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. Current Visit: Follow-up abnormal CXR
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: 2180 eosinophils 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 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:
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.