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?