Systemic sclerosis

Question 1

Define systemic sclerosis.

Answer 1

AKA scleroderma

A multi-system, autoimmune disease, characterised by functional and structural abnormalities of small blood vessels, fibrosis of skin and internal organs, and production of auto-antibodies.

Question 2

How common is systemic sclerosis?

Answer 2

Rare
~20 new cases per year per million adults in US
Peaks in 50yrs

Question 3

What is the aetiology of scleroderma?

Answer 3

Aetiology is unknown at present. However, several aetiological factors have been suggested.
Genetic - most monozygotic twins are concordant for autoantibodies but only < 5% concordant for systemic sclerosis
Immune - 90% have positive ANA and other antibodies
Environmental - e.g. exposure to silica dust

Systemic sclerosis is a polygenic auto-immune condition.

Question 4

What are the risk factors for SS?

Answer 4

• FH
• Immune dysregulation e.g. positive ANA
• Female - 4:1

Question 5

What other conditions are associated with ANA?

Answer 5

• SLE
• Sjogren’s
• Dermato/polymyositis

Question 6

What is the diagnosis?

Answer 6

Systemic sclerosis

Question 7

What are the patterns of systemic sclerosis?

Answer 7

Limited cutaneous systemic sclerosis (CREST)- face and distal limbs; anti-centromere abs
Diffuse cutaneous systemic sclerosis (CREST + other features) - trunk and proximal limbs, respiratory involvement, renal disease and HTN; anti-scl-70 abs

Question 8

What is scleroderma?

Answer 8

Skin involvement without organ involvement - e.g. tightening and fibrosis of skin which may manifest as plaques (morphoea) or linear

Question 9

What is shown?

Answer 9

Morphoea - feature of localised scleroderma

Question 10

What does CREST stand for and what other features are seen in limited cutaneous SS?

Answer 10

• Calcinosis
• Raynauds
• Oesophageal dysmotility
• Sclerodactyly
• Telangectasia
• Primary pulmonary hypertension

NB: In limited cutaenous SS skin involvement does not progress beyond forearms (although it may involve peri-oral skin)

Question 11

What are the clinical features of diffuse cutaneous systemic sclerosis?

Answer 11

NB: Skin involvement does progress beyond forearms

• CREST features
• More extensive gastrointestinal disease
• Interstitial pulmonary disease
• Scleroderma kidney / renal crisis

Question 12

Which autoantibodies are found in systemic sclerosis?

Answer 12

Limited cutaneous SS - anti-centromere
Diffuse cutanoeus SS - anti-Scl-70/ anti-topoisomerase I (nucleolar pattern of staining)

ANA stains for LCSS (left) and DCSS (right)

Question 13

What is shown?

Answer 13

Hand demonstrating sclerodactyly with finger curling, shiny skin at the fingers, and telangiectasias

Question 14

What is shown?

Answer 14

Telangiectasias of the fingers

Question 15

What may be the cause of proximal myopathy in SS?

Answer 15

Co-existing inflammatory myositis

Question 16

What are the causes of cough and breathlessness in systemic sclerosis?

Answer 16

• ILD
• Pulmonary hypertension
• Chronic aspiration pneumonitis
• Cardiomyopathy

Question 17

Why might systemic sclerosis patients be anaemic?

Answer 17

Blood loss from gastric antral vascular ectasia

Question 18

What is the management of systemic sclerosis?

Answer 18

Skin dryness - emollient, antihistamine/corticosteroid (for pruritus)
Raynaud’s - conservative, CCB (e.g. amlodipine), topical GTN 12hr patches, PDE-5 inhibitors (e.g. sildenafil) if ulcers.
Renal crisis - ACEi as prevention
GORD - PPI +/- prokinetic agent (e.g. low dose erythromycin)
ILD - observation +/- immunomodulator (e.g. MMF, cyclophosphamide, azathioprine), oxygen therapy, lung transplant
Pulmonary arterial hypertension - endothelin receptor antagonist or PDE-5 inhibitor e.g. sildenafil.

Question 19

What are the complications of systemic sclerosis?

Answer 19

• Skin ulcers, infection, osteomyelitis, digital amputation
• Sicca - xerostomia, xerophthalmia
• Malabsorptive diarrhoea, steatorrhoea, weight loss
• Hypothyroidism
• Pulmonary artery hypertension
• Oesophageal stricture, aspiration pneumonia, Barrett’s oesophagus,
• Dysmotility with inability to maintain nutrition
• Cardiac arrhythmias

Question 20

What is the prognosis with systemic sclerosis?

Answer 20

• Better with limited than diffuse
• Some with limited will still have significant visceral involvement
• Severe and life-threatening renal disease develops in 10% to 15% of scleroderma patients
• Mean survival 12 yrs after diagnosis