A Slice of PIE

1. A Slice of PIE Neal Waechter, MD

2. Disclosure and Objectives • No financial support • Present case • Discuss approach to case • Discuss outcome of case

3. Case 30 year old woman with chronic cough HPI: • 10 weeks ago: first “asthma exacerbation” (mild exercise-induced asthma for years), reports to urgent care (Visit #1) • Symptoms: • Cough • Moderate to severe dyspnea • Fever 101 • Fatigue/malaise • Treatment: • nebulizer • Advair inhaler

4. Case HPI • 8 weeks ago: Return to urgent care still feeling ill (visit #2) • Symptoms • still febrile (101) • still dyspneic despite using Advair as prescribed • cough now productive of green, sometimes dark brown sputum • Treatment • Amoxacillin x 10 days

5. Case HPI • 5 weeks ago: Return to urgent care with same complaints (Visit #3) • Symptoms • Improved very slightly after amoxacillin, but promptly returned to previous levels • Persistent fever, productive cough, dyspnea • Treatment • Azithromycin x 5 days

6. Case HPI • 1.5 weeks ago: Return to urgent care with persistent symptoms (Visit #4) and new chest pain • Symptoms • Unchanged fever, cough, dyspnea, no help from azithromycin • New onset of sharp left-sided pleuritic chest pain, thought she broke a rib • Diagnostic tests • CXR – “patchy airspace disease in RUL, suspicious for pneumonia” • Treatment • Augmentin 875 BID x 10 days

7. Case HPI • 1 week ago: Follow-up with PCP (Visit #5) • Symptoms: unchanged • Exam: • Temp 100.2 • Diffuse wheezing • Treatment • Continue antibiotics • Resume Advair • Follow-up CXR in one week

8. HPI • Current Visit: Follow-up abnormal CXR • Symptoms: • Still intermittent fever up to 101 • Chest pain has largely resolved • Dyspnea, productive cough continue w/o hemoptysis

9. ROS • Negative leg pain, h/o DVT/PE (VQ performed 2 years ago during pregnancy for chest pain was negative), arthralgia, rash, dysuria, GI symptoms • Positive for mild myalgias, occasional headaches

10. Case PMH • Mild intermittent/exercise-induced asthma, long history • Allergic rhinitis • Migraine • Depression SH • Non-smoker • One child age one, currently breastfeeding • Work – case manager and social worker in Geriatrics, currently not working Exposure History • No known exposure to TB, last PPD April 2002, negative • No birds, exotic pets • No recent travel FH: • Mother had DVT when bedridden with acute viral hepatitis • GM had DVT, unknown risk factor Allergies: Cephalexin Meds: Albuterol, Pirbuterol, Advair

11. Case Exam • 230 pounds, BP 110/80, HR 76, T 96.7 • Appeared comfortable, no resp distress • Decreased breath sounds upper right posterior lung field, egophony • Normal percussion and tactile fremitus • No wheezes or rales • No clubbing or cyanosis • Normal ENT, lymph node, cardiovascular, abdominal, musculoskeletal, skin

12. Case CXR (IMAGE)

13. What next? • What are the likely possibilities? • What can we not miss?

14. Initial Thoughts – “Can’t Miss” • Atypical infectious pneumonias • Fungal • TB/mycobacterial • Collagen Vascular Diseases • Vasculitis (esp. Churg-Strauss) • Cancer • Venous Thromboembolism and other embolic disease

15. Initial Plan Diagnostics • CBC: WBC 12.7, Hgb 13.3, Plt 315 • ESR: 50 • CRP: 2 • Chem: Cr 0.7, ALT 26 • UA: Sp gr >1.030, 2-5 wbc, 0-1 rbc, neg dip • One sputum for AFB (difficulty producing adequate specimen) pending

17. Case Summary So Far • History of mild intermittent asthma • Chronic Cough • Dyspnea • Intermittent fever • Leukocytosis • Persistent pulmonary infiltrates on CXR • Multiple areas of airspace disease on CT, upper lobe/peripheral predominance

18. Differential Diagnosis • Airway Disorders • Asthma • CF • Pulmonary infections • TB • Other mycobacteria • Fungi • Parasites • Opportunistic organisms • Cancer

19. Differential Diagnosis • Pulmonary vascular disorders • Pulmonary embolism/infarction • Vasculitis and Pulmonary Renal Syndromes • Wegener’s • Goodpasture’s • Churg-Strauss • Environmental/Occupational Lung disease • Hypersensitivity pneumonitis

20. Differential Diagnosis • Interstitial Lung Diseases • Idiopathic Fibrosing Interstitial Pneumonias • UIP (IPF) • RB-ILD (DIP) • AIP • NSIP • BOOP • Sarcoidosis • Collagen Vascular Diseases • Amyloidosis • Pulmonary Alveolar proteinosis • Pulmonary Infiltrates with Eosinophilia (PIE)

21. “Light bulb” • Recall cases of eosinophilic pulmonary syndromes from residency with similar presentation • No sig exposure to TB, no evidence of PE, cancer, on CT, no occupational exposures, no sig travel, doesn’t really fit other diagnoses on list • Patient has a history of asthma • Elevated WBC, but no diff – could this be eosinophilia? Plan: Add differential to yesterday’s blood

22. On to something… • Diff: • 6950 neutrophils • 3210 lymphs • 40 basophils • 302 monocytes • 2180 eosinophils

23. PIE • Pulmonary Infiltrates with Eosinophilia (PIE) • Infections • Helminths • Loffler’s syndrome (Ascaris, hookworm, strongyloides) • Non life cycle pulmonary invasion (paragonimiasis,others) • Tropical pulmonary eosinophilia (Wucheria) • Sometimes, Coccidiomycosis • Rarely, TB • Medications/crack cocaine • NSAIDS/Salicylates • Minocycline • Trimethoprim/sulfamethoxazole • ABPA • Churg-Strauss • Idiopathic Hypereosinophilic syndromes • Idiopathic eosinophilic pneumonia • Acute eosinophilic pneumonia • Chronic eosinophilic pneumonia

24. Coming to a diagnosis ABPA • Typically a sino-pulmonary syndrome with prominent sinus symptoms • Must have skin prick test or serum IGE/IGG positive for Aspergillus • Typical CT finding is widespread proximal bronchiectasis with upper lobe predominance, mucus plugging, and patchy infiltrates/atelectasis In this case… • Not entirely ruled out – did not do skin test or serum antibody tests • No sinus disease symptoms/signs • CT findings not characteristic (does not exclude diagnosis) Possible…

25. Coming to a diagnosis Churg-Strauss Vasculitis (Allergic granulomatosis and angiitis) • Eosinophilic, small arterial and venous vasculitis • Asthma in >95% of cases, usually severe requiring chronic corticosteroids • Multiple organ involvement (mononeuritis in >70%, skin rash in majority, eosinophilic gastroenteritis in majority) • P-ANCA positive in >70% • CT may show enlarged peripheral pulmonary arteries, fleeting patchy infiltrates, pulmonary nodules, pulmonary hemorrhage, pleural effusions • Pleural effusions are eosinophilic, exudative • Gold standard for diagnosis is open lung biopsy In this case… • P-ANCA and C-ANCA are negative • CT findings are not characteristic • Asthma is not severe enough, and there does not appear to be involvement of other organs REJECTED

26. Coming to a diagnosis Idiopathic Hypereosinophilic syndromes • Rare, multi-organ progressive syndromes with high morbidity • Chronic peripheral eosinophilia, >1500 for >6 months • No identifiable cause (helminths, etc) • Significant organ involvement (not benign eosinophilia) In this case… • Disease is limited to lungs • Relatively benign course • Only ~ 2 months of symptoms REJECTED

27. Coming to a diagnosis Acute eosionphilic pneumonia • Less than 7 days of illness at presentation • Hypoxemic respiratory failure is common (>50% of patients) • Peripheral eosionphilia may be a late finding, but BAL fluid and lung tissue/pleural fluid are highly eosinophilic • Radiographic findings are diffuse, patchy infiltrates without a pattern In this case… • Symptoms have been present for too long • Respiratory symptoms are fairly mild • CT findings are not characteristic - in this patient they are peripheral, not random REJECTED

28. Coming to a diagnosis Idiopathic Chronic Eosinophilic Pneumonia (AKA Carrington’s Disease) • Twice as common in women as in men • Pre-existent asthma in majority, not necessarily severe • No association with cigarettes • Syndrome Characterized by • Respiratory and systemic symptoms including fever • Absence of extrathoracic organ involvement • Alveolar and peripheral eosionophilia in nearly all • Elevated inflammatory markers in most • Elevated serum total IGE levels in majority • Pulmonary infiltrates, usually peripheral on X-ray (“photographic negative” of pulmonary edema). While not specific enough to be pathognomonic, this pattern is rare in other diseases. In this case… • A good match • patient demographic • symptoms • lab findings • x-ray findings

29. Idiopathic Chronic Eosinophilic Pneumonia • Treatment • Little research evidence • Could not find randomized controlled trials • Few prospective case series • Several review articles offering expert opinion • Expert consensus: uniformly responsive to corticosteroids • Prednisone, 40-60mg/day standard initial therapy • Gradual taper over 6-12 months • Unknown role for inhaled corticosteroids

30. Idiopathic Chronic Eosinophilic Pneumonia • Outcome • Nearly complete remission of symptoms expected within a few days of treatment • Relapses are the rule as steroids are tapered • Perhaps half will require long-term corticosteroids for symptoms • Benign course: <5% develop BOOP with pulmonary fibrosis, even fewer with clinically significant fibrosis

31. Back to the case • Patient referred to Pulmonary Clinic once diagnosis became clear • Prednisone was initiated at 60mg/day, tapered to 15mg/day over 3 weeks • The Advair was continued • She felt much better within a few days. Fever completely resolved. • CXR improved by 7 days • CXR cleared at two months • As of 11/4, she has some residual cough and chest tightness, with albuterol rescue 2 - 4 times per week (vast improvement but worse than before the onset of this illness)

33. Bibliography • Up to Date • Current Medical Diagnosis and Treatment, 2004 • Robbins Pathologic Basis of Disease • Marchand, E et al. “Idiopathic Eosinophilic Pneumonia. A Clinical and Follow-up Study of 62 cases.” Medicine. 1998; 77: 299-312 • Marchand, E et al. “ICEP and Asthma. How Do They Influence Each Other?” Eur Respir J. 2003; 22: 8-13 • Marchand, E et al. “Idiopathic Chronic Eosinophilic Pneumonia.” Orphanet Encyclopedia, updated June 2004.