Progressive Systemic Sclerosis

ACMS Dept of Medicine 2010 Batch VIII Term

PSS: Definition

• Systemic sclerosis (previously called 'scleroderma') is a generalised disorder of connective tissue affecting-

• The skin • Internal organs and • Vasculature.

PSS: Hallmark

The clinical hallmark is the presence of • Sclerodactyly in combination with • Raynaud's phenomenon or • Digital ischaemia

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

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).

PSS: ClassificationIt 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).

CREST syndrome

Systemic Manifestations

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.

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).

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.

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.

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

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

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.

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'.

PSS: Skin DiseaseIn 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.

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.

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.

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.

Watermelon Stomach

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.

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

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.

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

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).

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.

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.