Systemic sclerosis..scleroderma
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This document provides information on systemic sclerosis (SSc), a chronic autoimmune disease characterized by thickening and hardening of the skin, and involvement of internal organs. It can present as either limited or diffuse cutaneous forms. Key clinical features include Raynaud's phenomenon, skin thickening and tightening, digital pitting scars, and internal organ involvement such as interstitial lung disease, gastrointestinal issues, and renal crisis. Diagnosis involves clinical examination and the presence of autoantibodies. Differential diagnoses include other conditions presenting with similar skin or vascular changes. Complications can affect multiple organ systems and are a leading cause of mortality.
Systemic sclerosis..scleroderma
- 2. It is much simpler to buy books than to read them and easier to read them than to absorb their contents. SIR WILLIAM OSLER
- 3. BackgroundScleroderma is derived from the greek words skleros (hard or indurated) and derma (skin). HIPPOCRATES first described this condition as thickened skin.First detailed description by Carlo Curzio in 1752.Term scleroderma --- GiovambattistaFantonettiSystemic nature of the disease by Robert H.Goetz.
- 4. IntroductionDr.a.g.mauriceraynaudChronic systemic disorder of unknown etiology.Characterised by thickening of the skin (scleroderma) and distincitive involvement of multiple internal organs most notably lungs , GIT , heart ,kidneys.Skin induration limited to fingers( sclerodactyly)No skin induration (SSc sine scleroderma)RAYNAUD’S phenomenon is predominant feature seen.
- 5. CASEA 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. Five weeks earlier, her hands had been swollen, erythematous, and pruritic, but these symptoms resolved without treatment.
- 7. The patient also described flulike symptoms during this same period of time.
- 8. The review of systems was significant for slight dyspnea without chest pain, heartburn, difficulty swallowing pills, bloating, and abdominal distention.
- 9. The patient's work-up included pulmonary function tests, which revealed a reduction in vital capacity and a decreased lung compliance.The results of her blood work included an elevated sedimentation rate, positive antinuclear antibodies, and positive anticentromere antibodies…Scleroderma with calcinosis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangiectasia (the CREST variant of limited scleroderma).
- 10. DefinitionSSc 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.Leads to hidebound skin,damage of GIT,Lungs,Kidney,Heart.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)
- 11. Diagnostic criteriaThe AMERICAN COLLEGE OF RHEUMATOLOGY (ACR) criteria for the classification of systemic sclerosis.One major criteria,two or more minor criteria for diagnosis.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.MINOR1.SCLERODACTYLY – thickening,induration,tightening of the skin limited only to fingers.2.DIGITAL PITTING SCARS/LOSS OF SUBSTANCE FROM THE FINGER PAD–due to ischemia.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
- 14. Incidence is 9-19 cases/million/year.
- 18. Non mendelian pattern of inheritance.
- 19. Concordance among twins is low.,but ANA is high..
- 20. Juvenile onset systemic sclerosis is uncommon.
- 21. No data on the prevalence of scleroderma in INDIA.EtiologyExact etiology is unclear.Environmental factors triggers or acclerators for the development of SSc - silica exposure,vinylchloride,trichloroethylene,epoxy resins,benzene,CCl4Radiation exposure /radiotherapyCMV,HHV 5,PBV B19 Drugs– bleomycin,pentazocine.l-tryptophanCommon in coal and gold miners.Do not explain the spontaneously developed disease.
- 22. PathologyFollowing pathogenic mechanisms always present:Endothelial cell injuryFibroblast activationCellular and humoral immunologic derangement.Activation of the immune system is an outstanding disease feature. –autoantibodies,perivascular lymphocytes (cd4 T )Chronic forms of GVHD shares features of SSc.
- 23. pathogenesis
- 24. Pathogenesis
- 25. Clinical descriptionThe condition may be divided into different subtypesDIFFUSE CUTANEOUS SSc (DcSSc)LIMITED CUTANEOUS SSc (LcSSc )SYSTEMIC SCLEROSIS SINE SCLERODERMADcSSc – abrupt in onset,RP is common,thickening of trunk ,acral skin edema –earliest features,TFRs,Pfbirosis,renal crises.LcSSc – RP years before ,skin induration limited to hands,face,feet—CREST.SSSc ---visceral disease without skin involvement.
- 26. SUBSETS OF SYSTEMIC SCLEROSIS
- 29. Clinical featuresRAYNAUD’S PHENOMENON:Episodic vasoconstriction in the fingers and toes.
- 30. Tip of the nose , earlobes can also be affected.
- 31. Triggers – exposure to cold, temperature,stress,vibration.
- 32. frequency ,severity in winter.
- 33. Typical attack : PALLOR CYANOSIS ERYTHEMA. Vasoconstriction ischemia reperfusion. women > men
- 34. PRIMARY –exaggerated physiological response to cold.
- 35. SECONDARY --complication of SSc…Raynaud’s phenomenonPrimary – no underlying causes
- 37. Absence of digital necrosis
- 38. No ulceration , gangrene
- 39. Negative ANA test
- 40. Secondary ---- > 30 yrs
- 41. More severe
- 42. Assosciated with ischemia,infarction of digits.
- 43. NAIL FOLD MICROSCOPY – normal with regularly spaced vascular loops – primary,distorted widened ,irregular loops,dilatedlumen,vascular dropouts.
- 44. Raynaud like abn. Activity ---pulmonary,renal ,GIT,coronaryA, early SSc pattern; B, active SSc pattern; C, late SSc pattern and D, normal pattern (200x)Cutolo M et al. Rheumatology 2006;45:iv43-iv46© 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
- 45. SKIN featuresClinically evident skin thickening is the HALLMARK of SSc—distinguishes it from others..
- 46. Symmetrical ,B/L
- 47. In diffuse type – edema replaced by skin thickening..distal to proximal – centripetal fashion.
- 48. Skin is firm ,coarse and thickened.
- 49. Darkly pigmented extremities and trunk.
- 50. Diffuse tanning in the absence of exposure to sun –very early feature.
- 51. Vitiligo like hypopigmentation –in dark skinned individuals.
- 52. Pigment loss spares perifollicluar areas – salt and pepper appearance of skin –scalp ,upperback ,chest.
- 53. Obliteration of appendages of hair.
- 54. Loss of transverse creases on dorsum of fingers
- 55. Fixed flexion deformity of fingers FACE – mauskopf appearance –
- 56. Skin is firmly bound to subcutaneous fat –thinning and atrophy.MACULAR telangiectasia –localised scleroderma
- 57. Resembles of HHT .face,lip,oral cavity.
- 58. ATROPHY of skin – slow healing ulceration on extensor surface of PIP joints.,volar pads.
- 59. DIGTIAL pits – healed ischemic ulcers.
- 60. Resorption of terminal phalanges – acroosteolysis.
- 61. Calcium deposits in skin ,soft tissue.. CREST syndrome – calcium hydroxyapatite crystals.
- 63. Firm ,non tender subcutaneous lumps– ulcerate through skin –chalky white matter. Salt and pepper appearance of skinsclerodactylyHide bound skin
- 66. Pulmonary featuresLeading cause of death.
- 67. ILD,PAH
- 68. Less frequently –aspiration pneumonitis , pulmonary hemorrhage , obliterativebronchiolitis , pleural involvement , restrictive ventilatory defect due to chest wall fibrosis , spontaneous pneumothorax.
- 69. broncho alveolar carcinoma
- 71. Most frequent symptoms of pulmonary inv. Are subtle .
- 72. Velcro crackles at lung base.
- 73. PFT for detection -- FVC, DLCO ,,,DLCO FVCINTERSTITIAL LUNG DISEASE90% cases at autopsy.HRCT –85%cases.
- 74. 16-43% are affected.
- 76. At risk are MALE,AFRICAN,diffuse skin inv.,severeGERD,topoisomerase I autoAb.
- 77. Rapid progression in first 3 yrs of onset –32% /year.
- 79. HRCT more sensitive,reticular linear opacities in lower lobes,mediastinallymphadenopathy,ground glass appearance.
- 80. Non specific interstitial pneumonitis –better prognosis.
- 81. KL– 6 ,A GLYCOPROTEIN,type II pneumocytes,alveloar macrophages –earlier detection of ILD Pulmonary Arterial HypertensionMean Pulmonary arterial pressure > 25 mm Hg at rest.
- 82. 12-25% have PAH
- 83. In assosciation with ILD/solitary.
- 84. Usually downhill course –RHF –death.
- 85. At risk are – Ls SSc with anticentromereantibodies,late age of onset,severe raynauds,U1 –RNP,U3 RNP fibrillarin,B23 Ab.
- 87. PASP >40 mm Hg at rest in 2d echo.
- 88. Decreased DLCO
- 89. Right heart catheterisation accurate.
- 90. Increased BNP,Nt BNP levels
- 91. Prognosis degree of pulmonary artery pressure elevation. GASTROINTESTINAL 90% Pts.
- 93. Abn motility of intestines.
- 94. Prominent atrophy ,fibrosis of smooth muscle,intactmucosa,obliterative small vessel vasculopathy – all over GIT .
- 96. Xerostomia
- 97. Oral aperture
- 99. GERD – early
- 100. LES pressure
- 101. clearance
- 103. Gastroparesis – early satiety
- 104. Distention,abd pain
- 105. Increased reflux
- 106. Radionuclide studies GITGASTRIC VASCULAR ECTASIAs – seen in the antrum.
- 108. Diffuse small vessel vsculopathy
- 110. Recurrent GI bleed occult
- 111. Fat ,protein malabsorption,vitamin b12
- 112. Wide mouth sacculations in the colon occur –perforation.
- 114. Primary biliary cirrhosis may coexist.
- 115. May present with acute abdominal pain recurrent –differentiate from pseudoobstruction. RENAL HTN,chronic non progressive proteinuria.
- 116. SCLERODERMA renal CRISIS –dreadful complication of SSc.
- 117. 20-25% pts
- 118. < 4 yrs of onset of diseases
- 119. Survival <10 % until ACEI
- 120. It is due to OBLITERATIVE VASCULOPATHY of renal cortical arteries.
- 121. RBF JGA hyperplasia renin secretion RAAS renal vasoconstriction malignant HTN.
- 123. At risk -- africanamerican,male,diffuse skin involvement,ab to RNA polymerase III
- 124. Impending renal crises – palpable tendon friction rubs,pericardialeffusion,new unexplained anemia,thrombocytopenia.
- 125. Localised scleroderma –infrequent development.
- 126. Prednisolone to be avoided.RENALPresentation –abrupt onset of malignant HTN, severe headache,blurredvision,chest pain.
- 127. 10% normal BP – normotensive renal crises.
- 128. Urinalysis -- proteinuria,microscopichematuria,fragmented RBCs
- 129. Rapidly progressive oliguric renal failure follows
- 130. D.D – TTP commonly misdiagnosed.
- 131. Creatnine > 3 mg/dl at presentation –poor prognosis.—permanent hemodialysis –high mortality,
- 132. Prompt use of ACEI to make BP under control before renal failure occurs –imporved prognosis.Cardiac Myocardial ,pericardial ,conduction abnormalities.
- 133. Can occur secondary to renal ,pulmonary involvement.
- 134. LVDD is frequent.
- 135. LVDD –due to HTN ,myocardial fibrosis.
- 136. Asymptomatic until HF ,arryhthmias occurs.
- 137. Myocarditis in assosciation with inflammatroypolymyositis.
- 138. Conduction defects due to fibrosis of conduction system.
- 139. Pericardial effusion –symptoms– rarely tamponade. MusculoskeletalCARPAL TUNNEL SYNDROME –may be a presenting feature.Early disease –generalisedarthralgia,stiffness.Joint mobility affected in diffuse disease.HANDS –PIP joints,wrists.Tendon friction rubs are present.—extensive fibrosis,adhesion of tendon sheaths.True joint inflammation is reduced.Muscle weakness due to disuse,malnutrition.Chronic noninflammatroymyopathy is usually seen.Bone resorption –a freq late complication –terminal phalanges –loss of distal tufts –ACRO OSTEOLYSIS.Mandible affected—biting difficulty Ribs,distal clavicle
- 141. Other disease manifestationsDry eyes,dry mouth –SICCA complex.
- 142. Biopsy of the minor salivaryglands –fibrosis rather than lymphocytic infitration.(sjogren’s syndrome)
- 143. Hypothyroidism –fibrosis of gland.
- 144. CNS is generally spared . Sensory trigeminal neuropathy due to fibrosis /vasculopathy can occur.
- 145. Pregnancy -adverse outcomes
- 146. Cardiopulmonary complications,new onset renal crises can occur.
- 147. Erectile dysfunction in the male. Laboratory featuresAnemia – frequent
- 148. Most common is mild normocytic /microcytic anemia –chronic inflammation
- 149. Serum iron is low or normal,ferritin is elevated.
- 150. Iron deficiency anemia –occult GI bleed (WATERMELON STOMACH),chronic esophagitis.
- 151. Macrocytic anemia – vitmainb12,folate,bacterial overgrowth,drugs
- 152. Acute microangiopathic anemia –mechanical trauma—renal crises
- 153. Thrombocytopenia ,leukopenia –DRUG toxicity.
- 154. ESR is normal
- 155. Increased ESR –MYOSITIS ./MALIGNANCYANTINUCLEAR ANTIBODIESAll patients of SSc
- 156. Highly specific are anti topoisomerase –I (Scl 70) and anti centromereAb
- 157. Specific ab profile remains stable over time.
- 158. Topoisomerase I ab 31% of dcSSc ,13% of lcSSc
- 159. Anticentromereab in 38% of lcSSc,2% of dcSSc.
- 160. U3RNP fibrillarin –characteristic nucleolarfluoroscencepattern,Th/To,PM/Scl .
- 161. No direct pathogenic role has been established for SSc associated autoantibodies..
- 162. Antibody titers correlate with disease severity . Auto antibodies in SSc
- 164. DiagnosisDiagnosis on clinical grounds.
- 165. Presence of skin induration with a characteristic symmetrical distibutionpattern,typical visceral organ manifestation-establishes the diagnosis with high certainity.
- 166. Full thickness biopsy – required for diagnosis of scleredema,scleromyoxedema,nephrogenic systemic fibrosis.
- 167. lcSSC– CREST for diagnosis
- 168. Nail fold microscopy for differentiation from primary raynaud’s
- 169. Diffuse edema of fingers..
- 170. SSc sine scleroderma– anticentromereabDifferential diagnosis
- 171. Differential diagnosisBased on vascular changes:1.PRIMARY raynaud’s phenomenon
- 172. 2.physical trauma –jack hammer
- 173. 3.chemical exposure
- 174. 4.drugs toxins – toxic oil syndrome,ergotamine,Bblockers ,carbidopa,5HT .
- 175. 5.SLE,DM/PM,RA.,cryoglobulinemia.Based on skin changes1.localized scleroderma
- 176. 2.scleroderma like skin changes
- 177. 3.metabolic –genetic disorders –scleredema/scleromyxedemaBased on visceral involvement1.idiopathic pulmonary HTN
- 179. 3.sarcoidosis
- 180. 4.amyloidosisTreatmentNo therapy has been shown significantly to alter the natural h/o SSc till date.
- 181. Multiple interventions are avialable in alleviating the symptoms –slowing progression of organ damage.
- 182. Treatment approaches to be individually tailored.
- 183. Optimal management – prompt,accuratediagnosis,classification,riskstratify,earlyrecogntion of organ based complicatyions,regular monitoring of progression,diseaseactivity,response to treatment,[patient education.
- 184. Holistic approach is needed.
- 185. Combination of drugs are used.
- 186. Physician –patient relationship to be mainatined. Disease modifying treatmentsImmunosuppressive agents –modest or no benefit in Rx of SSc.
- 187. Glucocorticoids - stiffness and aching in pts with early stage disease.
- 188. Do not influence the progression of skin/internal organ involvement.
- 189. ↑risk of scleroderma renal crises at high doses.
- 190. Avoid if possible.
- 191. Low dose ,brief periods.
- 192. Cyclophosphamide –daily oral/IV in SSc related ILD.
- 193. Reduces the progression of ILD ,stabilises,improvement in skin induration.
- 194. Early stage SSc/extensive pulmonary involvement –candidate
- 195. Rx for 6- 12 months ,optimal duration not known.
- 197. Bonemarrowsuppression,oppinfections,hemorhhagiccystitis,bladder Ca.Disease modifying treatmentsMethotrexate – modest therapeutic benefit
- 198. Potential profibrotic effects --? Use in fibrotic phase
- 199. Mycophenolatemofetil– improvement in skin induration
- 200. Well tolerated
- 202. Immune ablation with high dose chemotherapy followed by autologous peripheral stem cell reconstitution
- 203. Stem cell transplantation –experimental.Drugs that interfere with fibrotic processD penicillamine– antifibrotic agent
- 205. Prevents cross linkage of collagen fibres.
- 207. Prevents new organ involvement
- 208. Improved survival
- 209. No effect in early active SSc
- 210. 750 mg/d
- 211. Minocycline
- 212. Recombinant relaxin
- 213. IFN Vascular therapy Dress warmly
- 214. Minimize cold exposure.,Avoid drugs
- 215. Biofeedback therapy.
- 216. CCBs –diltiazem,nifedipine –ADVERSE effects
- 217. ACEI –not effective
- 218. ARBs –losartan well tolerated.
- 219. 1 blocker –prazosin
- 220. Sildenafil ,Fluoxetine ,Topical NTG, IV PROSTAGLANDINS.
- 221. Empiric treatment with statins,antioxidants
- 222. Low dose asprin,dipyridamole –useful
- 223. Digital sympathetectomy in severe cases
- 224. Bosentan prevents new ulcers Rx of GI complicationsElevate head end of the bed.Eat frequent small mealsPPIs ,H2B at higher doses are effective.Laser photocoagulation –recurrent bleeding from watermelon stomachMetronidazole,erythromycin,tetracycline –bacterial overgrowth.Parenteral nutrition in case of severe disease.Hypomotility of the gut –octreotide.
- 225. Rx of PAH SCREEN ON REGULAR BASIS.
- 226. Symptomatic –oral endothelin receptor antagonist
- 227. Diuretics
- 228. Oral anticoagulants
- 229. Digoxin
- 230. Bosentan –increases exercise tolerance,decreases PAH progression.
- 231. 0 2 –nasal cannula
- 232. Sildenafil –short term benefit
- 233. Parenteral prostaglandin analogues –epoprostenol,teprostinil IV/sc infusion.
- 234. Iloprost –inhalation
- 235. Lung transplantationRx of Renal CrisesMedical emergency
- 236. Outcome determined by amount of renal damage
- 238. Rx –ACEI ,short term dialysis.
- 239. Kidney transplantation.Skin care 5 mg prednisone
- 240. D penicillamine
- 241. Cyclophosphamide
- 242. Regular skin massage
- 243. Telangiectasia –laser pulse dyed laser
- 244. Finger tip ulcerations –occlusive dressings
- 245. Infected ulcers –topical Abs
- 246. Surgical debridement
- 247. No therapy effectvie in preventing the formation of calcific deposits.Course,PrognosisDcSSc has more progressive disease than lcSSc.
- 248. Early inflamatory changes subside in 2-4 yrs..organ involvement occurs here.
- 249. New organ involvement is rare after skin involvement reaches peak.
- 250. Skin regression occurs in the order of occurrence
- 253. dcSSc –5 ,10 YR SURVIVAL RATES –70%,55%
- 254. lcSSc – 90% ,75% Poor prognosisMale gender
- 255. young age of onset
- 258. Truncal involvement
- 260. Topoisomerase I ab
- 261. Increased ESR ,anemia ,proteinuria on initial presentation –high mortality… futureIMATINIB mesylate
- 262. Scope for research
- 263. Unresolved questions
- 264. Etiology
- 265. Pathogenesis
- 266. Therapuetic potential of various regimensTrials141 TRIALSSleep Disturbances and Pulmonary Artery/Aorta Diameter in Scleroderma Patient
- 267. High Dose Cyclophosphamide for Treatment of Scleroderma
- 268. Digital Ischemic Lesions in Scleroderma Treated With Oral TreprostinilDiethanolamine (DISTOL-1)
- 269. Pulmonary Involvement in Scleroderma: A Clinical Study of the Safety and Efficacy of MycophenolateMofetil in Scleroderma Patients With Lung Involvement
- 270. Sildenafil Effect on Digital Ulcer Healing in sClerodErma SEDUCE STUDY
- 271. Effect of Bosentan in Scleroderma Renal Crisis (ScS-REINBO)
- 272. Efficacy and Safety of Imatinib in Scleroderma (SCLEROGLIVEC)
- 273. Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II) (SLSII)Take home messageSSc is a chronic systemic disorder.
- 274. RULE out other causes.
- 275. Anti topoisomerase –dcSSc,anticentromereab -LcSSc
- 276. After diagnosis risk stratify the patient.
- 277. Regular follow up and monitoring.
- 278. Patient education is needed.
- 280. Renal crises is an emergency.
- 281. ACEI are to be started in a pt with HTN.
- 282. No treatment for calcinosis cutis
- 283. Imatinib in near future….
- 284. Scope for research ..ReferencesHARRISON’S principles of internal medicine ,17 th Ed www.medscape.comwww.clinicaltrials.govwww.scleroderma.orgwww.dermatologylib.comwww.ncbl.nbi.comwww.google.comwww.dailyquotes.comwww.orpha.net
- 286. sagittarian