SM_239a: Scleroderma Flashcards
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)
+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)
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)
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
Describe limited cutaneous systemic sclerosis
Limited cutaneous systemic sclerosis
- CREST: calcinosis, Raynaud, esophageal involvement, sclerodactyly, telangiectasia
- Antibody: anticentromere
- Slow progression
- Better prognosis
- Long survival
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
Limited cutaneous systemic sclerosis antibody is ____
Limited cutaneous systemic sclerosis antibody is anticentromere
Describe diffuse cutaneous systemic sclerosis
Diffuse cutaneous systemic sclerosis
- Diffuse skin induration
- Truncal involvement
- Antibody: anti-topoisomerase
- Rapid progression
- Poor prognosis
- Poor survival
Diffuse cutaneous systemic sclerosis is ____
Diffuse cutaneous systemic sclerosis is anti-topoisomerase
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
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)
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
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
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
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
Describe steps involved in systemic sclerosis pathogenesis on a cellular level
Systemic sclerosis pathogenesis
- Exposure (oxidative stress, virus, auto-antibodies, toxin) causes endothelial cell injury and apoptosis
- Impaired vasculogenesis, increased platelet activation and thrombus formation, ischemia-reperfusion injury leading to ROS generation, vasoconstrictors > vasodilators, impaired angiogenesis
- Increased adhesion molecules and anti-endothelial cell antibodies
- Increased fibroblast recruitment
- Increasec ollagen and other ECM proteins lead to late stage fibrosis
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
____ Raynaud is more indicative of systemic sclerosis than ____
Secondary Raynaud is more indicative of systemic sclerosis than primary Raynaud
(secondary Raynaud indicative of ischemia)
This is a _____
This is a telangiectasia
(manifestation of systemic sclerosis microangiopathy)
_____ are indicative of avascularity in systemic sclerosis
Nailfold capillary changes are indicative of avascularity in systemic sclerosis
Describe the phases of Raynaud phenomenon
Raynaud phenomenon (vasospasm of fingers)
- Trigger: cold exposure
- Blanching
- Cyanosis
- Can lead to ischemic finger ulcers: tip ulcers, mummification, and amputation
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
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
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)
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
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
Systemic sclerosis is uniquely defined by ____
Systemic sclerosis is uniquely defined by simultaneous multi-organ fibrosis
(liver not affected)
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
Describe fibrotic tissue
Fibrotic tissue
- Stiff/rigid
- Shrunken
- Pale
- Irregular
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
Summarize systemic sclerosis
Systemic sclerosis
- Multi-systemic disease with chronic and variable course, potentially lethal complications, and excess mortality
- Complex pathogenesis (tripartite): vascular, inflammatory, fibrotic processes - cause unknown but genetics + environment
