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Clinicopathological Conference
The Johns Hopkins Hospital
December 1, 2009
Clinical Discussant: David B. Pearse, M.D.
Pulmonary and Critical Care Medicine
Timeline
• March 08:
 SOB, cough, pul infiltrates;
 Idiopathic Bronchiolitis Obliterans Organizing
Pneumonia (BOOP) Dxed
• June 08:
 Successfully tapered off steroids
• Early December 08 to early Jan 09:
increasing SOB, cough
 bilat pul infiltrates, refractory hypoxemia
 corticosteroids, antibiotic started

Timeline
• Mid Jan 09:
 Sicker
 Lung bx: BOOP
• End Jan 09:
 Febrile on 100 mg/day methylprednisilone
 Diffuse nodular infiltrates, LLL consolidation
 Severe hypoxemic
respiratory failure
 Refractory atrial arrhythmias; death
Idiopathic BOOP
(or Cryptogenic Organizing Pneumonia)
• Middle aged or older; non or ex-smokers
• Subacute URI presentation
 Persistent cough, dyspnea, fever
 Patchy bilateral alveolar/interstitial infiltrates
• Path: organizing pneumonia with granulation
tissue buds in alveoli and bronchioles
• No other associated diseases
Cordier JF. Cryptogenic organizing pneumonia. Clin Chest Med 25:727-738, 2004
Idiopathic BOOP
• 80% steroid responsive
• 1 or 2 relapses common during steroid taper
but relapses
 remain steroid responsive
 do not affect overall mortality
Cordier JF. Cryptogenic organizing pneumonia. Clin Chest Med 25:727-738, 2004
BOOP (or Organizing Pneumonia)
• Bacterial infections:
 Strep, Staph, Chlamydia, Legionella, Mycoplasma,
Nocardia
• Viruses:
 HSV, HIV, Influenza, Parainfluenza, CMV
• Fungi:
 Cryptococcus, Pneumocystis
• Drugs/Toxins
• Connective Tissue Disease
• Transplantation
Cordier JF. Cryptogenic organizing pneumonia. Clin Chest Med 25:727-738, 2004
BOOP (or Organizing Pneumonia)
• Bacterial infections:
 Strep, Staph, Chlamydia, Legionella, Mycoplasma,
Nocardia
• Viruses:
 HSV, HIV, Influenza, Parainfluenza, CMV
• Fungi:
 Cryptococcus, Pneumocystis
• Drugs
• Connective Tissue Disease
• Transplantation
Cordier JF. Cryptogenic organizing pneumonia. Clin Chest Med 25:727-738, 2004
Approach to Patient
• Initial illness likely idiopathic BOOP
 Consistent host and presentation
 Consistent transbronchial
biopsy
 Complete response to steroid treatment
Approach to Patient
What was the second illness in Dec 08?
Approach to Patient
What was the second illness in Dec 08?
Assuming this was a single illness………
Second Illness: Key Findings
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Subacute presentation (2 weeks)
Corticosteroid, cephalosporin- unresponsive
Bilat upper lobe nodular interstitial onset
Progressed to alveolar-filling process
Fever despite 100 mg methylprednisilone
Lung biopsy: ?BOOP
Differential Dx of Progressive Alveolar-Filling
with Respiratory Failure
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•
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Pulmonary edema
Infection
Autoimmune
Idiopathic
Malignant
Differential Dx of Alveolar-Filling with
Respiratory Failure
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•
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Pulmonary edema
Infection
Autoimmune
Idiopathic
Malignant
Water
Pus
Blood
Cells
Alveolar-Filling with Subacute Respiratory Failure
• Infection
• Autoimmune
 Pulmonary hemorrhage syndromes
•
•
•
•
Wegener’s Granulomatosis
Microscopic polyangitis
Goodpasture’s Syndrome
Systemic Lupus Erythematosis
• Idiopathic
• Malignant
Alveolar-Filling with Subacute Respiratory Failure
• Infection
• Autoimmune
 Pulmonary hemorrhage syndromes
•
•
•
•
Wegener’s Granulomatosis
Goodpasture’s Syndrome
Systemic Lupus Erythematosis
Microscopic polyangitis
• Idiopathic
 Idiopathic BOOP
 Eosinophilic Pneumonia
 Desquamative Interstitial Pneumonitis
 Pulmonary Alveolar Proteinosis
• Malignant
Alveolar-Filling with Subacute Respiratory Failure
• Infection
• Autoimmune

Pulmonary hemorrhage syndromes
•
•
•
•
Wegener’s Granulomatosis
Goodpasture’s Syndrome
Systemic Lupus Erythematosis
Microscopic polyangitis
• Idiopathic




Acute Interstitial Pneumonia (Hamman Rich)
Eosinophilic pneumonia
Desquamative Interstitial Pneumonitis
Pulmonary alveolar proteinosis
• Malignant


Alveolar cell carcinoma
lymphoma
Most Likely Diagnosis: Infection
• Case-specific requirements for infectious agent:
 Able to infect with near-normal immunity
 Subacute (weeks) presentation
 Bilateral upper lobe interstitial/nodular
infiltrates
 Exacerbated by steroids, progress to resp failure
 Unresponsive to typical broad-spectrum antibiotics
 Can have BOOP or BOOP-like pathology
 Not routinely cultured, culture difficult or takes time
Infections that Reasonably Fit
• Bacteria
 Nocardia asteroides*
 Mycobacterium tuberculosis
 Nontuberculous mycobacteria
• Fungi
 Cryptococcus neoformans *
 Histoplasma capsulatum
 Blastomyces dermatitis
 Coccidioides immitis
 (Pneumocystis jiroveci *)
• Virus
 Cytomegalovirus *
*Associated with BOOP on lung biopsy
Differential Dx: My Short List
1)
2)
3)
4)
5)
6)
Cryptococcus
Nocardia
Cytomegalovirus
Progressive Disseminated Histoplasmosis
Mycobacteria tuberculosis (or M. kansasii)
(Pneumocystis)
If BOOP was present on lung biopsy:
1) Cryptococcus
2) Nocardia
3) Cytomegalovirus
If BOOP was not present on lung biopsy:
Favor Histoplasmosis because of calcified
lung nodule
Histoplasmosis
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Most common endemic mycosis in US
After inhalation, transient RES dissemination
Can see lower lobe calcified histoplasmoma
Latent infection until immunity suppressed
Upper lobe reactivation mimics TB
Exacerbated by steroids, may not see granulomas
Pericarditis and endocarditis with arrhythmias
Dismukes et al. Disseminated histoplasmosis in corticosteroid-treated patients. JAMA 240:
1495-98, 1978
Kauffman C. Histoplasmosis. Clin Chest Med 30:217-25, 2009