Systemic Sclerosis Flashcards
What is the core triad of systemic sclerosis?
Autoimmunity
Noninflammatory vasculopathy
Collagen deposition with fibrosis
Who tends to get systemic sclerosis?
Classic occurs in middle-aged females in their 40s-50s
What is the underlying pathogenesis of systemic sclerosis?
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.
What is localized vs systemic scleroderma?
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.
What is the difference between limited and diffuse systemic sclerosis in terms of skin involvement?
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.
How does the onset of Reynaud’s phenomenon differ between limited and diffuse scleroderma (systemic sclerosis)?
Limited - Reynaud’s may start years ahead of time
Systemic - Usually coincident with skin involvement
What is the most common form of limited scleroderma and what antibody is associated? What are the features?
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
What antibody is associated with diffuse scleroderma?
Anti-Scl-70, think scleroderma-70
This is an anti-DNA-topoisomerase I antibody.
How does the musculoskeletal, lung, and renal involvement differ between limited and diffuse scleroderma?
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.
How is the face of someone with scleroderma described?
Mouse-like -> pursed lips, shiny skin with some muscle atrophy. Complete absence of wrinkles since the skin is pulled tight with contractures.
Who tends to be afflicted with localized scleroderma? Is it associated with Reynaud’s phenomenon or other complications? What is the main concern?
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
What is morphea?
Type of localized scleroderma -> Solitary or multiple circular patches of thick skin
Generally has central sclerosis with peripheral inflammation
What is linear scleroderma? What problems can it cause?
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
What marks the early phase skin involvement of diffuse systemic sclerosis?
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
What marks the late phase of skin involvement in diffuse systemic sclerosis?
Skin induration, progressive contractures, alopecia, and reduced production of skin oils (dry skin)
Why is the first few years of diffuse systemic sclerosis critical?
Pulmonary and renal involvement occurs most rapidly in the initial 4 years -> rapid recognition and treatment reduces morbidity and mortality
What is one condition of the liver associated with CREST syndrome?
Primary biliary cholangiitis -> autoimmune reaction associated with anti-mitochondrial antibodies. Destruction of intralobular bile ducts.
Where does subcutaneous calcinosis occur in CREST syndrome and what is it made of?
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)
What is thought to be the cause of ulcers on the fingertips vs extensor aspects of the hands in CREST syndrome?
Fingertips - ischemic, due to secondary Raynaud’s
Extensor surfaces - Mechanical, due to increased stretching of the skin / recurrent microtrauma
What characterizes the nailfold capillaries in late-stage CREST syndrome?
Giant capillaries as well as microhemorrhages and “drop-outs” or lost capillaries. The capillaries don’t look uniform at all.
What is the leading cause of death in systemic sclerosis?
Pulmonary involvement -> progressive dyspnea, cough, and bibasilar crackles due to alveolitis, pulmonary fibrosis, and pulmonary hypertension (medial hypertrophy)
What are the features of scleroderma renal crisis (important)? When does it occur?
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
What is the best way to reduce mortality in scleroderma renal crisis?
Since it is caused by activation of the renin-angiotensin system, best thing to do is use an ACE inhibitor
What GI involvement characterizes scleroderma?
Esophageal dysmotility, estophageal strictures and narrowing, dysphagia, delayed gastric emptying, hypomotility, malabsorption due to fibrosis
What is systemic sclerosis sine scleroderma? Will they have Raynaud’s?
Internal manifestations of scleroderma without cutaneous involvement detectable.
Very rare, but yes, will still have Raynaud’s phenomenon.
What antibody, when associated with diffuse systemic sclerosis, is most specific for causing scleroderma renal crisis?
Anti-RNA polymerase I/II
What medication may be useful in the prevention of interstitial lung disease in scleroderma and when must it be given?
Cyclophosphamide
Must be given early on the disease course before significant damage has occurred (cytotoxic therapy)
What is the cardiac involvement of diffuse systemic sclerosis and how can it be treated?
Pericarditis -> NSAIDs, corticosteriods, drainage
Right-sided heart failure due to pulmonary HTN
Conduction defects -> pacemaker
Restrictive cardiomyopathy
Features of what diseases overlap in mixed connective tissue disease? What antibody characterizes it? Pattern on IF?
- SLE
- Systemic sclerosis
- Polymyositis / dermatomyositis
Characterized by anti-U1 RNP antibodies (speckled pattern on IF)
What’s the treatment of MCTD? Is Rheumatoid Factor often positive?
Treatment is same as lupus pretty much. Responds will to low-dose corticosteroids.
Rheumatoid factor is often positive, yes.
