Unusual cause of complicated pneumoniaMyMy Buu, MDPediatric Pulmonary FellowStanford University School of Medicine

Referral from pediatrician

2 year old male, fraternal twin born at term, previously healthy.

Reason: Persistent pneumonia with effusion despite antibiotic treatment.

History of Present Illness•9 weeks prior to referral: • Low grade high temperatures 99-100. • Loss of appetite, lost 3 pounds. •Sleep disturbance with arousals.

•7 weeks prior: • T102.9. No source of fever found on

physical exam by PMD.•2 days later: •Returned to PMD for persistent fevers. CXR

done.

Clinical course

•Treated with ▫IM ceftriaxone x 2 days, then▫Oral cefdinir x 10 days

•Clinical symptoms: •O2 saturation 100% RA. No respiratory

symptoms. •Continued to have temps 99-100. Fatigue.

•Returned to PMD 1 day after completing abx. Surveillance CXR obtained.

Admitted to a community hospital•Recap: 5 week history of fatigue, high

normal temperatures, and completion of 10 days of oral antibiotics.

•Admitted for right sided pneumonia with effusion.

•Started treatment with antibiotics▫IV Ceftriaxone (10 days)▫IV Vancomycin (7 days)▫PO Azithromycin (5 days)

Video assisted thoracoscopyat the community hospital•Pleural fluid: ▫150ml hazy, pale yellow fluid. ▫26 WBC: 1% N, 91% L, 4% E, 1% Baso.▫23 RBC. Gluc 83. Prot 5.5. pH>7.75

•Pleurolysis of dense adhesions.•Gram stain: Rare RBC. •Cultures: Aerobic and anaerobic bacterial

and fungal negative. AFB smear and culture negative.

Hospital course at community hospital•Chest tube in place for 5 days.•Fevers resolved.•PPD neg.•Mycoplasma IgG, IgM: neg.•Labs: Date WBC (K/uL) CRP

(mg/dL)

2 weeks prior to admission

18.8

Admission 16.8, 64%N 8.6

HD#3 (post VATS) 15 24.3

HD#8 (discharge) 14.1, 65%N 4

Interval history since discharge

•Mild fatigue, “sluggish.”•Occasional temperature of 100.•No respiratory symptoms. Gaining weight

(1.9 pounds), improved appetite. •2 weeks after discharge: •CRP 4.85. ESR 94. WBC 9.1, 54%

neutrophils.•Surveillance CXR by PMD.

Referral

•Referral to Pediatric Pulmonary after 9 weeks of illness.

•Reason: Persistent pneumonia with effusion despite antibiotic treatment.

Differential diagnoses?

Past Medical History

•Ex-38 week fraternal twin, C-section.•No recurrent sinopulmonary infections. •Surgeries: None.• Immunizations: Up to date.

Family History•Dad: Allergic rhinitis to cats and pollen.•Twin brother: Multiple food allergies.

Social History

•Lives with Mom, Dad, 6yo sister, 2 yo fraternal twin brother.

•Mom: Counselor at local high school•Dad: Construction manager at VA hospital•Attends daycare.

Travel History•Travelled to Michigan in early summer.

Physical Examination•Ht 25-50%tile. Wt 25-50%tile.•VS: T36. HR 138. RR 28. O2 sat 96% RA.• Gen: NAD, playful, non-toxic.• HEENT: TMs nl. Nasal turbinates nl. Tonsils 1+.• Neck: No LAD.•Lungs: Decreased BS in right base

anteriorly and posteriorly. No wheeze, crackles, rhonchi. Nl effort, chest shape.

• CV, Abd: Nl. Skin: No rashes. Ext: no cyanosis, clubbing.

Differential diagnosis?• Inadequately treated community acquired

pneumonia with effusion:▫Inadequate duration of treatment▫Resistant organism▫Non-bacterial organism

•Structural abnormality:▫Congenital malformations▫Airway foreign body▫Pulmonary or extra-pulmonary mass

• Immunodeficiency

Next steps?

•Evaluate effusion▫Chest US▫Chest CT

•Diagnostic bronchoscopy▫Airway examination▫BAL

• Immunodeficiency work up•Serology testing

Bronchoscopy

•Normal airway anatomy, mild mucosal edema, scant secretions.

•No foreign body. •Bronchoaveolar lavage: ▫Colorless, clear, frothy.▫WBC 259: 3% N, 72% L, 22% M, and 2% E.▫RBC 330.▫GMS neg.

BAL cultures

•Gram stain: Rare polys, small mononuclear cells. +GP cocci in pairs.

•Bacterial culture: Normal resp flora.•KOH neg. Fungal culture neg.•Viral DFA neg. CMV PCR neg. •AFB smear neg. AFB culture neg.•Legionella culture neg.•Pneumocystis stain neg.

Immune work up

•QuIG and IgG subclasses: normal.•Tetanus and strep pneumoniae titers:

normal.•HIV neg.•T and B cell subsets: normal.•Dihydrorhodamine: 100% oxidation

positive neutrophils.

Serology work up•Strep pneumonia Ag (urine and serum): neg.•Quantiferon neg. •Coccidiomyces ID: neg.•Histoplasma ab: neg.•Hisptoplasma Ag serum: neg, Ag urine: <0.6•Blastomyces Ab CF: 1:32, 1:64.•Blastomyces Ab immunodiffusion:

positive.•Blastomyces serum Ag: neg.

Blastomyces dermatitidis

•Epidemiology•Clinical presentation•Diagnosis•Treatment•Prognosis

Ecology

•Thermally dimorphic fungus.▫Mycelial form in earth, Conidia inhaled,

budding yeast at body temperature.•Found in wet earth (animal

droppings,decaying vegetation).•Ohio and Mississippi river valleys, Midwest

states and Canadian provinces that border Great Lakes and St Lawrence River, esp north central Wisconsin and Ontario.

Geographic distribution of B. dermatitidis

Clinics in Chest Medicine, 2009.

Drummond Island, Michigan

www.drummondislandchamber.com

Epidemiology

•Transmission: Inhalation of airborne conidia or direct cutaneous inoculation.

•Usually affects men.▫Likely related to environmental exposures.

•Same incidence regardless of immune status.

•Disease more severe in immunocompromised patients.

Clinical manifestations

•Acute: Fever, cough, myalgia, arthralgia.•Pulmonary: ▫Asymptomatic radiograph abnormality▫Acute or chronic pneumonia▫Alveolar or mass-like infiltrate▫ARDS▫Massive effusion uncommon and cavitation

uncommon

•Skin: ▫Verrucous: raised crusted,

irregular shape and sharp border

▫Ulceration: subQ abscess•Bones: ▫Osteomyelitis: vertebrae,

ribs, skull, long bones•CNS: Masses, meningitis

Clin Microbio Reviews, 2010.

Diagnosis

•Stains: KOH, GMS•Culture: ▫Regular medium and selective medium

(cycloheximide) for 4-6 weeks▫Identify by DNA probe (crossreacts with

paracoccidioiodes)•Histology: Giemsa, PAS•Source: BAL, biopsy, sputum, gastric

lavage*

Clin Microbio Reviews, 2010. *Peds ID J, 2010

Serologies

•Antibody: Serum▫Complement fixation: sensitivity 40-57%,

specificity 30-100%▫Immunodiffusion: sensitivity 65-80%,

specificity 100%•Antigen: Serum, urine, BAL, CSF ▫Urine: sensitivity 92%, specificity 79%▫Crossreacts with histoplasmosis,

paracoccidiomycosis.

Clin Microbio Reviews, 2010. Peds ID, 2006.

Treatment

•Amphotericin B (AmB): Moderate-severe disease.

• Itraconazole: Solution more consistent serum levels than capsules, capsules require acidity for absorption.

•Fluconazole: 2nd line agent, less efficacious than itraconazole.

•Voriconazole and posaconazole: May be effective, little experience.

Treatment for pediatric patientsDisease Treatment Dose

Mild-moderate pulmonary

Itraconazole x 6-12 months

10mg/kg/day (max 400mg)

Moderate-severe pulmonary

AmB x 1-2 weeks, then itraconazole x 12 months

AmB 0.7-1mg/kg/dayLipid AmB 3-5mg/kg/day

CID, 2008.

Treatment monitoring

• Itraconazole levels >1 mcg/ml @ 2 weeks.•Hepatotoxicity: Liver enzymes @ 2 weeks,

4 weeks, then q3 months.

CID, 2008.

Back to our patient…

•Only positive result was the blastomyces antibody CF and ID.

•We presumed pulmonary blastomycosis and initiated treatment.

Treatment

•Ceftriaxone and clindamycin (7 days)• Itraconazole 10mg/kg po daily (6-12

months)

Treatment responseDate CRP (mg/dL) ESR (mm/hr)

Oct 1 4.85 94

Oct 7 6.8

Oct 9 6 75

Oct 11 6.9 99

Oct 15 5.3 86

Oct 26 <0.2 20

Itra initiate

d

Discharge

Referral

Long term sequelae of pulmonary blastomycosis•Case series of 8 pediatric patients.•6/8 patients had normal pulmonary

function at 4.5 +/- 3.5 years after illness.•2 patients with a prolonged course with

residual radiographic abnormalities had mild restriction and obstruction.

Clinical Pediatrics, 2000.

Seasonal variation

Medical Mycology, 2008.

Take home messages

•Clinical suspicion for Blastomycosis.•Diagnostic testing to consider: ▫Antigen testing of BAL, urine.▫Gastric aspirates for KOH, GMS, culture.

Questions?

References• Saccente, M, Woods, G. Clinical and laboratory

update on Blastomycosis. Clin Microbiology Reviews, 2010;23:367-381.

• Chapman, S, et al. Clinical practice guidelines for the management of Blastomycosis: 2008 update by the IDSA, CID, 2008;46:1801-12.

Thank you!