Systemic sclerosis

Question 1

What is systemic sclerosis?

Answer 1

Autoimmune disorder of connective tissue

Results in fibrosis affecting skin, internal organs and vasculature

Characteristics: Raynaud’s, digital ischaemia, sclerodactyly, cardiac, lung, gut, renal disease

Mainly 40-50 yrs old

F>M; 4:1

Subdivided: diffuse cutaneous sclerosis (30%) and limited cutaneous (70%)

Diffuse cutaneous: poor prognosis (5 year survival rate – 70%)

Poor prognosis: older age, diffuse skin disease, proteinuria, high ESR, low gas transfer factor for carbon monoxide (TLCO), pulmonary hypertension

Question 2

SS - pathophysiology

Answer 2

Cause not completely understood

Genetic component
- Associations with alleles at HLA locus

Immunologic dysfunction

• T lymphocytes (Th17 subtype) infiltrate skin
• Abnormal fibroblast activation -> increased production of ECM in dermis, primarily type I collagen
• Symmetrical thickening, tightening and induration of skin (Scleroderma)

Arterial and arteriolar narrowing occurs due to intimal proliferation and vessel wall inflammation

Endothelial injury → release of vasoconstrictors and platelet activation → further ischaemia (exacerbates fibrotic process)

Question 3

SS - clinical features

Answer 3

Skin

• Initially, non-pitting oedema of fingers and flexor tendon sheaths
• Skin becomes shiny and taut, distal skin creases disappear
• Can have capillary loss
• Face + neck – thinning of lips and radial furrowing
• Skin involvement restricted to sites distal to elbow/knee (apart from face) = limited cutaneous sclerosis
• Involvement proximal to the knee and elbow and on trunk = diffuse disease

Raynaud’s

• May precede other features by many years
• Small blood vessel involvement in extremities → critical tissue ischaemia → localised distal skin infarction & necrosis

Musculoskeletal features

• Arthralgia & flexor tenosynovitis
• Restricted hand function – is due to skin rather than joint disease
• Muscle weaknes/wasting may result from myositis

GI

• Smooth muscle atrophy and fibrosis in lower 2/3 of oesophagus lead to reflux with erosive oesophagitis
• Dysphagia and odynophagia may also occur
• Involvement of stomach – early satiety, occasionally outlet obstruction
• Small intestine involvement – may lead to malabsorption due to bacterial overgrowth, intermittent bloating, pain or constipation

Pulmonary

• Pulmonary hypertension complicates long-standing disease (more common in limited cutaneous
• Presents with insidiously evolving exertional dyspnoea & signs of right heart failure
• Interstitial lung disease common in patients with diffuse disease, who have topoisomerase 1 antibodies

Renal

• One of the main causes of death = hypertensive renal crisis
• Rapidly developing accelerated phase hypertension and renal failure
• More likely to occur in diffuse disease

Question 4

SS - history

Answer 4

CREST

Calcinosis → “Have you noticed any skin changes?”

Raynaud’s → “Do you notice that your fingertips change colour, particularly in the cold or during stress?”

Eospheageal dysmotility → “Do you ever find it difficult to swallow?”

Sclerodactyly → “Have you noticed any thickening/tightening of the skin on your fingers?”

Telangiectasia → “Have you noticed small spider-like red lines on your face or anywhere else on your body?”

Question 5

SS - examinations

Answer 5

Hand - tight, shiny skin, sclerodactyly, flexion contractors of the fingers

Question 6

SS - investigations

Answer 6

Routine haematology, renal, liver and bone function tests and urinalysis

ANA +ve – 70%

30% with diffuse disease – have antibodies to topoisomerase 1
60% with limited cutaneous – anticentromere antibodies

CXR, transthoracic echocardiography and lung function to asses for ILD and pulmonary hypertension (low corrected transfer factor may indicate early pulmonary hypertension)

High-resolution lung CT – if suspect ILD

Suspect pulmonary hypertension – right heart catheter measurements

Barium swallow – assess oesophageal involvement

Hydrogen breathe test – indicate bacterial overgrowth

Question 7

SS - management

Answer 7

No treatments available to halt/reverse fibrotic changes that underlie disease
Focus of management: slow effects of disease on target organs

Raynauds / digital ulcers

• Avoid cold exposure, thermal insulating gloves/socks, maintenance of high core temp.
• If bad consider - Ca channel blockers, losartan, fluoxetine, sildenafil
• IV prostacyclin for severe disease and critical ischaemia (6-8 hours daily for 5 days)
• Bosentan (endothelin-1 antagonist) treat ischaemic digital ulcers
• Digital tip tissue health can be maintained with regular use of fucidin-hydrocortisone cream

GI

• Oesophageal reflux – PPI and anti-reflux agents
• Rotating courses of antibiotics may be required for bacterial overgrowth (rifaximin, a tetracyclin, metronidazole)
• Dysmotility/pseudo-obstruction – metoclopramide or domperidone

Hypertension
- Aggressive treatment with ACEi, even if renal impairment present

Joint

• Analgesics and/or NSAID
• If synovitis is present & both RA and OA have been ruled out, low dose methotrexate can be of value

Progressive pulmonary hypertension

• Early treatment with bosentan is required
• Severe/progressive disease – heart-lung transplant may be considered

ILD
- Glucocorticoids and (pulse intravenous) cyclophosphamide are the mainstays of treatment in patients who have progressive ILD