Dr Victoria Flower was awarded funding by SRUK to research non-invasive methods of skin assessment in scleroderma. Last month, her work was published in The Journal of Rheumatology, discussing the potential use of High Frequency Ultrasound as a more objective and detailed measure of skin involvement in scleroderma.
Dr Victoria Flower, from Bath’s Royal National Hospital for Rheumatic Diseases, has carried out a project that has been funded by SRUK, to assess the ways in which how scleroderma progresses. Her work involved assessing changes in skin fibrosis over time – something that must be done accurately and using a non-invasive method. Currently, the modified Rodnan skin score is used in routine clinical practice, however this method has significant limitations, which are discussed below. Therefore, an alternative is needed. This month, The Journal of Rheumatology published Dr Flower’s work exploring the potential of using High Frequency Ultrasound (HFUS) as this alternative.
Skin deep – the effects of scleroderma on the skin
Fibrosis is one of the hallmarks of scleroderma, and can impact significant portions of the body including the internal organs. Commonly, the skin is affected and here the fibrosis occurs in three distinct phases.
- Oedematous phase – tight, puffy fingers
- Indurative phase – thickened, tight skin
- Atrophic phase – softening of fibrosis, leading to thinner skin
There are subtle differences in skin thickness between each phase, in particular within the atrophic phase (no. 3); since although the skin itself is thinner, it is tethered to the subcutaneous fat which sits below it, causing the skin to be immobile. This causes the skin to appear thicker than it really is, making it challenging to accurately assess thickness. Being able to differentiate between these phases using a quick and non-invasive method would be extremely useful and would benefit both individuals with scleroderma as part of routine clinical care; as well as in clinical trials that measure fibrosis and skin thickness as an outcome.
Measuring Skin Thickness
Currently, skin thickness is measured using the modified Rodnan Skin Score (mRSS), where clinicians use callipers or their fingers to determine skin thickness across the body. A non-invasive and quick method of assessing the skin, it is used to monitor progressions in the clinic and can indicate whether patients are responding to either prescribed treatments or to new drugs being tested in clinical trials. The mRSS requires significant training, despite which the results can vary between clinicians, and this method is unable to distinguish the skin condition phases outlined above. This reduces the precision of mRSS results; something that was considered partly responsible for the failure of two potential scleroderma treatments (Tocilizumab and Riogicaut), to progress from their phase two clinical trials in 2016, to phase 3 where the treatments would be trialled in a larger cohort for a number of years after neither drug could demonstrate statistically significant improvements in the mRSS of the scleroderma patients.1,2,3
This makes the work of Dr Flower and her team particularly exciting. As part of their SRUK-funded research into skin and blood vessel changes during the progression of scleroderma, they have evaluated the use of ultrasound as an alternative method of measuring and detecting changes in fibrotic skin.
The need for objectivity?
What is needed is a technique that can give an objective reading of skin fibrosis, cutting out the limitations of existing techniques like the mRSS. Ultrasound is an example of existing technology which could be quickly re-purposed to measure skin thickness and changes. A more hands-off method of assessment, it is an objective measure, rather than a clinician-controlled subjective one. Dr Flower sought to discover how viable this alternative is.
The study involved 53 participants with either diffuse or limited cutaneous scleroderma, as well as 15 healthy controls. Skin thickness readings were taken from three different body sites; the hand, the forearm, and the abdomen. High Frequency Ultrasound (HFUS) gave comparable readings to the mRSS when used to assess skin thickening, and skin stiffness at some sites on the body. HFUS was equally capable of measuring skin thickness and stiffness using the measurement of collagen deposition in the skin through skin biopsy as a comparator. This means that in the future, taking skin biopsies may not be required to measure dermal collagen deposition, saving patients an invasive process. Finally, HFUS was also found to be capable of identifying atypical changes in skin tissue, even when the skin was of a normal thickness, and was clinically normal to palpitation. These findings shows that High Frequency Ultrasound could be a viable alternative to the modified Rodnan skin score at certain sites on the body – enabling the use of a more ‘hands off’ method of evaluation which can provide more detail to the clinician and patient.
This research is preclinical, meaning that before ultrasound can be considered for use in a patient setting, there is a lot of work still to be done. Whilst High Frequency Ultrasound is a non-invasive method just like mRSS, more expensive and complex equipment and training are required to be able to use this. Although the quality and detail of the results may be higher by using HFUS, there is a balance to be found between this and the accessibility of treatments. Nonetheless, this research has provided preliminary data that strongly supports further investigation of High Frequency Ultrasound as a method of assessing fibrosis. Research teams in Polandand Australiahave also reported similar findings. Dr Flower has added to the growing body of literature which highlights ultrasound as the next step in enabling more detailed assessment of fibrotic skin, helping to support continued research into this area, with the ultimate aim of improving patient care.
Read more like this?
- What's the outcome? Measuring the effectiveness of new treatments in clinical trials | SRUK
- SRUK’s co-funded project with World Scleroderma Foundation seeking to improve the Combined Response Index in SSc Score. | SRUK
- SRUK – recent research news | SRUK - For the most recent articles on Raynaud’s and Scleroderma research
High-frequency Ultrasound Assessment of Systemic Sclerosis Skin Involvement: Intraobserver Repeatability and Relationship With Clinician Assessment and Dermal Collagen Content | The Journal of Rheumatology (jrheum.org)