1. Systemic sclerosis

2. definition
Systemic sclerosis (previously called 'scleroderma') is a generalized disorder of connective tissue affecting the skin, internal organs and vasculature. The clinical hallmark is the presence of sclerodactyly in combination with Raynaud's phenomenon or digital ischemia. The peak age of onset is in the fourth and fifth decades, and overall prevalence is per with a 4:1 female: male ratio

3. Scleroderma –, Raynaud’s phenomenon , esophageal dysmotility , sclerodactyly and telangiectasia

4. Etiological factors Environmental factors:- Genetic factors:
increased frequency in coal & gold minors.
induced scleroderma like syndrome ; exposure to polyvinyl chloride, bleomycine therapy & silicone breast implants.
scleroderma like lesions in GVHD.
Genetic factors:
.High risk in 1st degree relative.

5. pathology
Early in the disease there is skin infiltration by T lymphocytes and abnormal fibroblast activation that leads to increased production of extracellular matrix in the dermis, primarily type I collagen. This results in symmetrical thickening, tightening and induration of the skin (sclerodactyly). There is arteriolar narrowing due to intimal proliferation and vessel wall inflammation. Endothelial injury causes release of vasoconstrictors and platelet .activation, resulting in ischemia

6. The initial phase of skin disease is characterised by non-pitting oedema of the fingers and flexor tendon sheaths. Subsequently, the skin becomes shiny and taut, and distal skin creases disappear. There is usually erythema and tortuous dilatation of capillary loops in the nail-fold bed, readily visible with an ophthalmoscope set to +20. The face and neck are usually involved next, with thinning of the lips and radial furrowing.

7. Scleroderma: edematous changes, hands
Swelling of the distal limbs may develop early in the course of systemic sclerosis. Puffy hands are shown here. #
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8. Systemic sclerosis Fibrotic contractures .
Acrolysis of the distal phalanges .
Pigmentation .
Spots of depigmentation .
Scleroderma: calcinosis and acrolysis (radiograph)
Extensive soft-tissue calcification can be seen in the index finger. Scattered calcium flecks are present in the remaining fingers. Acrolysis with partial resorption of distal bony phalanges is visible in the middle and ring fingers. #

9. Skin involvement restricted to sites distal to the elbow or knee (apart from the face) is classified as 'limited cutaneous disease' or CREST syndrome … Involvement proximal to the knee and elbow and on the trunk is classified as 'diffuse cutaneous disease'. fingertips.

10. Scleroderma Head and Neck Manifestations
tight skin, thin lips, vertical perioral furrows
dermal and subcutaneous inflammatory process
edema preceeds epidermal atrophy, loss of appendages

11. Head and Neck Manifestations
Scleroderma
Head and Neck Manifestations
decreased mouth opening
Peaked nose
Tight neck bands

12. Scleroderma: facial changes marked telangiectasia
Scleroderma: Mauskopf, facial changes
This patient demonstrates the facial and mucous membrane telangiectasia characteristic of CREST syndrome. These telangiectasias can be blanched by pressure. They may be confused with hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease). CREST is an acronym for calcinosis, Raynaud's disease, esophageal involvement, sclerodactyly, and telangiectasias. #

13. Scleroderma: Raynaud’s phenomenon, blanching of hands
The marked pallor of the fourth and fifth digits on the left hand and of the fifth digit on the right hand is characteristic of Raynaud’s phenomenon. Vasospastic changes are common in systemic sclerosis but may also occur in rheumatoid arthritis, systemic lupus erythematosus, and idiopathic Raynaud’s disease. #
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14. Musculoskeletal features
Arthralgia, morning stiffness and flexor tenosynovitis are common. Restricted hand function is due to skin rather than joint disease and erosive arthropathy is uncommon. Muscle weakness and wasting are usually due to myositis.

15. Gastrointestinal features
Gut involvement is common. Smooth muscle atrophy and fibrosis in the lower two-thirds of the oesophagus lead to acid reflux with erosive oesophagitis. Since this may progress to further fibrosis, adequate treatment of reflux (usually with proton pump inhibitors) is important. Dysphagia and odynophagia (painful dysphagia) may also occur

16. Cardiorespiratory features
Pulmonary involvement is a major cause of morbidity and mortality. Fibrosing alveolitis mainly affects patients with diffuse disease, particularly those with antibodies to topoisomerase 1. Pulmonary hypertension is a complication of long-standing disease and is six times more prevalent in limited than in diffuse disease.

17. Renal features
One of the main causes of death is hypertensive renal crisis characterized by rapidly developing malignant hypertension and renal failure. Treatment is by angiotensin-converting enzyme (ACE) inhibition even if renal impairment is present. Hypertensive renal crisis is much more likely to occur in patients with diffuse rather than limited disease

18. Scleroderma: acrosclerosis
Flexion contractures of the fingers are secondary to a tightened indurated skin. This type of change in the fingers is called acrosclerosis (sclerodactyly) and is characteristic of systemic sclerosis. However, skin changes proximal to the metacarpophalangeal joints are more specific for systemic sclerosis than changes only in the fingers. Areas of increased and decreased pigmentation are also visible. #
Copyright © American College of Rheumatology Slide Collection. All rights reserved.

19. CREST syndrome: calcinosis cutis, fingers
Calcinosis is evident in the fingers of this patient with the CREST variant of systemic sclerosis. The calcinosis appears as irregular, hard nodules. In places, the overlying skin is thin, and the underlying calcific material appears as small yellowish patches. Surrounding areas of erythema and tenderness may accompany these lesions. At the tip of the index finger is a healing ulcer from which calcific material was previously extruded. This finger also demonstrates distal pulp atrophy. #

20. Scleroderma: calcinosis and acrolysis (radiograph)
Extensive soft-tissue calcification can be seen in the index finger. Scattered calcium flecks are present in the remaining fingers. Acrolysis with partial resorption of distal bony phalanges is visible in the middle and ring fingers. #

21. Laboratory findings -1-
Raised inflammatory markers.
Anemia:
of chronic illness.
Microangiopathic hemolytic anemia (hemolysis is caused by factors in the small blood vessels) .
malabsorption.
Complication related e.g. renal failure findings and restrictive lung function tests.

22. Laboratory findings -2-
Autoantibodies
Anticentromere Abs:40-80% of cases with limited SSc or CREST. Rare (2-5%) in diffuse SSc & in other connective tissue disorders.
Antitopoisomerase 1 Abs: about 40% of cases of diffuse SSc specially with visceral involvement. Rare in other disorders.
Antinucleolar Abs :near 20-30% of SSc. High speceficity.
ANA in up to 90% of patients (poor specificity) .

23. prognosis 5-years survival is about 70%.
Bad prognostic features include:
-diffuse cutaneous form.
-onset at an older age.
-male gender.
-renal involvement.
-pulmonary hypertension.

24. Management
Five-year survival is approximately 70%. Risk factors at presentation that associate with a poor prognosis include older age, diffuse skin disease, proteinuria, high ESR, a low gas transfer factor for carbon monoxide (TLCO) and pulmonary hypertension. Self-management to maintain core body temperature and avoid peripheral cold exposure is important. Infection of ulcerated skin should be treated with prompt antibiotic therapy. Antibiotics penetrate poorly into the skin lesions of systemic sclerosis and therefore need to be given at higher dose for longer periods (e.g. flucloxacillin 500 mg 6-hourly for 14 days).

25. Calcium antagonists (e. g
Calcium antagonists (e.g. nifedipine, amlodipine) or angiotensin II receptor antagonists (e.g. valsartan) may be effective for Raynaud's symptoms. For severe digital ischaemia, intermittent infusions of epoprostenol may be helpful. Corticosteroids and cytotoxic drugs are indicated in patients with myositis or alveolitis. No agent has been shown to arrest or improve skin changes

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