A Slice of PIE

A Slice of PIEA Slice of PIE

Neal Waechter, MDNeal Waechter, MD

Disclosure and ObjectivesDisclosure and Objectives

No financial supportNo financial support

Present casePresent case Discuss approach to caseDiscuss approach to case Discuss outcome of caseDiscuss outcome of case

CaseCase

30 year old woman with chronic cough30 year old woman with chronic cough

HPI:HPI: 10 weeks ago: first “asthma exacerbation” (mild exercise-induced 10 weeks ago: first “asthma exacerbation” (mild exercise-induced

asthma for years), reports to urgent care (Visit #1)asthma for years), reports to urgent care (Visit #1) Symptoms:Symptoms:

CoughCough Moderate to severe dyspnea Moderate to severe dyspnea Fever 101Fever 101 Fatigue/malaiseFatigue/malaise

Treatment:Treatment: nebulizernebulizer Advair inhalerAdvair inhaler

CaseCase

HPIHPI 8 weeks ago: Return to urgent care still feeling 8 weeks ago: Return to urgent care still feeling

ill (visit #2)ill (visit #2) SymptomsSymptoms

still febrile (101)still febrile (101) still dyspneic despite using Advair as prescribedstill dyspneic despite using Advair as prescribed cough now productive of green, sometimes dark brown cough now productive of green, sometimes dark brown

sputumsputum

TreatmentTreatment Amoxacillin x 10 daysAmoxacillin x 10 days

CaseCase

HPIHPI 5 weeks ago: Return to urgent care with 5 weeks ago: Return to urgent care with

same complaints (Visit #3)same complaints (Visit #3) SymptomsSymptoms

Improved very slightly after amoxacillin, but Improved very slightly after amoxacillin, but promptly returned to previous levelspromptly returned to previous levels

Persistent fever, productive cough, dyspneaPersistent fever, productive cough, dyspnea TreatmentTreatment

Azithromycin x 5 daysAzithromycin x 5 days

CaseCase

HPIHPI 1.5 weeks ago: Return to urgent care with persistent 1.5 weeks ago: Return to urgent care with persistent

symptoms (Visit #4) and new chest painsymptoms (Visit #4) and new chest pain SymptomsSymptoms

Unchanged fever, cough, dyspnea, no help from azithromycinUnchanged fever, cough, dyspnea, no help from azithromycin New onset of sharp left-sided pleuritic chest pain, thought she New onset of sharp left-sided pleuritic chest pain, thought she

broke a ribbroke a rib Diagnostic testsDiagnostic tests

CXR – “patchy airspace disease in RUL, suspicious for CXR – “patchy airspace disease in RUL, suspicious for pneumonia”pneumonia”

TreatmentTreatment Augmentin 875 BID x 10 daysAugmentin 875 BID x 10 days

CaseCase

HPIHPI 1 week ago: Follow-up with PCP (Visit #5)1 week ago: Follow-up with PCP (Visit #5)

Symptoms: unchangedSymptoms: unchanged Exam: Exam:

Temp 100.2Temp 100.2 Diffuse wheezingDiffuse wheezing

TreatmentTreatment Continue antibioticsContinue antibiotics Resume AdvairResume Advair Follow-up CXR in one weekFollow-up CXR in one week

HPIHPI Current Visit: Follow-up abnormal CXRCurrent Visit: Follow-up abnormal CXR

Symptoms: Symptoms: Still intermittent fever up to 101Still intermittent fever up to 101 Chest pain has largely resolvedChest pain has largely resolved Dyspnea, productive cough continue w/o Dyspnea, productive cough continue w/o

hemoptysishemoptysis

ROSROS Negative leg pain, h/o DVT/PE (VQ Negative leg pain, h/o DVT/PE (VQ

performed 2 years ago during pregnancy for performed 2 years ago during pregnancy for chest pain was negative), arthralgia, rash, chest pain was negative), arthralgia, rash, dysuria, GI symptomsdysuria, GI symptoms

Positive for mild myalgias, occasional Positive for mild myalgias, occasional headachesheadaches

CaseCase

PMHPMH Mild intermittent/exercise-induced asthma, long historyMild intermittent/exercise-induced asthma, long history Allergic rhinitisAllergic rhinitis MigraineMigraine DepressionDepression

SHSH Non-smokerNon-smoker One child age one, currently breastfeedingOne child age one, currently breastfeeding Work – case manager and social worker in Geriatrics, currently not workingWork – case manager and social worker in Geriatrics, currently not working

Exposure HistoryExposure History No known exposure to TB, last PPD April 2002, negativeNo known exposure to TB, last PPD April 2002, negative No birds, exotic petsNo birds, exotic pets No recent travelNo recent travel

FH:FH: Mother had DVT when bedridden with acute viral hepatitisMother had DVT when bedridden with acute viral hepatitis GM had DVT, unknown risk factorGM had DVT, unknown risk factor

Allergies: CephalexinAllergies: Cephalexin

Meds: Albuterol, Pirbuterol, Advair Meds: Albuterol, Pirbuterol, Advair

CaseCase

ExamExam 230 pounds, BP 110/80, HR 76, T 96.7230 pounds, BP 110/80, HR 76, T 96.7 Appeared comfortable, no resp distressAppeared comfortable, no resp distress Decreased breath sounds upper right posterior Decreased breath sounds upper right posterior

lung field, egophonylung field, egophony Normal percussion and tactile fremitusNormal percussion and tactile fremitus No wheezes or ralesNo wheezes or rales No clubbing or cyanosisNo clubbing or cyanosis Normal ENT, lymph node, cardiovascular, Normal ENT, lymph node, cardiovascular,

abdominal, musculoskeletal, skinabdominal, musculoskeletal, skin

CaseCase

CXRCXR

(IMAGE)(IMAGE)

What next?What next?

What are the likely possibilities?What are the likely possibilities? What can we not miss?What can we not miss?

Initial Thoughts – “Can’t Miss”Initial Thoughts – “Can’t Miss”

Atypical infectious pneumoniasAtypical infectious pneumonias FungalFungal TB/mycobacterialTB/mycobacterial

Collagen Vascular DiseasesCollagen Vascular Diseases Vasculitis (esp. Churg-Strauss)Vasculitis (esp. Churg-Strauss) CancerCancer Venous Thromboembolism and other Venous Thromboembolism and other

embolic diseaseembolic disease

Initial PlanInitial Plan

DiagnosticsDiagnostics CBC: WBC 12.7, Hgb 13.3, Plt 315CBC: WBC 12.7, Hgb 13.3, Plt 315 ESR: 50ESR: 50 CRP: 2CRP: 2 Chem: Cr 0.7, ALT 26Chem: Cr 0.7, ALT 26 UA: Sp gr >1.030, 2-5 wbc, 0-1 rbc, neg dipUA: Sp gr >1.030, 2-5 wbc, 0-1 rbc, neg dip One sputum for AFB (difficulty producing One sputum for AFB (difficulty producing

adequate specimen) pendingadequate specimen) pending

Case Summary So FarCase Summary So Far

History of mild intermittent asthmaHistory of mild intermittent asthma Chronic CoughChronic Cough DyspneaDyspnea Intermittent feverIntermittent fever LeukocytosisLeukocytosis Persistent pulmonary infiltrates on CXRPersistent pulmonary infiltrates on CXR Multiple areas of airspace disease on CT, Multiple areas of airspace disease on CT,

upper lobe/peripheral predominance upper lobe/peripheral predominance

Differential DiagnosisDifferential Diagnosis

Airway DisordersAirway Disorders AsthmaAsthma CFCF

Pulmonary infectionsPulmonary infections TBTB Other mycobacteriaOther mycobacteria FungiFungi ParasitesParasites Opportunistic organismsOpportunistic organisms

CancerCancer


Pulmonary vascular disordersPulmonary vascular disorders Pulmonary embolism/infarctionPulmonary embolism/infarction Vasculitis and Pulmonary Renal SyndromesVasculitis and Pulmonary Renal Syndromes

Wegener’sWegener’s Goodpasture’sGoodpasture’s Churg-StraussChurg-Strauss

Environmental/Occupational Lung Environmental/Occupational Lung diseasedisease Hypersensitivity pneumonitisHypersensitivity pneumonitis


Interstitial Lung DiseasesInterstitial Lung Diseases Idiopathic Fibrosing Interstitial PneumoniasIdiopathic Fibrosing Interstitial Pneumonias

UIP (IPF)UIP (IPF) RB-ILD (DIP)RB-ILD (DIP) AIPAIP NSIPNSIP BOOPBOOP

SarcoidosisSarcoidosis Collagen Vascular DiseasesCollagen Vascular Diseases AmyloidosisAmyloidosis Pulmonary Alveolar proteinosisPulmonary Alveolar proteinosis Pulmonary Infiltrates with Eosinophilia (PIE)Pulmonary Infiltrates with Eosinophilia (PIE)

““Light bulb”Light bulb”

Recall cases of eosinophilic pulmonary syndromes Recall cases of eosinophilic pulmonary syndromes from residency with similar presentationfrom residency with similar presentation

No sig exposure to TB, no evidence of PE, cancer, on No sig exposure to TB, no evidence of PE, cancer, on CT, no occupational exposures, no sig travel, doesn’t CT, no occupational exposures, no sig travel, doesn’t really fit other diagnoses on listreally fit other diagnoses on list

Patient has a history of asthmaPatient has a history of asthma Elevated WBC, but no diff – could this be eosinophilia?Elevated WBC, but no diff – could this be eosinophilia?

Plan: Add differential to yesterday’s bloodPlan: Add differential to yesterday’s blood

On to something…On to something…

Diff:Diff: 6950 neutrophils6950 neutrophils 3210 lymphs3210 lymphs 40 basophils40 basophils 302 monocytes302 monocytes

2180 eosinophils2180 eosinophils

PIEPIE

Pulmonary Infiltrates with Eosinophilia (PIEPulmonary Infiltrates with Eosinophilia (PIE)) InfectionsInfections

HelminthsHelminths Loffler’s syndrome (Ascaris, hookworm, strongyloides)Loffler’s syndrome (Ascaris, hookworm, strongyloides) Non life cycle pulmonary invasion (paragonimiasis,others)Non life cycle pulmonary invasion (paragonimiasis,others) Tropical pulmonary eosinophilia (Wucheria)Tropical pulmonary eosinophilia (Wucheria)

Sometimes, CoccidiomycosisSometimes, Coccidiomycosis Rarely, TBRarely, TB

Medications/crack cocaineMedications/crack cocaine NSAIDS/SalicylatesNSAIDS/Salicylates MinocyclineMinocycline Trimethoprim/sulfamethoxazoleTrimethoprim/sulfamethoxazole

ABPAABPA Churg-StraussChurg-Strauss Idiopathic Hypereosinophilic syndromesIdiopathic Hypereosinophilic syndromes Idiopathic eosinophilic pneumoniaIdiopathic eosinophilic pneumonia

Acute eosinophilic pneumoniaAcute eosinophilic pneumonia Chronic eosinophilic pneumoniaChronic eosinophilic pneumonia

Coming to a diagnosisComing to a diagnosis

ABPAABPA Typically a sino-pulmonary syndrome with prominent sinus Typically a sino-pulmonary syndrome with prominent sinus

symptomssymptoms Must have skin prick test or serum IGE/IGG positive for Must have skin prick test or serum IGE/IGG positive for

AspergillusAspergillus Typical CT finding is widespread proximal bronchiectasis with Typical CT finding is widespread proximal bronchiectasis with

upper lobe predominance, mucus plugging, and patchy upper lobe predominance, mucus plugging, and patchy infiltrates/atelectasisinfiltrates/atelectasis

In this case…In this case… Not entirely ruled out – did not do skin test or serum antibody testsNot entirely ruled out – did not do skin test or serum antibody tests No sinus disease symptoms/signsNo sinus disease symptoms/signs CT findings not characteristic (does not exclude diagnosis)CT findings not characteristic (does not exclude diagnosis)

Possible…Possible…


Churg-Strauss Vasculitis Churg-Strauss Vasculitis (Allergic granulomatosis and angiitis)(Allergic granulomatosis and angiitis) Eosinophilic, small arterial and venous vasculitisEosinophilic, small arterial and venous vasculitis Asthma in >95% of cases, usually severe requiring chronic corticosteroidsAsthma in >95% of cases, usually severe requiring chronic corticosteroids Multiple organ involvement (mononeuritis in >70%, skin rash in majority, Multiple organ involvement (mononeuritis in >70%, skin rash in majority,

eosinophilic gastroenteritis in majority)eosinophilic gastroenteritis in majority) P-ANCA positive in >70%P-ANCA positive in >70% CT may show enlarged peripheral pulmonary arteries, fleeting patchy infiltrates, CT may show enlarged peripheral pulmonary arteries, fleeting patchy infiltrates,

pulmonary nodules, pulmonary hemorrhage, pleural effusionspulmonary nodules, pulmonary hemorrhage, pleural effusions Pleural effusions are eosinophilic, exudativePleural effusions are eosinophilic, exudative Gold standard for diagnosis is open lung biopsyGold standard for diagnosis is open lung biopsy

In this case…In this case… P-ANCA and C-ANCA are negativeP-ANCA and C-ANCA are negative CT findings are not characteristicCT findings are not characteristic Asthma is not severe enough, and there does not appear to be involvement of Asthma is not severe enough, and there does not appear to be involvement of

other organsother organs

REJECTEDREJECTED


Idiopathic Hypereosinophilic syndromesIdiopathic Hypereosinophilic syndromes Rare, multi-organ progressive syndromes with high Rare, multi-organ progressive syndromes with high

morbiditymorbidity Chronic peripheral eosinophilia, >1500 for >6 monthsChronic peripheral eosinophilia, >1500 for >6 months No identifiable cause (helminths, etc)No identifiable cause (helminths, etc) Significant organ involvement (not benign eosinophilia)Significant organ involvement (not benign eosinophilia)

In this case…In this case… Disease is limited to lungsDisease is limited to lungs Relatively benign courseRelatively benign course Only ~ 2 months of symptomsOnly ~ 2 months of symptoms

REJECTEDREJECTED


Acute eosionphilic pneumoniaAcute eosionphilic pneumonia Less than 7 days of illness at presentationLess than 7 days of illness at presentation Hypoxemic respiratory failure is common (>50% of patients)Hypoxemic respiratory failure is common (>50% of patients) Peripheral eosionphilia may be a late finding, but BAL fluid and Peripheral eosionphilia may be a late finding, but BAL fluid and

lung tissue/pleural fluid are highly eosinophiliclung tissue/pleural fluid are highly eosinophilic Radiographic findings are diffuse, patchy infiltrates without a Radiographic findings are diffuse, patchy infiltrates without a

patternpattern

In this case…In this case… Symptoms have been present for too longSymptoms have been present for too long Respiratory symptoms are fairly mildRespiratory symptoms are fairly mild CT findings are not characteristic - in this patient they are CT findings are not characteristic - in this patient they are

peripheral, not randomperipheral, not random

REJECTEDREJECTED


Idiopathic Chronic Eosinophilic Pneumonia Idiopathic Chronic Eosinophilic Pneumonia (AKA Carrington’s Disease)(AKA Carrington’s Disease) Twice as common in women as in menTwice as common in women as in men Pre-existent asthma in majority, not necessarily severePre-existent asthma in majority, not necessarily severe No association with cigarettesNo association with cigarettes Syndrome Characterized bySyndrome Characterized by

Respiratory and systemic symptoms including feverRespiratory and systemic symptoms including fever Absence of extrathoracic organ involvementAbsence of extrathoracic organ involvement Alveolar and peripheral eosionophilia in nearly allAlveolar and peripheral eosionophilia in nearly all Elevated inflammatory markers in mostElevated inflammatory markers in most Elevated serum total IGE levels in majorityElevated serum total IGE levels in majority Pulmonary infiltrates, usually peripheral on X-ray (“photographic negative” of pulmonary 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 edema). While not specific enough to be pathognomonic, this pattern is rare in other diseases.diseases.

In this case…In this case… A good matchA good match

patient demographicpatient demographic symptomssymptoms lab findingslab findings x-ray findingsx-ray findings

Idiopathic Chronic Idiopathic Chronic Eosinophilic PneumoniaEosinophilic Pneumonia

TreatmentTreatment Little research evidenceLittle research evidence

Could not find randomized controlled trialsCould not find randomized controlled trials Few prospective case seriesFew prospective case series Several review articles offering expert opinionSeveral review articles offering expert opinion

Expert consensus: uniformly responsive to Expert consensus: uniformly responsive to corticosteroidscorticosteroids

Prednisone, 40-60mg/day standard initial therapyPrednisone, 40-60mg/day standard initial therapy Gradual taper over 6-12 monthsGradual taper over 6-12 months Unknown role for inhaled corticosteroidsUnknown role for inhaled corticosteroids

Idiopathic Chronic Idiopathic Chronic Eosinophilic PneumoniaEosinophilic Pneumonia

OutcomeOutcome Nearly complete remission of symptoms Nearly complete remission of symptoms

expected within a few days of treatmentexpected within a few days of treatment Relapses are the rule as steroids are Relapses are the rule as steroids are

taperedtapered Perhaps half will require long-term Perhaps half will require long-term

corticosteroids for symptomscorticosteroids for symptoms Benign course: <5% develop BOOP with Benign course: <5% develop BOOP with

pulmonary fibrosis, even fewer with clinically pulmonary fibrosis, even fewer with clinically significant fibrosissignificant fibrosis

Back to the caseBack to the case

Patient referred to Pulmonary Clinic once diagnosis Patient referred to Pulmonary Clinic once diagnosis became clearbecame clear

Prednisone was initiated at 60mg/day, tapered to Prednisone was initiated at 60mg/day, tapered to 15mg/day over 3 weeks15mg/day over 3 weeks

The Advair was continuedThe Advair was continued She felt much better within a few days. Fever She felt much better within a few days. Fever

completely resolved.completely resolved. CXR improved by 7 daysCXR improved by 7 days CXR cleared at two monthsCXR cleared at two months As of 11/4, she has some residual cough and chest As of 11/4, she has some residual cough and chest

tightness, with albuterol rescue 2 - 4 times per week tightness, with albuterol rescue 2 - 4 times per week (vast improvement but worse than before the onset of (vast improvement but worse than before the onset of this illness)this illness)

BibliographyBibliography

Up to DateUp to Date Current Medical Diagnosis and Treatment, 2004Current Medical Diagnosis and Treatment, 2004 Robbins Pathologic Basis of DiseaseRobbins Pathologic Basis of Disease Marchand, E et al. “Idiopathic Eosinophilic Pneumonia. Marchand, E et al. “Idiopathic Eosinophilic Pneumonia.

A Clinical and Follow-up Study of 62 cases.” Medicine. A Clinical and Follow-up Study of 62 cases.” Medicine. 1998; 77: 299-3121998; 77: 299-312

Marchand, E et al. “ICEP and Asthma. How Do They Marchand, E et al. “ICEP and Asthma. How Do They Influence Each Other?” Eur Respir J. 2003; 22: 8-13Influence Each Other?” Eur Respir J. 2003; 22: 8-13

Marchand, E et al. “Idiopathic Chronic Eosinophilic Marchand, E et al. “Idiopathic Chronic Eosinophilic Pneumonia.” Orphanet Encyclopedia, updated June Pneumonia.” Orphanet Encyclopedia, updated June 2004.2004.

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