Pulmonary Manifestations of Polymyositis/Dermatomyositis Sj

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Pulmonary Manifestations ofPolymyositis/Dermatomy
ositisSjögrens SyndromeandAnkylosing
Spondylitis

• Fellows Conference 11/10/10
• Cheryl Pirozzi, MD

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Case 1

• 41 yo woman p/w weakness in shoulders and thighs,
  and progressive DOE. Exam reveals crackles and
  the following rash

dermatology.cdlib.org
jfponline.com
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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

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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

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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 292403-40
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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
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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 32273-284.
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Polymyositis and DermatomyositisDiffuse lung
disease

• Am J Respir Crit Care Med 2001 1641182-1185
• 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

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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
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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
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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
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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
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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
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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
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 1641182-1185.
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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

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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

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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

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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 2278(4)377-386

Constantopoulos. Chest 1985 Aug88(2)226-9
Gardiner P. Primary Sjögren's syndrome. Bailliere
s Clin Rheumatol  1993 759-7
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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 Nov130(5)1489-95 Am J Respir Crit
Care Med 2005 Mar 15171(6)632-8
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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 Nov130(5)1489-95 Am J Respir Crit
Care Med 2005 Mar 15171(6)632-8
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Sjögren's syndrome- Diffuse lung disease

• Parambil. Chest. 2006 Nov130(5)1489-95
• CXR, HRCT, and biopsy of 18 pts with pSS ILD

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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 2278(4)377-386
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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
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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 Nov130(5)1489-95
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Sjögren's syndrome- Diffuse lung disease

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

Chest. 2006 Nov130(5)1489-95
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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 2278(4)377-386
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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
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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 119471 UpToDate.com
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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

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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

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Ankylosing Spondylitis

• Seronegative spondyloarthritis
• 0.05-1.5 of population, malefemale 101
• Associated with HLA-B27
• Inflammation-gt fibrosis-gt 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
Oct52(10)641-9
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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
Oct52(10)641-9 Sampaio-Barros. Clin Rheumatol
(2007) 26 225230
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Ankylosing Spondylitis

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

Kanathur N. Clin Chest Med - 01-SEP-2010 31(3)
547-54
Murray and Nadel Mayo Clin Proc. 1977
Oct52(10)641-9
Rev. Bras. Reumatol. online. 2009, vol.49, n.5
cited  2010-11-09, pp. 630-637
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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
Oct52(10)641-9
ERJ March 1, 2004 vol. 23 no. 3 488-489
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Ankylosing Spondylitis

• Small airway disease
• Bronchiectasis
• Paraseptal emphysema
• Spontaneous pneumothorax 0.29 of AS pts,
  increased risk with apical fibrobullous dz

Sampaio-Barros. Clin Rheumatol (2007) 26 225230

• Kanathur N. Clin Chest Med - 01-SEP-2010 31(3)
  547-54
• Murray and Nadel
• Mayo Clin Proc. 1977 Oct52(10)641-9

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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 Oct52(10)641-9

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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
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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
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
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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.

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References

• Rosenow E, Strimlan CV, Muhm JR, Ferguson RH Pleu
  ropulmonary manifestations of ankylosing
  spondylitis. Mayo Clin Proc  1977 52641-649
• 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 18277.  
• Bronchoalveolar lavage and transbronchial biopsy
  in spondyloarthropathies. Kchir MM Mtimet S
  Kochbati S Zouari R Ayed M Gharbi T Hila. J
  Rheumatol 1992 Jun19(6)913-6
• Bohan A, Peter J. Polymyositis and
  dermatomyositis. N Engl J Med  1975 292403-407
• Douglas WW, Tazelaar HD, Hartman TE, et al
  Polymyositis-dermatomyositisassociated
  interstitial lung disease. Am J Respir Crit Care
  Med 2001 1641182-1185.
• 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
  32273-284.
• Shi JH Liu HR Xu WB Feng RE Zhang ZH Tian
  XL Zhu YJ. Pulmonary Manifestations of
  Sjogren's Syndrome. Respiration. 2009 Apr
  2278(4)377-386.

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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 119471
• 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