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MS/Rheum > Systemic Sclerosis > Flashcards

Flashcards in Systemic Sclerosis Deck (14):
1

Epidemiology

women > men and AA > whites

2

Susceptibility genes

HLA, PTN22, IRF5, STAT4, BANK1, TNFSF4. T-bet

3

Environmental predisposition

silica, heavy metals, mercury, organic chemicals,
drugs: bleomycin, cocaine, taxol

4

SSc manifests as __ + ___ => _____

immune dysregualtion + microangiopathy → systemic fibrosis

5

Pathogenesis of immune dysregualtion

•Inciting event (drug, infection, oxidative damage, etc.)
•Activation of TLR (by autoAg) on dendritic cell which produce INF-gamma
•INF-gamma activate Th2 which activate B cells
•B cells make AutoAbs against the AutoAg
•Immune complexes form → more INF-gamma released along with profibrotic cytokines (TGF-beta)

**INF-gamma!!!!!!!

6

Pathogenesis of vasculopathy

insult --> endothelial dysfunction -->
•Inc apoptosis and ICAM-expression on endothelial cells
•Dec NO, PGI
•Inc endothelin-1 and thrombin
•ROS generation
--> vasoconstrition and ischemia
+ luminal narrowing/remodeling de to shear stress, platelet aggregation, and thrombosis
--> T cells come in a release cytokine that elicit inflammation and recruit fibroblasts
--> fibrosis and vascular obliteration

7

Clinical features of SSc

CREST
AutoAb (Scl70, U3-RNP, RNA pol III)
widening capillary loops

crest = Calcinosis, Raynauds, Esophageal dysmotitiy, Sclerodacyly, Telangiectasias

8

Abs assc with limited sclerosis
diffuse sclerosis
both

limited = centromere, Th/To, cardiolipin, B2-GP1
diffuse = Scl70 (topo1), RNA pol III
both = U3-RNP and B23

9

How is early limited scleroderma diff from early diffuse scleroderma

Early Limited / Early Diffuse

Raynauds is 1st symptom / Raynaud’s is delayed

Rarely have general symptoms / Acute onset of many generalized symptoms

Minimal arthralgias / Arthralgias

Puffy fingers / Puffy hands

Limited skin thickening / More skin thickening

Anti-centromere Ab/ Anti-Scl 70 and Anti-RNA pol III Abs

10

histo findings in..
vasculature
skin
lung
renal

vasculature: onion skin
skin: loss of hair follicles and sebaceuos glands
lung: ILD/fibrosis (NSIP pattern)
renal: fibinoid necrosis and thrombosis

11

Describe effect of SSc on lungs

PSIP pattern
PAH
restrictive PFTs and dec DLCO
ground glass on CT

12

Acute, sever HTN →HF or seizures
Grade II retinopathy
Presence of anti-RNA polymerase I and III antibody

Treated with ACEi

sclerodermal renal crisis”

13

kid with isolated circular patch of thickened skin

plaque morphea

14

multiple lesions involving extensive areas of skin and can occasionally coalesce, mimicking skin changes of systemic sclerosis

generalized morphea