Systemic and localised scleroderma

Question 1

Scleroderma (systemic sclerosis or SSc)

Answer 1

A multisystemic disease which involves the internal organs and is associated with vasospasm (Raynaud’s)
It has the highest case-specific mortality of any ARD

Question 2

Morphoea

Answer 2

‘Localised’ or ‘circumcribed’ scleroderma - either patches or linear
thickening and hardening of the skin due to increased collagen production – presents in a number of syndromes linked by a lack of deeper tissue involvement – more common in <20yrs
Does not progress and very rarely coexists although may be ANA positive

Question 3

Epidemology of SSc

Answer 3

1/100,000 with M:F/1:3 and ethnic variations in clinical features -- rare in child, peak onset 30-50yrs
Some heritability (MZ>DM concordance) but mainly environmental

Question 4

Environmental risk factors for SSc

Answer 4

Vinyl-chloride
Siliac dust 
Adulterated rapeseed oil
Trichlorethylene
Drugs (bleomycin)

Question 5

Pathogenesis of SSc

Answer 5

An initial vascular lesion in small arteries, arterioles and capillaries causes vasoconstriction, increasing vascular permeability & cytokine release –> Cytokines, immune cell activation and matrix infiltration activates fibroblasts –> increase production of collagen I & III (+fibronectin & glycosaminoglycans)

Question 6

Clinical presentations of SSc

Answer 6

Raynaud’s phenomenon - >99% - may precede disease onset
Limited cutaneous scleroderma (LcSSc) – 70%
Diffuse cutaneous scleroderma (DcSSc) – 30%

Question 7

Consequences of increased collagen production

Answer 7

lower dermal fibrosis & obliterative vasculopathy – this causes ischemia leading to necrosis and secondary infections

Question 8

Raynaud’s phenomenon

Answer 8

Seen in almost all cases of SSc and precedes full disease by up to 15yrs – excessively reduced blood flow due to cold or emotional stress, causing discoloration of the fingers or toes
Can be primary (Raynaud’s disease) or secondary to an ARD

Question 9

Limited cutaneous scleroderma (LcSSc)

Answer 9

Only affects skin on hands, feet, face and Forearms

GI involvement is common and pulmonary HTN/interstitial fibrosis develops in 10-15% – Used to be called CREST syndrome

Question 10

Autoantibodies in SSc

Answer 10

RF is positive in 30% of SSc
ANA is positive in 95%
LcSSc – Anti-centromere abs occur in 70%
DcSSc – Anti-Scl-70 abs occur in 30%, also anti-RNA polymerase I,II,III positive in 20-25% of cases

Question 11

Diffuse cutaneous scleroderma (DcSSc)

Answer 11

Starts with oedema which rapidly develops into stiffness, sclerosis and eventually atrophy - can cover most of the body in bad cases - Raynaud’s develops just before or along with oedema – Early organ involvement occurs with lethargy, anorexia and weight loss

Question 12

Hand Changes in LcSSc

Answer 12

Tight skin can produce flexion deformities
Painful digital ulcers can form and ischemia can lead to gangrene
Dilated nail fold capillary loops and generalised telangiectasia can also occur

Question 13

Facial Changes in LcSSc

Answer 13

Skin changes and tightness produce a characteristic ‘beak-like’ nose and small mouth (microstomia)

Question 14

CREST syndrome

Answer 14

Calcinosis,
Raynaud's phenomenon
Esophageal involvement
Sclerodactyly
Telangictasia
Now replaced with LcSSc

Question 15

Organ involvement in DcSSc

Answer 15

GI involvement is very common and characteristic. Renal involvement can be acute or chronic – major cause of death but reduced with ACEis and better dialysis. Lung disease — fibrosis leading to pulmonary hypertension (PHT can also occur alone). Myocardial fibrosis (causing arrhythmias/conduction defects) and rarely pericarditis

Question 16

Gastrointestinal problems in SSc

Answer 16

Reflux or dysphagia –> oesophageal involvement is v. common
Anal incontinence can occur
Dilation and atony of the small bowel (and rarely the large bowel) - can cause bacterial overgrowth leading to malabsorption
Pseudo-obstruction is also a know complication

Question 17

Sine scleroderma

Answer 17

Systemic features without skin involvement

A rare subtype of scleroderma

Question 18

Blood tests, urine and imaging for SSc

Answer 18

FBC – anaemia of chronic disease and microangiopathic haemolytic anaemia in some pts with renal disease
U+Es –> Urea and creatinine will rise in acute kidney disease
Urine -> microscopy and proteinuria if kidney disease
Imaging –> CXR/CT for lung problems and barium swallow to confirm oesophageal dismotility

Question 19

Hand X-rays in SSc

Answer 19

Looking for calcium deposition around the fingers

And if severe disease acrosteolyisis (resorption of the bone of the distal phalanges) - can be diffuse or bandlike

Question 20

Management of SSc

Answer 20

Exercise and skin lubrication
ACE-I or A2RBs
Cyclophosphamide for organ involvement

Question 21

Anti-PDGFR antibodies

Answer 21

It has been suggested that autoantibodies to platelet derived growth factor receptor stimulates fibroblasts because they have been found in the blood of pts with SSc but it is not usually tested

Question 22

Use of corticosteroids and immunosuppressants in SSc

Answer 22

Rarely used unlike other ARDs

Used in SSc related pulmonary fibrosis

Question 23

Treatment of Raynaud’s

Answer 23

Hand warmers and oral vasodilators are 1st line (CCBs or ACEis)
In more severe cases stronger vasodilators and sympathectomy can be used (lumbar for feet & digital or thoracic for hands)

Question 24

Treatment of Oesophageal symptoms of SSc

Answer 24

Most are significantly improved by PPIs and prokinetic agents

Question 25

Treatment of Renal involvement of SSc

Answer 25

Tight control of HTN is important – ACEi are first line
Hypertensive scleroderma renal crisis (SRC) is critical and must be treated – early-stage, rapidly progressing DcSSc are most at risk
Risk may also be increased by high dose corticosteroids

Question 26

Treatment of pulmonary disease in SSc

Answer 26

PHT is treated with oral vasodilators, warfarin and oxygen –> if severe give prostacyclins or endothelin blockers
Treat right sided HF as normal (consider lung transplant)
Pulmonary fibrosis is treated with cyclophosphamide or azathioprine+low dose pred

Question 27

Prognosis of SSc

Answer 27

70% 10yr survival in LcSSc as it is generally mild – early death is renal and late death is PHT - 50% of SSc death is pulmonary
DcSSc is more severe and aggressive and pts die of pulmonary, cardiac or renal problems

Question 28

Relapsing polychondritis

Answer 28

Attacks cartilage (floppy pinna etc)
Assoc: aortic valve disease, polyarthritis, vasculitis
Treat w/steroids and Immunosuppresion