Case Discussion

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A 54-Day-old Premature Girl with Respiratory
Distress and Persistent Pulmonary Infiltrates

• Case Discussion
• FAU Erlangen 13.12.2002

Wolfgang Freisinger
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Chief Complaint

• A 54-day-old girl was admitted to the hospital
  because of recurrent respiratory distress and
  failure to gain weight

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SH - Mother

• 38-year old woman ( gravida 2, para 0 )
• Group B, Rhesus positive blood
• Immune to rubella, negative serologic test for
  syphilis
• Smoking during pregnancy
• Less than 1 pack a day
• Respiratory tract infection several weeks before
  delivery
• Treatment with erythromycine was successfull

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PMH - Child

• Delayed fetal growth
• Born at 35 ½ weeks gestation by urgent cesarean
  section, performed after detection of meconium on
  amniocentesis and increased fetal heart rate
• Birth weight was 1520g
• Is she a high-risk-infant ?
• Yes, because of underweight, premature birth,
  mother smoking, meconium stained fluid
• APGAR 7 after one minute, 8 at five minutes, no
  resuscitation was required

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PMH - Child (2)

• Stable during and after brief administration of
  supplemental oxygen
• No evidence of meconium aspiration
• Placenta was small and showed a small, healed
  infarct
• Tests for CMV and toxoplasmosis were negative

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• 9.400 34.00054-623-5
• 25-333-71-30-0,75
• 1,500-3,000/mm³84,000-478,00048-69

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HPI 4th day of life

• child was transferred elsewhere for feeding and
  growth

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HPI 8th day of life

• Development of a diaper rash
• No response to multiple measures
• Alternatives to cow milk dont bring any benefit
  

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HPI 26th Day of Life

• Child is in tachypnea, with intercostal
  retractions

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CXR 26th day of life
Anteroposterior Film of the Chest on the 26th Day
of Life. The lungs are hyperinflated, with
bilateral streaky opacities in a parahilar,
peribronchial distribution. The heart appears
normal, and the superior mediastinal contour is
narrow. There is a bone-within-bone appearance of
the vertebral bodies and anterior flaring of the
ribs.
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CXR 26th Day of Life
Lateral Film of the Chest on the 26th Day of
Life. The lungs are hyperinflated, with
bilateral streaky opacities in a parahilar,
peribronchial distribution. The heart appears
normal, and the superior mediastinal contour is
narrow. There is a bone-within-bone appearance of
the vertebral bodies and anterior flaring of the
ribs.
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HPI 26th Day of Life

• Management ?
• Specimens were obtained for culture
• Administration of Gentamicin and Ampicilline

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CXR 30th day of life

• Air space Disease in the right upper lobe, a
  finding consistent with the presence of
  atelectasis

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HPI 30th Day of Life

• Blood cultures were positive for
  coagulase-negative streptococci
• Administration of antibiotics for additional 11
  days
• Condition improved

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HPI 36th Day of Life

• Radiographic findings had improved

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HPI 40th Day of Life

• Three days after the end of the antibiotic
  treatment tachypnea recurred
• But another radiograph still shows improvement
• What would you do?
• Administration of Cefuroxime, Clindamycin and
  Cisapride
• Babys conditon improves again

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HPI 44th Day of Life

• CXR again shows abnormalities
• Infant ist transferred to hospital this day

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PE

• Axillary Temp. 36,2C
• Pulse 99
• Respirations 70 / min while breathing oxygen by
  nasal cannula
• BP 105/90

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PE

• Length 41cm (below 2 SD of new born)
• Weight 2100g (below 2 SD of new born)
• Head circumference 34.5 cm (1 SD below the mean)
• Lungs occasional wheezes and scattered fine
  crackles are heard bilaterally
• Minimal subcostal retractions
• Liver edge palpable 5mm below right costal margin

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Assessment

• 44-day-old premature girl with recurrent
  respiratory distress, severe lymphopenia and
  failure to gain weight

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Cultures and serologic studies

• No evidence of
• Chlamydia
• RSV
• Adenovirus
• Influenza A Virus

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Stool specimen

• No ova or parasites

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Initial Treatment

• Erythromycine and multivitamin
• Albuterol by nebulizer
• Axillary temperature does not exceed 37.7 but is
  normal on most occasions

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Stained blood smear

• Anisocytosis ()
• Poikilocytosis ()
• Polychromatophilia ()
• Hypochromia ()
• Many microcytes
• Few macrocytes
• Rare teardrop cells and schistocytes
• 2 nucleated red cells per 100 white cells

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Effect of the therapy

• Infants condition improves and remains stable
  for several days
• Considerable mucus production and coughing
• Moderate respiratory distress (50-60/min)
• Axillary temp 36,4C
• Pulse 179 /min
• SpO2 89

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ABG

• While breathing supplemental oxygen
• Oxygen 137 mmHg
• Carbon Dioxide 46 mmHg
• pH 7.39
• Bicarbonate 28 mmol/l

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CXR After Initial Treatment

• Resolution of pulmonary abnormalities

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Upper GI Series

• Normal findings

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DD

• AIDS/ HIV Infection
• Intestinal Lymphangiectasia
• Severe Combined Immunodeficiency SCID

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AIDS

• Could explain this form of prolonged and profound
  lymphopenia in adults
• But in this case
• There is no evidence for HIV-Infection of the
  mother
• No risk factors of the mother are known
• CD4 Lyomphopenia is manifested later in life
• No clinical features or lymphadenopathy
  characterisic of pediatric AIDS

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Intestinal lymphangiectasia

• Leads to extensive lymphopenia and accumulation
  of lymphocytes in the gut
• BUT
• Infants are immunocompetent and do not aquire
  early opportunistic infections
• The absence of diarrhea makes this diagnosis
  unlikely

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Forms of Severe Combined Immunodeficiency ( SCID )

• SCID with deficient T- cells and normal or high
  levels of B-cells
• X-linked form (common ?-chain-deficiency)
• Autosomal recessive form Janus kinase 3 (JAK3)
  deficiency
• SCID with deficient T-cells and B-cells
• Adenosine deaminase (ADA) deficiency
• Defect in Recombinase activating gene (RAG) 1 or
  2
• Reticular dysgenesis

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Red Cell Studies

• Absence of adenosine deaminase activity and
  elevated levels of deoxyadenosine triphosphate
• Levels of purine nucleoside phosphorylase normal

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Peripheral blood lymphocytes

• No proliferative response to phytohemagglutinin

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SCID due to ADA-Deficiency

• Autosomal - recessive form 20 of all SCID
  patients
• Due to various mutations in the ADA gene
• Accumulation of adenosine, deoxyadenosine
  deoxyadenosine triphosphate and
  S-Adenosy-L-homocysteine are toxic to lymphocytes
  ? this causes the
  immunodeficiency
• ADA-SCID presents with a more severe lymphopenia
  than other forms of SCID (absol. counts lt
  500/mm³)

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Clinical Presentation of SCID due to ADA

• Lymphopenia with marked depletion of T and B
  lymphocytes
• Normal or increased NK Cells
• No corticomedullary demarcation of the thymus
  (Absence of Hassalls bodies and thymocytes)
• Lymphnodes retain their normal architecture but
  contain only very few lymphocytes
• Rib cage abnormalities similar to rachitic
  rosary, predominantly at the costochondral
  junctions, the apophyses of the iliac bones and
  in the vertebral bodies

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Clinical Presentation of SCID due to ADA (2)

• Circulating B-cells may present in some patients
• Severity depends on the type of mutation in the
  ADA gene and the resulting degree of the ADA
  definciency
• Growth and developmental abnormalities, including
  neurologic and osseous findings, have been
  observed

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SCID Treatment of the Patient

• Our patient was treated with polyethylene-glycol
  modified adenosine intramuscularly, initially
  twice a week, guided by the levels of ADA and the
  toxic metabolites
• She began smiling and interacting with the
  environment already after two doses of ADA
• Suspected P. carinii infection was treated with
  Trimethoprim-Sulfamethoxazole i.v.

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SCID Treatment

• HLA identical or haploidentical bone marrow
  transplantation without chemotherapy
• first perfomed in 1969
• graft-versus-host disease is uncommon
• Survival 100 for HLA identical and 78 for
  haploidentical graft
• Gene therapy
• Substitution of the enzyme

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Follow Up

• 500 mg immunoglobuline per kilogram every three
  or four weeks will give her enough protection
• No live vaccinating agents
• She is expected to grow and develop normally
• The cartilaginous abnormalities should disappear
• She can have a normal diet

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Thank you for your attention