Rheumatoid Lung Disease

1. Rheumatoid Lung Disease Christopher V. Tehlirian, MD Rheumatology Grand Rounds June 2, 2006

2. Disclosures NONE

3. Objectives • Natural History of Rheumatoid lung disease • Patterns of Rheumatoid lung disease • Risk Factors of Rheumatoid lung disease • Differentiating MTX lung from RA lung • Clinical Implications

4. Case 1 • 79 yo WF with seropositive erosive nodular (RF 122, CCP 116) RA dx’d in 1960 (age 35) • Previous RA Treatments: • NSAIDS • IM Gold • Prednisone (2-5mg/day) • MTX 7.5 mg (for 3 months in 1999) • Arava 20 mg (2003)

5. PMH: HTN RA Osteopenia Bilateral cataracts OA Nondispalced pelvic fx s/p fall GERD Breast CA 1993 Surgical History: s/p right mastectomy 1993 L wrist fusion 1983 with revison in 1997 L ankle fusion 1990 R TKR 1999 R 5th MTP head resection 1995 Case 1 Continued

6. Case 1 Continued • Allergies: Codeine-rash, ACEI ? • Medications: • MTX 12.5 mg +Entanercept 50 mg (12/05) • Prednisone 5mg • Raloxifen 60 mg • Ranitidine 300 BID • Atenolol 50 mg • Celebrex 200mg • Naprosyn 375 BID • Amlodipine 5 mg • Calcium +Vit D

7. Case 1 Continued • FMH: Mother died of breast CA age 77 Father died of MI age 60 Sister has Gyn CA • SocH: Nun at catholic school in Dundalk No tobacco, ETOH or Illicits

8. Case 1 Continued Came to Bayview ER 1/21/06 with hip pain but was admitted with hypoxia (84% RA, PaO2 40)

9. Case 1 Continued

10. Case 1 Continued

11. Case 1 Continued

12. Case 2 • 84 yo WF dx’d with PMR 2002 (age 80) started on Prednisone 20 mg. RF was low positive (1:116) • 11/03 seen in Pulmonary Clinic with chronic dry cough and found to have bronchiectasis on Chest CT. • 2/05 had rheumatoid distribution of synovitis found to have RF 1500 and CCP 139. • 3/05 started MTX 15

13. Case 2 Continued • PMH: • collagenous colitis • breast CA 1982 • PVD • Osteoporosis • Hypercholesterolemia • OA • subclinical hypothyroidism • Past surgical history: 1) left second and third MCP arthroplasty 12/2003 • Allergies: naprosyn-GI upset • FMH: Father died in his 30s with TB, Mother died in her 60s with colon CA. • SocH: 1ppd for 10 years quit in 1950.

14. Case 2 continued • 11/05 Admitted to Bayview hospital with DOE, cough, and 78-80% O2 sat on RA after 1 week febrile prodrome.

15. Case 2 Continued

16. Case 2 Continued

17. Case 2 Continued

18. Case 3 • 57 yo WF dx’d with Sjogrens syndrome 1985 and seropositive erosive nodular RA in 1989. • Previous treatments: • Hydroxychloroquine • D-penicillamine • IM Gold • Prednisone • MTX +Etanercept 1999

19. Case 3 Continued • PMH: • Sjogrens syndrome 1985 • RA 1989 • Achilles tendon rupture • Allergies: NKDA • FMH: 5 sisters and 1 brother all essentially healthy.  Her mother died of pancreatic cancer. Father died of colorectal cancer. • SocH: Occ ETOH, no tobacco, no illicits. Worked as a librarian.

20. Case 3 Continued • 5/03 seen in pulmonary clinic for 3 years of non-productive cough and 5 months of worsening DOE (2 flights of stairs). • CXR 2002-revealed slightly increased lung volumes. • HRCT- reviewed by pulmonary with normal parenchyma and mild bronchial wall thickening. • PFTs from 09/03: FEV1/FVC of 50 (79%) FEV1 of 0.34 (36%) FVC 1.7 (56%) TLC (109%) DLCO (86%)

21. Rheumatoid Arthritis (RA) • Systemic chronic autoimmune inflammatory disease • Prevalence of RA is around 1% worldwide • Male : Female=1:2 • The articular manifestations are the sine qua non of the disease. • Extra-articular manifestations are present in 40% of all RA patients.

22. 20Gabriel at al. Arthritis and Rheum 2003

23. Rheumatoid Lung Disease • On autopsy of 1246 RA pts 18% died due to lung disease (infxn 27%)1. 1Toyoshina et al. Ryumachi 1993

24. 19Turesson et al. Current Opinion in Rheumatology May 2004

25. 20Gabriel at al. Arthritis and Rheum 2003

26. Extra-articular Manifestations of RA2 • Sicca symtpoms • Rheumatoid nodules • Pulmonary involvement • Cardiac involvement • Hematologic manifestations • Cervical Myelopathy • Opthalmologic involvement • Vasculitis • Amyloid

27. The History of Rheumatoid Lung • Ellman and Ball are the first to publish case report on RA with pulmonary involvement in 1948. 3 (3 cases of RA with ILD) • Caplan in 1953 describes rheumatoid nodules in coal miners suffering from RA.4 • In 1954, rheumatoid lung nodules found in RA patients without pneumoconiosis.5

28. The History of Rheumatoid Lung • In 1955, case series of RA patients’ autopsies demonstrate twice the incidence o pleural disease compared to normal population.6 • In 1961, Cudkowicz et al describe the clinical, pathologic, and spirometric findings in RA patients with “rheumatoid lung” disease.7

29. Rheumatoid Lung Disease • What exactly is “Rheumatoid Lung Disease”?

30. Rheumatoid Lung • Pleural involvement (pleurisy, effusions) • Pulmonary parenchymal nodules • Rheumatoid associated interstitial lung disease • Bronchiolitis obliterans organizing pneumonia • Obliterative bronchiolitis (obstructive lung disease/bronchiectasis) • Rheumatoid associated pulmonary hypertension • Pulmonary vasculitis/arteritis • Shrinking lung syndrome • Miscellaneous: MTX, cricoarytenoid arthritis, infxn, cancer

31. Pleural Involvement • Pleural involvement is the most common pulmonary manifestation of RA. (debated) • Approximately 15-20% of RA patients have pleurisy.8 • Risk factors: Men, 50s, nodules • It is estimated that >40% of RA patients have pleural inflammation on autopsy.9 8 Bacon, PA. Philadelphia, PA, Lea & Febiger. 1993. 9 Shannon et al.. J Thoracic Imaging 1992.

32. Pleurisy and Pleural Effusions • Pleurisy is more common men than in women.10 • Usually in the 4th and 5th decade of life with active arthritis and nodules. • Pleurisy is typically asymptomatic, it is often noticed on physical exam (pleural rub) and/or radiologic finding.11 10 Walker et al. Ann Rheum Dis 1967 11 Macfarlane et al. Br J Dis Chest 1978

33. Pleural Effusions • Pleural effusions (3-5% of RA pts) are typically small and asymtpomatic. • The effusions are bilateral in more than 25% of cases, and 25% may precede joint disease.10 • Effusions may be present with other RA pulmonary manifestations (nodules, ILD). • Pleural fluid is yellowish-green (cholesterol crystals), WBC 100-8000 cells/µl predominately lymphocytes, high LDH (>1000 U/L), low glucose (<25), low complement, and high RF.

34. Pleural Effusions

35. Rheumatoid Lung Nodules • Pulmonary rheumatoid lung nodules (specific to RA) are also more common in men than in women, with nodules and positive RF.8 • Frequently in the periphery of the right middle or both upper lobes (single or multiple). • Central cavitation occurs in 50% of the lung nodules without calcification. • The clinical course of lung nodule is variable, typically benign but can cause pneumothorax, hemoptysis, can get secondarily infected, or form bronhopleural fistulas.

36. Rheumatoid Nodule

37. Rheumatoid Lung Nodules

38. Caplan’s Syndrome • Caplan’s syndrome is pulmonary nodulosis in RA and pneumoconiosis related to exposure of coal dust, silica, or asbestos. • Characterized by multiple >1cm peripheral lung nodules. • Prevalence 2-6% of patients with RA but declining as the coal mining industry declines. • Spontaneous remission has been described. 9 Shannon et al. J Thoracic Imaging 1992

39. Caplan’s Syndrome

40. Interstitial Lung Disease in RA • Prevalence reported from 1.6% to 40% in RA pts in various studies. • Walker et al defines ILD by radiograph in 1.6% of 516 RA pts.12 • Frank et al. show diminished DLCO in 40% of 41 RA pts, but only 18% of those have radiographic abnormalities.13 • Clinical manifestations similar to idiopathic pulmonary fibrosis.

41. Interstitial Lung Disease in RA 21Roschmann et al. Semin in Arthritis and Rheum 1987

42. Interstitial Lung Disease in RA • Arthritis precedes ILD in 70-90% of cases by a mean of 37 months.14 • Male to female ratio between 3:1 to 1:1 (debated). • Age of onset between 33 to 75 years of age. • HLA-DRB1 association as well as α1-anitrypsin phenotype. • >50% of RA pts with ILD have Rheumatoid nodules • 65% have high titer RF >1:128 • 75% have ESR persistently above 40 mm/h

43. Interstitial Lung Disease in RA • Smoking appears to be an additional independent risk factor. • BAL can show both lymphocytic or neutrophilic predominance. 25 • Heterogenous biopsy findings in single RA patient. • PFTs show early restrictive pattern and DLCO drop by at least 15% predicted. • HRCT correlates with lung biopsy of ILD approximately 90%.24

44. RA-ILD

45. RA-ILD 23Dawson et al. Thorax 2001.

46. RA-ILD 23Dawson et al. Thorax 2001.

47. RA-ILD

48. RA-ILD

49. RA-ILD • Therapy consists of corticosteroids (44% response), MTX (case reports), D-penicillamine, Azathioprine, Cyclophosphamide and Cyclosporine. • Prognosis is variable: from spontaneous remission which has been reported, slowly progressive ILD (over 10 years), to rapidly progressive ILD (over 4 months). • Most commonly mean survival is 3.2 years such as idiopathic ILD • Survival was not related to degree of PFT impairment, RF, or ESR. • Survival was improved by early response to corticosteroids, less fibrosis on imaging and high cellularity on BAL. 21 Roschmann et al. Seminars in Arthritis and Rheum 1987.

50. Bronchiolitis Obliterans Organizing Pneumonia (BOOP) • BOOP specific interstitial pneumonitis with an unknown etiology • Male to female ratio 1:1 (?female predominance) • Mean age 56 usually between ages 45-75 • 30% of BOOP cases preceded by febrile flu-like illness • Patients complain of non-productive cough and SOB.