1. Clinicopathological Conference   The Johns Hopkins Hospital December 1, 2009
Clinical Discussant: David B. Pearse, M.D.
Pulmonary and Critical Care Medicine

2. Timeline March 08: June 08: Early December 08 to early Jan 09:
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

3. Timeline Mid Jan 09: End Jan 09: Sicker Lung bx: BOOP
Febrile on 100 mg/day methylprednisilone
Diffuse nodular infiltrates, LLL consolidation
Severe hypoxemic respiratory failure
Refractory atrial arrhythmias; death

4. 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: , 2004

5. 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: , 2004

6. 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: , 2004

7. 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: , 2004

8. Approach to Patient Initial illness likely idiopathic BOOP
Consistent host and presentation
Consistent transbronchial biopsy
Complete response to steroid treatment

9. Approach to Patient
What was the second illness in Dec 08?

10. Approach to Patient
What was the second illness in Dec 08? Assuming this was a single illness………

11. Second Illness: Key Findings
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

12. Differential Dx of Progressive Alveolar-Filling with Respiratory Failure
Pulmonary edema
Infection
Autoimmune
Idiopathic
Malignant

13. Differential Dx of Alveolar-Filling with Respiratory Failure
Pulmonary edema
Infection
Autoimmune
Idiopathic
Malignant
Water
Pus
Blood
Cells

14. Alveolar-Filling with Subacute Respiratory Failure
Infection
Autoimmune
Pulmonary hemorrhage syndromes
Wegener’s Granulomatosis
Microscopic polyangitis
Goodpasture’s Syndrome
Systemic Lupus Erythematosis
Idiopathic
Malignant

15. 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

16. 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

17. 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

18. 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

19. Differential Dx: My Short List
Cryptococcus
Nocardia
Cytomegalovirus
Progressive Disseminated Histoplasmosis
Mycobacteria tuberculosis (or M. kansasii)
(Pneumocystis)

20. If BOOP was present on lung biopsy:
Cryptococcus
Nocardia
Cytomegalovirus

21. If BOOP was not present on lung biopsy:
Favor Histoplasmosis because of calcified lung nodule

22. Histoplasmosis 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: , 1978
Kauffman C. Histoplasmosis. Clin Chest Med 30:217-25, 2009