Ứng Dụng Laser Trong Da Liễu Và Y Học (2018)

446
device is the Liposonix® device (Solta Medical
Inc., Hayward, CA). In a retrospective series of
85 patients, the waist circumference was
decreased by an average of 4.6  cm after
3 months. No hyperpigmentation was reported,
however, skin phototypes were not specified.
Due to the deep nature of the treatment pigmen-
tary changes are not likely. This novel treatment
for unwanted fat may offer patients with skin of
color another option without significant risks.
[57, 58].
Cryolipolysis works by selectively cooling fat
resulting in apoptosis without compromising the
epidermis or dermis. CoolSculpting® (Zeltiq
Aesthetics, Pleasanton, CA) utilizes this cryoli-
polysis technology. Side effects include ery-
thema, bruising, pain and altered sensation [59].
In a retrospective analysis of 396 patients who
received this cryolipolysis treatment on the back,
flank and/or abdomen, patient satisfaction was
attained via phone interview in 201 subjects.
Data was compared between FST I–III (n = 122)
and SPT IV–VI (n = 79) and were comparable.
Minor side effects reported included bruising
(16%), swelling (20%), both bruising and swell-
ing (4%). No pigmentary changes were noted in
any subjects. [60].
Conclusion
With the population steadily becoming more
diverse, there is an increasing demand for the
use of lasers and light-based therapies in
individuals with skin of color. As this demand
increases, the need for clinicians familiar
with devices and treatment parameters that
are safe in darker skin is essential. There is
an expanding array of efficacious and safe
lasers and light-based devices available for
use in this population including laser hair
removal, nonablative lasers, skin tightening,
and laser lipolysis among others. Knowledge
of the potential for dyschromia and scarring
in skin of color is needed to ensure use of
effective treatment protocols. Due to these
risks, the treatment of pigmentary disorders
and specifically melasma with lasers still
remains a challenge and should be pursued
with caution.
As the laser armamentarium continues to grow,
it is important that clinicians are well informed on
risks, benefits, technique and appropriate patient
selection. Device selection is important and their
use in skin of color should be reserved for those
devices that have been studied and have demon-
strated safety in this population. With this approach
clinicians can achieve the best possible clinical
outcome while avoiding undesirable side effects
when utilizing lasers in patients with skin of color.
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© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Laser Applications in Children
Jessica Cervantes, Sebastian H. Verne,
and Mercedes E. Gonzalez
Abstract
Lasers can be used to treat a wide variety of
dermatological disorders in children. This
chapter outlines the conditions amenable to
laser surgery in children (Table  1) and dis-
cusses the special issues surrounding parental
counseling, heightened anxiety and safety pre-
cautions when performing laser surgery in
children.
Keywords
Lasers · Children · Vascular lesions · Port
wine stains · Infantile hemangioma ·
Potassium Titanyl Phosphate (KTP) ·
Pigmented lesions
Introduction
Lasers can be used to treat a wide variety of der-
matological disorders in children. This chapter
outlines the conditions amenable to laser surgery
in children (Table 27.1) and discusses the special
issues surrounding parental counseling, height-
ened anxiety and safety precautions when per-
forming laser surgery in children.
Lasers for Vascular Lesions
Oxyhemoglobin, the target chromophore in blood
vessels, has absorption peaks at 418, 542 and
577 nm and thus the best suited lasers for treat-
ment of vascular lesions emit light in this range
(see Table 27.2). The earliest lasers used to treat
J. Cervantes (*) · S. H. Verne · M. E. Gonzalez
Department of Dermatology, University of Miami
Miller School of Medicine, Miami, FL, USA
e-mail: J.Cervantes1@umiami.edu;
s.verne@umiami.edu
27
Table 27.1  Dermatologic conditions in the pediatric
population amenable to laser therapy
Vascular lesions
  Port-wine stains
  Superficial hemangiomas
  Telangiectasias
  Spider angiomas
  Pyogenic granulomas
  Facial angiofibromas
  Lymphangiomas
Pigmented lesions
  Café Au Lait
  Small congenital nevi
  Nevus of ota
  Nevus of ito
  Lentigines
  Becker’s nevus
Other conditions
  Viral warts
  Molluscum contagiosum
  Hypertrophic scars
  Morphea
  Hypertrichosis
  Vitiligo
  Acne and acne scarring

450
vascular lesions in children were the quasi-con-
tinuous lasers such as the Argon pumped tunable
dye, copper bromide and copper vapor lasers but
these have since fallen out of favor due to the
high risk of hypertrophic scarring and textural
changes [1]. In 1989, the flashlamp-pumped
pulsed dye laser (PDL) revolutionized the treat-
ment of vascular lesions, and today it is the treat-
ment of choice for port-wine stains, some
hemangiomas, and telangiectasias in children [2].
The PDL uses a flashlamp to energize rhoda-
mine dye and generates a pulse of yellow light.
Today, the most commonly used PDL systems emit
wavelengths of 585 or 595 nm and are used not only
for vascular lesions but also to target blood vessels
in non-vascular lesions in children. Modern day
PDLs have longer wavelengths (595 and 600 nm),
larger spot sizes (10–12 mm), longer pulse dura-
tions (1.5–40 ms), and higher peak fluence poten-
tial, allowing for more precise treatments according
to vessel size and depth. As long as the pulse dura-
tion is shorter than or equal to the thermal relaxation
time of target vessels, the laser can achieve selective
destruction of target vessels without damage to the
surrounding ­normal tissue. Larger blood vessels
have longer thermal relaxation times (TRT) and
thus longer pulse durations can be used. In addition,
most all PDL systems have excellent dynamic cool-
ing devices which reduce epidermal damage and
intraoperative pain [3].
Other lasers such as the 532 nm KTP, 755 nm
alexandrite, 1064 Nd:Yag or Intense Pulsed light
(IPL) are occasionally used in combination with
PDL for resistant lesions.
Port Wine Stains
Port-wine stains (PWS) are benign vascular mal-
formations composed of ectatic capillary-sized
blood vessels in the papillary dermis that are usu-
ally present at birth [4]. They occur in 0.3–0.5%
of newborns. Early in life, PWS are pink and
macular (see Fig.  27.1). After puberty some
become darker, resembling the color of “port
wine,” and hypertrophy. They are usually unilat-
eral and are commonly found on the head and
neck. Port wine stains have a somatic activating
mutation in the GNAQ gene (encoding the gua-
nine nucleotide binding protein G-alpha-q sub-
unit), which results in dysregulation of angiogenic
signaling and represents a potential future treat-
ment target [5]. The natural history of port-wine
stains is progressive growth, darkening and
hypertrophy of associated tissue, occasionally
nodules and pyogenic granulomas may develop
within the lesion [4].
The flashlamp-pumped PDL is the estab-
lished, gold-standard treatment for PWS in chil-
dren. Treatment with a pulsed dye laser will lead
to subjective and objective lightening at any age
[6]. However, the earlier the treatment begins, the
Table 27.2  Vascular lesions
Lasers used to treat vascular lesions in children
Quasi continuous lasers
Argon pumped tunable dye
577–585 nm/
yellow
Copper bromide
578 nm/yellow
Copper vapor
578 nm/yellow
Krypton
568 nm/yellow
Pulsed lasers
Flashlamp-pumped pulsed dye
laser (PDL)
585 nm/yellow
Long pulsed dye laser (LPDL)
595 nm/yellow
Potassium titanyl phosphate (KTP)
532 nm/green
Fig. 27.1  Post-treatment purpura secondary to blood
vessel destruction typically resolves within several days
J. Cervantes et al.

451
greater the likelihood of complete resolution [7].
In infancy, the lesion size is proportionately
smaller and the thickness of skin is lesser, allow-
ing deeper penetration of the light [8]. Starting
the treatment early may also require fewer treat-
ments [9, 10]. Numerous studies now show that
treating PWS before 1 year of age, and treating
frequently, at 2–4 week intervals, will result in
superior outcomes [11, 12]. Aging PWS thicken
and develop nodularity, which can lead to asym-
metrical deformity of the face and become more
difficult to treat.
When they are on the face or other cosmeti-
cally significant location, PWS can have a pro-
found effect on a child’s social and psychosocial
adjustment. For this reason, many physicians
have suggested that treatment of PWS is a medi-
cal necessity [13, 14]. According to a psychology
study, children develop their body self-awareness
around the latter half of the second year of age
[15]. The development of body self-awareness in
toddlers is the foundation of ego development
and self-esteem later in life [16]. Many families
choose to begin treatment before children start
school to reduce their psychosocial impact.
Studies have shown that adult patients with PWS
have lower self-confidence, which increases after
a treatment PDL treatment [17].
There are no standard recommended settings
of PDL for treatment of due to the lack of con-
trolled studies with a single parameter difference.
In general, the ranges of parameters are: 585–
600 nm wavelength, 7–12 J/cm2 fluence, 0.45–
40 ms pulse duration and 2–12 mm spot size [18].
Longer wavelengths and larger spot sizes may
allow the laser beam to penetrate deeper into the
lesion [19]. Pulse durations should be chosen
according to the presumed size of the blood ves-
sels within the lesion. In port-wine stains, the tar-
get vessels are 10–500  μm capillaries and
post-capillary venules in the papillary and reticu-
lar dermis. The TRT ranges from 0.45–10  ms
[20]. The desired clinical endpoint is a transient
gray to blue discoloration that evolves into pur-
pura [18]. This represents thermolysis of the tar-
get vessels, histologically there is a neutrophilic
and lymphocytic infiltrate within 24 h of treat-
ment resulting in a decreased number and size of
blood vessels. Post-treatment purpura secondary
to this blood vessel destruction, typically resolve
within several 5–14 days (see Fig. 27.2). Some
vessels, if not sufficiently damaged, may recover
[18]. Topical rapamycin, an anti-angiogenic
mTOR inhibitor, when used after PDL treatments
on the PWS can reduce angiogenic signals and
has been shown to improve clinical outcomes in
some studies [ 21].
Many clinicians choose the initial fluence
based on experience and adjust the fluence based
on the PWS appearance immediately after the
laser pulse [22]. Some physicians prefer to per-
form a test spot and gauge PDL settings based on
the patient’s response. Modern day PDL system
that have a cooling device can help reduce epi-
dermal damage and intraoperative pain. PDL
with a cryogen cooling spray device was found to
enhance clinical efficacy and safety because
higher fluences could be used without an
increased risk of permanent scarring or dyspig-
mentation due to epidermal protection [18]. In
skin phototypes I–III, excellent safety profiles
have been established, while in phototypes IV
and V transient hyperpigmentation and hypertro-
phic scarring occur more frequently.
Fig. 27.2  Hemangioma of infancy involving upper eye-
lid may threaten function and therefore require treatment
27  Laser Applications in Children

452
Multiple treatment sessions are necessary and
should be scheduled at 2–4 week intervals [12].
There is no agreement on how many treatment
sessions required to achieve complete clearance
of the lesion. Studies show approximately 10%
improvement per treatment session with an over-
all 50–90% clearance [18]. For facial PWS, the
average number of sessions is between 9 and 12 to
achieve ~80% clearance [14]. Predictive factors
for improvement have been examined by several
studies. A study of 91 children with an average
age of 4.5 years found that the maximal improve-
ment is noted in the first five treatments in all
patients regardless of age, location or size of the
lesion [11]. The best result of treatment was
observe when treating lesions over bony promi-
nences of the face such as the central fore-head,
size less than 20 cm2 and those in children less
than 1 year of age [11]. Lesions of the head and
neck require fewer treatments than those on the
trunk and extremities and those in the V2 derma-
tomal distribution of the trigeminal nerve light-
ened significantly less with the same number of
treatments than those in the V1, V3 and C2/C3
regions [23]. One study in 16 children recom-
mended that using higher fluences (11–12 J/cm2)
and longer pulse durations (1.5 ms) can achieve
faster lightening; >75% clearance was attained in
four treatment sessions [24]. The number of treat-
ments is often determined by when the patient
and/or family are cosmetically pleased with the
result, or decide not to continue the treatment.
Challenging PWS with larger and deeper
blood vessels tend to require more treatment ses-
sions. Repetitive treatments, even when greater
than 20 does not increase the risk of side effects
and can offer additional lightening [25]. About
20–30% of PWSs are very resistant and do not
respond to repetitive treatments with PDL [18].
Combination treatments with longer wavelength
lasers such as 595–600  nm LPDL, 755  nm
Alexandrite, 1064 nm Nd:Yag, and 532 nm KTP
may be required.
IPL produces non-coherent, broadband light of
380–1200 nm that can be used when non-purpuric
therapy with minimal side effects is desired, or
when
laser
treatment
is
unavailable
[18].
Photodynamic therapy (PDT), although not consid-
ered a laser per se, is newer treatment option for
PWS. PDT can be used alone or in combination
with other laser and light therapies. Studies have
suggested superior efficacy of PDT when compared
to the standard PDL treatments. Zhang et  al.
reported preferable response to PDT treatment
using hemoporfin and copper laser (25%) in com-
parison with PDL (11%) in children ages 3–10 [26].
It is important to note that redarkening can
occur after treatment. In a 10  year follow up
study of 51 patients who received PDL for PWS,
35% reported re-darkening of their stains [27].
The further out from last treatment, the more
likely the patient is to report recurrence [28].
Infantile Hemangiomas
Infantile hemangiomas (IH) are the most com-
mon benign tumor of infancy and are composed
of capillary-sized blood vessels, with an esti-
mated incidence of 5% [1, 29]. Their natural his-
tory is characterized by three stages: rapid
proliferation (usually the first 5–8  months of
life), plateau and gradual involution. Although
the vast majority of hemangiomas undergo spon-
taneous involution leaving minimal residual
defect; hemangiomas that pose a significant risk
for cosmetic disfigurement or those that are life
or function-threatening, require treatment (see
Fig.  27.3) [29]. Ulceration, the most common
complication that occurs in IH, has been reported
Fig. 27.3  Deeper hemangiomas may be less amenable to
treatment with lasers
J. Cervantes et al.

453
to occur in 10–30% of hemangiomas [29].
Ulceration usually presents in the proliferative
phase and often results in atrophic scarring. Some
hemangiomas can leave behind cosmetically sig-
nificant, redundant or fibrofatty tissue and telan-
giectasias. In addition, hemangiomas in certain
locations such as on the upper eyelid or mucosal
lip can interfere with normal functioning and
infant development.
With the emergence of systemic and topical
beta-blockers as a reliable, safe and highly effec-
tive treatment for infantile hemangiomas, laser
treatment, now plays a less prominent role in the
management of IH. Nonetheless, vascular lasers,
usually PDL, are still used, most often in three
clinical scenarios: (1) as an adjunctive treatment
with topical or systemic beta-blockers; (2) for
treatment of ulcerated hemangiomas; (3) to treat
residual telangiectasias of involuted IH.  IH are
also sometimes used for thin superficial lesions
in cosmetically sensitive areas early in the prolif-
erative period to prevent rapid growth; for IH that
are not beta-blocker candidates or in early recur-
rences after discontinuation of beta blocker
therapy.
A systematic review on lasers for treatment of
IH found significant variability in the efficacy
amongst studies [30]. Although studies have
shown that PDL treatment compared to active
non-intervention did not achieve superior clinical
outcomes [31, 32], PDL is of benefit as an adjunc-
tive modality. In a retrospective study, facial seg-
mental IH that were treated with the combination
of propranolol and PDL demonstrated more rapid
clearance and required a lower cumulative dose
of propranolol to achieve near-complete clear-
ance when compared to patients who were treated
with either propranolol alone or PDL alone [33].
In another report that compared topical timolol
alone with timolol plus PDL in 102 children with
superficial IH, there was a significantly greater
improvement in the combination arm as com-
pared to timolol alone [34].
In addition, PDL treatment in ulcerating hem-
angiomas can effectively decrease pain and
improve healing of the affected area [35, 36]. In a
study of 78 patients with ulcerated hemangiomas,
91% of patients experienced epithelialization of
the ulceration after an average of two laser treat-
ments. No significant complications were noted
in this study [35].
In a retrospective chart review of therapy of
169 ulcerated IH at a tertiary care hospital more
than 40% were treated with PDL in addition to
other measures. The authors concluded that
pulsed dye laser was a useful adjunct to promote
healing and pain relief when a clean pink granu-
lating base is present but crusts should not be
removed with the PDL as this will impair heal-
ing [36].
When treating hemangiomas, it is important to
recognize how HOI differ from PWS. As opposed
to PWS, IH are neoplasms of endothelial-like
cells, which can be superficial, deep or mixed
(both superficial and deep components) [37].
Vessel channels are small early on and thus the
target chromophore, oxyhemoglobin, may be
less. In the proliferative phase both angiogenesis
and vasculogenesis occurs [37]. In general lower
fluences and shorter pulse durations (than those
used for PWS) are recommended. Although there
is no consensus on the optimal settings of PDL,
the average parameters used in PDL treatment for
hemangioma studies are: 585–595  nm wave-
length, 5–10 J/cm2 fluence (5–7 J/cm2 in the pro-
liferative phase and higher energies in involuting
phase) 0.3–1.5 ms pulse duration and a 3–10 mm
spot size. PDL should always be performed with
cryogen cooling device as this will allow for
higher fluences and thus lead to fewer treatment
sessions needed and greater improvements in
volume and texture [38]. Treatment sessions are
usually repeated every 2–6 weeks.
While the efficacy of PDL is limited to treat-
ing the superficial components of IH; the combi-
nation of PDL and Nd:YAG (1064 nm) lasers can
reach the deeper components of mixed or deep
hemangiomas (see Fig. 27.4) [39]. In a compara-
tive study the use of sequential PDL followed by
Nd:YAG led to superior clinical outcomes when
compared to treatment with timolol in mixed
hemangiomas [40].
Newer devices combining PDL, Nd:YAG
and radiofrequency are on the horizon and
will ­penetrate even deeper allowing for better
treatment of mixed and deep hemangiomas.
27  Laser Applications in Children

454
For post-involution telangiectasias and fibrofatty
residua or scars, the combination of PDL and
ablative fractional resurfacing lasers or CO2
lasers have been used with a great improvement
[41].
Other Lesions Amenable to Vascular
Laser Therapy
In addition to PWS and hemangiomas, spider tel-
angiectasias, pyogenic granulomas and angiofi-
bromas can be effectively treated with vascular
lasers [4, 42]. Most of the time, spider telangiec-
tasias only require a single treatment of PDL
[42]. PDL tends to be more effective for smaller
(<5 mm), flatter PGs and angiofibromas [43, 44].
Several studies have shown that PDL is useful
in treatment of verrucae vulgaris (VV) [45] and
in molluscum contagiosum [46]. VV, or common
wart, is estimated to occur in 10–22% of children
and young adults with a peak incidence between
12 and 16 years of age [47]. Nearly two-thirds of
warts resolve spontaneously within 2 years and
treatment options include topical salicylic acid,
cryotherapy, intralesional candida or bleomycin.
PDL, is a more recent addition to the armamen-
tarium and is often used as an adjunctive treat-
ment when first line methods fail [48]. The
mechanism of PDL in the treatment of warts is
still unknown, but thought to through targeting of
oxyhemoglobin in dilated capillaries within the
lesions, or by inducing apoptosis in the heat sen-
sitive human papilloma virus ladden cells [49].
In a large literature review of 44 studies, PDL
was found to most effective for simple, anogenital
and facial warts with palmar plantar warts showing
a more variable response [50]. Overall treatment
with PDL was well tolerated with few side effects,
most commonly mild pain and erythema. In one
study of 56 children less than 12 years of age, warts
were pre-treated with EMLA, then pared down
with a razor, and treated with the 585-nm flash-
lamp-pumped PDL (5-mm spot size, 7–10 J/cm2,
double pulsed with a 1  mm overlap, 2–3  week
intervals). The overall clearance rate was 48.1%
with an average of three visits needed to achieve
complete remission [49]. The most effective flu-
ences for eradication is between 8.5 and 9.5 J/cm2.
The authors concluded that PDL is safe, tolerable
and relatively effective to treat VV in children and
can be considered a therapy for recalcitrant warts,
but not as the first line therapy. Expansion of this
study with treatment of 78 pediatric patients in total
found an overall clearance rate of 50.7%. Most
improvement was seen in the treatment of flat warts
with a clearance rate of 69.2%, followed by periun-
gual warts (55.6%), plantar warts (46.0%), and
common warts (43.4%) [51].
PDL is also a safe, quick and effective treat-
ment for molluscum contagiosum [52]. Using a
585 nm PDL with pulse duration of 0.450 ms, a
7-mm spot size and fluence of 6–7 J/cm2, nearly
84% of children had complete remission with
one treatment and the remainder responded by
the third treatment session. All patients tolerated
the treatment well [46]. Another study used
585 nm PDL (3-mm spot size, fluence of 8.0 J/
cm2, 300  ms pulse duration) to treat resistant
molluscum contagiosum in 15 children. The cure
rate was 99% [53]. Using pulse durations of
0.25–0.45  ms, fluences of 5–10  J/cm2 for 1–3
­sessions can also give a successful treatment of
the lesion [54, 55].
Fig. 27.4  Overlapping 2 × 2-in. gauzes may be held in
place over the child’s eyes and may be an alternative to
standard safety goggles
J. Cervantes et al.

455
PDL has been effective in the early treatment
of hypertrophic scars, with scars on the face
being most responsive [56]. Other pediatric con-
ditions that have been successfully treated by
using PDL include inflammatory linear verru-
cous epidermal nevus, [57] morphea [58], granu-
loma annulare [59] and lymphangiomas [60].
Potassium Titanyl Phosphate (KTP)
Given the efficacy, safety, reliability and wide
availability of the PDL, use of the KTP laser is
typically limited for treatment of vascular lesions
that are either resistant to PDL treatment or in
cases when PDL treatment is not available. KTP
laser has demonstrated significant clinical effi-
cacy for lightening PDL treatment-resistant
PWS.  Over 50% of the patients showed >25%
improvement and 17% showed >50% response,
with the best results achieved at fluences ranging
from 18 to 24 J/cm2 with pulse width 9–14 ms
[61]. Interestingly, patients described less dis-
comfort during treatment and less post-treatment
purpura with KTP, as compared to PDL.  In
another similar study that included children, this
laser was shown to be safe and effective treat-
ment for common superficial cutaneous vascular
lesions, specifically in patients with Fitzpatrick
skin types I–III [62]. Because of its shorter wave-
length, KTP laser may only be able to effectively
treat these superficial lesions [63]. Also, the shal-
low penetration of the laser results in an increase
targeting of epidermal melanin and thus a greater
risk for non-specific tissue injury in darker skin
types [63]. KTP laser has also been used for
recalcitrant viral warts. In one study, 80% of
patients responded to therapy with 532-nm KTP
continuous wave laser, with complete clearance
observed in nearly 50% of the group [64].
Quasi Continuous Lasers
The argon pumped tunable dye (577–585  nm/
yellow), Copper bromide (578  nm/yellow)
Copper Vapor (578  nm/ yellow), and Krypton
(568 nm/yellow) lasers were used in the past for
the treatment of vascular skin lesions. Their use
has fallen out of favor due to the superior efficacy
and safety of PDL.
Pigmented Lesions
Lasers used to treat pigmented lesions in children
Potassium-titanyl-phosphate (KTP) laser
532 nm
Q-Switched alexandrite
755 nm
Q-Switched ruby
694 nm
Q-Switched Nd:YAG, frequency-doubled
532 nm
Q-Switched Nd:YAG
1064 nm
Lasers used to treat pigmented lesions in children
are those that selectively target melanin and
include the short pulse duration Q-switched lasers
such as the 532 nm frequency doubled Nd:YAG;
the 694 nm, Ruby, the 755 nm Alexandrite or the
1064 nm Nd:YAG laser [4]. Melanin has a wide
absorption spectrum ranging from 300 to
1000 nm, and slowly decreasing from the ultravi-
olet to the near infrared. In general, pigment-spe-
cific lasers tend to have very short pulse durations,
which minimize heat spread from the melano-
some to surrounding tissue, allowing for single
pigment cell destruction. Based upon the depth of
the lesion being treated (epidermal, dermal or
mixed), individual laser systems can be optimally
selected to treat the target lesion [4]. While treat-
ment efficacy decreases as the wavelength of light
increases, longer wavelength laser systems may
be required for improved penetration and treat-
ment of deeper lesions [65].
Indications and Contraindications
• Indications
–– Epidermal Lesions
Lentigines
Café Au Lait Macules
Nevus Spilus
–– Dermal Lesions
Nevus of Ota or Ito
Traumatic tattoos
–– Mixed Lesions
Congenital Melanocytic Nevi (Still con-
troversial at this time)
27  Laser Applications in Children

456
• Contraindications
–– Patients with unrealistic expectations.
–– Patients who tend to scar will be at a greater
risk for this post-operative complication.
–– Patients with clinically atypical melano-
cytic nevus.
Lentigenes are small, flat darkly-pigmented
lesions that can involve any cutaneous surface in
a spotty distribution, commonly found on sun
exposed areas in children [66]. Lentigenes result
from an increased number of melanocytes at the
dermo-epidermal junction without the formation
of nests and enlarged melanosomes throughout
the epidermis. Although lentigines can be effec-
tively treated by pigment-specific lasers, it is not
commonly performed in clinical practice in chil-
dren given their benign nature and the likelihood
of recurrence. The anxiety and pain associated
with laser treatment is often not worth the benefit
of removing a benign lesion. Nonetheless, if the
lentigenes are causing significant psychosocial
distress to the child, such as in the setting of cer-
tain genodermatoses associated with numerous
lentigenes or lentigenes in cosmetically sensitive
areas Q-switched ruby, alexandrite and Nd:YAG
(frequency doubled 532 and 1064 nm) are highly
effective. Lentigenes will usually clear after one
or two treatments but lesions commonly recur
and post-inflammatory hyperpigmentation has
been reported in 17–28% of patients. In one study
using the 694-nm Q-switched ruby laser, with
4.5–7.5 J/cm2 and pulse duration of 40 ns nearly
all lentigenes cleared after a single treatment
[67]. Similarly, using the frequency-doubled
Q-switched Nd:YAG laser can lead to >75%
clearance after a single treatment using 2.0-mm
spot size, 10 ns pulse duration, and fluences of
2–5  J/cm2 [68]. One study used a ruby laser
(6  mm spot size, fluence 20  J/cm2, and pulse
duration of 450 μs) to treat two pediatric patients
with Peutz-Jeghers syndrome. They experienced
complete and almost complete resolution with
two and four treatments, respectively [69].
Use of the long pulsed lasers such as the 595-
nm LPDL (9–13  J/cm2 and 1.5  ms), 532  nm
Nd:YAG or intense pulsed light devices may
reduce risk of post-inflammatory hyperpigmenta-
tion but will require more treatment sessions
[70]. Newer picosecond technology further
reduces the risk of post treatment hyperpigmen-
tation without requiring more treatments. In one
study of six patients (Fitzpatrick type 4 skin) with
a total of 255 lentigenes. With a single treatment
using a 4.5 mm spot size, fluence of 0.65 J/cm2
and pulse rate of 1.67 Hz, 78% of patients noted
75–100% improvement after a single treatment
and post-inflammtory hyperpigmentation was
noted in only 2 of the 255 treated lesions [71].
Café-au-lait macules are flat, sharply-demar-
cated lesions of uniformly light tan to brown,
with uniform melanin pigmentation. The lesions
can range from a few millimeters to 20  cm in
diameter. Solitary café-au-lait macules are not
uncommon and can be founded in 10–28% of
normal individuals, with the prevalence increas-
ing during infancy and decreasing in adult life
[66]. The response to laser treatment is variable,
not only among different lasers treatments but
also among café-au-lait macules treated with the
same laser [4]. The macules may darken, lighten,
or recur after laser treatment. Given the benign
nature of these lesions, they are not routinely
treated in the pediatric population except in cases
where they are causing significant psychosocial
distress. Taylor and Anderson demonstrated sub-
stantial clearing of café au lait with the 694-nm
Q-switched ruby laser using fluences of 4.5 and/
or 7.5 J/cm2 and a pulse duration of 40 ns [67].
A comparative study of the Q-switched ruby
laser and Q-switched Nd:YAG laser showed sim-
ilar efficacy, with the ruby laser having slightly
better treatment response [72]. Another study of
café au lait macules, compared the QS 532 nm
laser, settings: 2.6 mm, 1.2 J/cm2, 2 Hz to ashen
grey endpoint; three treatments at 4 week inter-
vals to the QS 1064 nm laser six treatments at
2  week intervals using settings: 2.6–3  J/cm2,
10  Hz, three passes until mild erythema. At
3 months follow up, the QS 1064 nm group had
better outcomes, treatments were less painful,
there was less associated downtime and lower
recurrence rate (17% versus 33%). The smaller
lesions and those on the face had superior out-
comes. Six of 16 patients (37.5%) experienced
complete response [73]. Newer combination
J. Cervantes et al.

457
devices combine fractional photothermolysis and
Q-switched technology can lead to superior out-
comes with fewer treatments needed [74].
Nevus spilus is a well-defined patch of hyper-
pigmentation with scattered smaller, darker pig-
mented macules or papules, frequently found on
the trunk or extremities. Size can vary from 1 to
20 cm in diameter and the prevalence of nevus
spilus is <1% in newborns [66]. The lesion con-
sists of café-au-lait and nevocellular melanocytic
components. The melanocytic component can
range from lentigines to melanoma, therefore,
any suspicious lesions should be biopsied and
followed [75]. The Q-switched ruby, Q-switched
alexandrite,
Q-switched
frequency-doubled
Nd:YAG lasers, as well as the non Q-switched
ruby and alexandrite lasers, have all been used to
treat nevus spilus [4].
Like café-au-lait macules, the treatment out-
come of nevus spilus is unpredictable. There is
no agreement upon standard laser therapy for
nevus spilus, each lesion has variable amounts of
café au lait and nevus components and thus
requires a unique approach.
One report used the 694-nm Q-switched ruby
laser with a 40 ns pulse duration and fluences of
4.5 and 7.5  J/cm2 for small and large lesions,
respectively. Initial improvement was seen after
two treatments in small lesions and one treatment
in larger lesions at the higher fluence; however,
there was a nearly complete return of background
pigment observed at 1  year [76]. The 755-nm
Q-switched alexandrite laser achieved greater
than 50% clearance in 32.1% of Japanese patients
with at least one treatment [77].
Combining different laser modalities may
lead to superior outcomes. In one study the coher-
ent fractional CO2 laser was followed by MedLite
C6 laser at two different parameter settings
(1064 nm wavelength, 4.0 J/cm2 fluence, 3 mm
spot size and then 532 nm, 1.2 J/cm2, and 2 mm)
to treat ten patients, including six children with
nevus spilus. At the 3  month follow-up, all
patients had >50% improvement, with six experi-
encing >90% improvement [78].
Nevus of Ito and Nevus of Ota are both char-
acterized by dermal melanocytosis that appears
as blue-gray patch of the skin. Nevus of Ota is
most commonly seen in Asian and African-
American populations, as a unilateral, irregular
blue-gray patch along areas innervated by the
first and second branches of the trigeminal nerve
[4]. Greater than 50% of the lesions are present at
birth, whereas 40% manifest during puberty.
Nevus of Ito is patchy blue-gray patch that typi-
cally occurs on upper trunk [79]. Given the depth
of melanosis, pigmented lasers with longer wave-
lengths tend to clear lesions more quickly than
those with shorter wavelengths. Treatment with
Q-switched ruby or Alexandrite lasers have
shown to selectively destroy dermal melanocytes.
Using the 755-nm Q-switched alexandrite laser
(pulse duration 100  ns and 4.75–7.0  J/cm2 flu-
ences) at 8–12  week intervals, Alster and
Williams demonstrated 50% clinical clearance
after two treatments and 100% after five treat-
ments in most patients [80]. In another study of
15 patients between 6 and 52 years of age, using
694-nm Q-switched ruby laser with pulse dura-
tion of 40  ns and fluences 6–10  J/cm2 showed
complete clearing of the lesion in nearly 30% of
patients and >50% lightening in the remaining
patients [81]. In a larger study with 46 children,
Q-switched ruby laser used in children produced
complete clearance of the lesion faster than in
adults, demonstrating the advantage of early
treatment of Nevus of Ota in the pediatric popu-
lation [82]. Early treatment is further supported
by a study using Q-switched Nd:YAG (7–8 mm
spot size, fluence adjusted from 2.5  J/cm2,
5–10 ns pulse duration, and 10-Hz repeat rate).
This study found that a significantly lower mean
fluence was required for patients younger than
10  years, with 18 patients reaching near total
improvement after a mean of 11.4 sessions [83].
In a split-face study of bilateral nevus of ota the
QS Nd:YAG and the QS alexandrite lasers
showed equal efficacy [84].
Laser type should be chosen based on the
background skin color, color of the lesion and
depth of melanocytes [85]. When QS lasers alone
do not work, the addition of fractionated laser
modalities may help clear the lesion [86].
Tattoos result from pigment deposition pri-
marily in the dermis, either via professional
application or trauma. Laser treatment for profes-
27  Laser Applications in Children

458
sional tattoos on adult patients will be discussed
elsewhere in this book. Traumatic tattoos, such as
those from the graphite from pencil tips, are the
most frequently seen in the pediatric population.
Traumatic tattoos are effectively treated with
Q-switched ruby, Q-switched alexandrite or
Q-switched Nd:YAG after single treatment [87].
In one report, single treatment using the
Q-switched ruby laser successfully cleared a
traumatic tattoo from a pencil tip injury 1 year
prior [88]. Another study reported successful out-
come using the Q-switched alexandrite to treat
traumatic tattoos from blacktop, surgical pen,
gravel tattoos, and even fireworks [89].
Congenital melanocytic nevi (CMN) are col-
lections of melanocytes that may present as mac-
ular, papular, or plaque-like pigmented lesions in
various shades of brown. CMN usually present at
birth or shortly thereafter and can range in size
from a few centimeters to 5–50% of the body sur-
face area [4]. Laser treatment can be effective in
improving the appearance of CMN by lightening
or removing superficial cutaneous pigment, how-
ever their role in treatment of CMN is controver-
sial and limited to use in cases when excision of
CMN is desired but not feasible. Treatment with
ablative (e.g., carbon dioxide, erbium:YAG) or
pigment-specific lasers have resulted in signifi-
cant cosmetic improvement of lesions [90].
Ablative lasers remove the epidermis and upper
portion of the dermis are most effective during
the first 1–2 months of life, when nevomelano-
cytes are concentrated within the upper dermis
and there is a lower likelihood of excessive scar-
ring [91]. Early treatment with Er:YAG laser
resurfacing in the first weeks of life in ten patients
with large and giant CMN was well tolerated and
led to significant lightening of the lesion but six
out of ten patients had spots of repigmentation
and two patients with large GCMN on the trunk
developed hypertrophic scars and skin atrophy
[92]. Reports of frequent repigmentation and
future development of melanoma arising several
years after ablative laser highlights the partial
nature of this treatment modality and points to
the need for continued vigilance [92, 93].
Both QS and ablative lasers have been suc-
cessfully used for small and medium-sized CMN.
Waldorf et al. demonstrated that Q-switched ruby
laser effectively lightens and may clear pigmen-
tation and eliminate superficial nevus cells from
small and medium congenital nevi safely without
scarring [94]. In this study there was 57% clear-
ance of pigmentation in all nevi by the fourth ses-
sion and an average maximum clearance of 76%
after approximately eight sessions. However,
authors emphasize that results are not permanent
and should not be considered definitive treatment
[94]. Combination of ablation (CO2 laser, pulse
duration 1 ms, fluence 300 mJ/cm2) followed the
QS alexandrite was more effective than QS alex-
andrite alone [94]. Similarly in a report of 55
patients with medium-sized CMN (mean age,
18 years) treated with both carbon dioxide laser
and QS Nd:YAG with a mean of five and six
treatments at 3 month intervals, carbon dioxide
laser treatment was most effective for head and
neck nevi with a papillomatous surface, whereas
flat truncal CMN responded best to frequency-
doubled Nd:YAG laser therapy [95].
It is important to remember that while lasers
improve cosmesis of CMN they only remove
melanocytes in the epidermis and upper dermis
thus partial repigmentation with a speckled
appearance is quite common after laser treatment
and the need for vigilance for malignant changes
is remains. For these reasons, most authors agree
that the primary role of laser treatment is for cos-
metically disfiguring and surgically unresectable
lesions [96].
Ablative Lasers in Children
Carbon dioxide (CO2) laserErbium:Ytrium-Alu-
minum-Garnet (Er:YAG) laser
• Ablative lasers, including the CO2 and Er:YAG
laser, have been utilized to treat a variety of
lesions in the pediatric population, including a
variety of nevi, acne scars, keloids, and epi-
dermal nevi.
Ablative (or resurfacing) lasers were first
designed for use in the adult population to remove
or reduce wrinkles. They are now utilized in
J. Cervantes et al.

459
pediatric patients for many conditions, including
acne scar, keloid, VV, epidermal nevus and
inflammatory linear verrucous epidermal nevus
(ILVEN), angiofibroma, and CMN.
Indications and Contraindications
• Indications
–– Epidermal Nevus
–– Scars (acne and keloid)
–– Congenital Melanocytic Nevus
–– Verrucae Vulgaris (Older treatment option)
–– Angiofibromas
• Contraindications
–– Patients with unrealistic expectations
–– Patients who tend to scar will be at a greater
risk for this post-operative complication
Epidermal nevi (EN) are benign hamartomas
of epidermis and papillary dermis, and usually
occur within the first year of life. Most lesions
appear as well-circumscribed, hyperpigmented,
papillomatous papules that are asymptomatic.
Over time, the nevus may become more thick-
ened and verrucous, developing into a significant
cosmetic concern. Since topical therapies are of
limited utility, most treatment methods attempt to
ablate the lesion and decrease its thickness with
resurfacing lasers, such as the CO2 and Er:YAG
lasers. One such report of the pulsed 2940-nm
Er:YAG laser (0.4–0.45 J/cm2, spot size 2 mm)
demonstrated excellent clinical results for the
treatment of superficial or small, discrete lesions
which could be ablated accurately; however, they
did not evaluate the efficacy of laser therapy for
larger, thicker EN which may be more difficult to
treat [97]. Additionally, CO2 laser was effective
in some of thicker EN not responsive to argon
laser, but there was a high incidence of post-treat-
ment hypertrophic scar [98]. Another group
showed that the variable-pulsed Er:YAG laser
(pulse duration 500  ms, fluence 7.0–7.5  J/cm2)
and the dual-mode Er:YAG laser (pulse duration
350  ms, fluence 6.3  J/cm2) were effective and
safe for ILVEN with complete clearance in 75%
of patients in one treatment, although 25% did
have a relapse within 1 year [99]. In summary,
both CO2 and Er:YAG lasers can be effective for
the treatment of EN, and its efficacy depends on
the size and thickness of the lesion.
Similarly, CMN can also be treated with abla-
tive lasers. Ostertag et al. has shown that Er:YAG
laser was effective to treat CMN in neonates.
Overall, the treatment was well tolerated, with
good clinical and histological results. Eighty per-
cent of patients had minimal to no repigmenta-
tion clinically, and disappearance of heavily
pigmented cells in the upper part of the dermis
histologically as well [92]. CMN can also be
effectively treated with CO2 laser, but this appli-
cation may be limited by the slightly higher inci-
dence of observed hypertrophic scarring [100].
Ablative lasers have also been utilized as an
alternative therapy for treatment resistant viral
warts. A 2002 study has shown that single treat-
ment of recalcitrant warts with CO2 laser had
response rates between 56% and 81% [101].
Another group used the CO2 laser and vaporized
the base of the wart and 5 mm margins. This tech-
nique provided a high success rate with no recur-
rence at 12 months and was well tolerated by the
patients; however, hypopigmentation was noted
in about 25% of the cases [102].
Both CO2 and Er:YAG lasers have been useful
in the treatment of keloids and hypertrophic scars
[103]. The pulsed Er:YAG laser with a 2-mm
hand-piece at 500–1200 mJ/pulse at 3.5–9 W was
used with an improvement of more than 50% in
hypertrophic, depressed and burn scars [104].
Adverse Events
Fortunately, the safety and efficacy of PDL has
made it an ideal laser system for treatment of vas-
cular lesions in children. Potential adverse effects
include dyspigmentation and hypertrophic or
atrophic scarring [4]. Purpura is a desired effect
but occasionally prolonged purpura lasting up to
14 days can occur and is distressing. The risk of
post inflammatory hyperpigmentation is higher
in darker-skinned and tanned patients because of
the possible competitive absorption of melanin.
To treat this subset of patients, a longer interval
between treatments is recommended [105].
27  Laser Applications in Children

460
Pain is common during and immediately after
the procedure. Pain can be minimized when using
a cooling device with PDL. An ice pack to the
treated area can help lessen pain. Infection can
also occur as a consequence of a diminished skin
barrier following epidermal damage. This risk
may be higher in patients with coexisting atopic
dermatitis [106].
Another concern in children is psychological
sequelae from the treatment. The pain, restraint
and darkness associated with the procedure can
be psychologically scarring and can lead to fear
and stress in future doctor visits. Techniques to
allay anxiety and analgesic and sedative agents
for laser treatments will be discussed in more
detail later in the chapter.
Special Considerations in Children
Preoperative Management
Laser treatment of children poses a unique chal-
lenge for a variety of reasons. The approach to a
child prior to laser treatments is different than
their adult counterparts.
First, parents may be more apprehensive and
have more questions about the procedure than if
they themselves were the patient. Thus, pre-treat-
ment counseling sessions may be longer as both
parent and child should have their questions
answered. During the visit, the parent and the
child should informed of what will happen step
by step on treatment day as well as what to expect
post-treatment including risk of dyspigmentation
and scarring. Parental expectations should be
explored and all questions are answered.
Expected outcomes and usual number of treat-
ments are discussed as well. Using before and
after photographs of previously treated patients
may help allay anxieties in parents [107].
Secondly, laser treatment produces sufficient
discomfort and may not be as easily tolerated by
children. Laser treatments are painful and have
been likened to the sensation of flicking a rubber
band on the skin [108]. There is not one specific
age at which you can plan that a child will sit still
and cooperate with the procedure. The age at
which a child will cooperate with such a proce-
dure depends on several factors, including matu-
rity level among other things. For example, a
3-year-old child who has been in and out of sur-
geries for congenital heart disease may sit still for
laser treatments while an immature 10-year-old
may be uncooperative. In general, rapid and lim-
ited treatments seem to be tolerated well in young
infants and mature adolescents with no anesthe-
sia at all, or with topical anesthesia alone [107].
Some form of anesthesia should be considered
for all children undergoing laser treatments. The
kind of anesthetic and how it will be adminis-
tered should be discussed in the pre-treatment
counseling session. At a minimum, a topical local
anesthetic such as lidocaine 4% or 5% cream
(LMX®) or eutectic mixture of local anesthetics
(EMLA) should be applied to the area to be
treated. EMLA, which is half lidocaine and half
prilocaine, has been occasionally associated with
local and systemic side effects in the pediatric
population [105, 109, 110]. In addition, some
groups discourage its use before laser treatment
as it can vasoconstrict the target area. LMX® has
a longer duration of anesthesia, does not require
occlusion and does not have any reported side
effects [106]. According to the package insert, to
avoid systemic absorption, LMX should not be
applied over an area greater than 100 cm2 in a
child less than 10 kg or to an area greater than
600 cm2 in a child weighing 10–20 kg [4]. In our
practice, we use LMX® 4% invariably for younger
children and in older children with large lesions.
The cream is applied with tegaderm or saran
wrap occlusion (to keep the cream in place) on
the target area by our medical staff when the
patient first checks in to their appointment. They
then wait 15–30 min in the waiting room prior to
laser treatments. A dressing with gauze or a
­permeable bandage prevents optimal absorption
of LMX® into the skin. Our technique has been
successful and we have had 6 year olds cooperate
with procedure using LMX® only. Localized
intradermal injections and local intradermal
nerve block have also been used. In younger chil-
dren who will not tolerate the discomfort associ-
ated with the procedure even with local
anesthesia, then oral, intravenous and/or general
anesthesia can be used.
J. Cervantes et al.

461
Procedural anesthesia (formerly known as con-
scious sedation) is another method that can should
be performed under the supervision of an experi-
enced pediatric anesthesiologist to allow for the
procedure to be done in an outpatient setting. In
addition, oral agents such as chloral hydrate, ben-
zodiazepines and codeine have been used for light
sedation during in office procedures. These agents
carry the risk of respiratory depression and their
duration of action are unpredictable and thus
should only be used by and experienced team.
While these agents provide light sedation, they do
not provide any anesthetic effect.
In children with large lesions who require pro-
longed treatment and in younger children when
immobilization cannot be obtained, deep seda-
tion with IV sedatives or general anesthesia
should be considered. When preformed in a pedi-
atric hospital with pediatric anesthesiologists
present there is no increased risk of morbidity or
mortality from deep or general sedation [111,
112]. An increased complication risk with gen-
eral anesthesia is seen in the first year of life with
a greater risk in the first months of life (<6 months)
[113]. Despite the low rate of complications, the
added risk of general anesthesia and the unknown
long term effects on the developing brain needs
to be considered versus the benefits of PDL treat-
ments. Lesions that represent significant health
risks, cause functional impairment or a deformity
in which a superior cosmetic result would be
obtained with early surgical or laser intervention
or which may impact significantly psychosocial
development may necessitate early surgical inter-
vention despite the added risk inherent in general
anesthesia. In other cases, parents may choose to
wait until the child is old enough to cooperate
with the procedure as an outpatient.
Intra Operative Management
Even with local anesthesia and a seemingly coop-
erative, prepared child, secure positioning is of
utmost importance when treating children with
lasers. We believe a minimum of three personnel
should be in the room when treating a child with
a laser; one to perform the laser surgery, one at
the head of the table, holding the head and eye
protection in place, and one at the foot of the
table (see Fig. 27.5). We often also include a par-
ent on the opposite side of the laser to aid in hold-
ing the child and ease their anxiety.
Age-appropriate eye safety is also very impor-
tant. The standard safety goggles may be too
large and provide inadequate protection [114]. As
an alternative, overlapping 2  ×  2  in. pieces of
white gauze can be used held in place by staff or
medical personnel. These patches can absorb or
reflect laser light. Smaller metal corneal shields
can also be used. White gauze can also be used to
cover an area within the spot size diameter that
should not be treated or has already been ade-
quately treated [4].
Creativity comes into play when interacting
with young children in the procedure room. Our
group frequently uses distraction anesthesia
where by children are distracted by a DVD or
handheld game of their choice [115]. Another
technique often used is the pinching of the skin
prior to the injection of lidocaine to distract away
from the initial sting. Other authors have sug-
gested creating a “parent  – child tent” such as
with a gown or a sheet [116], this can be espe-
cially useful when the site to be treated is away
from the face. Songs or counting can also be used.
Dressing the surgical site with an age appropriate,
child friendly dressing can help the patient feel
more comfortable at the end of the procedure.
Fig. 27.5  Distraction anesthesia may be employed with
the use of handheld DVD or gaming device of their choice
27  Laser Applications in Children

462
Conclusions
Lasers can be safely and effectively used in
children when the aforementioned special
considerations are employed. Perhaps the
most far-reaching example is the success in
the treatment of PWS in young infants.
Understanding the composition and natural
history of pediatric skin lesions and the
mechanics of skin and laser interactions is one
step towards providing effective treatment for
children. Laser surgery is an important part of
the therapeutic armamentarium in children.
With advancing technology in laser surgery,
there will be an even greater role in the treat-
ment of children.
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27  Laser Applications in Children

467
© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Dressing/Wound Care for Laser
Treatment
Ariel E. Eber, Vincent M. Hsu, Stephen C. Davis,
and Keyvan Nouri
Abstract
Laser procedures have become quite com-
monplace in the field of dermatology.
Advancing technology, coupled with better
management and prevention of side effects,
has resulted in a large increase in laser proce-
dures. As mentioned throughout this text,
lasers are an appealing therapy for scars,
photo-damage, ritides, and pigmentary disor-
ders. Ablative lasers have been used effec-
tively for years however with concerns of side
effects and/or complications. Patient are also
often dissuaded by the down-time required
after ablative laser procedures. Furthermore,
the demand for ablative procedures has
decreased with non-ablative techniques dra-
matically on the rise. The non-ablative how-
ever, tend to have diminished efficacy
compared to ablative techniques for many
indications. With the rapid advances in laser
technology there is a need to investigate opti-
mal postoperative regimens so that we may
deliver better outcomes and increase patient
satisfactions.
Keywords
Laser procedures · Ablative lasers · Wound
dressing · Wound care
Introduction
Laser procedures have become quite common-
place in the field of dermatology. Advancing
technology, coupled with better management and
prevention of side effects, has resulted in a large
increase in laser procedures. As mentioned
throughout this text, lasers are an appealing ther-
apy for scars, photo-damage, ritides, and pigmen-
tary disorders. Ablative lasers have been used
effectively for years however with concerns of
side effects and/or complications. Patient are also
often dissuaded by the down-time required after
ablative laser procedures. Furthermore, the
demand for ablative procedures has decreased
with non-ablative techniques dramatically on the
rise. The non-ablative however, tend to have
diminished efficacy compared to ablative tech-
niques for many indications. With the rapid
advances in laser technology there is a need to
A. E. Eber
University of Miami Miller School of Medicine,
Miami, FL, USA
e-mail: a.eber@med.miami.edu
V. M. Hsu
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine,
Miami, FL, USA
e-mail: Vincent.hsu@med.miami.edu
S. C. Davis (*) · K. Nouri
Department of Dermatology and Cutaneous Surgery,
University of Miami Miller School of Medicine,
Miami, FL, USA
e-mail: sdavis@med.miami.edu; knouri@med.miami.edu
28

468
investigate optimal postoperative regimens so
that we may deliver better outcomes and increase
patient satisfactions.
Since there are more complications with abla-
tive techniques, we will focus the below discus-
sion on ablative postoperative care. In the skin,
lasers function through basic principles of pho-
tothermolysis [1, 2]. Water is the targeted chro-
mophore for conventional ablative lasers. As
water is ubiquitous within tissue, there is usually
ablation of the entire epidermis with subsequent
effects on the dermis. Thermal injury to the der-
mis results in collagen denaration, contraction,
shrinking, and tightening of tissue. Furthermore,
the normal cellular and molecular cascade asso-
ciated with injury and wound healing results [3].
As a result, the treated skin regains some of its
youthful elasticity and firmness.6 Although vari-
ous pulsing techniques and cooling strategies are
aimed at reducing adverse events, all skin reju-
venation procedures carry with them some risk
of side effects, even in the hands of experts [4].
Varying degrees of erythema, pain, swelling and
crust formation are associated with thermal
injury. As with any surgical procedure, infec-
tions are possible, and if they do occur, tend to
do so early in the recovery process. Scarring, and
dyspigmentation can also occur, but more
uncommonly [4].
Available Post-Operative
Treatments
Following laser surgery there are various wound
care options including semi-occlusive, occlu-
sive dressings and/or a number of topical
agents. The use of topical agents only is com-
monly referred to the “open” technique, where
the use of occlusive dressing is considered the
“closed” technique. It has been determined that
keeping wounds moist with an occlusive dress-
ing allows for faster epithelization, greater
growth factor viability, pain alleviation, and
reduced scar formation [5]. As different postop-
erative treatments can affect the quality of heal-
ing, it is important to remember that an ideal
dressing or topical agent for post-surgical care
should stimulate healing, reduce pain, be easy
to apply and provide optimal cosmetic results
[6]. The best way to approach post-operative
care is by evaluating and managing the most
immediate risks given the phase of healing
(Table 28.1).
Care should be taken immediately after com-
pletion of the procedure to minimize the proba-
bility of scar formation and infection. This is
accomplished by using cooling techniques like
cold water or ice, anti-inflammatory medications
like corticosteroids, and antibiotics/antivirals.
After 72 h, gentle moisturizers can be incorpo-
rated into the treatment regimen to enhance
water retention in the healing tissue. This will
also minimize the probability of scar formation.
One week post-surgery, patients can begin using
gentle cleansers to remove crust or necrotic
debris. During the same time period, patients can
begin using hypoallergenic make-up to cover
residual erythema. After the third week of recov-
ery, patients should focus on sun protection and
conditioning masks to hydrate skin. One month
after the procedure, one can begin pigment cor-
rection if necessary while maintaining sun pro-
tection. Scar treatment can begin, should it be
necessary.
Table 28.1  Treatment schedule and indications for post-­
operative recovery
Time
post-operation
Treatment
Indication
0–48 h
Topicals/dressings
Anti-­
inflammatory
Antiseptic
Cooling
Enhance healing
Reduce swelling
Infection
prevention
72 h–1 week
Moisturizers
Antibiotics
Antivirals
Minimize
scarring
Infection
prevention
1–2 weeks
Cleansers
Make-up
Anti-erythema
Remove crusting
Cover and treat
erythema
3–4 weeks
Sunblock
Anti-erythema
Sun protection
Residual
erythema
4+ weeks
Vitamins,
colorants or
bleaching agents
Dyspigmentary
conditions
A. E. Eber et al.

469
Immediate Post-Operative
Treatment (0–48 h)
Ice packs can be applied to a patient to alleviate
the burning sensation that is commonly experi-
enced immediately after completion of the laser
procedure. Petrolatum can be applied to the
treated area within 2  h of completion [7, 8].
Petrolatum provides some relief and a moist
environment conducive to proper healing.
Petrolatum is sometimes replaced by the addition
of an antibiotic ointment. Mupirocin or gentamy-
cin ointment is frequently recommended how-
ever, over-the-counter antibiotics are a common
cause of contact dermatitis and should be avoided
[9]. Corticosteroids can be combined to reduce
inflammation [10]. Dilute vinegar soaks over pet-
rolatum can be used to gently wash the area sev-
eral times daily to prevent infection. Petrolatum
should be reapplied afterward. The soaks should
be gentle enough that debris is not removed for
several days until the skin underneath has healed
[8]. Importantly, in a study by Walia and Alster, a
significantly higher rate of infection occurred in
patients receiving combination intraoperative
and/or postoperative antibiotic prophylaxis. The
most frequently cultured organisms included
Enterobacter and Pseudomonas species [11].
Cautious use of antibiotics is suggested in high-­
risk patients, certain anatomic locations, and in
the presence of infection [12].
Anti-Inflammatory Agents
• Corticoids—Corticosteroids play a major role
in the stress response of the body. They serve
to modulate the immune system and various
inflammatory mechanisms. Corticoids can be
used to suppress the inflammatory response
due to laser injury but should be used with
caution. Although, they have potent anti-­
inflammatory action, some corticoids can
inhibit healing through their interactions with
inflammatory cytokines, which are essential
of adult mammalian healing [13].
• Alpha bisabolol—Alpha bisabolol is a cyclic
monosaturated sesquiterpinic alcohol isolated
from the horse chestnut. The compound is
more of an anti-irritant than an anti-­
inflammatory although it does have some
anti-­inflammatory activity. The agent is
highly vasoactive (constrictive) and reduces
vessel permeability. These activities are
attributed to blockage of 5-lipoxygenase and
cyclooxigenase in the arachadonic acid path-
way [10, 14, 15].
• Enoxolone (glycyrrhetinic acid)—Enoxolone
has been used to reduce inflammation by
ancient civilizations since the third century
B.C.  Evidence of its use has been found in
China, Greece, Rome, and Egypt [16]. It is iso-
lated from licorice root and was first described,
in modern times, as a potent anti-­inflammatory
in 1958 [17]. The compound functions as a
non-steroidal antiinflammatory but at high
doses may induce swelling, redness, and
edema
by
inhibiting
11-hydroxy-­
steroiddehydrogenase [18]. At low concentra-
tions, enoxolone has been shown to interfere
with steroid metabolism in renal tissues, result-
ing in global anti-inflammatory action [19].
In addition to topical agents, various dressing
materials have been used post-operatively for
laser resurfacing. Occlusive dressings can pro-
vide a moist environment, protect the wound
from bacterial invasion and depending on their
composition influence the micro environment
[20, 21]. Furthermore, some dressings may alle-
viate symptoms and reduce erythema [20, 22–
27]. The fear of infection which is often associated
with the use of occlusive dressings has made
many practitioners avoid their use. However,
studies have shown lower infection rates with
wounds which are covered with certain types of
occlusive dressings [28–31]. Laser sites in a por-
cine model covered with different dressing mate-
rials epithelized quicker than untreated control
sites [6]. Therefore, when used properly, dress-
ings can enhance patient discomfort, simplify
postoperative wound care and do not increase the
risk of infection or other complications.
Importantly, optimal postoperative treatment reg-
imens have not been clearly defined and it appears
that the choice of dressing is at the discretion of
28  Dressing/Wound Care for Laser Treatment

470
the practitioner. Below is a list of various dress-
ing materials with a brief description and men-
tion of potential benefits and disadvantages
(Table 28.2).
Early Post-Operative Treatment
(72 h to 1 Week)
During the first week of recovery, remnant epi-
dermal debris may present as darkened skin.
Though essential for optimal healing, the debris
also functions as a readily available nutrient
source for bacteria. Therefore, antibiotic treat-
ment should be continued to prevent infection.
Antibiotics may be combined with moisturizers
to soften the residual epidermal tissue, and pro-
vide a moist environment for healing.
Moisturizers
• Squalene oil (olive oil)—Olive oil high in
squalene content has been used for centuries
to treat burns and wounds, and is thought to
play a role in the reduced rate of various types
of cancers in Mediterranean societies [32]. In
addition to its anti-cancer properties, squalene-­
rich olive oil has been implicated in acceler-
ated wound healing [10]. Squalene is a
triterpene and an intermediate in cholesterol
biosynthesis [33]. Squalene-rich olive oil has
been shown to have antioxidant properties and
protect skin lipids from oxidation induced by
UV radiation.
• Hyaluronic acid—Hyaluronic acid is a natu-
rally occurring component of the skin.
Elevated amounts of hyaluronic acid in the
skin, such as in the developing fetus [34], have
been associated with scarless healing, or
reduced scar formation [35]. The compound’s
unique structure is responsible for its hygro-
scopic, rheological, and elastic properties,
which contribute to the effects it has on the
skin. As a component of the skin’s extracellu-
lar matrix, hyaluronic acid helps maintain
moisture and elasticity [36]. Both characteris-
tics may play essential roles in healing and in
the relief of itching sometimes associated with
laser procedures. Increased elasticity of the
treated skin may enhance results.
• Bovine mucopolysaccharide-cartilage complex
(MCC)—Preparations of MCC have been used
for over 25 years to treat chronic wounds origi-
nating from pressure, trauma, vascular insuffi-
ciency, or venous stasis. MCC has been shown
to reduce inflammation and edema, and
enhance wound healing [37, 38]. Cartilage is
made primarily of collagen that provides a scaf-
fold for chemotactic and cellular factors in
wound healing. This scaffolding enables the
migration and stabilization of granulocytes,
macrophages, and fibroblasts, all of which
serve major roles in cutaneous healing [39]. A
Table 28.2  Dressings available after laser procedures
Dressing
Description/benefits/disadvantages
Example
Transparent
films
Polymer sheets (most common—polyurethane) Easy to observe area through
dressing Does not absorb exudate
Opsite,
Tegaderm, Silon
TSR
Foams
Foamed polymers (most common—polyurethane) Adheres to normal skin,
absorbs exudate Cannot see through dressing material
Flexzan,
Revitaderm
Hydrogel
Hydrophillic polymers (cross linked) Cooling effect for patient’s pain
Enhances healing of burn wounds Not adhesive to normal skin
Second skin,
Vigilon
Polymer mesh
Partially transparent polyethylene or silicon polymers allow the passage of
blood and fluids. Semi-occlusive Can be adhesive or non-adhesive to normal
skin Does not provide optimal moist environment
N-Terface,
Mepitel
Hydrocolloids
Estomeric, adhesive and gelling agents Absorbs exudate well and adheres to
normal skin Cannot see through dressing material
DuoDerm
Alignates
Derived from seaweed—hydrophilic gelAbsorbs exudate, hemostatic Can be
difficult to remove
Kaltostat
A. E. Eber et al.

471
comparison of MCC to standard of care for
Er:YAG treated skin showed a consistent reduc-
tion in the severity of erosion, edema, and
inflammation in the MCC treated skin [40].
• Silicone ointment—Silicone ointment can be
used as a moisturizer for the first week of post-­
operative care. Silicone creates a barrier and
prevents the skin’s exudative process. The
trapped water is reabsorbed into the tissue to
create a moist environment for cellular migra-
tion [10].
Intermediate Post-Operative
Treatment (1–2 Weeks)
The intermediate recovery period is a transitional
time between active healing and modification in
the skin to the remodeling period, which will
result in near-final results. During this period,
infections, or actively healing tissues should be
addressed with more intensive therapies [10]. In
most cases, the current treatment regimen can be
maintained, but should any erythema or edema
remain, it is acceptable to incorporate hypoaller-
genic make-up as cover. These make-up prepara-
tions may include some of the aforementioned
anti-inflammatory agents [41]. Alpha bisabolol is
particularly popular in the cosmetic industry for
its anti-irritant effects [42].
Late Post-Operative Treatment
(3–4 Weeks)
During and after the third week of recovery, the
patient should be encouraged to incorporate pho-
toprotective agents into any ongoing regimen.
Protection from UV rays is highly recommended
as the skin is in a depleted, highly sensitive state
following laser treatment. UV protection serves
as a precautionary measure to avoid abnormal
pigmentation throughout recovery. Because of
the initial ablation of melanocytes, the skin may
not be fully capable of photoprotection, increas-
ing its susceptible to DNA damage. This increased
vulnerability may increase a patient’s risk of skin
cancer as well as inconsistent pigmentation. Sun-­
blocks with moisturizers, and equivalent UV-A
and UV-B protection factors, along with micron-
ized titanium dioxide, avobenzene, methoxycin-
namate, or d-panthenol should be applied.
Ideally, patients should incorporate hats and
sleeved protective clothing under prolonged sun
exposure as most, if not all, sun-blocks offer only
limited overall protection [43].
Post-Recovery Pigment Correction
(>4 Weeks)
One of the least appealing results of laser resur-
facing is irregular pigmentation. Cosmetically
obtrusive, hypo- and hyperpigmentation can
inflict serious psychosocial stress on a patient.
Though most pigmentation abnormalities self-­
resolve, in some cases, adjunct laser therapy or
chemical treatments may be necessary [44].
• Hydroquinone—Hydroquinone is the most
efficient and commonly used pigment correc-
tion agent [24]. It prevents tyrosine action and
interferes with melanosome development [10].
• Wildberry extract and kojic acid—Both prep-
arations contain variants of active forms of
hydroquinone, and due to slightly different
mechanisms of actions, yields different
results. Wildberry extract contains hydroqui-
none glycosides, which is a very powerful yet
extremely stable isoform. Kojic acid contains
a copper kelant, which produces a powerful
hydroquinone-like activity [10].
• Vitamin C—Vitamin C is often to enhance and
complement the effects of depigmentating
agents by stimulating fibroblasts and protect-
ing the skin from photodamage [45].
• Retinoic acid—Retinoic acid is employed as a
bleaching agent to treat post-inflammatory
hyperpigmentation. However, retinoic acid
may cause skin discomfort so it should be
used in combination with anti-irritants [9].
Although the mechanism of action of retinoic
acid is unclear, some studies suggest that it
inhibits
the
detoxification
enzyme
­glutathione-­S-­transferase thereby increasing
melancytotoxicity [46].
28  Dressing/Wound Care for Laser Treatment

472
Scarring
Hypertrophic scarring is a serious, but rare side-­
effect of laser resurfacing. In addition to the bur-
den of cosmetic psychosocial implications,
hypertrophic scars may also inflict significant
physical pain and result in loss of function.
Various factors can contribute to hypertrophic
scarring. Lackluster surgical technique or inap-
propriate laser parameters can erroneously pene-
trate and damage deeper tissue, resulting in
extensive thermal necrosis and scarring. Certain
anatomical locations require more thorough, sen-
sitive post-operative care and milder surgical/
laser techniques to prevent such occurrences. For
example, the mandibular and anterior neck
regions are more susceptible to scarring and
should be treated with caution [47]. Post-­
operative infection, family history, previous
dermabrasion, or isotretinoin treatment may
increase the likelihood of scar formation [47].
• Class I corticosteroids—Corticosteroids regu-
late the body’s inflammatory and immunolog-
ical response. Topical and intralesional
treatment may aid in halting scar progression.
The treatment regimen should begin immedi-
ately upon detection of abnormal erythema
with tissue induration [48].
• Silicone gel—Silicone gels have been success-
ful in the treatment of hypertrophic scars due to
burn injuries. Treatment moderately improved
scar thickness and pigmentation [49].
The precise mechanism of healing remains
unclear though clinical trials have elucidated sili-
cone gels ability to halt the progression of and
soften newly forming scars [50]. Trials on estab-
lished scars have been equally as successful in
reducing firmness and improving elasticity of
1–6 month old scars [51].
• Imiquimod 5% cream—Imiquimod cream is a
topical immune response modulator. It stimu-
lates pro-inflammatory cytokines, particularly
interferon-α, which mediates collagen break-­
down. Although treatments frequently result
in some erythema, local pain, and pinpoint
bleeding, imiquimod results in significant
improvement in scar quality, elevation, and
color [52].
Conclusion
There are few well-controlled studies that elu-
cidate the most optimal treatment regimen
post-­laser therapy. Whether a specific combi-
nation of agents and/or dressings provide the
best environment to allow beneficial cosmetic
effects while reducing potential complica-
tions, remains to be seen. With an increase in
novel laser technological advances, as well as
innovative clinical uses for existing lasers,
additional, well-designed clinical trials dedi-
cated to determining the postoperative care
treatments that yield most beneficial results
are urgently needed.
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© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Prevention and Treatment of Laser
Complications
Rachael L. Moore, Juan-Carlos Martinez,
Ken K. Lee, Yun Ehrlich, Brian Simmons,
and Keyvan Nouri
Abstract
Lasers are useful for treating a variety of der-
matologic conditions but have a number of
potential complications associated with their
use. A basic understanding of laser mechanics
is paramount in preventing and troubleshoot-
ing complications.
Keywords
Dermatologic lasers · Complications ·
Postoperative complications · Complication
Prevention · Postoperative complication
reduction
• Lasers are useful for treating a variety of der-
matologic conditions but have a number of
potential complications associated with their
use.
• A basic understanding of laser mechanics is
paramount in order to prevent and trouble-
shoot complications.
• Wavelength, fluence, pulse duration and spot
size can be varied to achieve the desired effect
on tissue.
• The innovation of coupling surface cooling
with laser treatment has allowed for the use of
increased fluence to maximize treatment
R. L. Moore · J.-C. Martinez · K. K. Lee
Dermatologic and Laser Surgery, Oregon Health and
Sciences University, Portland, OR, USA
Y. Ehrlich · B. Simmons (*)
Department of Dermatology, University of Miami
Miller School of Medicine, Miami, FL, USA
e-mail: bjsimmons@med.miami.edu
K. Nouri
Department of Dermatology, University of Miami
Miller School of Medicine, Miami, FL, USA
Dermatology Services at Sylvester Comprehensive
Cancer Center, University of Miami Hospital and
Clinics, Miami, FL, USA
MOHS, Dermatologic & Laser Surgery,
University of Miami, Miami, FL, USA
Surgical Training, University of Miami,
Miami, FL, USA
Dermatology, University of Miami, Miami, FL, USA
Ophthalmology, University of Miami,
Miami, FL, USA
Otolaryngology, University of Miami,
Miami, FL, USA
Dermatologic Surgery, University of Miami,
Miami, FL, USA
Department of Dermatology and Cutaneous Surgery,
University of Miami Medical Group,
University of Miami, Miami, FL, USA
29

476
­efficacy while minimizing damage to the
overlying epidermis.
• Complications can be avoided by keeping the
operating room safe. This includes the use of
eye protection and smoke evacuators, when
indicated. Operating suites should have well
marked signs and restricted entry. Lasers
should be kept in standby mode when not in
use.
• Only adequately trained physicians should
evaluate patients and determine their candi-
dacy for laser treatment and select treatment
parameters. This will help ensure that lasers
are not being used inadequately to treat poten-
tially hazardous indications such as skin
cancers.
• Patients that give a history of pigmentary dis-
orders, connective tissue diseases or abnormal
scarring are at increased risk of having an
adverse event following laser therapy. Those
on certain medications or with dark or tanned
skin are also at increased risk.
• Pain, erythema and edema, crusting and vesic-
ulation, purpura, dyspigmentation and scar-
ring are side effects caused by treatment with
most dermatologic lasers to varying degrees.
These side effects can be minimized or
avoided entirely when proper precautions are
taken.
• Other side effects are unique to treatment of
specific conditions. For example, tattoo
removal can be associated with allergic con-
tact dermatitis or paradoxical tattoo darken-
ing, while resurfacing procedures pose an
increased risk of infection.
Introduction
Dermatologic laser therapy was initially intro-
duced in the 1960s; however, it was not until the
theory of selective photothermolysis was intro-
duced that their use became widespread. There
are a variety of side effects and complications
associated with laser therapy. Some of these are
unavoidable
but
many
are
preventable.
Understanding laser mechanics and how to vary
wavelength, fluence, pulse duration and spot size
to achieve the desired effect can help minimize or
prevent adverse events. Cooling has allowed for
the use of increased fluence to maximize treat-
ment efficacy by protecting the epidermis from
excess thermal damage.
Since the introduction of lasers into the derma-
tologic field by Dr. Leon Goldman in 1963 [1],
they have become both standard treatment for
many dermatoses and a source of future innova-
tions. While generally considered safe and well
tolerated, their potential to cause adverse events
should not be underestimated. A thorough under-
standing of lasers and their applications is para-
mount in managing predictable side effects and
avoiding complications. This chapter will briefly
outline laser mechanics, provide a detailed descrip-
tion of both common and uncommon complica-
tions, and discuss their prevention and treatment.
Laser Mechanics
The word laser is an acronym for light amplifica-
tion by the stimulated emission of radiation [2].
Laser light is unique in that it is composed of a
single wavelength and all emitted photons are in
the same phase. These properties are termed
monochromatic and coherent, respectively. The
wavelength of light is determined by the optical
medium, which can be a solid (e.g., alexandrite),
liquid (e.g., pulsed dye laser) or gas (e.g., carbon
dioxide laser). When laser light hits the skin, it is
absorbed, reflected, transmitted, or scattered. The
desired treatment effect occurs when the light is
absorbed and the energy is converted to heat
(photothermal), acoustic waves (photomechani-
cal) or used in chemical reactions (photo-chemi-
cal). The majority of dermatologic lasers employ
photothermal reactions.
In 1983, the theory of selective photothermoly-
sis was introduced, revolutionizing the applica-
tion of lasers [3]. This theory posits that because
each chromophore has a unique photo absorption
spectrum, it can be selectively targeted and
destroyed using specific wavelengths. Endogenous
chromophores include melanin, hemoglobin and
water [2]. Tattoo ink is an ­exogenous chromo-
phore frequently targeted with laser therapy.
R. L. Moore et al.

477
A basic understanding of laser physics is
required to troubleshoot complications and diffi-
cult-to-treat patients. By varying wavelength, flu-
ence, pulse duration and spot size, the desired
effect can be achieved (see Table 29.1 for defini-
tions). The wavelength of light used determines
which tissue chromophores will be targeted. The
energy per area emitted by the laser is the flu-
ence. High fluence can result in untoward dam-
age to tissue, while insufficient fluence will lead
to incomplete treatment. The concept of pulse
duration is vital in minimizing damage to the sur-
rounding tissue. The ideal pulse duration is gen-
erally the same [4] or shorter [2] than the thermal
relaxation time (TRT) of the target. Immediately
following photon absorption, the chromophore
loses this newly absorbed energy in the form of
heat. TRT is the time required for a chromophore
to lose 50% of its heat to the surrounding tissue
and is directly proportional to the square of its
diameter. Thus, there is a positive relationship
between pulse duration, TRT and diameter of the
target. Destruction of targets with a small diam-
eter, such as melanosomes, requires small pulse
durations in order to limit damage to surrounding
tissue. Those with a larger diameter, such as
blood vessels, can be treated with longer pulse
durations. For this reason, Quality- or Q-switched
(QS) lasers (see Table  29.1 for definitions) are
often used for pigmented lesions, while pulsed
dye lasers (PDL), with pulse durations in the mil-
lisecond range, are used for vascular lesions.
Spot size and wavelength can each impact the
depth of penetration of the laser. Depth of penetra-
tion is determined by both the amount of light
absorption in the tissue and the scatter [2]. In gen-
eral, larger spot sizes (10–15  mm) and longer
wavelengths (1000–1200  nm) have less scatter
than smaller spot sizes (3–5 mm) and shorter wave-
lengths (300–400 nm) and penetrate deeper into the
tissue. However, when wave-lengths exceed
approximately 1300 nm, such as the CO2 resurfac-
ing laser at 10,600  nm, depth is limited to the
superficial epidermis due to absorption by water,
the primary targeted chromophore in this range.
Cooling
The ideal laser settings will provide enough ther-
mal energy and selectivity to damage the targeted
chromophore while minimizing injury to the sur-
rounding skin [5]. However, the energy required
to damage the target often exceeds that which is
needed to harm the overlying epidermis. In order
to overcome this obstacle, cooling devices have
been implemented. Many laser hand pieces are
now equipped with cryogen spray cooling or sap-
phire contact plates that cool the skin immedi-
ately prior to the laser pulse. The epidermis is
then selectively cooled, raising the threshold for
thermal damage, while temperatures for the
intended (deeper) dermal targets are relatively
unaffected. Pre-cooling with ice-packs, gel and
aluminum rollers can also be used but these are
generally not as effective as the incorporated
cooling devices. In addition to increasing the
treatment efficacy of lasers, cooling also plays a
prominent role in providing anesthesia during
therapy.
Table 29.1  Common laser definitions
Terms
Definition
Unit of
measurement
Fluence
Energy delivered
per unit area
J/cm2
Pulse duration
(pulse length or
pulse width)
The time it takes
a waveform to
reach 50% of its
full amplitude
•  Q-switched
•  Long-pulsed
•  Q-switch is an
optical valve in
a laser that
allows for rapid
energy build-up
before it is
open to allow
light out
10−9–10−12 s
10−3 s
Thermal
relaxation time
(TRT)
Time required for
a target to lose 50
of its heat to the
surrounding
environment TRT
α (directly) to the
target diameter [2]
s
Spot size
The diameter of
the opening
through which
the laser beam is
emitted
cm
29  Prevention and Treatment of Laser Complications

478
General Considerations
Safety in the operating suites, professional errors
and certain patient factors should be initially con-
sidered to help limit adverse events. The operat-
ing suites should have well marked signs and
restricted access, and lasers should be kept in
standby mode when not in use. Use of eye protec-
tion and smoke evacuators should be employed
when indicated. An appropriately trained physi-
cian should evaluate all patients to determine
candidacy prior to laser treatment. This will limit
improper laser treatment of various diseases,
such as skin cancers. The laser parameters should
also be set by the clinician. Patients with a history
of pigmentary disorders, connective tissue dis-
ease or abnormal scarring may be at increased
risk for laser treatment. Additionally, those with
dark or tanned skin or taking certain medications
may suffer from additional side effects.
Laser Devices Malfunction
An additional resource to look at the safety of
lasers devices is the Manufacturer and User
Facility Device Experience (MAUDE) database.
This database covers the U.S.  Food and Drug
Administration (FDA) reported adverse events
and product problems since 1993 with the final
phase in 1996 that includes facility, distributor
and manufacturing reports. For instance, between
2006 and 2011 MAUDE reported the top five
manufacturers device complications due to
device malfunction were Lumenis (204), Candela
(66), Rhytec (65), Cutera (50), and solta (46) [6].
This database is a valuable tool for practitioners
to look at specific lasers and assess the risk of
malfunction on an individual basis based on laser
type and use.
Safety in the Operating Rooms
Lasers are useful medical devices but can be dan-
gerous. The operating staff and patient are suscep-
tible to a number of hazards, including burns,
accidental fires, infection and ocular injury. General
safety measures, such as a visible door sign when
the laser is in use and controlled access into the
laser areas, are important. All lasers should be kept
in standby mode when not in use and have a rapid
deactivation mode to prevent unintentional firing.
To avoid accidental fires, the use of oxygen and
alcohol-based cleansing methods should be mini-
mized. Each laser should have its own outlet, limit-
ing the use of extension cords. Since human
papilloma virus (HPV) [7] and human immunode-
ficiency virus (HIV) [8] particles have been found
in aerosolized material after laser therapy, a smoke
evacuator should be employed when lasers with
significant potential to splatter aerosolized particles
(such as CO2 resurfacing) are used.
Lasers can subject the unprotected eye to sig-
nificant damage, including visual loss. The degree
of ocular damage is determined by the wavelength
of light as well as the amount and duration of
energy exposure [9]. Within the eye, there is a
broad absorption spectrum resulting from three
primary chromophores: melanosomes, found in
the retinal epithelium, iris, sclera and choroid;
hemoglobin, found in retinal vasculature; and
water, found primarily in the cornea and lens. The
symptoms associated with damage to these ocular
structures are summarized in Table 29.2. Especially
important to remember is that absorption of light
outside the visual spectrum is visually undetect-
able. Additionally, due to their lack of sensory
innervation, absorption damage to the retina, iris,
choroid and sclera can be painless. Thus, ocular
exposure to wavelengths in the near infrared range
(700–1400 nm), which is primarily absorbed by
these pigmented eye structures, can lead to pro-
nounced injury without symptoms [9, 10].
To prevent untoward injury, wavelength-spe-
cific eye protection should be worn any time the
laser is in operation. Metal contact lenses should
be placed on the patient when treating periorbital
skin, and metal goggles should be worn for the
treatment of facial lesions. Plastic goggles should
be avoided in these cases due to the risk of melt-
ing. Pediatric and smaller patients should have
size-specific goggles; if these are not available,
the use of a thick layer of white gauze (which
non-specifically absorbs and reflects laser light)
can be used.
R. L. Moore et al.

479
Professional Errors
According to MAUDE database, professional
(user) errors make up 30% of the most common
laser surgery complications. The common errors
include improper laser settings, treatment param-
eters and cleaning laser tips, failure to perform a
skin patch test before procedure, wearing protec-
tive eyewear, replacing old or malfunctioning
components on the laser device, and failure to
follow laser device manufacturer guidelines [11].
An appropriately trained physician should
evaluate all patients prior to laser treatment to
determine whether they will be appropriate can-
didates for therapy. Some patients are at increased
risk of sustaining complications (see Sect. 2.4
below), and these factors should be considered
prior to choosing laser parameters. In some cases
these risk factors may prove to be contraindica-
tions to laser treatment, as the risk of complica-
tions may outweigh the benefits. Verbal and
written informed consent, including an explana-
tion of the potential risks and benefits, alternative
treatment options, number of treatment sessions,
and cost per session should be obtained prior to
the planned procedure which can help avoid the
patient feeling pressured into making a quick
decision [12].
The indication for laser therapy must be
appropriate. While treatment of rhytides may
seem straightforward, treatment of other lesions,
such as those on photo-damaged skin, may pres-
ent more challenges to the non-dermatologist.
Often, only minor differences distinguish a solar
lentigo from a melanoma, or an actinic keratosis
from a nonmelanoma skin cancer. These subtle-
ties may not be obvious to the untrained clinician.
Any lesion in question should be biopsied prior
to treatment.
Furthermore the extant or number of areas to
be treated by lasers needs to be taken into consid-
eration. According to a review of 373 cases, one
body location involvement in CO2 fractionated
laser skin treatment is associated with a relatively
low complication rate, but three concurrent treat-
ments of body locations increases the complica-
tion rate significantly [13].
Troubleshooting complications requires a firm
understanding of laser mechanics. A skilled oper-
ator will not only choose appropriate laser set-
tings, but will be attentive in monitoring the
tissue reaction to the laser treatment. An immedi-
ate white/gray discoloration can indicate signifi-
cant thermal damage requiring modification of
laser settings. Ideally, test spots should be done at
least 2 weeks prior to the planned procedure.
Patient Factors
Patient factors must be taken into account in the
assessment of an individual’s risk profiles. Patients
with dark or tanned skin are at increased risk of
hypopigmentation if treated with lasers that target
melanosomes. Any history of abnormal scarring,
vasculopathy or vitiligo should be elicited, as these
conditions may indicate a propensity toward hyper-
trophic scarring, bruising and dyspigmentation
respectively. Treatment should be avoided in areas
with concurrent infection or inflammation as it can
exacerbate these conditions. Connective tissue dis-
eases, which can be a marker for photosensitivity,
may be a contraindication to laser therapy [14].
One study reported new-onset discoid lupus ery-
Table 29.2  Ocular structures at risk for laser injury [9, 10]
Wavelength
(nm)
Susceptible ocular
structure
Chromophore
Mechanism
Associated symptoms
180–400
Cornea and lens
Tissue
proteins
Photochemical
Pain
400–700
Retina, iris, choroid,
sclera
Melanin
Photochemical
Color flash and afterimage
700–1400
As above
As above
As above
No symptoms until significant
visual loss
1400–10,600
Cornea and lens
Water
As above
Immediate burning pain
29  Prevention and Treatment of Laser Complications

480
thematosus thought to be from thermal injury sus-
tained after argon laser treatment for facial
telangiectases [15]. Debate exists in the literature,
however, as others have successfully treated dis-
coid lupus with similar lasers [16]. Additionally,
there are several medications (summarized in
Table 29.3) that may confer an increased risk of
complications. These should be considered and
avoided if possible [17, 18, 21, 22]. There are no
published reports of adverse effects of laser treat-
ment in patients taking photosensitive medications.
Thus, patients should not be refused for laser treat-
ment solely on the basis of taking a photosensitive
medication [23]. However, patient compliance
with post treatment instructions needs to be taken
into consideration as well. One study showed that
4.5% of post laser treatment complications are due
to patient error, such as failure to use sunscreen or
avoid sun exposure after laser treatment [6].
General Laser Complications
Dermatologic lasers share a number of side
effects that can be minimized or avoided when
proper pre-cautions are taken. Wavelength, flu-
ence, pulse duration, spot size and cooling can all
impact the degree of side effects experienced.
Overlapping pulses and high fluences may help
achieve a desired affect, but can increase the risk
of complications. In general, ablative resurfacing
procedures have an increased incidence of these
complications
compared
with
other
laser
modalities.
Lasers can be used to treat a wide variety of
conditions and each laser has its own unique
properties (see Table 29.4). An innovative xenon–
chloride (excimer) pulsed laser is a form of ultra-
violet laser, which is capable of delivering higher
energy density with lower heat production. It has
been used mainly for psoriasis and vitiligo
­treatment, however FDA has approved for psoria-
sis treatment only [24, 25].
A complication, or adverse event, can be
defined as any undesirable or unforeseen out-
come after a particular treatment. This is to be
distinguished from a side effect, which is
expected after therapy. However, many side
effects, if severe, can lead to complications.
The most common complications, which can
occur with any laser, are pain, erythema and edema,
crusting, vesiculation, purpura, dyspigmentation
and scarring. Identifying the causative factor for
each of these common complications can aide in
Table 29.3  Medications potentially associated with increased risk of laser therapy complications
Medication
Possible associated complications
Recommendations
Blood thinning agents:
•  Aspirin
•  Coumadin
•  Vitamin E
•  Anti-platelet agents
Increased bruising, bleeding
Consider discontinuation if using laser with
high bruising potential (e.g. PDL)
Indomethacin
Increased scarring potential shown
in murine models [17]
Not good evidence for discontinuation, but
may consider if high risk of scarring
Isotretinoin
Hypertrophic scarring reported
after dermabrasion [18]; other
studies have shown no increased
risk [19, 20]
Consider discontinuation 6 months prior,
especially if using lasers with high scarring
potential (e.g., ablative resurfacing) [21];
evidence for this, however, is weak
Drugs that induce
pigmentation:
•  Minocycline
•  Amiodarone
•  Anti-malarials
•  Tricyclic anti-
depressants
(e.g., desipramine,
imipramine)
Dyspigmentation
Consider discontinuation prior to procedure if
there is increased risk of dyspigmentation
(e.g., dark or tanned skin, ablative resurfacing
procedures)
Gold (parenteral)
Localized chrysiasis after QS laser
treatment [22]
Consider avoiding treatment in patient with
history of parenteral gold therapy
R. L. Moore et al.

481
their prevention and treatment. It is important to
ask the following:
• Am I treating the correct indication and
patient with the correct laser?
• Was the fluence appropriate?
• Was the pulse duration appropriate?
• Was the correct spot size used?
• Was the cooling appropriate?
• Was there too much pulse overlap or stacking
of passes?
The purpose of this section will be to review
each of these common side effects and discuss
their prevention and management.
Pain
Risk Factors for Excess Pain
• Inadequate anesthesia
• High fluence
• Insufficient cooling
Although certain lasers are associated with
more pain than others, some level of mild pain is
an expected side effect of most laser therapy.
Unexpected or excessive pain, however, can occur
with inadequate anesthesia or inappropriate laser
settings (excess fluence or insufficient cooling).
Prevention and Treatment
It is imperative to appropriately anesthetize
patients, as needed, prior to their procedure.
Some lasers (e.g., the PDL) often do not require
pre-treatment anesthesia, while use of other
lasers (e.g., resurfacing lasers) require significant
pain control. Anesthetics can be injected subcuta-
neously to provide local relief, whereas regional
nerve blocks can provide anesthesia over a larger
area. For those patients unable to tolerate the pain
from injection of local anesthetic, pre-cooling
with aluminum rollers or ice packs for several
minutes or application of topical anesthetic com-
pounds 1 hour prior to needle insertion can mini-
mize their discomfort. Pretreatment with Er:YAG
pulses followed by topical lidocaine may mini-
mize needle insertion pain even further [26].
Anesthesia may also be achieved with only
topical treatment. A randomized, placebo con-
trolled trial with 30 patients found topical
­lidocaine/tetracaine (S-Caine) peels successful in
adequately relieving pain associated with tattoo
removal [27]. In addition, an FDA-approved lido-
caine/tetracaine
topical
anesthetic
cream
(Pliaglis®) was shown to be safe and effective
when used with common laser therapies such as
ablative and nonablative laser resurfacing, laser
hair removal, laser treatment of vascular lesions,
and laser tattoo removal [28]. A set protocol with
hot compresses, topical lidocaine and oral anxio-
lytics (vicodin, diazepam or ketorolac) provided
adequate pain relief in 190 of 200 patients who
underwent CO2 resurfacing in a recent case series
[29]. The disadvantage of using topical treat-
ments, however, is the additional time required
for the anesthetic to take effect.
Cooling devices have played a large role in
minimizing pain and optimizing treatment of
specific lesions. Decreased pain was associated
with concomitant cooling in both the treatment of
port-wine stains with the PDL [30] and pigmented
Table 29.4  Commonly used lasers listed by indication
Vascular lesions
Pigmented lesions
Tattoo removal
Photoepilation
Resurfacing
PDL
(585–600 nm)
QS Ruby (694 nm)
QS Ruby (694 nm)
LP Ruby (694 nm)
Carbon dioxide
(10,600 nm)
LP Nd:YAG
(1064 nm)
QS Nd:YAG (532,
1064 nm)
QS Nd:YAG (532,
1064 nm)
LP Nd:YAG
(1064 nm)
Er:YAG (2490 nm)
LP KTP (532 nm)
QS Alexandrite
(755 nm)
QS Alexandrite
(755 nm)
LP Alexandrite
(755 nm)
Fractional (1540 nm)
IPL
IPL
LP Diode (800 nm)
Xenon-Chloride
(Excimer)
IPL
Er:YAG erbium:yttrium aluminum garnet, IPL intense pulsed light, KTP potassium titanyl phosphate, Nd:YAG
neodymium:yttrium aluminum garnet, PDL pulsed dye laser, QS Q-switched, LP long-pulsed
29  Prevention and Treatment of Laser Complications

482
lesions with the QS Alexandrite [31]. Pre-cooling
(e.g., with aluminum rollers or ice packs) may
also significantly reduce pain [32].
Erythema and Edema
Risk Factors for Excess Erythema
and Edema
• Pulse stacking, multiple passes
• High energy settings
• Location (periocular > other areas)
• Patient factors (fair skin > dark skin; history of
acne rosacea)
• Use of topical tretinoin prior to procedure
• Inadequate post-treatment cooling
Erythema and edema are expected side effects
of most laser therapies. Although these are usu-
ally transient, they can persist for months. A ret-
rospective study of 500 patients who underwent
CO2 laser resurfacing found that all patients
experienced post-operative erythema lasting an
average of 4.5 months [33]. Prolonged erythema
and edema occurs in preventable situations.
Excess pulse stacking or passes [34], treatment of
periocular areas, and use of high energy settings
can all lead to prolonged erythema and edema.
Additionally, patients with fair skin or a history
of acne rosacea may be predisposed to intense
erythema. Use of irritating medications, such as
topical tretinoin, may also worsen erythema [35].
Prevention and Treatment
If possible, unnecessary risks should be avoided.
However, treatment efficacy is often maximized
with pulse stacking and use of high-energy set-
tings. Ensuring the patient is aware of these risks
and that their expectations are appropriate cannot
be overemphasized. Management of erythema
and edema is supportive: application of post-
treatment cold packs, head elevation and sun pre-
cautions
are
important.
Topical
or
oral
corticosteroids can be used in severe cases.
Topical ascorbic acid may be effective in decreas-
ing the post-operative severity and duration of
erythema after ablative resurfacing procedures
[36]. Furthermore, a 635  nm-wavelength Light
emitting diode (LED) device has been shown to
reduce the duration and intensity of erythema
after fractional CO2 laser treatment [37]. In addi-
tion, IPL devices and PDL have been considered
useful to reduce the resistant erythema after laser
CO2 resurfacing [38].
Crusting and Vesiculation
Risk Factors for Excess Crusting
and Vesiculation
• High fluence
• Insufficient cooling
• Small spot size
• Short wavelengths
Crusting and vesiculation are manifestations
of epidermal damage that generally results from
excess thermal injury. This is commonly due to
high
fluence
and/or
insufficient
cooling.
Additionally, treatment with small spot sizes and
shorter wavelengths imparts a higher risk of epi-
dermal damage due to shallower depth of pene-
tration. It is important to keep in mind. However,
some superficial crusting is an expected side
effect for many lasers.
Prevention and Treatment
Treatment is supportive. Keeping wounds moist
with petrolatum may help speed the recovery
process and minimize the risk of scarring. Use of
over-the-counter antibiotic ointments should be
avoided as neomycin and bacitracin are some of
the most common causes of allergic contact der-
matitis [39] and bacitracin has shown no wound
healing benefit over white petrolatum [40].
Petrolatum has also shown better epithelial con-
fluence and general wound appearance scores
with less crusting, erythema and edema, com-
pared to Arnebia euchroma ointments (AEO)
[41]. Variations on petrolatum-based ointments
exist that have smaller amounts of petrolatum
and can offer patients alternatives to oilier high
percent petrolatum products, while offering
effective and faster improvements in wound heal-
ing compared to antibiotic-containing treatments,
such as Neosporin and Polysporin [42]. Sun pre-
R. L. Moore et al.

483
cautions are recommended. Patients should be
instructed not to unroof blisters, if they form.
Symptomatic bullae can be lanced in a sterile
fashion.
Purpura
Risk Factors for Excess Purpura
• High fluence
• Long wavelengths
• Treatment with pulsed dye lasers (purpura
mode)
Purpura results when there is damage to small
vessels and subsequent extravasation of red blood
cells. It is common following treatment with the
PDL and is, in fact, a therapeutic endpoint when
treating certain vascular lesions with short pulse
durations and high fluences (so-called purpura-
mode). Nevertheless, unexpected bruising can
occur with use of other lasers if the fluence is set
too high. Lasers with long wavelengths penetrate
deeper and have a greater risk of damaging der-
mal blood vessels. Cooling, which primarily pro-
tects the epidermis, has little impact on the
amount of damage to dermal blood vessels.
Prevention and Treatment
If possible, all patients should be off anti-coagu-
lant and anti-platelet agents at least several days
prior to the planned procedure. Discontinuing a
medication, even if transiently, should always be
discussed with the patient’s prescribing physician
first.
Lowering fluence and increasing pulse dura-
tion (in the PDL) can help minimize purpura.
Because many vascular lesions, such as port wine
stains and hemangiomas, cannot be effectively
treated with non-purpuric parameters, patients
should be aware of the potential down-time post-
treatment. This is particularly important for peo-
ple with high cosmetic demands. In one study,
45% of patients with purpura after treatment of
their port-wine stain reported significant restric-
tion in activity, primarily due to the bruising [43].
It has been suggested that the use of topical
Vitamin K will help both prevent and minimize
post-treatment bruising. A small randomized
controlled study found decreased bruising sever-
ity with twice-daily application of vitamin K
cream for 2 weeks following laser treatment with
the PDL [44]. However, the same study found
that pre-treatment with vitamin K cream for
2 weeks did not seem to alter the bruising. An
Alternative herbal remedy of 20% Arnica
(Arnica montana) has shown been shown more
effective than 1% vitamin K with 0.3% retinol
[45]. However, the efficacy of Arnica in concen-
trations less than 10% is not supported by cur-
rent studies [46].
Dyspigmentation
Risk Factors for Dyspigmentation
• High fluence
• Inadequate cooling
• Patients factors (dark, tanned > fair skin)
• Short wavelength
• Small spot size
Dyspigmentation can be transient or perma-
nent and takes on two forms: hyper- or hypopig-
mentation. Hyperpigmentation is a common
manifestation of post-inflammatory change in the
tissue. Following resurfacing procedures, it is
seen in one-third of all patients and nearly all of
those with Fitzpatrick type IV–VI skin [35]. It
generally appears 3–4  weeks post-operatively
and spontaneously resolves over the next several
months, though permanent hyperpigmentation
can occur.
Hypopigmentation occurs when lasers inad-
vertently target melanin (Figs. 29.1 and 29.2).
QS lasers and IPL often cause a transient
hypopigmentation during treatment due to the
absorption of light by melanin and subsequent
injury to individual melanosomes (Fig.  29.1).
Following resurfacing procedures, “relative
hypopigmentation” can be seen where treated
areas lie adjacent to untreated, photodamaged
(darker) skin [35]. However, if the fluence is
too high or cooling is inadequate, thermal
injury can extend beyond the melanosome and
damage melanocytes and other tissue struc-
29  Prevention and Treatment of Laser Complications

484
tures, causing permanent hypopigmentation.
Rarely,
permanent
hypopigmentation
can
appear 6–12  months after resurfacing proce-
dures (“delayed hypopigmentation”) due to
thermal injury.
In general, patients with dark or tanned skin
have a greater risk of dyspigmentation (Fig. 29.2).
For such patients, treatment with lasers with shal-
lower depths of penetration (i.e., shorter wave-
lengths and smaller spot sizes) confers greater
injury to epidermal melanocytes and should be
avoided.
Prevention and Treatment
Patients should be aware of dyspigmentation
risks and have appropriate expectations. For
those with darker skin types, lasers with longer
wavelengths and larger spot sizes should be con-
sidered, as the depth of penetration will be greater
and risk of injury to epidermal melanocytes
smaller [47]. If these options are not available,
treatment with lower fluences is prudent.
Caution should be used when treating patients
who are tan. To prevent sun exposure to planned
treatment areas, patients should be advised to
keep tattoos or other sites covered, if possible, for
1  month prior to the procedure [47]. For areas
such as the face, sun avoidance and regular use of
sun-screen with an SPF > 30 should be advocated
prior to laser treatment. This is particularly
important for resurfacing procedures where there
is a high risk of dyspigmentation [35].
Pre-treatment of dark skin with alpha-hydroxy
acids or bleaching agents combined with a topi-
cal steroid may help reduce epidermal pigment
and therefore prevent hypopigmentation due to
laser therapy [47]. Additionally, many of these
topical agents may cause minor inflammation
that can hasten removal of dermal (tattoo)
pigment.
For ablative resurfacing procedures, some
authors advocate pre- and postoperative use of
topical bleaching agents, tretinoin cream and
­steroid compounds to help minimize post-inflam-
matory hyperpigmentation [48]. However, a pro-
spective study of 100 patients undergoing CO2
laser resurfacing found no significant difference
in the incidence of post-inflammatory hyperpig-
mentation between patients pre-treated 2 weeks
with glycolic acid cream or combination treti-
noin/hydroquinone creams versus no pretreat-
ment [49]. In a 23 patient prospective study using
1064  nm Q-switched Nd:YAG laser with Hori
nevus, there was no significant difference in the
incidence of post-inflammatory hyperpigmenta-
tion when using fucidic acid cream vs. betameth-
asone with fucidic acid [50]. The regiment of
topical vitamin C, hydroquinone, retinoic acid,
and sunscreen pre- and post-operative was effec-
tive in treating patients with post-inflammatory
hyperpigmentation [51]. Ablative fractional pho-
Fig. 29.2  Hypopigmentation and scar formation after
IPL treatment. Treatment took place when the patient was
tan, potentially leading to this complication
Fig. 29.1  Reticulated hypopigmentation after IPL treat-
ment. This likely resulted from actinic bronzing that
caused increased absorption of light. This is transient;
with subsequent treatments the dyspigmentation will
even out
R. L. Moore et al.

485
tothermolysis (AFP) and nonablative fractional
photothermolysis (NAFP) that introduce a micro-
scopic, pixilated pattern of wounding in the der-
mis have been found potentially effective in the
treatment of a variety of pigmentation conditions,
including post-inflammatory hyperpigmentation,
and laser-induced hypo- and hyperpigmentation
of the face and neck [52].
Use of petrolatum and strict sun avoidance can
hasten epidermal healing and help minimize post
inflammatory dyspigmentation; however, correc-
tion of dyspigmentation, once it occurs, can be
difficult. Bleaching creams, superficial chemical
peels, kojic and retinoic acid may help blend
lines of demarcation. These products should be
avoided, however, in the first post-operative
month after resurfacing procedures, as they can
cause profound irritation and worsen hyperpig-
mentation. For hypopigmentation, use of topical
PUVA (oxsoralen and UVA light therapy) has
been used to induce melanogenesis [35].
Scarring
Risk Factors for Excess Scarring
• High fluence
• Inadequate cooling
• Pulse stacking, multiple passes
• Wrong laser
• Patient factors (history of isotretinoin, keloid
formation or radiation therapy)
• Location (mandible, anterior neck, infraor-
bital > other areas)
• Poor post-operative wound care regimen (for
resurfacing procedures)
• Infection
Scarring is a rare but potentially severe side
effect of laser therapy. The terminology in the lit-
erature can be confusing. For some, textural
change describes a transient phenomenon where
there is a change in the contour of the skin, truly
differentiating it from a permanent scar [53].
However, others use textural change to describe a
subtle, but potentially severe, reticular pattern of
scarring. Because of this lack of consensus in ter-
minology, many early articles underreported the
incidence of scarring, listing the complication
instead as textural change. It is the authors’ opin-
ion that the term textural change should be
reserved for non-scarring processes only.
The most likely cause of scar formation fol-
lowing laser treatment is excessive thermal injury
to the treated tissue. Pulse stacking or multiple
passes [54], high-energy fluences or inadequate
cooling can all precipitate thermal injury. Dermal
depressions can be caused by vessel dissolution
or thermal injury. Inadequate contact cooling
(e.g., over the alar groove) or high fluences can
lead to this finding. Selection of an appropriate
laser and use of the correct treatment parameters,
for a given indication, is paramount in avoiding
excessive tissue damage and scarring. Patients
with a history of recent isotretinoin therapy,
keloid scar formation or radiation therapy may be
at increased risk for hypertrophic scar formation
following
resurfacing
procedures
[18].
Additionally, postoperative resurfacing compli-
cations, such as infection and contact dermatitis,
may also lead to scarring.
Treatment of certain anatomical locations,
including the mandible, anterior neck and infra-
orbital areas are more likely to scar [33]. Reduced
laser parameters are recommended in these areas.
Prevention and Treatment
A skilled clinician will monitor the skin for evi-
dence of excessive thermal injury both during
and after laser treatment. Marked erythema or
graying of the epidermis during treatment may
indicate significant damage and the need to dis-
continue treatment or adjust parameters. Multiple
test spots with varying fluences and/or pulse
durations can be performed prior to treatment,
particularly in patients with an increased risk of
scarring. These can often be performed at the
time of initial consultation.
After resurfacing procedures, focal areas of ery-
thema and induration often precede the formation
of hypertrophic scars [35]. These areas should be
cultured and the patient treated, if infection is sus-
pected. If infection is ruled out, prompt application
or intralesional injection of corticosteroids can halt
the progression of hypertrophic scars. Silicone gel
sheeting or topical imiquimod may also be useful
29  Prevention and Treatment of Laser Complications

486
in preventing and/or treating hypertrophic scar for-
mation [55]. Silicone gel or a silicone sheet is the
most recognized first line method for the treatment
and prevention of hypertrophic scars. Based on
specific indications, other methods include cryo-
therapy, pressure garments, corticosteroid injec-
tions, onion extract gel, and bleomycin [50, 56].
Two to ten cryotherapy sessions with 25 days
interval maybe used to diminish keloids by caus-
ing tissue necrosis and sloughing. Cryotherapy
with intralesional steroid injections can lead to an
84% reduction in keloids. Hypopigmentation
could be a side effect due to the sensitivity of
melanocytes to cold temperatures. In cases of
extensive scarring one could consider surgical
graft or flap repair [57].
Intralesional steroids, 5-fluorouracil (5-FU)
and laser therapy have proved beneficial in the
treatment of hypertrophic scars [58–60]. PDL
treatment has been reported to improve the symp-
toms, pliability and color and decrease the size of
hypertrophic scars [58, 60, 61]. A recent single-
blinded study with 69 patients compared treat-
ment of hypertrophic scars with intralesional
triamcinolone (TAC) alone or in combination
with intralesional 5-FU or intralesional 5-FU and
PDL therapy [59]. Combination therapy with
TAC and 5-FU, both with and without PDL ther-
apy, provided statistically significant improve-
ment in the overall erythema, pruritus, pliability
and size of the scars compared with TAC alone.
Patients reported the most improvement with the
triple TAC, 5-FU and PDL therapy, however.
Depressed scars may improve over a period of
several months [53]. Ablative or non-ablative
resurfacing procedures and dermal fillers can be
used to correct the contour defects depending on
their severity.
Idiosyncratic Complications
There are a number of complications unique to
treating specific lesions. Perhaps the best known
example of this is during removal of tattoos.
Upon laser treatment, tattoo pigment is released
extracellularly, exposing it to immunologic cells
and oxidizing radicals, and can lead to allergic
contact dermatitis or paradoxical darkening.
Resurfacing procedures not only pose a risk of
profound scarring (albeit rarely), but the loss of
the epidermal barrier also makes one more sus-
ceptible to infection, acne and milia formation.
Treatment of vascular and pigmented lesions and
photoepilation are also associated with unique,
though uncommon, side effects.
There are a handful of complications that are
unique to treating specific dermatologic condi-
tions with certain lasers. These complications
and their management will be discussed in the
following section.
Photoepilation
Hypertrichosis
Several studies have documented paradoxical
hypertrichosis following laser hair removal [61,
62]. This primarily occurs after several treat-
ments have been performed on the face and neck
of female patients with darker skin types. The
mechanism that triggers the conversion of these
vellus to terminal hairs is unknown, but may be
related to inflammation induced by the laser
therapy itself. Management of this uncommon
complication is with further photoepilation.
Leukotrichia
Photoepilation is most commonly performed
with the long-pulsed Ruby, Alexandrite and
Diode lasers. Patients with darker skin tones
may be treated with the long-pulsed Nd:YAG
lasers. These lasers target melanin and penetrate
deep enough to reach the hair follicle. By using
millisecond instead of nanosecond pulse dura-
tions, thermal damage extends beyond the mela-
nocytes to involve other structures within the
follicle important for hair growth [63]. This
leads to the desired destruction of the targeted
follicle. With sub-therapeutic fluence levels, fol-
licular melanocytes may be destroyed in the
absence of other follicular injury, resulting in
leukotrichosis.
R. L. Moore et al.

487
Reticulate Erythema
Persistent reticulate erythema has been described
in at least ten patients following hair removal
with the Diode laser [64]. Pernio, and perhaps
other connective tissue diseases, as well as high-
energy fluences seem to be potential risk factors.
Most patients are female.
Urticarial-Like Plaques
Pruritic, urticarial-like plaques have been described
following photoepilation [14]. Unlike urticaria,
however, lesions may last several days to weeks.
Topical and oral corticos-teroids and anti-hista-
mines can be used for symptomatic relief.
Pigmented Lesions
Leukotrichia
Melanin, located in the epidermis, dermis and
follicular structures, is the primary chromophore
targeted in the treatment of various pigmented
lesions. Melanocytes within the hair follicle can
be destroyed inadvertently when using high flu-
ences and more deeply penetrating, longer, wave-
lengths. Permanent leukotrichia can result.
Limiting the fluences and selecting lasers with
shorter wavelengths, if possible, will minimize
this complication.
Studies show the Er:YAG laser and micro-
dermabrasion could introduce moderate to
marked pigmentation by inducing the chemical
mediator secretion to activate melanocytes,
enhance narrow band UVB penetration and 5-flu-
rouracial ointment absorption [65]. In a 31
patients study, leukotrichia was improved by
using a non-cultured epidermal suspension trans-
plantation, taking methylcobalamin, and daily
sun exposure after dressing removal [66].
Tissue Splatter and Pinpoint Bleeding
Tissue splatter and pinpoint bleeding are expected
side effects of treatment with Q-switched lasers.
When tissue targets are heated to destructive lev-
els over nanosecond (QS) pulse durations, parti-
cles can become aerosolized creating tissue
splatter and blood vessels can rupture leading to
pinpoint bleeding and petechiae. Predictably, this
is worsened with the use of high fluences.
Fluences should therefore be kept to a minimum
to maintain the desired effect. Smoke evacuators
should be used when expecting tissue splatter as
viral particles have been found in aerosolized
material [7, 8]. Laser treatment through a water-
based gel dressing, such as Vigilon (CR Bard,
Inc, Covington, GA) or 2nd Skin (Spenco Medical
Corp, Waco, TX) minimizes tissue splatter and
bleeding by acting as a heat sink and protecting
the epidermis [47].
Resurfacing
Acne and Milia
Acne flares and milia formation are relatively
common complications that result from use of
occlusive dressings and petrolatum. Aberrant fol-
licular re-epithelialization may also play a role in
their development [35]. Those with a history of
acne are at increased risk.
Generally, eruptions tend to resolve on their
own once occlusive ointments and dressings are
removed. For those with more severe, recalcitrant
acne flares, oral tetracyclines can be used. Once
the skin has re-epithelialized, topical retinoids or
manual extraction can be used to treat milia.
Contact Dermatitis
Contact dermatitis is a frequent complication,
occurring up to 65% of the time, and is generally
irritant in nature [35]. Loss of the epidermal bar-
rier lends susceptibility to irritants and allergens.
Bland, non-fragranced emollients should be used
preventively. Patients should be counseled to
avoid use of topical antibiotics, the most fre-
quently cited allergens, and other over-the-coun-
ter products and herbal remedies. If an irritant or
allergic contact dermatitis occurs, all suspected
inciting agents should be promptly discontinued.
This alone may result in resolution of the derma-
titis. Topical corticos-teroids, cold compresses
and oral anti-histamines are additional measures
that can be taken to alleviate symptoms. Oral
prednisone is reserved for severe cases.
29  Prevention and Treatment of Laser Complications

488
Ectropion
Ectropion is another potential serious complica-
tion of ablative resurfacing procedures. Those
patients with a history of lower blepharoplasties
and other eyelid surgeries are at increased risk
[35]. Pre-operatively, a “snap” test should be per-
formed to assess the elasticity of the eyelid, and
patients with low elasticity should be treated with
caution. Use of lower fluences and reduced pass
number are important around periocular areas.
Intraoperatively, the dermatologic surgeon should
observe excess collagen contraction that may
indicate lid eversion. Treatment of ectropion,
should it occur, is surgical.
Infection
Any laser treatment that disrupts the epidermal
barrier carries a potential risk for infection.
However, due to the extent of such wounding
associated with ablative resurfacing procedures,
the risk of viral, bacterial and fungal infections
following these procedures is significantly higher.
Reactivation of herpes simplex virus (HSV) is
the most common infection, observed in 7% of
500 patients in a retrospective analysis, regard-
less of prior HSV history [33]. The infection may
not have the typical defining characteristic of
grouped vesicles and crusts on an erythematous
base due to the lack of intact epithelium. Any ero-
sions, often subtle, should warrant further work
up. Prophylactic antiviral medications are com-
monly initiated 1–2 days prior to the procedure
and continued for 7–14 days afterwards, or until
re-epithelialization is complete [35, 67]. Hospital
admission for initiation of intravenous antiviral
medication is indicated for the rare, but serious,
disseminated viral infection.
Bacterial (e.g., Staphylococcus aureus and
Pseudomonas sp.) and fungal (e.g., Candida sp.)
infections are less common but equally serious
complications. Significant scarring [11] and pru-
ritus [68] have been associated with such infec-
tions. Use of occlusive dressings is thought to
increase the risk of these infections, which gener-
ally occur within the first 10 days after laser treat-
ment [69]. The moist, warm environment
provides an ideal growing medium for many
opportunistic pathogens. Occlusive dressings,
such as biobrane, are often used in the first post-
operative days to help minimize pain and poten-
tially speed the healing process.
Good wound care instructions are essential.
Hands should be washed with an antibacterial
soap prior to all dressing changes. Dressings
should be changed multiple times a day, and can
be soaked in dilute acetic acid; they should not be
re-used.
Significant debate exists among dermatologic
surgeons regarding use of prophylactic antibiot-
ics for ablative resurfacing procedures. To date,
there have been no prospective, randomized con-
trolled studies done to evaluate their efficacy.
Some studies have suggested that use of intraop-
erative and postoperative antibiotics may increase
infection rates and potentially select for more
pathogenic bacteria, such as Enterobacter sp.
[70] Fluconazole may promote re-epithelialization
when given post-operatively between days 3 and
8 [71].
Signs and symptoms of acute infections
include increased pain, erythema, erosions, puru-
lent discharge, and delayed wound healing. If an
infection is suspected, wound cultures should be
taken and the patient placed on a broad-spectrum
antibiotic until the sensitivities return.
Tissue Splatter
During ablative resurfacing procedures, the epi-
dermal barrier is destroyed and tissue particles
commonly become aerosolized. (See above Sect.
4.2 for more detail.) As with QS lasers, it is
important to use smoke evacuators, or a water
based gel dressing to avoid inhaling potentially
harmful viruses that may be harbored in the air-
borne tissue.
Tattoos
Allergic and Photoallergic Contact
Dermatitis
During laser treatment of tattoos, pigment is
released from intra- to extracellular sites expos-
ing these antigens to the immune system. Rarely,
a type-IV hypersensitivity reaction or photoaller-
gic reaction to the components in the pigment can
R. L. Moore et al.

489
develop [72]. Cinnabar, found in red tattoo pig-
ment, is the most common contact allergen, [73]
while cadmium, which is found in yellow tattoo
pigment, is the most frequent photoallergen [47].
Those who have a contact dermatitis to pigment
often give a history of pruritus and raised red
areas over their tattoo sites. In photodermatitis,
this reaction is heightened when exposed to
sunlight.
Laser removal of tattoos in those with a pig-
ment allergy has successfully been demonstrated
with the concomitant use of intralesional or topi-
cal corticosteroids [74, 75]. However, because a
local allergy can progress to a potentially life-
threatening anaphylactic response, one should
exercise extreme caution in treating these patients
[47]. Some may consider a tattoo pigment allergy
an absolute contraindication to laser treatment
because of this risk. Ablative resurfacing proce-
dures can be used for tattoo removal with less
risk of mounting an allergic response. However, a
localized allergic reaction has been reported to
become generalized following CO2 laser removal
of a tattoo in one patient [76].
Combustion
Treatment of tattoos that contain combustible
material should be avoided. Sparks and incipient
pox-like scars occurred after QS Ruby laser treat-
ment of a traumatic tattoo containing firework
debris [77]. If the composition of the pigment is
unknown, a biopsy and/or test spot should be per-
formed to help elucidate the material [47].
Paradoxical Tattoo Darkening
Paradoxical darkening of certain tattoo pigments
has been reported with QS laser treatments [78–
80]. The exact mechanism is unknown, but the
reduction of ferric oxide to ferrous oxide may
play a role [78]. Titanium dioxide may also be
implicated in paradoxical darkening through a
similar mechanism [9, 80]. Ferrous oxide is
found in some red, orange, peach or other skin-
colored pigments and titanium dioxide is found
in white pigments, often used alone or in con-
junction with other colors to brighten them. As
such, specific areas of tattoos containing these
colors should undergo spot testing prior to full
treatment with a QS laser. Once paradoxical
darkening has occurred, correction can be diffi-
cult. Repeated laser treatments have been suc-
cessful [81], as well as ablative resurfacing
procedures [82].
Tissue Splatter and Pinpoint Bleeding
See explanation in above Sect. 4.2.
Vascular Lesions
Reticulated Purpura
Purpura is a common, and usually expect side
effect of the PDL. Often a reticulated pattern of
purpura develops after treatment due to the
Gaussian distribution of energy of each laser
pulse. Overlapping pulses by 18% can minimize
this complication [83].
Conclusions
Complications in dermatologic laser therapy
can often be prevented by employing safety
precautions and having a thorough knowledge
of laser mechanics and patient risk profiles
prior to treatment. Once complications do
occur, it is important to ascertain the cause in
order to prevent, or minimize, future prob-
lems. The most common complications can
generally be avoided or minimized by care-
fully selecting patients, managing their expec-
tations, using proper anesthetics when
indicated, and by meticulously selecting
appropriate laser settings.
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R. L. Moore et al.

493
© Springer International Publishing AG, part of Springer Nature 2018
K. Nouri (ed.), Lasers in Dermatology and Medicine,
Ethical Issues
Abel Torres, Tejas Desai, Alpesh Desai,
William T. Kirby, and Maren C. Locke
Abstract
Ethical behavior transcends legal implica-
tions, and represents the level of professional-
ism, humanity and morality a physician should
possess in order to address his/her patient’s
care. If a physician upholds his/her ethical
responsibility to a higher standard than a legal
obligation, the patient’s best interests may be
addressed. The Hippocratic Oath may not
address specific ethical problems unique to the
utility of lasers, therefore many professional
associations have devised tenets to follow. The
simple acronym, “E-T-H-I-C-A-L” may help
guide a physician to uphold the highest ethical
standard when performing a laser procedure.
Financial gain may entice a physician to not
optimize care for a patient. It is ethical for a
physician to remain honest about their experi-
ence and training. Full disclosure of pertinent
information to the patient may be sensible so
he/she may remain the autonomous decision-­
maker without physician biases.
Keywords
Ethics · Lasers · Ethical · Economics
Training · Heart to heart discussion between
physician and patient · Interests · Contraindi­
cations · Advertising and Libel versus letting
authorities know of misconduct
In general, ethics can be considered the science
of moral duty, of ideal human character, and of
the ideal ends of human action [1]. Ethics is
closely tied to morals, and it can be said that eth-
ics is the science of morals, and morals are the
practice of ethics [1]. The legal standard of care
is usually the minimum required, while ethics
usually pertains to a higher standard. If a physi-
cian upholds his/her ethical responsibility to a
higher standard than a legal obligation, the
patient’s best interests may be addressed. It is a
physician’s ethical commitment to the patient,
himself/herself and the profession of medicine
that may guide a successful laser procedure.
Laser treatments in dermatology may create
an ethical dilemma for physicians since some
procedures are elective. Clinical endpoints for
laser therapy can be difficult to objectively quan-
tify, and patient satisfaction often becomes the
A. Torres (*)
Department of Dermatology, Loma Linda University
School of Medicine, Loma linda, CA, USA
e-mail: atorres3@metrohealth.org
T. Desai · A. Desai
Heights Dermatology and Aesthetic Center,
Houston, TX, USA
W. T. Kirby
Kirby Dermatology, Hermosa Beach, CA, USA
M. C. Locke
Department of Dermatology, MetroHealth System,
Cleveland, OH, USA
30

494
cornerstone of treatment efficacy. Furthermore,
cosmetic patients may have unrealistic expecta-
tions, and instilled in the public, is a media-driven
mentality that lasers are generally safe devices
without complications.
The continued, heightened controversy in
recent years is the result of one looming question:
is aging a physical illness [1, 2]? Whether the
aging face needs rejuvenation may spark dead-
end debates even among colleagues in dermatol-
ogy [2, 3]. The Hippocratic Oath may not address
specific problems unique to the utility of lasers,
therefore many professional associations includ-
ing the American Medical Association (AMA),
American Society of Dermatologic Surgery
(ASDS), American Academy of Dermatology
(AAD), American Osteopathic College of
Dermatology (AOCD), and American Society of
Laser Medicine and Surgery (ASLMS) have
established tenets in terms of patients’ best inter-
ests, professionalism, and personal conduct.
These guidelines serve to establish standards for
non-medically necessary care in an ever-chang-
ing, cosmetic world. In addition, physicians’
ethical responsibilities sometimes differ from
their legal ones [4]. They are not solely limited to
clinical practice, but also include the moral treat-
ment of human subjects in laser medicine and
surgery research. Multiple issues may be encoun-
tered between a practitioner’s moral duty and the
patient’s best interests. A simple acronym,
“ETHICAL” (Economics, Training, Heart to
Heart Discussion Between Physician and Patient,
Interests, Contraindications, Advertising and
Libel versus Letting Authorities Know of
Misconduct) can serve as a guide to help remind
physicians of their ethical responsibilities to
patients.
Economics
Financial gain may entice a physician to not opti-
mize care for a patient. It is wise and ethical for
the physician to uphold the dignity of the patient,
and not exploit or abuse the relationship for
financial matters. Gifts, kickbacks and other
financial gain received in exchange for operating
one laser brand over another may be considered
unethical without the consent of the patient. The
definition of equipment tampering is any safety
bypass allowing the unauthorized reuse of the
product [5]. Replacing approved equipment with
equipment that is not approved for use may result
in negative outcomes for the patient. Furthermore,
the resale of lasers to non-physicians is not advo-
cated and may be subject to penalties under the
labeling requirements of the Food Drug and
Cosmetic Act [5]. This action may contribute to
non-medical workers operating lasers on patients
without the proper training. Moreover, economic
bias may sometimes be difficult for physicians to
preclude, when they may feel obligated to
endorse a product because they receive monies
for company lectures and/or research.
Training
It is ethical for a physician to remain honest about
their experience and training. A recent survey
conducted by the ASDS showed that nearly 41%
of responding dermasurgeons reported an
increase in patients seeking treatment due to
injury caused by untrained, non-physicians per-
forming laser and light rejuvenation techniques
[5]. To further support this finding, an analysis of
litigation related to laser surgery shows an
increase in cases involving non-physician opera-
tors from 36.3% in 2008 to 77.8% in 2011 [6]. A
majority of the litigated procedures in lasers
involve laser hair removal. Despite the fact that
physicians perform two-thirds of these proce-
dures, non-physician operators represent 85.7%
of hair removal lawsuits. Of these lawsuits, 64%
were performed outside a traditional medical set-
ting [6]. Therefore, it is prudent to disclose to a
patient when medical personnel and extenders
will be part of the treatment and their level of
training, since some clinics have nurses or physi-
cian assistants operating lasers or light devices.
Depending on the state, non-medical person-
nel may perform treatments which often requires
that a physician is on site should a complication
or issue arise. As a general rule, non-physicians
must have appropriate documented training in the
A. Torres et al.

495
physics, safety, and surgical techniques for each
procedure performed [5]. Formal procedural der-
matology training can assist in demonstrating
competency in selected laser procedures, includ-
ing their proper use and management of compli-
cations. The ASLMS recommends physician
extenders complete a basic training program
devoted to the principles of lasers, their instru-
mentation and safety issues [7]. A minimum
8–10  h is suggested by the American National
Standards Institute (ANSI) standards with 40%
of the time allocated to practical sessions [7]. It is
also recommended that such medical personnel
spend time in a clinical setting or preceptorship
[7]. It is encouraged for the novice to first per-
form procedures with the supervision by the
expert if state law permits independent practice
[7]. The issue of laser training is becoming a seri-
ous problem in some states because there may be
no legal requirements for training, no quality
control measures, no official quality standards or
guidelines [8]. Even if there is no legal standard,
ethically physicians should address these issues.
One study showed that dermatologists as opposed
to non-medical, laser operators were more likely
to support clinical regulations that placed licensed
physicians in control, supporting this ethical obli-
gation [9].
Heart to Heart Discussion Between
Physician and Patient
Full disclosure of pertinent information to the
patient may be essential so he/she may remain
the autonomous decision- maker without physi-
cian biases. This helps promote a lasting relation-
ship, build patient trust and most of all, serves the
patient to the fullest. Cosmetic dermatology
using medical lasers provides patients with the
anticipation of positive appearance, body image
and good emotional health. This may elicit
patient sensitivity and vulnerability and places
physicians in an influential role. This physician-­
patient relationship is the central focus of all ethi-
cal
concerns
[10].
This
relationship
is
unintentionally not equal because a physician has
the knowledge of medicine and the patient does
not [1]. If physicians only accommodate patients’
wishes, then patients are left to dictate the physi-
cian’s behavior, causing the patient to become an
object of a business transaction [8]. Hence, an
ethical strain may be placed on the physician–
patient relationship. The physician has the
responsibility to put the emphasis back on the
patient as the beneficiary of their liaison, counsel
the patient and when appropriate refer the patient
accordingly.
Interests
Conflicts of interest affect human behavior,
sometimes unconsciously [11]. They may cause a
physician to not utilize an optimal laser treatment
for a patient. Unreported interests may not only
be financially unethical but also may promote
biased research and conclusions based on false
pretenses. Relationships that permit or encourage
product promotion using the names of academic
medical centers and departments may be ethi-
cally unsound and are best subjected to careful
ethical review when contemplated [12]. This may
not only sacrifice the dignity of patients, but also
the physician and his/her moral standard.
Disclosure of conflicts of interest becomes more
of an issue when clinical research is involved.
The role of an institutional board review (IRB) is
to evaluate both the risk-benefit ratio of the pro-
posed study and the appropriateness of consent
that is obtained from the voluntary research sub-
jects [13]. An IRB should have little difficulty
determining the appropriateness of dermatologi-
cal surgical research consent [13]. However,
judging the suitability of a cosmetic dermatologic
study may be perplexing at times. Moreover,
many currently available lasers receive nonspe-
cific skin FDA clearance. One study by Perkins
et al. demonstrated many physicians do not men-
tion evidence of ethics review from an IRB. Out
of 150 prospective studies submitted to the
Journal of American Academy of Dermatology
(JAAD), a whopping 36% had no mention, and
when asked to resubmit IRB approval, 22% were
withdrawn, 12% were never resubmitted, and
12% responded that ethical review was not
30  Ethical Issues