Rheum #5: Systemic Sclerosis And Raynaud's

Front 1

What is the broad category of disease that scleroderma falls under?

What two components must it fulfill?

Back 1

Collagen Vascular Disease

1. Collagen (excess/abnormal CT production)
2. Vascular anomalies

Front 2

What is the incidence of scleroderma? What demographic is typically affected?

Back 2

Uncommon (2-12/ million/ year)

F>M (4:1). Mostly appears in middle age.

Front 3

What is localized scleroderma (comes in two forms)?

Back 3

Localized Scleroderma= just a disease of skin, almost never becomes systemic.

1. morphea
2. linear scleroderma

Front 4

What type of systemic sclerosis does this individual have? What antibody is associated with this condition?

Back 4

Diffuse Cutaneous systemic sclerosis (dc-SSc)-

Systemic disease: IPF, renal failure, mycoardial disease, diffuse GI. TRUNCAL and acral skin affected.

Scl-70 positive (antibody to topoisomerase I). Rapidly progressive onset and sick patients :(

Front 5

How does limited cutaneous systemic sclerosis (Lc-SSc) differ from diffuse systemic sclerosis (dc-SSc)?

Back 5

Limited- RP involvement for years, limited skin involvement, anti-CENTROMERE antibody. Insidious onset of PHTN (pulmonary hypertension).

Also, much better survival than dc-SSc

Front 6

What are some presenting symptoms in scleroderma?

Back 6

- Raynaud's
- swelling of hand/feet and stiffness (can look arthritic)
- tightening of skin (rapid onset, within few months)
- consistutioal sxs or things related to organ involvement (GI, renal, etc.)

Front 7

What is the "Vascular Paradox" associated with SSc (Systemic Sclerosis, i.e. Scleroderma)?

Back 7

Patients can have BOTH Vasoconstriction and Vasodilatation.

Vasoconstriction: Raynaud's, Digital ulcer
Vasodilation: Telangiectasia, Nailfold capillary dilation

Front 8

Just by looking at this person, what diagnosis would you give them? What is the formal criteria for diagnosing this?

Back 8

Raynaud's Phenomenon (red, white, and blue- erythema, pallor, cyanosis) in response to cold/stress. Episodic.

Formally- need to have episodic vasospastic color change, bilaterality, absence of gangrene, normal pulsations of arteries and symptoms LONGER THAN 2 YEARS!

Front 9

What is the prevalence of raynauds? Why is it different in men and women?

Back 9

Women ~5%, men ~4%

Women have higher density of α-adrenergic receptor (increase under influence of E2). Vasoconstrict under sympathetic control.

Front 10

What two things regulate acral cutaneous blood flow?

Back 10

1) AV shunts (controlled by CNS and ANS- including sympathetic and parasympathetic)

2) Nutritive Capillaries (secrete local endothelin, neuropeptides to control vasculature in skin)

Front 11

Why does RP treatment focus more on blocking alpha adrenergic Receptors and relaxing vascular smooth muscle than activating B-adrenergic receptors?

Back 11

There are more alpha adrenergic receptors in the peripheral vessels (B-adrenergics drop out in the periphery). Thus stimulating the B-adrenergics won't have as much of an effect.

Front 12

The pathogenesis of systemic sclerosis involves what three main things?

Back 12

1) fibrosis
2) vascular abnormalities
3) immune dysregulation

Front 13

What immune abnormalities are seen in Scleroderma?

Back 13

Ag driven process (but the Ag is unknown). Lymphocytes are seen early on.

Th2 cells --> produce IL-4 --> activates macrophage --> release TGFB and PDGF --> induce fibroblast collagen production

Front 14

What is shown in this biopsy? Do you see inflammation?

Back 14

Scleroderma vascular changes --- Don't see inflammatory cell! (this is not a vasculitis)

- intimal proliferation
- intense medial hypertrophy
- adventitial fibrosis

Front 15

What potent vasoconstrictor is responsible for the vascular changes seen in Scleroderma? What are some factors that balance out its effect?

Back 15

Vasoconstrictor- ET-1

Vasodilator- NO, and EDHF

*note the hypertrophied artery seen in this condition

Front 16

What is shown here? What condition is this seen in (note: it is a condition associated with systemic sclerosis)?

Back 16

Plexiform lesion (from active vasoconstriction)

- seen in PHT (pulmonary HTN)

Front 17

Primary anti-fibrotic cytokines in SSc? What type of cell secretes them?

Primary pro-fibrotic cytokines in SSc? What type of cell secretes them?

Back 17

Anti-fibrotic (Th1). TNFα and INFg

Pro-fibrotic (Th2). TGFβ and PDGF

Front 18

How does TGFβ cause fibrosis in SSc? What about PDGF?

Back 18

TGFβ bind to receptor --> causes Smad signaling cascade --> Smad translocates to nucleus causes gene expression of collagen.

Platelet derived growth factor binds to receptor --> via ERK-ROS signaling causes increased gene expression of collagen, inflammatory genes, and antiapoptotic genes.

*note: TGFB upregulates PDGF (work synergistically)

Front 19

What is seen in this picture?

Back 19

Sclerosis of the skin, can be disfiguring. There are distal contractures of the skin and retraction of soft tissue at finger tip --> causing digital ulcers.

Front 20

What is seen on this histologic image?

Back 20

Infiltration of collagen. Initially patients have vascular engorgement and edema (increased swelling and stiffness of skin) which is later replaced by collagen.

Deposition begins on lower dermis and there is LOSS of hair follicles, sweat glands, etc.

*trichrome stain shows extensive collagen

Front 21

What is this condition called?

Back 21

Subcutaneous calcinosis in the finger and elbows. Can be seen on xray.

very characteristic of Scleroderma.

Front 22

What is the problem with the barium swallow of a patient with Scleroderma?

Back 22

There is no esophageal peristalsis. In addition, the lower esophageal sphincter is wide open and patients can get reflux.

Fibrosis in the GI smooth muscle results in hypomotility throughout tract (in addition to dilatation, malabsorption, etc.)

Front 23

What unique GI systems are spared in patients with Scleroderma?

Back 23

Liver and Pancreas!

Front 24

What are the two main pulmonary findings in patients with SSc?

Back 24

1) Pulm vascular disease- obliterative arteriopathy (small pulmonary arteries affected, develop HTN --> cor pulmonale)

2) Interstitial fibrosis

Front 25

Would you expect this chest x-ray to come from a patient with lc-SSc or dc-SSc?

Back 25

dc-SSc (you tend to see more interstitial fibrosis in these patients). In lc-SSc you see more pulm HTN.

Note the honeycombing and parenchymal infiltrates. Patient likely has impaired gas exchange, dyspnea and cough.

Front 26

What cardiac problems can a person with Scleroderma present with?

What do you notice in this histologic image of a kidney?

Back 26

Cardiac- mostly Right side heart failure (Cor pulmonale, HTN)

Renal- note onion skinning of artery --> patients can develop malignant HTN, renal crisis (azotemia --> increased SCr). They can also get necrosis of capillaries in the glomerulus.

Front 27

In a person with scleroderma, what lab values would you predict for the following:

- Hb
- ESR
- RF
- ANA

Back 27

- low Hb (mild anemia)
- ↑ ESR (inflammatory marker- seen early on)
- RF +
- ANA + (in 90-95% of patients)

Front 28

What is shown here?

If someone with Raynaud's syndrome came in and had this pattern, what would you tell them?

Back 28

Different patterns of ANA (periphral, diffuse, speckled, nucleolar). Many people have ANA and they also can have Raynaud's. Want to be cautious and do other tests, specifically look for Ab's to centromere or topoisomerase.

Diagnosis of scleroderma will come over time if skin changes, arthritis, etc. are seen

Front 29

What is shown here? What type of systemic sclerosis does this individual likely have?

Back 29

Anti-centromere antibodies (this is seen in lc-SSc or limited cutaneous scleroderma)

Front 30

How do you treat scleroderma?

Back 30

- symptomatic therapy
- physiotherapy (so they don't get contractures early on)

*difficult to treat. Lack of response to steroids.