Systemic Sclerosis

Question 1

Define systemic sclerosis.

Answer 1

Rare connective tissue disease characterised by functional and structural abnormalities of small blood vessels, fibrosis of skin and internal organs, and production of auto-antibodies. AKA scleroderma

Spectrum of diseases.

Question 2

What are the main 3 components of systemic sclerosis?

Answer 2

1. Vasculopathy
2. Fibrosis
3. Immune system activation with autoimmunity.

Question 3

What does the systemic sclerosis spectrum of diseases include? (4)

Answer 3

Pre-scleroderma - Raynaud’s phenomenon, nail-fold capillary changes and antinuclear antibodies

Diffuse cutaneous systemic sclerosis - (~40%) - Raynaud’s phenomenon followed by skin changes with truncal involvement, tendon friction and joint contractures, early lung, heart, GI and renal disease, nail-fold capillary dilation

Limited cutaenous systemic sclerosis (~60%) - previously known as CREST (calcinosis, Raynaud’s, oesophageal dysmotility, sclerodactyly, telangiectasia)

Sine scleroderma (~1%) - internal organ disease with no skin changes

Question 4

What is the aetiology of systemic sclerosis?

Answer 4

Unknown
Genetic, immunological and environmental factors (e.g. vinyl chloride, epoxy resisns) have been suggestes.

Question 5

What is the pathogenesis of systemic sclerosis?

Answer 5

Exact pathogenesis unclear but specific antibodies (humoral immunity) and activated monocytes, macrophages and lymphocytes (cellular immunity) may interact with:

• Endothelial cells --> endothelial cell damage, platelet activation, myointmal cell proliferation and narrowing of blood vessels
• Fibroblasts –> lay down of collagen in the dermis

Question 6

What are the most common auto-antibodies found in systemic sclerosis?

Answer 6

Summary: 90% are ana positive and 30–40% have anticentromere antibodies

ANA is found in 90% of patients by indirect immunofluorescence. Among this group, there are subsets auto-antibodies associated with distinct clinical phenotypes:

• Anti-topoisomerase I (anti-Scl 70) in ~20% of cases; associated with increased risk of ILD and diffuse skin involvement
• Anti-RNA polymerase III (also about 20% of cases) associated with renal crisis
• Anti-centromere antibodies (20% to 25% of cases) associated with limited skin involvement and better overall prognosis
• The remaining 40% have scleroderma but do not have an as-yet-identified scleroderma-specific auto-antibody.

Question 7

How common is systemic sclerosis? Who is most affected?

Answer 7

• 1/10,000 incidence
• Age of onset 30-60yrs
• 3:1 female:male ratio

Question 8

What is Raynaud’s phenomenon?

Answer 8

Exaggerated vascular response to cold temperature or emotoinal stress (abnormal vasoconstriction of digital arteries and cutaenous arterioles)

Presents with colour change of white to blue (cyanosis) to red (reactive hyperaemia)

May be primary, with no associated disorder, or secondary and associated with an illness like SLE or systemic scleorosis.

Question 9

Describe the presentation of Raynaud’s phenomenon.

Answer 9

Hands - initially swollen oedematous painful fingers, then become thickened, tight and shiny and bount to underlying structures. Changes in pigmentation and finger ulcers.

Face - microstomia (puckering and furring of perioral skin), telangiectasia

Question 10

What are the effects of systemic sclerosis on lungs, heart and GI system?

Answer 10

Lung: Pulmonary fibrosis leading to pulmonary hypertension.

Heart: Pericarditis or pericardial effusion, myocardial fibrosis, heart failure or arrhythmias.

GI: Dry mouth, oesophageal dysmotility (dysphagia), reflux oesophagitis, gastric paresis
(nausea, vomiting, anorexia), watermelon stomach, bacterial overgrowth, small bowel
pseudo-obstruction,colonichypomotility (constipation),anal incontinence,angiodysplasia.

Question 11

What are the effects of systemic sclerosis on kidney, neuromuscular and other systems?

Answer 11

Kidney: Hypertensive renal crisis, chronic renal failure.

Neuromuscular: Trigeminal neuralgia, muscular wasting or weakness.

Other: Hypothyroidism, impotence, dryness of mucus membranes can cause dyspareunia.

Overlap syndromes with polymyositis and SLE.

Question 12

What investigations would you do for systemic sclerosis (including those for organ complications)

Answer 12

Blood:

• Antinuclear antibodies:
• Anti-centromere: 70% positive in limited cutaneous systemic sclerosis.
• Anti-topoisomerase (anti-Scl-70): 30% positive in diffuse cutaneous systemic sclerosis.
• Anti-nucleolar antibodies. PmScl (associated with myositis).
• Anti-RNA-polymerase (associated with renal crisis).

Nail-fold capillary ophthalmoscopy or microscopy: To detect fine nail-fold changes.

Investigations for complications:

• Lung: CXR, pulmonary function tests, high-resolution CT scan.
• Heart: ECG, echocardiography.
• GI: Endoscopy, barium studies, gastric/oesophageal scintigraphy.
• Kidney: U&E and measurement of creatinine clearance.
• Neuromuscular: Electromyography, nerve conduction studies, biopsy.
• Joints: Radiography (for subcutaneous calcification, acro-osteolysis, flexion deformities).
• Skin: Biopsy (to exclude fasciitis, rarely necessary), muscle biopsy for associated myositis.

Question 13

Distinguish rheutamtological diseases by the antibodies present.

Answer 13