IDIOPATHIC PLEURAL EFFUSIONS AND
RHEUMATOID LUNG
Melissa Mattison, M.D.
January 24, 2003
Mechanism of Pleural Fluid Accumulation: steady state of pleural fluid formation and reabsorption is altered, such
that more fluid is produced or less is resorbed (or both).
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Increased fluid entry: increase in permeability or microvascular pressure changing the balance of
hydrostatic and osmotic forces across the semipermeable membrane of the microvessels. Decreases in
pleural pressure or plasma osmotic pressure can also increase fluid entry.
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Decreased fluid exit: Due to intrinsic factors (e.g., endotoxin formation, endocrine abnl such as
hypothyroidism, injury due to XRT, chemotherapy, infiltration of lymphatics, anatomic abnl) or extrinsic
factors (e.g., extrinsic lymphatic compression, such as in pulmonary fibrosis, limitation of respiratory motion,
decreased intrapleural pressure, increased systemic venous pressure)
Diagnosis – accomplished by pleural fluid analysis. Indication for thoracentesis is any new pleural effusion.
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Light’s Criteria – if any one of the three are present, it’s an exudates:
o Pleural Fluid (PF) protein/Serum protein ratio > 0.5
o PF LDH/Serum LDH > 0.6
o PF LDH > 2/3 upper limits of normal of the serum LDH
Transudate = due to imbalance of hydrostatic and oncotic pressure
Exudate = caused by pleural and lung inflammation or impaired lymphatic drainage (either way leading to
an increase in protein in the pleural space).
Parapneumonic Effusion – occurs in the setting of pneumonia (occurs in 40% of patients admitted
with pna). Divided into uncomplicated, complicated and thoracic empyema
Idiopathic Pleural Effusion
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13-20% of patients with pleural effusion have no obvious cause despite an exhaustive work-up.
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Controversy exists over optimal management (i.e., conservative versus more invasive). In the past, if a
patient had a positive PPD and an “idiopathic” pleural effusion, anti-TB therapy was recommended.
However, more recent data suggests that if the adenosine deaminase level is not elevated, this is not
warranted.
o In fact, in a prospective study of 40 patients with idiopathic pleural effusion, mean age 58, followed
for 10 years, effusions resolved in a mean time of 5.6 months. 32 cases (80%) had no identifiable
cause. 3 patients had asbestos-related effusions, one each with the following: pulmonary
adenocarcinoma, mesothelioma, hepatic cirrhosis, congestive heart failure and rheumatoid arthritis.
TB was not found in any of the patients despite a positive PPD in 19 of the patients. (Note: ADA
levels were not elevated in any of the 40 patients enrolled in the study.)
Diagnostic approach to an effusion begins with thoracentesis and determination of transudate vs. exudate.
If exudate, see if etiology is clear, such that AFB, cytology, infection, esophageal rupture etc are considered.
If no diagnosis yet, consider Pulmonary Embolism as cause. If still no diagnosis, proceed to needle biopsy
of the pleura. Check for AFB, culture of TB etc, rule out malignancy. If still not diagnostic, consider
thoracoscopy or open pleural biopsy.
Rheumatoid Arthritis
Definition: Progressive, systemic, autoimmune process characterized by chronic symmetrical erosive synovitis +/nonarticular manifestations (e.g., subQ nodules, vasculitis, pericarditis, mononeuritis multiplex, episcleritis, pleural or
pulm abnl)
Incidence 0.2-0.3/1000 person years, rising incidence with increasing age, up until 70’s
Male to female ratio 1:2 to 1:4
Criteria for Diagnosis: Need at least 4 of the following:
1. Morning stiffness (lasting > 1 hour)
2. Arthritis (soft-tissue swelling or fluid) of 3 or more joints (PIP, MCP, wrist, elbow, ankle, MTP joints)
3. Arthritis of hand joints (swelling of at least one wrist, MCP or PIP joint)
4. Symmetric arthritis
5. Rheumatoid Nodules
6. Serum RF positivity
7. Radiographic hand or wrist changes typical of RA
Generally, 1-2 years between symptom onset and diagnosis. Symptoms often start out in a non-specific fashion with
fatigue, generalized weakness, anorexia, vague musculoskeletal symptoms and eventually synovitis. 10% of
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patients present acutely with a more fulminant symptomatology with rapid development of polyarthritis and other
constitutional symptoms, including fever, lymphadenopathy, splenomegaly.
Extraarticular Lung Manifestations – can be difficult to differentiate from infection secondary to immunosuppression,
overlapping clinical syndrome or medical condition, drug-related disease from side effect of drugs used to treat RA.
Epidemiology – difficult to estimate, but Interstitial Lung Disease and pleural disease are probably the most common.
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Interstitial Lung Disease (ILD) – most common manifestation of rheumatoid lung disease. RA-ILD is very
similar to idiopathic pulmonary fibrosis (IPF). More common in patients with severe RA. RA-ILD can be
asymptomatic. Smoking is a risk factor. ILD become symptomatic as the disease severity worsens. RAILD usually post-dates the onset of joint symptoms by up to 5 years, but it can occasionally precede joint
disease. Symptoms are usually insidious at onset (e.g., DOE, nonproductive cough, fever, chest pain).
Physical findings (i.e., bibasilar rales, clubbing, signs of pulmonary hypertension and respiratory failure) are
often only evident late in the course of the illness.
o Biopsy – typical histological findings include Usual Interstitial Pneumonitis (UIP), Nonspecific
Interstitial Pneumonitis (NSIP), Lymphocytic Interstitial Pneumonitis (LIP), Desquamative Interstitial
Pneumonitis (DIP)
o Imaging findings:
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CXR – bibasilar alveolar opacities, reticulonodular shadowing, honeycombing
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HRCT – high res CT – shows abnl sooner than CXR, and will reveal a range of
parenchymal abnl, including bonchiectasis or bronchiolectasis without fibrosis, ground
glass attenuation, nonseptal linear attenuation, honeycombing
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Pleural Disease – very common but usually sub clinical, male predominance. Autopsy studies estimate
frequency of pleural disease to be 38-73% but only 21% of patients c/o pleurisy (as do 12% of controls).
Pleural disease often coexists with rheumatoid nodules and ILD in 30% of patients. Only 5% have
radiographic evidence of effusion, thus they are usually small moderate in size, and unilateral. Usually
occurs in patients with long-standing history of rheumatoid arthritis, but may predate the diagnosis.
o Symptoms: Chest pain, and/or fever. Dyspnea if large enough of an effusion
o Thoracentesis: typical findings include:
o Wbc < 5000/mm3
o Serous to a milky-green appearance
o Protein > 3 g/dL (exudate)
o Glucose < 5 mmol
o LDH > 1000 U/mL
o pH 7
o RF > 1:320
o Complement = low
o Cytology
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cell # < 5000/mm3
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cell type : lymphocytes (neutrophils and eos acutely) and the “RA cell”
(neutrophil with inclusion bodies)
o Management: thoracentesis to diagnose the effusion and rule out other process (i.e., infection,
malignancy). Symptomatic pleuritis and effusions from RA generally resolve spontaneously over
months, but initial treatment includes NSAIDs (indomethacin). Can also consider systemic
corticosteroids or even intrapleural corticosteroids
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Bronchiolitis Obliterans Organizing Pneumonia (BOOP) – patients with RA who develop BOOP present
with cough, dysnpea, malaise, weight loss and fever. Diagnosis typically made with transbronchial or
throacoscopic lung biopsy.
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Other : Obliterative bronchiolitis, Follicular bronchiolitis, Vasculiltis, Nodules
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