Persistent Pneumonia in a Newborn

1
Persistent Pneumonia in a Newborn

• Julie Gutman, MD
• CIS Summer Course
• September, 2008

2
HPI

• JG is a 3 month old white male who presented with
  a few days of increasing nasal discharge,
  wheezing, progressive respiratory distress, and
  hypoxemia.
• Denies fever, conjunctivitis, vomiting, and
  diarrhea.
• No history of pneumonia, otitis media, or
  wheezing.
• Chronic rash since birth, skin is diffusely dry
  and scaly with mild erythema and fine papules on
  trunk.
• Diagnosed with viral bronchiolitis due to
  tachypnea and hypoxia, initial viral culture was
  negative for RSV and other respiratory viruses.

3
PMH

• Admitted DOL16 for hypocalcemic seizures
• Hyperphosphatemia and low PTH levels confirmed
  primary hypoparathyroidism
• Thymic absence on chest x-ray
• Genetics consulted for hypocalcemia and
  hypoparathyroidism in combination with left
  microtia and previous diagnosis of Goldenhar
  syndrome
• FISH probe for 22q11.2 deletion was normal
• Newborn History 38 weeks gestation, BW- 7lb
  10ounces
• induced vaginal delivery due to bleeding/ruptured
  membranes
• Complications Terbutaline X2 months and bedrest.
  
• Denies any infections. GBS negative.
• Lives with mother, father, and a dog. Both
  parents smoke.
• Family history significant for a 1st cousin with
  Goldenhar sequence and 22q11 deletion
• Aunt (40y/o) with Cystic Fibrosis

4
Hospital Course

• JG was noted to have
• Lymphopenia (ALC 1,800)
• Lymphopenia present at 1st admission as well.
• Eosinophilia (abs. range 3,300- 6,370)
• Hypogammaglobulinemia
• IgG 150 mg/dl, IgM 80 mg/dl, IgA 21 mg/dl
• Mild eczematous rash.
• JG became progressively hypoxic.
• Diagnostic bronchoscopy/ BAL
• BAL sample was positive for RSV, Moraxella, and
  S. pneumoniae, treated with antibiotics.
• Received IVIG for hypogammaglobulinemia
• JG slowly improved, and was discharged after a
  month long hospitalization on Bactrim prophylaxis

5
Differential Diagnosis

• DiGeorge syndrome
• Omenn syndrome or another SCID variant
• Tracheo-esophageal fistula
• Cystic fibrosis
• Primary ciliary dyskinesia
• Langerhans Cell Histiocytosis
• Chylothorax/ lymphangiectasia

6
LABS

• Lymphocyte subsets T -/B/NK pattern
• CD3 cells- 321, 26
• CD4 cells- 117, 9.7
• CD8 cells- 98, 8.1
• CD19 (B) cells- 751, 22
• CD16/56 (NK) cells- 89, 7.4
• IgG 150 (?), IgM 80, IgA 21, IgE 316 (?), CH50 88
• Lymphocyte proliferation no response to
  mitogen, but inconclusive as there were few T
  cells. On repeat, modest response to
  Phytohemagglutinin and concanavalin A. Borderline
  response to Pokeweed Mitogen. No response to
  antigens.
• Dihydrorhodamine (DHR) unable to run
• FISH for 22q11 microdeletion- negative
• Chromosomal microarray panel negative
• HIV EIA and viral load - negative

7
Readmission with respiratory distress 3 weeks
after discharge

• Chest x-ray large right pleural effusion with
  central lucency and a lingular density
• CT showed a multilobar pneumonia with small
  loculated air collections in the RLL
• Bronchoscopy to evaluate for a TE fistula.
• Cultures grew MRSA, Pseudomonas aeruginosa, and
  Enterobacter these were treated
• JG remained critically ill and required multiple
  chest tubes and high frequency ventilation.
• Due to concerns for immunodeficiency, JG was
  started on prophylactic Bactrim and Diflucan.
• Repeat DHR (neutrophil oxidative burst)- normal
• Surfactant B and C deficiency testing- negative

8
CT Chest obtained on Re-admission
L
R
9
Differential Dx for lymphopenia

• HIV
• SCID
• Omenn (RAG1 and RAG2 mutations) (TB-NK)
• Artemis deficiency (TB-NK)
• IL-7Ra (T-BNK)
• CD3-gamma deficiency (T-BNK)
• IL-2Rg (T-BNK-)
• JAK3 deficiency (T-BNK-)
• Adenosine Deaminase (ADA) deficiency (T-B-NK-)
• Purine Nucleotide Phosphorylase (PNP) deficiency
  (T-B-NK-)
• DiGeorge
• Ataxia Telangiectasia
• Wiskott Aldrich
• Cartilage Hair Hypoplasia

Nelsons Pediatrics
10
Differential Dx for lymphopenia

• HIV
• SCID
• Omenn (RAG1 and RAG2 mutations) (TB-NK)
• Artemis deficiency (TB-NK)
• IL-7Ra (T-BNK)
• CD3-gamma deficiency (T-BNK)
• IL-2Rg (T-BNK-)
• JAK3 deficiency (T-BNK-)
• Adenosine Deaminase (ADA) deficiency (T-B-NK-)
• Purine Nucleotide Phosphorylase (PNP) deficiency
  (T-B-NK-)
• DiGeorge
• Ataxia Telangiectasia
• Wiskott Aldrich
• Cartilage Hair Hypoplasia

Nelsons Pediatrics
11
Ah ha!

• Additional testing
• IL7r-alpha and CD3-gamma deficiency (negative)
• One month into the hospitalization, JG developed
  bradycardia.
• As part of the work-up for bradycardia, JG was
  noted to be hypothyroid.
• Significant thymic defect (T-BNK)
  hypothyroidism hypoparathyroidism otic
  abnormality supports a diagnosis of
• Complete DiGeorge without 22q deletion.

Choi et al, 2005. Horm Res, 63(6)
294-9 Weinzimer, 2001. Genet Med, 3(1) 19-22
12
DiGeorge

• Thymic and parathyroid defects
• Conotruncal cardiac defects
• 22q11 hemizygosity
• Estimated incidence 1 in 3000- 4000 live births.
• Often in combination with CHARGE association
• lt1 are athymic Complete DiGeorge
• Presentation may be confused with severe atopic
  dermatitis or forms of SCID (Omenn syndrome,
  Artemis deficiency)
• Only half of patients with complete DiGeorge
  anomaly are 22q11 hemizygous.
• Need high level of clinical suspicion!!

Sullivan, 2008. Immunol All Clin N Am. 28
353-366.