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Case Discussion

FAU Erlangen 13.12.2002

Wolfgang Freisinger

A 54-Day-old Premature Girl with Respiratory Distress and

Persistent Pulmonary Infiltrates

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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 – 34.000

54-623-5

25-33

3-71-30-0,75

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 don‘t 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

• Baby‘s 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. 36,2°C

• 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

• Infant‘s condition improves and remains stable for several days

• Considerable mucus production and coughing

• Moderate respiratory distress (50-60/min)

• Axillary temp 36,4°C

• 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 < 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 Hassall‘s 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