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Pulmonary Manifestations of Polymyositis/Dermatomyositis Sjgrens Syndrome and Ankylosing Spondylitis Fellows Conference 11/10/10 Cheryl Pirozzi, MD Slide 2 Case 1 41 yo woman p/w weakness in shoulders and thighs, and progressive DOE. Exam reveals crackles and the following rash: dermatology.cdlib.orgjfponline.com Slide 3 Case 1 The serology most closely associated with her disease and ILD is A) Anti- Jo-1 B) c-ANCA C) Anti-Ro (SS-A) D) HLA-B27 Slide 4 Case 1 The serology most closely associated with her disease and ILD is A) Anti- Jo-1 B) c-ANCA C) Anti-Ro (SS-A) D) HLA-B27 Slide 5 Polymyositis and Dermatomyositis Inflammatory myopathies Clinical features: Polymyositis: Symmetrical proximal muscle weakness Myositis on muscle biopsy and EMG serum muscle enzymes Dermatomyositis: the above plus rash: Gottrons papules Violaceous heliotrope rash Bohan A, Peter J: Polymyositis and dermatomyositis. N Engl J Med 1975; 292:403-40 Slide 6 Polymyositis and Dermatomyositis Lung manifestations of PM/DM: Diffuse lung disease: Interstitial pulmonary fibrosis Acute pneumonitis (with diffuse alveolar damage) Organizing pneumonia Pulmonary vasculitis and alveolar hemorrhage Respiratory muscle weakness Aspiration pneumonia Murray and Nadel 5 th edition Slide 7 Polymyositis and Dermatomyositis Diffuse lung disease Diffuse lung disease Most common manifestation, up to 32% of pts Pulmonary fibrosis: NSIP most common pattern Acute pneumonitis rapidly progressive DAD histopath Organizing pneumonia Semin Arthritis Rheum 2003; 32:273-284. Slide 8 Polymyositis and Dermatomyositis Diffuse lung disease Am J Respir Crit Care Med 2001; 164:1182-1185 70 pts with ILD and PM or DM Surgical lung biopsies in 22 pts NSIP in 82% diffuse alveolar damage (DAD) in 9% BOOP in 4% UIP in 4% Slide 9 Polymyositis and Dermatomyositis Diffuse lung disease Nonspecific interstitial pneumonia (NSIP) most common pattern Path: Lymphoplasmocytic infiltration, thickening of alveolar structures HRCT: Patchy interstitial pattern with GGOs Murray and Nadel 5 th edition Slide 10 Polymyositis and Dermatomyositis Diffuse lung disease Clinical features Presenting sxs: dyspnea, nonproductive cough, DOE, hemoptysis (if capillaritis) Pulm sxs can develop before systemic dz or at any point Severity of pulm involvement does not correlate with severity of musculoskeletal sxs Murray and Nadel 5 th edition Slide 11 Polymyositis and Dermatomyositis Diffuse lung disease Evaluation PFTs: restrictive pattern, DLCO If hemorrhage or severe myopathy, DLCO may be disproportionately preserved BAL: lymphocytosis and neutrophilia (worse prognosis) Murray and Nadel 5 th edition Slide 12 Polymyositis and Dermatomyositis Diffuse lung disease Evaluation Labs: AutoAbs to tRNA synthetases correlate with ILD: Jo-1 (in 50-100% of pts with ILD) (antisynthetase syndrome = myositis, ILD, and arthritis) Other: Ku, PL-12, PL-7, EJ, OJ Low CK associated with more severe ILD Murray and Nadel 5 th edition Slide 13 Polymyositis and Dermatomyositis Other lung manifestations of PM/DM: Respiratory muscle weakness Aspiration pneumonia Hypercapneic respiratory failure Bilateral diaphragm paralysis Murray and Nadel 5 th edition Slide 14 Polymyositis and Dermatomyositis Treatment Corticosteroids: PO prednisone 0.75-1.0 mg/kg/d IV steroids in severe/rapidly progressive dz Taper after 1 month, depending on response If steroid resistant or unable to tolerate: Cyclophosphamide, Cyclosporine A, Azathioprine, MTX, IVIG Murray and Nadel 5 th edition Slide 15 Polymyositis and Dermatomyositis Prognosis About 50% of pts with ILD have good response to steroids Similar survival to idiopathic NSIP 60% at 5 yrs Am J Respir Crit Care Med 2001; 164:1182-1185. Slide 16 Case 2 50 yo woman has long h/o dry eyes, dry mouth, and Anti-Ro (SS-A) Abs. She presents with 2 month h/o progressive DOE. Exam reveals crackles. PFTs show a restrictive pattern and decreased DLCO. HRCT and lung biopsy are most likely to show which of the following? A) Lymphocytic interstitial pneumonia B) UIP C) NSIP D) diffuse interstitial amyloidosis E) Lots of aspirated peanuts Slide 17 Case 2 50 yo woman has long h/o dry eyes, dry mouth, and Anti-Ro (SS-A) Abs. She presents with month h/o progressive DOE. Exam reveals crackles. PFTs show a restrictive pattern and decreased DLCO. HRCT and lung biopsy are most likely to show which of the following? A) Lymphocytic interstitial pneumonia B) UIP C) NSIP D) diffuse interstitial amyloidosis E) Lots of aspirated peanuts Slide 18 Sjgren's syndrome Autoimmune disorder of lymphocytic infiltration of the lachrymal, salivary, conjunctival, and pharyngeal mucosal glands Cardinal clinical features: keratoconjunctivitis sicca (dry eyes) and xerostomia (dry mouth) Primary Sjgren's syndrome (sicca sxs in isolation) or secondary (associated with CTDs such as RA, SSc, or SLE). Anti-Ro (SS-A) or anti-La (SS-B) Abs Slide 19 Sjgren's syndrome Pulm involvement is common (25%-75% in pSS) Due to lymphocytic infiltration similar to that in salivary gland Wide spectrum of lung processes: Diffuse interstitial lung disease Tracheobronchial and small airway disease ILD and airway disease occur together in about 50% Respiration. 2009 Apr 22;78(4):377-386 Constantopoulos. Chest 1985 Aug;88(2):226-9 Gardiner P. Primary Sjgren's syndrome. Baillieres Clin Rheumatol 1993; 7:59-7 Slide 20 Sjgren's syndrome- Diffuse lung disease Interstitial lung disease (25% in pSS) Clinical presentation: p/w dry cough, dyspnea, crackles Evaluation: BAL: lymphocytic alveolitis, occas neutrophil predominance PFTs: restrictive defect, DLCO CXR: reticular or nodular opacities with basilar prominence HRCT Lung biopsy (not always needed) Multiple distinct histiologic patterns Chest. 2006 Nov;130(5):1489-95 Am J Respir Crit Care Med 2005 Mar 15;171(6):632-8 Slide 21 Sjgren's syndrome- Diffuse lung disease ILD: Many diffferent histiologic patterns: Nonspecific interstitial pneumonia (NSIP) (20-60%) Lymphocytic interstitial pneumonia (14-20%) Pseudolymphoma Primary pulmonary lymphoma Organizing pneumonia usual interstitial pneumonia (UIP) diffuse interstitial amyloidosis Chest. 2006 Nov;130(5):1489-95 Am J Respir Crit Care Med 2005 Mar 15;171(6):632-8 Slide 22 Sjgren's syndrome- Diffuse lung disease Parambil. Chest. 2006 Nov;130(5):1489-95 CXR, HRCT, and biopsy of 18 pts with pSS ILD Slide 23 Sjgren's syndrome- Diffuse lung disease Nonspecific interstitial pneumonia (NSIP) most common pattern Lymphoplasmocytic infiltration of interstitial compartment HRCT: Patchy interstitial pattern with GGOs Respiration. 2009 Apr 22;78(4):377-386 Slide 24 Sjgren's syndrome- Diffuse lung disease Lymphocytic interstitial infiltration: Lymphocytic interstitial pneumonia Diffuse lymphocytic infiltrate, most prominent around bronchioles HRCT: thin-walled cysts, GGO, centrilobular and subpleural nodules Murray and Nadel 5 th edition Slide 25 Lymphocytic interstitial infiltration: Pseudolymphoma: nodular lymphoid hyperplasia- infiltrates of mature lymphocytes Pulm lymphoma: interstitial vs discrete masses Prevalence of lymphoma increased 40-50x in Sjogrens, mst common NHL Chest. 2006 Nov;130(5):1489-95 Sjgren's syndrome- Diffuse lung disease Slide 26 Other: follicular bronchiolitis, Organizing pneumonia, usual interstitial pneumonia (UIP), diffuse interstitial amyloidosis UIP Chest. 2006 Nov;130(5):1489-95 Slide 27 Sjgren's syndrome- Large and/or small airways disease Chronic bronchitis/lymphocytic bronchiolitis: lymphocytic infiltration around bronchioles Can present like COPD. HRCT: bronchial thickening, bronchiectasis, centrilobular nodules, mosaic attenuation PFTs: If primarily small airway dz- obstruction. If both ILD and small airway dz- mixed pattern. Path: Follicular bronchiolitis with lymphoid infiltrates Respiration. 2009 Apr 22;78(4):377-386 Slide 28 Sjgren's syndrome- Large and/or small airways disease Xerotrachea: loss of mucous secretion in trachea Up to 25% pts, atrophy of mucous glands with lymphoplasmocytic infiltrate Chronic severe dry cough Murray and Nadel 5 th edition Slide 29 Sjgren's syndrome- Treatment No prospective randomized trials of rx in SS and ILD If asymptomatic, follow Rx if symptomatic and functional deterioration Prednisone 1 mg/kg/d PO x 6 months with taper If resistant or not tolerant of steroids: Azathioprine Cyclophosphamide Cyclosporine Hunninghake, GW, Fauci, AS. Am Rev Respir Dis 1979; 119:471 UpToDate.com Slide 30 Case 3 35 yo man with a h/o back pain and recurrent uveitis p/w SOB and hemoptysis. Chest CT shows cavitary lesions in the RUL and LUL. These are most likely to be colonized by which pathogen? A) TB B) Aspergillus fumigatus C) beta hemolytic streptococcus D) Mycobacterium avium intracellulare E) Coccidioidomycosis Slide 31 Case 3 35 yo man with a h/o back pain and recurrent uveitis p/w SOB and hemoptysis. Chest CT shows cavitary lesions in the RUL and LUL. These are most likely to be colonized by which pathogen? A) TB B) Aspergillus fumigatus C) beta hemolytic streptococcus D) Mycobacterium avium intracellulare E) Coccidioidomycosis Slide 32 Ankylosing Spondylitis Seronegative spondyloarthritis 0.05-1.5% of population, male:female = 10:1 Associated with HLA-B27 Inflammation-> fibrosis-> ankylosis of vertebral joints Peripheral joint arthritis (1/3) Extra-articular features: aortic regurg, uveitis, pulmonary disease and chest wall restriction Murray and Nadel Mayo Clin Proc. 1977 Oct;52(10):641-9 Slide 33 Ankylosing Spondylitis Lung disease occurs in up to 30% of patients Subclinical lung abnormalities are found on HRCT in 40-88% of pts Pulmonary abnormalities: Upper lobe fibrosis Upper lobe fibrobullous disease Small airway disease Bronchiectasis Paraseptal emphysema Pneumothorax Chest wall restriction Murray and Nadel Mayo Clin Proc. 1977 Oct;52(10):641-9 Sampaio-Barros. Clin Rheumatol (2007) 26: 225230 Slide 34 Ankylosing Spondylitis Upper zone fibrosis Most common finding, usually asymptomatic Unilateral -> progresses to bilateral fibrobullous dz Murray and Nadel Mayo Clin Proc. 1977 Oct;52(10):641-9 Kanathur N. Clin Chest Med - 01-SEP-2010; 31(3): 547-54 Rev. Bras. Reumatol. [online]. 2009, vol.49, n.5 [cited 2010-11-09], pp. 630-637 Slide 35 Ankylosing Spondylitis Apical fibrobullous disease with upper lobe cavitation Fungal or mycobacterial superinfection of cavities in up to 1/3 of pts Aspergillus is most common pathogen Others: atypical mycobacteria, candida Can be complicated by life-threatening hemoptysis or spontaneous pneumothorax Murray and Nadel Mayo Clin Proc. 1977 Oct;52(10):641-9 Kanathur N. Clin Chest Med - 01-SEP-2010; 31(3): 547-54 ERJ March 1, 2004 vol. 23 no. 3 488-489 Slide 36 Ankylosing Spondylitis Small airway disease Bronchiectasis Paraseptal emphysema Spontaneous pneumothorax 0.29% of AS pts, increased risk with apical fibrobullous dz Kanathur N. Clin Chest Med - 01-SEP-2010; 31(3): 547-54 Murray and Nadel Mayo Clin Proc. 1977 Oct;52(10):641-9 Sampaio-Barros. Clin Rheumatol (2007) 26: 225 230 Slide 37 Ankylosing Spondylitis Chest wall restriction due to costovertebral ankylosis- usually mildly reduced lung volumes OSA: 12-23% of pts Increased risk with dz duration, older pts May be due to restrictive pulm dz, airway obstruction due to TMJ involvement, or compression of medullary respiratory center by cervical spinal dz Kanathur N. Clin Chest Med - 01-SEP-2010; 31(3): 547-54 Murray and Nadel Mayo Clin Proc. 1977 Oct;52(10):641-9 Slide 38 Ankylosing Spondylitis Evaluation CXR: diffuse reticular opacities in upper zones, symmetrical HRCT Sampaio-Barros P. Clin Rheumatol (2007) 26: 225230 52 asymptomatic AS pts 40% HRCT abnormalities Murray and Nadel Slide 39 Ankylosing Spondylitis Evaluation BAL: often normal, may show lymphocytic alveolitis Sputum cx for mycobacterium or fungi Histology: mix of lymphocytic infiltration, fibrosis, bullous change PFTs: may have mild restriction (mostly due to thoracic cage compliance rather than apical fibrosis). DLCO usually nl. Murray and Nadel Kanathur N. Clin Chest Med - 01-SEP-2010; 31(3): 547-54 Slide 40 Ankylosing Spondylitis Treatment No treatment has been shown to alter the clinical course of apical fibrobullous disease Rx pulmonary superinfections with antifungal or antibacterial agents (systemically or into cavities) Medical rx of Aspergillus infected cavitary lesions often unsuccessful, may require surgical excision. Kanathur N. Pulmonary manifestations of ankylosing spondylitis. Clin Chest Med - 01-SEP-2010; 31(3): 547-54 Slide 41 Conclusions Pulmonary disease is common in PM/DM, Sjogrens, and ankylosing spondylitis. In polymyositis and dermatomyositis the most common form of pulm disease is ILD, usually NSIP. In Sjogrens the most common abnormality is ILD, which occurs in a wide variety of histologic patterns, most commonly NSIP, then LIP. In ankylosing spondylitis the most common finding is upper lobe fibrosis, which can be complicated by cavitation and superinfection. Slide 42 Slide 43 References Rosenow E, Strimlan CV, Muhm JR, Ferguson RH: Pleuropulmonary manifestations of ankylosing spondylitis. Mayo Clin Proc 1977; 52:641-649 Sampaio-Barros P, Cerqueira E, Rezende S, et al: Pulmonary involvement in ankylosing spondylitis. Clin Rheumatol (2007) 26: 225230 Boushea, DK, Sundstrom, WR. The pleuropulmonary manifestations of ankylosing spondylitis. Semin Arthritis Rheum 1989; 18:277. Bronchoalveolar lavage and transbronchial biopsy in spondyloarthropathies. Kchir MM; Mtimet S; Kochbati S; Zouari R; Ayed M; Gharbi T; Hila. J Rheumatol 1992 Jun;19(6):913-6 Bohan A, Peter J. Polymyositis and dermatomyositis. N Engl J Med 1975; 292:403- 407 Douglas WW, Tazelaar HD, Hartman TE, et al: Polymyositis-dermatomyositis associated interstitial lung disease. Am J Respir Crit Care Med 2001; 164:1182- 1185. Schnabel A, Reuter M, Biederer J, et al: Interstitial lung disease in polymyositis and dermatomyositis: Clinical course and response to treatment. Semin Arthritis Rheum 2003; 32:273-284. Shi JH; Liu HR; Xu WB; Feng RE; Zhang ZH; Tian XL; Zhu YJ. Pulmonary Manifestations of Sjogren's Syndrome. Respiration. 2009 Apr 22;78(4):377-386. Slide 44 References Kanathur N. Pulmonary manifestations of ankylosing spondylitis. Clin Chest Med - 01-SEP-2010; 31(3): 547-54 Hunninghake, GW, Fauci, AS. Pulmonary involvement in the collagen vascular disease. Am Rev Respir Dis 1979; 119:471 T. Franquet, N.L. Mller and J.D. Flint. A patient with ankylosing spondylitis and recurrent haemoptysis. European Respiratory Journal. March 1, 2004 vol. 23 no. 3 488-48 Ribeiro de Carvalho, Deheinzelin D, Kairalla R, King T. Interstitial lung disease associated with Sjgren's syndrome. UpToDate.com