Systemic sclerosis..scleroderma

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Systemic sclerosis..scleroderma

  1. 1. SYSTEMIC SCLEROSIS<br />Dr.PRAVEEN NAGULA<br />
  2. 2. It is much simpler to buy books than to read them and easier to read them than to absorb their contents. <br />SIR WILLIAM OSLER<br />
  3. 3. Background<br />Scleroderma is derived from the greek words skleros (hard or indurated) and derma (skin). <br />HIPPOCRATES first described this condition as thickened skin.<br />First detailed description by Carlo Curzio in 1752.<br />Term scleroderma --- GiovambattistaFantonetti<br />Systemic nature of the disease by Robert H.Goetz. <br />
  4. 4. Introduction<br />Dr.a.g.mauriceraynaud<br />Chronic systemic disorder of unknown etiology.<br />Characterised by thickening of the skin (scleroderma) and distincitive involvement of multiple internal organs most notably lungs , GIT , heart ,kidneys.<br />Skin induration limited to fingers( sclerodactyly)<br />No skin induration (SSc sine scleroderma)<br />RAYNAUD’S phenomenon is predominant feature seen. <br />
  5. 5. CASE<br /><ul><li>A 40-year-old white woman with a 2-year history of Raynaud's phenomenon presented because the skin on her hands was beginning to feel tight.
  6. 6. Five weeks earlier, her hands had been swollen, erythematous, and pruritic, but these symptoms resolved without treatment.
  7. 7. The patient also described flulike symptoms during this same period of time.
  8. 8. The review of systems was significant for slight dyspnea without chest pain, heartburn, difficulty swallowing pills, bloating, and abdominal distention.
  9. 9. The patient's work-up included pulmonary function tests, which revealed a reduction in vital capacity and a decreased lung compliance.</li></li></ul><li><ul><li>The results of her blood work included an elevated sedimentation rate, positive antinuclear antibodies, and positive anticentromere antibodies…</li></ul>Scleroderma with calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia (the CREST variant of limited scleroderma).<br />
  10. 10. Definition<br />SSc is a multisystemic ,autoimmune disease affecting small arteries,microvessels and fibroblasts resulting in vascular obliteration,collagen accumulation and scarring (fibrosis) of skin and internal organs.<br />Leads to hidebound skin,damage of GIT,Lungs,Kidney,Heart.<br />Serologic specificity of the disease is the presence of ANA ,directed against cellular nuclear enzymes, like DNA topoisomerase -1 (anti –Topo 1 ) and RNA polymerase,as well as centromeric proteins (anticentromereAb)<br />
  11. 11. Diagnostic criteria<br />The AMERICAN COLLEGE OF RHEUMATOLOGY (ACR) criteria for the classification of systemic sclerosis.<br />One major criteria,two or more minor criteria for diagnosis.<br />MAJOR criterion : PROXIMAL scleroderma –characterized by SYMMETRICAL thickening,tightening and induration of the skin of the fingers and the skin proximal to the MCP /MTP joints. these changes may affect the entire extremity,face,neck,trunk.<br />MINOR<br />1.SCLERODACTYLY – thickening,induration,tightening of the skin limited only to fingers.<br />2.DIGITAL PITTING SCARS/LOSS OF SUBSTANCE FROM THE FINGER PAD–due to ischemia.<br />3.BIBASILAR PULMONARY FIBROSIS-b/l reticular pattern of linear or lineonodular densities in basilar portions of the lung on CXR.diffuse mottling/honey comb lung not attributable to primary pulmonary disease<br />
  12. 12. Epidemiology<br /><ul><li>Acquired sporadic disease
  13. 13. Affects all races.
  14. 14. Incidence is 9-19 cases/million/year.
  15. 15. Female predominance.
  16. 16. Child bearing ages.
  17. 17. African americans >whites..earlier age
  18. 18. Non mendelian pattern of inheritance.
  19. 19. Concordance among twins is low.,but ANA is high..
  20. 20. Juvenile onset systemic sclerosis is uncommon.
  21. 21. No data on the prevalence of scleroderma in INDIA.</li></li></ul><li>Etiology<br />Exact etiology is unclear.<br />Environmental factors triggers or acclerators for the development of SSc - silica exposure,vinylchloride,trichloroethylene,epoxy resins,benzene,CCl4<br />Radiation exposure /radiotherapy<br />CMV,HHV 5,PBV B19 <br />Drugs– bleomycin,pentazocine.l-tryptophan<br />Common in coal and gold miners.<br />Do not explain the spontaneously developed disease.<br />
  22. 22. Pathology<br />Following pathogenic mechanisms always present:<br />Endothelial cell injury<br />Fibroblast activation<br />Cellular and humoral immunologic derangement.<br />Activation of the immune system is an outstanding disease feature. –autoantibodies,perivascular lymphocytes (cd4 T )<br />Chronic forms of GVHD shares features of SSc. <br />
  23. 23. pathogenesis<br />
  24. 24. Pathogenesis<br />
  25. 25. Clinical description<br />The condition may be divided into different subtypes<br />DIFFUSE CUTANEOUS SSc (DcSSc)<br />LIMITED CUTANEOUS SSc (LcSSc )<br />SYSTEMIC SCLEROSIS SINE SCLERODERMA<br />DcSSc – abrupt in onset,RP is common,thickening of trunk ,acral skin edema –earliest features,TFRs,Pfbirosis,renal crises.<br />LcSSc – RP years before ,skin induration limited to hands,face,feet—CREST.<br />SSSc ---visceral disease without skin involvement. <br />
  26. 26. SUBSETS OF SYSTEMIC SCLEROSIS<br />
  27. 27. Limited SSc/diffuseSSc<br />
  28. 28. SYSTEMIC SCLEROSISclinical features-management<br />Dr.PraveenNagula<br />
  29. 29. Clinical features<br />RAYNAUD’S PHENOMENON:<br /><ul><li>Episodic vasoconstriction in the fingers and toes.
  30. 30. Tip of the nose , earlobes can also be affected.
  31. 31. Triggers – exposure to cold, temperature,stress,vibration.
  32. 32.  frequency ,severity in winter.
  33. 33. Typical attack : PALLOR  CYANOSIS  ERYTHEMA.</li></ul> Vasoconstriction  ischemia  reperfusion.<br /><ul><li> women > men
  34. 34. PRIMARY –exaggerated physiological response to cold.
  35. 35. SECONDARY --complication of SSc…</li></li></ul><li>Raynaud’s phenomenon<br /><ul><li>Primary – no underlying causes
  36. 36. Positive family h/o
  37. 37. Absence of digital necrosis
  38. 38. No ulceration , gangrene
  39. 39. Negative ANA test
  40. 40. Secondary ---- > 30 yrs
  41. 41. More severe
  42. 42. Assosciated with ischemia,infarction of digits.
  43. 43. NAIL FOLD MICROSCOPY – normal with regularly spaced vascular loops – primary,distorted widened ,irregular loops,dilatedlumen,vascular dropouts.
  44. 44. Raynaud like abn. Activity ---pulmonary,renal ,GIT,coronary</li></li></ul><li>A, early SSc pattern; B, active SSc pattern; C, late SSc pattern and D, normal pattern (200x)<br />Cutolo M et al. Rheumatology 2006;45:iv43-iv46<br />© The Author 2006. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org<br />
  45. 45. SKIN features<br /><ul><li>Clinically evident skin thickening is the HALLMARK of SSc—distinguishes it from others..
  46. 46. Symmetrical ,B/L
  47. 47. In diffuse type – edema replaced by skin thickening..distal to proximal – centripetal fashion.
  48. 48. Skin is firm ,coarse and thickened.
  49. 49. Darkly pigmented extremities and trunk.
  50. 50. Diffuse tanning in the absence of exposure to sun –very early feature.
  51. 51. Vitiligo like hypopigmentation –in dark skinned individuals.
  52. 52. Pigment loss spares perifollicluar areas – salt and pepper appearance of skin –scalp ,upperback ,chest.
  53. 53. Obliteration of appendages of hair.
  54. 54. Loss of transverse creases on dorsum of fingers
  55. 55. Fixed flexion deformity of fingers </li></li></ul><li><ul><li>FACE – mauskopf appearance –
  56. 56. Skin is firmly bound to subcutaneous fat –</li></ul>thinning and atrophy.<br /><ul><li>MACULAR telangiectasia –localised scleroderma
  57. 57. Resembles of HHT .face,lip,oral cavity.
  58. 58. ATROPHY of skin – slow healing ulceration on extensor surface of PIP joints.,volar pads.
  59. 59. DIGTIAL pits – healed ischemic ulcers.
  60. 60. Resorption of terminal phalanges – acroosteolysis.
  61. 61. Calcium deposits in skin ,soft tissue.. CREST syndrome – calcium hydroxyapatite crystals.
  62. 62. Finger pads,palms,extensor surfaces.
  63. 63. Firm ,non tender subcutaneous lumps– ulcerate through skin –chalky white matter. </li></li></ul><li>Salt and pepper appearance of skin<br />sclerodactyly<br />Hide bound skin<br />
  64. 64.
  65. 65. Skin features<br />Calcinosistelangiectsias<br />
  66. 66. Pulmonary features<br /><ul><li>Leading cause of death.
  67. 67. ILD,PAH
  68. 68. Less frequently –aspiration pneumonitis , pulmonary hemorrhage , obliterativebronchiolitis , pleural involvement , restrictive ventilatory defect due to chest wall fibrosis , spontaneous pneumothorax.
  69. 69.  broncho alveolar carcinoma
  70. 70. Asymptomatic until advanced.
  71. 71. Most frequent symptoms of pulmonary inv. Are subtle .
  72. 72. Velcro crackles at lung base.
  73. 73. PFT for detection -- FVC,  DLCO ,,,DLCO  FVC</li></li></ul><li>INTERSTITIAL LUNG DISEASE<br /><ul><li>90% cases at autopsy.HRCT –85%cases.
  74. 74. 16-43% are affected.
  75. 75. NORMAL FLOW RATES.
  76. 76. At risk are MALE,AFRICAN,diffuse skin inv.,severeGERD,topoisomerase I autoAb.
  77. 77. Rapid progression in first 3 yrs of onset –32%  /year.
  78. 78. CXR,HRCT,BAL,LUNG BIOPSY.
  79. 79. HRCT more sensitive,reticular linear opacities in lower lobes,mediastinallymphadenopathy,ground glass appearance.
  80. 80. Non specific interstitial pneumonitis –better prognosis.
  81. 81. KL– 6 ,A GLYCOPROTEIN,type II pneumocytes,alveloar macrophages –earlier detection of ILD </li></li></ul><li>Pulmonary Arterial Hypertension<br /><ul><li>Mean Pulmonary arterial pressure > 25 mm Hg at rest.
  82. 82. 12-25% have PAH
  83. 83. In assosciation with ILD/solitary.
  84. 84. Usually downhill course –RHF –death.
  85. 85. At risk are – Ls SSc with anticentromereantibodies,late age of onset,severe raynauds,U1 –RNP,U3 RNP fibrillarin,B23 Ab.
  86. 86. Asymptomatic,exertionaldyspnea.
  87. 87. PASP >40 mm Hg at rest in 2d echo.
  88. 88. Decreased DLCO
  89. 89. Right heart catheterisation accurate.
  90. 90. Increased BNP,Nt BNP levels
  91. 91. Prognosis  degree of pulmonary artery pressure elevation. </li></li></ul><li>GASTROINTESTINAL <br /><ul><li>90% Pts.
  92. 92. Asymptomatic /weight loss
  93. 93. Abn motility of intestines.
  94. 94. Prominent atrophy ,fibrosis of smooth muscle,intactmucosa,obliterative small vessel vasculopathy – all over GIT .
  95. 95. Oropharyngeal – common
  96. 96. Xerostomia
  97. 97. Oral aperture
  98. 98. Periodontal disease
  99. 99. GERD – early
  100. 100. LES pressure
  101. 101.  clearance
  102. 102. Increased emptying time.
  103. 103. Gastroparesis – early satiety
  104. 104. Distention,abd pain
  105. 105. Increased reflux
  106. 106. Radionuclide studies </li></li></ul><li>GIT<br /><ul><li>GASTRIC VASCULAR ECTASIAs – seen in the antrum.
  107. 107. Subepithelial lesions
  108. 108. Diffuse small vessel vsculopathy
  109. 109. Watermelon appearance
  110. 110. Recurrent GI bleed occult
  111. 111. Fat ,protein malabsorption,vitamin b12
  112. 112. Wide mouth sacculations in the colon occur –perforation.
  113. 113. Pneumatosiscystoidesintestinalis
  114. 114. Primary biliary cirrhosis may coexist.
  115. 115. May present with acute abdominal pain recurrent –differentiate from pseudoobstruction. </li></li></ul><li>RENAL <br /><ul><li>HTN,chronic non progressive proteinuria.
  116. 116. SCLERODERMA renal CRISIS –dreadful complication of SSc.
  117. 117. 20-25% pts
  118. 118. < 4 yrs of onset of diseases
  119. 119. Survival <10 % until ACEI
  120. 120. It is due to OBLITERATIVE VASCULOPATHY of renal cortical arteries.
  121. 121. RBF  JGA hyperplasia  renin secretion  RAAS  renal vasoconstriction malignant HTN.
  122. 122. RBF  vasospasm,dehyration,hypotension.
  123. 123. At risk -- africanamerican,male,diffuse skin involvement,ab to RNA polymerase III
  124. 124. Impending renal crises – palpable tendon friction rubs,pericardialeffusion,new unexplained anemia,thrombocytopenia.
  125. 125. Localised scleroderma –infrequent development.
  126. 126. Prednisolone to be avoided.</li></li></ul><li>RENAL<br /><ul><li>Presentation –abrupt onset of malignant HTN, severe headache,blurredvision,chest pain.
  127. 127. 10% normal BP – normotensive renal crises.
  128. 128. Urinalysis -- proteinuria,microscopichematuria,fragmented RBCs
  129. 129. Rapidly progressive oliguric renal failure follows
  130. 130. D.D – TTP commonly misdiagnosed.
  131. 131. Creatnine > 3 mg/dl at presentation –poor prognosis.—permanent hemodialysis –high mortality,
  132. 132. Prompt use of ACEI to make BP under control before renal failure occurs –imporved prognosis.</li></li></ul><li>Cardiac <br /><ul><li>Myocardial ,pericardial ,conduction abnormalities.
  133. 133. Can occur secondary to renal ,pulmonary involvement.
  134. 134. LVDD is frequent.
  135. 135. LVDD –due to HTN ,myocardial fibrosis.
  136. 136. Asymptomatic until HF ,arryhthmias occurs.
  137. 137. Myocarditis in assosciation with inflammatroypolymyositis.
  138. 138. Conduction defects due to fibrosis of conduction system.
  139. 139. Pericardial effusion –symptoms– rarely tamponade. </li></li></ul><li>Musculoskeletal<br />CARPAL TUNNEL SYNDROME –may be a presenting feature.<br />Early disease –generalisedarthralgia,stiffness.<br />Joint mobility affected in diffuse disease.<br />HANDS –PIP joints,wrists.<br />Tendon friction rubs are present.—extensive fibrosis,adhesion of tendon sheaths.<br />True joint inflammation is reduced.<br />Muscle weakness due to disuse,malnutrition.<br />Chronic noninflammatroymyopathy is usually seen.<br />Bone resorption –a freq late complication –terminal phalanges –loss of distal tufts –ACRO OSTEOLYSIS.<br />Mandible affected—biting difficulty <br />Ribs,distal clavicle<br />
  140. 140.
  141. 141. Other disease manifestations<br /><ul><li>Dry eyes,dry mouth –SICCA complex.
  142. 142. Biopsy of the minor salivaryglands –fibrosis rather than lymphocytic infitration.(sjogren’s syndrome)
  143. 143. Hypothyroidism –fibrosis of gland.
  144. 144. CNS is generally spared . Sensory trigeminal neuropathy due to fibrosis /vasculopathy can occur.
  145. 145. Pregnancy -adverse outcomes
  146. 146. Cardiopulmonary complications,new onset renal crises can occur.
  147. 147. Erectile dysfunction in the male. </li></li></ul><li>Laboratory features<br /><ul><li>Anemia – frequent
  148. 148. Most common is mild normocytic /microcytic anemia –chronic inflammation
  149. 149. Serum iron is low or normal,ferritin is elevated.
  150. 150. Iron deficiency anemia –occult GI bleed (WATERMELON STOMACH),chronic esophagitis.
  151. 151. Macrocytic anemia – vitmainb12,folate,bacterial overgrowth,drugs
  152. 152. Acute microangiopathic anemia –mechanical trauma—renal crises
  153. 153. Thrombocytopenia ,leukopenia –DRUG toxicity.
  154. 154. ESR is normal
  155. 155. Increased ESR –MYOSITIS ./MALIGNANCY</li></li></ul><li>ANTINUCLEAR ANTIBODIES<br /><ul><li>All patients of SSc
  156. 156. Highly specific are anti topoisomerase –I (Scl 70) and anti centromereAb
  157. 157. Specific ab profile remains stable over time.
  158. 158. Topoisomerase I ab 31% of dcSSc ,13% of lcSSc
  159. 159. Anticentromereab in 38% of lcSSc,2% of dcSSc.
  160. 160. U3RNP fibrillarin –characteristic nucleolarfluoroscencepattern,Th/To,PM/Scl .
  161. 161. No direct pathogenic role has been established for SSc associated autoantibodies..
  162. 162. Antibody titers correlate with disease severity . </li></li></ul><li>Auto antibodies in SSc<br />
  163. 163.
  164. 164. Diagnosis<br /><ul><li>Diagnosis on clinical grounds.
  165. 165. Presence of skin induration with a characteristic symmetrical distibutionpattern,typical visceral organ manifestation-establishes the diagnosis with high certainity.
  166. 166. Full thickness biopsy – required for diagnosis of scleredema,scleromyoxedema,nephrogenic systemic fibrosis.
  167. 167. lcSSC– CREST for diagnosis
  168. 168. Nail fold microscopy for differentiation from primary raynaud’s
  169. 169. Diffuse edema of fingers..
  170. 170. SSc sine scleroderma– anticentromereab</li></li></ul><li>Differential diagnosis<br />
  171. 171. Differential diagnosis<br />Based on vascular changes:<br /><ul><li>1.PRIMARY raynaud’s phenomenon
  172. 172. 2.physical trauma –jack hammer
  173. 173. 3.chemical exposure
  174. 174. 4.drugs toxins – toxic oil syndrome,ergotamine,Bblockers ,carbidopa,5HT .
  175. 175. 5.SLE,DM/PM,RA.,cryoglobulinemia.</li></ul>Based on skin changes<br /><ul><li>1.localized scleroderma
  176. 176. 2.scleroderma like skin changes
  177. 177. 3.metabolic –genetic disorders –scleredema/scleromyxedema</li></ul>Based on visceral involvement<br /><ul><li>1.idiopathic pulmonary HTN
  178. 178. 2.idiopathic pulmonary fibrosis
  179. 179. 3.sarcoidosis
  180. 180. 4.amyloidosis</li></li></ul><li>Treatment<br /><ul><li>No therapy has been shown significantly to alter the natural h/o SSc till date.
  181. 181. Multiple interventions are avialable in alleviating the symptoms –slowing progression of organ damage.
  182. 182. Treatment approaches to be individually tailored.
  183. 183. Optimal management – prompt,accuratediagnosis,classification,riskstratify,earlyrecogntion of organ based complicatyions,regular monitoring of progression,diseaseactivity,response to treatment,[patient education.
  184. 184. Holistic approach is needed.
  185. 185. Combination of drugs are used.
  186. 186. Physician –patient relationship to be mainatined. </li></li></ul><li>Disease modifying treatments<br /><ul><li>Immunosuppressive agents –modest or no benefit in Rx of SSc.
  187. 187. Glucocorticoids - stiffness and aching in pts with early stage disease.
  188. 188. Do not influence the progression of skin/internal organ involvement.
  189. 189. ↑risk of scleroderma renal crises at high doses.
  190. 190. Avoid if possible.
  191. 191. Low dose ,brief periods.
  192. 192. Cyclophosphamide –daily oral/IV in SSc related ILD.
  193. 193. Reduces the progression of ILD ,stabilises,improvement in skin induration.
  194. 194. Early stage SSc/extensive pulmonary involvement –candidate
  195. 195. Rx for 6- 12 months ,optimal duration not known.
  196. 196. Benefits  toxicities
  197. 197. Bonemarrowsuppression,oppinfections,hemorhhagiccystitis,bladder Ca.</li></li></ul><li>Disease modifying treatments<br /><ul><li>Methotrexate – modest therapeutic benefit
  198. 198. Potential profibrotic effects --? Use in fibrotic phase
  199. 199. Mycophenolatemofetil– improvement in skin induration
  200. 200. Well tolerated
  201. 201. Immunomodulation– cyclosporine,azathioprine,extraxorporealphotopheresis,thalidomide,rapamycin.
  202. 202. Immune ablation with high dose chemotherapy followed by autologous peripheral stem cell reconstitution
  203. 203. Stem cell transplantation –experimental.</li></li></ul><li>Drugs that interfere with fibrotic process<br /><ul><li>D penicillamine– antifibrotic agent
  204. 204. Immunosuppressive activity
  205. 205. Prevents cross linkage of collagen fibres.
  206. 206. Stabilises,improves skin induration
  207. 207. Prevents new organ involvement
  208. 208. Improved survival
  209. 209. No effect in early active SSc
  210. 210. 750 mg/d
  211. 211. Minocycline
  212. 212. Recombinant relaxin
  213. 213. IFN </li></li></ul><li>Vascular therapy <br /><ul><li>Dress warmly
  214. 214. Minimize cold exposure.,Avoid drugs
  215. 215. Biofeedback therapy.
  216. 216. CCBs –diltiazem,nifedipine –ADVERSE effects
  217. 217. ACEI –not effective
  218. 218. ARBs –losartan well tolerated.
  219. 219. 1 blocker –prazosin
  220. 220. Sildenafil ,Fluoxetine ,Topical NTG, IV PROSTAGLANDINS.
  221. 221. Empiric treatment with statins,antioxidants
  222. 222. Low dose asprin,dipyridamole –useful
  223. 223. Digital sympathetectomy in severe cases
  224. 224. Bosentan prevents new ulcers </li></li></ul><li>Rx of GI complications<br />Elevate head end of the bed.<br />Eat frequent small meals<br />PPIs ,H2B at higher doses are effective.<br />Laser photocoagulation –recurrent bleeding from watermelon stomach<br />Metronidazole,erythromycin,tetracycline –bacterial overgrowth.<br />Parenteral nutrition in case of severe disease.<br />Hypomotility of the gut –octreotide. <br />
  225. 225. Rx of PAH <br /><ul><li>SCREEN ON REGULAR BASIS.
  226. 226. Symptomatic –oral endothelin receptor antagonist
  227. 227. Diuretics
  228. 228. Oral anticoagulants
  229. 229. Digoxin
  230. 230. Bosentan –increases exercise tolerance,decreases PAH progression.
  231. 231. 0 2 –nasal cannula
  232. 232. Sildenafil –short term benefit
  233. 233. Parenteral prostaglandin analogues –epoprostenol,teprostinil IV/sc infusion.
  234. 234. Iloprost –inhalation
  235. 235. Lung transplantation</li></li></ul><li>Rx of Renal Crises<br /><ul><li>Medical emergency
  236. 236. Outcome determined by amount of renal damage
  237. 237. Avoid NSAIDs,glucocorticoids
  238. 238. Rx –ACEI ,short term dialysis.
  239. 239. Kidney transplantation.</li></li></ul><li>Skin care <br /><ul><li>5 mg prednisone
  240. 240. D penicillamine
  241. 241. Cyclophosphamide
  242. 242. Regular skin massage
  243. 243. Telangiectasia –laser pulse dyed laser
  244. 244. Finger tip ulcerations –occlusive dressings
  245. 245. Infected ulcers –topical Abs
  246. 246. Surgical debridement
  247. 247. No therapy effectvie in preventing the formation of calcific deposits.</li></li></ul><li>Course,Prognosis<br /><ul><li>DcSSc has more progressive disease than lcSSc.
  248. 248. Early inflamatory changes subside in 2-4 yrs..organ involvement occurs here.
  249. 249. New organ involvement is rare after skin involvement reaches peak.
  250. 250. Skin regression occurs in the order of occurrence
  251. 251. Sclerodactyly ;contractures persist.
  252. 252. lcSSc better prognosis.
  253. 253. dcSSc –5 ,10 YR SURVIVAL RATES –70%,55%
  254. 254. lcSSc – 90% ,75% </li></li></ul><li>Poor prognosis<br /><ul><li>Male gender
  255. 255. young age of onset
  256. 256. African american race
  257. 257. Extensive skin thickening
  258. 258. Truncal involvement
  259. 259. Visceral organ involvement
  260. 260. Topoisomerase I ab
  261. 261. Increased ESR ,anemia ,proteinuria on initial presentation –high mortality… </li></li></ul><li>future<br /><ul><li>IMATINIB mesylate
  262. 262. Scope for research
  263. 263. Unresolved questions
  264. 264. Etiology
  265. 265. Pathogenesis
  266. 266. Therapuetic potential of various regimens</li></li></ul><li>Trials<br />141 TRIALS<br /><ul><li>Sleep Disturbances and Pulmonary Artery/Aorta Diameter in Scleroderma Patient
  267. 267. High Dose Cyclophosphamide for Treatment of Scleroderma
  268. 268. Digital Ischemic Lesions in Scleroderma Treated With Oral TreprostinilDiethanolamine (DISTOL-1)
  269. 269. Pulmonary Involvement in Scleroderma: A Clinical Study of the Safety and Efficacy of MycophenolateMofetil in Scleroderma Patients With Lung Involvement
  270. 270. Sildenafil Effect on Digital Ulcer Healing in sClerodErma SEDUCE STUDY
  271. 271. Effect of Bosentan in Scleroderma Renal Crisis (ScS-REINBO)
  272. 272. Efficacy and Safety of Imatinib in Scleroderma (SCLEROGLIVEC)
  273. 273. Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II) (SLSII)</li></li></ul><li>Take home message<br /><ul><li>SSc is a chronic systemic disorder.
  274. 274. RULE out other causes.
  275. 275. Anti topoisomerase –dcSSc,anticentromereab -LcSSc
  276. 276. After diagnosis risk stratify the patient.
  277. 277. Regular follow up and monitoring.
  278. 278. Patient education is needed.
  279. 279. Treatment is individualised.
  280. 280. Renal crises is an emergency.
  281. 281. ACEI are to be started in a pt with HTN.
  282. 282. No treatment for calcinosis cutis
  283. 283. Imatinib in near future….
  284. 284. Scope for research ..</li></li></ul><li>References<br />HARRISON’S principles of internal medicine ,17 th Ed <br />www.medscape.com<br />www.clinicaltrials.gov<br />www.scleroderma.org<br />www.dermatologylib.com<br />www.ncbl.nbi.com<br />www.google.com<br />www.dailyquotes.com<br />www.orpha.net<br />
  285. 285.
  286. 286. sagittarian<br />

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