Pulmonary Alveolar Proteinosis
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1 January 2001 Pulmonary Alveolar Proteinosis Brady Case, Harvard Medical School 1
2 Our Patient Nelson is a 40 year-old male who presents with a 6 month history of: progressive dyspnea on exertion dry cough w/ occasional jello-like white sputum 7 kg weight loss fatigue mild chills 2
3 Past Medical History Longstanding bipolar disorder Question of alcoholic cirrhosis 3
4 Social History 40 pack-year smoking hx heavy alcohol abuse, with multiple rehabilitation failures 10 yr h/o crack cocaine use; last use 4 years ago; denies IVDU Last HIV test 1 year ago negative by report Chronic occupational silica exposure as a stone crusher 4
5 Physical Exam Low grade fever Tachycardia, tachypneia 90% O2 saturation on room air Mild bibasilar crackles on lung auscultation The pt was sent for a PA chest plain film 5
6 Posterior-Anterior Chest Plain Film Image courtesy BIDMC 6
7 Posterior-Anterior Chest Plain Film - Findings Left CVA is not included on the film Image courtesy BIDMC 7
8 Posterior-Anterior Chest Plain Film Left CVA is not included on the film Diffuse, bilateral, fluffy opacities with air bronchograms suggestive of... Image courtesy BIDMC 8
9 Posterior-Anterior Chest Plain Film Left CVA is not included on the film Diffuse, bilateral, fluffy opacities with air bronchograms suggestive of... alveolar consolidation Image courtesy BIDMC 9
10 DDx for Acute Bilateral Alveolar Infiltrates MORE COMMON LESS COMMON ARDS; Oxygen toxicity Edema, multiple etiologies Hyaline membrane disease Pneumonia, esp. opportunistic or atypical (eg - PCP, viral, mycoplasma, fungal, parasitic) Fat Embolism Hemorrhage 10
11 DDx for Chronic Bilateral Alveolar Infiltrates MORE COMMON Alveolar Proteinosis Bronchiolealveolar Carcinoma Interstitial Pneumonitis Desquamative or Lymphocytic Lymphoma Mycosis Fungoides Sarcoidosis 11
12 DDx for Chronic Bilateral Alveolar Infiltrates MORE COMMON LESS COMMON Alveolar Proteinosis Bronchiolealveolar Carcinoma Interstitial Pneumonitis Desquamative or Lymphocytic Lymphoma Mycosis Fungoides Sarcoidosis Alveolar Microlithiasis Lipoid Pneumonia (eg mineral oil aspiration) Hemorrhagic Metastases Silicoproteinosis Tuberculosis Other Infectious Fungal Etiologies 12
13 Narrowed DDx for Our Patient MORE COMMON LESS COMMON Alveolar Proteinosis Bronchio-Alveolar Carcinoma Silicoproteinosis Tuberculosis Other Infectious Fungal Etiologies 13
14 Further Diagnostics The patient was scheduled for high resolution computed tomography (HRCT) of the chest, fiberoptic bronchoscopy with transbronchial biopsy, and bronchoalveolar lavage. A preliminary helical CT scan revealed two lung findings of interest. 14
15 Routine Helical Chest CT Image courtesy BIDMC 15
16 Routine Helical Chest CT Film findings: Diffuse, bilateral, ground glass infiltrates Image courtesy BIDMC Ground glass opacification is focal or diffuse opacification of the lung which neither obscures pulmonary vasculature nor reveals air bronchograms 16
17 DDx for Ground Glass Opacification CHRONIC Image courtesy BIDMC Alveolar Proteinosis Bronchiolealveolar Carcinoma Interstitial Pneumonitis Desquamative or Lymphocytic Hypersensitivity pneumonitis Repiratory bronchiolitisassociated interstitial lung disease Sarcoidosis 17 17
18 Ground Glass Opacification in Different Conditions Image courtesy UptoDate Pulmonary Alveolar Proteinosis Pulmonary Edema after near-drowning Pulmonary Edema after cocaine freebasing Image courtesy UptoDate Image courtesy UptoDate 18
19 Back to Our Patient: High Resolution Chest CT Image courtesy BIDMC 19
20 High Resolution Chest CT Film findings: Ground glass opacification Thickened intralobular septae in typical polygonal formation, and reticular opacities present bilaterally and fairly symmetrically. This appearance is known as crazy paving --a finding exclusive to HRCT--and is highly associated with Image courtesy BIDMC Pulmonary Alveolar Proteinosis (PAP) 20
21 High Resolution Chest CT First Finding Film findings: Aunt Minnie for PAP Ground glass opacification Thickened intralobular septae in typical polygonal formation, and reticular opacities present bilaterally and fairly symmetrically. This appearance is known as crazy paving --a finding exclusive to HRCT--and is highly associated with Image courtesy BIDMC Pulmonary Alveolar Proteinosis(PAP) 21 21
22 Pulmonary Alveolar Proteinosis Diffuse lung disease characterized by accumulation of amorphous, periodic acid-schiff (PAS)-positive lipoproteinaceous material in distal air spaces 22
23 Pulmonary Alveolar Proteinosis (PAP) Diffuse lung disease characterized by accumulation of amorphous, periodic acid-schiff (PAS)-positive lipoproteinaceous material in distal air spaces Associated with primary or acquired macrophage disfunction; alveolar proteinosis may be instigated by silica dust (silicoproteinosis) and other particulate exposure, but has been associated with infection (PCP, viral, bacterial, mycobacterial), leukemia, allogenic bone marrow transplant 23
24 Pulmonary Alveolar Proteinosis Diffuse lung disease characterized by accumulation of amorphous, periodic acid-schiff (PAS)-positive lipoproteinaceous material in distal air spaces Associated with primary or acquired macrophage disfunction; alveolar proteinosis may be instigated by silica dust (silicoproteinosis) and other particulate exposure, but has been associated with infection (PCP, viral, bacterial, mycobacterial), leukemia, allogenic bone marrow transplant Presents w/ cough, dry or productive of chunky sputum, DOE, weight loss, fatigue; may present w/ crackles, clubbing, cyanosis; onset is insidious; elevated LDH 24
25 Pulmonary Alveolar Proteinosis Diffuse lung disease characterized by accumulation of amorphous, periodic acid-schiff (PAS)-positive lipoproteinaceous material in distal air spaces Associated with primary or acquired macrophage disfunction; alveolar proteinosis may be instigated by silica dust (silicoproteinosis) and other particulate exposure, but has been associated with infection (PCP, viral, bacterial, mycobacterial), leukemia, allogenic bone marrow transplant Presents w/ cough, dry or productive of chunky sputum, DOE, weight loss, fatigue; may present w/ crackles, clubbing, cyanosis; onset is insidious; elevated LDH Superinfections, particularly w/ Nocardia asteroides, are common 25
26 Pulmonary Alveolar Proteinosis Diffuse lung disease characterized by accumulation of amorphous, periodic acid-schiff (PAS)-positive lipoproteinaceous material in distal air spaces Associated with primary or acquired macrophage disfunction; alveolar proteinosis may be instigated by silica dust (silicoproteinosis) and other particulate exposure, but has been associated with infection (PCP, viral, bacterial, mycobacterial), leukemia, allogenic bone marrow transplant Presents w/ cough, dry or productive of chunky sputum, DOE, weight loss, fatigue; may present w/ crackles, clubbing, cyanosis; onset is insidious; elevated LDH Superinfections, particularly w/ Nocardia asteroides, are common Rare, (incidence of several hundred cases in the US), 2:1 Male:Female, years of age 26
27 Pulmonary Alveolar Proteinosis Diffuse lung disease characterized by accumulation of amorphous, periodic acid-schiff (PAS)-positive lipoproteinaceous material in distal air spaces Associated with primary or acquired macrophage disfunction; alveolar proteinosis may be instigated by silica dust (silicoproteinosis) and other particulate exposure, but has been associated with infection (PCP, viral, bacterial, mycobacterial), leukemia, allogenic bone marrow transplant Presents w/ cough, dry or productive of chunky sputum, DOE, weight loss, fatigue; may present w/ crackles, clubbing, cyanosis; onset is insidious; elevated LDH Superinfections, particularly w/ Nocardia asteroides, are common Rare, (incidence of several hundred cases in the US), 2:1 Male:Female, years of age Characteristic findings on plain film--diffuse bilateral alveolar infiltrates--and on High Resolution CT (HRCT)--ground glass infiltrate and crazy paving 27 27
28 Diagnostic Algorithm for PAP Our Patient: Fiberoptic bronchoscopy w/ transbronchial biopsy and diagnostic bronchoalveolar lavage were performed. Image courtesy UptoDate 28
29 Diagnosis of PAP Our Patient: Normal Lung Image courtesy UptoDate Transbronchial biopsy revealed findings of alveolar proteinosis: thickened alveolar septa and alveola filled with abundant lipoproteinaceous material that stains pink w/ PAS stain. Pulmonary Alveolar Proteinosis Image courtesy UptoDate 29
30 Diagnosis of Pulmonary Alveolar Proteinosis Lavage Fluid Image courtesy UptoDate Pulmonary Alveolar Proteinosis Our Patient: Bornchoalveolar lavage returned fluid with characteristic large acellular eosinophilic bodies and eosinophilic granules. Centrifuge and PAS stain of the fluid revealed abundant proteinaceous material. Image courtesy UptoDate 30
31 An Additional Finding A separate abnormality was demonstrated on the background findings of PAP. 31
32 Helical CT - Our Patient s Second Finding Complex, thick-walled multicystic cavitary lesion in the right upper lobe. The finding demonstrates Helical CT s role as a screening test... Image courtesy BIDMC 32
33 High Resolution CT - Our Patient s Second Finding The finding was confirmed on High Resolution CT. Image courtesy BIDMC 33
34 High Resolution CT - Second Finding Image courtesy BIDMC 34
35 DDx for Lung Cavitation MORE COMMON Abscess Bulla Bronchogenic Carcinoma (S) Fungal disease Metastasis Pneumocystis carinii pneumonia (M) Tuberculosis, other mycobacteria LESS COMMON Sarcoidosis (M) Amyloidosis Pneumoconioses Septic embolus Kaposi Sarcoma (M) Lymphoma Trauma Conditions that typically present with thin walled cavitation are presented here in non-bold print. Conditions that typically present only with single (S) or multiple (M) cavitations are so marked
36 DDx for Lung Cavitation in PAP Given the demonstrated assocation of pulmonary alveolar proteinosis with Nocardia superinfection, a presumptive diagnosis was made. 36
37 Our Patient: Further Findings Biopsy material and lavage gram stains and cultures ultimately ruled out PCP, fungal infection, nocardia (the presumed infectious agent) and other bacterial infection, and malignancy. However, acid fast stain revealed numerous red snappers. The patient was placed on precautions and begun on therapy for MDRTB pending definitive cultures. Approximately 1 hour after the procedures, the pt noted the acute onset of resting dyspnea. His O2 saturation dropped to 87% on 5L O2. A full expiration portable AP chest film was taken 37
38 AP Portable S/P Transbronchial Biopsy Image courtesy BIDMC 38
39 AP Portable S/P Transbronchial Biopsy The film is notable for a large right pneumothorax with associated findings of: shift of the mediastinum towards the left Image courtesy BIDMC 39
40 AP Portable S/P Transbronchial Biopsy The film is notable for a large right pneumothorax with associated findings of: shift of the mediastinum towards the left flattened right hemidiaphragm Image courtesy BIDMC 40
41 AP Portable S/P Transbronchial Biopsy The film is notable for a large right pneumothorax with associated findings of: shift of the mediastinum towards the left flattened right hemidiaphragm expansion of the ribcage on the right side. Image courtesy BIDMC 41
42 AP Portable S/P Transbronchial Biopsy The film is notable for a large right pneumothorax with associated findings of: shift of the mediastinum towards the left flattened right hemidiaphragm expansion of the ribcage on the right side. These findings demonstrate tension pneumothorax. Image courtesy BIDMC A right chest tube was inserted and another portable film was taken
43 AP Portable S/P Chest Intubation Image courtesy BIDMC 43
44 AP Portable S/P Chest Intubation The tension pneumo-thorax has resolved. Image courtesy BIDMC 44
45 AP Portable S/P Chest Intubation The tension pneumo-thorax has resolved. However, a small loculated pneumothorax is seen in the right lower lateral hemithorax... Image courtesy BIDMC 45
46 AP Portable S/P Chest Intubation The tension pneumo-thorax has resolved. However, a small loculated pneumothorax is seen in the right lower lateral hemithorax With stabilization, the patient was sent for consecutive bilateral, therapeutic whole lung broncheo-alveolar lavage. Image courtesy BIDMC 46 46
47 Whole Lung Bronchioalveloar Lavage Lavage returned milky fluid with a thick layer of dense, proteinaceous sediment. Lavage was continued until the returned fluid was clear. The patient made good progress, and underwent chest and endotracheal extubations. An AP chest film was taken. Image courtesy UptoDate 47
48 CXR S/P Bronchoalveolar Lavage The loculated pneumo-thorax has resolved. Compared with findings on the pt s original film, diffuse opacification is greatly reduced Image courtesy BIDMC 48
49 CXR S/P and Before Bronchoalveolar Lavage Image courtesy BIDMC After BAL Image courtesy BIDMC Before BAL 49 49
50 Treatment for Pulmonary Alveolar Proteinosis 30-40% of PAP patients require only one bronchoalveolar lavage; the remainder are treated with lavage every 6 to 12 months. Lavage is the mainstay of treatment. Image courtesy BIDMC 50
51 Endnotes Case Records of the Massachusetts General Hospital, Case N Engl J Med. 2001;344: Chan ED and King TE Jr. Pulmonary alveolar proteinosis. UpToDate. Aug. 15, Reeder MM and Bradley WG Jr. Reeder and Felson s Gamuts in Radiology. 3rd ed. Springer-Verlag. New York Stark P. High resolution computed tomography of the lungs. UpToDate. Sept. 15,
52 Acknowledgements Immense thanks to. Carlos Caceres, MD Beverlee Turner Stephen Weinberger, MD Larry Barbaras and Ben Crandall our WebMasters 52 52
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