ColombianCongressofRheumatology, Barranquilla 2011<br />Systemic Sclerosis,myths,  truths & challenges<br />Marco MatucciC...
SSc- myths,  truths & challenges<br /><ul><li>Myth-SScisasfibroticdisease…
Truth-SScis a dreadfuldisease…
Challenge-  SSc can bediagnosedveryearly…
Conclusions</li></li></ul><li>Myth-SScisasfibroticdisease…<br />“…wasteduntiloneisliterally a mummy,…”<br />              ...
Myth-SScisasfibroticdisease…<br />SScis more thanthat,<br />Itis  a vasculardisease… !!??<br />
Barbara G. May 2005<br />Paolieri<br />Lidia T. January 2005<br />G.P, March 2004<br />
          disease evolution <br />lung, heart, GI, kidney<br />intermediate<br />skin<br />thickness<br />early<br />late<...
What’s going on under the skin… into the vessels ?<br />Endothelial damage and apoptosis<br />Progressive arteriolar alter...
Fleischmajeret al, J amAcadDermatol 1980<br />
Tha<br />TAT<br />VIIa<br />IL-2<br />F 1+2<br />TF<br />IIa<br />IL-1<br />DS<br />Fb<br />t-PA<br />Lp<br />vW<br />VCAM...
Vasculopathy of SSc complications…“the challenge for the future”<br />Intimal proliferation<br />Adventitial fibrosis<br /...
Hypoxia,Thrombosis<br /> ROS<br />Continuous Vasospasm<br />  ENDOTHELIAL DAMAGE<br />  RAYNAUD’s Phenomenon<br />TELEANGE...
normal<br />early<br />active<br />late<br />
<ul><li> Calcium Channel blockers
 Iloprost </li></ul>January 2006<br />
August 2006<br /><ul><li> Nifedipine
 Iloprost weekly infusions
 Patient coming seldom for medication</li></li></ul><li>
Patient is painful again, the 5°  right finger is again problematic <br />
Digitalarterywith a thrombusformation due toendothelialcelldysfunction: increasedplateletactivity and increasedthrombogeni...
11.3.03<br />23.12.02<br />28.4.03<br />
Truth…SScis a dreadfuldisease…<br />William Osler (1849-1919)<br /> “Sclerodermais a shrinkingskinof steel”<br />   In its...
Self-portrait<br />Embrace<br />General Chef du Barbare<br />
1940<br />Captive <br />
Death and Fire, 1940<br />
Independent riskfactorsforincreasedmortality(Cox-proportional hazard model)<br />FVC<80%<br />Proteinuria<br />HR= <br />3...
Survival Curves of Scleroderma Patients With Pulmonary Hypertension, Lung Involvement, or No Major Organ Involvement<br />...
Scleroderma renal crisisClinical picture<br />Grade IV retinopathy<br /><ul><li>Rapidly progressive renal impairment
New-onset accelerated phase hypertension
Headaches
Visual disturbances
Encephalopathy with seizures
Flash pulmonary oedema
Fevers / malaise
Pericardial effusion
+/- MAHA
Hypereninaemia
ARF + occlusive renal vascular lesions may occur without hypertension at presentation (Helfrich 1989)</li></ul>Schistocyte...
Scleroderma renal crisis - biopsy features<br />thrombotic vascular occlusion<br />hypertensive vascular damage<br />glome...
Challenge<br />SSc can bediagnosedveryearly<br />
VeryEarlySystemicSclerosis<br />Raynaud’s  phenomenon<br />Pre-SSc<br />Puffy Fingers<br />UCTD<br />MCTD<br />Anti-nuclea...
Raynaud Fenomenus,Quo Vadis… ?<br />
 Patients suspect for very early SSc, characterised by   <br />Raynaud’s phenomenon,<br />puffy fingers/sclerodactily<br /...
  send patient to to other specialist </li></ul>HRCT , PFT  & Esophageal manometry <br />If  positive…<br />If negative…<b...
          Disease evolution<br />lung, heart, GI, kidney<br />intermediate<br />skin<br />thickness<br />early<br />late<b...
May we treat a very early SSc?<br />A Windowofopportunity<br />
          disease evolution <br />lung, heart, GI, kidney<br />intermediate<br />skin<br />thickness<br />early<br />late<...
Facts…<br />When observing a Raynaud’s ph an accurate diagnostic procedure should be used to differentiate between a  prim...
The facts<br />The Mythoffibrosisistoo late !!<br />WestillhaveTruths & Challenges…<br />
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Esclerodermia: mitos, verdades y retos

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Por: Dr. Marco Matucci Cerinic (ITA)
XIII Congreso Colombiano de Reumatologia 2011 Barranquilla

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Esclerodermia: mitos, verdades y retos

  1. 1. ColombianCongressofRheumatology, Barranquilla 2011<br />Systemic Sclerosis,myths,  truths & challenges<br />Marco MatucciCerinic<br />Dept Biomedicine, DivRheumatology<br />UnivFlorence, Italy<br />
  2. 2. SSc- myths,  truths & challenges<br /><ul><li>Myth-SScisasfibroticdisease…
  3. 3. Truth-SScis a dreadfuldisease…
  4. 4. Challenge- SSc can bediagnosedveryearly…
  5. 5. Conclusions</li></li></ul><li>Myth-SScisasfibroticdisease…<br />“…wasteduntiloneisliterally a mummy,…”<br /> William Osler 1898 <br />
  6. 6. Myth-SScisasfibroticdisease…<br />SScis more thanthat,<br />Itis a vasculardisease… !!??<br />
  7. 7. Barbara G. May 2005<br />Paolieri<br />Lidia T. January 2005<br />G.P, March 2004<br />
  8. 8. disease evolution <br />lung, heart, GI, kidney<br />intermediate<br />skin<br />thickness<br />early<br />late<br />DIFFUSE SSc<br />Dermal inflammation<br />Early dSSc<br />Established disease<br />pulmonary hypert., malabsorption<br />intermediate<br />late<br />early<br />LIMITED SSc<br /> 2 5 10 20<br />disease duration (years)<br />Medsger T & Steen V, SystemicSclerosis, 1995, p 51,Williams & Wilkins<br />
  9. 9. What’s going on under the skin… into the vessels ?<br />Endothelial damage and apoptosis<br />Progressive arteriolar alteration with intima hypertrophy and progressive stranglement of the vessel lumen<br />Skin, Lung, Kidney, Heart<br />
  10. 10. Fleischmajeret al, J amAcadDermatol 1980<br />
  11. 11. Tha<br />TAT<br />VIIa<br />IL-2<br />F 1+2<br />TF<br />IIa<br />IL-1<br />DS<br />Fb<br />t-PA<br />Lp<br />vW<br />VCAM<br />TNF<br />CF<br />PAI<br />G<br />vW<br />F<br />ICAM<br />PA<br />E-sel<br />GF<br />uPAr<br />of Endothelial Cells<br />Apoptosis <br />Collagen<br />Smooth<br />Muscle Cells<br />Fibroblasts<br />MatucciCerinicet al SeminarsArthritisRheum 2003<br />
  12. 12. Vasculopathy of SSc complications…“the challenge for the future”<br />Intimal proliferation<br />Adventitial fibrosis<br />Lumen narrowing & obliteration<br />Fingers<br />Lung<br />Kidney<br />Heart<br />PAH<br />Ulcers/gangrene<br />SRC<br />Infarct<br />
  13. 13. Hypoxia,Thrombosis<br /> ROS<br />Continuous Vasospasm<br /> ENDOTHELIAL DAMAGE<br /> RAYNAUD’s Phenomenon<br />TELEANGECTASIAS<br />ULCERS<br />
  14. 14. normal<br />early<br />active<br />late<br />
  15. 15. <ul><li> Calcium Channel blockers
  16. 16. Iloprost </li></ul>January 2006<br />
  17. 17. August 2006<br /><ul><li> Nifedipine
  18. 18. Iloprost weekly infusions
  19. 19. Patient coming seldom for medication</li></li></ul><li>
  20. 20. Patient is painful again, the 5° right finger is again problematic <br />
  21. 21.
  22. 22. Digitalarterywith a thrombusformation due toendothelialcelldysfunction: increasedplateletactivity and increasedthrombogenicity in SSc<br /> HE x 15, CourtesyofPetrosEfthimiou, MD, NY<br />
  23. 23. 11.3.03<br />23.12.02<br />28.4.03<br />
  24. 24. Truth…SScis a dreadfuldisease…<br />William Osler (1849-1919)<br /> “Sclerodermais a shrinkingskinof steel”<br /> In its more aggravatedformsof diffuse sclerodermaisoneof the mostterribleofallhumanills. LikeTithonustowitherslowly and likehimtobebeaten down and marred, wasteduntiloneisliterally a mummy, encased in anevershrinking, slowlycontractingskinof steel, is a fate notpictured in anytragedy, ancient or modern.<br />J Cutan & Genitourinar Dis 1898, 16, 49<br />
  25. 25. Self-portrait<br />Embrace<br />General Chef du Barbare<br />
  26. 26. 1940<br />Captive <br />
  27. 27. Death and Fire, 1940<br />
  28. 28.
  29. 29. Independent riskfactorsforincreasedmortality(Cox-proportional hazard model)<br />FVC<80%<br />Proteinuria<br />HR= <br />3.34<br />HR= <br />1.64<br />Pulmonary hypertension<br />Dyspnoea<br />(PAPsys >40 mmHg)<br />HR=<br />2.02<br />HR= <br />1.61<br />Huegleet al ARD 2010<br />
  30. 30. Survival Curves of Scleroderma Patients With Pulmonary Hypertension, Lung Involvement, or No Major Organ Involvement<br />100<br />90<br />80<br />None<br />70<br />60<br />Survival, %<br />50<br />Lung Involvement (without PHTN)<br />40<br />30<br />PHTN<br />20<br />10<br />0<br />0<br />1<br />2<br />3<br />4<br />5<br />6<br />7<br />8<br />9<br />10<br />11<br />12<br />13<br />Years From Diagnosis of PHT<br />Koh et al. BrJ Rheumatol. 1996;35:989-993.<br />
  31. 31. Scleroderma renal crisisClinical picture<br />Grade IV retinopathy<br /><ul><li>Rapidly progressive renal impairment
  32. 32. New-onset accelerated phase hypertension
  33. 33. Headaches
  34. 34. Visual disturbances
  35. 35. Encephalopathy with seizures
  36. 36. Flash pulmonary oedema
  37. 37. Fevers / malaise
  38. 38. Pericardial effusion
  39. 39. +/- MAHA
  40. 40. Hypereninaemia
  41. 41. ARF + occlusive renal vascular lesions may occur without hypertension at presentation (Helfrich 1989)</li></ul>Schistocytes - MAHA<br />Courtesy of Dr C Denton, RFH, UK<br />
  42. 42. Scleroderma renal crisis - biopsy features<br />thrombotic vascular occlusion<br />hypertensive vascular damage<br />glomerularischaemia<br />fibrosis<br />Courtesy of Dr C Denton, RFH, UK<br />
  43. 43. Challenge<br />SSc can bediagnosedveryearly<br />
  44. 44. VeryEarlySystemicSclerosis<br />Raynaud’s phenomenon<br />Pre-SSc<br />Puffy Fingers<br />UCTD<br />MCTD<br />Anti-nuclear antibodies<br />Capillaroscopy<br />MatucciCerinicet al , AnnRheumDis2009<br />
  45. 45. Raynaud Fenomenus,Quo Vadis… ?<br />
  46. 46. Patients suspect for very early SSc, characterised by <br />Raynaud’s phenomenon,<br />puffy fingers/sclerodactily<br />antinuclear antibodies<br />1st level<br />Red Flags<br />Suspicion<br />Evaluation of patients <br />Capillaroscopy & SSc-specific antibodies<br />2nd level<br />If either one is positive, diagnosis of very early SSc & further<br /> investigations<br />If negative…<br />diagnosis<br /><ul><li> differential diagnosis
  47. 47. send patient to to other specialist </li></ul>HRCT , PFT & Esophageal manometry <br />If positive…<br />If negative…<br />Choice of treament <br />Follow up<br />Avouacet al ARD 2010<br />
  48. 48. Disease evolution<br />lung, heart, GI, kidney<br />intermediate<br />skin<br />thickness<br />early<br />late<br />DIFFUSE SSc<br />pulmonary hypert., malabsorption<br />intermediate<br />late<br />LIMITED SSc<br />early<br /> 2 5 10 20<br />disease duration (years)<br />Medsger T & Steen V, SystemicSclerosis, 1995, p 51,Williams & Wilkins<br />
  49. 49. May we treat a very early SSc?<br />A Windowofopportunity<br />
  50. 50. disease evolution <br />lung, heart, GI, kidney<br />intermediate<br />skin<br />thickness<br />early<br />late<br />DIFFUSE SSc<br />Dermal inflammation<br />Early dSSc<br />Established disease<br />pulmonary hypert., malabsorption<br />intermediate<br />late<br />early<br />LIMITED SSc<br /> 2 5 10 20<br />disease duration (years)<br />Medsger T & Steen V, SystemicSclerosis, 1995, p 51,Williams & Wilkins<br />
  51. 51. Facts…<br />When observing a Raynaud’s ph an accurate diagnostic procedure should be used to differentiate between a primary or a secondary form<br /> Follow up of these patients is mandatory <br />Raynaud’s ph is the first sign of a very early Systemic Sclerosis<br /> “red flags” must always induce the suspect of a very early SSc !<br />
  52. 52. The facts<br />The Mythoffibrosisistoo late !!<br />WestillhaveTruths & Challenges…<br />
  53. 53. What are the followingcases ? An earlySSc or somethingveryearly ?Where do we position thesepatients in the diseaseevolution ?<br />
  54. 54.
  55. 55.
  56. 56.
  57. 57. Cardiac MRI<br />Patient dies 10 months after the diagnosis<br />
  58. 58. DE 15.4.04Finger edema & RaynaudNVC- Active patternAnticentromereposLES Dysfunction<br />
  59. 59. <ul><li>RP & puffyfingers
  60. 60. Topo I
  61. 61. NVC late
  62. 62. FVC & DLCO normal
  63. 63. chest HRCT normal</li></li></ul><li>RP<br />ANA/Topo I pos<br />NVC active<br />Simona C. December 2004<br />Are these already SSc ?<br />Early or very early ?<br />RP<br />ANA/ACA pos<br />NVC early<br />Claudia P. 2005<br />
  64. 64. DE 2010RPANA/ACA posNVC activeLES dysfunctionFVC & DLCO normal<br />
  65. 65. RP<br />ANA/Topo I pos<br />NVC active<br />Diffuse SSc- Six months<br />Simona C. December 2004<br />RP<br />ANA/ACA pos<br />NVC early<br />Limited SSc-Three years<br />Claudia P. 2005<br />
  66. 66. Do we really have to treat these patients… ?<br />WE DO NOT KNOW AS EVIDENCE BASE DATA ARE NOT AVAILABLE…<br />& predictors of evolution are missing but STILL REMAINS MANDATORY to block the disease evolution and organ damage<br />An early aggressive therapymightbechosenwhen:: <br /> Topo I antibodies/RNA pol III<br />rapidlyprogressingskininvolvement<br />Tendonfrictionrubs<br />
  67. 67. The window of opportunity…!!!<br />Paul Klee<br />The window<br />
  68. 68. Educationisofparamountimportance !!<br />
  69. 69. www.eustar.org<br />www.W-S-F.org<br />Scleroderma<br />Foundation<br />
  70. 70. VEDOSS Very Early Diagnosis Of SSc<br /><br /> Partnership between EULAR, EUSTAR and FESCA toestablisha programme to:<br />Create clinics devoted to the early diagnosis of SSc<br />Educate primary care professionals throughout Europe <br />In the earliest symptoms of SSc<br />(Raynaud’s, ANA  capillaroscopy / anti-nuclear antibody tests)<br />To send any patient presenting with Red Flags to special SSc clinics <br />Launch datetocoincidewithEuropean Scleroderma Awareness Day: 29th June 2010<br />
  71. 71. DeptRheumatology AVC<br />Dept Biomedicine & DivRheumatology AOUC<br />Dept Medicine & DENOtheCentre<br />UniversityofFlorence<br />Dr. ML Conforti<br />Dr A Righi<br />Dr G Baccano<br />Dr. S MaddaliBongi<br />Dr. A Del Rosso<br />Dr. D Melchiorre<br />Dr. M Maresca<br />Dr. F Bandinelli<br />Dr. S BellandoRandone<br />Dr. S Guiducci<br />Dr. G Salvadorini<br />Dr. F Porta<br />Dr. J Blagojevic<br />Dr. G Carnesecchi<br /> Dr F Galluccio<br />Dr S Cappelli<br />Dr V Denaro<br />Dr T Barskova<br />Dr R De Luca<br />Dr L Giovannini<br />Dr A Calabrò<br />Dr E Bellucci<br />Dr M Orlandi <br />Clinical Trial Unit<br />Dr. F Nacci<br />Dr. F Bartoli<br /> Dr F Peruzzi<br /> Dr C Bruni <br />DigitalUlcersUnit<br />Dr. G Fiori<br /> Signora F Braschi<br />RegionalReferenceCentreforSystemicSclerosis<br />Dottssa P Cerboni<br />LaboratoryUnit<br />Dr M Manetti<br />Dr C Ceccarelli<br />Dr E Romano<br />Young Adults Clinic<br />Prof F Falcini<br />

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