1. Systemic Sclerosis ANAS MUHANNAa MD,FACR AL-QUDS UNIVERSITY
FACULTY OF MEDICINE

2. Sclero / derma Hard Skin Definition:
Generalized disorder of connective tissue affecting the skin, internal organs and blood vessels.
F:M = 3-9 :1
Peak onset : years
Prevalence per 100,000

3. types I and III collagens (vinyl chloride, trichloroethylen)
Pathophysiology
pathogenic mechanisms
Endothelial cell injury
Fibroblast activation
Cellular and humoral immunologic derangement ??
types I and III collagens
glycosaminoglycans
fibronectin
Silica exposure
Solvent exposure
(vinyl chloride, trichloroethylen)
Radiation

4. The nature of the vascular dysfunction in SSc

6. Severe alterations in small blood vessels of skin and internal organs, including fibrosis and perivascular cellular infiltration with activated T cells, are almost always present in systemic sclerosis.

7. Histologic Findings
square morphology/ rigidity of the tissue biopsy specimen due to striking pan-dermal sclerosis. The number of adnexal structures is reduced, characteristic feature. A significant inflammatory cell infiltrate is not observed.

8. History of present illness …

9. Skin Diffuse pruritus Skin tightness and induration
Skin pigmentary changes (hyperpigmentation or hypopigmentation;

10. Cutaneous and mucosal telangiectasis
Vascular system
Raynaud phenomenon
Healed pitting ulcers in fingertips
Cutaneous and mucosal telangiectasis

11. Raynaud phenomenon 70% present with this symptom
95% eventually develop it during the course of their disease

12. pitting ulcers in fingertips

13. Gastrointestinal system
Gastroesophageal reflux (lead to hoarseness, aspiration pneumonia, and dysphagia)
Dyspepsia, bloating, and early satiety
Constipation alternating with diarrhea (may lead to malabsorption)

14. Destruction of enzymes
Cont:
Small int. wall
fibrosis
↑ bacteria
Destruction of enzymes
& bile salts
↓ motility
malabsorbtion

15. Musculoskeletal system
generalized arthralgias and morning stiffness mimic other systemic autoimmune diseases
Myalgia
Loss in joint range of motion
Symptoms of carpal tunnel syndrome
Muscle weakness
Respiratory system
Progressive dyspnea
Chest pain (precordial) due to pulmonary artery hypertension
Dry persistent cough due to restrictive lung disease

16. Cardiovascular system
Dyspnea due to pericardial effusion, congestive heart failure, or myocardial fibrosis
Palpitations, irregular heart beats, and syncope due to conduction abnormalities
Congestive heart failure
Renal system
Hypertension
Renal crisis
Chronic renal insufficiency

17. Ears, nose, and throat Sicca syndrome
Poor dentition due to sicca syndrome
Loosening of dentition due to alteration in the tooth suspensory ligament and thickening of the periodontal membrane
Hoarseness due to acid reflux or vocal cord fibrosis

18. Neurologic Genitourinary system Endocrine system Constitutional
Facial pain and hand paresthesias due to sensory peripheral entrapment neuropathy
Headache and stroke during hypertensive renal crisis
Genitourinary system
Erectile dysfunction
Dyspareunia (if introitus is affected)
Endocrine system
Hypothyroidism
Constitutional
Fatigue
Weight loss

19. Lets do examination…

20. skin

21. Salt-pepper appearance
Skin pigmentary changes
Salt-pepper appearance
Anterior chest demonstrating salt-and-pepper hypopigmentation and diffuse hyperpigmentation in a white woman.

22. Telangiectasias
dilated vessels located just beneath the dermis on any skin area, but they are most obvious in the face (perioral area), hands, and anterior chest.

23. swollen
Sclerodactyly
indurated sclerotic stage

24. Calcinosis

25. Acrosclerosis/sclerodactyly.

27. microstomia

28. Eyes, ears, nose, and throat
Salivary production may be decreased and spontaneous sublingual pooling of saliva may be absent.
Xerostomia and xerophthalmia may be part of the examination findings. D/D primary Sjögren syndrome.
Oropharyngeal and esophageal cancers are more common in persons with diffuse systemic sclerosis.

29. Cardiovascular system
Pericardial effusion is usually asymptomatic (30%)
Clinically significant pericarditis is rare.
Cor pulmonale may develop secondary to long-standing pulmonary fibrosis or pulmonary artery hypertension.
Conduction abnormalities, including complete A-V block,
Infiltrative cardiomyopathy with replacement of cardiac muscle by fibrous tissue can lead to arrhythmias, heart failure, or both.

30. Neurologic system
Trigeminal neuralgia (uncommon) and carpal tunnel symptoms result from peripheral entrapment neuropathies.
rare, sensory neuropathies unrelated to entrapment may be present.

31. Renal system Renal crisis occurs in 10% of all patients.
Renal crisis presents as accelerated hypertension, oliguria, headache, dyspnea, edema, and rapidly rising serum creatinine levels.
10% NO HTN.
Renal crisis is observed within 4 years of diagnosis in about 75%
men have a greater risk than women.
IF not treated aggressively invariably leads to renal failure, requiring dialysis or renal transplantation, or even death.
Preventing : Check blood pressure, monitor serum creatinine, and start (ACE) inhibitors early in at-risk patients.
Avoid high doses of corticosteroids since this is a significant risk factor for renal crisis.

32. Reflux due to decreased lower esophageal sphincter pressure
Gastrointestinal system
Reflux due to decreased lower esophageal sphincter pressure
Severe esophagitis
Barrett metaplasia (can lead to cancer)
Candida esophagitis
Esophageal strictures
Gastric vascular antral ectasia (dilated submucosal capillaries), also known as watermelon stomach
Primary biliary cirrhosis (PBC) associated with antimitochondrial antibodies
Wide-mouth colonic diverticula
Malabsorption , constipation, pseudo-obstruction, gastroparesis
Anal sphincter incompetence

33. Respiratory system
Dry rales may be the only physical examination finding
pulmonary artery hypertension. .
active alveolitis
interstitial fibrosis
Patients are at risk for aspiration pneumonia due to lower esophageal sphincter incompetence.

34. Musculoskeletal system
Clinically apparent synovitis is uncommon.
Hand and joint function may decline over time because of skin tightening rather than arthropathy.
Tendon friction rubs are found almost exclusively in diffuse systemic sclerosis and may be detected as the tendon is moved actively or passively.
Myositis may cause weakness and muscle wasting. Levels of serum creatine kinase (CK) and aldolase are elevated.
Acroosteolysis (ie, resorption or dissolution of the distal end of the phalanx) may occur.
Flexion contractures of any affected joint may occur.

35. Vascular changes
Raynaud phenomenon :may precede obvious systemic sclerosis features by months or even years.
Infarction / dry gangrene may be due to severe vasospasm or to structural vascular occlusion. involves the digits , the lips, nose, and ears.
Nail-fold capillary microscopy demonstrates fewer capillaries than normal

36. Nail-fold capillary microscopy
capillary loop drop/numerous dilated capillary loops

37. The American College of Rheumatology criteria for the classification of systemic sclerosis
Major criterion:
Minor criteria:
(2 of the 3)
Proximal scleroderma
Sclerodactyly
Digital pitting scar
Interstitial change on chest x-ray

38. Thick skin of fingers and hands (proximal scleroderma)

39. Thick skin of forearms (proximal scleroderma)

40. (proximal scleroderma)
Thick skin of torso
(proximal scleroderma)

41. Thick skin of face (proximal scleroderma)

42. Atrophic (thin) skin changes of face (proximal scleroderma)

43. Systemic sclerosis criteria
Major criterion:
Minor criteria:
Proximal scleroderma Sclerodactyly

44. Sclerodactyly (early puffy fingers)

45. Taut, thick skin of fingers

46. Taut, thin skin of fingers

47. Digital tip pitting scars

48. Systemic sclerosis criteria
Major criterion:
Minor criteria:
(2 of the 3)
Proximal scleroderma Sclerodactyly Digital pitting scar Interstitial change on chest x-ray

49. Interstitial change (x-ray)

50. Systemic sclerosis (SSc) criteria
LeRoy & Medsger have suggested two additional criteria to diagnose mild SSc:
Raynaud’s phenomenon (plus both):
nailfold capillary abnormalities
SSc-specific antibodies (anti-centromere, anti-SCL-70, anti-PM-Scl, etc)

51. Lab Studies
Antinuclear antibodies are present in about 95% of affected patients,
Topoisomerase I antibodies ( Scl-70) 30% of patients with diffuse disease (absent in limited disease) associated with pulmonary fibrosis.
Anticentromere antibodies : 80-90% in limited disease and are rare in diffuse disease.

52. Imaging Studies
HRCT scan evaluate pulmonary involvement. ground-glass appearance first abnormality observed during the development of lung fibrosis
Chest radiography is an insensitive, shows late findings of pulmonary fibrosis,
Extremity radiography should be performed to reveal calcinosis and resorption of the distal tufts of the digits.
Echocardiography: evaluate the patient's pulmonary artery pressure and to assess septal fibrosis or pericardial effusions. Roughly 30% of patients have asymptomatic pericardial effusions
Right-heart catheterization: This remains the standard criterion for diagnosing pulmonary hypertension and is performed after echocardiographic screening
Esophagraphy: Perform this test to document esophageal dysmotility and an incompetent LES.

53. Endoscopic image of peptic stricture, or narrowing of the esophagus near the junction with the stomach due to chronic gastroesophageal reflux. This is the most common cause of dysphagia, or difficulty swallowing, in scleroderma.

54. Medical Care
the US Food and Drug Administration (FDA) has not approved any therapies for systemic sclerosis.
Skin thickening can be treated with D-penicillamine and other experimental drugs or interventions
Myositis :steroids (first choice), methotrexate, and azathioprine.
Arthralgias can be treated with acetaminophen and NSAID

55. Con. A wide spectrum of clinical manifestations and severity
Disease modifying interventions (?)
- penicillamine
- methotrexate
- immunosuppressive agent: cyclosporin, IFN-
- recombinant human relaxin
Symptomatic (organ-specific) treatment

56. Raynaud’s phenomenon and ischemia
1) avoid cold exposure layers of warm, loose-fitting clothing
2) quit smoking
3) vasodilator therapy- calcium channel blocker (nifedipine),
4) finger / toe necrosis
- intravenous prostaglandin (PGE1, PGI2)
- sympathetic block
- amputation

57. 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 - proton-pump inhibitors 2) gastroparesis: promotility agent (metoclopramide) 3) malabsorption syndrome: broad spectrum antibiotics

58. Pulmonary
1) Interstitial fibrosis
- corticosteroids
- cyclophosphamide, azathioprine
2) pulmonary artery hypertension
- calcium channel blocker
- prostacyclin
- transplantation

59. Renal
1) renal crisis
- early detection and ACE inhibitor
1 year survival without captopril 15%
1 year survival with captopril %
- dialysis
Doses of prednisone greater than 40 mg/d are
associated with a higher incidence of sclerodermal renal
crisis.

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