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Flashcards in Scleroderma Deck (45):
1

three pathogenic processes in systemic scleroderma

immune dysregulation, vascular dysfunction, fibrosis

2

most important cytokine in scleroderma

TGF-B

3

mechanism that leads to increased collagen synthesis in scleroderma

increased collagen gene transcription

4

primary clinical consequences of scleroderma

skin fibrosis & ischemia/fibrosis of visceral organs

5

what does scleroderma mean?

hard skin

6

definition of systemic scleroderma

an autoimmune connective tissue disorder of unknown etiology characterized by the triad of fibrosis, vascular dysfunction, and immune dysregulation

7

gross appearance of skin in patients with scleroderma

tight and shiny. sebacous glands, hair follicles, and sweat glans get occluded. salt and pepper pigment changes.

8

name when scleroderma affects fingers?

sclerodactyly

9

raynaud's phenomenon

spastic effect on vessels in fingers, which completely occlude and blood pools near base. not unique to scleroderma

10

calcinosis

calcium deposits in tissue. not unique to scleroderma

11

effect of scleroderma on GI?

esophageal dysmobility. difficulty swallowing and digesting

12

telangiectasias

dilated ends of vessels. not unique tp scleroderma. most common cause of a GI bleed in scleroderma though

13

most common cause of death in scleroderma patients?

bilateral interstitial lung fibrosis

14

classification of scleroderma

Systemic (diffuse, limited, overlap) & localized (morpheme, linear scleroderma)

15

systemic vs localized scleroderma

in systemic, internal organs are always involved. just the skin is affected in localized scleroderma

16

diffuse cutaneous scleroderma

symmetric, widespread skin fibrosis that starts at the toes and moves up to head. RAPID progression and early visceral involvement. poor prognosis (10 yrs)

17

limited cutaneous scleroderma

symmetric skin fibrosis limited to the distal extremities and face. Raynauds manifests ten years before skin and late appearing organ manifestations. SLOW progression. good prognosis

18

anticentromere antibody

present in limited cutaneous scleroderma

19

CREST (scleroderma symptoms)

calcinosis, raynauds phenomenon, esophageal dysmotility, sclerodactyly, telangectasias

20

overlap syndromes (of systemic scleroderma)

mix of diffuse and limited scleroderma. often associated with other rheumatic disease

21

common facial characteristics of scleroderma

beaking nose, pursed lips, facial muscle atrophy, tightening of skin, telangestasias on forehead

22

pathogenesis of scleroderma

genetic predisposition + environmental trigger=immune system activation. Causes B cells to start producing autoantibody and T cells to activate and infiltrate skin/vascular epithelium and release profibrotic cytokines (TGF-B).

23

antibodies produced in scleroderma

ANA (90%), anti-scl, anti-centromere, anti-topoisomerase, anti-RNA polymerase 3

24

anti-scl 70

antibody indicative of diffuse cutaneous scleroderma (African Americans)

25

anticentromere antibody

antibody indicative of limited cutaneous scleroderma (Caucasians)

26

genes whose transcription is unregulated in scleroderma

COL1A2 (type 1 collagen), TGF-B1, Fibrillin-1

27

tight skin mouse model

mutate fibrillin gene leads to disorganized, unstable microfibrils that inappropriately signal fibroblasts to increase TGF-B and deposit type 1 collagen in ECM

28

tissue inflammation in early scleroderma

lymphocyte infiltrates skin (mostly CD4 T cells) and release cytokines and growth factors. CD8 T cells predominate in lung tissue

29

important cytokines released by inflammatory cells of scleroderma

TGF-B, CTGF, PDGF

30

TGF-B

sensitizes fibroblasts to stay persistently active and decreases the production of collagen degrading metaloproteinases

31

role of cytokines released by inflammatory cells in scleroderma

induce alterations of the ECM gene expression

32

CTGF (connective tissue growth factor)

stimulated by TGF-B. sensitizes fibroblasts to stay persistently activated

33

PDGF (platelet derived growth factor)

TGF-B increases PDGF receptors on fibroblasts, which make them more sensitive to the mitogenic effects of PDGF (which is required for cellular division)

34

characteristics of damaged vessel walls in scleroderma

thickened and damaged wall, occluded lumen, up regulation of agents that cause vasoconstriction, and down regulation of agents that cause vasodilation. presence of myofibroblasts rather than fibroblasts

35

how can you easily/quickly test a patient for scleroderma vs Raynauds?

Do exam, get history, test for ANA and ESR. Then look at the capillaries of their nail folds. If someone has autoimmune scleroderma, you will see dilated loops.

36

tissue fibrosis in scleroderma

overproduction of type 1 collagen and other ECM macromolecules by fibroblasts. (up regulation of COL1A1)

37

clinical consequences of skin fibrosis in scleroderma

inflammatory infiltrates sparse, thickened dermis, replacement of dermis and subcutaneous fat with collagen bundles, loss of skin appendages, late atrophy of epidermis

38

clinical consequence of renal necrosis in scleroderma

vascular damage (narrowing/ischemia/cortical hemorrhage/onion skin) leading to scleroderma renal crisis. occurs early with rapidly progressing skin thickening. abrupt onset of malignant hypertension

39

how to prevent renal damage?

ACE inhibitors forever once symptoms appear. needs to be caught early though

40

clinical consequence of lung fibrosis in scleroderma?

interstitial lung disease (diffuse fibrotic tissue replacement, anti-topoisomerase) & pulmonary hypertension

41

GI manifestations of scleroderma

gastroparesis, malabsorption, pseudoobstruction, diverticuli, anorectal sphincter dysfunction, biliary cirrhosis

42

immune dysregulation in scleroderma

activated b cells, autoantibody production
an early predominant t cell inflammatory infiltrate

43

vascular abnormalities in scleroderma

initial unknown endothelial cell injury leading to structural damage, local production of GFs and cytokines, thickening of vessel wall, increased contractility of vessel

44

fibrosis in scleroderma

fibroblast chemotaxis and proliferation, excessive production of type 1 collagen, excessive production of other ECM molecules

45

most important cytokine in scleroderma

TGF-B