Respiratory failure in a 10-month-old: Pursuing a diagnosis
Todd D Green Children’s Hospital of Pittsburgh November 4, 2007
Case Presentation
10 mo male transferred from outside hospital
Admission 8 months for bilat pneumonia, pneumothorax WBC 4.4 k/ul, ALC 1628/mm3, ANC 2288/mm3, AEC 308/mm3
Resp failure, intubation, ECMO
BAL unremarkable (including Pneumocystis, fungal) ET sputum: Klebsiella, Stenotrophomonas, Serratia Urine negative for CMV, adenovirus EBV PCR negative Negative molecular testing for CF Skin biopsy “contact dermatitis”, resolved with steroids
Macular rash with eosinophilia (2500/mm3)
Case Presentation
PMH
Chronic clear rhinorrhea since 1-2 months Recurrent otitis media beginning 4 months
PE tubes placed 7 months, continued infections
Rashes with azithromycin and amoxicillin No chronic thrush, diarrhea, failure to thrive
FH
4 yo brother with JRA, mat first cousin with CF No consanguinity, PID, early childhood deaths
Case Presentation
Medications on admission
Bactrim, Zosyn, Vancomycin Prednisolone Methadone, diuretics, sedatives
Exam: Ht 5th %ile, Wt 5th %ile, HC 25th %ile
HEENT: intubated (tonsils later visualized) Nodes: 2 mm node rt axilla, 3 mm node lt groin Liver 4-5 cm below rcm No murmur, rash
Differential?
Combined immunodeficiency SCID Omenn’s Syndrome MHC I or II Antigen Deficiency p56 Lck deficiency DiGeorge Syndrome Hyper-IgM Syndrome CGD CVID XLP XLA Others…
10 month old male with respiratory failure
History chronic rhinorrhea, OM History eosinophilia and rash
Tonsils and lymph nodes present Lymphopenic
Further assessment:
IgG 38 mg/dL, IgA 9 mg/dL, IgM 9 mg/dL, IgE ≤2 U/mL Abs lymph count 2046/mm3 (3400-9000) CD3+ 1550/mm3 (19005900) CD4+ 500/mm3 (1400-4300) 33% 4/45RA/62L (58-91) CD8+ 1053/mm3 (500-1700) 69% 8/45RA/62L (47-87) CD19+ 308/mm3 (610-2600) Lymphocyte prolif normal to mitogens, absent antigens
Clinical course:
Gradual recovery No rash 300-2700/mm3 eosinophils during 4 wk admission Bone marrow biopsy nl trilineage hematopoesis, no malignancy Home on IVIG, presumptive CVID
Normals from Shearer et al., J Allergy Clin Immunol 2003
Follow-Up
Continued recurrent OM, mult sets PE tubes Recurrent rhinorrhea, diarrhea, slow wt gain Resolution eosinophilia, no further rash Developed PCP at 15 months
LE thromboses during hospitalization, diagnosed with MTHFR gene mutation (1p36.3)
Generally well since Recurrent nephrolithiasis with ammonium urate stones (unusual in US) at 31 months
Follow-up: Immunologic Parameters
19 months
ALC CD3+ CD4+ CD8+ CD4:8 CD16/56+ CD19+ CD45RA/62L 4320 (3600-8900) 2458 (2100-6200) 760 (1300-3400) 1659 (620-2000) 0.46 151 (180-920) 1581 (720-2600) 53% of T-cells
31 months
2695 (2300-5400) 1730 (1400-3700 507 (700-2200) 1145 (490-1300) 0.44 137 (130-720) 776 (390-1400) 70% of T-cells
Normals from Shearer et al., J Allergy Clin Immunol 2003
Follow-up: Immunologic Studies
Mitogen Prolif Antigen Prolif IgA IgM IgE
19 months Normal Absent 0 mg/dL 0 mg/dL 4 IU/mL 31 months Normal Absent 0 mg/dL 0 mg/dL 5 IU/mL
Bacteriophage Φx-174 immunization response abnormal: No detectable antibody after primary immunization, but with phage clearance, suggesting presence of neutralizing antibody Very low antibody titer after second (no IgG isotype)
Further Immunologic Workup
ADA, PNP activity Common gamma chain sequencing (pt, mom) SH2D1A sequencing BTK sequencing CD40Ligand sequencing CH50 Platelet size, number
All normal
Summary
Now 3 3/12 yo, h/o PCP Agammaglobulinemia with normal % B-cells Abnormal response to bacteriophage immunization Low CD4 %, o/w normal lymphocyte populations, including CD45RA/62L T-cell fxn with nl mitogen prolif, absent antigen
Where to next?