SM_239a: Scleroderma Flashcards Preview

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Flashcards in SM_239a: Scleroderma Deck (31)
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1

Rodnan skin score is ____

Rodnan skin score is semi-quantitative measure of the extent of skin induration (fibrosis)

 

  • Normal skin: 0
  • Unable to pinch skin: 3+
  • Max score is 51 (because 17 sites)

2

+ANA with _____ pattern is specific for systemic sclerosis

+ANA with nucleolar pattern is specific for systemic sclerosis

 

 

(note that ANA is positive in some healthy people)

3

Describe systemic sclerosis

Systemic sclerosis

  • Chronic multi-system disease
  • Orphan disease
  • Much more common in females, especially in post-childbearing years
  • Heterogeneous: multiple disease subsets or endophenotypes (diffuse cutaneous, limited cutaneous)

4

Describe the major organ manifestations of systemic sclerosis

Systemic sclerosis

  • Two types: limited cutaneous and diffuse cutaneous
  • Oral, upper GI, lower GI, MSK, pulmonary, cardiac, renal, skin, and vascular
  • Small to medial vasculopathy in fingers -> digital necrosis
  • Severe hypomotility in GI
  • Watermelon stomach
  • Honeycombing or ground glass in lung
  • Onion skinning in kidney (no lumen left): increased ischemia, increased renin, and repeat
  • Soft tissue calcifications

5

Describe limited cutaneous systemic sclerosis

Limited cutaneous systemic sclerosis

  • CREST: calcinosis, Raynaud, esophageal involvement, sclerodactyly, telangiectasia
  • Antibody: anticentromere
  • Slow progression
  • Better prognosis
  • Long survival

6

Limited cutaneous systemic sclerosis is also called ____ because of ____, ____, ____, ____, and ____

Limited cutaneous systemic sclerosis is also called CREST because of calcinosis, Raynaud, esophageal involvement, sclerodactyly, and telangiectasia

7

Limited cutaneous systemic sclerosis antibody is ____

Limited cutaneous systemic sclerosis antibody is anticentromere

8

Describe diffuse cutaneous systemic sclerosis

Diffuse cutaneous systemic sclerosis

  • Diffuse skin induration
  • Truncal involvement
  • Antibody: anti-topoisomerase
  • Rapid progression
  • Poor prognosis
  • Poor survival

9

Diffuse cutaneous systemic sclerosis is ____

Diffuse cutaneous systemic sclerosis is anti-topoisomerase

10

Diffuse cutaneous systemic sclerosis has a ____ progression, ____ prognosis, and ____ survival than lateral cutaneous systemic sclerosis

Diffuse cutaneous systemic sclerosis has a more rapid progression, worse prognosis, and poorer survival than lateral cutaneous systemic sclerosis

11

Systemic sclerosis is characterized by ____ pathogenesis comprised of ____, ____, and ____

Systemic sclerosis is characterized by tripartite pathogenesis comprised of immune, vascular, and fibrotic

 

(vascular and fibrotic complications account for high mortality)

12

Describe pathogenesis of systemic sclerosis

Systemic sclerosis pathogenesis

  • Microangiopathy (small blood vessels): Raynaud phenomenon, pulmonary arterial hypertension, scleroderma renal crisis, and mucocutaneous telangiectasia
  • Inflammation and autoimmunity: T cells, B cells, monocytes / macrophages, dendritic cells; cytokines, adipkines, chemokines; ANA, highly disease-specific autoantibodies
  • Fibrosis (scar) in multiple organs: skin, pulmonary, heart, GI, tendons

13

Vascular pathogenesis of systemic sclerosis is _____

Vascular pathogenesis of systemic sclerosis is microangiopathy (small blood vessels)

 

  • Raynaud phenomenon
  • Pulmonary arterial hypertension
  • Scleroderma renal crisis
  • Mucocutaneous telangiectasia

14

Immune pathogenesis of systemic sclerosis involves ____ and ____

Immune pathogenesis of systemic sclerosis involves inflammation and autoimmunity

 

  • T cells, B cells, monocytes/macrophages, dendritic cells
  • Cytokines, adipokines, chemokines
  • Plasma cells: ANA, disease-specific autoantibodies

15

Fibrotic pathogenesis in systemic sclerosis involves _____

Fibrotic pathogenesis in systemic sclerosis involves fibrosis in multiple organs

 

  • Skin fibrosis
  • Pulmonary fibrosis, also heart / GI / tendon fibrosi

16

Describe steps involved in systemic sclerosis pathogenesis on a cellular level

Systemic sclerosis pathogenesis

  1. Exposure (oxidative stress, virus, auto-antibodies, toxin) causes endothelial cell injury and apoptosis
  2. Impaired vasculogenesis, increased platelet activation and thrombus formation, ischemia-reperfusion injury leading to ROS generation, vasoconstrictors > vasodilators, impaired angiogenesis
  3. Increased adhesion molecules and anti-endothelial cell antibodies
  4. Increased fibroblast recruitment
  5. Increasec ollagen and other ECM proteins lead to late stage fibrosis

17

Four cardinal manifestations of systemic sclerosis microangiopathy are ____, ____, ____, and ____

Four cardinal manifestations of systemic sclerosis microangiopathy are mucocutaneous telangiectasia, Raynaud phenomenon, pulmonary arterial hypertension, and scleroderma renal crisis

 

  • Scleroderma renal crisis: accelerated malignant HTN with microangiopathy, rapidly progressive oliguria, and chronic kidney disease

18

____ Raynaud is more indicative of systemic sclerosis than ____

Secondary Raynaud is more indicative of systemic sclerosis than primary Raynaud

 

(secondary Raynaud indicative of ischemia)

19

This is a _____

This is a telangiectasia

 

(manifestation of systemic sclerosis microangiopathy)

20

_____ are indicative of avascularity in systemic sclerosis

Nailfold capillary changes are indicative of avascularity in systemic sclerosis

21

Describe the phases of Raynaud phenomenon

Raynaud phenomenon (vasospasm of fingers)

  1. Trigger: cold exposure
  2. Blanching
  3. Cyanosis
  4. Can lead to ischemic finger ulcers: tip ulcers, mummification, and amputation

22

Describe scleroderma renal crisis

Scleroderma renal crisis

  • Up to 15% of systemic sclerosis patients - more common in diffuse cutaneous systemic sclerosis
  • Acute hypertension
  • Malignant hypertension
  • Progressive oliguric renal failure

23

Describe clinical presentation of scleroderma renal crisis

Scleroderma renal crisis clinical presentation

  • Accelerated / malignant hypertension
  • Stroke
  • Blindness
  • Heart attack
  • Heart failure
  • Kidney failure
  • 50% mortality at one year

24

Pathogenesis of scleroderma renal crisis involves ____ and ____

Pathogenesis of scleroderma renal crisis involves renal ischemia and possibly intra-renal complement activation

 

(onion-skin vascular lesion, glomerular ischemia and collapse)

25

Pathogenesis of scleroderma cycle involves a vicious cycle of repeatedly _____ and _____

Pathogenesis of scleroderma cycle involves a vicious cycle of repeatedly increased BP, increases plasma renin activity, and kidney damage

 

 

  • ACE inhibitors block ACE
  • ARBs block action of angiotesin II on AT1 receptor
  • Renin inhibitors (aliskiren) directly block renin

26

Describe autoantibodies in systemic sclerosis

Systemic sclerosis autoantibodies

  • Serum antibodies (ANA, others) detected in >90% of systemic sclerosis patients: >8 antibodies, antibodies distinct from other autoimmune diseases
  • Mutually exclsuvie
  • Useful for diagnosis/classification/stratification: Scl-70 predicts lung disease / bad outcome, anti-centromere predicts relatively benign course, anti-RNA polymerase II increases renal crisis / cancer risk, Th/T0 predicts ILD

27

Systemic sclerosis is uniquely defined by ____

Systemic sclerosis is uniquely defined by simultaneous multi-organ fibrosis

 

(liver not affected)

28

Describe fibrosis in diffuse cutaneous systemic sclerosis

Diffuse cutaneous systemic sclerosis fibrosis

  • Skin - induration diffuse
  • Lung - ILD, NSIP or UIP patterns, leading cause of death

29

Describe fibrotic tissue

Fibrotic tissue

  • Stiff/rigid
  • Shrunken
  • Pale
  • Irregular

30

Describe the micro-structure of fibrotic structure

Micro-structure of fibrotic structure

  • Loss of architecture
  • ECMH accumulation
  • Capillary loss
  • Variable inflammation

Leads to loss of function

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