JBUR-4316; No. of Pages 9 burns xxx (2014) xxx–xxx
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/burns
Longitudinal burn scar quantification Bernadette Nedelec a,b,c,*, Jose´ A. Correa d, Ana de Oliveira b,c, Leo LaSalle c, Isabelle Perrault b a
School of Physical and Occupational Therapy, McGill University, Canada Centre de recherche du Centre Hospitalier de l’Universite´ de Montre´al (CHUM), Canada c Hoˆpital de re´adaptation Villa Medica, Canada d Department of Mathematics and Statistics, McGill University, Montreal, Quebec, Canada b
article info
abstract
Article history:
Quantitative studies of the clinical recovery of burn scars are currently lacking. Previous
Accepted 6 March 2014
reports validate the objective, precise, diagnostic capabilities of high-frequency ultrasound to measure thickness, the Cutometer1 to measure pliability and the Mexameter1 to
Keywords:
measure erythema and pigmentation of scars. Thus, we prospectively quantified clinical
Hypertrophic scar
characteristics of patient-matched, after burn hypertrophic scar (HSc), donor site scar (D)
Burns
and normal skin (N) using these instruments. One investigator measured 3 sites (HSc, D, N)
Skin injuries
in 46 burn survivors at 3, 6, and 12 months after-burn. A mixed model regression analysis,
Cutometer
adjusting p-values for multiplicity of testing, was used to compare means among sites and
Mexameter
time points. Participants were 41.2 13.5 years old, 87% males, predominantly Caucasian,
High-frequency ultrasound
with an average of 19.5% body surface area burned. HSc thickness decreased significantly
scanning
between 3 and 6, 6 and 12, and 3 and 12 months (all p < 0.0001), but remained thicker than D and N skin (all p < 0.0001). Pliability differed significantly between HSc, D and N sites at all time points (all p < 0.0001), with HSc and D increasing between 3 and 12 months ( p < 0.05) but not reaching normal. HSc and D sites were significantly more erythematous than normal skin ( p < 0.05) at 3 and 6 months but D sites approached normal by 12 months. The only time points at which pigmentation significantly differed were the HSc and D sites at 6 months. Thickness, pliability, erythema and pigmentation of N skin remained similar over the 12 months. We found that post-burn HSc thickness, pliability and erythema differed significantly from D and N skin at 3, 6, and 12 months and does not return to normal by 12 months after-injury; however, significant improvements towards normal can be expected. Donor sites are redder than normal skin at 3 and 6 months but can be expected to return to normal by 12 months. Although the color of HSc and D sites change markedly with time these color changes are primarily due to changes in redness of the site, not melanin in this primarily Caucasian population. # 2014 Elsevier Ltd and ISBI. All rights reserved.
* Corresponding author at: McGill University Faculty of Medicine, 3654 Promenade Sir William Osler, Montreal, Quebec H3G 1Y5, Canada. Tel.: +1 514 398 1275; fax: +1 514 398 8193. E-mail address: [email protected] (B. Nedelec). http://dx.doi.org/10.1016/j.burns.2014.03.002 0305-4179/# 2014 Elsevier Ltd and ISBI. All rights reserved.
Please cite this article in press as: Nedelec B, et al. Longitudinal burn scar quantification. Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.03.002
JBUR-4316; No. of Pages 9
2
burns xxx (2014) xxx–xxx
1.
Introduction
The formation of hypertrophic scars (HSc) is one of the most important long-term morbidities after a burn injury. A hypertrophic scar is defined as a raised, red, rigid scar that may be hypo or hyper-pigmented and is often itchy and/or painful. It is associated with the formation of contractures [1,2], functional limitations, psychological distress [3,4] and decreased quality of life [3,5]. One of the limitations that have impaired our ability to advance our understanding of the pathophysiology and clinical recovery profile of HSc is that subjective scar evaluation scales have typically been used as outcome measures [6–9], but the nature of such scales renders them prone to bias. Although it continues to be important to obtain the patient’s subjective impression of the outcome of their scar, the availability of objective evaluation instruments that provide more accurate data now allows for precise quantification of the physical scar characteristics [10–12]. The physical characteristics that are most commonly included in subjective assessment scales include thickness, pliability, vascularity and pigmentation [6–9,13,14]. Each of these characteristics can be evaluated with objective evaluation instruments. The use of high-frequency ultrasound scanners to quantify scar thickness was initially proposed by Katz et al. in the 1980s [15]. More recently high-frequency, high-resolution ultrasound has been shown to provide reliable thickness measurements of HSc [16,17] that were able to clearly discriminate HSc from normal scar and normal skin [16] and showed good concurrent validity with the modified Vancouver Scar Scale (mVSS) [17]. The Cutometer1 determines skin elasticity based on the suction and elongation measuring principle [17]. It was first deployed for the evaluation of HSc by Fong et al. [18] in the late 1990s and later by Draaijers et al. [19], with both groups reporting good inter-rater reliability. This foundational work was more recently expanded upon with the demonstration that the Cutometer also exhibits good intra-rater reliability and can clearly discriminate HSc from normal scar and normal skin [16]. The measurement of vascularity (erythema) and pigmentation (melanin) in HSc has been objectively evaluated using a number of different instruments [20] that basically fall into two categories: tristimulus colorimeters and narrow-band simple reflectance metres. The Mexameter1 falls into the latter category and has been shown to have good intra- and interrater reliability and concurrent validity with the mVSS subscales [17]. An important attribute of both the Cutometer and the Mexameter is that the central portion of the measurement probe is spring-mounted to maintain consistent pressure during and between measurements, which has been shown to be an important consideration when evaluating skin characteristics [21]. Investigation of factors that may predict the formation of HSc had revealed that increased risk is associated with wounds that take longer than 3 weeks to heal [22], gender, age, anatomical location, multiple surgical procedures and meshed skin grafts [23]. However, the clinical recovery profile over time once HSc has developed has not been investigated. Thus, the objective of this study was to prospectively quantify
the thickness, pliability, vascularity and pigmentation of patient-matched, after burn HSc, donor site or normal scar and normal skin using the DermaScan C1 (high-frequency ultrasound), the Cutometer and the Mexameter.
2.
Methods
2.1.
Study population
Forty-six subjects with significant HSc were recruited for this study according to the following inclusion criteria: (1) HSc development in a healed burn wound, (2) skin graft donor site present, (3) age greater than 18 years, and (4) informed consent was obtained. Exclusion criteria included: (1) had a diagnosed psychiatric illness that impaired their ability to participate in the study or provide informed consent, (2) had a dermatological condition in the region of the evaluation site that could interfere with the study results such as psoriasis, eczema, etc., (3) had a suspected or known allergy to ultrasound gel, or (4) had refused to give informed consent. This study was approved by the Research Ethics Committees of CHUM – Hoˆtel-Dieu and Villa Medica Rehabilitation Hospital as well as by the Institutional Review Board of McGill University, Faculty of Medicine.
2.2.
Measurement procedures
Three sites were selected for evaluation on each participant including: (1) their most severe scar, (2) a donor site, and (3) a normal skin site corresponding to the same or an adjacent anatomic site as that of the most severe scar. For the most severe scar all sites would have been rated as 1 on the Vancouver Scar Scale for height, pliability and vascularity. Measurements were conducted in a temperature-controlled room (218 2 8C) with the participant in the same position for each consecutive measurement (supine on an examination table with their arms at their sides). If participants were wearing pressure garments or gels they were asked to remove them at least 20 min before their appointment and were rested for a minimum of 5 min prior to any measurements being completed. A transparent film (Transflexcast Film, Omer DeSerres, Montreal, Canada) was applied to the region to be measured and notable landmarks were traced on the film to facilitate identification of the measurement site(s) as previously described [16,17]. A circular template, approximately 3 cm in diameter, was drawn on the film where the measurements were to be taken. This was then drawn on the skin with a water-soluble pen to facilitate consistency between measurement tools. The test sites were photographed to further identify their location for serial measurements. All 3 sites were evaluated by the same observer on 3 different days (3, 6, and 12 months after injury), using several instruments: the DermaScan C, the Cutometer and the Mexameter. For each evaluation session, the observer was blinded to the previous measurement results.
2.3.
Measurement tools
The DermaScan C (Cortex Technology, Handsund, Denmark) is a high-frequency (20 MHz), ultrasound scanner that captures
Please cite this article in press as: Nedelec B, et al. Longitudinal burn scar quantification. Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.03.002
JBUR-4316; No. of Pages 9 burns xxx (2014) xxx–xxx
and reproduces high-resolution soft tissue images. Image processing software (Dermavision 2D, Dscan C v. 3, Cortex Technology, Handsund, Denmark) allows skin thickness measurement. A medium focus transducer with a 12 mm wide viewing field that was able to penetrate to 15 mm below the skin surface was used for this study. Prior to each measurement a thin layer of conducting ultrasound gel (EcoGel 100 Imaging Ultrasound Gel, Eco-med Pharmaceutical Inc., Mississauga, ON, Canada) was applied to the transducer to provide contact between the clear plastic diaphragm and the skin surface. The transducer was held perpendicular to the site while the echographic image was recorded. The thickness measurements were later generated by the investigator using the dedicated computer software. The distance between the outer surface of the echogenic stratum corneum and the inner surface of the dermis, which is the boundary of the hypoechogenic subcutaneous fat, was recorded as the total skin thickness in millimeters. All measurements were performed with the ultrasound velocity set at 1580 m/s. The Cutometer (MPA 580, Courage & Khazaka Electronic GmbH, Koln, Germany) is an electronic instrument that assesses skin elasticity based on the suction and elongation measuring principle. The device generates negative pressure, which draws the skin into a hollow aperture in the centre of the probe and estimates skin penetration depth with an optical measuring system. Four different measurement modes feature pre-programmed sequences of ‘‘on/off’’ pressure cycles. For this study mode 1 was chosen as it delivers cycles of negative air pressure (450 mbar) for 2 s followed by 2 s of no pressure. The results are expressed as the means of 3 measurement cycles. The probe with a 6 mm hollow aperture, determined to most efficiently measure the viscoelasticity of the dermis [24,25], was used for this study. The 10.2 cm long probe has a spring-mounted central measurement portion (2.5 cm in diameter) to ensure constant pressure on the skin throughout the measurement cycle. Prior to the measurement cycle, the probe is applied lightly on the skin, without the outer ring contacting the skin surface, at a perpendicular axis to the skin. During the measurement cycle, it is important that neither the subject nor the probe move. Skin elasticity parameters are traditionally expressed as either absolute parameters (Ua, Ue, Uf, Ur, Uv) or relative parameters (Rparameters). However, since the R0 = Uf parameter (which represents the maximum deformation or extension of the skin) has previously been shown to provide the most reliable measurement of scar tissue when using the Cutometer [16,26], only this measurement was used for analysis in this study. The Cutometer was cleaned and calibrated biweekly as per the manufacturer’s specifications. The Mexameter (MX18, Courage & Khazaka Electronic GmbH) quantifies scar erythema and melanin based on the tissue’s narrow wavelength light absorption. The probe has 16 light-emitting diodes that send 3 defined wavelengths of light (568, 660, and 880 nm). A receiver then measures the light reflected by the skin. Since the quantity of emitted light is known, the absorption rate of defined wavelengths can be ascertained, which are selectively absorbed by melanin (660 nm) pigments or haemoglobin (568 nm). The measurement area is 5 mm in diameter although the total skin surface contacted by the probe is 2 cm in diameter. Like the
3
Cutometer, the central portion of the Mexameter is spring mounted to maintain constant pressure on the skin. For each measurement, the probe was held perpendicular to the skin. It lightly touched the skin surface, without the outer ring making contact, activating the light emitter. The reflected light was measured by the receiver and the erythema and melanin index (range 1–1000) was immediately displayed on the console, thus the probe only remains in contact with the skin for several seconds.
2.4.
Statistical analyses
We reported descriptive statistics as counts and percentages for categorical variables. For continuous variables we reported means and standard deviations if there was evidence that the distribution of values followed a normal distribution, and median and inter-quartile range (IQR) otherwise. Differences in means between areas at each time point as well as differences in means between times at each site were calculated for all parameters with a mixed model regression analysis, taking into account two sources of within-subject correlation: one due to measurements on three sites for each subject and the other to the repeated measurements over time. We also adjusted for the continuous covariates age and TBSA, as well as the categorical covariates gender, site, and etiology. Post hoc multiple comparisons were performed by calculating all-pair of means contrasts and adjusting p-values for multiplicity of testing. We used the SAS macro %SimTests with the unconstrained step-down method, a closed testing procedure to account for logical dependencies between the hypotheses [27]. All hypothesis tests were two-sided and were performed at the 0.05 level of significance. All analyses were done using SAS, version 9.2 (SAS Institute Inc., Cary, NC).
3.
Results
3.1.
Study population
The demographics of the participants and the clinical characteristics of the sites chosen for evaluation are reported in Table 1. A total of 46 participants were recruited into this study with the majority being male (87%). Their mean age was 41.2 13.5 years, with a median percent total body surface area (TBSA) burned of 19.5% (IQR 9.5–34.0). The most common mechanism of injury was fire/flame, followed by scalding. All participants were categorized as Fitzpatrick’s skin type I–V with the majority categorized as types II–IV (83%). All participants underwent skin grafting and all of the chosen scar sites were located at grafted sites. The scar sites were more commonly located on the upper extremity, but the donor sites were mostly on the lower extremity. For 82.6% of the participants the normal skin site evaluated matched the HSc site, but, for the remainder, site-matched normal skin was not available; therefore, the closest available anatomical site was chosen. All participants had been prescribed pressure garments and moisturizers or lubricants for the treatment of their scar sites and moisturizers or lubricants for their donor sites but pressure therapy is generally not prescribed for donor sites
Please cite this article in press as: Nedelec B, et al. Longitudinal burn scar quantification. Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.03.002
JBUR-4316; No. of Pages 9
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Table 1 – Participant demographics and clinical characteristics of the skin sites evaluated.
months = 1.61 0.12 mm, 12 months = 1.49 0.1 mm) and normal skin thickness (3 months = 1.52 0.11 mm, 6 months = 1.5 0.12 mm, 12 months = 1.39 0.1 mm) did not significantly differ and did not significantly change over time (Tables 2 and 3 and Fig. 1A).
Clinical characteristics (n = 46) Gender Female Male Age Mean SD Maximum Minimum % TBSA burned Median (IQR) Maximum Minimum Etiology Fire/Flame Scalding Fitzpatrick’s skin phototype I II III IV V VI
Location Upper extremity Abdomen/back Hand Lower extremity
6 (13%) 40 (87%)
3.4. 41.2 13.5 years 74 20 19.5 (9.5–34.0)% 75 2 38 8 7 (15%) 17 (37%) 11 (24%) 10 (22%) 1 (2%) 0 (0%)
HSc
D
N
22 10 10 4
3 6 0 37
21 10 3 12
Pliability
The pliability of the HSc, donor and normal skin sites were significantly different from each other at all time points (All p < 0.0001) (Table 2). There was no significant change in pliability of normal skin over time, but the pliability of HSc increased between 6 (0.24 0.04 mm) and 12 months (0.35 0.05 mm) ( p = 0.03) and three (0.21 0.04 mm) and 12 months ( p = 0.02). The pliability of the donor sites also increased between 3 (0.39 0.04 mm) and 6 months (0.49 0.04 mm) ( p = 0.03) and three and 12 months (0.58 0.05 mm) ( p = 0.02), but by 12 months neither the donor sites nor the HSc reached normal skin pliability (3 months = 0.67 0.05 mm, 6 months = 0.74 0.05 mm, 12 months = 0.77 0.05 mm) (Tables 2 and 3 and Fig. 1B).
3.5.
Erythema
The mean difference between the four skin characteristics: thickness, pliability, erythema and pigmentation are presented in Tables 2 and 3. In Table 2 the mean difference of these characteristics are compared between the three different sites; HSc, donor sites or normal scar and normal skin, and the adjusted p-values provided. In Table 3 the mean difference of these skin characteristics are compared at the three different time points: 3, 6 and 12 months, and the p-values provided.
The HSc (3 months = 413.30 15.04, 6 months = 398.86 11.63, 12 months = 361.31 12.39) and donor (3 months = 361.99 16.92, 6 months = 288.46 14.30, 12 months = 245.96 15.10) sites were significantly more erythematous than normal skin (3 months = 228.40 14.85, 6 months = 208.75 12.36, 12 months =220.25 14.24) at 3 and 6 months but by 12 months the erythema of the donor site had reduced to near normal skin levels. Although the erythema index of the donor site was significantly higher than normal skin at 3 and 6 months, it was significantly lower than HSc at all time points. The erythema reduction at the donor sites was statistically significant between all time points (All p < 0.0001), with a total reduction (from 3 to 12 months) of 116 units where the average erythema index reading of normal skin was approximately 220 units when averaged across all time points. Conversely, there was no change of the erythema of HSc between 3 and 6 months but there was a significant reduction between 6 and 12 months ( p = 0.001) and 3 and 12 months ( p = 0.004). The total reduction of the HSc erythema index between 3 and 12 months was 51.98 units. The erythema of normal skin sites did not significantly change over time (Tables 2 and 3 and Fig. 1C).
3.3.
3.6.
TBSA = total body surface area; HSc = hypertrophic scar; D = donor; N = normal skin site; SD = standard deviation; % = percent.
unless HSc develops; however, compliance was not monitored as part of this study.
3.2.
Skin characteristics
Thickness
The HSc site was significantly thicker than the donor site and the normal skin site at three (4.35 0.17 mm), six (3.75 0.17 mm) and twelve (2.99 0.15 mm) months after injury (All p < 0.0001) (Table 2). The HSc significantly decreased in thickness over the time spans 3–6 months, 6–12 months and 3–12 months (All p < 0.0001). The average total reduction in HSc thickness between 3 and 12 months was 1.38 mm (Table 3). In spite of this substantial reduction the HSc did not return to normal or donor site thickness by 12 months after injury, and in fact continued to be approximately twice as thick as normal skin 12 month after injury (Table 2). At all time points the donor site (3 months = 1.67 0.11 mm, 6
Pigmentation
The only time point at which the melanin index significantly varied between the HSc (3 months = 108.61 16.02 units, 6 months = 106.25 15.42 units, 12 months = 146.93 13.93 units), donor (3 months = 148.27 15.97, 6 months = 152.66 15.42, 12 months = 140.84 13.93) and normal skin (3 months = 130.97 15.97, 6 months = 128.99 15.42, 12 months = 129.73 13.93) sites was between HSc and donor at 6 months ( p = 0.02). There was no significant change of the melanin index at the donor site with time but there was a significant increase of the HSc melanin index between 6 and 12 months ( p = 0.003) and between 3 and 12 months ( p = 0.02). The normal skin site did not change significantly with time (Tables 2 and 3 and Fig. 1D).
Please cite this article in press as: Nedelec B, et al. Longitudinal burn scar quantification. Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.03.002
JBUR-4316; No. of Pages 9
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burns xxx (2014) xxx–xxx
Table 2 – Comparison of mean difference between sites at 3, 6 and 12 months for thickness, pliability, erythema and pigmentation. Skin characteristic Thickness
Time
Site
Mean difference
p-value
3 months
HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N
2.71 2.86 0.16 2.16 2.27 0.12 1.50 1.60 0.10 0.18 0.47 0.28 0.25 0.50 0.25 0.20 0.41 0.20 51.3 184.9 133.6 110.4 190.1 79.7 115.3 141.1 25.7 39.7 22.4 17.3 46.4 22.7 23.7 6.1 17.2 11.1
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.elsevier.com/locate/burns
Longitudinal burn scar quantification Bernadette Nedelec a,b,c,*, Jose´ A. Correa d, Ana de Oliveira b,c, Leo LaSalle c, Isabelle Perrault b a
School of Physical and Occupational Therapy, McGill University, Canada Centre de recherche du Centre Hospitalier de l’Universite´ de Montre´al (CHUM), Canada c Hoˆpital de re´adaptation Villa Medica, Canada d Department of Mathematics and Statistics, McGill University, Montreal, Quebec, Canada b
article info
abstract
Article history:
Quantitative studies of the clinical recovery of burn scars are currently lacking. Previous
Accepted 6 March 2014
reports validate the objective, precise, diagnostic capabilities of high-frequency ultrasound to measure thickness, the Cutometer1 to measure pliability and the Mexameter1 to
Keywords:
measure erythema and pigmentation of scars. Thus, we prospectively quantified clinical
Hypertrophic scar
characteristics of patient-matched, after burn hypertrophic scar (HSc), donor site scar (D)
Burns
and normal skin (N) using these instruments. One investigator measured 3 sites (HSc, D, N)
Skin injuries
in 46 burn survivors at 3, 6, and 12 months after-burn. A mixed model regression analysis,
Cutometer
adjusting p-values for multiplicity of testing, was used to compare means among sites and
Mexameter
time points. Participants were 41.2 13.5 years old, 87% males, predominantly Caucasian,
High-frequency ultrasound
with an average of 19.5% body surface area burned. HSc thickness decreased significantly
scanning
between 3 and 6, 6 and 12, and 3 and 12 months (all p < 0.0001), but remained thicker than D and N skin (all p < 0.0001). Pliability differed significantly between HSc, D and N sites at all time points (all p < 0.0001), with HSc and D increasing between 3 and 12 months ( p < 0.05) but not reaching normal. HSc and D sites were significantly more erythematous than normal skin ( p < 0.05) at 3 and 6 months but D sites approached normal by 12 months. The only time points at which pigmentation significantly differed were the HSc and D sites at 6 months. Thickness, pliability, erythema and pigmentation of N skin remained similar over the 12 months. We found that post-burn HSc thickness, pliability and erythema differed significantly from D and N skin at 3, 6, and 12 months and does not return to normal by 12 months after-injury; however, significant improvements towards normal can be expected. Donor sites are redder than normal skin at 3 and 6 months but can be expected to return to normal by 12 months. Although the color of HSc and D sites change markedly with time these color changes are primarily due to changes in redness of the site, not melanin in this primarily Caucasian population. # 2014 Elsevier Ltd and ISBI. All rights reserved.
* Corresponding author at: McGill University Faculty of Medicine, 3654 Promenade Sir William Osler, Montreal, Quebec H3G 1Y5, Canada. Tel.: +1 514 398 1275; fax: +1 514 398 8193. E-mail address: [email protected] (B. Nedelec). http://dx.doi.org/10.1016/j.burns.2014.03.002 0305-4179/# 2014 Elsevier Ltd and ISBI. All rights reserved.
Please cite this article in press as: Nedelec B, et al. Longitudinal burn scar quantification. Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.03.002
JBUR-4316; No. of Pages 9
2
burns xxx (2014) xxx–xxx
1.
Introduction
The formation of hypertrophic scars (HSc) is one of the most important long-term morbidities after a burn injury. A hypertrophic scar is defined as a raised, red, rigid scar that may be hypo or hyper-pigmented and is often itchy and/or painful. It is associated with the formation of contractures [1,2], functional limitations, psychological distress [3,4] and decreased quality of life [3,5]. One of the limitations that have impaired our ability to advance our understanding of the pathophysiology and clinical recovery profile of HSc is that subjective scar evaluation scales have typically been used as outcome measures [6–9], but the nature of such scales renders them prone to bias. Although it continues to be important to obtain the patient’s subjective impression of the outcome of their scar, the availability of objective evaluation instruments that provide more accurate data now allows for precise quantification of the physical scar characteristics [10–12]. The physical characteristics that are most commonly included in subjective assessment scales include thickness, pliability, vascularity and pigmentation [6–9,13,14]. Each of these characteristics can be evaluated with objective evaluation instruments. The use of high-frequency ultrasound scanners to quantify scar thickness was initially proposed by Katz et al. in the 1980s [15]. More recently high-frequency, high-resolution ultrasound has been shown to provide reliable thickness measurements of HSc [16,17] that were able to clearly discriminate HSc from normal scar and normal skin [16] and showed good concurrent validity with the modified Vancouver Scar Scale (mVSS) [17]. The Cutometer1 determines skin elasticity based on the suction and elongation measuring principle [17]. It was first deployed for the evaluation of HSc by Fong et al. [18] in the late 1990s and later by Draaijers et al. [19], with both groups reporting good inter-rater reliability. This foundational work was more recently expanded upon with the demonstration that the Cutometer also exhibits good intra-rater reliability and can clearly discriminate HSc from normal scar and normal skin [16]. The measurement of vascularity (erythema) and pigmentation (melanin) in HSc has been objectively evaluated using a number of different instruments [20] that basically fall into two categories: tristimulus colorimeters and narrow-band simple reflectance metres. The Mexameter1 falls into the latter category and has been shown to have good intra- and interrater reliability and concurrent validity with the mVSS subscales [17]. An important attribute of both the Cutometer and the Mexameter is that the central portion of the measurement probe is spring-mounted to maintain consistent pressure during and between measurements, which has been shown to be an important consideration when evaluating skin characteristics [21]. Investigation of factors that may predict the formation of HSc had revealed that increased risk is associated with wounds that take longer than 3 weeks to heal [22], gender, age, anatomical location, multiple surgical procedures and meshed skin grafts [23]. However, the clinical recovery profile over time once HSc has developed has not been investigated. Thus, the objective of this study was to prospectively quantify
the thickness, pliability, vascularity and pigmentation of patient-matched, after burn HSc, donor site or normal scar and normal skin using the DermaScan C1 (high-frequency ultrasound), the Cutometer and the Mexameter.
2.
Methods
2.1.
Study population
Forty-six subjects with significant HSc were recruited for this study according to the following inclusion criteria: (1) HSc development in a healed burn wound, (2) skin graft donor site present, (3) age greater than 18 years, and (4) informed consent was obtained. Exclusion criteria included: (1) had a diagnosed psychiatric illness that impaired their ability to participate in the study or provide informed consent, (2) had a dermatological condition in the region of the evaluation site that could interfere with the study results such as psoriasis, eczema, etc., (3) had a suspected or known allergy to ultrasound gel, or (4) had refused to give informed consent. This study was approved by the Research Ethics Committees of CHUM – Hoˆtel-Dieu and Villa Medica Rehabilitation Hospital as well as by the Institutional Review Board of McGill University, Faculty of Medicine.
2.2.
Measurement procedures
Three sites were selected for evaluation on each participant including: (1) their most severe scar, (2) a donor site, and (3) a normal skin site corresponding to the same or an adjacent anatomic site as that of the most severe scar. For the most severe scar all sites would have been rated as 1 on the Vancouver Scar Scale for height, pliability and vascularity. Measurements were conducted in a temperature-controlled room (218 2 8C) with the participant in the same position for each consecutive measurement (supine on an examination table with their arms at their sides). If participants were wearing pressure garments or gels they were asked to remove them at least 20 min before their appointment and were rested for a minimum of 5 min prior to any measurements being completed. A transparent film (Transflexcast Film, Omer DeSerres, Montreal, Canada) was applied to the region to be measured and notable landmarks were traced on the film to facilitate identification of the measurement site(s) as previously described [16,17]. A circular template, approximately 3 cm in diameter, was drawn on the film where the measurements were to be taken. This was then drawn on the skin with a water-soluble pen to facilitate consistency between measurement tools. The test sites were photographed to further identify their location for serial measurements. All 3 sites were evaluated by the same observer on 3 different days (3, 6, and 12 months after injury), using several instruments: the DermaScan C, the Cutometer and the Mexameter. For each evaluation session, the observer was blinded to the previous measurement results.
2.3.
Measurement tools
The DermaScan C (Cortex Technology, Handsund, Denmark) is a high-frequency (20 MHz), ultrasound scanner that captures
Please cite this article in press as: Nedelec B, et al. Longitudinal burn scar quantification. Burns (2014), http://dx.doi.org/10.1016/ j.burns.2014.03.002
JBUR-4316; No. of Pages 9 burns xxx (2014) xxx–xxx
and reproduces high-resolution soft tissue images. Image processing software (Dermavision 2D, Dscan C v. 3, Cortex Technology, Handsund, Denmark) allows skin thickness measurement. A medium focus transducer with a 12 mm wide viewing field that was able to penetrate to 15 mm below the skin surface was used for this study. Prior to each measurement a thin layer of conducting ultrasound gel (EcoGel 100 Imaging Ultrasound Gel, Eco-med Pharmaceutical Inc., Mississauga, ON, Canada) was applied to the transducer to provide contact between the clear plastic diaphragm and the skin surface. The transducer was held perpendicular to the site while the echographic image was recorded. The thickness measurements were later generated by the investigator using the dedicated computer software. The distance between the outer surface of the echogenic stratum corneum and the inner surface of the dermis, which is the boundary of the hypoechogenic subcutaneous fat, was recorded as the total skin thickness in millimeters. All measurements were performed with the ultrasound velocity set at 1580 m/s. The Cutometer (MPA 580, Courage & Khazaka Electronic GmbH, Koln, Germany) is an electronic instrument that assesses skin elasticity based on the suction and elongation measuring principle. The device generates negative pressure, which draws the skin into a hollow aperture in the centre of the probe and estimates skin penetration depth with an optical measuring system. Four different measurement modes feature pre-programmed sequences of ‘‘on/off’’ pressure cycles. For this study mode 1 was chosen as it delivers cycles of negative air pressure (450 mbar) for 2 s followed by 2 s of no pressure. The results are expressed as the means of 3 measurement cycles. The probe with a 6 mm hollow aperture, determined to most efficiently measure the viscoelasticity of the dermis [24,25], was used for this study. The 10.2 cm long probe has a spring-mounted central measurement portion (2.5 cm in diameter) to ensure constant pressure on the skin throughout the measurement cycle. Prior to the measurement cycle, the probe is applied lightly on the skin, without the outer ring contacting the skin surface, at a perpendicular axis to the skin. During the measurement cycle, it is important that neither the subject nor the probe move. Skin elasticity parameters are traditionally expressed as either absolute parameters (Ua, Ue, Uf, Ur, Uv) or relative parameters (Rparameters). However, since the R0 = Uf parameter (which represents the maximum deformation or extension of the skin) has previously been shown to provide the most reliable measurement of scar tissue when using the Cutometer [16,26], only this measurement was used for analysis in this study. The Cutometer was cleaned and calibrated biweekly as per the manufacturer’s specifications. The Mexameter (MX18, Courage & Khazaka Electronic GmbH) quantifies scar erythema and melanin based on the tissue’s narrow wavelength light absorption. The probe has 16 light-emitting diodes that send 3 defined wavelengths of light (568, 660, and 880 nm). A receiver then measures the light reflected by the skin. Since the quantity of emitted light is known, the absorption rate of defined wavelengths can be ascertained, which are selectively absorbed by melanin (660 nm) pigments or haemoglobin (568 nm). The measurement area is 5 mm in diameter although the total skin surface contacted by the probe is 2 cm in diameter. Like the
3
Cutometer, the central portion of the Mexameter is spring mounted to maintain constant pressure on the skin. For each measurement, the probe was held perpendicular to the skin. It lightly touched the skin surface, without the outer ring making contact, activating the light emitter. The reflected light was measured by the receiver and the erythema and melanin index (range 1–1000) was immediately displayed on the console, thus the probe only remains in contact with the skin for several seconds.
2.4.
Statistical analyses
We reported descriptive statistics as counts and percentages for categorical variables. For continuous variables we reported means and standard deviations if there was evidence that the distribution of values followed a normal distribution, and median and inter-quartile range (IQR) otherwise. Differences in means between areas at each time point as well as differences in means between times at each site were calculated for all parameters with a mixed model regression analysis, taking into account two sources of within-subject correlation: one due to measurements on three sites for each subject and the other to the repeated measurements over time. We also adjusted for the continuous covariates age and TBSA, as well as the categorical covariates gender, site, and etiology. Post hoc multiple comparisons were performed by calculating all-pair of means contrasts and adjusting p-values for multiplicity of testing. We used the SAS macro %SimTests with the unconstrained step-down method, a closed testing procedure to account for logical dependencies between the hypotheses [27]. All hypothesis tests were two-sided and were performed at the 0.05 level of significance. All analyses were done using SAS, version 9.2 (SAS Institute Inc., Cary, NC).
3.
Results
3.1.
Study population
The demographics of the participants and the clinical characteristics of the sites chosen for evaluation are reported in Table 1. A total of 46 participants were recruited into this study with the majority being male (87%). Their mean age was 41.2 13.5 years, with a median percent total body surface area (TBSA) burned of 19.5% (IQR 9.5–34.0). The most common mechanism of injury was fire/flame, followed by scalding. All participants were categorized as Fitzpatrick’s skin type I–V with the majority categorized as types II–IV (83%). All participants underwent skin grafting and all of the chosen scar sites were located at grafted sites. The scar sites were more commonly located on the upper extremity, but the donor sites were mostly on the lower extremity. For 82.6% of the participants the normal skin site evaluated matched the HSc site, but, for the remainder, site-matched normal skin was not available; therefore, the closest available anatomical site was chosen. All participants had been prescribed pressure garments and moisturizers or lubricants for the treatment of their scar sites and moisturizers or lubricants for their donor sites but pressure therapy is generally not prescribed for donor sites
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Table 1 – Participant demographics and clinical characteristics of the skin sites evaluated.
months = 1.61 0.12 mm, 12 months = 1.49 0.1 mm) and normal skin thickness (3 months = 1.52 0.11 mm, 6 months = 1.5 0.12 mm, 12 months = 1.39 0.1 mm) did not significantly differ and did not significantly change over time (Tables 2 and 3 and Fig. 1A).
Clinical characteristics (n = 46) Gender Female Male Age Mean SD Maximum Minimum % TBSA burned Median (IQR) Maximum Minimum Etiology Fire/Flame Scalding Fitzpatrick’s skin phototype I II III IV V VI
Location Upper extremity Abdomen/back Hand Lower extremity
6 (13%) 40 (87%)
3.4. 41.2 13.5 years 74 20 19.5 (9.5–34.0)% 75 2 38 8 7 (15%) 17 (37%) 11 (24%) 10 (22%) 1 (2%) 0 (0%)
HSc
D
N
22 10 10 4
3 6 0 37
21 10 3 12
Pliability
The pliability of the HSc, donor and normal skin sites were significantly different from each other at all time points (All p < 0.0001) (Table 2). There was no significant change in pliability of normal skin over time, but the pliability of HSc increased between 6 (0.24 0.04 mm) and 12 months (0.35 0.05 mm) ( p = 0.03) and three (0.21 0.04 mm) and 12 months ( p = 0.02). The pliability of the donor sites also increased between 3 (0.39 0.04 mm) and 6 months (0.49 0.04 mm) ( p = 0.03) and three and 12 months (0.58 0.05 mm) ( p = 0.02), but by 12 months neither the donor sites nor the HSc reached normal skin pliability (3 months = 0.67 0.05 mm, 6 months = 0.74 0.05 mm, 12 months = 0.77 0.05 mm) (Tables 2 and 3 and Fig. 1B).
3.5.
Erythema
The mean difference between the four skin characteristics: thickness, pliability, erythema and pigmentation are presented in Tables 2 and 3. In Table 2 the mean difference of these characteristics are compared between the three different sites; HSc, donor sites or normal scar and normal skin, and the adjusted p-values provided. In Table 3 the mean difference of these skin characteristics are compared at the three different time points: 3, 6 and 12 months, and the p-values provided.
The HSc (3 months = 413.30 15.04, 6 months = 398.86 11.63, 12 months = 361.31 12.39) and donor (3 months = 361.99 16.92, 6 months = 288.46 14.30, 12 months = 245.96 15.10) sites were significantly more erythematous than normal skin (3 months = 228.40 14.85, 6 months = 208.75 12.36, 12 months =220.25 14.24) at 3 and 6 months but by 12 months the erythema of the donor site had reduced to near normal skin levels. Although the erythema index of the donor site was significantly higher than normal skin at 3 and 6 months, it was significantly lower than HSc at all time points. The erythema reduction at the donor sites was statistically significant between all time points (All p < 0.0001), with a total reduction (from 3 to 12 months) of 116 units where the average erythema index reading of normal skin was approximately 220 units when averaged across all time points. Conversely, there was no change of the erythema of HSc between 3 and 6 months but there was a significant reduction between 6 and 12 months ( p = 0.001) and 3 and 12 months ( p = 0.004). The total reduction of the HSc erythema index between 3 and 12 months was 51.98 units. The erythema of normal skin sites did not significantly change over time (Tables 2 and 3 and Fig. 1C).
3.3.
3.6.
TBSA = total body surface area; HSc = hypertrophic scar; D = donor; N = normal skin site; SD = standard deviation; % = percent.
unless HSc develops; however, compliance was not monitored as part of this study.
3.2.
Skin characteristics
Thickness
The HSc site was significantly thicker than the donor site and the normal skin site at three (4.35 0.17 mm), six (3.75 0.17 mm) and twelve (2.99 0.15 mm) months after injury (All p < 0.0001) (Table 2). The HSc significantly decreased in thickness over the time spans 3–6 months, 6–12 months and 3–12 months (All p < 0.0001). The average total reduction in HSc thickness between 3 and 12 months was 1.38 mm (Table 3). In spite of this substantial reduction the HSc did not return to normal or donor site thickness by 12 months after injury, and in fact continued to be approximately twice as thick as normal skin 12 month after injury (Table 2). At all time points the donor site (3 months = 1.67 0.11 mm, 6
Pigmentation
The only time point at which the melanin index significantly varied between the HSc (3 months = 108.61 16.02 units, 6 months = 106.25 15.42 units, 12 months = 146.93 13.93 units), donor (3 months = 148.27 15.97, 6 months = 152.66 15.42, 12 months = 140.84 13.93) and normal skin (3 months = 130.97 15.97, 6 months = 128.99 15.42, 12 months = 129.73 13.93) sites was between HSc and donor at 6 months ( p = 0.02). There was no significant change of the melanin index at the donor site with time but there was a significant increase of the HSc melanin index between 6 and 12 months ( p = 0.003) and between 3 and 12 months ( p = 0.02). The normal skin site did not change significantly with time (Tables 2 and 3 and Fig. 1D).
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Table 2 – Comparison of mean difference between sites at 3, 6 and 12 months for thickness, pliability, erythema and pigmentation. Skin characteristic Thickness
Time
Site
Mean difference
p-value
3 months
HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N HSc-D HSc-N D-N
2.71 2.86 0.16 2.16 2.27 0.12 1.50 1.60 0.10 0.18 0.47 0.28 0.25 0.50 0.25 0.20 0.41 0.20 51.3 184.9 133.6 110.4 190.1 79.7 115.3 141.1 25.7 39.7 22.4 17.3 46.4 22.7 23.7 6.1 17.2 11.1
