Workup of Scleroderma

Question 1

Give a quick rundown of what systemic sclerosis is.

Answer 1

This is a disease that is best described as widespread fibrosis throughout the body. There are three main ‘parts’ to consider

(1) chronic inflammation thought to be the result of autoimmunity,
(2) widespread damage to small blood vessels, and eventually
(3) progressive interstitial and perivascular fibrosis in the skin and multiple organs.

Question 2

Main difference between diffuse and limited scleroderma?

Answer 2

Diffuse scleroderma is widespread often from the get-go and visceral organ involvement including heart, GI, lungs, and kidneys is rapid, whereas in limited, the skin involvement is typically limited to the face and distal extremities and visceral involvment takes longer to development

Question 3

How is autoimmunity suggested to be a cause of scleroderma?

Answer 3

• CD4 T cells respond to a yet unID’d antigen and release cytokines that activation inflammation and fibroblasts (cytokines of importance: TGF-B and IL-13)
• The common presence of ANAs also suggests humoral involvement

Question 4

What might be one of the first things you see in scleroderma? Why?

Answer 4

Microvascular disease especially in the digital arteries including distorted nailfold capillary loops

What causes the vascular injury is not known; it could be the initiating event or the result of chronic inflammation, with mediators released by inflammatory cells inflicting damage on microvascular endothelium. Repeated cycles of endothelial injury followed by platelet aggregation lead to release of platelet and endothelial factors (e.g., PDGF, TGF-β) that trigger perivascular fibrosis. Eventually, widespread narrowing of the microvasculature leads to ischemic injury and scarring.

Question 5

The skin is going to be the most affected organ in scleroderma. Describe its typically progression.

Answer 5

Skin damage typically begins in the fingers and begins to extend to the upper arms, shoulders and head. This is typically the result of pervascular infiltrates of CD4 T cells which promote inflammation and thickening of capillaries. Fibrosis then begins to play a bigger role predominantly in the dermis which can clinically lead to ‘thick skin’ and eventually ROM becomes decreased and cutaneous ulcerations can result from loss of blood supply.

Question 6

If a patient walked in and you suspected scleroderma, what are some other organs that you need to consider being damaged?

Answer 6

• GI tract in up to 90% of patients
• MS system
• Kidneys
• Lungs
• Heart

Question 7

Why would the GI tract be frequently involved with scleroderma? What parts? What are you looking for clinically?

Answer 7

You typically see progressive atrophy and fibrosis at any level of the gut but the esophagus is where to be particularly vigilant. The lower esophagus can become VERY inflexible and so GERD is common, including its sequelae like Barrett’s esophagus.

Clinically: look for trouble swallowing. Very common! Periodontal disease, reduced oral apeture, xerostomia, and resorption of the mandibular condyles

Question 8

The MS system can also be involved. How?

Answer 8

there can be some synovitis assoicated with hypertrophy in the early stages and then fibrosis in the late stages that look like RA but keep in mind that in scleroderma you wont really see joint destruction commonly

Question 9

How are the kidneys affected by scleroderma?

Answer 9

Renal involvement is the 3rd most common common system to look for in scleroderma patients, seen in over 2/3 (aka scleroderma renal crisis). You will see vascular lesions particularly in the interlobular arteries that may lead to HTN (check BP regularly!). Typically, the glomeruli are spared.

NOTE: the development of HTN is very bad in scleroderma. These patients see more fibrinoid necrosis and often die of renal failure

Question 10

How can the lungs be impacted by scleroderma?

Answer 10

Lung involvement is common (50%) and manfests most commonly as PAH or IPF (so be wary of new onset of non-productive cough, dyspnea on exertion; clinically: auscultate for velcro rales in the lower lung fields, a prominent P2; and may consider HRCT scan or RHCWP test- should be under 15 mm Hg)

Question 11

How can the heart be impacted by scleroderma?

Answer 11

Mostly seen as pericarditis with effusion and mycardial fibrosis (make sure to auscultate)

How it may present: sharp pain, worse when lying down

How to detect: ask patient to lean forward and auscultate using diaphragm listen to left sternal border

Question 12

What is the typical patient for scleroderma?

Answer 12

mostly female and peaks in 50-60 age

Question 13

T or F. Raynaud’s is common in scleroderma

Answer 13

TRUE. seen in over 70% of cases and can precede other symptoms.

Question 14

How would you approach a patient that you suspect has scleroderma

Answer 14

1) Hx- what kinds of symptoms are they having? Any Raynaud’s?
2) Physical- check for skin thickening on extremities, Raynaud’s/ulcerations,
3) Labs- Abs (Topo 1 (Scl70), Centromere B/C, Pm/Sci, U1-RNP)
4) Imaging- probably not needed up front?

Question 15

How would you approach a patient that you know has scleroderma during checkups

Answer 15

1) Hx- any new changes? ROS: Any throat pain, seizures, problems urinating, chest pain, non-productive cough, dyspnea on exertion, fatigue (anemia)? What drugs are you taking? Four of interest: steroids, NSAIDs, cyclosporin (SRC), and methotrexate (IPF)
2) Physical- take BP and check for papilledema (scleroderma renal crisis)- start on an ACEI immediately
3) Labs- urinalysis (elevated creatine, proteinuria); CBC- anemia

Question 16

What cytokines are upregulated in scleroderma? Downregulated?

Answer 16

In scleroderma, CD4 cells show a dominantly TH2 response, upregulating pro-fibrotic markers such as TGF-B, CTGF, and fibronectin. TH1 response is suppressed and antifibrotic proteins such as TNF-a and IFN-y are suppressed.