Clinical Pathology Correlate Conference

Katrina Cannon, MD

Internal Medicine

Case Presentation 50 yo African American female with 2 year hx

of intermittent dyspnea presented to ER with marked SOB and respiratory distress

Pulmonary clinic 6 months prior for dyspnea and abnormal CXR; recommended further evaluation including CT; not completed

Significant dyspnea ~ 2 weeks new heart palpitations

ER coursePhysical Exam

Gen: significant respiratory distress, cool but no diaphoresis, no pain

VS: HR 120-130 and BP 160/100 CV: distant heart sounds, no m/r Lungs: poor breath sounds, expiratory

wheezes and “tightness”Treatment: oxygen by facemask

Acute Respiratory FailureContinued SOB, appeared hypoxicABG: pH 7.15, PaCO2 51, PaO2 200 Decreasingly responsiveRapid Sequence Intubation

Sedation: versed, fentanyl Paralyzed: succinylcholine,vecuronium Intubation: ETT placed

ER coursePhysical Exam

VS: BP 80/60 Extremities: mottled, cool, hypoperfused

EKG/CXR/labs obtained

EKG

CXR

LabsGlucose 230Na 130, K 3.6, Cl 106, HCO3 22BUN 10, Cr 0.8WBC 8.7 (54% bands, 10% lymphs),

Hgb 9.5, Platelets 347,000CK 53, LDH 218, Trop T WNL

ER Course continues…Hypotension tx: IVF and DopamineCardiology Consult: abnormal EKG,

persistent hypotension and tachycardia ? possible AMI with cardiogenic shock

Cardioversion attempted-unsuccessfulEchocardiogram

EchocardiogramMild generalized hypokinesisMore focal wall motion in anterior apical

wallEF mildly reduced- difficult to assess

due to tachycardiaLVHNo acute valvular disordersSmall pericardial effusion

ER Course continues…Adenosine (transient AV block) revealed

underlying atrial rate of ~240Digoxin initiatedDopamine Neo-Synephrine startedBP responded, blood gas improved:

ABG pH 7.3 35/135 HCO3 17Transferred to ICU

ICU Course: Day 1Respiratory: ventilatorCardiovascular:

digoxin + procainamide HR 100-110 atrial tachycardia persisted

Diuresed with brisk responseNeo-Synephrine tapered off

PA CatheterPCWP = 13 (12-18)RA = 9 (2-6)PAP = 46/32 (25/10)CO = 5.4 (5.4 - 7.2)CI = 2.9 (2.9 - 3.9)PVR = 829 (<250 dyne) Initially on Neo-Synephrine (then off)

ICU CourseDay 2: extubated but continued O2

support for moderate dyspneaDay 3: EP consult for atrial tachycardia

Dx: automatic atrial tachycardia Tx: added Flecainide

Day 4: Sinus rhythm restored and maintained

Follow-up EKG

Follow-up Test ResultsEcho: LVH, recovery of LV function with

mildly depressed EF, no focal wall motion abnormalities

Cardiac biomarkers: negative

CXR

Transferred to FloorRespiratory: Pulmonary consult to

continue workup of dyspnea and abnormal CXR

Cardiovascular: continued on flecainide and digoxin, diuretic, + lisinopril (HTN)

Pulmonary Function TestsFVC = 1.39 L (42% predicted)FEV1 = 1.15 L (43% predicted)DLCO = 10.4 ml/min/mmHg (42% predicted) Interpretation:

Moderately severe restrictive change Severely reduced diffusing capacity Significant gas transfer disorder Mild airways obstruction

CT ScanBilateral interstitial infiltratesParticularly at the basesPerihilar adenopathy

Additional Laboratory Data Anemia: Hbg 9.5 11 with 2 PRBC Electrolytes/BUN/Cr: normalized Blood Cultures: negative Serum Protein Electrophoresis: normal ACE level: 40 (7-46) ABG: “normal”

Persistent hypoxia, wheezing and dyspnea on exertion

Day 5: BronchcoscopyStenotic lobar and segmental airway

involvement of entire tracheobronchial tree with compromised 50-60% of lumen diameter

Brush washings, transbronchial Bx, mucosal Bx and Cx obtained

Tx: steroids

Day 7: Hospital Discharge Improved clinically with less wheezing

and dyspneaDischarged: prednisone, lisinopril,

HCTZ, digoxin and flecainideF/U with Pulmonary and Cardiology

A Diagnostic Result was revealed.

Problem List: Dyspnea Respiratory

Acute Respiratory Failure Chronic Progressive Dyspnea Abnormal CXR/CT: interstitial infiltrates and perihilar

adenopthay Abnormal PFTs: restrictive lung disease with decreased

DLCO Cardiovascular

Tachyarrhythmia: automatic atrial tachycardia LVH Anemia Hypotension HTN

Respiratory: Dyspnea Acute Respiratory Failure ~tachyarrhythmia Chronic Dyspnea ~ 2 year history intermittent

and progressive SOB

CHRONIC DYSPNEA

Chronic Airway Disease: COPD, asthma Interstitial Lung Disease Chronic Cardiac Disease

Chronic Dyspnea Good Information: History, PE, labs, old and

recent CXR, CT, PFTs, and Bronchoscopy

Abnormal CXR/CT: bilateral interstitial infiltrates, particularly at the bases with perihilar adenopathy

Abnormal PFTs: restrictive lung disease with decreased diffusing capacity

Bronchoscopy: compromised lumen diameter

Interstitial Lung Disease

Intersitial Lung Disease ILD: parenchymal lung

involvement Alveoli Aveolar epithelium Capillary endothelium Interstitial space between Perivascular and lymphatic

tissues HUGE differential: >200

known diseases Non-malignant and non-

infectious

Diffuse Parenchymal Lung Disease

K n ow n C au se :D ru g s /Trea tm en t

E n viron m en ta l E xp osu reC o llag en V asc D isease

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Primary Disease associated with Interstitial Lung Disease Sarcoidosis PLCH Vasculitides Hemorrhagic syndromes Amyloidosis Lymphangiolieomyomatosis (LAM) Lymphangitic Carcinomatosis Congenital/Hereditary Chronic Pulmonary Edema Alveolar Proteinosis Pulmonary Veno-occlusive Disease

ILD: History Timing: Chronic (months to years)

Idiopathic Pulmonary Fibrosis Sarcoidosis Pulmonary Langerhans Cell Histiocytosis (PLCH,

Histiocytosis X, Eosinophilic Granuloma)

Age (50) Sarcoid, PLCH, CVD, LAM, inherited ~20-40 IPF >50

History continued…Family History: negative

Neurofibromatosis Tuberous Sclerosis Hermansky-Pudlak syndrome

Occupational/Drug Exposure: none no amiodarone ACE induced cough Procainamide ~drug-induced SLE

History continued… Gender: LAM, tuberous sclerosis only in

premenopausal women

Race: African American Sarcoidosis 3-4 times more common in blacks,

lifetime risk 2.4% v. whites 0.85%

Smoking History: non-smoker +tob: PLCH, DIP, IPF, respiratory bronchiolitis -tob: sarcoidosis, hypersensitivity pneumonitis

Physical Exam Dyspnea, wheezing No cough, no hemoptysis, no chest pain

BOOP/COP Respiratory bronchiolitis Hypersensitivity pneumonitis Diffuse alveolar hemorrhage syndromes Granulomatous vasculitides Maligancy

No extrapulmonary findings

LabsNormal electrolytesNormal renal functionMild Anemia, stableABG: respiratory acidosis-resolved

Labs continued…ACE level 40 (7-46) upper limits of normal:

Increased 35-80% sarcoidosis But can be normal (sensitivity 57%) Less likely increased in chronic sarcoidosis Also increased Silicosis, TB, LIP

No ANCA: Wegner’s granulomatosisNo Anti-BM ab: Goodpasture’s

syndrome

CXR/CT 6 months prior Current

ILD plus Perihilar Adenopathy Sarcoidosis Lymphoma Lymphangitic carcinomatosis Infectious: TB or Fungal Disease

(histoplasmosis) Lymphocytic interstitial pneumonia Amyloidosis Pneumoconioses (Beryllium, Silicosis) Bronchiogenic Carcinoma

Sarcoidosis Evidence For

Race: African American Age: <50 CXR/CT:Bilateral

Pulmonary infiltrates and perihilar adenopathy

PFTs: restrictive, DLCO Bronch: endobronchial

lesions CV: tachyarrhythmia

Evidence Against CXR/CT: Lower lung

zone Bronch: stenosis Lab: ACE ? No extrapulmonary

manifestations…

Sarcoidosis Stage I: bilateral hilar

adenopathy Stage II: bilateral hilar

adenopathy + interstitial infiltrates (upper > lower)

Stage III: interstitial disease with shrinking hilar nodes

Stage IV: advanced fibrosis

Sarcoidosis Evidence For

Race: African American Age: <50 CXR/CT:Bilateral

Pulmonary infiltrates and perihilar adenopathy

PFTs: restrictive, DLCO Bronch: endobronchial

lesions CV: tachyarrhythmia

Evidence Against CXR/CT: Lower lung

zone Bronch: stenosis Lab: ACE ? No extrapulmonary

manifestations…

Sarcoid and Cardiovascular Disease

Not uncommon: 5% clinically significant 25-30% postmortem

Granulomatous infiltration

Conduction disturbances Atrial Tachycardia*

Conclusion50 yo AAF with Chronic DyspneaPulmonary SarcoidosisFocal Atrial Tachycardia ~ CV sarcoidAcute Respiratory Failure:

CHF/Pulmonary EdemaCardiac: diuresis and antiarrhythmicsTx: Steroids

Dx: SarcoidosisClinical and Radiographic findings

supportive of SarcoidosisR/O infection:TB and fungal diseaseHistologic evidence of noncaseating

granulomas

Diagnostic ResultNoncaseating Granulomas

SARCOIDOSIS

The End

1. Proceed to the post test2. Download the post test3. Complete the post test4. Return the post test to Dr. S. Oliver

407i TAMUII

Post test question 1Sarcoidosis is most often diagnosed in

which of the following EXCEPT: Young adults (20-40 years old), Nonsmokers Hispanic-Americans Roughly equal in Caucasian men and

women

Post test question 2Sarcoidosis is usually treated initially

with which of the following:1. Steroids2. Methotrexate3. Thalidomide4. Cytoxin

References ACC/AHA/ESC Guidelines for the Management of Patients with

Supraventricular Arrhythmias; JACC Vol. 42. No. 8, 2003, Oct 15 2003: 1513-1516.

Braunwald, E; Essential Atlas of Heart Disease; Current Medicine 1997; Philadelphia, PA; pg 5.9.

Colucci, W; Braunwald, E; Atlas of Heart Failure: Cardiac Function and Dysfunction; 2nd Ed; Current Medicine 1999; Philadelphia, PA; pg 3.11.

Schwarz, M; King, T; Interstitial Lung Disease 4th Ed.; BC Decker Inc.; Hamilton London; 2003.

Uptodate: Approach to the Adult with Interstial Lung Disease, Evaluation of Diffuse Lung Disease by Plain Chest Radiography, Overview of Sarcoidosis, Atrial Tachycardias