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Dermatology Research and Practice
Volume 2010, Article ID 893080, 13 pages
doi:10.1155/2010/893080
Review Article
Acne Scars: Pathogenesis, Classification and Treatment
Gabriella Fabbrocini, M. C. Annunziata, V. D’Arco, V. De Vita, G. Lodi,
M. C. Mauriello, F. Pastore, and G. Monfrecola
Division of Clinical Dermatology, Department of Systematic Pathology, University of Naples Federico II,
Via Sergio Pansini 5, 80133 Napoli, Italy
Correspondence should be addressed to Gabriella Fabbrocini, gafabbro@unina.it
Received 17 March 2010; Revised 7 September 2010; Accepted 28 September 2010
Academic Editor: Daniel Berg
Copyright © 2010 Gabriella Fabbrocini et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly
cited.
Acne has a prevalence of over 90% among adolescents and persists into adulthood in approximately 12%–14% of cases with
psychological and social implications. Possible outcomes of the inflammatory acne lesions are acne scars which, although they can
be treated in a number of ways, may have a negative psychological impact on social life and relationships. The main types of acne
scars are atrophic and hypertrophic scars. The pathogenesis of acne scarring is still not fully understood, but several hypotheses
have been proposed. There are numerous treatments: chemical peels, dermabrasion/microdermabrasion, laser treatment, punch
techniques, dermal grafting, needling and combined therapies for atrophic scars: silicone gels, intralesional steroid therapy,
cryotherapy, and surgery for hypertrophic and keloidal lesions. This paper summarizes acne scar pathogenesis, classification and
treatment options.
1. Introduction
Acne has a prevalence of over 90% among adolescents [1]
and persists into adulthood in approximately 12%–14%
of cases with psychological and social implications of high
gravity [2,3].
All body areas with high concentrations of pilosebaceous
glands are involved, but in particular the face, back and chest.
Inflammatory acne lesions can result in permanent scars,
the severity of which may depend on delays in treating acne
patients. The prevalence and severity of acne scarring in the
population has not been well studied, although the available
literature is usually correlated to the severity of acne [4].
2133 volunteers aged 18 to 70 from the general population
showed that nearly 1% of people had acne scars, although
only 1 in 7 of these were considered to have “disfiguring
scars” [5]. Severe scarring caused by acne is associated with
substantial physical and psychological distress, particularly in
adolescents.
2. Pathogenesis
The pathogenesis of acne is currently attributed to multiple
factors, such as increased sebum production, alteration of
the quality of sebum lipids, androgen activity, proliferation
of Propionibacterium acnes (P. acnes) within the follicle and
follicular hyperkeratinization [6]. Increased sebum excretion
contributes to the development of acne. Neutral and polar
lipids produced by sebaceous glands serve a variety of roles in
signal transduction and are involved in biological pathways
[7]. Additionally, fatty acids act as ligands of nuclear
receptors such as PPARs. Sebaceous gland lipids exhibit
direct pro- and anti-inflammatory properties, whereas the
induction of 5-lipoxygenase and cyclooxygenase-2 pathways
in sebocytes leads to the production of proinflammatory
lipids [8]. Furthermore, hormones like androgens control
sebaceous gland size and sebum secretion. In cell culture,
androgens only promote sebocyte proliferation, whereas
PPAR ligands are required for the induction of differentiation
and lipogenic activity [9]. On the other hand, keratinocytes
and sebocytes may be activated by P. acnes via TLR, CD14,
and CD1 molecules [10]. Pilosebaceous follicles in acne
lesions are surrounded by macrophages expressing TLR2
on their surface. TLR2 activation leads to a triggering of
the transcription nuclear factor and thus the production of
cytokines/chemokines, phenomena observed in acne lesions.
Furthermore, P. acnes induces IL-8 and IL-12 release from
TLR2 positive monocytes [11].
2Dermatology Research and Practice
All these events stimulate the infrainfundibular inflam-
matory process, follicular rupture, and perifollicular abscess
formation, which stimulate the wound healing process.
Injury to the skin initiates a cascade of wound healing events.
Wound healing is one of the most complex biological process
and involves soluble chemical mediators, extracellular matrix
components, parenchymal resident cells as keratinocytes,
fibroblasts, endothelial cells, nerve cells, and infiltrating
blood cells like lymphocytes, monocytes, and neutrophils,
collectively known as immunoinflammatory cells. Scars
originate in the site of tissue injury and may be atrophic or
hypertrophic. The wound healing process progresses through
3 stages: (1) inflammation, (2) granulation tissue formation,
and (3) matrix remodeling [12,13].
(1) Inflammation. Blanching occurs secondary to vaso-
constriction for hemostasis. After the blood flow
has been stopped, vasodilatation and resultant ery-
thema replace vasoconstriction. Melanogenesis may
also be stimulated. This step plays an important
role in the development of postacne erythema
and hyperpigmentation. A variety of blood cells,
including granulocytes, macrophages, neutrophils
lymphocytes, fibroblasts, and platelets, are activated
and release inflammatory mediators, which ready
the site for granulation tissue formation [14]. By
examining biopsy specimens of acne lesions from the
back of patients with severe scars and without scars,
Holland et al. found that the inflammatory reaction
at the pilosebaceous gland was stronger and had a
longer duration in patients with scars versus those
without; in addition, the inflammatory reaction was
slower in those with scars versus patients who did
not develop scars. They showed a strong relationship
between severity and duration of inflammation and
the development of scarring, suggesting that treating
early inflammation in acne lesions may be the best
approach to prevent acne scarring [15].
(2) Granulation Tissue Formation. Damaged tissues are
repaired and new capillaries are formed. Neu-
trophils are replaced by monocytes that change
into macrophages and release several growth factors
including platelet-derived growth factor, fibroblast
growth factor, and transforming growth factors αand
β, which stimulate the migration and proliferation
of fibroblasts [16]. New production of collagen by
fibroblasts begins approximately 3 to 5 days after the
wound is created. Early on, the new skin composition
is dominated by type III collagen, with a small
percentage (20%) of type I collagen. However, the
balance of collagen types shifts in mature scars
to be similar to that of unwounded skin, with
approximately 80% of type I collagen [17].
(3) Matrix Remodelling. Fibroblasts and keratinocytes
produce enzymes including those that determine the
architecture of the extracellular matrix metallopro-
teinases (MMPs) and tissue inhibitors of MMPs.
MMPs are extracellular matrix (ECM) degrading
enzymes that interact and form a lytic cascade
Acne scars subtypes
Icepick Rolling Boxcar Skin
surface
SMAS
Figure 1: Acne scars subtypes.
Figure 2: Icepick scars.
for ECM remodeling [18]. As a consequence, an
imbalance in the ratio of MMPs to tissue inhibitors
of MMPs results in the development of atrophic
or hypertrophic scars. Inadequate response results
in diminished deposition of collagen factors and
formation of an atrophic scar while, if the healing
response is too exuberant, a raised nodule of fibrotic
tissue forms hypertrophic scars [19].
3. Morphology, Histology, and Classification
Scarring can occur as a result of damage to the skin during
the healing of active acne. There are two basic types of scar
depending on whether there is a net loss or gain of collagen
(atrophic and hypertrophic scars). Eighty to ninety percent
of people with acne scars have scars associated with a loss of
collagen (atrophic scars) compared to a minority who show
hypertrophic scars and keloids.
3.1. Atrophic Scars. Atrophic acne scars are more common
than keloids and hypertrophic scars with a ratio 3 : 1. They
have been subclassified into ice pick, boxcar, and rolling scars
(Figure 1 and Tabl e 1). With atrophic scars, the ice pick type
represents 60%–70% of total scars, the boxcar 20%–30%,
and rolling scars 15%–25% [20].
Icepick: narrow (2mm), punctiform, and deep scars are
known as icepick scars. With this type of scar, the opening
is typically wider than the deeper infundibulum (forming a
“V” shape) (Figure 2).
Dermatology Research and Practice 3
Tab le 1: Acne scar morphological classification (adapted from [20]).
Acne Scars Subtype Clinical Features
Icepick Icepick scars are narrow (<2 mm), deep, sharply marginated epithelial tracts that extend vertically
to the deep dermis or subcutaneous tissue.
Rolling
Rolling scars occur from dermal tethering of otherwise relatively normal-appearing skin and are
usually wider than 4 to 5 mm. Abnormal fibrous anchoring of the dermis to the subcutis leads to
superficial shadowing and a rolling or undulating appearance to the overlying skin.
Boxcar
Shallow
<3 mm diameter
>3 mm diameter
Boxcar scars are round to oval depressions with sharply demarcated vertical edges, similar to
varicella scars. They are clinically wider at the surface than icepick scars and do not taper to a
point at the base.
Deep
<3 mm diameter
>3 mm diameter
They may be shallow (0.1–0.5 mm) or deep (≥0.5 mm) and are most often 1.5 to 4.0 mm in
diameter.
Figure 3: Boxcar scars.
Rolling: dermal tethering of the dermis to the subcutis
characterizes rolling scars, which are usually wider than 4 to
5 mm. These scars give a rolling or undulating appearance to
the skin (“M” shape). Boxcar: round or oval scars with well-
established vertical edges are known as boxcar scars. These
scars tend to be wider at the surface than an icepick scar
and do not have the tapering V shape. Instead, they can be
visualized as a “U” shape with a wide base. Boxcar scars can
be shallow or deep (Figure 3).
Sometimes the 3 different types of atrophic scars can
be observed in the same patients and it can be very
difficult to differentiate between them. For this reason
several classifications and scales have been proposed by other
authors. Goodman and Baron proposed a qualitative scale
and then presented a quantitative scale [21,22]. Dreno et
al. introduced the ECCA scale (Echelle d’Evaluation Clinique
des Cicatrices d’Acn´
e) [23].
The qualitative scarring grading system proposed by
Goodman and Baron [9] is simple and universally applicable.
According to this classification, four different grades can be
used to identify an acne scar, as shown in Table 2 .Often
(especially in those affected with mild acne) the pattern and
grading is easy to achieve but, in the observation of severe
cases, different patterns are simultaneously present and may
be difficult to differentiate. The standard approach adopted
by Goodman and Baron describes a grading pattern and
they developed a quantitative global acne scarring assessment
tool [22] based on the type of scar and the number of
scars. This system assigns fewer points to macular and mild
atrophic scores than to moderate and severe atrophic scores
(macular or mildly atrophic: 1 point; moderately atrophic: 2
points; punched out or linear-troughed severe scars: 3 points;
hyperplastic papular scars: 4 points). The multiplication
factor for these lesion types is based on the numerical range
whereby, for one to ten scars, the multiplier is 1; for 11–20 it
is2;formorethan20itis3.
The ECCA (Echelle d’Evaluation clinique des Cicatrices
d’acn´
e) for facial acne scarring is also a quantitative scale,
designed for use in clinical practice with the aim of
standardizing discussion on scar treatment and it is based
on the sum of individual types of scars and their numerical
extent. Scar types considered to be more visibly disfiguring
were weighted more heavily. Specific scar types and their
associated weighting factors were the following: atrophic
scars with diameter less than 2 mm: 15; U-shaped atrophic
scars with a diameter of 2–4 mm: 20; M-shaped atrophic
scars with diameter greater than 4 mm: 25; superficial elastol-
ysis: 30; hypertrophic scars with a less than 2-year duration:
40; hypertrophic scars of greater than 2-year duration: 50.
A semiquantitative assessment of the number of each of
these scar types was then determined with a four-point scale,
in which 0 indicates no scars, 1 indicates less than five
scars, 2 indicates between five and 20 scars, and 3 indicates
more than 20 scars. With this method, the relative extent of
scarring for each scar type was calculated. The total score
can vary from 0 to 540. In recent studies on the reliability
of this scale, seven dermatologists underwent a 30-min
training session prior to the evaluation of ten acne patients.
There was no statistical difference in score grading between
participating dermatologists. The global scores, however,
varied from a minimum of 15 to a maximum of 145.
Unfortunately, a statistical estimate of reliability within and
between raters was not provided. The potential advantages
of this system include independent accounting of specific
scar types, thereby providing for separate atrophic and
hypertrophic subscores in addition to total scores. Potential
shortcomings include restriction to facial involvement, time
intensity, and undetermined clinical relevance of score ranges
[21].
4Dermatology Research and Practice
Tab le 2: Qualitative scarring grading system (adapted from [21]).
Grades of Post
Acne Scarring Level of disease Clinical features
1Macular
These scars can be erythematous, hyper- or hypopigmented flat marks.
They do not represent a problem of contour like other scar grades but of
color.
2 Mild
Mild atrophy or hypertrophy scars that may not be obvious at social
distances of 50 cm or greater and may be covered adequately by makeup or
the normal shadow of shaved beard hair in men or normal body hair if
extrafacial.
3Moderate
Moderate atrophic or hypertrophic scarring that is obvious at social
distances of 50 cm or greater and is not covered easily by makeup or the
normal shadow of shaved beard hair in men or body hair if extrafacial, but
is still able to be flattened by manual stretching of the skin (if atrophic).
4Severe
Severe atrophic or hypertrophic scarring that is evident at social distances
greater than 50 cm and is not covered easily by makeup or the normal
shadow of shaved beard hair in men or body hair if extrafacial and is not
able to be flattened by manual stretching of the skin.
3.2. Hypertrophic and Keloidal Scars. Hypertrophic and
keloidal scars are associated with excess collagen deposi-
tion and decreased collagenase activity. Hypertrophic scars
are typically pink, raised, and firm, with thick hyalinized
collagen bundles that remain within the borders of the
original site of injury. The histology of hypertrophic scars
is similar to that of other dermal scars. In contrast, keloids
form as reddish-purple papules and nodules that proliferate
beyond the borders of the original wound; histologically,
they are characterized by thick bundles of hyalinized acellular
collagen arranged in whorls. Hypertrophic and keloidal scars
are more common in darker-skinned individuals and occur
predominantly on the trunk.
4. Treatment
New acquisitions by the literature have showed that preven-
tion is the main step in avoiding the appearance of post-acne
scars. Genetic factors and the capacity to respond to trauma
are the main factors influencing scar formation [24]. A
number of treatments are available to reduce the appearance
of scars. First, it is important to reduce as far as possible the
duration and intensity of the inflammation, thus stressing
the importance of the acne treatment. The use of topical
retinoids is useful in the prevention of acne scars but more
than any other measure, the use of silicone gel has a proven
efficacy in the prevention of scars, especially for hypertrophic
scars and keloids.
4.1. Atrophic Scars
4.1.1. Chemical Peels. By chemical peeling we mean the
process of applying chemicals to the skin to destroy the outer
damaged layers and accelerate the repair process [25].
Chemical peeling is used for the reversal of signs of skin
agingandforthetreatmentofskinlesionsaswellasscars,
particularly acne scars. Dyschromias, wrinkles, and acne
scars are the major clinical indications for facial chemical
peeling [26,27].
As regards acne scars, the best results are achieved in
macular scars. Icepick and rolling scars cannot disappear
completely and need sequential peelings together with home-
care treatment with topical retinoids and alpha hydroxy acids
[28,29]. The level of improvement expected is extremely
variable in different diseases and patients. For example, ice
pick acne scars in a patient with hyperkeratotic skin are only
mildly improved even if skin texture is remodeled. On the
other hand, a patient with isolated box scars can obtain a
significant improvement by application of TCA at 50%–90%
on the single scars.
Several hydroxy acids can be used.
(A) Glycolic Acid. Glycolic acid is an alpha-hydroxy acid,
soluble in alcohol, derived from fruit and milk sugars. Gly-
colic acid acts by thinning the stratum corneum, promoting
epidermolysis and dispersing basal layer melanin. It increases
dermal hyaluronic acid and collagen gene expression by
increasing secretion of IL-6 [30]. The procedure is well tol-
erated and patient compliance is excellent, but glycolic acid
peels are contraindicated in contact dermatitis, pregnancy,
and in patients with glycolate hypersensitivity. Side effects,
such as temporary hyperpigmentation or irritation, are not
very significant [31]. Some studies showed that the level of
skin damage with glycolic acid peel increases in a dose- and
time-dependent manner. The acid at the higher concentra-
tion (70%) created more tissue damage than the acid at the
lower concentration (50%) compared to solutions with free
acid. An increase in the transmembrane permeability coeffi-
cient is observed with a decrease in pH, providing a possible
explanation for the effectiveness of glycolic acid in skin treat-
ment [32]. The best results achieved for acne scars regard five
sequential sessions of 70% glycolic acid every 2 weeks.
(B) Jessner’s Solution. Formulated by Dr. Max Jessner, this
combination of salicylic acid, resorcinol, and lactic acid
Dermatology Research and Practice 5
in 95% ethanol is an excellent superficial peeling agent.
Resorcinol is structurally and chemically similar to phenol. It
disrupts the weak hydrogen bonds of keratin and enhances-
penetration of other agents [33]. Lactic acid is an alpha
hydroxy acid which causes corneocyte detachment and
subsequent desquamation of the stratum corneum [34].
As with other superficial peeling agents, Jessner’s peels
are well tolerated. General contraindications include active
inflammation, dermatitis or infection of the area to be
treated, isotretinoin therapy within 6 months of peeling
and delayed or abnormal wound healing. Allergic contact
dermatitis and systemic allergic reactions to resorcinol are
rare and need to be considered as absolute contraindications
[35,36].
(C) Pyruvic Acid. Pyruvic acid is an alpha-ketoacid and
an effective peeling agent [37]. It presents keratolytic,
antimicrobial and sebostatic properties as well as the ability
to stimulate new collagen production and the formation of
elastic fibers [38]. The use of 40%–70% pyruvic acid has
been proposed for the treatment of moderate acne scars
[39,40]. Side effects include desquamation, crusting in areas
of thinner skin, intense stinging, and a burning sensation
during treatment. Pyruvic acid has stinging and irritating
vapors for the upper respiratory mucosa, and it is advisable
to ensure adequate ventilation during application.
(D) Salicylic Acid. Salicylic acid is one of the best peeling
agents for the treatment of acne scars [41]. It is a beta hydroxy
acid agent which removes intercellular lipids that are cova-
lently linked to the cornified envelope surrounding cornified
epithelioid cells. The most efficacious concentration for acne
scars is 30% in multiple sessions, 3–5 times, every 3-4 weeks
[42–44]. The side effects of salicylic acid peeling are mild and
transient. These include erythema and dryness. Persistent
postinflammatory hyperpigmentation or scarring are very
rare and for this reason it is used to treat dark skin [45].
Rapid breathing, tinnitus, hearing loss, dizziness, abdominal
cramps, and central nervous system symptoms characterize
salicylism or salicylic acid toxicity. This has been observed
with 20% salicylic acid applied to 50% of the body surface
[46]. Grimes has peeled more than 1,000 patients with the
current 20 and 30% marketed ethanol formulations and has
observed no cases of salicylism [47].
(E)TrichloroaceticAcid.The use of trichloroacetic acid
(TCA) as a peeling agent was first described by P.G. Unna, a
German dermatologist, in 1882. TCA application to the skin
causes protein denaturation, the so-called keratocoagulation,
resulting in a readily observed white frost [48]. For the
purposes of chemical peeling, it is mixed with 100 mL
of distilled water to create the desired concentration. The
degree of tissue penetration and injury by a TCA solution
is dependent on several factors, including percentage of
TCA used, anatomic site, and skin preparation. Selection
of appropriate TCA-concentrated solutions is critical when
performing a peel. TCA in a percentage of 10%–20% results
in a very light superficial peel with no penetration below the
stratum granulosum; a concentration of 25%–35% produces
a light superficial peel with diffusion encompassing the full
thickness of the epidermis; 40%–50% can produce injury to
the papillary dermis; and finally, greater than 50% results
in injury extending to the reticular dermis. Unfortunately
the use of TCA concentrations above 35% TCA can produce
unpredictable results such as scarring. Consequently, the
medium depth chemical peel should only be obtained with
the combination of 35% TCA. The use of TCA in con-
centrations greater than 35%, should be avoided. It can be
preferred in some cases of isolated lesions or for treatment of
isolated icepick scars (TCA CROSS) [49]. When performed
properly, peeling with TCA can be one of the most satisfying
procedures in acne scar treatment but it is not indicated
for dark skin because of the high risk of hyperpigmentation
[50].
(F) TCA Cross. In our experience the TCA CROSS technique
has shown high efficacy in the case of few isolated scars
on healthy skin. CROSS stands for chemical reconstruction
of skin scars method and involves local serial application
of high concentration TCA to skin scars with wooden
applicators sized via a number 10 blade to a dull point to
approximate the shape of the scar. No local anesthesia or
sedation is needed to perform this technique [51]. Unlike
the reports found in the literature, in which 90% TCA is
suggested, our experiences have shown that a lower TCA
concentration (50%) has similar results and much less
adverse reactions [52]. TCA is applied for a few seconds
until the scar displays a white frosting. Emollients then needs
to be prescribed for the following 7 days and high photo-
protection is required. The procedure should be repeated at
4-week intervals, and each patient receives a total of three
treatments. Our experiences have shown that, compared
with other procedures, this technique can avoid scarring
and reduce the risk of hypopigmentation by sparing the
adjacent normal skin and adnexal structures [53] (Figures 4
and 5).
4.1.2. Dermabrasion/Microdermabrasion. Dermabrasion
and microdermabrasion are facial resurfacing techniques
that mechanically ablate damaged skin in order to promote
reepithelialisation. Although the act of physical abrasion of
the skin is common to both procedures, dermabrasion, and
microdermabrasion employ different instruments with a
different technical execution [54]. Dermabrasion completely
removes the epidermis and penetrates to the level of the
papillary or reticular dermis, inducing remodeling of the
skin’s structural proteins. Microdermabrasion, a more
superficial variation of dermabrasion, only removes the
outer layer of the epidermis, accelerating the natural process
of exfoliation [55,56]. Both techniques are particularly
effective in the treatment of scars and produce clinically
significant improvements in skin appearance. Dermabrasion
is performed under local or general anaesthesia. A motorized
hand piece rotates a wire brush or a diamond fraise. Several
decadesago,thehandpiecewasmadeofaluminumoxideor
sodium bicarbonate crystals, whereas now diamond tips have
replaced these hand pieces to increase accuracy and decrease
irritation. There is often a small pinpoint bleeding of the raw
6Dermatology Research and Practice
Figure 4: TCA Cross: patient before the treatment.
Figure 5: TCA Cross: patient after the treatment.
wound that subsides with appropriate wound care. Patients
with darker skin may experience permanent skin discol-
oration or blotchiness. As regards the technique of microder-
mabrasion, a variety of microdermabraders are available. All
microdermabraders include a pump that generates a stream
of aluminum oxide or salt crystals with a hand piece and
vacuum to remove the crystals and exfoliate the skin [57].
Unlike dermabrasion, microdermabrasion can be repeated
at short intervals, is painless, does not require anesthesia
and is associated with less severe and rare complications,
but it also has a lesser effect and does not treat deep scars
[58,59].
It is essential to conduct a thorough investigation of the
patient’s pharmacological history to ensure that the patient
has not taken isotretinoin in the previous 6–12 months.
As noted by some studies [60], the use of tretinoin causes
delayed reepithelialization and development of hypertrophic
scars.
4.1.3. Laser Treatment. All patients with box-car scars
(superficial or deep) or rolling scars are candidates for laser
treatment. Different types of laser, including the nonablative
and ablative lasers are very useful in treating acne scars.
Ablative lasers achieve removal of the damaged scar tissue
through melting, evaporation, or vaporization. Carbon
dioxide laser and Erbium YAG laser are the most commonly
used ablative lasers for the treatment of acne scars. These
abrade the surface and also help tighten the collagen fibers
beneath. Nonablative lasers do not remove the tissue, but
stimulate new collagen formation and cause tightening of
the skin resulting in the scar being raised to the surface.
Among the nonablative lasers the most commonly used are
the NdYAG and Diode lasers [61].
The ablative lasers are technologies with a high selectivity
for water. Therefore, their action takes place mainly on the
surface but the depth of action is certainly to be correlated to
the intensity of the emitted energy and the diameter of the
spot used. Among the ablative lasers, Erbium technologies
are so selective for water that their action is almost exclusively
ablative. CO2lasers, which present lower selectivity for water,
besides causing ablation are also capable of determining
a denaturation in the tissues surrounding the ablation
and a thermal stimulus not coagulated for dermal protein.
CO2lasers have a double effect: they promote the wound
healing process and arouse an amplified production of
myofibroblasts and matrix proteins such as hyaluronic acid
[62].
Clinical and histopathologic studies have previously
demonstrated the efficacy of CO2laser resurfacing in the
improvement of facial atrophic acne scars, with a 50%–
80% improvement typically seen. The differences in results
reported with apparently similar laser techniques may be
due to variations in the types of scar treated. Candidates
must present a skin disease with acne offfor at least 1 year;
they should have stopped taking oral isotretinoin for at least
1 year; they should not have presented skin infections by
herpes virus during the six months prior to treatment; they
must not have a history of keloids or hypertrophic scarring.
Patients with a high skin type phototype are exposed to
a higher risk of hyperpigmentation after treatment than
patients with low phototype.
All ablative lasers showed high risk of complications
and side effects. Adverse reactions to the first generation of
ablative lasers can be classified into short-term (bacterial,
herpetic or fungal infections) and long-term (persistent ery-
thema, hyperpigmentation, scarring) [63,64]. In particular,
scarring after CO2laser therapy may be due to the over
treatment of the areas (including excessive energy, density,
or both), lack of technical aspects, infection, or idiopathic. It
is necessary to take into account these aspects when sensitive
areas such as the eyelids, upper neck, and especially the lower
neck and chest are treated [65,66].
Nonablative skin remodeling systems have become
increasingly popular for the treatment of facial rhytides
and acne scars because they decrease the risk of side
effects and the need for postoperative care. Nonablative
technology using long-pulse infrared (1.450 nm diode, 1320
and 1064 nm neodymium-doped yttrium aluminum garnet
(Nd:YAG), and 1540 nm erbium glass) was developed as
a safe alternative to ablative technology for inducing a
controlled thermal injury to the dermis, with subsequent
neocollagenesis and remodeling of scarred skin [67–72].
Although improvement was noted with these nonablative
lasers, the results obtained were not as impressive as the
results from those using laser resurfacing [71].
For this reason, a new concept in skin laser therapy,
called fractional photothermolysis, has been designed to
Dermatology Research and Practice 7
create microscopic thermal wounds to achieve homogeneous
thermal damage at a particular depth within the skin,
a method that differsfromchemicalpeelingandlaser
resurfacing. Prior studies using fractional photothermolysis
have demonstrated its effectiveness in the treatment of acne
scars [73] with particular attention for dark skin to avoid
postinflammatory hyperpigmentation [74].
Newer modalities using the principles of fractional
photothermolysisdevices(FP)tocreatepatternsoftiny
microscopic wounds surrounded by undamaged tissues are
new devices that are preferred for these treatments. These
devices produce more modest results in many cases than
traditional carbon dioxide lasers but have few side effects
and short recovery periods [75]. Many fractional lasers
are available with different types of source. A great deal
of experience with nonablative 1550 nm erbium doped
fractional photothermolysis has shown that the system can
be widely used for clinical purposes.
An ablative 30 W CO2laser device uses ablative fractional
resurfacing (AFR) and combines CO2ablation with an FP
system. By depositing a pixilated pattern of microscopic
ablative wounds surrounded by healthy tissue in a manner
similar to that of FP [76], AFR combines the increased
efficacy of ablative techniques with the safety and reduced
downtime associated with FP.
Topographic analysis performed by some authors has
shown that the depth of acneiform scars has quantifiable
objective improvement ranging from 43% to 80% with
a mean level of 66.8% [77]. The different experiences
of numerous authors in this field have shown that, by
combining ablative technology with FP, AFR treatments con-
stitute a safe and effective treatment modality for acneiform
scarring. Compared to conventional ablative CO2devices
the side effects profile is greatly improved and, as with
FP, rapid reepithelization from surrounding undamaged
tissue is believed to be responsible for the comparatively
rapid recovery and reduced downtime noted with AFR
[78–80].
Pigmentation abnormalities following laser treatment is
always a concern. Alster and West reported 36% incidence
of hyperpigmentation when using conventional CO2resur-
facing compared to a minority of patients treated with AFR
treatments, probably linked to shortened period of recovery
and posttreatment erythema [81]. The treatment strategy
is linked to establishing the optimal energy, the interval
between sessions, and a longer follow-up period to optimize
treatment parameters.
4.1.4. Punch Techniques. Atrophic scarring is the more
common type of scarring encountered after acne. Autologous
and nonautologous tissue augmentation, and the use of
punch replacement techniques has added more precision and
efficacy to the treatment of these scars [82].
The laser punch-out method is better than even depth
resurfacing for improving deep acne scars and can be com-
bined with the shoulder technique or even depth resurfacing
according to the type of acne scar [83].
Laser skin resurfacing with the concurrent use of punch
excision improves facial acne scarring [84].
4.1.5. Dermal Grafting. Acne scars may be treated surgically
using procedures such as dermabrasion and/or simple scar
excision, scar punch elevation, or punch grafting [85].
The useful modalities available are dermal punch graft-
ing, excision, and facelifting. The selection of these tech-
niques is dependent on the above classification and the
patient’s desire for improvement [86].
Split-thickness or full-thickness grafts “take” on a bed of
scar tissue or dermis following the removal of the epidermis.
The technique is useful in repairing unstable scars from
chronic leg ulcers or X-ray scars. It can also camouflage acne
scars, extensive nevi pigmentosus, and tattoos [87,88]. It is
prepackaged dermal graft material that is easy to use, safe,
and effective [89].
4.1.6. Tissue Augmenting Agents. Fat transplantation. Fat is
easily available and it has low incidence of side effects [90].
The technique consists of two phases: procurement of the
graft and placement of the graft. The injection phase with
small parcels of fat implanted in multiple tunnels allows the
fat graft maximal access to its available bloody supply. The fat
injected will normalize the contour excepted where residual
scar attachments impede this.
4.1.7. Other Tissue Augmenting Agents. There are many
new and older autologous, nonautologous biologic, and
nonbiologic tissue augmentation agents that have been used
in the past for atrophic scars, such as autologous collagen,
bovine collagen, isolagen, alloderm, hyaluronic acid, fibrel,
artecoll, and silicon, but nowadays, because of the high
incidence of side effects, the recommended material to use
is hyaluronic acid [91].
4.1.8. Needling. Skin needling is a recently proposed tech-
nique that involves using a sterile roller comprised of a
series of fine, sharp needles to puncture the skin. At first,
facial skin must be disinfected, then a topical anesthetic is
applied, left for 60 minutes. The skin needling procedure is
achieved by rolling a performed tool on the cutaneous areas
affected by acne scars (Figure 6), backward and forward with
some pressure in various directions. The needles penetrate
about 1.5 to 2 mm into the dermis. As expected, the skin
bleeds for a short time, but that soon stops. The skin
develops multiple microbruises in the dermis that initiate
the complex cascade of growth factors that finally results
in collagen production. Histology shows thickening of skin
and a dramatic increase in new collagen and elastin fibers.
Results generally start to be seen after about 6 weeks but
the full effects can take at least three months to occur and,
as the deposition of new collagen takes place slowly, the
skin texture will continue to improve over a 12 month
period. Clinical results vary between patients, but all patients
achieve some improvements (Figures 7and 8). The number
of treatments required varies depending on the individual
collagen response, on the condition of the tissue and on the
desired results. Most patients require around 3 treatments
approximately 4 weeks apart. Skin needling can be safely
performed on all skin colours and types: there is a lower
8Dermatology Research and Practice
Figure 6: Needling: the procedure.
Figure 7: Needling: patient before the treatment.
risk of postinflammatory hyperpigmentation than other
procedures, such as dermabrasion, chemical peelings, and
laser resurfacing. Skin needling is contraindicated in the
presence of anticoagulant therapies, active skin infections,
collagen injections, and other injectable fillers in the previous
six months, personal or familiar history of hypertrophic and
keloidal scars [92,93].
4.1.9. Combined Therapy. There is a new combination
therapy for the treatment of acne scars. The first therapy
consists of peeling with trichloroacetic acid, then followed
by subcision, the process by which there is separation of the
acne scar from the underlying skin and in the end fractional
laser irradiation. The efficacy and safety of this method was
investigated for the treatment of acne scars. The duration
of this therapy is 12 months. Dot peeling and subcision
were performed twice 2-3 months apart and fractional laser
irradiation was performed every 3-4 weeks. There were no
significant complications at the treatment sites. It would
appear that triple combination therapy is a safe and very
effective combination treatment modality for a variety of
atrophic acne scars [94].
Figure 8: Needling: patient after the treatment.
4.2. Hypertrophic Scars
4.2.1. Silicone Gel. Silicone-based products represent one of
the most common and effective solutions in preventing and
also in the treatment of hypertrophic acne scars. The silicone
gel was introduced in the treatment of hypertrophic acne
scars to overcome the difficulties in the management of sil-
icone sheets. Indeed, the silicone gel has several advantages:
it is transparent, quick drying, nonirritating and does not
induce skin maceration, it can be used to treat extensive
scars and uneven areas of skin. The mechanism of action is
not fully understood but several hypotheses [95]havebeen
advanced: (1) the increase in hydration; (2) the increase in
temperature; (3) protection of the scar; (4) increased tension
of O2; (5) action on the immune system. There is, currently,
only one observational open label study, conducted on 57
patients. In this study, the gel was applied on the scars 2
times daily for 8 weeks with an average improvement in
the thickness estimated between 40% and 50% compared to
baseline.
As regards the treatment of already formed hypertrophic
scars, the gel should be applied in small amounts, twice daily
for at least 8 weeks to achieve a satisfactory aesthetic result.
Whereas for the purposes of prevention, the same dosage is
recommended for at least 12–16 weeks; the treatment should
be started as soon as possible after the risk of a patient
developing hypertrophic acne scars has been identified.
Treatment with silicone gel can be used in patients of any
age and women of childbearing age. Moreover, the silicone
gel can be used throughout the year, including summer.
4.2.2. Intralesional Steroid Therapy. Intralesional injection
of steroids is one of the most common treatments for
keloids and hypertrophic scars. It can be used alone or
as part of multiple therapeutic approaches. Corticosteroids
may reduce the volume, thickness, and texture of scars, and
they can relieve symptoms such as itching and discomfort
[96]. The mechanisms of action have not been completely
clarified: in addition to their anti-inflammatory properties,
Dermatology Research and Practice 9
it has been suggested that steroids exert a vasoconstrictor
and an antimitotic activity. It is believed that steroids
arrest pathological collagen production through two distinct
mechanisms: the reduction of oxygen and nutrients to the
scar with inhibition of the proliferation of keratinocytes
and fibroblasts [96]; the stimulation of digestion of collagen
deposition through block of a collagenase-inhibitor, the
alpha-2-microglobulin [97]. During the injection the syringe
needle should be kept upright [24]. It is always preferable for
the injections to be preceded by the application of anesthetic
creams or be associated with injections of lidocaine [97].
Intralesional steroid therapy may be preceded by a light
cryotherapy with liquid nitrogen, 10–15 minutes before
injection, to improve the dispersion of the drug in scar
tissue and minimize the deposition in the subcutaneous and
perilesional tissue [98]. The steroid that is currently most
frequently used in the treatment of hypertrophic scars and
keloids is triamcinolone acetonide (10–40 mg/mL) [99]. The
most common adverse reactions are hypopigmentation, skin
atrophy, telangiectasia, and infections [100]. As for injuries
to the face, the use of intralesional steroids is recommended
for the treatment of individual elements which are
particularly bulky and refractory to previous less invasive
methods.
4.2.3. Cryotherapy. Cryotherapy with liquid nitrogen can
significantly improve the clinical appearance of hypertrophic
scars and keloids and also determine their complete regres-
sion.
The low temperatures reached during cryotherapy ses-
sions cause a slowing of blood flow and cause the formation
of intraluminal thrombus hesitant to anoxia and tissue
necrosis [101]. Age and size of the scar are important factors
conditioning the outcome of this technique: younger and
smaller scars are most responsive to cryotherapy [102].
Compared with intralesional injections of corticosteroids,
cryosurgery is significantly more effective than alternative
methods for richly vascularized injuries 12 months younger
[103]. During each session of cryotherapy the patient is
usually subjected to 2-3 cycles, each lasting less than 25
seconds. Cryotherapy can also be used before each cycle
of intralesional injections of steroids to reduce the pain of
injection therapy and to facilitate the injection of cortisone,
generating a small area of edema at the level of the scar tissue
to be treated [98]. Possible adverse reactions are represented
by hypo- and hyperpigmentation, skin atrophy, and pain
[102]. With regard to localized lesions to the face, the
possible outcomes of freezing restrict the use of cryotherapy
in these areas, especially in cases where the scars are
numerous or for dark phenotypes. Therefore, cryotherapy
can be taken into consideration especially for scars located
on the trunk or for particularly bulky scars on the face.
4.2.4. Pulsed Dye Laser. The use of lasers for hypertrophic
scars and keloids was first proposed by Apfelberg et al.
[104]andCastroetal.[105] in the 1980s, and since then
more lasers with various wavelengths have been introduced.
Unfortunately, laser therapy for hypertrophic scars has
had only variable success in the past due to the minimal
improvement in a high percent of patients [106–108].
On the contrary, the use of pulsed dye laser (PDL) has
provided encouraging results in the treatment of hyper-
trophic/keloidal scars over the past 10 years. Several studies
have been conducted to investigate how the PDL works on
hypertrophic/keloidal scars. They have revealed that PDL
decreases the number and proliferation of fibroblasts and
collagen fibers appear looser and less coarse [109]. Moreover,
PDL also produces an increase in MMP-I3 (collagenese-
3) activity and a decrease in collagen type III deposition
[110]. As a consequence, PDL flattens and decreases the
volume of hypertrophic scars [111,112], improves texture
[113], and increases elasticity [114], usually after two to three
treatments [115]. Additionally, pruritis and pain within the
scars are significantly improved [116]. Besides, no recurrence
or worsening of PDL-treated scars occurs during the 4-
year followup after cessation of treatment [116]. The most
common side effect of the PDL is purpura which can last
as long as 7–10 days. Blistering can also occur as well as
hypo- and hyperpigmentation which is more likely in darker
skinned individuals [117]. Therefore, the ideal candidates
for PDL are patients with lighter skin types (Fitzpatrick
Types I–III) because less melanin is present to compete with
hemoglobin laser energy absorption [118,119].
4.2.5. Surgery. For the correction of large facial scars, W-
plasty seems to be optimal [12]. This therapeutic procedure
causes a disruption of the scar which makes the lesion
less conspicuous. Especially in facial surgery, autologous
skin transplants, namely, full thickness skin transplant or
composite fat-skin graft, are another valuable alternative
for achieving wound closure with minimal tension. The
preferred donor sites for skin graft used for facial defects are
the retro- and preauricular sites as well as the neck [120].
4.2.6. Other Approaches. Other treatment options for hyper-
trophic acne scars and keloids that can be taken into
account include elastic compression, intralesional injection
of 5-fluorouracil, imiquimod, interferon, radiotherapy, and
bleomycin. All these approaches, however, are more effective
for the treatment of hypertrophic scars not caused by acne
and their use is not recommended due to their impracticality
(elastic compression), the lack of clinical experience in the
literature (5 FU, interferon, radiotherapy, bleomycin) the
lack of efficacy (imiquimod), and the high costs (interferon).
5. Conclusion
There are no general guidelines available to optimize acne
scar treatment. There are several multiple management
options, both medical and surgical, and laser devices are use-
ful in obtaining significant improvement. Further primary
research such as randomized controlled trials is needed in
order to quantify the benefits and to establish the duration
of the effects, the cost-effective ratio of different treatments,
and the evaluation of the psychological improvement and the
quality of life of these patients.
10 Dermatology Research and Practice
References
[1] S. Z. Ghodsi, H. Orawa, and C. C. Zouboulis, “Prevalence,
severity, and severity risk factors of acne in high school
pupils: a community-based study,” JournalofInvestigative
Dermatology, vol. 129, no. 9, pp. 2136–2141, 2009.
[2] C. Williams and A. M. Layton, “Persistent acne in women:
implications for the patient and for therapy,” American Jour-
nal of Clinical Dermatology, vol. 7, no. 5, pp. 281–290, 2006.
[3] B. Capitanio, J. L. Sinagra, V. Bordignon, P. C. Fei, M.
Picardo, and C. C. Zouboulis, “Underestimated clinical
features of postadolescent acne,” Journal of the American
Academy of Dermatology, vol. 63, no. 5, pp. 782–788, 2010.
[4] A. M. Layton, C. A. Henderson, and W. J. Cunliffe, “A clinical
evaluation of acne scarring and its incidence,” Clinical and
Experimental Dermatology, vol. 19, no. 4, pp. 303–308, 1994.
[5] W. J. Cunliffe and D. J. Gould, “Prevalence of facial acne
vulgaris in late adolescence and in adults,” British Medical
Journal, vol. 1, no. 6171, pp. 1109–1110, 1979.
[6] I. Kurokawa, F. W. Danby, Q. Ju et al., “New developments
in our understanding of acne pathogenesis and treatment,”
Experimental Dermatology, vol. 18, no. 10, pp. 821–832, 2009.
[7] C. C. Zouboulis, “Acne and sebaceous gland function,”
Clinics in Dermatology, vol. 22, no. 5, pp. 360–366, 2004.
[8] T. Alestas, R. Ganceviciene, S. Fimmel, K. M¨
uller-Decker,
and C. C. Zouboulis, “Enzymes involved in the biosynthesis
of leukotriene B4 and prostaglandin E2 are active in
sebaceous glands,” Journal of Molecular Medicine, vol. 84, no.
1, pp. 75–87, 2006.
[9] E. Makrantonaki and C. C. Zouboulis, “Testosterone
metabolism to 5α-dihydrotestosterone and synthesis of
sebaceous lipids is regulated by the peroxisome proliferator-
activated receptor ligand linoleic acid in human sebocytes,”
British Journal of Dermatology, vol. 156, no. 3, pp. 428–432,
2007.
[10] I. Nagy, A. Pivarcsi, K. Kis et al., “Propionibacterium
acnes and lipopolysaccharide induce the expression of
antimicrobial peptides and proinflammatory cytokines/
chemokines in human sebocytes,” Microbes and Infection,
vol. 8, no. 8, pp. 2195–2205, 2006.
[11] J. Kim, M.-T. Ochoa, S. R. Krutzik et al., “Activation of
toll-like receptor 2 in acne triggers inflammatory cytokine
responses,” Journal of Immunology, vol. 169, no. 3, pp.
1535–1541, 2002.
[12] D. Wolfram, A. Tzankov, P. P¨
ulzl, and H. Piza-Katzer,
“Hypertrophic scars and keloids—a review of their
pathophysiology, risk factors, and therapeutic management,”
Dermatologic Surgery, vol. 35, no. 2, pp. 171–181, 2009.
[13] A. J. Cowin, M. P. Brosnan, T. M. Holmes, and M. W. J.
Ferguson, “Endogenous inflammatory response to dermal
wound healing in the fetal and adult mouse,” Developmental
Dynamics, vol. 212, no. 3, pp. 385–393, 1998.
[14] P. Martin and S. J. Leibovich, “Inflammatory cells during
wound repair: the good, the bad and the ugly,” Trends in Cell
Biology, vol. 15, no. 11, pp. 599–607, 2005.
[15] D.B.Holland,A.H.T.Jeremy,S.G.Roberts,D.C.Seukeran,
A. M. Layton, and W. J. Cunliffe, “Inflammation in acne
scarring: a comparison of the responses in lesions from
patients prone and not prone to scar,” British Journal of
Dermatology, vol. 150, no. 1, pp. 72–81, 2004.
[16] W. K. Stadelmann, A. G. Digenis, and G. R. Tobin,
“Physiology and healing dynamics of chronic cutaneous
wounds,” American Journal of Surgery, vol. 176, no. 2A, pp.
26S–38S, 1998.
[17] C. L. Baum and C. J. Arpey, “Normal cutaneous wound heal-
ing: clinical correlation with cellular and molecular events,”
Dermatologic Surgery, vol. 31, no. 6, pp. 674–686, 2005.
[18]K.S.Midwood,L.V.Williams,andJ.E.Schwarzbauer,
“Tissue repair and the dynamics of the extracellular matrix,”
International Journal of Biochemistry and Cell Biology, vol.
36, no. 6, pp. 1031–1037, 2004.
[19] M. Chivot, H. Pawin, C. Beylot et al., “Acne scars: epide-
miology, physiopathology, clinical features and treatment,”
Annales de Dermatologie et de Venereologie, vol. 133, no. 10,
pp. 813–824, 2006.
[20] C. I. Jacob, J. S. Dover, and M. S. Kaminer, “Acne scarring:
a classification system and review of treatment options,”
Journal of the American Academy of Dermatology, vol. 45, no.
1, pp. 109–117, 2001.
[21] G. J. Goodman and J. A. Baron, “Postacne scarring: a
qualitative global scarring grading system,” Dermatologic
Surgery, vol. 32, no. 12, pp. 1458–1466, 2006.
[22] G. J. Goodman and J. A. Baron, “Postacne scarring—a
quantitative global scarring grading system,” Journal of
Cosmetic Dermatology, vol. 5, no. 1, pp. 48–52, 2006.
[23] B. Dreno, A. Khammari, N. Orain et al., “ECCA grading
scale: an original validated acne scar grading scale for clinical
practice in dermatology,” Dermatology, vol. 214, no. 1, pp.
46–51, 2006.
[24] R. S. English and P. D. Shenefelt, “Keloids and hypertrophic
scars,” Dermatologic Surgery, vol. 25, no. 8, pp. 631–638,
1999.
[25] I. Ghersetich, B. Brazzini, and T. Lotti, “Chemical peeling,”
in European Handbook of Dermatological Treatments,T.M.
Lotti and A. D. Katsambas, Eds., Springer, Berlin, Germany,
2nd edition, 2003.
[26] I.Ghersetich,P.Teofoll,M.Gantcheva,M.Ribuffo, and P.
Puddu, “Chemical peeling: how, when, why?” Journal of the
European Academy of Dermatology and Venereology, vol. 8,
no. 1, pp. 1–11, 1997.
[27] M. Landau, “Chemical peels,” Clinics in Dermatology, vol.
26, no. 2, pp. 200–208, 2008.
[28] G. J. Goodman, “Management of post-acne scarring: what
are the options for treatment?” American Journal of Clinical
Dermatology, vol. 1, no. 1, pp. 3–17, 2000.
[29] G. J. Goodman, “Postacne scarring: a review of its
pathophysiology and treatment,” Dermatologic Surgery,
vol. 26, no. 9, pp. 857–871, 2000.
[30] E. F. Bernstein, J. Lee, D. B. Brown, R. Yu, and E. Van Scott,
“Glycolic acid treatment increases type I collagen mRNA
and hyaluronic acid content of human skin,” Dermatologic
Surgery, vol. 27, no. 5, pp. 429–433, 2001.
[31] S. M. Javaheri, S. Handa, I. Kaur, and B. Kumar, “Safety and
efficacy of glycolic acid facial peel in Indian women with
melasma,” International Journal of Dermatology, vol. 40, no.
5, pp. 354–357, 2001.
[32] F. F. Becker, F. P. J. Langford, M. G. Rubin, and P. Speelman,
“A histological comparison of 50% and 70% glycolic acid
peels using solutions with various pHs,” Dermatologic
Surgery, vol. 22, no. 5, pp. 463–465, 1996.
[33] A. Rook, D. S. Wilkinson, and F. J. G. Ebling, Te xt book of
Dermatology, Blackwell Scientific, Oxford, UK, 1972.
[34] E. J. Van Scott and R. J. Yu, “Hyperkeratinization, corneocyte
cohesion and alpha hydroxy acids,” Journal of the American
Academy of Dermatology, vol. 11, no. 5, pp. 867–879, 1984.
Dermatology Research and Practice 11
[35] B. S. Lynch, E. S. Delzell, and D. H. Bechtel, “Toxicology
review and risk assessment of resorcinol: thyroid effects,”
Regulatory Toxicology and Pharmacology, vol. 36, no. 2, pp.
198–210, 2002.
[36] A. Barbaud, P. Modiano, M. Cocciale, S. Reichert, and J.-L.
Schmutz, “The topical application of resorcinol can provoke
a systemic allergic reaction,” British Journal of Dermatology,
vol. 135, no. 6, pp. 1014–1015, 1996.
[37] T. D. Griffin, E. J. Van Scott, and S. Maddin, “The use
of pyruvic acid as a chemical peeling agent,” Journal of
Dermatologic Surgery & Oncology, vol. 15, p. 1316, 1989.
[38] G. D. Monheit, “Medium-depth combination peels,”
Dermatologic Therapy, vol. 13, no. 2, pp. 183–191, 2000.
[39] E. J. Van Scott and R. J. Yu, “Alpha hydroxy acids: therapeutic
potentials,” Canadian Journal of Dermatology, vol. 1, no. 5,
pp. 108–112, 1989.
[40] E. Berardesca, N. Cameli, G. Primavera, and M. Carrera,
“Clinical and instrumental evaluation of skin improvement
after treatment with a new 50% pyruvic acid peel,”
Dermatologic Surgery, vol. 32, no. 4, pp. 526–531, 2006.
[41] P. G. Unna, “Therapeutiques generales des maladies de la
peau,” 1882.
[42] N. D. Lazo, J. G. Meine, and D. T. Downing, “Lipids
are covalently attached to rigid corneocyte protein
envelopes existing predominantly as β-sheets: a solid-state
nuclear magnetic resonance study,” Journal of Investigative
Dermatology, vol. 105, no. 2, pp. 296–300, 1995.
[43] J. M. Swinehart, “Salicylic acid ointment peeling of the hands
and forearms: effective nonsurgical removal of pigmented
lesions and actinic damage,” Journal of Dermatologic Surgery
and Oncology, vol. 18, no. 6, pp. 495–498, 1992.
[44] S. Imayama, S. Ueda, and M. Isoda, “Histologic changes in
the skin of hairless mice following peeling with salicylic acid,”
Archives of Dermatology, vol. 136, no. 11, pp. 1390–1395,
2000.
[45] P. E. Grimes, “The safety and efficacy of salicylic acid
chemical peels in darker racial-ethnic groups,” Dermatologic
Surgery, vol. 25, no. 1, pp. 18–22, 1999.
[46] J. M. Swinehart, “Salicylic acid ointment peeling of the hands
and forearms: effective nonsurgical removal of pigmented
lesions and actinic damage,” Journal of Dermatologic Surgery
and Oncology, vol. 18, no. 6, pp. 495–498, 1992.
[47] G. Fabbrocini, M. P. De Padova, and A. Tosti, “Chemical
peels: what’s new and what isn’t new but still works well,”
Facial Plastic Surgery, vol. 25, no. 5, pp. 329–336, 2009.
[48] M. I. Dinner and J. S. Artz, “The art of the trichloroacetic
acid chemical peel,” Clinics in Plastic Surgery,vol.25,no.1,
pp. 53–62, 1998.
[49] J. W. Slavin, “Trichloroacetic acid peels,” Aesthetic Surgery
Journal, vol. 24, no. 5, pp. 469–470, 2004.
[50] M. M. Al-Waiz and A. I. Al-Sharqi, “Medium-depth chemical
peels in the treatment of acne scars in dark-skinned individ-
uals,” Dermatologic Surgery, vol. 28, no. 5, pp. 383–387, 2002.
[51] J. B. Lee, W. G. Chung, H. Kwahck, K. H. Lee, and G.
Monheit, “Focal treatment of acne scars with trichloroacetic
acid: Chemical reconstruction of skin scars method,”
Dermatologic Surgery, vol. 28, no. 11, pp. 1017–1021, 2002.
[52] G. Fabbrocini, S. Cacciapuoti, N. Fardella, F. Pastore, and G.
Monfrecola, “CROSS technique: chemical reconstruction of
skin scars method,” Dermatologic Therapy,vol.21,no.3,pp.
S29–S32, 2008.
[53] A. Yug, J. E. Lane, M. S. Howard, and D. E. Kent, “Histologic
study of depressed acne scars treated with serial high-
concentration (95%) trichloroacetic acid,” Dermatologic
Surgery, vol. 32, no. 8, pp. 985–990, 2006.
[54] L. Alkhawam and M. Alam, “Dermabrasion and micro-
dermabrasion,” Facial Plastic Surgery,vol.25,no.5,pp.
301–310, 2009.
[55] E. K. Shim, D. Barnette, K. Hughes, and H. T. Greenway,
“Microdermabrasion: a clinical and histopathologic study,”
Dermatologic Surgery, vol. 27, no. 6, pp. 524–530, 2001.
[56] B. M. Freedman, E. Rueda-Pedraza, and S. P. Waddell,
“The epidermal and dermal changes associated with
microdermabrasion,” Dermatologic Surgery, vol. 27, no. 12,
pp. 1031–1034, 2001.
[57] R. Shpall, F. C. Beddingfield III, D. Watson, and G. P. Lask,
“Microdermabrasion: a review,” Facial Plastic Surgery, vol.
20, no. 1, pp. 47–50, 2004.
[58] R.-Y. Tsai, C.-N. Wang, and H.-L. Chan, “Aluminum oxide
crystal microdermabrasion: a new technique for treating
facial scarring,” Dermatologic Surgery,vol.21,no.6,pp.
539–542, 1995.
[59] J. R. Lloyd, “The use of microdermabrasion for acne: a pilot
study,” Dermatologic Surgery, vol. 27, no. 4, pp. 329–331,
2001.
[60] S. H. Mandy, “Tretinoin in the preoperative and postopera-
tive management of dermabrasion,” Journal of the American
Academy of Dermatology, vol. 15, no. 4, pp. 888–889, 1986.
[61] S. Nelson, “An introduction to laser and laser-tissue
interactions in dermatology,” in Principles and Practices in
Cutaneous Laser Surgery,A.N.B.Kauvar,Ed.,p.70,Taylor
and Francis Group, Boca Raton, Fla, USA, 2005.
[62] K. J. Smith, H. G. Skelton, J. S. Graham, C. G. Hurst, and B.
E. Hackley Jr., “Increased smooth muscle actin, factor XIIIa,
and vimentin-positive cells in the papillary dermis of carbon
dioxide laser-debrided porcine skin,” Dermatologic Surgery,
vol. 23, no. 10, pp. 891–895, 1997.
[63]E.M.Graber,E.L.Tanzi,andT.S.Alster,“Sideeffects
and complications of fractional laser photothermolysis:
experience with 961 treatments,” Dermatologic Surgery, vol.
34, no. 3, pp. 301–305, 2008.
[64] H. H. L. Chan, D. Manstein, C. S. Yu, S. Shek, T. Kono,
andW.I.Wei,“Theprevalenceandriskfactorsofpost-
inflammatory hyperpigmentation after fractional resurfacing
in Asians,” Lasers in Surgery and Medicine, vol. 39, no. 5, pp.
381–385, 2007.
[65] D. J. Fife, R. E. Fitzpatrick, and C. B. Zachary, “Complications
of fractional CO2laser resurfacing: four cases,” Lasers in
Surgery and Medicine, vol. 41, no. 3, pp. 179–184, 2009.
[66] M. M. Avram, W. D. Tope, T. Yu, E. Szachowicz, and J.
S. Nelson, “Hypertrophic scarring of the neck following
ablative fractional carbon dioxide laser resurfacing,” Lasers
in Surgery and Medicine, vol. 41, no. 3, pp. 185–188,2009.
[67] N. Fournier and S. Mordon, “Nonablative remodeling with
a 1,540 nm erbium:glass laser,” Dermatologic Surgery, vol. 31,
no. 9, pp. 1227–1235, 2005.
[68] P. M. Friedman, M. H. Jih, G. R. Skover, G. S. Payonk, A.
Kimyai-Asadi, and R. G. Geronemus, “Treatment of atrophic
facial acne scars with the 1064-nm Q-switched Nd:YAG
laser: six-month follow-up study,” Archives of Dermatology,
vol. 140, no. 11, pp. 1337–1341, 2004.
[69] G. M. Lipper and M. Perez, “Nonablative acne scar reduction
after a series of treatments with a short-pulsed 1,064-nm
Neodymium:YAG laser,” Dermatologic Surgery,vol.32,no.8,
pp. 998–1006, 2006.
12 Dermatology Research and Practice
[70]A.C.Bhatia,J.S.Dover,K.A.Arndt,B.Stewart,and
M. Alam, “Patient satisfaction and reported long-term
therapeutic efficacy associated with 1,320 nm Nd:YAG laser
treatment of acne scarring and photoaging,” Dermatologic
Surgery, vol. 32, no. 3, pp. 346–352, 2006.
[71] E. L. Tanzi and T. S. Alster, “Comparison of a 1450-nm
diode laser and a 1320-nm Nd:YAG laser in the treatment
of atrophic facial scars: a prospective clinical and histologic
study,” Dermatologic Surgery, vol. 30, no. 2, pp. 152–157,
2004.
[72] T. S. Alster and J. R. Lupton, “Are all infrared lasers equally
effective in skin rejuvenation,” Seminars in Cutaneous
Medicine and Surgery, vol. 21, no. 4, pp. 274–279, 2002.
[73] T. Hasegawa, T. Matsukura, Y. Mizuno, Y. Suga, H.
Ogawa, and S. Ikeda, “Clinical trial of a laser device called
fractional photothermolysis system for acne scars,” Journal
of Dermatology, vol. 33, no. 9, pp. 623–627, 2006.
[74]E.M.Graber,E.L.Tanzi,andT.S.Alster,“Sideeffects
and complications of fractional laser photothermolysis:
experience with 961 treatments,” Dermatologic Surgery, vol.
34, no. 3, pp. 301–305, 2008.
[75] T. S. Alster, E. L. Tanzi, and M. Lazarus, “The use of fractional
laser photothermolysis for the treatment of atrophic scars,”
Dermatologic Surgery, vol. 33, no. 3, pp. 295–299, 2007.
[76] B. M. Hantash, V. P. Bedi, B. Kapadia et al., “In vivo
histological evaluation of a novel ablative fractional
resurfacing device,” Lasers in Surgery and Medicine, vol. 39,
no. 2, pp. 96–107, 2007.
[77] A. M. Chapas, L. Brightman, S. Sukal et al., “Successful
treatment of acneiform scarring with CO2ablative fractional
resurfacing,” Lasers in Surgery and Medicine, vol. 40, no. 6,
pp. 381–386, 2008.
[78] J. Waibel, K. Beer, V. Narurkar, and T. Alster, “Preliminary
observations on fractional ablative resurfacing devices:
clinical impressions,” Journal of Drugs in Dermatology, vol. 8,
no. 5, pp. 481–485, 2009.
[79] B. M. Hantash, V. P. Bedi, K. F. Chan, and C. B. Zachary,
“Ex vivo histological characterization of a novel ablative
fractional resurfacing device,” Lasers in Surgery and Medicine,
vol. 39, no. 2, pp. 87–95, 2007.
[80] B. M. Hantash, V. P. Bedi, B. Kapadia et al., “In vivo
histological evaluation of a novel ablative fractional
resurfacing device,” Lasers in Surgery and Medicine, vol. 39,
no. 2, pp. 96–107, 2007.
[81] T. S. Alster and T. B. West, “Resurfacing of atrophic facial
acne scars with a high-energy, pulsed carbon dioxide laser,”
Dermatologic Surgery, vol. 22, no. 2, pp. 151–155, 1996.
[82] G. J. Goodman, “Postacne scarring: a review of its
pathophysiology and treatment,” Dermatologic Surgery,
vol. 26, no. 9, pp. 857–871, 2000.
[83] S. H. Koo, E. S. Yoon, D. S. Ahn, and S. H. Park, “Laser
punch-out for acne scars,” Aesthetic Plastic Surgery, vol. 25,
no. 1, pp. 46–51, 2001.
[84] J. M. Grevelink and V. R. White, “Concurrent use of laser
skin resurfacing and punch excision in the treatment of
facial acne scarring,” Dermatologic Surgery,vol.24,no.5,pp.
527–530, 1998.
[85] L. Y. Matsuoka, “Acne and related disorders,” Clinics in
Plastic Surgery, vol. 20, no. 1, pp. 35–41, 1993.
[86] D. A. Ellis and M. J. Michell, “Surgical treatment of acne
scarring: non-linear scar revision,” Journal of Otolaryngology,
vol. 16, no. 2, pp. 116–119, 1987.
[87] J. R. Trimble, “Dermal overgrafting in dermatology,” Journal
of Dermatologic Surgery and Oncology, vol. 9, no. 12, pp.
987–993, 1983.
[88] S. A. Burres, “Recollagenation of acne scars,” Dermatologic
Surgery, vol. 22, no. 4, pp. 364–367, 1996.
[89] B. Besecker and C. G. Hart, “A new treatment option for acne
scars: allograft dermis,” Dermatology nursing / Dermatology
Nurses” Association, vol. 11, no. 2, pp. 111–114, 1999.
[90] R. Ellenbogen, “Invited comment on autologous fat
injection,” Annals of Plastic Surgery, vol. 24, p. 297, 1990.
[91] G. J. Goodman, “Postacne scarring: a review of its patho-
physiology and treatment,” Dermatologic Surgery, vol. 26, no.
9, pp. 857–871, 2000.
[92] D. Fernandes, “Minimally invasive percutaneous collagen
induction,” Oral and Maxillofacial Surgery Clinics of North
America, vol. 17, no. 1, pp. 51–63, 2005.
[93] G. Fabbrocini, N. Fardella, A. Monfrecola, I. Proietti, and D.
Innocenzi, “Acne scarring treatment using skin needling,”
Clinical and Experimental Dermatology, vol. 34, no. 8, pp.
874–879, 2009.
[94] W.H.Kang,Y.J.Kim,W.S.Pyo,S.J.Park,andJ.H.Kim,
“Atrophic acne scar treatment using triple combination ther-
apy: dot peeling, subcision and fractional laser,” Journal of
Cosmetic and Laser Therapy, vol. 11, no. 4, pp. 212–215, 2009.
[95]B.Berman,O.A.Perez,S.Kondaetal.,“Areviewofthe
biologic effects, clinical efficacy, and safety of silicone elasto-
mer sheeting for hypertrophic and keloid scar treatment
and management,” Dermatologic Surgery, vol. 33, no. 11, pp.
1291–1302, 2007.
[96] T. A. Mustoe, R. D. Cooter, M. H. Gold et al., “International
clinical recommendations on scar management,” Plastic and
Reconstructive Surgery, vol. 110, no. 2, pp. 560–571, 2002.
[97] A. P. Kelly, “Medical and surgical therapies for keloids,”
Dermatologic Therapy, vol. 17, no. 2, pp. 212–218, 2004.
[98] A. J. Nemeth, “Keloids and hypertrophic scars,” Journal
of Dermatologic Surgery and Oncology, vol. 19, no. 8, pp.
738–746, 1993.
[99] B. S. Atiyeh, “Nonsurgical management of hypertrophic
scars: evidence-based therapies, standard practices, and
emerging methods,” Aesthetic Plastic Surgery, vol. 31, no. 5,
pp. 468–492, 2007.
[100] W. Manuskiatti and R. E. Fitzpatrick, “Treatment response
of keloidal and hypertrophic sternotomy scars: comparison
among intralesional corticosteroid, 5-fluorouracil, and
585-nm flashlamp-pumped pulsed-dye laser treatments,”
Archives of Dermatology, vol. 138, no. 9, pp. 1149–1155, 2002.
[101] F. Boutli-Kasapidou, A. Tsakiri, E. Anagnostou, and O.
Mourellou, “Hypertrophic and keloidal scars: an approach
to polytherapy,” International Journal of Dermatology, vol.
44, no. 4, pp. 324–327, 2005.
[102] L. Rusciani, G. Rossi, and R. Bono, “Use of cryotherapy in
the treatment of keloids,” Journal of Dermatologic Surgery
and Oncology, vol. 19, no. 6, pp. 529–534, 1993.
[103] A. M. Layton, J. Yip, and W. J. Cunliffe, “A comparison of
intralesional triamcinolone and cryosurgery in the treatment
of acne keloids,” British Journal of Dermatology, vol. 130, no.
4, pp. 498–501, 1994.
[104] D. B. Apfelberg, M. R. Maser, and H. Lash, “Preliminary
results of argon and carbon dioxide laser treatment of keloid
scars,” Lasers in Surgery and Medicine, vol. 4, no. 3, pp.
283–290, 1984.
Dermatology Research and Practice 13
[105] D. J. Castro, R. P. Abergel, and C. Meeker, “Effects of the
Nd:YAG laser on DNA synthesis and collagen production
in human skin fibroblast cultures,” Annals of Plastic Surgery,
vol. 11, no. 3, pp. 214–222, 1983.
[106] J. E. C. Norris, “The effect of carbon dioxide laser surgery on
the recurrence of keloids,” Plastic and Reconstructive Surgery,
vol. 87, no. 1, pp. 44–53, 1991.
[107] W. T. Lawrence, “In search of the optimal treatment of
keloids: report of a series and a review of the literature,”
Annals of Plastic Surgery, vol. 27, no. 2, pp. 164–178, 1991.
[108] R. Sherman and H. Rosenfeld, “Experience with the Nd:YAG
laser in the treatment of keloid scars,” Annals of Plastic
Surgery, vol. 21, no. 3, pp. 231–235, 1988.
[109] Y.-R. Kuo, W.-S. Wu, S.-F. Jeng et al., “Activation of ERK
and p38 kinase mediated keloid fibroblast apoptosis after
flashlamp pulsed-dye laser treatment,” Lasers in Surgery and
Medicine, vol. 36, no. 1, pp. 31–37, 2005.
[110] Y.-R. Kuo, W.-S. Wu, S.-F. Jeng et al., “Suppressed TGF-
β1 expression is correlated with up-regulation of matrix
metalloproteinase-13 in keloid regression after flashlamp
pulsed-dye laser treatment,” Lasers in Surgery and Medicine,
vol. 36, no. 1, pp. 38–42, 2005.
[111] T. S. Alster and C. M. Williams, “Treatment of keloid
sternotomy scars with 585 nm flashlamp-pumped pulsed-
dye laser,” Lancet, vol. 345, no. 8959, pp. 1198–1200, 1995.
[112] T. Alster, “Laser scar revision: Comparison study of 585-nm
pulsed dye laser with and without intralesional corticos-
teroids,” Dermatologic Surgery, vol. 29, no. 1, pp. 25–29, 2003.
[113] T. S. Alster and C. A. Nanni, “Pulsed dye laser treatment of
hypertrophic burn scars,” Plastic and Reconstructive Surgery,
vol. 102, no. 6, pp. 2190–2195, 1998.
[114] T. Alster and L. Zaulyanov-Scanlon, “Laser scar revision: a
review,” Dermatologic Surgery, vol. 33, no. 2, pp. 131–140,
2007.
[115] W. Manuskiatti, R. Wanitphakdeedecha, and R. E.
Fitzpatrick, “Effect of pulse width of a 595-nm flashlamp-
pumped pulsed dye laser on the treatment response of
keloidal and hypertrophic sternotomy scars,” Dermatologic
Surgery, vol. 33, no. 2, pp. 152–161, 2007.
[116] C. Dierickx, M. P. Goldman, R. E. Fitzpatrick, and T. S.
Alster, “Laser treatment of erythematous/hypertrophic and
pigmented scars in 26 patients,” Plastic and Reconstructive
Surgery, vol. 95, no. 1, pp. 84–92, 1995.
[117] L. E. Bowes, K. Nouri, B. Berman et al., “Treatment of
pigmented hypertrophic scars with the 585 nm pulsed dye
laser and the 532 nm frequency-doubled Nd:YAG laser in the
Q-switched and variable pulse modes: a comparative study,”
Dermatologic Surgery, vol. 28, no. 8, pp. 714–719, 2002.
[118] W. Manuskiatti, R. Wanitphakdeedecha, and R. E.
Fitzpatrick, “Effect of pulse width of a 595-nm flashlamp-
pumped pulsed dye laser on the treatment response of
keloidal and hypertrophic sternotomy scars,” Dermatologic
Surgery, vol. 33, no. 2, pp. 152–161, 2007.
[119] M. P. Goldman and R. E. Fitzpatrick, “Laser treatment of
scars,” Dermatologic Surgery, vol. 21, no. 8, pp. 685–687,
1995.
[120] F. Riedel and K. Hormann, “Plastic surgery of skin defects in
the face. Principles and prospective,” HNO, vol. 53, no. 12,
pp. 1020–1036, 2005.
