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08 2019 manila difficult pleural management pdf
1. Professor, University of Western Australia
Director, Pleural Services, Sir Charles Gairdner Hospital
Head, Pleural Medicine Unit, Institute for Respiratory Health
MRFF Practitioner Fellow
Y C Gary Lee
MBChB PhD FCCP FRCP FRACP
Difficult / Uncommon
Pleural Effusion Management
2. • Pleural effusion: 3000 / million population each yr
• Annual incidence of pleural effusions in USA
CONGESTIVE HEART FAILURE 500,000
PNEUMONIA 300,000
MALIGNANT EFFUSION 200,000
PULMONARY EMBOLISM 150,000
UNDIAGNOSED (?VIRAL) 100,000
POST-CABG 50,000
CIRRHOSIS WITH ASCITES 50,000
GASTROINTESTINAL DISEASE 25,000
CONNECTIVE TISSUE DISEASE 6,000
TUBERCULOSIS 3,000
Pleural Effusions
6. TB Pleural Effusion
• Rising incidence (eg AIDS; immunosuppressants)
Overall ~ 1 in 30 patients with TB
TB patients with HIV (38% in one series from S. Africa)
• Geographical variations in incidence:
USA ~3000 cases/yr; Endemic areas: commonest exudates
Textbook of Pleural Disease 3rd ed; Light RW and Lee YCG
• TB Effusions often difficult to diagnose
Diagnosis often delayed in non-endemic areas because of
lack of clinical suspicion
Over-diagnosis common in endemic regions
7. TB Pleural Effusion: Etiology
Rupture of peripheral loci of mycobacteria in the lung
(often undetectable) ► pleural cavity
• Actual bacterial load is usually very small
• Bacteria need not be viable: culture often –ve
Mycobacterial protein elicits a type IV (delayed)
hypersensitivity reaction in pleura
• Caseating granulomata characteristic
• Diffuse involvement of the pleura
Hypersensitivity inflammatory reaction
• ↑ vascular permeability; exudative effusions
8. • Symptoms non-specific: Constitutional, Cough, SOB
• Often no known TB contact: reactivated latent infection
• Up to 50% have no detectable TB elsewhere
• Size: most small to moderate; 5% are massive effusions
• Occur in any age group/origin (next slide)
TB Pleuritis: diagnostic challenge
Typical Pleural Fluid characteristics:
• Exudative: Protein often high (eg >50g/L)
• Lymphocytic predominant: >50% WBC in 95% pts
• Few mesothelial cells in fluid: Generalized pleuritis
‘covered’ the mesothelium, minimizing shedding
10. Diagnosis often based on caseating
granuloma in pleural tissue
Most patients diagnosed with TB effusions do not have
microbiologic confirmation
• Closed (Blind) pleural biopsy
Abram needle or Cope’s needle
• Thoracoscopic biopsy
• Image-guided biopsy (especially CT)
11. Diacon AH et al. Eur Respir J 2003
• Randomized study of diagnosis of TB pleuritis:
pleuroscopy biopsy vs closed Abram biopsy
• Pleuroscopy sensitivity 100%
Abram biopsy 79%
Indication: Diagnosis of TB Pleuritis
As the pleura is diffusely involved, blind biopsy often is
adequate to detect granuloma
Should be used in initial workup in endemic areas
12. • Adenosine Deaminase (ADA)
• Polymerase Chain Reaction (PCR)
• Interferon- (IFN)
• ‘ELISPOT’ or Quantiferon test
TB Effusion: Search for a diagnostic marker
Routine workup of effusion in many countries
• An enzyme present in lymphocytes; Activity in vitro
related to proliferation / differentiation
• ADA unit: Enzymatic activity to produce 1 mol of
ammonia/min from adenosine at standard assay conditions
13. Valdes L et al. Eur Respir J 1996
False positives:
• Empyema
• Rheumatologic
• Other lymphocytic
e.g. lymphoma,
malignant, chylothorax
etc.
• Limiting ADA testing to lymphocytic effusions
can easily avoid most of the false +ve
14. ADA for TB pleural effusions
Applies Pediatrics Mishra et al. Arch Dis Child 2006
Immunosuppressed
Renal transplant Chung JH et al. Yonsei Med J 2004
HIV/AIDS patients Riantawan P et al. Chest 1999
Meta-analysis (63 studies):
Sensitivity 92%; Specificity 90%
Positive likelihood ratio: 9.0
Negative likelihood ratio: 0.1
Diagnostic odds ratio: 110.1
Liang Q-L Respir Med 2008
15. ADA for TB pleural effusions
Negative Predictive Values
• 99% (n=410 lymph effusions)
Castro D et al. ERJ 2003
• 94% (endemic area)
Chen ML et al. Clin Chim Acta 2004
• post-test prob 0.4% (non-endemic)
Greco et al. IJTLD 2004
Very valuable test to rule out TB in lymphocytic
effusions esp in non-endemic countries (avoid bx)
16. TB pleural effusion: Natural Course
• Most TB effusions spontaneously resolve within
2-4 months [historic data, Finnish Armed Forces 1939-45]
• ~10% develop pleural thickening - usually mild
with no functional sequalae
• Pleural fibrosis is not reduced by
⸱ drainage of effusion ⸱ corticosteroids
So why do we treat TB pleuritis?
17. TB pleural effusion: Natural Course
• Mycobacteria enters the pleura via other organs
(usually the lung)
• TB pleuritis usually heals with / without treatment,
but untreated patients high risk (~60%) of
developing active TB elsewhere (usually lung)
within a few years of the pleural effusion
18. Treatment
• Standard TB Treatment according to local
resistance pattern
• Use of high dose oral corticosteroid controversial
- improve fluid drainage; improve symptoms
- no difference to long-term outcome
- steroid side effects
- risk of Kaposi’s sarcoma in HIV +ve
• Drainage of effusion if symptomatic
- Pleurodesis not indicated as fluid should settle
21. Rheumatoid Pleuritis
• ~40% of RA patients have pleural disease at autopsy
• ~20% pleuritic pain; 5% clinically evident pleural disease
• Usually with severe arthritis and subcutaneous nodules
• M>F; mean age 51
• Dx of exclusion Pleural EffusionsPleural Effusions
• Uncommon 2-3%
• Usually small; resolve spontaneously
• 25% bilateral, no predilection for side
• Fluid analysis does not differentiate:
Exudative; pH & glucose, LDH
• Pleural fluid Rheum Factor not useful
• ADA may be elevated in RA
Pleural fluid cytology
27. Chylothorax Pseudochylothorax
Biochemistry Triglyceride Cholesterol
Fluid color Creamy Creamy
Features Chylomicrons Cholesterol crystal
Light RW & Lee YCG.
In: Murray & Nadel’s Textbook of Respiratory Diseases, 5th ed, 2010
If chylous; then need to separate
28. Pseudochylothorax
• TB and Rheumatoid pleuritis most common causes
• Conventional textbooks all said pseudochylothorax only
occurs with very thickened pleura
• Now disproved, at least in RA-related Pseudochylothorax
• Wrightson et al CHEST 2009
29. Pleural Amyloidosis
• Protein folding disorders:
insoluble B-rich fibrils into organs
• Refractory effusions: usually in AL (6-18%)
• 60% transudative, often unilateral
• Dx: Biopsy with amyloid infiltration on Apple green
birefringence/Congo red stain
32. Drug related effusion
Bilateral eosinophilic effusions
presumed related to clozapine
Bx usually non-specific inflammation +/- granuloma
Dx by exclusion; re-challenge rarely advisable
33. Pulmonary emboli related effusion
Pleural effusion in 48% of pts with CTPA proven PE
Effusions are inevitably small. If large, consider
alternative causes
Yap E et al Respirology 2008
34. IgG4-Related Disease
• Systemic, immune-mediated disease
- Characterised by
- raised serum IgG4
- tissue infiltration by IgG4+ plasma cells
• Relatively new disease
- 1961 - “Autoimmune pancreatitis”
- 2001 - Association with IgG4 established
- 2003 - Extra-pancreatic manifestations recognized
37. Diagnosis
• Requires high index of suspicion
- Clinical features & raised serum IgG4
(>1.35 g/L) are suggestive
• Histopathology essential for diagnosis
- Lymphoplasmacytic infiltration:
- >10 IgG4+ cells per HPF
- >40% IgG+ plasma cells are IgG4
- Fibrosis with storiform features
- Obliterative phlebitis
38. IgG4 Disease Management
• Most cases respond to steroids
- Prednisolone (0.6mg/kg/day x 2-4wks)
- Maintenance 2.5-5mg/day for up to 3yrs
• Steroid-sparing therapy (AZA, MMF, Mtx)
• Reports of response to rituximab
• Monitor IgG4 levels & for end-organ damage
- IgG4 remains elevated in 63%
• 25-50% relapse, chronic disease
• Future malignancy risk
39. What is the diagnosis
Intercostal artery bleed
What should we do next?
a) Urgent thoracotomy/VATS
b) Intercostal artery embolisation
c) CT angiogram
40. • Resuscitated
IV fluids and blood transfusions
Chest drain inserted – drained 100ml blood/15 min
• Remained hypotensive & hemodynamically
unstable
Case 5
41. Intercostal Artery Bleeding
• Highest risk posteriorly
- vessels are not protected by
rib flange till angle of rib
- increased vessel tortuosity
Carney et al. Chest 1979
Fox et al. Radiology 2003
• Avoid the first 10 cm of
the ICA
• Avoid choosing pleural
puncture sites at the
posterior medial aspects
42. Intercostal Artery Bleeding
Specific Management
• External pressure over intercostal space
• Suture around the rib medial to pleural entry site
• Thoracic surgery is often required (especially if large
residual clots that need evacuation)
• ICA embolisation is an alternative option if available
43. Points to Ponder
• > 60 causes of pleural effusions
• Most effusions given one diagnosis and assumed to
arise from a single etiology. Too simplistic?
• Disease-specific markers now can help decode co-
existing diseases and contributing etiologies
44. pleura.com.au
THE PLEURAL MEDICINE UNIT
Sir Charles Gairdner Hospital,
Harry Perkins Institute of Medical Research, Perth, Australia
gary.lee@uwa.edu.au