Seventeen-point dermal ultrasound scoring systema reliable measure of skin thickness in patients with systemic sclerosis
T. L. Moore1,
M. Lunt3,
B. McManus2,
M. E. Anderson1 and
A. L. Herrick1,3
1University of Manchester Rheumatic Diseases Centre and 2Radiology Directorate, Hope Hospital, Salford M6 8HD and 3ARC Epidemiology Unit, University of Manchester M13 9PT, UK.
Correspondence to:
A. Herrick, University of Manchester Rheumatic Diseases Centre, Clinical Sciences Building, Hope Hospital, Salford M6 8HD. E-mail: aherrick{at}fs1.ho.man.ac.uk
 |
Abstract
|
---|
Objective. Our objective was to develop a 17-site ultrasound method of measuring skin thickness in patients with systemic sclerosis (SSc) and to assess its inter- and intra-observer variability.
Methods. Dermal thickness (using a 22 MHz ultrasound probe) was measured at 17 sites (corresponding to those assessed in the modified Rodnan skin score) in 39 patients with SSc (26 limited cutaneous, 13 diffuse) and 34 healthy controls. The sum of the thicknesses (at the 17 sites) and the maximal thickness were also documented. Because skin thickness varies between sites, each measurement was converted to a z-score. Inter- and intra-observer variability were assessed in 35 patients/33 controls, and 20 patients/15 controls respectively.
Results. Measurement precision was good for the dermal measurementsintraclass correlation coefficients at the 17 sites ranged from 0.65 to 0.94 for the inter-observer variability (0.86 for maximum thickness) and from 0.55 to 0.96 for the intra-observer variability (0.92 for maximum thickness).
Conclusion. Our results suggest that the 17-point dermal ultrasound scoring system is extremely reliable and may therefore be a useful measure of outcome, including in clinical trials.
KEY WORDS: Scleroderma, Skin score, Dermal ultrasound.
 |
Introduction
|
---|
The degree of skin involvement is a very important outcome measure in patients with systemic sclerosis (SSc), as this predicts mortality [1]. Thus skin score (usually a modified Rodnan) is the primary end-point in most clinical trials aimed at investigating potential new disease modifying treatments for patients with early diffuse cutaneous SSc [2, 3]. The skin scoring method has now been validated in a number of studies [4]. Yet there are problems inherent in this method including concerns about both intra- and inter-observer variability (estimated at 12 and 25%, respectively [5]), and the insensitivity of the technique to detect small but clinically relevant changes in skin thickness over time. Although using the same observer for all visits circumvents the inter-observer variability problem, this presents practical difficulties in multicentre studies. The ability to measure reliably small changes in skin thickness (studying several body sites) using an outcome measure that is more sensitive to change than skin score would be of considerable benefit in facilitating clinical trials of diffuse cutaneous disease, because this would permit studies involving smaller numbers of patients than are currently recommended to be sufficiently highly powered to provide clinically meaningful results. This is a key issue because it is often difficult to recruit sufficient patient numbers into studies of early diffuse disease, and this has undoubtedly hindered clinical research. The importance of identifying outcome measures that are sensitive to change in patients with SSc is well recognized [6].
Against this background, we set out to develop an ultrasound method of measuring skin thickness in patients with SSc which is reliable and sensitive to change. While several authors have previously suggested that ultrasound might be useful in the assessment of sclerodermatous skin [715], what is new about the current study is that we have looked at multiple sites, mainly corresponding to the 17 sites of the modified Rodnan skin score [16]. Although this method is time consuming, we hypothesized that by using multiple sites we might increase the sensitivity of the technique to detect change over time. However, the first step, reported below, was to assess the reliability of this 17-site technique.
Because some authors have examined full skin thickness (a composite of epidermis and dermis) whereas others have measured dermis only (and in some papers this choice is unclear), we chose to measure both epidermis and dermis separately.
 |
Patients and methods
|
---|
Patients and controls
Skin thickness measurements were made in 39 patients with SSc (8 male, 31 female; median age 52 yr, range 2772 yr) and 34 healthy control subjects (5 male, 29 female; median age 46 yr, range 2674 yr). Of the patients with SSc, 26 had limited cutaneous (LCSSc) and 13 had diffuse cutaneous (DCSSc) disease [17]. Thirty-seven of the patients fulfilled the American Rheumatism Association criteria for the disease [18]. Of the two remaining patients, both had severe Raynauds phenomenon, sclerodactyly and nailfold abnormalities and in addition one had upper gastrointestinal involvement. The study was approved by the Salford and Trafford Local Research Ethics Committee, all subjects signed informed consent.
Methods
Ultrasound. Measurements were obtained at the same time of day (between 0900 h and 1200 h), as it is recognized that there is a diurnal variation in dermal oedema [19], after an acclimatization period of 20 min. A Diasus ultrasound machine (Dynamic Imaging Ltd, Livingston, Scotland) fitted with a 22 MHz probe was used. The probe was placed perpendicularly to the skin using a moderate thickness of ultrasonic gel in order to separate the epidermal echo from the front face of the probe echo on the image. Measurements were made from the two-dimensional B-mode image. An electronic calliper was used to measure epidermis and dermis by identifying the surfaceepidermis, epidermisdermis and dermissubcutis interfaces (Fig. 1). Seventeen sites for measurement (approximating to those of the modified Rodnan skin score) were identified by the following landmarks:
- right and left middle finger (dorsum of middle phalanx), dorsum of the hand (index/middle metacarpal interspace, 2 cm proximal to the metacarpophalangeal joints), the anterior (flexor) aspect of the forearm (10 cm proximal to the ulnar styloid), the anterior aspect of the upper arm (10 cm proximal to the medial epicondyle) (8 sites);
- the forehead (centre of), the anterior chest between the sternal angle and the sternal notch, the anterior abdomen 10 cm distal to the sternum (3 sites);
- right and left thigh (10 cm proximal to the patella), the anterolateral aspect of the lower leg (10 cm proximal to the lateral malleolus), the dorsum of the foot (in the first web space 2 cm proximal to the metatarsophalangeal joints) (6 sites).

View larger version (95K):
[in this window]
[in a new window]
|
FIG. 1. Two-dimensional B-mode dermal images from (top) normal and (bottom) sclerodermatous skin (dorsum of hand) showing (a) surfaceepidermis, (b) epidermisdermis and (c) dermissubcutis interfaces.
|
|
All measurements were performed during the same morning visit. Each set of measurements took in the order of 20 min. Therefore the testing of both inter- and intra-observer variability took approximately 60 min in any one patient.
Assessment of inter-observer variability. Thirty-five patients and 33 controls were examined by a second observer.
Assessment of intra-observer variability. Twenty patients and 15 controls were examined twice by the first observer.
Analysis
In addition to examining skin scores at the different sites, both the sum (of the 17 sites) and the maximum thickness (max) at any site within each individual were documented. Since the normal skin thickness varies between the different sites assessed, each measurement was converted to a z-score by subtracting the mean thickness in controls at that site and dividing by the standard deviation.
The inter- and intra-observer variability was measured using the intraclass correlation coefficient. This represents a theoretical upper bound on the amount of observed variation that is due to genuine differences between individuals. If there were no measurement error, the intraclass correlation coefficient would take the value 1, whereas if there were no variation between individuals, and all the observed variation were due to error, it would take the value 0.
 |
Results
|
---|
Ultrasound measurements of epidermal and dermal thickness
These measurements are shown in Table 1. Results shown in Table 1 relate to Observer 1, Measurement 1.
Inter- and intra-observer variability
The intraclass correlation coefficients for the measurements of the thickness of the dermis and epidermis are given in Table 2. The precision of the measurements of the epidermis is poor, whilst the precision of the measurements of the dermis is good at most sites.
View this table:
[in this window]
[in a new window]
|
TABLE 2. Inter- and intra-observer variability (measurement precision) of epidermal and dermal ultrasound measurements
|
|
 |
Discussion
|
---|
Our results from this cross-sectional study suggest that the 17-point dermal ultrasound scoring method is extremely reliable for measurements of dermis. An important aspect of our study was the separate measurement of epidermis and dermis. Because the precision of epidermal measurements was poor, together with the the fact that epidermal measurements varied very little between sites compared with dermal measurements, it would seem appropriate to include only dermal measurements in future studies. This lack of precision of epidermal measurements is unsurprising, given the poor correlation commented upon by Hoffmann et al. [11] between what they defined as their entry echo and epidermal thickening, as measured histologically. Although the dermissubcutis interface is more readily discernable at some sites (for example forehead and abdomen) than at others (for example hand and fingers, where the dermis lies on fibrous tissue as opposed to fat), reproducibility of dermal measurements was reassuringly high across all sites.
We set out to measure reproducibility in patients with SSc and healthy controls, but did not recruit enough subjects in the different disease subtypes to be able to make meaningful comparisons between subtypes. However, although this was a cross-sectional study including patients with both limited and diffuse cutaneous disease, the fact that reliability of dermal measurements was high for all 17 sites suggests that this scoring system is likely to be useful for measuring change within an individual over time, looking either at a small number of skin sites (for example in the patient with limited cutaneous disease) or, more importantly, at all sites in patients with diffuse cutaneous disease. It is in following patients with early diffuse cutaneous disease, either to assess natural history or response to drug treatment, that we feel our technique may be particularly valuable, although this needs to be tested in prospective studies. To date, ultrasound has not been used in therapeutic trials in patients with SSc. In patients with localized scleroderma, Kerscher et al. [20] reported reduction in ultrasonic skin thickening after UVA1 phototherapy and responses to other treatments have also been reported [21, 22]. We included 34 healthy control subjects in our study because although it was not our primary aim to compare patients and controls, none the less we felt it would be useful to gain experience in applying the technique in healthy controls, and to obtain data that might be compared with those from other studies.
Despite its promise, there have been relatively few studies examining the use of dermal ultrasound in patients with SSc, although there is substantial literature on morphoea. Initial studies using dermal ultrasound in the assessment of scleroderma utilized 10 MHz [9] and 15 MHz [7] probes. Broadly speaking, the higher the resolution, the more accurate the measurement of skin thickness is likely to be, and later studies have used 20 [13, 14], 25 [10] and 30 MHz [12] probes. The highest commercially available frequencies are 2030 MHz, although higher frequencies (up to 100 MHz) are used by researchers and, if these become available, should increase the potential of detecting tiny but possibly still clinically relevant changes in skin thickness [23].
Scheja and Akesson [13] using a 20 MHz probe in a cross-sectional study of 41 patients with SSc and 41 healthy controls, examined three skin sites and reported an inter-observer variability of 1.0% for proximal phalanx, 4.2% for hand and 0.0016% for forearm. These reproducibilities relate to dermal measurements only (the epidermis was not included). In our study we assessed both intra- and inter-observer variability. While we confined ourselves to measuring skin thickness, Scheja and Akesson [13] also examined mean echogenicity and discussed the potential value of this parameter (as well as skin thickness) in examining disease progression over time. Seidenari et al. [15] also described differences in echogenicity between SSc patients and controls.
In conclusion, the reliability of the dermal ultrasound measurements suggests that this technique has the potential of being sufficiently accurate to measure small but clinically important changes over time. By measuring multiple sites, our ability to detect change over time in patients with early diffuse cutaneous disease will be maximized. Prospective studies, looking for change over time, are now required to assess further whether our 17-point scoring system might be included as an outcome measure of skin involvement in future clinical trials.
 |
Acknowledgments
|
---|
We are grateful to the Raynauds and Scleroderma Association for their sponsorship of this research.
Conflict of interest
The authors have declared no conflicts of interest.
 |
References
|
---|
- Clements PJ, Lachenbruch PA, Ng SC, Simmons M, Sterz M, Furst DE. Skin score. A semiquantitative measure of cutaneous involvement that improves prediction of prognosis in systemic sclerosis. Arthritis Rheum 1990;33:125663.[ISI][Medline]
- White B, Bauer EA, Goldsmith LA et al. Guidelines for clinical trials in systemic sclerosis (scleroderma). Arthritis Rheum 1995;38:35160.[Medline]
- Black CM, Silman AJ, Herrick AL et al. Interferon-alpha does not improve outcome at one year in patients with diffuse cutaneous scleroderma. Results of a randomized double-blind placebo-controlled trial. Arthritis Rheum 1999;42:299305.[CrossRef][ISI][Medline]
- Black CM. Measurement of skin involvement in scleroderma. J Rheumatol 1995;22:12179.[ISI][Medline]
- Clements P, Lachenbruch P, Seibold J et al. Inter- and intra-observer variability of total skin thickness score (modified Rodnan TSS) in systemic sclerosis. J Rheumatol 1995;22:12815.[ISI][Medline]
- Pope JE, Bellamy N. Outcome measurement in scleroderma clinical trials. Semin Arthritis Rheum 1993;23:2233.[ISI][Medline]
- Serup J. Quantification of acrosclerosis: measurement of skin thickness and skin-phalanx distance in females with 15 MHz pulsed ultrasound. Acta Derm Venereol 1984;64:3540.[ISI][Medline]
- Serup J. Localized scleroderma (morphoea): thickness of sclerotic plaques as measured by 15 MHz pulsed ultrasound. Acta Derm Venereol 1984;64:2149.[ISI][Medline]
- Akesson A, Forsberg L, Hederstrom E, Wollheim F. Ultrasound examination of skin thickness in patients with progressive systemic sclerosis (scleroderma). Acta Radiol Diagn 1986;27:914.[ISI]
- Myers SL, Cohen JS, Sheets PW, Bies JR. B-mode ultrasound evaluation of skin thickness in progressive systemic sclerosis. J Rheumatol 1986;13:57780.[ISI][Medline]
- Hoffmann K, Gerbaulet U, el-Gammal S, Altmeyer P. 20-MHz B-mode ultrasound in monitoring the course of localized scleroderma (morphea). Acta Derm Venereol 1991;Suppl(Vol. 71)164:316.
- Ihn H, Shimozuma M, Fujimoto M et al. Ultrasound measurement of skin thickness in systemic sclerosis. Br J Rheumatol 1995;34:5358.[ISI][Medline]
- Scheja A, Akesson A. Comparison of high frequency (20 MHz) ultrasound and palpation for the assessment of skin involvement in systemic sclerosis (scleroderma). Clin Exp Rheumatol 1997;15:2838.[ISI][Medline]
- Brocks K, Stender I, Karlsmark T, Ullman S, Halberg P, Jacobsen S. Ultrasonic measurement of skin thickness in patients with systemic sclerosis. Acta Derm Venereol 2000;80:5960.[CrossRef][ISI][Medline]
- Seidenari S, Belletti B, Conti A. A quantitative description of echographic images of sclerotic skin in patients with systemic sclerosis, as assessed by computerized image analysis on 20 MHz B-scan recordings. Acta Derm Venereol 1996;76:3614.[ISI][Medline]
- Brennan P, Silman A, Black C et al. on behalf of the UK Scleroderma Study Group. Reliability of skin involvement measures in scleroderma. Br J Rheumatol 1992;31:45760.[ISI][Medline]
- LeRoy EC, Black C, Fleischmajer R et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988;15:2025.[ISI][Medline]
- Subcommittee for Scleroderma Criteria of the American Rheumatism Association Diagnostic and Therapeutic Criteria Committee. Preliminary criteria for the classification of systemic sclerosis (scleroderma). Arthritis Rheum 1980;23:58190.[ISI][Medline]
- Gniadecka M, Serup J, Sondergaard J. Age-related changes of dermal oedema: evaluation by high frequency ultrasound. Br J Dermatol 1994;131:84955.[ISI][Medline]
- Kerscher M, Volkenandt M, Gruss C et al. Low dose UVA1 phototherapy for treatment of localized scleroderma. J Am Acad Dermatol 1998;38:216.[ISI][Medline]
- Mohrenschlager M, Jung C, Ring J, Abeck D. Effect of penicillin G on corium thickness in linear morphea of childhood: an analysis using ultrasound technique. Ped Dermatol 1999;16:3146.[CrossRef][ISI]
- Szymanska E, Nowicki A, Mlosek K et al. Skin imaging with high frequency ultrasoundpreliminary results. Eur J Ultrasound 2000;12:916.[CrossRef][Medline]
- Hoffmann K, Dirting K, Stucker M, el-Gammal S, Wilmert M, Altmeyer WP. History of high frequency sonography. Ultraschall Med 1994;15:1927.[ISI][Medline]
Submitted 17 December 2002;
Accepted 14 May 2003