Unusual cause of complicated pneumonia

1. Unusual cause of complicated pneumonia MyMy Buu, MD Pediatric Pulmonary Fellow Stanford University School of Medicine

2. Referral from pediatrician 2 year old male, fraternal twin born at term, previously healthy. Reason: Persistent pneumonia with effusion despite antibiotic treatment.

3. 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.

6. 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.

11. 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)

12. 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.

14. Hospital course at community hospital • Chest tube in place for 5 days. • Fevers resolved. • PPD neg. • MycoplasmaIgG, IgM: neg. • Labs:

16. 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.

19. Referral • Referral to Pediatric Pulmonary after 9 weeks of illness. • Reason: Persistent pneumonia with effusion despite antibiotic treatment.

20. Differential diagnoses?

21. 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.

22. 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.

23. 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.

24. 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

25. Next steps? • Evaluate effusion • Chest US • Chest CT • Diagnostic bronchoscopy • Airway examination • BAL • Immunodeficiency work up • Serology testing

28. 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.

29. 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.

30. 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.

31. 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.

32. Blastomyces dermatitidis • Epidemiology • Clinical presentation • Diagnosis • Treatment • Prognosis

33. 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.

34. Geographic distribution of B. dermatitidis Clinics in Chest Medicine, 2009.

35. Drummond Island, Michigan

36. www.drummondislandchamber.com

37. 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.

38. 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

39. 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.

40. 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

41. 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.

42. 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.

43. Treatment for pediatric patients CID, 2008.

44. Treatment monitoring • Itraconazole levels >1 mcg/ml @ 2 weeks. • Hepatotoxicity: Liver enzymes @ 2 weeks, 4 weeks, then q3 months. CID, 2008.

45. Back to our patient… • Only positive result was the blastomyces antibody CF and ID. • We presumed pulmonary blastomycosis and initiated treatment.

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

47. Treatment response Referral Itra initiated Discharge

50. 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.