Keywords
extracorporeal shock wave - hypertrophic scar - wound healing - scar prevention
Introduction
Hypertrophic scar occurs from an abnormal wound healing process that involves excessive
dermal collagen production. It may affect patients in several ways, such as pruritic
sensation, scar tenderness, and limited range of motion. These negatively impact the
quality of life of patients.[1]
The reported incidences of hypertrophic scars following surgical incision wounds ranged
from 40 to 70%. However, incidences of up to 90% have been reported after burns, especially
in individuals with a higher Fitzpatrick skin tone.[2] Approximately 1,200 patients seek hypertrophic scar treatment annually at our outpatient
plastic surgery department.
Currently, there is no established gold standard for hypertrophic scar treatment since
the responses to treatment and recurrence rates have varied. Several treatment modalities
have been combined for hypertrophic scar treatment, such as intralesional steroid
injections, pressure dressings, surgical excision, pulsed dye lasers, and radiation
therapy. However, no combination proved to be successful curative therapy. Furthermore,
most modalities require multiple treatment sessions and have adverse effects associated
with their use. Therefore, a noninvasive treatment modality with good efficacy could
be a preferable treatment option.[2]
[3]
Extracorporeal shock wave therapy (ESWT) has been widely used as a noninvasive and
well-tolerated treatment for tendinopathy in general. It is also used for other orthopaedic
diseases, nephroureterolithiasis, ischemic cardiovascular disease, burn wound scars,
acute and chronic wounds. The wide range of applications highlights the versatile
benefits and regenerative potential of ESWT.[4]
[5]
[6]
[7]
[8]
[9]
[10]
[11] ESWT transmits a mechanical force via an acoustic wave to facilitate wound healing.
The force stimulates the release of neuropeptides from nerve endings and improves
wound healing. Furthermore, it also stimulates fibroblasts, which are mechanoresponsive
cells and play a role in remodeling of the extracellular matrix in wound healing and
scars.[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
The molecular mechanism of ESWT has not yet been fully identified. However, induction
of angiogenesis via stimulation of toll-like receptor 3 during ESWT was proposed in
the literatures, possibly indicating the benefits of soft tissue regeneration.[21]
[22] In the research by Fioramonti et al, the effectiveness of ESWT for burn scars was
found to be promising, with no adverse events observed.[4] This study aimed to investigate the effectiveness of ESWT for hypertrophic scars.
Methods
Study Design
This study was approved by the Institutional Review Board (approval number 295/2016).
The Declaration of Helsinki protocol was followed. The study was conducted at the
outpatient department of plastic surgery unit from September 2016 to November 2017.
Twenty-nine patients were enrolled and gave written informed consent.
Patients aged between 18 and 75 years old and had persistent hypertrophic scars for
more than 6 months prior to the study were included. Exclusion criteria were a history
of hypertrophic scar-related treatment within 2 months prior to enrolment; conditions
or risk factors for impaired wound healing (such as an immunocompromised state, connective
tissue disease, and smoking); a concurrent active systemic infection; and pregnancy.
Study Protocol
All patients underwent preoperative assessments of their hypertrophic scars. They
involved the determination of the Patient and Observer Scar Assessment Scale (POSAS),
the erythema index and the melanin index; evaluation of scar pliability; and photographic
documentation ([Fig. 1]).
Fig. 1 Study design, treatment protocol, and treatment evaluation. *The POSAS consisted
of a patient scar assessment and an observer scar assessment. **Physical properties
of the scar, such as elasticity index, erythema index, scar area and thickness. ESW,
extracorporeal shock wave; HTS, hypertrophic scars; POSAS, Patient and Observer Scar
Assessment Scale.
ESWT was performed once a week for 6 consecutive weeks by using Dermagold 100 (MTS
Europe GmbH, Konstanz, Germany). The settings were 0.1 mJ/mm2 energy, 4 Hz frequency, and 350 pulses + 10 pulses/cm2.
At 4 weeks after completion of treatment, hypertrophic scars were reassessed with
the POSAS, the erythema index, the melanin index, the pliability of the scars, and
photographic documentation. Evaluation was performed in the same manner as for preoperative
assessments.
Hypertrophic Scar Evaluation
Hypertrophic scars were evaluated with POSAS, a validated assessment tool for scar
treatment. It consists of two numerical scales: patient-scar assessment and observer-scar
assessment.[23]
[24]
[25]
[26]
The patient scar assessment scale includes pain, pruritic sensation, dyspigmentation,
pliability, thickness, irregularity, and overall opinion of scar. The parameters in
observer scar assessment scale consist of vascularity, pigmentation, thickness, relief,
pliability, and surface area.
To assess the physical properties of scars, their areas were measured using the widest
part of each scar as the scar width and the most extended section as the scar length.
In addition, the thickness of the scars was measured three times to establish the
average value of the thickest part of each scar. The measurement points were noted,
and the calculations at subsequent visits used the same points. The same portion of
each scar was documented, measured, and evaluated before and after each ESWT session
to ensure that comparisons were accurate.
The erythema and melanin indices were measured with a Mexameter MX 18 (Courage + Khazaka
Electronic GmbH, Cologne, Germany). The erythema index has an arbitrary number of
0 to 999. The higher the value is, the greater the degree of erythema present. The
melanin index also has a scale number and a similar interpretation guide. The greater
the melanin index value is, the greater the melanin content present.[27]
For the scar pliability, the Cutometer dual MPA 580 (Courage + Khazaka Electronic
GmbH, Cologne, Germany) was used. The elasticity index of the R2 parameter represents
the gross elasticity of a hypertrophic scars. It is one of the most widely used parameters
in the literatures.[27]
[28]
[29]
Statistical Analysis
The primary outcome was the improvement in hypertrophic scars, indicated by the POSAS.
All other results were defined as secondary outcomes. To estimate the sample size,
we relied on the work of Fioramonti et al.[4] The sample size was calculated using the PS Power and Sample Size Calculation program
at an α level of 0.05, a maximum tolerated error of 0.15, and a 10% dropout. According
to the calculation, 30 patients were needed. A paired t-test was used for continuous data with normal distribution. However, an independent
t-test was used for continuous data in the subgroup analyses.
All statistical data were analyzed by PASW Statistics for Windows, version 18.0 (SPSS
Inc., Chicago, IL). A p-value less than 0.05 was considered statistically significant.
Results
Twenty-nine patients with 34 hypertrophic scars were enrolled. Their average age was
42.06 ± 15.57 years. The scars had persisted for between 6 months and 30 years. Most
had developed after surgical incision wounds (55.88%) following by traumatic wounds
(20.59%), burn wounds (11.76%), and infected wounds (11.76%). The chest and upper
extremities were the main areas of scar occurrence (each was 35.29%), followed by
the face, abdomen, and lower extremities (each was 8.82%; [Table 1]). The surgical incision wounds and traumatic wounds were all closed primarily. Burn
wounds were healed by secondary intention or skin grafts if indicated. The infected
wounds were healed by delayed primary closure or secondary intention if indicated.
Table 1
Demographic profile of patients
|
Number of cases
|
n
|
|
Number of patients
|
29
|
|
Number of lesions
|
34
|
|
Mean ± SD
|
|
Age, years
|
42.06 ± 15.57
|
|
Sex
|
n (%)
|
|
Female
|
29 (85.29%)
|
|
Male
|
5 (14.71%)
|
|
Mean (range)
|
|
Duration of scar, years
|
4 (0.5–30)
|
|
n (%)
|
|
Causes of HTS
|
|
Surgical wound
|
19 (55.88%)
|
|
Traumatic wound
|
7 (20.59%)
|
|
Burn wound
|
4 (11.76%)
|
|
Infected wound
|
4 (11.76%)
|
|
Site of HTS
|
|
Chest
|
12 (35.29%)
|
|
Upper extremity
|
12 (35.29%)
|
|
Lower extremity
|
3 (8.82%)
|
|
Face
|
3 (8.82%)
|
|
Abdomen
|
3 (8.82%)
|
|
Back
|
1 (2.94%)
|
Abbreviations: HTS, hypertrophic scars; SD, standard deviation.
At 4 weeks after completion of treatment, almost of POSAS subscales and total scores
had improved from both the patients' and observers' aspects. The scar color, scar
stiffness, scar thickness, scar irregularity, overall scar, and total score of POSAS
patient scale were significantly improve (p < 0.01). Improvements were also observed in the pain and pruritic subscale of POSAS
patient scale, but the differences were not statistically significant (p = 0.66 and 0.34, respectively). The scar vascularity, scar thickness, relief, pliability,
and total score of POSAS observer scale were significantly improved (p < 0.01). The observer-evaluated surface area improvement in POSAS observer scale
was also significantly improved (p < 0.05). However, the observer-evaluated scar pigmentation also displayed improvement
without significance (p = 0.09) ([Table 2]).
Table 2
Comparison of the results of the parameters of the hypertrophic scars
|
Before treatment (mean ± SD)
|
After treatment (mean ± SD)
|
p-Value
|
|
POSAS patient scale
|
|
Pain sensation
|
4.41 ± 0.43
|
4.16 ± 0.48
|
0.66
|
|
Pruritic sensation
|
5.53 ± 0.38
|
5.03 ± 0.49
|
0.34
|
|
Scar color
|
8.00 ± 0.37
|
5.40 ± 0.44
|
<0.01[a]
|
|
Scar stiffness
|
7.88 ± 0.37
|
5.31 ± 0.45
|
<0.01[a]
|
|
Scar thickness
|
8.00 ± 0.33
|
6.06 ± 0.45
|
<0.01[a]
|
|
Surface irregularity
|
8.09 ± 0.41
|
6.22 ± 0.44
|
<0.01[a]
|
|
Overall scar
|
9.00 ± 0.28
|
6.22 ± 0.48
|
<0.01[a]
|
|
Total score
|
49.36 ± 2.20
|
38.42 ± 2.43
|
<0.01[a]
|
|
POSAS observer scale
|
|
Scar vascularity
|
5.18 ± 0.41
|
3.35 ± 0.35
|
<0.01[a]
|
|
Scar pigmentation
|
3.18 ± 0.31
|
2.76 ± 0.31
|
0.09
|
|
Scar thickness
|
5.41 ± 0.39
|
4.38 ± 0.36
|
<0.01[a]
|
|
Relief
|
4.94 ± 0.41
|
3.76 ± 0.30
|
<0.01[a]
|
|
Pliability
|
5.38 ± 0.36
|
4.24 ± 0.35
|
<0.01[a]
|
|
Surface area
|
4.56 ± 0.37
|
3.94 ± 0.27
|
<0.05[a]
|
|
Total score
|
28.65 ± 1.49
|
22.44 ± 1.52
|
<0.01[a]
|
|
Physical properties
|
|
R2 parameter
|
0.61 ± 0.02
|
0.63 ± 0.02
|
0.48
|
|
Melanin index
|
285.65 ± 24.88
|
283.83 ± 23.24
|
0.87
|
|
Erythema index
|
439.18 ± 14.92
|
435.16 ± 14.74
|
0.70
|
|
Scar area (cm2)
|
24.83 ± 6.58
|
25.25 ± 6.74
|
0.60
|
|
Scar thickness (cm)
|
0.81 ± 0.20
|
0.84 ± 0.26
|
0.88
|
|
n
(%)
|
|
|
Adverse events
|
8 (23.53%)
|
|
|
Pruritic sensation
|
5 (62.50%)
|
|
|
Well-tolerated pain
|
3 (37.50%)
|
|
Abbreviations: POSAS, Patient and Observer Scar Assessment Scale; SD, standard deviation.
a Nearly all results of POSAS subscales were statistically significantly improved (p < 0.05).
For the physical properties of the scars, the pliability (represented by the R2 parameter)
improved from 0.61 ± 0.02 to 0.63 ± 0.02 (p = 0.48). Likewise, the melanin index improved from 285.65 ± 24.88 to 283.83 ± 23.24
(p = 0.87). Although the erythema index also improved from 439.18 ± 14.92 to 435.16 ± 14.74,
the difference was insignificant (p = 0.70). The scar area went up from of the scars increased from 24.83 ± 6.58 cm2 to 25.25 ± 6.74 cm2, and the thickness rose from 0.81 ± 0.20 cm to 0.84 ± 0.26 cm. However, neither increase
was statistically significant (p = 0.60 and 0.88, respectively; [Figs. 2] and [3]).
Fig. 2 Improvement in a hypertrophic scar after extracorporeal shock wave therapy (ESWT).
The hypertrophic scar at the right jawline; note the redness, vascularity, and thickness
before treatment (A). Improvement in redness, vascularity, and thickness of the hypertrophic scar 4 weeks
after the completion of ESWT (B).
Fig. 3 Improvement in a hypertrophic scar after extracorporeal shock wave therapy (ESWT).
The hypertrophic scar had erythema and hyperpigmentation at before treatment (A). Improvement in erythema and hyperpigmentation of the hypertrophic scar 4 weeks
after the completion of ESWT (B).
Adverse events, which were short-term temporary symptoms occurring only during ESWT
sessions, were found in 23.5% of the cases. About 62.5% of the patients experienced
the pruritic sensation when applied the ESWT to the hypertrophic scars and well-tolerated
pain was reported by 37.5% of patients during application of ESWT. No serious adverse
effects were found.
Subgroup analyses were performed to compare the etiology of scars and differences
by the location on the body. The POSAS, scar pliability, melanin index, and erythema
index of each subgroup were compared. There was no statistically significant difference
in the etiology of scars resulting from surgical and nonsurgical wounds. Additionally,
the hypertrophic scar properties were not different between body locations (chest
and back versus other areas). The subgroup analysis data are detailed in [Supplementary Table S1] (available in the online version).
Discussion
Hypertrophic scarring is an abnormal wound healing process in which fibroblasts and
excessive collagen production play roles. Most hypertrophic scars are self-limiting.
However, they appear to be persistent for patients susceptible to hypertrophic scarring.
The scars can limit the range of motion, initiate pruritic sensations, and decrease
patients' quality of life. Although several treatment modalities have been used, their
response rates have not been consistent. Therefore, a gold-standard treatment for
hypertrophic scars has not yet been established. Furthermore, current treatments have
adverse events associated with their use.[2]
[3]
An ideal properties of hypertrophic scar treatment should be easy-to-use, noninvasive,
well-tolerated, available at outpatient setting, and less adverse events. ESWT meets
all of these attributes.[4]
[30]
[31]
[32] ESWT is a noninvasive modality for hypertrophic scar treatment. Although its mechanism
of action is still under investigation, complex biological responses are known to
be activated by ESWT. Among them are the release of growth factors, cytokines, and
chemokines, and the regulation of fibroblasts. These responses lead to wound and scar
remodeling.[12]
[13]
[16]
[17]
[31]
Fioramonti et al examined the use of ESWT for hypertrophic scars following burn wounds.
The researchers found an improvement in the visual analog scales used for scar assessment.[4] However, as the scores of visual analog scale represent subjective evaluations,
they vary with the observer. In this study, we used both subjective and objective
evaluations. The POSAS, which is validated scale in both patient and observer aspect,
was used for subjective evaluation. To evaluate hypertrophic scars objectively, we
used a Cutometer for pliability evaluations and Mexameter to assess melanin and erythema
indices. The results showed a significant improvement in almost all POSAS subscales
for both the patient and observer aspects, but no significant improvements in size,
thickness, scar pliability, and erythema and melanin indices. The underlying cause
of the nonsignificant improvements in some parameters could be the effect of the irregularity
of the scar surface, confounding the results.[4]
In addition, there were several studies about the mechanism of improvement in hypertrophic
scars after ESWT.[2]
[3]
[4]
[5]
[6] We transformed the effects of ESWT on hypertrophic scars into the clinical results
as POSAS scores, and most of the POSAS subscales were significantly improved after
treatment. Apart from the previous studies, which included only the hypertrophic scars
following burn wounds,[4]
[8]
[15] the current study also included the various etiologies of hypertrophic scars to
extend the indications of using ESWT in other causes of hypertrophic scars.
For further study improvement, errors in area measurements might be resolved using
a computer-assisted method. The use of ultrasound might also reduce thickness measurement
errors. Ultrasound is consistent due to its accuracy and reproducibility.[33]
As to the nature of hypertrophic scars, some parts of the scars had more stiffness
than the surrounding skin, whereas other parts demonstrated more noticeable deformation
than the nearby skin. Heterogeneity within lesions results in lower reliability of
scar pliability measurements.[34] Results might not represent the properties of the whole scar, leading to inconsistent
measurements.
This study observed outcomes 4 weeks after treatment. However, this time point might
not capture the maximum efficacy or long-term effects of hypertrophic scar treatment
with ESWT. Further research on the long-term effects might be considered.
In conclusion, ESWT demonstrated promising improvements in hypertrophic scars, as
evaluated by POSAS. This study served as support data for further investigations of
the use of ESWT for the treatment of hypertrophic scars.
