1. Scleroderma Lung Disease Robert Schilz DO, PhD University Hospitals Case Medical Center Cleveland, OH

2. Outline of Discussion: Scleroderma Lung Concerns Lung Problems Interstitial Lung Disease Pulmonary Vascular Disease Infections Drug Toxicity (Rare) Screening for Problems Immunizations

3. Changing Patterns of Mortality in Scleroderma SRC PAH GI PF Heart Multi-organ 1972- 1976 1977- 1981 1982- 1986 1987- 1991 1992- 1996 1997- 2001 Steen VD & Medsger TA. Ann Rheum Dis. 2007;66:940-944. PAH p=0.05 GI p=0.43 Heart p=0.26 50 40 30 20 10 0 Year of death p<0.0001(SRC) p<0.001 (PF) Frequency (%)

4. Interstitial Lung Disease Some changes in the lungs in patients with scleroderma are common Serious lung impairment in 13% of Patients Symptoms Shortness of breath “Dry” Cough

5. Incidence of Pulmonary Fibrosis in Various Rheumatologic Conditions Scleroderma - 71% (Steen et al. Rheu 28:759-767, 1985) Rheumatoid Arthritis - 10-47% (Remy-Jardin et al. Radiol 193:375-382, 1994) MCTD - 21% (Prakash et al. Mayo Clin Proc 60:813-821, 1985) IIM (Polymyositis/Dermatomyositis) - 30-80% (Schwartz Clin Chest Med19(4):701-712, 1998) Sjögren ’ s Syndrome - 8-30% (Papathananasiou et al. Chest 90:370-374, 1986)

6. A suggested approach for the long-term follow-up of patients with systemic sclerosis-interstitial lung disease. Joshua J. Solomon et al. Eur Respir Rev 2013;22:6-19 ©2013 by European Respiratory Society

7. Xray Pictures of Pulmonary Fibrosis

8. Extent of interstitial lung disease (ILD) in patients with systemic sclerosis-associated ILD. A simple stratification that utilises pulmonary function tests (PFTs) and extent of disease on high- resolution computed tomography (HRCT) to provide discriminatory... Joshua J. Solomon et al. Eur Respir Rev 2013;22:6-19

9. Histopathology results from a patient with systemic sclerosis and nonspecific interstitial pneumonia showing cellular interstitial infiltrates in a temporally uniform distribution. Joshua J. Solomon et al. Eur Respir Rev 2013;22:6-19 Normal Lung NSIP in Scleroderma

10. Histopathology results from a patient with systemic sclerosis and usual interstitial pneumonia showing patchy interstitial fibrosis in close proximity to unaffected lung tissue. Joshua J. Solomon et al. Eur Respir Rev 2013;22:6-19 ©2013 by European Respiratory Society

11. Mycophenolate mofitil is as effective as cyclophosphamide in treating interstitial lung disease in patients with scleroderma lung disease Design of Scleroderma Lung Study II 142 Patients 2 years of Mycophenolate mofitil (upt to 1500 mg BID) vs cyclophosphamide for 1 year (up to 2 mg/kg) Analyzed PFTs, CT scans, Rodnan Skin Scores and symptoms Results PFTs, CT scans, Rodnan Skin Scores and symptoms were better in both groups and similar (P< 0.05) 36 patients dropped out of cyclophosphamide group, 20 from MMF 23% of cyclophosphamide group received additional immunosuppression 4% of MMF group received additional immunosuppression Clements et al. Adapted from Online Summary from Presentations at the American Rheumatology Association Annual Conference San Francisco, CA Nov 8, 2015)

12. Pulmonary Arterial Hypertension

13. It’s not “hypertension” It’s “pulmonary hypertension” High blood pressure in the lungs Pulmonary Hypertension

14. Action for Initial Screening at Diagnosis

15. Echocardiogram (ECHO)

16. Treatment -> Future Lectures

17. Infections

18. EULAR Registry Tyndall AJ, Bannert B, Vonk M, et al. Causes and risk factors for death in systemic sclerosis: a study from the EULAR Scleroderma Trials and Research (EUSTAR) database. Ann Rheum Dis 2010; 69: 1809–1815.

19. CDC Advisory Committee for Immunization Practices (ACIP) Recommendations for Fluvax Who should receive fluvax? Everyone > 6 months old Contraindications Guillain-Barre following previous immunization IIV Contraindications: Severe egg allergy -> use RIV Severe immunosuppression -> no LAIV (nasal)

20. CDC ACIP Recommendations for Pneumococcal Pneumonia PPSV23 is recommended for: All adults 65 years of age and older, Anyone 2 through 64 years of age with certain long-term health problems, Anyone 2 through 64 years of age with a weakened immune system, Adults 19 through 64 years of age who smoke cigarettes or have asthma.

21. New Recommendations ACIP PCV13

22. Summary Interstitial Lung Disease Some changes common, severe disease less so Screening should occur by pulmonary function studies CT scan very useful for diagnosis Treatment should be considered for advancing or severe disease Pulmonary Arterial Hypertension Less common Screening should occur by echocardiography Diagnosis is only by right heart catheterization Treatment should proceed once diagnosis unequivocally proven Infections Preventable infections occur and can be serious Immunizations discussed