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Pneumonia MimicsPneumonia MimicsPneumonia MimicsPneumonia Mimics

Jim Allen, MD,Professor of Internal Medicine

Division of Pulmonary & Critical Care MedicineOhio State University Medical Center

Causes of Community-Acquired Pneumonia in Outpatients

Causes of Community-Acquired Pneumonia in Outpatients

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JulyJuly87 year old woman with community-acquired

Case #1

acqu edpneumoniaImproves partially with empiric antibiotics

AugustAugustRe-admitted with recurrent pneumonia

Case #1

pneumoniaImproves partially with empiric antibiotics

OctoberOctoberRe-admitted with recurrent pneumoniaN i t

Case #1

No improvement with empiric antibioticsUndergoes BAL; cultures all negative

OctoberOctoberAfter 4 admissions to th h it l

Case #1

the hospital, transferred for long-term antibiotics

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NovemberNovemberAfter 3 weeks, BAL now growing acid fast bacteria

Case #1

bacteriaAfter 4 weeks, identified as M. tuberculosisInfection control nightmare begins

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Tuberculosis in 2011

Tuberculosis in 2011

“Shoot first, ask questions later”RespiratorRespiratory isolation when TB suspected4 drug treatmentAlways check drug sensitivities

The moral of the story:Don’t get bit by red snappers

The moral of the story:Don’t get bit by red snappers

HistoryHistory80 year old man admitted with hypoglycemia and status epilepticus

Case #2

status epilepticusPersistent anoxic encephalopathy and respiratory failureTransferred for ventilator weaning after 6 days in ICU

After 4 weeks:Still ventilator dependentDaily fevers to 102

Case #2

yF despite 1 week of empiric antibioticsBlood eosinophil count 570BAL: 11% eosinophils; no pathogens

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Diagnosis: phenytoin-induced lung diseaseDiagnosis: phenytoin-induced lung diseaseAntibiotics stoppedPnenytoin stopped

Case #2

Pnenytoin stoppedShort course corticosteroidsFever & pulmonary infiltrates resolvedRespiratory failure resolved and weaned off of the ventilator

Can be very easy to missClues:

Peripheral pulmonary

Drug-induced lung disease:Drug-induced lung disease:

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pulmonary infiltratesBlood eosinophilia (>350/cmm)BAL eosinophiliaSkin rash

Diagnosis of exclusion

Common Drugs:Common Drugs:

PhenytoinMacrodantin

SulfasalazineCocaine

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AmiodaroneMinocyclineMethotrexateBleomycin

ACE inhibitors (cough)Sulfa-containing antibiotics

Mesalamine (Asacol)Mesalamine (Asacol)

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Macrobid(macrodantin)

Macrobid(macrodantin)

Drug-induced lung disease may be very difficult to confirmRe-challenge is riskywww.pneumotox.com is a great resourceD t di th

The morals of the story:The morals of the story:

Doctors cause more disease than we realize

79 year old manCough and dyspnea onset in November 2009

Case #3

Hospitalized with pneumonia in February 2010 and treated with empiric antbioticsImproved but not back to normal when seen in April 2010

Former smokerLandscaperExam: crackles in the lower left lung

Case #3

gLabs: eosinophil count = 460Not taking any candidate drugs for drug-induced lung disease

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Case #3

Case #3

Anti-strongyloides antibody positiveAnti-strongyloides antibody positive

Case #3

Case #3After treatment with After treatment with ivermectinivermectin

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StrongyloidesStrongyloidesLives in the intestineOnce infected, always infectedCorticosteroids are wormCorticosteroids are worm fertilizerSerology is the best diagnostic test

Strongyloides is sneaky

Strongyloides is sneaky

87 year old mother of OSU physicianRecurrent “colitis”, eosinopilia pulmonaryeosinopilia, pulmonary infiltrates and cough for 20 yearsPositive anti-strongyloides antibodySymptoms resolved with ivermectin

35 YO CM with tuberous sclerosis and severe mental retardationR t f &

You’ll miss it if you only order the regular stool

O&P examYou’ll miss it if you only order the regular stool

O&P exam

Recurrent fevers & pseudomonas pneumoniaPersistent fevers and blood eosinophilia (up to 2,700/mcL)Stool O&P negative (antigenic)

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Worms are everywhereNon-resolving pneumonia + peripheral eosinophilia = order a strongyloides antibody titer

The morals of the story:The morals of the story:

y

HistoryHistory64 yr old man exposed to black dust in ceiling tiles during remodeling Feb, 2004Diagnosed with RLL pneumonia by CXR

Case #4

Diagnosed with RLL pneumonia by CXR and symptoms improved with ATBSubsequent CXRs and CTs showed progression of infiltrates

History (cont)History (cont)

PMH – no illnessesSx – architectural designer; 100 PY

Case #4

smoker; son is a radiology residentROS – all negativeMoist crackles RLL posterior; no egophony

Labs (Dec, 2004)Labs (Dec, 2004)Fungal serologies, urine histo antigen all negBAL – 52% MP, 27% N, 15% L, 6% E;

Case #4

negative AFB, fungal cultures; cytology negativeTransbronchial biopsy – calcified granuloma with histo organisms seenBrushings – negative cytology

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May, 2005May, 2005Repeat BAL: negative cultures, negative cytology

Case #4

Surgical lung biopsy: possible cryptogenic organizing pneumonia

Clinical Course (con’t)Clinical Course (con’t)Trial of prednisone 40 mg/day – no subjective improvementRepeat BAL Dec 2005: 71% MP 18% N

Case #4

Repeat BAL Dec, 2005: 71% MP, 18% N, 10% L, 1% E; negative cultures and cytologyTransbronchial biopsy = no cancer

February, 2006February, 2006Severe hypoxemiaAdmitted to ICU and subsequently has 6 week hospitalization for

Case #4

week hospitalization for antibiotics & steroidsDeclined 2nd surgical lung biopsyEventually discharged home with hospiceDied January, 2007

Case #4

Autopsy slides

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Bronchoalveolarcarcinoma

Bronchoalveolarcarcinoma

The great impersonatorOften hard to

Radiographic presentations:

Lobar consolidation

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Often hard to diagnose in life even with surgical biopsy

Solitary pulmonary noduleDiffuse patchy infiltratesMultiple pulmonary nodules

Non-small cell lung cancers

Non-small cell lung cancers

AdenocarcinomaSquamous cell carcinomaLarge cell undifferentiated carcinomaBronchoalveolar carcinoma

The moral of the story:Non-resolving pneumonia is usually not pneumonia

The moral of the story:Non-resolving pneumonia is usually not pneumonia

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69 year old woman admitted with cough in November 2009Improved transiently with cefpodoxime but relapsed after 2 weeks

Case #5

but relapsed after 2 weeksRe-admitted in February 2010 and improved again with levafloxacin; BAL bacterial, fungal, AFB cultures negative

Normal IgGNegative anti-CCPNegative ANA

Normal fungal titersNormal hypersensitivity

Case #5

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gNormal QuantiferonNormal alpha-1-antitrypsin

panelNormal serum protein electrophoresisNormal CBC

Case #5

Sent home and told to not take antibioticsReturned for bronchoscopy when antibiotic-free

Case #5

antibiotic freeBAL:

34% macrophages54% neutrophils11% lymphocytes1% eosinophils

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Bronchial washings and BAL = Mycobacterium avium complex

Case #5

Mycobacterium avium complex

Case #5

After initiation of 3-drug treatment3-drug treatment

M. avium complexM. avium complexOccurs in:

Naturally occurring water sourcesAnimalsHeated waterHeated water systems

Incidence probably underestimatedJust growing it doesn’t mean you’ve got it!

Frequency of non-tuberculousmycobacterial infections

Frequency of non-tuberculousmycobacterial infections

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M. avium complex: four main clinical syndromes

M. avium complex: four main clinical syndromes

1. HIV-associated2. Cavitary lung disease

MalePre-existing lung di

3. Cystic fibrosis-associated

4. Mid-lung diseaseOtherwise healthy women

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diseaseAgeAlcoholism Upper lobe infiltrates or cavities

womenOver age 50 yrsLingular or RML nodular diseasePresent with cough and no systemic symptoms“Lady Windermere Syndrome”

Lady Windermere’s Fan (1892) Lady Windermere’s Fan (1892)

Reich JM & Johnson RE. Mycobacterium avium complex pulmonary disease presenting as p gisolated lingular or middle lobe pattern: The Lady Windermere Syndrome. Chest 1992; 101:1605

Oscar Wilde

M. avium complex: other pulmonary syndromes

M. avium complex: other pulmonary syndromes

Infection associated with pectus excavatumSolitary pulmonary noduleHypersensitivity pneumonitis (“hot tub lung”)

44 year old woman with:44 year old woman with:

Lichen planus treated with a TNF inhibitor Lymphoma treated with rituxamabRecurrent pneumoniaRespiratory failure requiring transfer to LTACH for ventilator weanBAL = Mycobacterium abscessus

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45 year old man with ‘refractory pneumonia’45 year old man with

‘refractory pneumonia’

51 year old woman withchronic lymphocytic

leukemia

51 year old woman withchronic lymphocytic

leukemiaRecurrent bronchitis & pneumoniaTransiently improves with antibioticsBAL = M. avium complex

Mycobacterium AviumComplex: Treatment

Mycobacterium AviumComplex: Treatment

Clarithromycin (1,000mg) or azithromycin (500mg) three times a week Rifampin (600 mg) or rifabutin (300 mg) three times a weekEthambutol (25mg/kg) three times a weekStreptomycin two to three times per week should be considered for the first eight weeks as toleratedTreat for a long, long, long time

ATS/IDSA Statement: Diagnosis, Treatment, and Prevention of Disease Caused by Nontuberculous Mycobacteria. Am J Respir Crit Care Med2007: 175: 367-416

Bronchiectasis + Nodules = MACBronchiectasis + Nodules = MAC

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58 year old woman with recurrent pneumonia and

cough

58 year old woman with recurrent pneumonia and

cough

BronchiectasisBronchiectasis Nodules

The moral of the story:A high-resolution chest CT sometimes paints a picture

worth a thousand chest x-rays

The moral of the story:A high-resolution chest CT sometimes paints a picture

worth a thousand chest x-rays

19 yr old OSU undergraduate student3 days of increasing:

Case #6

3 days of increasing:DyspneaPleuritic chest painFeverMyalgias

Physical exam:Tachypneic with labored respirations

Laboratory studies:

WBC = 15,000O2 46

Case #6

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respirationsTemperature = 101 FLungs = scant bi-basilar crackles

pO2 = 46 (room air)

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Intubated on presentationBAL:

Case #6

60% eosinophils20% macrophages15% lymphocytes5% neutrophils

All cultures negative

Acute Eosinophilicpneumonia

Acute Eosinophilicpneumonia

Presentation:Average symptoms 4 daysAverage age 29

Exam:Average temperature 101 degrees F

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yrsSymptoms:

Cough 100%Dyspnea 95%Chest pain 73%Myalgias 50%

>40% “beginner” smokers

gAverage respiratory rate 32/minCrackles in 80%

Acute Eosinophilic pneumoniaAcute Eosinophilic pneumoniaChest X-ray:

Kerley B linesInterstitial infiltratesAlveolar infiltrates

Lab:Average WBC 17,000

Blood eosinophils not usually elevated

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Pleural effusionselevated

Average pO2 57 mmIgE sometimes elevatedPFTs:

RestrictionLow diffusing capacity

Acute Acute EosinophilicEosinophilic Pneumonia Day #1Pneumonia Day #1

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Acute Acute EosinophilicEosinophilic Pneumonia Day #2Pneumonia Day #2

Acute Acute EosinophilicEosinophilic Pneumonia Day #3Pneumonia Day #3

Acute Acute EosinophilicEosinophilic Pneumonia Day #7Pneumonia Day #7

Acute EosinophilicPneumonia

Acute EosinophilicPneumonia

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Acute Eosinophilicpneumonia

Acute Eosinophilicpneumonia

Typical BAL:37% eosinophils20% lymphocytes15% neutrophils28% macrophages

Lung biopsy:Intra-alveolar eosinophils

Acute EosinophilicPneumonia Treatment:

Acute EosinophilicPneumonia Treatment:Methylprednisolone 125 mg/6 hours until respiratory failure resolvesPrednisone 60 mg/d - taper over a monthRelapses do not occur

Acute Eosinophilic Pneumonia: Causes/MimicsAcute Eosinophilic Pneumonia: Causes/Mimics

IdiopathicCigarette smokingPrescription drugsStreet drugsOrganic dust inhalationParasites

Acute eosinophilic pneumonia among US Military personnel

deployed in or near IraqShorr, et al. JAMA 2004: 292:2997-3005

Acute eosinophilic pneumonia among US Military personnel

deployed in or near IraqShorr, et al. JAMA 2004: 292:2997-3005

18 cases out of 183,000 deployed military78% recently beginning to smokeBAL = 40% eosinophils2/3 required mechanical ventilation2 diedSurvivors recovered completely

Acute eosinophilic pneumonia among US Military personnel deployed in or near Iraq. Shorr AF, Scoville SL, Cersovsky SB, et al. JAMA. 2004;292(24):2997-3005

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Why eosinophils and football don’t mix

Why eosinophils and football don’t mix

September 30, 1995

The moral of the story:A bronchoscopy can be a

powerful thing

The moral of the story:A bronchoscopy can be a

powerful thing

51 year old man with cough and dyspnea for 3 weeks. No improvement after a course of azithromycin and albuterolNon-smoker who works in sales. He has a hot tub

Case #7

Exam: dry crackles on the rightPFTs: restriction with low diffusing capacityLab: autoimmune serologies, fungal serologies, hypersensitivity serologies all negative

Case #7

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Case #7

Case #7

Cryptogenic organizing pneumonia

Cryptogenic Organizing Pneumonia

Cryptogenic Organizing Pneumonia

Clinical presentation:40-60 years oldSymptoms less than 2 months

C t i diti dCauses: autoimmune conditions, drugs, idiopathicLung biopsy required for confident diagnosisTreatment:

Prednisone (2/3 patients respond)Duration = >6 months

Cryptogenic organizing pneumonia (aka “BOOP”: Bronchiolitis Obliterans

Organizing Pneumonia)(aka crytogenic organizing pneumonia)

Cryptogenic organizing pneumonia (aka “BOOP”: Bronchiolitis Obliterans

Organizing Pneumonia)(aka crytogenic organizing pneumonia)

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Sub-pleural clearing in BOOPSub-pleural clearing in BOOP

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The moral of the story:A non-resolving pulmonary infiltrate and a non-diagnostic bronchoscopyis an invitation to a surgical biopsy

The moral of the story:A non-resolving pulmonary infiltrate and a non-diagnostic bronchoscopyis an invitation to a surgical biopsy

HistoryHistory66 yr old with severe emphysemaHome O2 for 4 yearsMeds: inhaled steroid tiotropium

Case #8

Meds: inhaled steroid, tiotropium, PRN albuterolFormer banker; quit smoking 8 years ago

History leading to admission

History leading to admission

October - COPD exacerbation treated with steroids & doxycycline

Case #8

with steroids & doxycyclineNovember - admitted with RUL pneumonia treated with moxifloxacinMarch - RUL pneumonia treated with moxifloxacinApril – still had RUL infiltrate

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Case #8

BronchoscopyBronchoscopyRight upper lobe occluded by an endobronchial mass

C l i

Case #8

Cultures negativeCytology and endobronchial biopsy negative

Repeat BronchoscopyRepeat BronchoscopyWashings/brushings negativeBiopsy - respiratory epithelium with moderate mixed acute and chronic i fl ti f t f f i

Case #8

inflammation; fragment of foreign material consistent with vegetable materialFollowing the bronchoscopy, he expectorated a mummified kernel of corn

Bronchoalveolar lavageBronchoalveolar lavageCell differential = 84% neutrophilsGram positive cocci, Gram positive rods Gram positive

Case #8

positive rods, Gram positive beaded bacilliRe-review of BAL and both biopsies by GMS stain indicate branching filamentous bacteria consistent with actinomyces

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Pulmonary ActinomycesPulmonary ActinomycesAll ages - peak age = 4th & 5th decadesMale:female = 2:1 to 4:1Risk factors: poor dental hygieneRisk factors: poor dental hygiene, emphysma, chronic bronchitis, alcoholism, bronchiectasisUsual presentation = abnormal x-rayNot usually associated with immunosuppression

ActinomycosisActinomycosisAnaerobic (often won’t grow)Tends to cross thoracic boundariesOften has “companion bacteria”Th t tiThree presentations:

CervicofacialAbdominopelvicThoracic

RadiologyRadiology

Pneumonia - like patternTends to cross fissuresCan invade adjacent tissuesCan invade adjacent tissues

CT:Airspace consolidationMassPleural effusions (small)Mediastinal adenopathy

Upper lobe consolidationUpper lobe consolidation

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Right middle lobe consolidation

Right middle lobe consolidation

Pulmonary nodulePulmonary nodule

Mass-like with erosion into chest wall and ribsMass-like with erosion into chest wall and ribs

Actinomycosis: TreatmentActinomycosis: Treatment

PenicillinDrainage when possibleg pAlternative antibiotics:

DoxycyclineErythromycinClindamycin

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The morals of the story:1. The gram stain report may have more information than the culture report2. Corn does not belong in the airway

The morals of the story:1. The gram stain report may have more information than the culture report2. Corn does not belong in the airway

HistoryHistory48 year old man with pneumonia and anemia Progressive dyspnea for 2 months

Case #9

for 2 monthsBlood and bronchoalveolar lavage cultures all negativeReferred for antibiotics & pulmonary rehabilitation

Fails to improve despite 3 weeks of antibioticsSed rate 120

Case #9

Sed rate 120 secondsReferred for surgical lung biopsy

Case #9

Image of lung in at the time of VATS

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Wegener’s granulomatosisWegener’s granulomatosisCase #9

Wegener’s granulomatosisWegener’s granulomatosisCase #9

Wegener’s with cavityWegener’s with cavity

Wegener’s granulomatosisWegener’s granulomatosisConsider in:

Alveolar hemorrhageLung cavitiesPulmonary infiltrate + hematuria

Elevated cANCA highly suggestive (but not diagnostic)Diagnosis requires biopsyTreatment = steroids plus cyclophosphamide

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The moral of the story:Maintain a healthy sense of skepticism about referral diagnoses that don’t make sense

The moral of the story:Maintain a healthy sense of skepticism about referral diagnoses that don’t make sense

41 year old woman with dyspnea and cough for 2 months. No improvement after a course of azithromycinPMH: hypertension and hypothyroidism

Case #10

SH: non-smoker; teacher’s aid for MRDD pre-school childrenExam: basilar right-sided crackles

Sent for evaluation for possible surgical lung biopsy

Case #10

And then she said…And then she said…“And oh by the way, did I tell you that we raise goats and donkeys in the barn in our back yard?”“And oh by the way, did I tell you we have

Case #10

y y, ya Quaker Parrot? And Cockatiels? And Parakeets?”“And oh by the way, did I tell you we have birds living in our attic and there’s a hole in my closet ceiling so that my clothes are covered with bird feathers and bird poop?”

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Antibody Normal Value Patient

Canary Feathers <17 34 (H)

Finch Feathers <12 59 (H)

Case #10

Parrott Droppings <14 91 (H)

Parrott Proteins <12 50 (H)

Pigeon Droppings <70 78 (H)

Pigeon Feathers <22 60 (H)

Hypersensitivity PneumonitisHypersensitivity PneumonitisEtiology often hard to identify

BirdsHot tubsOccupation

Treatment:Remove offending antigenPrednisone

Outcome:

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OccupationDrug

T-suppressor cell alveolitis

Outcome:Complete resolutionChronic fibrosis

Hot TubHypersensitivity

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Drug-inducedHypersensitivity

Feather pillowHypersensitivity

The moral of the story:

The moral of the story:

Birds are badFeather pillows are just as badHot tubs are worse

Clinical approach to non-resolving infiltrates

Clinical approach to non-resolving infiltrates

Take a history!Never, ever, ever, ever miss tuberculosistuberculosisChest CT scanBronchoscopySurgical lung biopsy if all else fails

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The moral of the The moral of the story:story:

Sometimes nonSometimes non--l il i

The moral of the The moral of the story:story:

Sometimes nonSometimes non--l il iresolving resolving

pneumonia is just pneumonia is just pneumoniapneumoniaresolving resolving

pneumonia is just pneumonia is just pneumoniapneumonia