History

Leslie Case 3 • A 38 year old woman presents with shortness of breath, night sweats Acute Lung Injury and fevers. She is treated empirically with antibiotics, but “One ring to rule them all” progresses, eventually requiring a surgical lung biopsy. “R/O atypical infection”

Supplemental History Supplemental History

• 38F previously healthy, ex-smoker (quit 5 yr • PAST MEDICAL HISTORY: migraine before), homemaker hospitalized for headaches, chronic allergies, sinus congestion, persistent (bilateral pulmonary bilateral breast augmentation. infiltrates). • Cough, dyspnea, fever, arthralgias past 3 • SOCIAL HISTORY: Previous smoker. Social weeks. alcohol use. Owns a cat. • Treated first with levofloxacin, then • FAMILY HISTORY: Father is a trial attorney, clarithromycin without improvement. specializing in malpractice law. Mother is alive – Serologies (mycoplasma, legionella, and well. chlamydia, coccidioides, histoplasma, etc.) – Recent outside bronchoscopy-- • CURRENT MEDICATIONS: Depakote for nondiagnostic. migraine headache.

Supplemental History

• P. EXAM: moderately dyspneic, occasional Clinical Course cough. Stable vital signs (T = 36.2 ºC). Diffuse inspiratory crackles but no wheezing. SaO2 96% • Bronchoscopy with BAL and cultures negative on 6L/min via NC. • Hgb 10.6 g/dL, WBC 19.9 (87% )

• Transferred to ICU • HIV, cocci, legionella, mycoplasma titers negative • ANA and RF negative

• Histoplasma urinary antigen negative

• Blood cultures negative August 2002 August 2002

August 2002 Diffuse Consolidative Pattern

• Acute: infections, pulmonary , aspiration, diffuse alveolar hemorrhage, AIP, AEP, acute drug- induced or inhalational injury, cryptogenic or secondary OP

• Chronic: eosinophilic , cryptogenic or secondary OP, lymphoproliferative diseases, PAP, , infections, aspiration, lymphoma, adenocarcinoma (bronchoalveolar cell)

Case Presentation • The patient deteriorated and required intubation.

Diagnosis? A VATS lung biopsy was performed…

CXR One Month Later Clinical-Radiological- (Treated with IV methylprednisolone, then prednisone x Histopathological Diagnosis 4 wk)

Acute

In a follow-up visit, the patient revealed that she had been smoking crack cocaine for the previous 6 weeks.

Diffuse Lung Disease

Acute Diseases Subacute Diseases Chronic Diseases

Diffuse alveolar damage Organizing pneumonia Pneumoconioses (shock/infection) Hypersensitivity Lymphangitic tumor Acute eosinophilic Chronic eosinophilic RBILD/DIP/PLCH pneumonia pneumonia Sarcoidosis/ Diseases related to drugs and RBILD/DIP/PLCH Diseases related to toxins CVD Sarcoidosis/Berylliosis Diseases related to CVD Alveolar proteinosis Diseases related to CVD Vascultitis/DAH Small airways disease Diseases related to drugs AIP Amyloidosis NSIP Acute exacerbation of IPF (UIP) UIP

Phases of ARDS

Exudative Transition Proliferative Fibrotic 100

Edema Hyaline membranes

Progressive Fibrosis Biopsy Inflammation Stabile Fibrosis Biopsy Biopsy Resolution

Maximal Prominence Maximal Fibroplasia 0 0 1 2 3 4 5 6 7 Later Day Phases of ARDS

Exudative Transition Proliferative Fibrotic 100 Hyaline membranes Edema

Progressive Fibrosis Inflammation Stabile fibrosis

% of Maximal Biopsy Fibroplasia Resolution

0 Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Later

Phases of ARDS

Exudative Transition Proliferative Fibrotic 100 Hyaline membranes Edema

Progressive Fibrosis Inflammation Stabile Biopsy fibrosis % of Maximal Fibroplasia Resolution

0 Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Later

Phases of ARDS Diffuse Lung Diseases with Acute Manifestations

Exudative Transition Proliferative Fibrotic 100 Trauma/Shock Edema Hyaline membranes Progressive Fibrosis Immunologic Inflammation DAD Drugs Stabile Diseases Acute Interstitial fibrosis IdiopathicPneumonia % of Maximal Fibroplasia Resolution Infection/ 0 Day 0 Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7 Later Toxins Diffuse Lung Diseases with Acute Manifestations Diffuse Lung Diseases with Acute Manifestations DIFFUSE ALVEOLAR DAMAGE The “Litany” in Cases of Acute Lung Injury From infection From CVD From unknown cause (AIP) From drug or toxin From ARDS ACUTE EOSINOPHILIC PNEUMONIA First: Look for Bugs From unknown cause (Idiopathic) Next: Rule out Drugs From drug VASCULITIC AND IMMUNOLOGIC DISEASES Still in doubt: Check the serology + CBC + Sed rate Wegener’s Systemic connective tissue diseases Goodpasture’s Churg-Strauss syndrome When all else fails: Call it “idiopathic” Microscopic polyangiitis ACUTE EXACERBATION OF IPF

UIP Survival

Chronic diseases 100 90 80 70 in 60 50 40 Percent Percent 30 acute exacerbation 20 UIP 10 0 0 1 2 3 4 5 6 7 8 Survey years

(from Bjoraker, et al)

Acute Exacerbation of IPF

Step theory of UIP/IPF progression Respiratory Respiratory Acute exacerbation? function/symptoms function/symptoms

Years Trichrome Stain for Collagen Eosinophilic pneumonia Overview • Many causes (parasites, drug reaction, asthma, polyarteritis nodosa, idiopathic)

• Acute and chronic eosinophilic pneumonia overlap histologically

Eosinophilic pneumonia Eosinophilic pneumonia Clinical Presentation Chest Imaging • Symptoms vary: Minimal and self-limited, to severe and prolonged • Considerable radiologic variability • Flu-like symptoms with cough, dyspnea • Diffuse and bilateral, simulating DAD and pleuritic pain • Transient bilateral infiltrates (migratory) • Patients may be severely hypoxic • Family history of allergy or asthma common • “Ground glass” opacities on CT • Blood eosinophilia usually occurs at onset • Often peripheral and apical (chronic) of symptoms Eosinophilic Pneumonia Pearl

• Even very brief steroid therapy before biopsy can eliminate or decrease tissue eosinophilia