Systemic sclerosis (scleroderma) Flashcards
Systemic sclerosis (scleroderma) is divided into:
Systemic sclerosis frequently involves multisystem vasculopathy affecting several vessel beds, including distal extremities (digital ischemia), kidneys (renal crisis), and pulmonary arteries.
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Diffuse cutaneous systemic sclerosis: widespread skin involvement, pulmonary fibrosis and interstitial lung disease, myocardial fibrosis (pericarditis), renal crisis.
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Limited cutaneous systemic sclerosis (CREST): Calcinosis on fingers, Raynaud’s, esophageal dysmotility, Sclerodactyly, telangiectasia, and pulmonary hypertension.
What is the underlying pathology associated with systemic sclerosis?
Systemic sclerosis is driven by abnormal inflammatory and fibroproliferative signaling (eg, transforming growth factor beta), leading to neointimal/medial thickening and luminal narrowing. Histologically, vessels have a concentric onion-skin, sclerotic appearance.
What is the most common cause of mortality in patients with diffuse cutaneous systemic sclerosis (dcSSc)?
Pulmonary arterial hypertension (PAH), a leading cause of mortality in patients with systemic sclerosis. Pulmonary diseases in systemic sclerosis can manifest as interstitial lung disease (Diffuse cutaneous systemic sclerosis) or pulmonary arterial hypertension (CREST), however, PAH is the most common cause of mortality. Scleroderma renal crisis (Diffuse cutaneous) is a life-threatening complication, but it is not the most common cause of mortality.
What are the 2 primary pulmonary complications seen in systemic sclerosis (scleroderma)?
- Interstitial lung disease (ILD) — progressive fibrosis of the alveoli seen in diffuse cutaneous systemic sclerosis.
- Pulmonary arterial hypertension (PAH) — intimal hyperplasia of pulmonary arteries seen in CREST (limited systemic sclerosis).
How does Pulmonary arterial hypertension (PAH) present in systemic sclerosis?
Pulmonary vascular remodeling is progressive and relentless. Over time, the right ventricle cannot pump against the increased afterload, leading to right ventricular failure. PAH is suggested by a prominent pulmonic component of S2 (ie, loud P2, reflecting high pressure in pulmonary artery) with signs of right-sided venous congestion (eg, hepatomegaly, lower extremity edema).
Systemic sclerosis can induce extrapulmonary restriction via chest wall skin tightening that limits thoracic expansion (clear lungs are expected on auscultation and imaging), what would show on pulmonary function testing to suggest this limitation of thoracic expansion?
PFTs would show a restrictive pattern, low FVC, low TLC, but a normal or increased forced expiratory volume in 1 second to forced vital capacity ratio (FEV₁/FVC) – since both FEV₁ and FVC are proportionally reduced, the ratio remains normal or slightly elevated.
How do you screen for pulmonary disease in patients with systemic sclerosis?
- Pulmonary function tests (PFTs) to assess for restrictive lung disease.
- High-resolution chest CT (HRCT) to detect interstitial lung disease (ILD).
- Right heart catheterization for suspected pulmonary arterial hypertension (PAH).
A complication of systemic sclerosis is pericardial fibrosis, which has to similar symptoms of pulmonary disease, such as right-sided heart failure due to impaired diastolic filling of the right ventricle. What physical exam finding would be able to distinguish pulmonary disease from pericardial disease?
A loud P2 is not expected in pericardial disease and is associated with pulmonary disease.
What is the classic presentation of Raynaud’s phenomenon in systemic sclerosis?
Color changes: White (pallor) → Blue (cyanosis) → Red (reperfusion).
Triggered by cold or stress.
Leads to digital ulcers and autoamputation of fingertips.
What is a key difference with Diffuse cutaneous systemic sclerosis?
Early organ involvement
Renal crisis in diffuse systemic sclerosis is associated with … ?
MAHA
oliguria
thrombocytopenia
What is the diagnostic measure for systemic sclerosis?
Clinical Picture
Serology (antibodies)
Biopsy of the capillary nail bed.
Which autoantibodies are associated with systemic sclerosis (scleroderma)?
ANA (usually a non-specific screening method)
Anti-Scl-70 (anti-topoisomerase I) — associated with diffuse cutaneous systemic sclerosis and interstitial lung disease (ILD).
Anti-centromere antibodies — associated with limited cutaneous systemic sclerosis (CREST syndrome).
Anti-RNA polymerase III — associated with scleroderma renal crisis.
What are the immunotherapies used for systemic sclerosis?
mycophenolate mofetil
cyclophosphamide
methotrexate
azathioprine.
For systemic sclerosis, what is important to note regarding the treatment approach, especially for diffuse systemic sclerosis?
Treatments are by Organ System
What immunpsuppressing agent is first-line for ILD in systemic sclerosis?
Mycophenolate mofetil is often the first-line agent for ILD due to its favorable side effect profile compared to cyclophosphamide.
Nintedanib ia specifically for treatment of interstitial lung disease (ILD) in systemic sclerosis and works by inhibiting multiple tyrosine kinases involved in fibrosis, reducing lung fibrosis progression.
What is the preferred treatment for Interstitial Lung Disease (ILD) in systemic sclerosis?
Mycophenolate mofetil (preferred) or cyclophosphamide.
Nintedanib for progressive ILD.
Why are steroids not really used in systemic sclerosis?
Corticosteroids should be used with caution, as they increase the risk of scleroderma renal crisis.
What is the preferred treatment for pulmonary hypertension in systemic sclerosis?
Endothelin receptor antagonists: Bosentan, Ambrisentan.
Phosphodiesterase-5 inhibitors: Sildenafil, Tadalafil.
Prostacyclin analogs: Epoprostenol, Treprostinil, Iloprost.
What modalities are used to monitor lungs in systemic sclerosis?
High-resolution CT (HRCT) to assess for interstitial lung disease.
Pulmonary function tests (PFTs) every 6–12 months to assess for restrictive lung disease and DLCO.
Scleroderma Renal Crisis (SRC) is managed how?
Captopril or Lisinopril are first-line agents, regardless of creatinine levels.
How is skin fibrosis managed in systemic sclerosis?
Methotrexate for early skin disease.
Mycophenolate mofetil for progressive skin fibrosis.
Physical therapy to improve range of motion and prevent joint contractures.
Topical moisturizers to reduce dryness and cracking.
How are digital ulcers (due to Raynaud’s) managed in systemic sclerosis?
Calcium channel blockers: Nifedipine or Amlodipine (first-line).
Phosphodiesterase-5 inhibitors: Sildenafil for more severe Raynaud’s.
Prostacyclin analogs: Iloprost infusions for nonhealing digital ulcers.
Endothelin receptor antagonists: Bosentan (used to reduce recurrent ulcers).
What is given to manage the cardiac issues in systemic sclerosis?
Anti-arrhythmic medications (eg, beta-blockers, amiodarone, or implantable defibrillators if indicated).
ACE inhibitors and ARB therapy to control blood pressure.
Diuretics for heart failure (use cautiously due to the risk of scleroderma renal crisis).
How is the heart monitored in systemic sclerosis?
Perform echocardiograms annually to assess for right ventricular hypertrophy, pulmonary hypertension, or pericardial effusion.
Gastroesophageal Reflux Disease (GERD) and Dysphagia in systemic sclerosis is managed in what way?
Proton pump inhibitors (PPIs): Omeprazole, Pantoprazole (daily or twice daily).
Lifestyle modifications: Elevate head of bed, avoid late-night eating.
Other than GERD, what others GI complications can occur secondary to systemic sclerosis?
Small Bowel Bacterial Overgrowth (SIBO)
Treatment:
Rifaximin or metronidazole (antibiotics for bacterial overgrowth).
Constipation and Motility Issues
Treatment:
Prokinetic agents
(Metoclopramide or Domperidone to improve motility).
Musculoskeletal Involvement secondary to systemic sclerosis is managed in what way?
NSAIDs for pain relief.
Methotrexate or mycophenolate mofetil for inflammatory myopathy.
Physical therapy to improve range of motion and avoid contractures.
