This article appears in the following Rheumatology issue: Update in systemic sclerosis [View the issue table of contents]
Skin involvement in systemic sclerosis
1Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary, 2Pediatric Rheumatologic Clinic, Allgemeines Krankenhaus Eilbek, Hamburgm and 3Department for Internal Medicine and Rheumatology, Justus-Liebig University, Giessen, Germany.
Correspondence to: L. Czirják, Clinic Center, Department of Immunology and Rheumatology, University of Pécs, Pécs, Hungary H-7632, Akác u. 1. E-mail: laszlo.czirjak{at}aok.pte.hu
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Abstract |
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 Top Abstract IntroductionModified Rodnan skin scoreDurometryUltrasoundFurther mechanical devices to...Evaluation of irreversible late...AcknowledgementsReferences |
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Skin thickening is a characteristic feature of SSc. More extensive skin involvement coincides with more severe internal organ manifestation(s), poor prognosis and increased disability, at least in the early phase of the diffuse cutaneous scleroderma subset. The fully validated, feasible method (‘gold standard’) for measuring the dermal skin thickness is the modified Rodnan skin score (mRSS). The responsiveness of mRSS was somewhat modest in clinical trials, and a careful teaching process is necessary. Parallel method(s) for measuring skin thickness need to be used in the future. Ultrasound (US) measurement of the dermis with a 20–30 MHz probe is a valid, reproducible and responsive method in patients with dcSSc. However, US is time-consuming and requires a training process. Of the mechanical instruments available, only the durometer, which measures the hardness of skin, has been validated. The inter- and intra-observer reproducibility and sensitivity to change of durometry were good, and correlated with mRSS and US-measured skin thickness. Several further mechanical instruments exist including the elastometer, twistometer, cutometer and plicometer. They seem to distinguish between involved and non-involved skin, and therefore merit further evaluation. The measurement of late-stage, irreversible skin damage/atrophy should be resolved in the future through the development and validation of new instruments.
KEY WORDS: Scleroderma, Systemic sclerosis, Rodnan skin score, Durometer, Instrument, Skin, Atrophy, Ultrasound, Outcome
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Introduction |
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TopAbstractIntroductionModified Rodnan skin scoreDurometryUltrasoundFurther mechanical devices to...Evaluation of irreversible late...AcknowledgementsReferences |
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SSc is a multi-organ disease characterized by thickening, hardening and tightening of the skin. The extent of skin involvement is the major criterion in currently existing classification systems and subset classification for SSc. Skin thickening is a universal feature of SSc. At least in the dcSSc subset, more extensive skin involvement coincides with more severe internal organ manifestation(s), poor prognosis and increased disability [1, 2]. Skin thickness is caused by increased collagen, intercellular matrix formation in the dermis and by oedema probably caused by both microvascular injury and perhaps inflammation. Because of the accumulation of collagen and fluid, the skin becomes thickened, making it impossible to pinch it into a normal skin fold. This first phase is followed by the second, indurative phase. Besides skin thickening, the skin also becomes shiny, taut and adherent to the subcutis. Finally, in the end stage, the skin becomes thin, atrophic and often tightly tethered to the underlying tissue.
Each newly introduced outcome measurement of skin involvement should pass the ‘OMERACT filter’, which aims to evaluate and validate outcome measures in rheumatology [3, 4]. The major elements of the validation procedure are feasibility, truth and discrimination. Truth includes face, content and construct validities. In the discrimination domain, responsiveness and reliability are evaluated.
At present, the most important validated method (‘gold standard’) for measuring the dermal skin thickness is the modified Rodnan skin score (mRSS) [5].
Skin histology also seems to be an appropriate method for the evaluation of skin thickness in scleroderma. Both measuring the thickness of the dermis, and the amount of collagen deposition in skin biopsy specimens by histometric methods or biochemical assays, can be used for validation purposes. In fact, this method is not feasible but it has been used to confirm the validity of the mRSS [6, 7].
Further, fully or partially validated methods are durometry, which measures skin hardness, and ultrasound (US). Another imaging method, the MRI, is time-consuming and expensive, and therefore may not be feasible for use, for this purpose, in clinical practice.
Recently, the Scleroderma Clinical Trial Consortium conducted a Delphi exercise to reach consensus on a core set of measures for clinical trials of SSc. In the skin domain, mRSS, durometry and a visual analogue scale (VAS)/Likert scale evaluation of the skin by both the patients and the physician were recommended for clinical trials [8].
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Modified Rodnan skin score |
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TopAbstractIntroductionModified Rodnan skin scoreDurometryUltrasoundFurther mechanical devices to...Evaluation of irreversible late...AcknowledgementsReferences |
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At present, the mRSS is considered the most appropriate and reproducible technique for measuring skin involvement using palpation in SSc. The mRSS has been shown to be feasible, reliable, valid and responsive to change in multicentre clinical trials. Initial and follow-up skin scores are valuable tools for disease assessment. Although this method is an easily used and fully validated outcome measure in SSc, it has shown somewhat modest responsiveness in three randomized control trials, and there is some concern that mRSS may not be sensitive enough to detect small but clinically meaningful changes [4]. The administration of this simple method needs some experience, and a careful teaching process is also required. Besides the probable requirement of a repeated teaching process, investigators with established technique have difficulties in changing their already established approach to the appropriate skin measurement technique [9]. Furthermore, the intraclass correlation coefficient is low if mRSS is performed by inexperienced rheumatologists [9], making the administration of this particular method difficult in the everyday clinical setting. The mRSS is aimed to evaluate dermal skin thickness, and it is not clear how this technique differentiates skin thickness from other characteristic features of scleroderma skin involvement including either skin hardness or skin tethering.
The mRSS is appropriate predominantly for early dcSSc, although it can also improve in the placebo arm of the clinical trials indicating that some improvement occurring during the follow-up is rather a consequence of the natural history of the disease. This improvement in mRSS can occur even in the very early stage of diffuse SSc. Recently, it has also been suggested that there is no simple relationship between outcome and skin score. Patients with high first year mRSS (
35) showing no improvement have significantly increased mortality compared with dcSSc cases with low first year mRSS with a subsequent improvement, although some early dcSSc cases with a persistent high skin score (mRSS 35) will not develop severe internal organ complications [2].
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Durometry |
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TopAbstractIntroductionModified Rodnan skin scoreDurometryUltrasoundFurther mechanical devices to...Evaluation of irreversible late...AcknowledgementsReferences |
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Durometry is a painless and feasible method for measuring the hardness of skin using internationally standardized durometer units [10, 11]. Skin hardness is an important aspect of skin involvement and is at least partially distinct from thickness or elasticity, and probably affected by skin thickness, skin density, elasticity and oedema. Durometry has already undergone a single-centre and a multicentre validation procedure [10, 11]. The inter- and intra-observer reproducibility of durometry was good, and also correlated well with mRSS and US-measured skin thickness. This particular method was found to be reliable and sensitive to changes in skin hardness over time, although it is also clear that durometry measures a somewhat different aspect of skin involvement compared with mRSS. Durometer measurements could discriminate between the involved and uninvolved skin.
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Ultrasound |
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TopAbstractIntroductionModified Rodnan skin scoreDurometryUltrasoundFurther mechanical devices to...Evaluation of irreversible late...AcknowledgementsReferences |
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In single-centre studies, US using a 10–15 MHz probe was reproducible, but no comparison with histology or clinical examination has been performed. Measurement of the dermis with a 20–30 MHz probe can easily quantify skin thickening, is a valid, reproducible and responsive method, and differentiates between the skin of healthy volunteers and patients with dcSSc, but, in at least one study, was not able to differentiate between healthy controls and lcSSc patients. The correlation of US values to mRSS is also controversial probably because the mRSS measurement is influenced by skin texture and fixation in addition to skin thickness. The inter- and intra-observer reliability is good, but the responsiveness to change has not been defined yet, and early SSc cases should also be investigated in the future [12].
US is time-consuming and requires a training process, making it not feasible in either multicentre studies or routine clinical setting. The evaluation of US is also influenced by the different equipment used by different investigators.
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Further mechanical devices to measure properties of the skin |
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TopAbstractIntroductionModified Rodnan skin scoreDurometryUltrasoundFurther mechanical devices to...Evaluation of irreversible late...AcknowledgementsReferences |
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Besides skin thickening, the involved skin is also characterized by hardness and tethering. In the late stage of the disease, the involved skin becomes atrophic and thinned. Besides the aforementioned and already validated durometry, several other mechanical instruments have been developed that can exert a controlled physical force on the skin, such as lineal extension with an elastometer, rotation with a twistometer or skin suction by cutometer. The plicometer is an instrument that measures the skin thickness of cutaneous plica (folded part of the skin). All these tools seem to distinguish between involved and non-involved skin in scleroderma, and therefore merit further validation, although it is usually not clear to what extent the skin thickness, hardness and tethering is measured. Further, preferentially multicentre, work should determine the overall value of these particular methods [5].
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Evaluation of irreversible late-stage skin damage/atrophy |
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TopAbstractIntroductionModified Rodnan skin scoreDurometryUltrasoundFurther mechanical devices to...Evaluation of irreversible late...AcknowledgementsReferences |
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Recent investigations have focused on the evaluation of early diffuse scleroderma cases. Conversely, validated instruments for the evaluation of chronic late-stage skin changes are not available.
The Medsger severity score [5] evaluates the extent of skin thickening, but unfortunately does not include the evaluation of the final stage, atrophic skin changes, in spite of the fact that, in theory, severity should be evaluated as a combination of active skin changes (thickness) and irreversible damage (atrophy–thinning). In the late stage of disease, skin atrophy predominates. The originally thickened, involved skin may become either close to normal, or atrophic. The exclusive evaluation of skin thickness without measuring skin thinning/atrophy may ‘mix’ these two phenomena, although it is important to distinguish between skin improvement and progression of skin disease to an end-stage atrophic stage. Many patients in the indurative phase of skin involvement show both skin thickening and irreversible skin damage, and the follow-up of these particular cases should be solved in the future by developing new, validated instruments. Some validated follow-up measurements would be useful for lcSSc cases and also for late-stage dcSSc patients. The evaluation of the digits seems to be particularly useful, because this can strongly influence the hand function, and also the quality of life of the patients.
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Acknowledgements |
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TopAbstractIntroductionModified Rodnan skin scoreDurometryUltrasoundFurther mechanical devices to...Evaluation of irreversible late...AcknowledgementsReferences |
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Supplement: This paper forms part of the supplement entitled ‘Update in systemic sclerosis’. This supplement was supported by an unrestricted grant from Encysive.
Disclosure statement: U.M.-L. is supported by the EULAR scleroderma trials and research group (EUSTAR) and the Deutsches Netzwerk fuer Systemische Sklerose group (DNSS). The other authors have declared no conflicts of interest.
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TopAbstractIntroductionModified Rodnan skin scoreDurometryUltrasoundFurther mechanical devices to...Evaluation of irreversible late...AcknowledgementsReferences |
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