Scleroderma Horizon Scanning

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Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Francesco Del Galdo MD,PhD Associate Professor/Honorary Consultant Head of Scleroderma Programme, LMBRU Leeds Institute of Rheumatic and Musculoskeletal Medicine University of Leeds Horizon Scanning

Transcript of Scleroderma Horizon Scanning

  1. 1. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Francesco Del Galdo MD,PhD Associate Professor/Honorary Consultant Head of Scleroderma Programme, LMBRU Leeds Institute of Rheumatic and Musculoskeletal Medicine University of Leeds Horizon Scanning
  2. 2. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU What can we see Where do we really want to go? What do we need to get there
  3. 3. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU What can we see ?
  4. 4. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Systemic Sclerosis AUTOIMMUNE ACTIVATION TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells
  5. 5. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells AUTOIMMUNE ACTIVATION B cells, T cells, Macrophages, Eosinophils
  6. 6. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells TISSUE FIBROSIS Fibroblasts
  7. 7. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Systemic Sclerosis SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells
  8. 8. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells Systemic Sclerosis TISSUE FIBROSIS Fibroblasts AUTOIMMUNE ACTIVATION B cells, T cells, Macrophages, Eosinophils TISSUE FIBROSIS Fibroblasts
  9. 9. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Where do we really want to go?
  10. 10. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Target Systemic Sclerosis TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells AUTOIMMUNE ACTIVATION B cells, T cells, Macrophages, Eosinophils
  11. 11. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Target Systemic Sclerosis TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells AUTOIMMUNE ACTIVATION B cells, T cells, Macrophages, Eosinophils
  12. 12. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Reverse Translational approach Bed side to Bench Fibrotic phenotype Multiple mechanisms confounded Extreme clinical phenotype Identification of principal pathogenetic mechanism or marker Integration within general cohort
  13. 13. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Target Systemic Sclerosis TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells AUTOIMMUNE ACTIVATION B cells, T cells, Macrophages, Eosinophils
  14. 14. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU What do we need to get there
  15. 15. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Measure Scleroderma activity and severity 1) 1) Fibrotic process is systemic 2) 2) target organ function is affected 3) not only by fibrotic process 4) 3) Clinical signs of organ involvement 5) emerge at different time during 6) the disease course LUNG Heart GI
  16. 16. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells Measure Scleroderma activity and severity: Vasculopathy
  17. 17. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Ann Rheum Dis 2010;69:10921096. Rheumatology 2012;51:749755 VIDEOCAPILLAROSCOPY Measure Scleroderma activity and severity: Vasculopathy
  18. 18. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU TISSUE FIBROSIS Fibroblasts SMALL VESSEL VASCULOPATHY Endothelial cells Smooth muscle cells TISSUE FIBROSIS Fibroblasts Abignano, 2013 Measure Scleroderma activity and severity: Fibrosis
  19. 19. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU * P Clements, Rheuamtology 26% SE Measure Scleroderma activity and severity: Skin fibrosis
  20. 20. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Virtual skin biopsy by Optical Coherence Tomography: the first quantitative imaging biomarker for scleroderma OCT ARD, 2013 Nature Review Rheumatology, 2013 Measure Scleroderma activity and severity: Skin Fibrosis
  21. 21. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Abignano, 2013 ED PD RD K * * * * DEJ HealthySSc MRSS = 3 * * Virtual skin biopsy by Optical Coherence Tomography Skin fibrosis by OCT
  22. 22. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU
  23. 23. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU
  24. 24. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Diagnostic Evidence Cooperative
  25. 25. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU Combined index of progression 60m SSc sRP Full clinical + ECHO + PFT + HRCT+ Capillaroscopy Serum biomarkers PIINP + TIMP + NT-BNP + OCT
  26. 26. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU
  27. 27. Leeds Institute Rheumatic and Musculoskeletal Medicine NIHR LMBRU OCT as biomarker of skin involvement ELF serum test as surrogate outcome measure of fibrogenesis HO-1 as TGF-b induced mechanism of vasculopathy SFRP4 and non canonical WNT activation in SSc skin PEDF and melanocytes contribution to SSC vasculopathy VEDOSS HGLA shared epitope Local care in DU Healing and rate of infection VC of calcinosis Calsite study M. Buch Scleroderma Research Programme G. Abignano J Ellez-Gomez J. Gillespie V. Liakouli S Eng Research Nurse L. Loughrey B. Alcacher-Pitarch A. Redmond J Blagojevic Caveolin in modulation of Shh pathay in myofibroblasts K Kampsioras G. Lettieri Radiologist. Exploring MRI and ShearWave US to predict progression of SSc hand