SM 239a - Scleroderma Flashcards
A patient with long-standing systemic sclerosis is being treated with the endothelin-1 receptor antagonist bosentan. This class of drugs functions by inhibiting which of the following:
a. gastric acid secretion
b. bronchospasm
c. vasoconstriction
d. synovial inflammation
d. calcium deposition
e. collagen synthesis
c. vasoconstriction
What is the leading cause of death in diffuse cutaneous SSc?
Interstitial lung disese
If you see skin indurations but no Raynaud phenomenon, what would you suspect?
Scleroderma mimic
- >90% of people with true scleroderma have Raynaud phenomenon
Describe the presentation of limited cutaneous systemic sclerosis
Systemic sclerosis = scleroderma
-> CREST syndrome
- Calcinosis
- Raynaud
- Esophageal involvement
- Sclerodactyly
- Telengiectsia
Antibody = Anti-centromere
Slower progression, better prognosis than diffuse type
What are the 3 major contributors to the pathogenesis of systemic sclerosis?
Tripartite pathogenesis
- Microangiopathy (smll blood vessels)
- Inflammation and autoimmunity
- Fibrosis in multiple organs
- Skin, lungs, heart, GI tract, tendons
What is the treatment for a scleroderma renal crisis?
How effective is the treatment?
Treat immediately with ACE inhibitor
- Mortality risk is still 50% at one year
- Not great, but before ACE-I, scleroderm renal crisis was fatal within 1 week
These nail changes are characteristic of which autoimmune disorder?
Systemic sclerosis
Describe the role of fibroblasts in scleroderma
Normally, all tissues have fibroblasts
In scleroderma, they are activted and differentiated into myofibroblasts
Myofibroblasts -> Tissue remodeling -> hard, dense, scar tissue
What is the hallmark of scleroderma?
Hardening (induration) of the skin
Also:
- Multi-organ involvment
- Diffuse cutaneous or limited cutaneous presentation
Which antibodies predict lung disease in scleroderma?
Scl-70
Th/T0
Which antibody is associated with diffuse cutaneous SSc?
Anti-topoisomerase I
Which organ is spared from fibrosis in scleroderma?
Liver
What is a scleroderma renal crisis?
Describe the presentation
- Acute hypertension
- Malignant hypertension
- Renal ischemia
- -> Systemic damage
- Progressive oligouric failure
- Occurs in 15% of SSc patients
- More often in diffuse cutaneous SSc
- Usually in the 1st 4 years fo diagnosis
Treat with ACE inhibitor ASAP
What are the 4 cardinal manifestations of SSc Microangiopathy?
- Mucutaneous telangiectasia
- Raynaud phenomenon
- Pulmonary arterial hypertension
- -> Heart failure
- Scleroderma renal crisis
What is Raynaud phenomena?
What causes it?
Characteristic color changes in fingers triggered by cold exposure
- Result of reversible vasospasm of the finbers
- 1st phase = blanching (white)
- 2nd phase = cyanosis (purple)
- In patients with scleroderma, the cyanotic phase does not resolve and instead progresses to digitally ischemic ulcers.
- May heal, but can become infarcted resulting in mummification and autoamputation
What is the role of autoantibody analysis in the management of patients with SSc?
Antibodies in SSc are mutually exclusive; if you see one, you re unlikely to see others
Predictive of course/complications, but role in pathogenesis is unclear
- Anti-centromere
- Benign course (limited cutaneous SSc)
- Scl-70
- Lung disese
- Poor prognosis
- Anti-RNA polymerase III
- Renal crisis, cancer risk
- Th/T0
- Interstitial lung disease
A 45 yr-old previously healthy woman presents with episodic heartburn, increasing in frequency over the past 6 months. Her symptoms are worse at night. She has also had several episodes of near-choking on solid food. On further questioning, she notes that she has had “cold sensitivity” in her fingers for 2-3 years; and for past year, diffuse aching, and a fine rash on her face. Physical examination shows telangiectasia on her lips and cheeks, and erythema around her nailbeds (periungal). Her laboratory evaluation is most likely to show which of the following?
a. hematuria
b. serum antibody directed to double-stranded DNA
c. elevated level of serum complement 3 (C3)
d. serum antibody directed to centromere
e. low serum B12
d. serum antibody directed to centromere
Anti-centromere antibody is specific for scleroderma; often present in limited cutaneous SSc, predicts a benign course with few complications
Other scleroderma-specific antibodies:
- Anti-topoisomerase (diffuse cutaneous)
- Anti-RNA polymerase III (predicts renal crisis, cancer risk)
- Scl-70 (predicts lung disease, poor prognosis)
- Th/T0 (interstitial lung disese)
Which SSc antibody predicts a benign course?
Anti-centromere antibody
Which SSc antibody predicts renal crisis?
Anti-RNA polymerase III
What pattern of ANA immunofluorescence is specific for scleroderma (systemic sclerosis)
Nodular pattern
- Note: presence of ANA alone is not specific
Which SSc antibody predicts interstitial lung disease?
Th/T0
Describe the presentation of diffuse cutaneous systemic sclerosis
- Diffuse skin indurtion involving the trunk
- Antibody = anti-topoisomerse I
- Rapid progression, poor prognosis
Describe the fibrotic manifestations of scleroderma
Skin fibrosis
Pulmonary fibrosis
Heart, GI tract, tendons may also be involved
Describe the mucocutaneous manifestations of SSc
- Telangiectasia
- Nailfold capillary changes
- Hairpin-like small blood vessels, parallel to each other, perpendicular to the nail fold
