Pulmonary Manifestations of
Polymyositis/Dermatomyositis
Sjögren’s Syndrome
and
Ankylosing Spondylitis
Fellow’s Conference 11/10/10
Cheryl Pirozzi, MD
Case 1
• 41 yo woman p/w weakness in shoulders and
thighs, and progressive DOE. Exam reveals
crackles and the following rash:
jfponline.com
dermatology.cdlib.org
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 Dermatomyositis
Inflammatory myopathies
Clinical 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 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.
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%
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 5th edition
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 5th edition
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 5th edition
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 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 patterns
Chest. 2006 Nov;130(5):1489-95
Am 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):1489-95
Am 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
Sjögren's syndrome- Diffuse lung disease
• 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
• Other: follicular bronchiolitis, Organizing
pneumonia, usual interstitial pneumonia (UIP),
diffuse interstitial amyloidosis
– UIP
Chest. 2006 Nov;130(5):1489-95
Sjögren's syndromeLarge 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 syndromeLarge 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 taper
If resistant or not tolerant of steroids:
– Azathioprine
– Cyclophosphamide
– Cyclosporine
Hunninghake, GW, Fauci, AS. Am Rev Respir Dis 1979; 119:471
UpToDate.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 restriction
Murray and Nadel
Mayo 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 Nadel
Mayo Clin Proc. 1977 Oct;52(10):641-9
Sampaio-Barros. Clin Rheumatol (2007) 26: 225–230
Ankylosing Spondylitis
• Upper zone fibrosis
• Most common finding, usually asymptomatic
• Unilateral -> progresses to bilateral 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
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
Kanathur N. Clin Chest Med - 01-SEP-2010; 31(3): 547-54
Murray and Nadel
Mayo Clin Proc. 1977 Oct;52(10):641-9
ERJ March 1, 2004 vol. 23 no. 3
488-489
Ankylosing Spondylitis
• Small airway disease
• Bronchiectasis
• Paraseptal emphysema
Sampaio-Barros. Clin Rheumatol (2007) 26: 225–
230
• 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
Ankylosing Spondylitis
• Chest wall restriction due to costovertebral ankylosisusually 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
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.
Kanathur N. Clin Chest Med - 01-SEP-2010; 31(3): 547-54
Murray and Nadel
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
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•
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•
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; 292:403407
Douglas WW, Tazelaar HD, Hartman TE, et al: Polymyositis-dermatomyositis–
associated interstitial lung disease. Am J Respir Crit Care Med 2001; 164:11821185.
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
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•
•
•
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