Transcript CPC

CPC
Julye Carew, M.D.
December 11, 2003
CASE REVIEW
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41 yo AA male
No PMH, but allergic rhinitis
2 weeks of dyspnea and fever
3 ER visits-- ABX
CT angio of chest-- neg for PE, but with
bilateral lower lobe alveolar infiltrates
• Progressive course with development of
ARDS, hypoxic respiratory failure
CASE REVIEW
• MEDS: Zpack, antihistamine,
Hydrocodone, nasal steroid
• FH: NC
• SH: No habits, construction with ceramics,
fiberglass and flooring, no significant travel
CASE REVIEW
• ROS:
• POSITIVE: fever, chills, cough with clear
sputum, night sweats, fatigue
• NEGATIVE: NO hemoptysis, CP, rash,
meningismus, HA, N/V, GU or GI
symptoms
CASE REVIEW
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PE:
mild respiratory distress
T 103.6, tachycardic, tachypneic
HEENT and Neck-- negative
PULM: Inspiratory rales in bases and
dullness on left.
• Remainder of exam-- negative
• No mention of clubbing?
CASE REVIEW
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LABS:
Renal function is normal
TP 6.3, ALB 2.5
Mild transaminitis, total bilirubin 1.9
WBC mildly up, left shift and lymphopenia,
mildly anemic
• U/A minimal protein and no sediment
CASE REVIEW
• LABS cont:
• Negative serologies for Legionella, Histo,
Aspergillus, Blasto, Coccidio, Q-Fever,
CMV, CVL cath tip, blood, sputum cultures
negative
• ABG: 7.42/40/61 on 100%, large A-a
gradient ???, shunt
• CXR: LL alveolar filling process, LLL air
bronchograms
HOSPITAL COURSE
• Day 1: Started on broad-spectrum Abx and
coverage for Legionella
• Days 2-3: Fevers continue, Abx changed
and Fluconazole added for thrush
• Days 4-6: All cultures- negative. ARDS
worsens, on PC. HP panel, IV steroids,
becomes hypotensive
HOSPITAL COURSE
• Days 7-12: LFTs increase, drug effect? and
fevers continue
• Days 13-22: Multiple PTX, steroids
continued, Legionella, Haanta, CMV-negative
• Days 23-25: Worsening O2, bronch
unrevealing, persistent hypotension and
bradycardia, PEA.
What’s Missing?
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HIV???
Toxicology screen
Echocardiogram
BAL cell count
Lung biopsy
Approach
• Alveolar filling process-- pus, blood,
protein, fluid, cells (CA, immunologic)
• ARDS
• Subacute presentations of lung disease
ARDS
• Lung injury from some insult that causes
inflammatory cascade
• Three stages: Exudative (alveolar edema
and hyaline membranes)
Proliferative (fibrin ) >24 hr
Fibrotic (collagen) >2 wks
INTERSTITIAL LUNG DISEASES
PRODUCING AN ALVEOLAR-FILLING PATTERN ON CHEST RADIOGRAPH
Alveolar proteinosis (proteinaceous fluid)
Alveolar cell carcinoma (malignant cells)
Bronchioloalveolar metastases (malignant cells from pancreas, breast)
Pulmonary lymphoma (malignant lymphocytes)
Lymphocytic interstitial pneumonia (lymphoplasmacytic cells)
Alveolar sarcoid (lymphocyte-macrophage alveolitis or confluent granuloma)
Desquamative interstitial pneumonia (macrophages)
Diffuse alveolar hemorrhage (red blood cells; hemosiderin-filled macrophages)
Eosinophilic pneumonia (eosinophils, macrophages; lymphocytes)
Alveolar microlithiasis (calcium-phosphate microliths)
Bronchiolitis obliterans organizing pneumonia (collagen)
Mineral oil aspiration (lipid-filled macrophages)
Acute hypersensitivity pneumonia (lymphoplasmacytic cells)
Infections
• CAP: Pnemococcus, H. flu, Staph aureus,
Mycoplasma, Legionella, Chlamydia-treated with multiple broad-spectrum Abx
• Viral: Adenovirus, CMV, Haanta, HSV,
influenza, RSV, Varicella-- negative titers
for CMV, Haanta, wrong time course for
flu, no pustules for varicella
Infections
• Fungal: Histo, Blasto, Coccidio,
Aspergillus-- negative titers, Crypto usually
in immunocompromised hosts
• TB: possible, but probably too rapid
• Parasites: Toxo, Strongyloides, Filaria,
Trichinosis, Echinococcus (cysts),
Shistosomiasis-- no peripheral eosinophilia
• PCP??
Alveolar Hemorrhage
• Caused by bleeding in the small pulmonary
vessels, leading to syndrome known as
Diffuse Alveolar Hemorrhage
• “Pulmonary capillaritis” with PMN
infiltration
• Presentation: Cough, dyspnea and
hemoptysis-- often delayed
Alveolar Hemorrhage
• Fever may be present if the patient has an
underlying vasculitis (Goodpasture’s- antiGBM Ab, Wegener’s- cANCA)
• Drop in hematocrit
• BAL returns bloody fluid
Alveolar Hemorrhage
Etiologies of DAH
Isolated pulmonary
capillaritis
Wegner’s
Granulomatosis
Microscopic
Polyangiitis
Connective Tissue
Diseases-- SLE
Behcet’s Syndrome
Idiopathic Pulmonary
Hemosiderosis
Goodpasture’s
Syndrome
Mitral Stenosis
Pulmonary Venoocclusive Disease
Alveolar Hemorrhage
• No significant fall in hematocrit
• No urine sediment to suggest a
glomerulonephritis
• No evidence of a CTD or vasculitis
Pulmonary Alveolar Proteinosis
• Insoluble, proteinaceous material, rich in
phospholipids is deposited in alveoli
• Very little inflammatory response, just
hypoxemia
• Degradation of Type II pneumocytes
• BAL reveals PAS-positive fluid
• Nocardia is common secondary infection
PAP
• “CXR looks much worse than the patient”
• Patients can be severely hypoxic
• Require serial BAL to remove
proteinaceous material “whole lung lavage”
• Most patients do quite well
CHF
• Multiple cardiac causes for pulmonary
edema-- LVSF, valvular disease
• No report of cardiomegaly, pleural effusions
on CXR
Malignancies
• Bronchoalveolar cell carcinoma
subtype of adenocarcinoma which fills
alveoli
viral etiology is postulated (retrovirus)
role of tobacco is controversial
• Primary Pulmonary Lymphoma
occurs in immunocompromised hosts
Bronchoalveolar Cell CA
Drug Toxicities
• Multiple drugs which cause acute lung
injury and ARDS
• Predominantly drugs of abuse,
chemotherapeutics
Drug Toxicity
Heroin
Naloxone
Cocaine
Barbiturates
Salicylates
Amiodarone
Cyclosporine
MTX
Vinca
Alkaloids
Alkalating
agents
Retinoic Acid
(AML)
Tocolytic
therapy
HCTZ
Paraquat
(Insecticides)
Nitrofurantoin
Drug Toxicity
• “No habits”
• No exposure to chemotherapy
• Overdose-- not acute
Subacute Interstitial Diseases
• Bronchiolitis Obliterans with Organizing
Pneumonia
• Hypersensitivity Pneumonitis
• Acute Eosinophilic Pneumonia
• Pneumoconioses
• Sarcoidosis
• Acute Interstitial Pneumonia
BOOP
• Clinicopathologic diagnosis characterized
by “pneumonia-like” illness with
proliferation of granulation tissue within
small airways with chronic inflammation in
the surrounding alveoli
• Mean age at presentation is 58, M=F
• Flu-like illness with cough, fever, malaise,
fatigue and weight loss
BOOP
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Subacute presentation <2 months duration
Inspiratory crackles
Finger clubbing is rare
Labs are not helpful, with elevation of WBC
and eosinophilia in about 50%, elevated
ESR
BOOP
• CXR shows peripheral, bilateral, alveolar
filling with normal lung volumes
• CT reveals patchy air-space consolidation
with bronchial wall thickening and
dilatation
• PFTs show restrictive defect, with
significant hypoxemia. DLCO is often
reduced
BOOP
BOOP
• PATH: Intraluminal fibrotic buds (Masson
bodies) in respiratory bronchioles and
alveoli, foamy cells in alveolar spaces, Type
II cell hyperplasia, and fibrinous exudates
• Corticosteroid therapy results in complete
resolution in >2/3 of patients and is rapid
• Relapses can occur when steroids are
withdrawn
BOOP
• Presentation is consistent
• Steroid dose?
• Most patients who develop a progressive
fatal form of the disease have the diagnosis
delayed or missed
Hypersensitivity Pneumonitis
• “Extrinsic allergic alveolitis”
• Granulomatous, interstitial, bronchiolar, and
alveolar-filling lung disease resulting from
repeated inhalation of sensitization to a
wide variety of organic aerosols and lowmolecular weight chemical antigens
• Improvement or reversal if antigen exposure
ceases, continued exposure leads to
progressive fibrosis
HP
• List of specific agents is lengthy
• Three major categories of antigens:
Microbes
Animal Proteins
LMW Chemicals
• Antigen is deposited in alveoli, triggering Tlymphocyte inflammation
• Antigen is not digested and acts to fix
complement and increase inflammatory response
HP
• Presbyterian has 3 HP Panels
• “Extended” includes “farmer’s lung” and
“bird fancier’s”:
Aspergillus fumigatus and flavus, Aureobasidium
Actinomyces, Microsporidium
Pigeon feather antigen
DOES not include any other animal or chemical Ag
HP
• Microbes
• Animal: Avian antigens most common, also
laboratory animal handlers (pelts, serum
and excreta), miller’s lung (grain), silk
producers (larval secretions and cocoons)
and mollusk shell dust
• Chemicals: Isocyanates in adhesive, foams
and surface coatings and Ag in paints,
plastics and resins
HP
• Development of disease is dependent upon the
antigen, degree of exposure, host factors
• Repeated antigen exposure
• Immunologic sensitization of host to antigen
• Immune-mediated damage to the lung
• Exertional dyspnea, cough with sputum
production, malaise, fever. Often misdiagnosed as
infection, but patients improve b/c of removal
from Ag
HP
• Chronic presentation leads to crackles on
exam, clubbing and cor pulmonale
• Unfortunately precipitating Ab tests are
non-specific because of huge numbers of
Ag MOST IMPORTANT IS HISTORY
• CXR and CT reveal GG opacities and
micronodules
• BAL reveals lymphocyotosis with CD8
predominance
HP
HP
• Symptoms usually respond to removal of
antigen in acute cases
• Chronic forms with repeat exposures have
decline in lung function and fibrosis
• ?? Role for steroids
• This patient has no known exposure, and
worsened despite “removal of Ag”
Eosinophilic Pneumonias
Acute Eosinophilic Pneumonia
• thought to represent a hypersensitivity
reaction to an inhaled Ag
• Symptoms of fever, myalgias, hypoxemia
(severe) for a few hours to days
• WBCs elevated, eosinophilia in 1/3
• Diffuse infiltrates
• BAL with eosinophils (>25%)
Eosinophilic Pneumonias
• May require mechanical ventilation
• Respond to Solumedrol at high doses (60125 mg q 6 hours)
• Must document an absence of infection
• Do not develop relapses after steroids are
tapered
Eosinophilic Pneumonias
Chronic Eosinophilic Pneumonia
• Subacute presentation with cough, dyspnea,
fever and night sweats
• Mild hypoxemia
• Diffuse, peripheral infiltrates “-- CHF”
• Serum and BAL eosinophilia
• Response to steroids, but relapses occur
Eosinophilic Pneumonia
Eosinophilic Pneumonias
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CXR is not consistent
No response to steroids
No eosinophilia
Presentation too late for AEP and too short
for CEP
Sarcoid
• Alveolar pattern which is coalescence of
reticulonodular disease
• Wrong time frame for presentation in our
patient
Sarcoid
Occupational Exposures
• Patient works with ceramics, fiberglass, and
flooring
• Literature to suggest no significant degree
of lung fibrosis with fiberglass, but may be
carcinogenic
• Acute inhalational injury??
• HP
Pneumocystis
• PCP is the most common AIDS-defining
illness
• Ubiquitous fungus with transmission by
inhalation
• CD4<200 or chronic steroid therapy
• CXR shows bilateral GG opacities with
granularity, but any presentation is possible
(not pleural effusions or LAD)
PCP
• Diagnosis is by BAL/sputum for silver stain
or PCP-DFA
• RX: Mild (PaO2 > 70, A-a gradient <35),
Bactrim (TMP 15 mg/kg q 6 hours) PO
• RX: Mod-severe (PaO2 < 70, A-a > 35)
Bactrim IV plus Prednisone or Solumedrol
• High mortality rate assoc. with resp. failure
PCP
• Presentation is consistent
• Fever?
• Nothing from the history to suggest HIV
Acute Interstitial Pnemonia
• Rare, fulminant lung injury that presents in
days to weeks in a previously healthy
patient
• “Hamman-Rich Syndrome”
• Mean age is 50 years
• A prodromal illness lasting 7-14 days before
presentation is common
AIP
• Symptoms include fever, cough and
dyspnea
• Routine labs are not helpful
• Severe hypoxemia and respiratory failure
• Diffuse, bilateral airspace disease on CXR
• CT shows diffuse GG or air space
consolidation
AIP
• Surgical lung biopsy is required to confirm
DX of organizing diffuse alveolar damage
• Mortality is greater than 60%, death within
weeks- 3 months
• Those who recover may have recurrence
• Role for corticosteroids is not clear
AIP
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13 biopsy-proven patients
mean patient age was 54 years
12 required mechanical ventilation
Mortality was 33%
CXR revealed bilateral patchy densities that
progressed to diffuse alveolar filling
• Mean time from symptom onset to death
was 26 days
Vourlekis, et al. Medicine 2000.
AIP
• Outcome not related to steroid use
Vourlekis, et al, Medicine 2000
REVIEW
• 41 you AA male with 2 week h/o fever,
dyspnea and malaise
• He developed respiratory failure despite
antibiotics, and failed to improve with broad
antimicrobial coverage (all cultures
negative)
• ARDS requiring PC with development of
PTX, eventual PEA and death
Diagnosis
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AIP
BOOP if inadequate steroids
Eosinophilic pneumonia
PCP if HIV+
Influenza
Pathologic Diagnosis
• Extensive interstitial fibrosis on pathology with
sheets of Staphylococcus in the background
and consolidation.
• Also diffuse Aspergillus seen with an
approximately 13 cm Aspergillus abscess.
• Final: Acute Interstitial Pneumonia
– Precipitant ARDS with nosocomial pneumonia