Systemic Sclerosis

Question 1

Why do people die of systemic sclerosis?

Answer 1

Internal Organ involvment

Question 2

The interplay of what 4 factors leads to systemic sclerosis?

Answer 2

Question 3

What gender and ethnic group have a higher incidence of scleroderma?

Answer 3

African Americans and Women have increased incidence of scleroderma

Question 4

How does the composition of inflammatory cells change over time in scleroderma?

Answer 4

• T cell infiltration may develop into a monocytic infiltration as a results of IFN-gamma release. Then over time the monocytes differentiate into more of a fibroblastic type of cell.

Question 5

The figure here shows the involvment of different cell types in scleroderma.

Question 6

What is indicated by the presence of papilledema?

Answer 6

• Very high blood pressure

Question 7

What are the earliest pathologic changes in SSc and what causes these changes?

Answer 7

Changes in endothelial cell function with increased apoptosis, MHC class II (on APCs) and ICAM-1 (intracellular adhesion molecule) expression on endothelial cells.

• Increased endothelial activation will lead to platelet aggregation and digital artery occlusion. The occurance of this process on a chronic basis leads to vessel wall thickening/lumenal narrowing and telangiectasis of the vasa vasorum.

Question 8

What 3 steps does Raynaud’s occur in?

Answer 8

Loss of blood ciculation = white, then deoxgenated blood = blood, then hyperemia as bloodflow returns causes release of vasodilatory mediators like Adenosine and NO.

Question 9

What is shown here?
• is this a result of primary or secondary disease?

Answer 9

Capillary dropout from repeated ischemic injury is a feature of SECONDARY Raynaud’s not primary

Question 10

What features of Scleroderma are shown here?
• what are some treatment options for these patients?

Answer 10

A. Sclerodactyly
B. Thicked Skin Overlying Chest
C. Inflammatory Signs of Early Disease
D. Vitiligo

Treatment options:
• Sildenafil (viagra - PDE5 inhibition)
• Losartin (ACE receptor blocker)
• CCB’s

Question 11

What are some other locations this could show up?
• would you expect to happen if you pressed on it?

Answer 11

This is a Telangectasia of SSc, these are NON-blanching and typically are found on the face, tongue, and chest

Question 12

What are the 2 types of scleroderma?
• what are their subtypes?
• How do they differ?

Answer 12

Localized scleroderma consists of 2 types of scleroderma:
• Morphea - skin lesion biopsy will look like normal scleroderma but only invovles the skin
• Linear Scleroderma - shows a single line of thickening deep into muscle

Systemic Scleroderma:
• Limited Scleroderma - mostly skin with limited invovlment of internal organs.

• Diffusion Scleroderma - both skin and internal organs
• Sine Scleroderma - only involves internal organs

Question 13

How can you tell the difference between limited and diffuse scleroderma without looking at internal structures.

Answer 13

• Skin involvement pattens

Question 14

What are some organs commonly involved in Systemic Scleroderma?
• How are they involved?

Answer 14

GI:
• Esophageal Dysmotility; GAVE (gastric vascular vascular ectasia) Pancreatic Insufficiency; Primary Biliary Cirrhosis; Giant Diverticuli with decreased intestinal mobility

Cardiopulmonary:
• EFFUSIONS (common 1/5); Cardiac fibrosis; Pulmonary Artery HTN or pumonary fibrosis => Cor Pulmonale; Raynaud’s

Glands:
• Salivary (Sjorgren’s), Pancreatic

Musculoskeletal:
• Osteoporosis, Arthritis, Myositis

Question 15

What 4 antibody types are associated with scleroderma?

Answer 15

Question 16

What Phenotype of Scleroderma is associated with Anti-topoisomerase antibodies?

Answer 16

Question 17

What Phenotype of Scleroderma is associated with Anti-centromere antibodies?

Answer 17

Notice the SICCA syndrome association (dry eyes, mouth, etc.)

Question 18

What Phenotype of Scleroderma is associated with Anti-PM/scl antibodies?

Answer 18

Question 19

What Phenotype of Scleroderma is associated with Anti-U1-RNP antibodies?

Answer 19

MIXED disease

Question 20

_______________(a) was typically the cause of death in scleroderma before the advent of _______________(b)

Answer 20

Renal Crisis was typically the cause of death in scleroderma before the advent of Ace inhibitors

Question 21

What is scleroderma renal crisis (SRC)?
• how often does this occur?
• how do we control this potentially fatal condition?

Answer 21

Scleroderma Renal Crisis (SRC)
• Characterized by three main things: ¹Abrupt increase in blood pressure associated with increase in plasma renin activity that may precipitate ²acute kidney damage resulting in a ³mild proteinuria with only a few cell or casts.

Controlling Scleroderma Renal Crisis:
• Early pharmacologic intervention with ACE inhibitors is crucial and may reverse the condition.

Question 22

What are 3 important risk factors for developing Scleroderma Renal Crisis?
• what are some other associations?

Answer 22

3 important risk factors:

Risk Factors:
• Early diffuse skin disease
• Use of Corticosteroids
• ***Presence of anti-RNA pols III abs***

Other Associations:
• New anemia (schistocytes), New cardiac events (hrt failure, pericardial effusion), presence of anti-RNA pols I, use of drugs like NSAIDs, cyclcosporin.

Question 23

How commonly is the GI tract involved in scleroderma?
• Where do these symptoms typically manisfest?
• Associated progosis with different locations of involvment?

Answer 23

GI tract invovlment is a UNIVERSAL feature of scleroderma. Most commonly the Upper GI tract is involved in the disease, but the lower tract may also be involved and is associated with a poor prognosis.

Question 24

What manifestations of scleroderma are shown here?

Answer 24

A. Esophageal dysmotility with congestion and Dilation
B. Watermelon Stomach due to vascular ectasias (pathologic dilation of BVs) in the stomach
C/D. Gastric Dysmotility with pseudoobstruction

Question 25

What are your chances of having pulmonary manifestations of scleroderma if you have the disease?

Answer 25

**Pulmonary manifestations** are **likely** and there are many different ways disease may manifest. Commonly: **• Interstitial Lung Disease/Pulmonary Artery HTN • Lung Cancer of any type • Aspiration pneumonia • Pleural Effusions.**

Question 26

How might someone with scleroderma present whenever they become symptomatic with scleroderma pulmonary manifestations? • what underlying factors may be contributing? • When in the disease process does this happen?

Answer 26

Pulmonary involvment typically happens in **later stages** of diffuse scleroderma and may present as **dyspena, fatigue, dry cough, and/or GERD** with crackels and rhales on auscultation. Underlying causes are _most commonly_ **Interstitial Lung Disease** and **PAH.** • _Other contributatory causes may be Chest Wall Restriction due to fibrosis of chest wall skin, infection, and use of **MTX.**_

Question 27

What are some distinctive signs of pulumonary artery hypertension that you might see on a cardiopulmonary physical exam?

Answer 27

* LOUD P2 sound with a fixed split * Parasternal Heaves (i think...)

Question 28

Is PAH a symptom or CREST, Diffuse Scleroderma, or both?

Answer 28

PAH is a symptoms of BOTH Limited Scleroderma (CREST) associated with **anti-centromere antibodies**, and diffuse SSc with antifibrillairn antibodies (**Anti-U3RNP antibodies**).

Question 29

Its important to diagnose PAH EARLY so that you can treat it. DON'T mistake it for a lack of physical fitness.

Question 30

Linear Scleroderma • 5 subtypes?

Answer 30

5 subtypes: • **Plaque** morphea • **generalized** morphea • **Bullous** morphea • **Linear** Morphea • **Deep** morphea

Question 31

What is plaque morphea? • how common is this?

Answer 31

Plaque morphea is the most common subtype of localized scleroderma and is an **isolated circular patch of thickened skin**.

Question 32

What is generalized morphea?

Answer 32

**MULTIPLE lesions** involving **extensive areas of the skin** that **occasionally merge** to mimic changes seen in systemic sclerosis.

Question 33

What is keloid morphea?

Answer 33

**Nodular** form of localized scleroderma that **resembles keloids**

Question 34

What is bullous morphea?

Answer 34

**Subepithelial form** of localized scleroderma where **bullae form under epithelium (RARE)**

Question 35

What is Linear Scleroderma?

Answer 35

A form of **localized scleroderma** that forms a **linear streak** that **crosses dermatomes** and is associated with **atrophy of muscle and infiltrates in the the underlying bone and rarely the brain.** AKA **"en coup de sabre"** to decribe the jagged lesions see at the dermal-epidermal junction

Question 36

What is mixed connective tissue disease (MCTD)? • how rapidly does this disease onset? • **How** does it typically onset?

Answer 36

Mixed Connective Tissue disease is a disease with features of **lupus, scleroderma,** and **inflammatory myositis.** **Onset** of mixed connective tissue disease is **slow** and may take **several years** to develop. Typically this occurs with the **aquisition of one disease** (or feature of a disease) **at a time**.

Question 37

What antibody in scleroderma is associated with Mixed Connective tissue disease?

Answer 37

**U1-RNP**

Question 38

What key features should you look for in someone you suspect is presenting with MCTD? • what organ system is involved in 25% of cases? Disease(s)? • What typically kills these people?

Answer 38

**RAYNAUD's** =\> if they don't have this then reconsider your diagnosis. In 1/4 of patients **renal involvement** is manifested as **membranous glomerularnephritis.** Proliferative **GN** is rare. **Patients with this disease typically die of PAH**

Question 39

What key features should you look for in a skin lesion of scleroderma?

Answer 39

**¹Excessive Collagen Deposition, ²Deep Fibrosis and perivascular ³lymphohistiocytic infiltrates.**

Question 40

What is shown here? • key characterisitics?

Answer 40

this is normal skin, notice the fairly deep ridges at the dermal-epidermal junctionan the presence of blood vessels and glands in the dermis. There is also an absence of lymphocytes.

Question 41

What is shown here? \* Key features?

Answer 41

Skin seen in the **early stages of scleroderma.** There is some **loss of the papillae** at the dermal-epidermal junction. No blood vessels are apparent and we see a **lymphocytic** infiltrate (bottom right). With loss of follicles and glands.

Question 42

What is shown here? • key features?

Answer 42

This is late stage scleroderma. Lymphocytic infiltrates have regressed and and rete pegs (papilla a dermal-epidermal junction) are flattened. There is also an absence of glands. Notably pigment has been lost from the dermal epidermal junction possibly causing a vitiligo type effect in this person (see earlier picture below for comparison to early stage disease image)

Question 43

What is shown here? • where on the body of a scleroderma patient would this likely be found?

Answer 43

**Calcareous Lesions** - are related to tumoral calcinosis • these are large painful masses in the **periauricular soft tissue** composed of **hydroxyappetite**

Question 44

What changes might you see in the joints of someone with scleroderma?

Answer 44

Question 45

What is shown in each of these images?

Answer 45

Question 46

These changes are associated with Raynaud's Phenomenon. Would you expect them to be more associated with Primary or Secondary Raynauds?

Answer 46

These changes would be associated with SECONDARY Raynaud's. Vascular damage does not occur in primary Raynaud's. Note: 1-2% of ppl. with primary Raynaud's progress to SSc (may just be poorly diagnosed SSc)