Pulmonary Manifestations ofPolymyositis/Dermatomyositis

Sjögren’s Syndromeand

Ankylosing Spondylitis

Fellow’s Conference 11/10/10Cheryl Pirozzi, MD

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

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

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

Polymyositis and DermatomyositisInflammatory myopathiesClinical features:• Polymyositis:

– Symmetrical proximal muscle weakness– Myositis on muscle biopsy and EMG– ↑ serum muscle enzymes

• Dermatomyositis: the above plus rash:– Gottron’s papules– Violaceous heliotrope rash

Bohan A, Peter J: Polymyositis and dermatomyositis. N Engl J Med  1975; 292:403-40

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 5th edition

Polymyositis and DermatomyositisDiffuse 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.

Polymyositis and DermatomyositisDiffuse 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%

Polymyositis and DermatomyositisDiffuse 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 5th edition

Polymyositis and DermatomyositisDiffuse 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 5th edition

Polymyositis and DermatomyositisDiffuse 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 5th edition

Polymyositis and DermatomyositisDiffuse 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 5th edition

Polymyositis and Dermatomyositis

Other lung manifestations of PM/DM:• Respiratory muscle weakness

– Aspiration pneumonia– Hypercapneic respiratory failure– Bilateral diaphragm paralysis

Murray and Nadel 5th edition

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 5th edition

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.

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

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

Sjögren'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 Sjögren'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

Sjögren'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 Sjögren's syndrome. Baillieres Clin Rheumatol 1993; 7:59-7

Sjögren'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 patternsChest. 2006 Nov;130(5):1489-95Am J Respir Crit Care Med 2005 Mar 15;171(6):632-8

Sjögren'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):1489-95Am J Respir Crit Care Med 2005 Mar 15;171(6):632-8

Sjögren's syndrome- Diffuse lung disease

• Parambil. Chest. 2006 Nov;130(5):1489-95• CXR, HRCT, and biopsy of 18 pts with pSS ILD

Sjögren'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

Sjögren'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 5th edition

• 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

Sjögren's syndrome- Diffuse lung disease

Sjögren's syndrome- Diffuse lung disease

• Other: follicular bronchiolitis, Organizing pneumonia, usual interstitial pneumonia (UIP), diffuse interstitial amyloidosis

– UIP

Chest. 2006 Nov;130(5):1489-95

Sjögren'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

Sjögren'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 5th edition

Sjögren'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 taperIf resistant or not tolerant of steroids:– Azathioprine– Cyclophosphamide– Cyclosporine

Hunninghake, GW, Fauci, AS. Am Rev Respir Dis 1979; 119:471UpToDate.com

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

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

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 restrictionMurray and NadelMayo Clin Proc. 1977 Oct;52(10):641-9

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 NadelMayo Clin Proc. 1977 Oct;52(10):641-9Sampaio-Barros. Clin Rheumatol (2007) 26: 225–230

Ankylosing Spondylitis

• Upper zone fibrosis• Most common finding, usually asymptomatic• Unilateral -> progresses to bilateral fibrobullous dz

Murray and NadelMayo 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

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 NadelMayo Clin Proc. 1977 Oct;52(10):641-9

Kanathur N. Clin Chest Med - 01-SEP-2010; 31(3): 547-54ERJ March 1, 2004 vol. 23 no. 3 488-489

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): 547-54Murray and NadelMayo Clin Proc. 1977 Oct;52(10):641-9

Sampaio-Barros. Clin Rheumatol (2007) 26: 225–230

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): 547-54Murray and NadelMayo Clin Proc. 1977 Oct;52(10):641-9

Ankylosing Spondylitis

Evaluation• CXR: diffuse reticular opacities in upper zones,

symmetrical• HRCT

– Sampaio-Barros P. Clin Rheumatol (2007) 26: 225–230– 52 asymptomatic AS pts– 40% HRCT abnormalities

Murray and Nadel

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 NadelKanathur N. Clin Chest Med - 01-SEP-2010; 31(3): 547-54

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

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 Sjogren’s 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.

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: 225–230

• 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.

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. Müller 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 Sjögren's syndrome. UpToDate.com