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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!
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