Systemic Sclerosis

Question 1

What is the core triad of systemic sclerosis?

Answer 1

Autoimmunity
Noninflammatory vasculopathy
Collagen deposition with fibrosis

Question 2

Who tends to get systemic sclerosis?

Answer 2

Classic occurs in middle-aged females in their 40s-50s

Question 3

What is the underlying pathogenesis of systemic sclerosis?

Answer 3

Endothelial dysfunction leads to increased expression of adhesion molecules and secretion of cytokines including endothelin. This activates T cells and macrophages which activate fibroblasts via TGF-beta and PDGF, causing progressive fibrosis.

Question 4

What is localized vs systemic scleroderma?

Answer 4

Localized - limited to the skin only. Only causes the superficial skin manifestations

Systemic - includes diffuse and limited, and is the major subject of concern. This means it affects the skin as well as the internal organs.

Question 5

What is the difference between limited and diffuse systemic sclerosis in terms of skin involvement?

Answer 5

Limited - mostly spares the trunk and proximal lower extremities, but will still affect the distal extremities and face. Indolent onset, slowly progressive.

Systemic - covers the entire body. Rapidly progressive.

Question 6

How does the onset of Reynaud’s phenomenon differ between limited and diffuse scleroderma (systemic sclerosis)?

Answer 6

Limited - Reynaud’s may start years ahead of time

Systemic - Usually coincident with skin involvement

Question 7

What is the most common form of limited scleroderma and what antibody is associated? What are the features?

Answer 7

CREST syndrome - associated with anti-Centromere antibody

Calcinosis
Reynaud’s phenomenon - secondary, leading to pits, ulcers, and gangrene
Esophageal dysmotility
Sclerodactyly - tight pulling skin leading to contractures
Telangectasias

Question 8

What antibody is associated with diffuse scleroderma?

Answer 8

Anti-Scl-70, think scleroderma-70

This is an anti-DNA-topoisomerase I antibody.

Question 9

How does the musculoskeletal, lung, and renal involvement differ between limited and diffuse scleroderma?

Answer 9

Limited - Mild arthralgias, slowly progressive interstitial lung disease, pulmonary arterial hypertension is a late complication, and scleroderma renal crisis is very rare

Diffuse - Severe arthralgias with carpal tunnel syndrome and friction rubs. Early onset severe interstitial lung disease and pulmonary arterial hypertension. Scleroderma renal crisis of happens early and is fulminant.

Question 10

How is the face of someone with scleroderma described?

Answer 10

Mouse-like -> pursed lips, shiny skin with some muscle atrophy. Complete absence of wrinkles since the skin is pulled tight with contractures.

Question 11

Who tends to be afflicted with localized scleroderma? Is it associated with Reynaud’s phenomenon or other complications? What is the main concern?

Answer 11

Tends to occur in children

Is NOT complicated by Raynaud’s phenomenon or significant internal organ involvement

Main concern in children is contractures on the skin can pull and retard bone growth

Question 12

What is morphea?

Answer 12

Type of localized scleroderma -> Solitary or multiple circular patches of thick skin

Generally has central sclerosis with peripheral inflammation

Question 13

What is linear scleroderma? What problems can it cause?

Answer 13

A form of localized scleroderma where there are long stripes of thickening. Can lead to fibrosis and atrophy of underlying supporting structures including tendons and muscles

Question 14

What marks the early phase skin involvement of diffuse systemic sclerosis?

Answer 14

Edematous phase - soft tissue swelling, puffy fingers, and intense pruritis. Varying degrees of hypo and hyperpigmentation occurs
-> “salt and pepper rash” - hypopigmentation with hyperpigmentation around hair follicles due to relative sparing

Question 15

What marks the late phase of skin involvement in diffuse systemic sclerosis?

Answer 15

Skin induration, progressive contractures, alopecia, and reduced production of skin oils (dry skin)

Question 16

Why is the first few years of diffuse systemic sclerosis critical?

Answer 16

Pulmonary and renal involvement occurs most rapidly in the initial 4 years -> rapid recognition and treatment reduces morbidity and mortality

Question 17

What is one condition of the liver associated with CREST syndrome?

Answer 17

Primary biliary cholangiitis -> autoimmune reaction associated with anti-mitochondrial antibodies. Destruction of intralobular bile ducts.

Question 18

Where does subcutaneous calcinosis occur in CREST syndrome and what is it made of?

Answer 18

Occurs in olecranon and prepatellar bursae as well as finger pads. Can occur in areas where fibrosis is uncommon and make the skin feel fibrotic -> visualized on X-ray

Made of calcium hydroxyapatite (visualize with Alazarin red)

Question 19

What is thought to be the cause of ulcers on the fingertips vs extensor aspects of the hands in CREST syndrome?

Answer 19

Fingertips - ischemic, due to secondary Raynaud’s

Extensor surfaces - Mechanical, due to increased stretching of the skin / recurrent microtrauma

Question 20

What characterizes the nailfold capillaries in late-stage CREST syndrome?

Answer 20

Giant capillaries as well as microhemorrhages and “drop-outs” or lost capillaries. The capillaries don’t look uniform at all.

Question 21

What is the leading cause of death in systemic sclerosis?

Answer 21

Pulmonary involvement -> progressive dyspnea, cough, and bibasilar crackles due to alveolitis, pulmonary fibrosis, and pulmonary hypertension (medial hypertrophy)

Question 22

What are the features of scleroderma renal crisis (important)? When does it occur?

Answer 22

Accelerated hypertension (>150/90) and oliguric acute renal failure

• > fibrosis leads to activation of the renin-angiotensin aldosterone system
• > Leads to hypertensive crisis and congestive heart failure with pulmonary edema
• > occurs in the first few years of diffuse systemic sclerosis

Question 23

What is the best way to reduce mortality in scleroderma renal crisis?

Answer 23

Since it is caused by activation of the renin-angiotensin system, best thing to do is use an ACE inhibitor

Question 24

What GI involvement characterizes scleroderma?

Answer 24

Esophageal dysmotility, estophageal strictures and narrowing, dysphagia, delayed gastric emptying, hypomotility, malabsorption due to fibrosis

Question 25

What is systemic sclerosis sine scleroderma? Will they have Raynaud’s?

Answer 25

Internal manifestations of scleroderma without cutaneous involvement detectable.

Very rare, but yes, will still have Raynaud’s phenomenon.

Question 26

What antibody, when associated with diffuse systemic sclerosis, is most specific for causing scleroderma renal crisis?

Answer 26

Anti-RNA polymerase I/II

Question 27

What medication may be useful in the prevention of interstitial lung disease in scleroderma and when must it be given?

Answer 27

Cyclophosphamide

Must be given early on the disease course before significant damage has occurred (cytotoxic therapy)

Question 28

What is the cardiac involvement of diffuse systemic sclerosis and how can it be treated?

Answer 28

Pericarditis -> NSAIDs, corticosteriods, drainage

Right-sided heart failure due to pulmonary HTN

Conduction defects -> pacemaker

Restrictive cardiomyopathy

Question 29

Features of what diseases overlap in mixed connective tissue disease? What antibody characterizes it? Pattern on IF?

Answer 29

1. SLE
2. Systemic sclerosis
3. Polymyositis / dermatomyositis

Characterized by anti-U1 RNP antibodies (speckled pattern on IF)

Question 30

What’s the treatment of MCTD? Is Rheumatoid Factor often positive?

Answer 30

Treatment is same as lupus pretty much. Responds will to low-dose corticosteroids.

Rheumatoid factor is often positive, yes.