Pulmonary Manifestations Of Rheumatoid Arthritis

1
Pulmonary Manifestations Of Rheumatoid Arthritis

• Dr. Gina Rohekar

2
Overview

• Major catagories of pulmonary disease associated
  with RA
• Pleural effusion
• Nodular lung disease
• Diffuse interstitial fibrosis
• BOOP (bronchiolitis obliterans organizing
  pneumonia)
• Pulmonary vasculitis
• Alveolar hemmorhage
• Obstructive disease
• Infections

3
History

• Pulmonary manifestations of RA first described in
  1948 by Ellman and Ball
• Diffuse pulmonary fibrosis in 3 patients with RA

4
Rheumatoid Arthritis And The Lung

• Broad differential for pleuropulmonary disease in
  those with rheumatologic disorders
• Secondary to, or associated with the underlying
  rheumatic disease
• Secondary to immunosuppression (infection)
• Secondary to drug therapy
• Coexistant medical problems
• Overlap syndromes

5
Epidemiology

• Difficult to characterize the epidemiology of
  pulmonary manifestations
• Heterogenous patient populations
• Early versus late disease
• Community versus hospital studies
• Living versus autopsy findings
• Patients closely monitored and quickly treated

6
(No Transcript)
7
Pleural Effusion

• Most common pulmonary manifestation of RA
• Often incidental finding on CXR
• Post-mortem studies ? almost 50 of patients with
  RA have pleural effusions
• Can be uni- or bilateral, resolve, recur or
  persist for months

8
(No Transcript)
9
(No Transcript)
10
Pleural Effusion

• Patients often asymptomatic
• ?Reduced physical activity prevents symptoms
• Most common symptoms pleuritic pain, dyspnea,
  cough
• Pleural effusions can precede or occur
  simultaneously with joint symptoms in 25
• More common in men with high RF titer and active
  arthritis

11
Pleural Effusion

• Pleural effusion findings
• Exudative fluid
• Low compliment level
• Low glucose
• High LDH
• Low pH (lt7.2)
• High protein
• RF level higher than serum RF level
• High PMNs with RA cells and mononuclear cells
• RA cells ? polymorphonuclear leukocytes
  containing dense black granules
• Release rheumatoid factor when disintegrated

12
Unique pleural fluid findings in RA. Triad of
comet cells, giant cells and background of
granular material. Seen in as many as 80 of
pleural specimens and are considered unique to
RA. These findings are the result of the
exfoliation of pleural components from regions of
granulomatous pleuritis. The RA cell (or
ragocyte) is a leukocyte with small cytoplasmic
lipid inclusions containing RF. These may also
be seen in TB.
Source Johns Hopkins Arthritis
13
Pleural Effusion

• Treatment
• None needed if asymptomatic
• Repeated thoracentesis or pleurodesis
• NSAIDs, steroids
• Intrapleural steroids
• Probably best to control the underlying RA

14
Other Pleural Abnormalities

• Empyema
• Necrosis and cavitation of rheumatoid nodule
  leading to effusion
• Bronchopleural fistula
• Pyopneumothorax
• Chronic pleural thickening ? chyliform effusion
  or lung entrapment

15
Nodular Lung Disease

• Pulmonary nodules in RA first described by Caplan
  in 1953
• Discovered multiple bilateral nodules on CXR of
  coal miners with RA
• Caplans syndrome Pneumoconiosis in RA patient
  leading to multiple basilar pulmonary nodules and
  mild airflow obstruction
• Only pulmonary manifestation specific for RA
• Can occur before, with or after the joint
  manifestations of RA
• Usually asymptomatic, but can cause coughing and
  rarely hemoptysis

16
Nodular Lung Disease
17
Nodular Lung Disease

• Usually multiple, bilateral nodules
• Range from few millimeters to several centimeters
  in size
• Typically occur just below the pleura or
  associated with interlobular septa
• Can lead to bronchopleural fistula, pneumothorax,
  abcess or cavition
• Can remain static, resolve, increase in size or
  undergo malignant transformation
• More common in men, ?association with smoking

18
Nodular Lung Disease
19
Nodular Lung Disease
20
Nodular Lung Disease

• Histologically similar to RA nodules found
  elsewhere
• Central necrosis, palisading epithelioid cells,
  mononuclear cell infiltrate and associated
  vasculitis
• Caplans syndrome ? nodules often contain coal
  dust

21
Nodular Lung Disease
22
Nodular Lung Disease

• Management ? usually observation suffices
• Transbronchial biopsy or transthoracic needle
  aspiration to rule out malignancy or other
  pathologic process

23
Diffuse Interstitial Fibrosis

• Described in 40 of RA patients
• Frequently similar to IPF
• Chronic inflammatory changes in the alveolar wall
  with the presence of large mononuclear cells in
  the alveolar spaces
• As disease progresses ? fibrosis with
  obliteration of alveoli and dilatation of
  bronchioles
• Early disease tends to affect the lung bases
  late disease affects the apices

24
Diffuse Interstitial Fibrosis

• More common in those with severe RA
• Most modifiable risk factor smoking
• gt25 pack-year smoking history significantly more
  likely to have radiographic evidence of ILD
• More common age 50-60, in men and in seropositive
  and erosive joint disease
• Usually occurs about five years after joint
  symptoms present, but can predate them

25
Diffuse Interstitial Fibrosis

• Occurs mostly in those with subcutaneous nodules
  and high RF
• Symptoms progressive SOBOE and productive cough
  most common
• Also increased RR, clubbing, crepitations at
  lung bases, pulmonary hypertension
• CXR ? Reticulated pattern with progression to
  fine nodularity and honeycombing

26
(No Transcript)
27
Diffuse Interstitial Fibrosis

• Histology
• Usual interstitial pneumonitis (UIP), the
  pathologic correlate of IPF, which is most common
• Nonspecific interstitial pneumonitis (NSIP)
• Lymphocytic interstitial pneumonitis (LIP)
• Desquaminative interstitial pneumonitis (DIP)
• Bronchiolitis obliterans with organizing
  pneumonia (BOOP)
• Mixed morphology

28
(No Transcript)
29
Diffuse Interstitial Fibrosis

• Prognosis is poor, but appears better than for
  IPF
• Treatment usually includes corticosteroids,
  azathioprine or other immunomodulating
  medications (e.g., cyclophosphamide)
• ?Single lung tranplantation
• Usually better results in those with RA
  associated interstitial fibrosis than those with
  IPF
• Usually too many comorbidities for
  transplantation surgery (e.g., osteoporosis,
  decreased mobility)
• ?Newer therapies (e.g., TNF blockers)

30
Diffuse Interstitial Fibrosis
31
BOOP

• Number of studies have noted an association
  between RA and BOOP
• Study of open lung biopsies from 40 patients with
  parenchymal lung disease and RA ? BOOP second
  most common finding following rheumatoid nodules
• Patents present with cough, SOB, malaise, weight
  loss and fever
• Crackles noted on physical exam

32
BOOP

• Diagnostic tests
• ESR usually elevated
• CXR bilateral parenchymal opacities, often
  with preserved lung volume
• PFTs restrictive physiology with decreased
  DLCO and hypoxemia
• HRCT uni- or bilateral consolidation
• Often patchy and peripheral

33
(No Transcript)
34
BOOP

• Biopsy shows patchy intraluminal polypoid plugs
  of immature fibroblast tissue within bronchioles
• Terminal bronchioles and peribronchiolar alveolar
  spaces may also be involved

35
BOOP

• Prognosis good for those patients who receive
  treatment
• Most respond to oral corticosteroid therapy
• If not tolerated, cyclophosphamide used
• Antibiotics not helpful

36
Pulmonary Vasculitis

• Vascular inflammation can affect any organ site
  in those with RA
• Most commonly the skin
• Seen in patients with severe RA, high RF titers
• Usually other signs of systemic vasculitis
• Usually in Caucasians, uncommon in those of
  African ancestry
• Can lead to pulmonary hypertension

37
Pulmonary Vasculitis

• RA associated pulmonary vasculitis has been
  treated with corticosteroisds and cytotoxic
  medications (e.g., cylcophosphamide)
• Penacillamine and gold salts tried with varying
  results

38
Alveolar Hemorrhage

• Diffuse bleeding from the pulmonary vasculature
  leading to blood-filled alveoli
• Causes a classic triad
• Hemoptysis
• Diffuse infiltrates
• Anemia
• Erythrocytes and fibrin fill the airspaces
• Often also see hemosiderin-filled macrophages
• 88 of those with alveolar hemorrhage and RA have
  capillaritis limited to the alveolar wall

39
(No Transcript)
40
Alveolar Hemorrhage

• Diagnosis aided by measurement of DLCO
• DCLO will be increased due to carbon monoxide
  binding to the erythrocytes in the alveoli

41
Obstructive Pulmonary Disease

• Found in 38-68 of patients with RA
• Can be upper or lower obstruction
• Upper obstruction more common in women and those
  with longstanding disease
• Ankylosis of the cricoarytenoid joint
• Rheumatoid nodule on vocal cord
• Vasculitis of recurrent laryngeal or vagus nerves

42
(No Transcript)
43
Obstructive Pulmonary Disease

• Lower airway obstruction
• Difficult to estimate prevalence
• Some studies suggest as high as 60, but
  prevalence in non-smokers 0-24
• ? Association with underlying Sjögrens syndrome
• Primary abnormality on autopsy is fibrous
  narrowing or obliteration of airways 1-6 mm in
  diameter
• Present with SOB, crackles and high-pitched
  wheezes
• CXR shows hyperinflated lung

44
Infections

• Persistent problem in those with RA
• Many confounding factors, especially
  corticosteroid or immunosuppressive medication
• May mask the signs of infection
• Lymphocyte abnormalities in RA?
• Patients with RA have greater occurrence of
  bronchitis, bronchiectasis and pneumonia than
  controls with degenerative joint disease

45
Drug Related Pulmonary Disease
46
Drug Related Pulmonary Disease

• Methotrexate
• Presents with dyspnea, cough and fever
• Usually subacute
• 50 of cases diagnosed within 32 weeks of
  initiating MTX
• Re-challenge with MTX causes high rate of
  recurrence of lung injury
• 17 of patients who develop lung disease due to
  MTX will die of this complication

47
Summary

• Patient with RA presenting with respiratory
  symptoms needs to be completely evaluated
• Rheumatoid associated lung disease

Pleural effusion Nodular lung disease Diffuse
interstitial fibrosis BOOP (bronchiolitis
obliterans organizing pneumonia) Pulmonary
vasculitis Alveolar hemmorhage Obstructive
disease Infections
48
Summary

• Also remember
• Pulmonary disease secondary to medications used
  to treat RA
• Coexistent medical conditions (asthma, CHF)
• Overlapping clinical syndromes

49
Any Questions?

• Thank you!