Systemic Sclerosis

Question 1

Epidemiology

Answer 1

women > men and AA > whites

Question 2

Susceptibility genes

Answer 2

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

Question 3

Environmental predisposition

Answer 3

silica, heavy metals, mercury, organic chemicals,

drugs: bleomycin, cocaine, taxol

Question 4

SSc manifests as __ + ___ => _____

Answer 4

immune dysregualtion + microangiopathy → systemic fibrosis

Question 5

Pathogenesis of immune dysregualtion

Answer 5

• 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!!!!!!!

Question 6

Pathogenesis of vasculopathy

Answer 6

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

Question 7

Clinical features of SSc

Answer 7

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

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

Question 8

Abs assc with limited sclerosis
diffuse sclerosis
both

Answer 8

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

Question 9

How is early limited scleroderma diff from early diffuse scleroderma

Answer 9

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

Question 10

histo findings in..
vasculature
skin
lung
renal

Answer 10

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

Question 11

Describe effect of SSc on lungs

Answer 11

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

Question 12

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

Treated with ACEi

Answer 12

sclerodermal renal crisis”

Question 13

kid with isolated circular patch of thickened skin

Answer 13

plaque morphea

Question 14

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

Answer 14

generalized morphea