1. Systemic Sclerosis (Scleroderma)
By Dr. Zahoor

2. Systemic Sclerosis
Systemic Sclerosis (Scleroderma) is auto immune or connective tissue disorder
Systemic Sclerosis is called connective tissue disease but now word Auto immune Rheumatic disease (ARD) is used.
Why ?
Because clinical effects of ARD are not limited to connective tissue only

3. Mixed Connective Tissue Disorder (MCTD)
Mixed connective tissue disorders is old term, now we call Auto Immune Rheumatic Diseases
This term is used when there is overlap condition, where there are clinical features of SLE (Systemic Lupus Erythematosis), Systemic Sclerosis, Myositis
It commonly presents with synovitis and oedema of hands in combination of Raynaud's phenomenon and muscle pain/weakness

4. We will discuss Systemic Sclerosis or Scleroderma

5. Systemic Sclerosis
Systemic Sclerosis is chronic, multi system disease characterized by fibrosis and vasculopathy of skin and visceral organs

6. Systemic Sclerosis There are two overlapping forms:
1. Limited cutaneous Systemic Sclerosis (LcSSc)
It is limited to the skin of face, hands and feet.
Pulmonary hypertension occurs late in disease.
It is associated with CREST syndrome.
CREST (Calcinosis, Raynaud’s phenomenon, Esophageal
dysfunction, Sclerodactyly, Telangiestasias).
2. Diffuse cutaneous Systemic Sclerosis (DcSSc)
Affects more skin and there is risk of visceral organ
involvement – kidneys, heart, lungs, and GIT

7. Systemic Sclerosis (SSC)
The incidence of SSC is 10/million population per year with 3.1 female to male ratio
Peak age of SSC is 30 – 50 years
Aetiology
Familial cases are reported, genetic factors might be responsible
Environmental risk factors
- Exposure to silica, dust, vinyl chloride,
trichloroethylene
- Drugs e.g. Bleomycin

8. Systemic Sclerosis (Scleroderma)
Pathology and Pathogenesis
An early lesion is wide spread vascular damage involving small arteries, arterioles and capillaries
There is endothelial damage with release of cytokines, Endothelin 1 which causes vasoconstriction
Release of interleukin, platelet growth factor increased fibroblast activity resulting in abnormal growth of connective tissue

9. Systemic Sclerosis (Scleroderma)
Pathology and Pathogenesis (cont)
This causes vascular damage and fibrosis
Fibrosis occurs in skin, GIT and other internal organs
Damage to small blood vessels produces ischemia

10. Systemic Sclerosis (Scleroderma)
Clinical Features
- Raynaud's Phenomenon – seen in almost 100% of cases and can present before onset of disease by many years
Limited Cutaneous Scleroderma (LcSSc) - 70% of
the cases
This usually starts with Raynaud’s phenomenon many years before
Skin involvement is limited to hands, forearm, face, and feet
Skin is tight over the fingers and often produces flexion deformities of the fingers

11. Systemic Sclerosis – Hands showing tight shiny skin, flexion contractures of the fingers (sclerodactyly)

12. Scleroderma: Raynaud's Phenomenon, Cyanosis of the Hands

13. Calcinosis in long standing systemic sclerosis. 

14. Systemic Sclerosis (Scleroderma)
Limited Cutaneous Scleroderma (LcSSc) (cont)
Involvement of skin of face produces “beak like nose” and small mouth (microstomia)
Painful digital ulcers and telangiectasia are seen
Digital ischemia may lead to gangrene
GIT involvement is common
Pulmonary hypertension develops in 21% of people
Pulmonary interstial disease also occurs

15. Typical facial appearance in CREST syndrome

16. Facial appearance in Systemic Sclerosis - drawn pursed lips, shiny skin over the cheeks and forehead

17. Systemic Sclerosis (Scleroderma)
Diffuse cutaneous Systemic Sclerosis (DcSSc) –
30% of cases
Raynaud's phenomenon
Diffused swelling and stiffness of fingers is rapidly followed by more extensive skin thickening which can involve most of the body
Later, skin becomes atrophic
Other organs are involved with general symptoms of lethargy, anorexia and weight loss

18. Systemic Sclerosis (Scleroderma)
Diffuse cutaneous Systemic Sclerosis (cont)
GIT symptoms
- Heart burn, reflux, or dysphagie due to oesophageal involvement is almost present
- Malabsorption from bacterial over growth due to dilatation and atony of small bowel
Pseudo obstruction is known complication
- Rarely dilatation and atony of colon
- Anal incontinence occurs in many patients

19. Systemic Sclerosis (Scleroderma)
Renal Involvement
May be acute or chronic
Acute hypertensive renal crisis used to be common cause of death, but ACE inhibitors and Dialysis and Renal transplantation has changed this

20. Systemic Sclerosis (Scleroderma)
Lung involvement
Lung fibrosis
Pulmonary hypertension
Myocardial involvement
Myocardial fibrosis occurs and causes arrhythmias, conduction defects, pericarditis (occasionally)

21. Systemic Sclerosis (Scleroderma) Clinical Features

22. Systemic Sclerosis (Scleroderma)
Investigation
Full blood count
- Normocytic, Normochromic anemia
- Microangiopathic haemolytic anemia in some people
Urea and electrolyte rise in acute kidney injury
- Urine microscopy, proteinurea,
urine/creatinine ratio should be measured

23. Systemic Sclerosis (Scleroderma)
Investigations
Antibodies
a- Anti centromere anti bodies (ACAs) occur in 80% of cases in LcSSc
b- Anti topoisomerase-1 (called Anti-ScL-70) in 30% of cases in DcSSc
and Anti RNA Polymerase is associated with pulmonary fibrosis
c- ANA is positive in 95%
d- Rheumatoid factor is positive in 30%

24. Systemic Sclerosis (Scleroderma)
Imaging
CXR – to see cardiac size and lung disease
High resolution CT – to demonstrate fibrotic lung involvement
X-ray hands – look for deposits of calcium around fingers, in severe cases erosion and absorption of tufts of distal phalanges
Barium swallow
- impaired oesophageal motility
- upper GI endoscopy

25. Systemic Sclerosis (Scleroderma)
Treatment
Currently there is no cure
Treatment should be symptametic – organ based
Corticosteroids and Immuno suppressants are rarely used except SSC related pulmonary fibrosis
Counseling and family support are essential

26. Systemic Sclerosis (Scleroderma)
Treatment (cont)
Regular exercises and skin lubricants may limit contractures
Raynaud’s – oral vasodilators (calcium channel blockers, ACE inhibitors)
Esophageal symptoms are improved by proton pump inhibitors

27. Systemic Sclerosis (Scleroderma)
Treatment (cont)
Malabsorption symptoms require nutritional supplements and anti biotic to treat small intestinal bacterial over growth
Renal involvement – control of hypertension, first drug of choice is ACE inhibitors
Pulmonary hypertension is treated with oral vasodilator, oxygen, and warfarin

28. Systemic Sclerosis (Scleroderma)
Treatment (cont)
Pulmonary fibrosis is currently treated with Immuno suppression, cyclophosphamide or Azathioprine combined with low dose oral predinisolone
Prognosis – Patient with limited cutaneous scleroderma have good prognosis 70% survive for 10 years .
Patient with diffuse cutaneous scleroderma have 10 year survival of 55%. Death most often from pulmonary, heart or kidney involvement.

29. Thank you