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Unusual cause of complicated pneumonia. MyMy Buu, MD Pediatric Pulmonary Fellow Stanford 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.

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Unusual cause of complicated pneumonia

Unusual cause of complicated pneumonia

MyMy Buu, MD

Pediatric Pulmonary Fellow

Stanford University School of Medicine


Referral from pediatrician
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
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
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
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 thoracoscopy at the community hospital
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
Hospital course at community hospital

  • Chest tube in place for 5 days.

  • Fevers resolved.

  • PPD neg.

  • MycoplasmaIgG, IgM: neg.

  • Labs:


Interval history since discharge
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

  • Referral to Pediatric Pulmonary after 9 weeks of illness.

  • Reason: Persistent pneumonia with effusion despite antibiotic treatment.



Past medical history
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
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
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 turbinatesnl. 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
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
Next steps?

  • Evaluate effusion

    • Chest US

    • Chest CT

  • Diagnostic bronchoscopy

    • Airway examination

    • BAL

  • Immunodeficiency work up

  • Serology testing


Bronchoscopy
Bronchoscopy

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

  • No foreign body.

  • Bronchoaveolarlavage:

    • Colorless, clear, frothy.

    • WBC 259: 3% N, 72% L, 22% M, and 2% E.

    • RBC 330.

    • GMS neg.


Bal cultures
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
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
Serology work up

  • Strep pneumonia Ag (urine and serum): neg.

  • Quantiferon neg.

  • Coccidiomyces ID: neg.

  • Histoplasmaab: neg.

  • Hisptoplasma Ag serum: neg, Ag urine: <0.6

  • BlastomycesAb CF: 1:32, 1:64.

  • BlastomycesAbimmunodiffusion: positive.

  • Blastomyces serum Ag: neg.


Blastomyces dermatitidis
Blastomyces dermatitidis

  • Epidemiology

  • Clinical presentation

  • Diagnosis

  • Treatment

  • Prognosis


Ecology
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
Geographic distribution of B. dermatitidis

Clinics in Chest Medicine, 2009.




Epidemiology
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
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
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
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
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 monitoring
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
Back to our patient…

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

  • We presumed pulmonary blastomycosis and initiated treatment.


Treatment1
Treatment

  • Ceftriaxone and clindamycin (7 days)

  • Itraconazole 10mg/kg po daily (6-12 months)


Treatment response
Treatment response

Referral

Itra initiated

Discharge


Long term sequelae of pulmonary blastomycosis
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
Seasonal variation

Medical Mycology, 2008.


Take home messages
Take home messages

  • Clinical suspicion for Blastomycosis.

  • Diagnostic testing to consider:

    • Antigen testing of BAL, urine.

    • Gastric aspirates for KOH, GMS, culture.

Questions?


References
References

Thank you!

  • 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.


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