Progressive systemic sclerosis is a disorder affecting connective tissue in the skin, internal organs, and blood vessels. It is characterized by thickening and tightening of the skin, especially in the fingers and face. It can be classified as limited or diffuse cutaneous disease depending on the extent of skin involvement. Internal organ systems commonly impacted include the lungs, heart, kidneys, and gastrointestinal tract. Management involves treatments for symptoms such as Raynaud's phenomenon, digital ischemia, reflux, and pulmonary hypertension. Prognosis depends on factors like the extent of skin and organ involvement.

1. Progressive Systemic Sclerosis
ACMS Dept of Medicine
2010 Batch VIII Term

2. PSS: Definition
• Systemic sclerosis (previously called
'scleroderma') is a generalised disorder of
connective tissue affecting-
• The skin
• Internal organs and
• Vasculature.

3. PSS: Hallmark
The clinical hallmark is the presence of
• Sclerodactyly in combination with
• Raynaud's phenomenon or
• Digital ischaemia

4. PSS: Epidemiology
• The peak age of onset is in 4th & 5th decades
• Overall prevalence is 10-20 per 100 000
• 4:1 female: male ratio

5. PSS: Classification
It is subdivided into
• Diffuse cutaneous systemic sclerosis (DCSS)
• Limited cutaneous systemic sclerosis (LCSS)
• Many patients with LCSS have features which
are phenotypically grouped into the 'CREST'
syndrome (calcinosis, Raynaud's, oesophageal
involvement, sclerodactyly, telangiectasia).

6. PSS: Classification
It is subdivided into
• Diffuse cutaneous systemic sclerosis (DCSS)
• Limited cutaneous systemic sclerosis (LCSS)
• Many patients with LCSS have features which are
phenotypically grouped into the 'CREST'
syndrome (calcinosis, Raynaud's, oesophageal
involvement, sclerodactyly, telangiectasia).

8. CREST syndrome

9. Systemic Manifestations

10. PSS: Etiopathology
• Unknown,
• No consistent genetic, geographical or racial
associations.
• Environmental factors are important in
isolated cases that result from exposure to
–silica dust,
–vinyl chloride,
–hypoxy resins and
–trichloroethylene.

11. PSS: Etiopathology
Early in the disease there is
• Skin infiltration by T lymphocytes
• 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).

12. PSS: Etiopathology
Early in the disease there is
–Skin infiltration by T lymphocytes and
–Abnormal fibroblast activation
• In addition to skin changes there is arterial and
arteriolar narrowing due to intimal proliferation
and vessel wall inflammation.
• Endothelial injury causes release of
vasoconstrictors and platelet activation, resulting
in further ischaemia.

13. PSS Clinical Features and Diagnoais
• Systemic sclerosis is predominantly a clinical
diagnosis based on the presence of
sclerodactyly.
• Most patients are ANA-positive, and
• Approximately 30% of patients with diffuse
disease and
• 60% with limited disease have antibodies to
topoisomerase 1 and centromere respectively.

14. • Cutaneous changes Raynaud's phenomenon is
universal and may precede other clinical
features.

15. • Systemic sclerosis. Hands showing tight shiny
skin, sclerodactyly, flexion contractures of the
fingers and thickening of the left middle finger
extensor tendon sheath

16. PSS: Skin Disease
• 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.
• The face and neck are usually involved next, with
thinning of the lips and radial furrowing. In some
patients skin thickening stops at this stage.

17. PSS: Skin Disease
• 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'.

18. PSS: Skin Disease
In extremities-
• Intimal fibrosis and vessel wall inflammation may
combine to cause critical tissue ischaemia, skin
ulceration on pressure points
• Localised areas of infarction and
• Pulp atrophy at the fingertips.

19. PSS: 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.

20. PSS: GI 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
(proton pump inhibitors) is important.
• Dysphagia and odynophagia (painful
dysphagia) may also occur.

21. PSS: GI FEATURES
• Involvement of the stomach causes early satiety
and occasionally outlet obstruction.
• Recurrent occult upper GI bleeding may indicate
a 'watermelon stomach' (antral vascular ectasia),
which occurs in up to 20% of patients.
• Small intestine involvement may lead to
malabsorption, bacterial overgrowth and
intermittent bloating, pain or constipation.
• Dilatation of large or small bowel due to
autonomic neuropathy may cause pseudo-
obstruction.

22. Watermelon Stomach

23. PSS: Cardiorespiratory features
• Pulmonary involvement is a major cause of
morbidity and mortality.
• Fibrosing alveolitis mainly affects pts with diffuse
disease, esp those with antibodies to
topoisomerase 1.
• Pulmonary hypertension is a long-standing
complication. It is 6X more prevalent in limited
than diffuse disease.
• The clinical features are rapidly progressive
dyspnoea (more than ILD), RHF and angina with-
• often rapidly progressing digital ischaemia.

24. PSS: Cardiorespiratory features
Treatment strategies include
• Vasodilators
• Continuous infusions of epoprostenol
• The oral endothelin 1 antagonist bosentan and
• Heart-lung transplantation.

25. PSS: Renal features
• Main cause of death is hypertensive renal crisis
(rapidly developing malignant hypertension and
renal failure).
• Treatment is by ACE inhibition even in presence of
renal impairment.
• Hypertensive renal crisis is more likely in patients
with diffuse rather than limited disease.
• It is also more prevalent in patients with
topoisomerase 1 antibodies.
• Clinicians use prophylactic ACE Is for diffuse disease
to prevent this manifestation.

26. PSS: Management and prognosis
Five-year survival is approx70%.
Risk factors for a poor prognosis include
• Older age
• Diffuse skin disease
• Proteinuria
• High ESR
• A low gas transfer factor for carbon monoxide
(TLCO) and
• Pulmonary hypertension

27. PSS: Management and prognosis
• 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).

28. PSS: Management and prognosis
• 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.

29. PSS: Management and prognosis
• Corticosteroids and cytotoxic drugs are
indicated in patients with myositis or
alveolitis.
• No agent has been shown to arrest or improve
skin changes.