Bringing objectivity to early diagnosis of systemic sclerosis

  • Research type

    Research Study

  • Full title

    Bringing objectivity to early diagnosis of systemic sclerosis

  • IRAS ID

    247159

  • Contact name

    Ariane Herrick

  • Contact email

    ariane.herrick@manchester.ac.uk

  • Sponsor organisation

    The University of Manchester

  • Duration of Study in the UK

    1 years, 0 months, 1 days

  • Research summary

    Research summary-
    Systemic sclerosis (SSc) is a painful, disabling disease, with high mortality due to internal organ involvement. Approximately 10,000 people in the UK have SSc, around 50% of whom develop painful finger ulcers sometimes requiring amputation. In most people the first symptom is Raynaud's phenomenon (painful discoloration of the fingers in the cold) and so this provides a window of opportunity for early diagnosis and treatment. However Raynaud's is very common, affecting approximately 5% of the population, and is usually 'primary' (no underlying cause). It is possible to separate Raynaud's secondary to SSc from primary Raynaud's using a non-invasive technique called nailfold capillaroscopy, which examines the small blood vessels ('capillaries') of the nailbed by high-magnification optical imaging. In primary Raynaud's the capillaries have normal structure. In SSc they are usually abnormal (widened, sometimes bleeding, and few in number).
    Currently, relatively few rheumatologists use capillaroscopy because the reference standard equipment (high magnification videocapillaroscopy) is expensive, and images can be difficult to interpret. However, the revised international classification criteria for SSc include abnormal nailfold capillaries and this has fuelled increased interest in the technique.

    We aim to apply methods from computational imaging to support early diagnosis of SSc.
    To achieve this, we shall develop and validate a fully functional prototype software system to (a) acquire high-quality nailfold capillaroscopy images from low-cost, hand-held imaging devices (including dermatoscope, USB microscope) and (b) adapt previously developed software to measure capillary abnormality automatically. We believe this is important because, realistically, rheumatologists are unlikely to buy expensive equipment and automating the analysis will be helpful for 'non-experts'. The proposed study is to collect the image data described in part (a) above at Salford Royal Hospital. The study is funded by the NIHR.
    Lay Summary - Aims and objectives To support early diagnosis of systemic sclerosis by detecting subtle changes in the small blood vessels at the base of the fingernails (capillaroscopy):
    • imaging the vessels using an inexpensive, hand-held microscope;
    • developing computer software to recognise signs of disease automatically.

    Background
    Systemic sclerosis is a painful disabling disease affecting around 20,000 people in the UK. Starting treatment early can help to control symptoms and prevent life-threatening damage to internal organs. Capillaroscopy is key to early diagnosis, but is often not available because vessel images are difficult to acquire and interpret, leading to delayed diagnosis and poor patient outcomes.

    Methods
    We performed capillaroscopy on 106 systemic sclerosis patients and 101 healthy control subjects using three different low-cost, hand-held digital microscopes to obtain videos of the vessels.
    We developed fully automated computer software to:
    • select for analysis video frames where the blood vessels were clearly visible;
    • identify individual blood vessels and measure their widths, shapes and spacing;
    • combine the measurements to provide an abnormality score.
    We tested whether the abnormality score could identify which patients had systemic sclerosis and explored how the technology could be used in the NHS.

    Key findings
    We acquired good quality capillaroscopy videos from all subjects.
    Patients with systemic sclerosis could be identified with an accuracy of 90% using the abnormality score. This is better than human experts.
    An online analysis service using the technology would reduce costs while improving early diagnosis and patients’ quality of life.

    Dissemination, outputs and impact
    We have published four journal papers and presented the work to rheumatologists and patients.
    Comparison between low cost USB nailfold capillaroscopy and videocapillaroscopy – a pilot study
    https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F33232464%2FNBTI%2FYAu3AQ%2FAQ%2Fef30d093-a57e-4ecf-9b3e-7724532e21e8%2F2%2FyG9bKKw_31&data=05%7C02%7Cbrightonandsussex.rec%40hra.nhs.uk%7Cf401b1f56d7447a101b508dcb20d40eb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638581017225687409%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=rl2pA2kL3CDdtT86b%2F9uRw4gTuuDi8ARzqDgf84z6xs%3D&reserved=0

    Quantitative nailfold capillaroscopy-update and possible next steps.
    https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F33493310%252F%2FNBTI%2FYAu3AQ%2FAQ%2Fef30d093-a57e-4ecf-9b3e-7724532e21e8%2F3%2FaifJAI-Zv4&data=05%7C02%7Cbrightonandsussex.rec%40hra.nhs.uk%7Cf401b1f56d7447a101b508dcb20d40eb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638581017225699909%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=TLKCmfJeQN6o15CMBvjdwJA5LK4B81B3JYMauT1KCB4%3D&reserved=0

    Nailfold capillaroscopy: a survey of current UK practice and 'next steps' to increase uptake among rheumatologists.
    https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F35640131%252F%2FNBTI%2FYAu3AQ%2FAQ%2Fef30d093-a57e-4ecf-9b3e-7724532e21e8%2F4%2FeiZyFxPGDb&data=05%7C02%7Cbrightonandsussex.rec%40hra.nhs.uk%7Cf401b1f56d7447a101b508dcb20d40eb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638581017225709859%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=Ha8mSGiEaTQXCiagrf3e5Xdrgw4YnGvfjW3opX317sw%3D&reserved=0

    A deep learning system for quantitative assessment of microvascular abnormalities in nailfold capillary images.
    https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fpubmed.ncbi.nlm.nih.gov%252F36651676%252F%2FNBTI%2FYAu3AQ%2FAQ%2Fef30d093-a57e-4ecf-9b3e-7724532e21e8%2F5%2FFt-iDwSDuv&data=05%7C02%7Cbrightonandsussex.rec%40hra.nhs.uk%7Cf401b1f56d7447a101b508dcb20d40eb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638581017225718355%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=OtyDdNg4v0bc%2FldSawrbz70aEyjReVgOrGpWS%2FRhdHQ%3D&reserved=0

    Patient and public involvement
    We worked closely with a patient reference group and patient charity SRUK to understand patient needs.

    Conclusions and future plans
    The technology should be deployed in the NHS – the aim of an NIHR-funded follow-on project.

    Has the registry been updated to include summary results?: No
    If yes - please enter the URL to summary results:
    If no – why not?: The study is not included in a public registry.
    Did you follow your dissemination plan submitted in the IRAS application form (Q A51)?: Pending
    If yes, describe or provide URLs to disseminated materials:
    If pending, date when dissemination is expected: 31/01/2025
    If no, explain why you didn't follow it:
    Have participants been informed of the results of the study?: Yes
    If yes, describe and/or provide URLs to materials shared and how they were shared: Results have been disseminated to the Patient Reference Group, and through the SRUK website: https://gbr01.safelinks.protection.outlook.com/?url=https%3A%2F%2Fclick.pstmrk.it%2F3ts%2Fwww.sruk.co.uk%252F%2FNBTI%2FYAu3AQ%2FAQ%2Fef30d093-a57e-4ecf-9b3e-7724532e21e8%2F6%2FpxYfzYIPEH&data=05%7C02%7Cbrightonandsussex.rec%40hra.nhs.uk%7Cf401b1f56d7447a101b508dcb20d40eb%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C638581017225725868%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C0%7C%7C%7C&sdata=ySlpkpclgmqNIzqAx3EqoVTHsU08owFSO8%2F1BucHHe0%3D&reserved=0
    If pending, date when feedback is expected:
    If no, explain why they haven't:
    Have you enabled sharing of study data with others?: No
    If yes, describe or provide URLs to how it has been shared:
    If no, explain why sharing hasn't been enabled: We will make data available to other researchers in a timely manner; however, we do reserve the right to not share data until we have published / gained the required impact. Investigators outside of the research team are welcome to contact us and we will make the necessary arrangements for the transfer of data.
    Have you enabled sharing of tissue samples and associated data with others?: No
    If yes, describe or provide a URL:
    If no, explain why: Tissue samples were not collected as part of this study.

  • REC name

    London - Brighton & Sussex Research Ethics Committee

  • REC reference

    19/LO/1280

  • Date of REC Opinion

    16 Jul 2019

  • REC opinion

    Favourable Opinion