scleroderma interstitial lung diseases - what they are and what's new
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Scleroderma interstitial lung diseases - what they are and what’s new
Dean Schraufnagel, MDUniversity of Illinois at ChicagoMarch 15, 2014Nothing financial to disclose.
Lung disease -leading cause of deathSteen and Medsger. Ann Rheum Dis 2007; 66:940–4
Not one, but many diseases
What is “scleroderma lung?”
Respiratory diseases of SSc
• Vascular• Interstitial fibrosis• Alveolar ductitis (organizing
pneumonia)• Quiescent scarring• Aspiration-induced• Drug-induced
Respiratory diseases of SSc
• Neoplastic– 8.6/1000 person-years– Risk ratio 16.5– ↑ with fibrosis and smoking
• Extra pulmonary– Pleural– Chest wall restriction– Deconditioning– Drugs affecting breathing– Depression
Interstitial fibrosis
Fibrotic disease
• Present in 70-80% at autopsy• Inflammatory changes occur early• Progression variable– Exaggerated TGFß to injury
• Prognosis: better than IPF
Other forms
Alveolar ductitis - responds to steroids
Lymphoid follicles Scl-70 responsive T-cell clones
SSc woman with stable disease for many years
Aspiration
Aspiration
• Many studies relate to lung disease• SSc: Lower esophageal sphincter• Upper laryngopharyngeal reflexes• Acid vs bland contents• One of our interests
– Schraufnagel et al. Am J Roentgenol 2008;191:748-52.
What new in Ssc-ILD?
Classification
New classification scleroderma (2013)
– “Skin thickening of the fingers extending proximal to the metacarpophalangeal joints”
– If not present, 7 other criteria that include interstitial lung disease or pulmonary hypertension
– American College of Rheumatology and European League against Rheumatism. Arthritis Rheum 2013;65:2737-47
Basic Science
Basic science
• 843 genes differentially expressed in lung fibroblasts from SSc-ILD– These are therapy targets
• Lindahl et at., Respir Res. 2013;14:80
– TGFß and related molecules
• Many studies (770 in 2013) • Our interests– Endothelial cell rigidity (Levitan and
colleagues)– Caveolin-1 (Minshall and colleagues)
Treatments
Treatment
• Antifibrotic & anti-inflammatory drugs (ILD) – e.g. Pirfenidone, nintedanib, N-
acetylcysteine – Lota and Wells. Expert Opin Pharmacother 2013;14:79-
89.
• Lysophosphatidic acid receptor– Zhao and Natarajan. Biochim Biophys Acta
2013;1831:86-92
• Scleroderma mouse model– Castelino et al. Arthritis Rheum 2011;63:1405-15
Transplantation
• Survival - same nonconnective tissue ILD– Esophageal does not impact outcome
– Sottlie et al., Transplantation. 2013;95:975-80
• CRP predicts outcome - useful measure
– Liu et al., Arthritis Care Res 2013;65:1375-80.
Summary
Summary
• Scleroderma lung disease has many forms
• Take clues from Hx, Px, radiographs– Biopsy if need be
• Although Rx of SSc lung disease is generally poor, many components can be treated.
• Exciting research is helping to understand the basis of the disease
Questions?
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