Pulmonary Alveolar Proteinosis
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Transcript of Pulmonary Alveolar Proteinosis
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PULMONARY GRAND
ROUNDS
Salman Alim
Pulmonary Critical Care Fellow
Cleveland Clinic Florida
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HISTORY
CC: Shortness of breath
HPI:47 yo female who was presented to Northwest Medical Center on 08/18/14 for shortness of breath at rest
No history of fever and chills
Cough which is seldom productive,
No orthopnea, No PND or leg swelling
No history of wheezing, atopy
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10 days prior to presentation, she was
treated by urgent care with PO antibiotics
with a presumed diagnosis of pneumonia
3 months ago, she was told by her PCP
about abnormal CXR and was
recommended to have a CT Chest done
She did not have any respiratory symptoms
hence she did not get the CT Chest
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PMH & PSH Irritable bowel syndrome
Dyslipidemia
GERD
Anxiety
Dyslipidemia
PSH: History of gastric bypass, History of breast augmentation
Denied history of COPD, Asthma, history of lupus, arthritis, congestive heart failure
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MEDICATIONS
Xanax 0.5 mg QHS PRN
Nexium 40 mg PO Daily
Percocet 5/325 1 tab PO Q4 PRN
Potassium Chloride 20 meq PO Daily
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SOCIAL HISTORY
Smoker: ½ PPD x 20 yrs
Alcohol: Glass of wine with meals
nearly every night
Occupation: Works as a RN.
Exposures: Denies any exposure to
asbestos, does not have any birds or
cats in the house
Travel: Jamaica 2 yrs ago for vacation
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FAMILY HISTORY
No family history of connective tissue disease
No family history of lung cancer
Review of Systems
No weight loss, no changes in appetite
No problems with bowel or bladder reported
Denies morning stiffness of the joints
Denies any numbness, tingling or weakness in either
extremity
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PHYSICAL EXAM
General: AO x3, in no distress
HEENT: Moist mucus membranes
Skin: No ulcers, no rashes
Neck: Supple, No palpable thyroid
Chest: CTA B/L with basilar crackles
Abdomen: Soft Obese NT, + BS
Extremities: No edema B/L
Musculoskeletal: No joint deformities, no
synovitis
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ABG: 7.4/38/66 O2 Sat 93% on Room Air
CBC
Hb/Hct 13/38.6
WBC 8.22 (N-68%, Eos-0.1%, Lymph- 22.7)
Plt 200
BMP
Na 140, K 3.1, Cl 102, CO2 29,
BUN/Cr 12/0.96
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IMAGING STUDIES
CXR
CT CHEST
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ANA 1:80
RF negative
Anti CCP negative
Other rheumatological work up not
available
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Pulmonary Function Tests
(10/22/2014)Spirometry
FVC (2.28 L) 74%
FEV1 (2.06 L) 78%
FEV/FVC 90
Lung Volumes
• FRC 90%
• RV 103.6%
• TLC 83.5%
Lung Diffusion Capacity
• DLCO 56%
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PATHOLOGY
Underwent VATS wedge biopsy of the
left lung
Patchy air space filling process
Airspace exudate comprising granular
eosinophilic debris containing
occasional macrophages and “cell
ghosts”
Findings are diagnostic of PAP
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PULMONARY ALEVOLAR
PROTEINOSIS
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PAP OR PA
Phospholipoproteinosis Diffuse lung disease characterized by accumulation
of amorphous PAS positive lipoproteinaceous
material in the distal airways
Incidence: 3 per million, more common in males
Symptoms: Cough, Dyspnea, low grade fever.
1/3 of patients can be asymptomatic
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CAUSES OF PAP
CONGENITAL
Mutations in surfactant
Mutations in GM-CSF receptor
Secondary
Allogeneic bone marrow transplantation for myeloid malignancy
Hematologic malignancy
Infections (Nocarida, PCP, viral)
Pneumoconioses (Acute silica, aluminum dust, titanium)
Acquired or autoimmune
Anti GM CSF antibodies
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PATHOGENESIS
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Anti GM-CSF
Elevated anti GM-CSF titer is 100% sensitive and 91-98% specific for acquired PAP
BAL levels correlate better than serum
Useful in monitoring of disease activity
Concentration > 19 micrograms/ml is specific for autoimmune PAP while <10 has a good negative predictive value
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Diagnostic accuracy of PAS staining of fluid obtained
by BAL and tissue obtained by transbronchial biopsy
has reduced the need for open or throacoscopic lung
biosy
In a case series of 248 patients –
diagnosis was made by
HRCT and BAL 59%
HRCT, BAL and TBBX 34%
VATs biopsy 7%
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RADIOLOGY – “Crazy
Paving” Reticular pattern superimposed on
ground glass opacity
Appearance of paths made with
broken pieces of glass or concrete
Ground Glass – presence of airspace
abnormalities
Reticular pattern – thickening of the
intralobular interstitium
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Crazy Paving
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Differential Diagnosis of Crazy
Paving
Crazy paving is not pathognomic for PAP
Several other conditions can cause Crazy Paving
such as:
Infection: PCP
Neoplasm: Mucinous Bronchoalveolar
Idiopathic: Sarcoidosis
Inhalation: Lipoid Pneumonia
ARDS, Pulmonary Hemorrhage Syndrome
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TREATMENT
Whole Lung Lavage
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Clinical course is variable
30-40% of patients require only one
lavage
Rest require repeat lavages every 6-
12 months
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GM-CSF
(Sargramostim; Bayer) can be inhaled
or delivered subcutaneously
All data is derived from small trials
In a trial of 25 patients who received
subcutaneous GM-CSF, 48% improved
in terms of A-a gradient and 6 min walk
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Inahled GM-CSF
In a Japanese trial of 12 patients, 68%
of the patients showed improvement
Currently, a clinical trial using inhaled
GM CSF is underway being conducted
at Childrens Hospital of Cincinnati
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Rituximab
Monoclonal Ab directed against CD20 antigen on B
lymphocytes
Deplete antigen presenting B cells – affecting T cell
activation – decreasing cytokine production and
amount of plasma cells producing GM-CSF auto
antibodies
Current data about use of Rituximab is limited to
case reports only
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Plasmapheresis
Anti Gm-CSF titres are reduced
In some cases, CXR and A-a gradient
improvement has been described.
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Clinical Course of PAP
Rule of 1/3
1/3 remain stable
1/3 improve
1/3 are likely to develop progressive
disease
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Treatment Approach