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Scleroderma ( Systemic Sclerosis )

Scleroderma ( Systemic Sclerosis ). Definition. Systemic sclerosis (scleroderma) a multisystem disorder characterized by 1) functional and structural abnormalities of blood vessels 2) fibrosis of the skin and internal organs 3) immune system activation 4) autoimmunity

winifred-vazquez
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Scleroderma ( Systemic Sclerosis )

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  1. Scleroderma (Systemic Sclerosis)

  2. Definition • Systemic sclerosis (scleroderma) • a multisystem disorder characterized by • 1) functional and structural abnormalities of blood vessels • 2) fibrosis of the skin and internal organs • 3) immune system activation • 4) autoimmunity • Sclero=thickened, derma=skin

  3. Epidemiology • 1. Prevalence: 20 new cases per million per year • 2. Susceptibility: host factor • 1) age - peak occurrence: age 35-65 years • 2) gender - female : male = 4 : 1 • 3) genetic background • 4) enviromental factors • Occurs at a younger age and has a worse prognosis in African American women

  4. Classification • Systemic sclerosis • Diffuse cutaneous systemic sclerosis • Limited cutaneous systemic sclerosis • Overlap syndromes • 2. Localized scleroderma • Morphoea • Linear scleroderma • En coup de sabre

  5. Classification of systemic sclerosis • 1. Diffuse cutaneous systemic sclerosis • 1) proximal skin thickening • - distal and proximal extremity and often the trunk and face • 2) tendency to rapid progression of skin change • 3) rapid onset of disease following Raynaud’s phenomenon • 4) early appearance of visceral involvement • 5) poor prognosis

  6. Classification of systemic sclerosis 2. Limited cutaneous systemic sclerosis 1) symmetric restricted fibrosis - affecting the distal extremities and face/neck 2) prolonged delay in appearance of distinctive internal manifestation 3) the pacients usually have Raynaud’s phenomenon for years 4) prominence of calcinosis and telangiectasia 5) good prognosis * CREST syndrome - calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia

  7. Classification of systemic sclerosis • 3. Overlap syndromes • Features of systemic sclerosis together with those of at least one other autoimmune rheumatic disease, e.g. SLE, RA, or polymyositis

  8. Environmental factors 1) silica dust 2) organic solvents 3) biogenic amines 4) urea formaldehyde 5) polyvinyl chloride 6) rapeseed oil 7) bleomycin 8) L-tryptophan 9) silicone implant (?) Genetic predisposition Defective immunoregulation 1) cell mediated immunity CD4/CD8 , cytokines 2) humoral immunity hypergammaglobulinemia autoantibody production antinuclear antibody (+) > 95% Etiology

  9. Pathogenesis Susceptible host Exogenous events Immune system activation Endothelial cell activation/damage Fibroblast activation End stage pathology Obliterative vasculopathy Fibrosis

  10. Pathogenesis

  11. Pathogenesis • 1. Vasculopathy of small artery and capillary • - endothelial cell injury • - adhesion and activation of platelet • - PG F, thromboxane A2 release • - vasoconstriction & growth of endothelial cell and fibroblast • - narrowing or obliteration, increased permeability • 2. Fibrosis • - aberrant regulation of fibroblast cell growth • - increased production of extracellular matrix • (collagen, fibronectin, and glycosaminoglycan) • - thickening of the skin & fibrosis of internal organs

  12. Pathogenesis • 3. Immune system activation producing autoantibodies: • -anti-topoisomerase I (anti Scl 70) • -anti-centromere • -anti RNA polymerases • -anti U1 RNP • -anti B23

  13. Clinical features • 1. Vascular abnormalities • 1) Raynaud's phenomenon • - cold hands and feet or ears/ nose/ tongue • -with reversible skin color change (white to blue to red) • - induced by cold temperature or emotional stress • - initial complaint in 3/4 of patients • 2) digital ischemic injury

  14. Raynaud’s phenomenon-pallor phase

  15. Raynaud’s phenomenon-cyanotic phase

  16. Clinical features 2. Skin involvement (1) 1) stage - edematous phase - indurative phase - atrophic phase 2) firm, thickened bound to underlying soft tissue 3) decrease in range of motion, loss of facial expression, inability to open mouth fully, contractures

  17. Edematous phase

  18. Skin Induration

  19. Acrosclerosis

  20. Facial changes Tight, thin lips with vertical perioral furrows

  21. Salt and pepper pigmentation

  22. Clinical features • 2. Skin involvement (2) • ulceration, loss of soft tissue of finger tip, pigmentation, calcific deposit, capillary change • 3. Musculoskeletal system • Polyarthritis and flexion contracture • Muscle weakness and atrophy (primary /secondary)

  23. Terminal digit resorption

  24. Acrolysis

  25. Digital pitting scars

  26. CREST syndrome: C is for calcinosis

  27. CREST :R is for Raynaud

  28. CREST : E is for esophageal dysmotility • ... actually, you have to imagine this one • CREST : S is for Sclerodactyly

  29. CREST: T is for telangiectasia

  30. RODNAN score

  31. Clinical features 4. intestinal involvement 1) esophagus: hypomotility and retrosternal pain, reflux esophagitis, stricture 2) stomach: delayed emptying 3) small intestine: pseudo-obstruction, paralytic ileus, malabsorption, weight loss, cachexia 4) large intestine: chronic constipation and fecal impaction diverticula

  32. Abnormal motility Diverticula

  33. Clinical features • 4. exocrine glands • Xerostomia • xerophthalmia • 5. lungs • 1) 2/3 of patients affected • - leading cause of mortality and morbidity in later stage • of systemic sclerosis • 2) pathology • - interstitial fibrosis • - intimal thickening of pulmonary arterioles • (pulmonary hypertension)

  34. Pulmonary fibrosis

  35. Clinical features • 6. heart (10%): pericarditis, heart failure, arrhythmia, myocardial fibrosis • 7. kidney-scleroderm renal crisis Features: HTN, microangiopathic hemolytic anemia and oliguric renal failure. Risk Factors: • Diffuse disease within the first five years • Anti-RNA polymerase III antibody • Pericardial effusion • > 15 mg prednisone daily or • Cyclosporin therapy

  36. Laboratory findings • 1. ANA, RF • 2. anti-Scl-70 (DNA topoisomerase I) antibody • 1) 20-30% in diffuse scleroderma • 2) 10-15% in limited scleroderma • 3. anticentromere antibody • 1) 50-90% in limited scleroderma • 2) 5% in diffuse scleroderma • 4. Anti RNA polymerase III Ab: 10- 25% in Diffuse SSc, Renal Disease.

  37. Subsets of systemic sclerosis

  38. Diagnosis- ACR criteries • 1. major criteria: proximal scleroderma • 2. minor criteria: • 1) sclerodactyly • 2) digital pitting scar or • loss of substance from the finger pads • 3) bibasilar pulmonary fibrosis • *the major or 2 or more minor criteria for diagnosis

  39. Scoring Systems for Severity (?!?) • Disease burden: The Systemic Sclerosis Severity Scale Includes nine organ systems. • Functional Assessment: Scleroderma Health Assessment Questionnaire Disability Index (SHAQ) and Scleroderma Functional Score. • Quality of Life: Short Form Health Survey (SF-36) for psychological and mental functioning

  40. Differential dignosis • Raynaud phenomenon: primary Raynaud’s syndrome, SLE, systemic vasculitis, medication-induced. • Skin thickening: scleredema, scleromyxedema, POEMS syndrome, diabetic cheiroarthropathy, morphea • Overlapping clinical features: SLE, Sjogren syndrome, RA, inflammatory myopathies.

  41. Treatment • A wide spectrum of clinical manifestations and severity • - spontaneous improvement occurs frequently • Disease modifying interventions (?) • - methotrexate • - immunosuppressive agent: cyclosporin, cyclophosphamide,mycophenolate mophetil • - recombinant human relaxin • Symptomatic (organ-specific) treatment

  42. Treatment • Raynaud’sphenomenon and ischemia • 1) avoid cold exposure • layers of warm, loose-fitting clothing • 2) quit smoking • 3) vasodilator therapy • - calcium channel blocker (nifedipine), prazosin, ACE-i • 4) finger / toe necrosis • - intravenous prostaglandin (PGE1, PGI2) • - amputation

  43. Treatment • Gastrointestinal • 1) reflux esophagitis and dysphagia • - elevation of head of bed • - small frequent meal • - avoid lying down within 3-4 hours of eating • - abstaining from caffeine-containing beverages, • cigarette smoking • - H2 blocker, proton-pump inhibitor • 2) gastroparesis: promotility agent (metoclopramide) • 3) malabsorption syndrome: broad spectrum antibiotics

  44. Treatment Pulmonary 1) Interstitial fibrosis - corticosteroid - cyclophosphamide, azathioprine 2) pulmonary artery hypertension - calcium channel blocker - prostacyclin -sildenafil - transplantation Renal renal crisis: -early detection and ACE inhibitor 1 year survival without captopril 15% 1 year survival with captopril 76% - dialysis

  45. Prognosis • 1. quite variable and difficult to predict • 2. cumulative survival • diffuse limited • 5 yr 70% 90% • 10 yr 50% 70% • 3. major cause of death • 1) renal involvement • 2) cardiac involvement • 3) pulmonary involvement

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