13 - Systemic Sclerosis

Question 1

What is systemic sclerosis/scleroderma (SSc)?

Answer 1

Autoimmune or connective tissue disease characterized by thickening of the skin caused by accumulation of collagen, and by injuries to the smallest arteries

Question 2

What is the prevalence of SSc in the US?

Answer 2

276 per million

Question 3

What is the 10-year mortality rate of SSc?

Answer 3

23-45%

Question 4

True or false: There is no demonstrated disease-modifying therapy for SSc

Answer 4

True

Question 5

What are the subclassifications of SSc?

Answer 5

• Limited cutaneous SSc (lcSSc)
• Diffuse cutaneous SSc (dcSSc)

Question 6

What is the pathophysiology of SSc?

Answer 6

• Must incorporate the 3 cardinal features of the disease:
  
  • (1) vasculopathy (intimal hyperplasia, vessel obliteration, thrombosis)
  • (2) cellular and humoral autoimmunity (TGF-B, Th2 cytokines, PDGF, CTGF, chemokines)
  • (3) progressive visceral and vascular fibrosis in multiple organs (loss normal architecture, impaired function, organ failure)
• Autoimmunity and altered vascular reactivity may be the earliest manifestations
• Complex interplay between these processes is thought to initiate and then amplify the fibrotic process

Question 7

Anti-PM-Scl AAb

1. Main autoantigen target
2. Frequency
3. Clincal associations

Answer 7

1. PM-Scl 100 7 PM-Scl 70 components of human exosome
2. 5%
3. Overlap w/ myositis

Question 8

Anti-Th/To AAb

1. Main autoantigen target
2. Frequency
3. Clincal associations

Answer 8

1. Ribonuclease mitochondrial RNA processing & ribonuclease P complexes
2. 5%
3. lcSSc; ILD

Question 9

Anti-U3RNP AAb

1. Main autoantigen target
2. Frequency
3. Clincal associations

Answer 9

1. 34-kDa basic protein fibrillarin
2. 5%
3. pHTN; skeletal muscle involvement; AfAm predominance

Question 10

Anti-RNA polymerase III AAb

1. Main autoantigen target
2. Frequency
3. Clincal associations

Answer 10

1. RNA polymerase III
2. 10%
3. dcSSc; rapidly progressive skin dz; renal crisis

Question 11

Anti-Scl-70 AAb

1. Main autoantigen target
2. Frequency
3. Clincal associations

Answer 11

1. Topoisomerase I
2. 20%
3. dcSSc; ILD

Question 12

Anti-centromere AAb

1. Main autoantigen target
2. Frequency
3. Clincal associations

Answer 12

1. Centromere proteins
2. 30%
3. lcSSc; digital ischemia

Question 13

What are the clinical manifestations of SSc?

Answer 13

• Raynaud’s phenomenon
• Digital ulcerations
• Calcinosis
• GI manifestations
• Tendon friction rubs
• Fibrosis of skin
• Renal crisis
• ILD
• pHTN

Question 14

What is Raynaud’s phenomenon?

Answer 14

• Triphasic color change upon cold exposure
  
  • White –> blue –>