systemic sclerosis

Question 1

definition of systemic sclerosis

Answer 1

connective tissue disease characterised by small bv damage and fibrosis in the skin and internal organs

also called scleroderma

Question 2

spectrum of disease of systemic sclerosis

Answer 2

pre-scleroderma - raynaud’s, nail fold cap changes and ANA

diffuse cutaneous systemic sclerosis (40%) - raynaud’s phenomenon -> skin changes with truncal involvement, tendon friction, joint contractures, early lung, heart, GI and renal disease, nail-fold cap dilation. interstitial lung disease. scleroderma renal/kidney crisis. Antitopoisomerase-1 (SCL-70) antibodies in 40% and anti-RNA polymerase in 20%.

limited cutaneous systemic sclerosis (60%) - previously known as CREST (calcinosis, Raynaud’s, oesophageal dysmotility, sclerodactyly, telangiecstasia). Pul hypotn often present subclinically - can become rapidly life threatening. associated with anticentromere Ab in 70-80%. skin - hands, forearm, feet, lower leg

Scleroderma sine scleroderma (1%): Internal organ disease with no skin changes.

both limited and diffuse have potential for organ fibrosis, lung, cardiac, GI and renal - occurs later and in a limited subset

Question 3

aetiology of systemic sclerosis

Answer 3

unknown

genetic and env - vinyl chloride, epoxy resins

specific Ab (humoral immunity) and activated macrophages, monocytes and lymphocytes (cellular immunity) may interact with:

• endothelial cells = endothelial cell damage, platelet activation, myointimal cell proliferation and narrowing of bv
• fibroblasts = lay down of collagen in dermis

90% are ANA +ve and 30-40% have anticentromere Ab

Question 4

epidemiology of systemic sclerosis

Answer 4

rare

30-60yrs

more common females

annual incidence - 1 in 10000

Question 5

skin presenting symptoms of systemic sclerosis

Answer 5

raynaud’s

• exaggerated vascular response to cold temp or emotional stress
• abnormal vasoconstriction of digital arteries and cutaneous arterioles
• colour changes of skin: white -> blue (cyanosis) -> crimson (reactive hyperaemia)
• May be primary (without any associated disorder) or secondary (associated with a related illness, such as SLE or systemic sclerosis).

initially swollen oedaematous painful fingers

later - thinckened, tight, shiny, bound to underlying structures

change in pigmentation

finger ulcers

calcinosis

Question 6

face sx in systemic sclerosis

Answer 6

microstomia - puckering and furrowing of perioral skin

telangiectasia

Question 7

lung sx of systemic sclerosis

Answer 7

pul fibrosis -> pul HTN

interstitial lung disease - inflammation ->fibrosis

Question 8

heart sx of systemic sclerosis

Answer 8

pericarditis or pericardial effusion

myocardial fibrosis

HF

arrhythmias

Question 9

GI sx of systemic sclerosis

Answer 9

dry mouth

oesophageal dysmotility - dysphagia

reflux oesophagitis

gastric paresis - nausea, vomiting, anorexia

watermelon stomach

bacterial overgrowth

small bowel pseudo-obstruction

colonic hypomobility (constipation)

anal incontinence

angiodysplasia

Question 10

kidney sx of systemic scleritis

Answer 10

hypertensive renal crisis: ischemic -> increased RAAS -> renal hypertensive crisis

chronic renal failure

Question 11

neuromuscular sx of systemic sclerosis

Answer 11

trigeminal neuralgia

muscular wasting

weakness

Question 12

miscellaneous sx of systemic sclerosis

Answer 12

hypothyroidism

impotence

dryness of mucus membranes can cause dyspareunia

overlap syndromes with polymyositis and SLE

Question 13

Ix for systemic sclerosis

Answer 13

Blood

• ANA
  
  • 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

• detect fine nail-fold changes

Ix system with sx

Question 14

Ix for complications of systemic sclerosis

Answer 14

lung: CXR, pulmonary function tests, high-resolution CT scan
heart: ECG, echo

GI: endoscopy, barium studies, gastric/oesophageal scintigraphy

kidney: UE, creatinine clearance
neuromuscular: electromyography, nerve conduction studies, biopsy
joints: radiography for subcut calcification, acro-osteolysis, flexion deformities
skin: biopsy to exclude fasciitis, muscle biopsy for associated myositis

Question 15

pathophysiology of systemic sclerosis

Answer 15

loss of B cell tolerance to nuclear Ag - +ve ANA (anti-centromere Ab, anti-topoisomerase Ab ie Scl70)

inflammation with Th2 and Th17

cytokines -> activation of fibroblasts and development of fibrosis = tight skin

cytokines -> activation of endothelial cells -> microvascular disease

Question 16

CREST

Answer 16

calcinosis

raynauds - vascular

oesophageal dysmotility - fibrosis of GIT

sclerodactyly - tightening of the skin, initially inflammation adn then tightens and scars with fibrosis

telangiectasia