alopecia areata: a long
of male androgenetic alopecia: a randomized, double- term follow-up study of 191 patients. J Am Acad
blind, sham device-controlled, multicentre trial. Dermatol. 2006;55(3):438–41.
Clin Drug Investig. 2009;29(5):283–92. Touma DJ, Rohrer TE. Persistent hair loss 60 months after
Lee GY, Lee SJ, Kim WS. The effect of a 1550 nm frac- a single treatment with a 3-millisecond alexandrite
tional erbium-glass laser in female pattern hair loss. (755 nm) laser. Journal of the American Academy of
J Eur Acad Dermatol Venereol. 2011;25(12):1450–4. Dermatology. 2004;50(2):324–5.
Lin TY, Dierickx CC, Campos VB, Farinelli WA, Rosenthal J, Trelles MA, Mayayo E, Cisneros JL. Tratamiento de la
Anderson RR. Reduction of regrowing hair shaft size alopecia areata con laser HeNe. Investigacion Y Clinica
and pigmentation after ruby and diode laser treatment. Laser. 1984;1:15–7.
Arch Dermatol Res. 2000;292(2–3):60–7. Tsuboi R, Itami S, Invi S, et al. Guidelines for the manage-
Lubart R, Wollman Y, Friedmann H, Rochkind S, ment of androgenetic alopecia. Journal of Dermatol-
Laulicht I. Effects of visible and near-infrared lasers ogy. 2012;39:113–20.
244 J.R. Antonio et al.
van Zuuren EJ, Fedorowicz Z, Carter B. Evidence-based treatment accelerated hair regrowth in a rat model of
treatments for female pattern hair loss: a summary of a chemotherapy-induced alopecia (CIA). Lasers Med
Cochrane systematic review. Br J Dermatol. 2012;167 Sci. 2013;28(3):701–6.
(5):995–1010. Yamazaki M, Miura Y, Tsuboi R, Ogawa H. Linear polar-
Waiz M, Saleh AZ, Hayani R, Jubory SO. Use of the ized infrared irradiation using SuperLizer is an effec-
pulsed infrared diode laser (904 nm) in the treatment tive treatment for multiple-type alopecia areata. Int
of alopecia areata. J Cosmet Laser Ther. 2006;8 J Dermatol. 2003;42(9):738–40.
(1):27–30. Ye JN, et al. Pili bigeminy induced by low fluence therapy
Wikramanayake TC, Rodriguez R, Choudhary S, with hair removal Alexandrite and Ruby lasers.
Mauro LM, Nouri K, Schachner LA, Jimenez JJ, Dermatol Surg. 1999;25(12):969.
Leavitt M, Charles G, Heyman E, Michaels D. Yoo KH, Kim MN, Kim BJ. Treatment of alopecia areata
HairMax LaserComb laser phototherapy device in the with fractional photothermolysis laser. 2009. Disponível
treatment of male androgenetic alopecia: a randomized, em www.lutronic.com. Acesso em 11 July 2012.
double-blind, sham device-controlled, multicentre trial. Zarei M, Wikramanayake TC, Falto-Aizpurua L,
Clin Drug Investig. 2009;29(5):283–92. Schachner LA, Jimenez JJ. Low level laser therapy
Wikramanayake TC, Villasante AC, Mauro LM, Nouri K, and hair regrowth: an evidence-based review. Lasers
Schachner LA, Perez CI, Jimenez JJ. Low-level laser Med Sci. 2016;31(2):363–71.