Pediatrics

Question 1

rash progressively worsened and bilateral periorbital swelling developed. five day old infant was readmitted to hospital because of a rash. pregnancy had been complicated by a UTI. temp 37.2, pulse 144, bp 105/80. With the exception of the rash, the physical exam was unremarkable. The mucous membranes were normal, no lymphadenopathy was noted, the heart and lungs were normal.

Hct is low, WBC are high, Neutrophils low, lymphocytes low, see band forms and atypical lymphocytes + blasts.

Answer 1

ddx = lymphoproliferative disorder with markedly elevated white count

Question 2

myeloblast

Answer 2

high nuclear to cytoplasmic ratio, blastic, dispersed chromatin

myeloperoxidase +
most are CD34, HLA-DR and coexpress CD33 lineage

Question 3

promyelocyte

Answer 3

eccentric nucleus w/ prominent pale zones

myeloperoxidase +
CD34-, HLA-DR-,

Question 4

development stages of neutrophil?

Answer 4

myeloblast –> promyelocyte –> neutrophilic myelocyte –> neutrophilic metamyelocyte –> band neutrophil –> neutrophil

Question 5

neutrophilic myelocyte

Answer 5

round nucleus w/ condensed chromatin

myeloperoxidase +
leukocytic alkaline phosphate +,
CD34-, HLA-DR-

Question 6

band neutrophil

Answer 6

horshoe-shaped mature nucleus lacking discrete indentations
cytoplasm packed w/ discrete indentations

myeloperoxidase+
LAP +

CD34-, HLADR-

Question 7

neutrophil

Answer 7

has 3-5 discrete nuclear lobes, highly condensed chromatin

myeloperoxidase + LAP+, CD34-, HLA-DR-

Question 8

hx: rash, but otherwise well appearing. no lymphadenopathy, no fever.
Lab values:
- low hematocrit
- high WBC count
- low neutrophils, lymphocytes and monocytes
- see increased atypical lymphocytes, band forms, blasts and myelocytes/metamyelocytes
- platelets are elevated
- bilirubin levels are normal
- Creatinine is elevated
- elevated LDH

Answer 8

ddx: Transient myeloproliferative disorder with trisomy 21 mosaicism

other earlier ddx: Langerhans Cell Histiocytosis (LCH) aka “ Letterer-Siwe Disease”

most likely the multifocal multisystemic langerhans cell hisiocytosis where see cutaneous lesions over front and back of trunk and scalp

accompanied w/ anemia, thrombocytopena and increased infections

Question 9

Langerhans Cell Histiocytosis

Answer 9

Hallmark of LCH is proliferation of and accumulation of bone-marrow derived dendritic cells

No known cause

Peak age of diagnosis is at 2 years of age; however, it can occur at any age

Question 10

leukocytosis… causes?

Answer 10

defined as elevated number of white cells in the blood

1. Increased production in marrow:
   - chronic infection
   - HL
   - myeloproliferative disorder (CML)
2. increased release from marrow stores:
   - endotoxemia
   - infection
   - hypoxia
3. decreased margination:
   - exercise
   - catecholamines
4. decreased extravasation into tissues:
   - glucocorticoids

Question 11

Leukemoid reaction

Answer 11

elevation of normal leukocytes to counts greater than 50,000 cells/μL

must be distinguished from CML

Question 12

Leukemoid Reaction vs Congenital Leukemia

Answer 12

The peripheral smear did not show a morphological progression from blasts to mature forms. This observation is called the leukemic hiatus and suggests the blasts are autonomous suggesting a neoplastic process rather than an response to inflammation which would show the progression of elements of the granulocytic series

The elevated lactate dehydrogenase (LDH) level also suggests the rapid proliferation of cells as seen in a neoplastic disorder

Infant myeloid leukemia is associated with a propensity to extramedullary disease in the skin and CNS

Blasts were identified in the CNS

The skin lesions in this infant could also be a leukemic manifestation; however, the rash in this child was not typical

The elevated platelet count provides the best clue for what is happening - most consistent w/ transient myeloproliferative disorder

Question 13

Transient Myeloproliferative Disorder

Answer 13

• Elevated Platelets Most Consistent with Transient Myeloproliferative Disorder
• Transient myeloproliferative disorder originally thought to only occur in patients with trisomy 21
• Clinically appears identical to acute myeloid or acute megakaryocytic leukemia
• The only distinguishing factor is the spontaneous resolution of all the hematological abnormalities, usually by 12 weeks of age
• often see pustular rash that concentrate on face and spread to trunk mimicking erythema toxicum (true infant leukemia see more nodular)

Question 14

A 3 y/o boy presents to the clinic with pallor, bruising and intermittent fever for the past 3 weeks.

• Physical exam reveals no cause for his fever or pallor.
• Hgb is low, WBCs are low, mostly lymphocytes, platelets are low –> see pancytopenia
• peripheral smear shows mature lymphocytes and PT/PTT are normal
• bone marrow is completely replaced by myeloblasts

Answer 14

• Thinking ALL
• initial presentation was pancytopenia that mimicked aplastic anemia.

50% of children with ALL and 20-30% of children with AML present with WBC

Question 15

A 13 y/o girl presented with malaise and intermittent fever for 1 week. She had bilateral 2-3 cm nontender anterior cervical nodes and splenomegaly. EBV titers were equivocally high. A presumptive diagnosis of mononucleosis was made and laboratory studies were drawn.

Hgb was low, WBC count is high, platelets are low, LDH is elevated, WBC shows >95% blasts, bone marrow shows lymphoblasts that are CD2+ CD7+

Answer 15

ddx: TALL- high risk ALL
- High Risk ALL presents with rapid onset, high tumor burden due to marked leukocytosis with lymphadenopathy and/or hepatosplenomegaly and mediastinal disease

About 20 % of patients with WBC > 50,000 will have this presentation

** Sometimes the presentation is thought to be mononucleosis

Question 16

A 5 y/o girl presents with intermittent bilateral leg and wrist pain and fever as high as 103° F of 3 weeks duration. Physical exam is normal with the exception of the limp.

Labs: Hgb is low, MCV is low, WBC is low, shows 21% neutrophils and 79% mature lymphocytes, platelets normal, high sed rate

Answer 16

high sed rate is indicative of inflammation

diagnosis of juvenile rheumatoid arthritis is made and she is started on aspirin therapy. There is improvement over the next 2 days but then the pain worsens and she refuses to bear weight.

LDH is elevated
uric acid is normal
bone marrow aspirate shows pre-B cell lymphoblasts

Thus this is a common presentation of ALL

The presentation with bone pain and fever occurs more commonly in the younger child

Fever is secondary to cytokine release from lymphoblasts but could also indicate a life threatening infection due to neutropenia

The bone pain is secondary to marrow expansion
**

These patients will frequently have normal range WBC

*** Elevated LDH and uric acid levels suggest a malignant process

Question 17

Childhood leukemia

Answer 17

Acute lymphoblastic leukemia (ALL) most common accounting for 25% of all cancers in children < 15 years of age

• Peak incidence 2-5 years of age
• More common in males

AML and its variants accounts for 4% of all childhood cancers

• Incidence does not vary with sex, age or ethnicity
• Predisposing factors are exposure to chemotherapy and ionizing radiation

CML: is a myeloproliferative disorder characterized by the predominance of relatively mature myeloid cells

Question 18

genetic syndromes assoc/ w/ acute leukemias?

Answer 18

Down syndrome-15-20 fold increase
Fanconi syndrome
Klinefelter syndrome
Shwachman-Diamond syndrome

Question 19

WBC greater > 200,000 can lead to microemboli to brain or lungs suggesting a stroke or PE

Answer 19

think AML

Question 20

Respiratory distress, cough and facial edema suggest superior vena cava syndrome due mediasatinal compression of the airway or major vessels

Answer 20

think ALL

Question 21

life threatening bleeding secondary to DIC

Answer 21

think AML

Question 22

tx of childhood leukemias?

Answer 22

Survival rates are really outstanding

80-90% of children with ALL and 50 % with AML are cured

Survival attributable to therapy stratification based on risk characteristics at diagnosis

Lower risk factors include age 1-9 years and low to normal WBC at diagnosis

Higher risk factors include age >10, infants with high WBC and those with mature B-cell leukemia

Hyperdiploidy (>50 chromosomes/cell) confers better prognosis than normal karyotype

Hypodiploidy a worse prognosis

A t9:22 chromosomal alteration confers higher risk

Question 23

tx for ALL vs AML?

Answer 23

ALL :
Following induction, therapy for ALL extends for 2-3 years (2 for girls and 3 for boys)
Therapy in the first 6-12 months more aggressive
Patients with bad prognostic indicators receive more aggressive intensified therapy
CNS prophylactics provided in all treatment regiments-mostly intrathecal chemotherapy

AML:
AML treatment dramatically different with extremely intensive chemotherapy for about 1 year
If available, BMT from antigen identical sibling (found only 20% of the time) is optimal

Question 24

greatest risk of leukemia tx?

Answer 24

Greatest risk is infection

Management of fever is critical

Constant immunosuppressive therapy depresses lymphocyte function during therapy and for 3-12 months after therapy is completed

Live virus vaccines are CONTRINDICATED

Question 25

tumor lysis syndrome?

Answer 25

● Release of intracellular uric acid, potassium, and phosphate from rapid
turnover of malignant cells
● Usually precipitated by chemotherapy, but can occur before
● Most often with high tumor burden or T-cell leukemia
● Components of tumor lysis:
—Hyperuricemia
—Renal precipitation can progress to acute renal failure
—Hyperkalemia
—Can progress to fatal arrhythmia
—Hyperphosphatemia/Hypocalcemia
—Increased phosphate can cause hypocalcemia and renal precipitation can
progress to renal failure

Question 26

management of tumor lysis syndrome?

Answer 26

Provide hydration and diuresis
● Avoid supplemental potassium
● Treat hyperkalemia emergently, if necessary
● Decrease uric acid with allopurinol or urate oxidase
● Consider oral phosphate binders
● Initiate dialysis for acute renal failure
● Transfer urgently to a pediatric oncology tertiary care center

Question 27

hemoglobin vs. hematocrit?

Answer 27

Hemoglobin: the measure of hemoglobin in whole blood, expressed in grams/dl

Hematocrit: fractional volume of red blood cells in whole blood, expressed as a %.

Hematocrit roughly 3 times hemoglobin.

Question 28

pallor, jaundice, and splenomegaly

Answer 28

think autoimmune hemolytic anemia

• may present with signs of cardiovascular compromise if hemolytic process is rapid

Autoimmune hemolytic anemic (AHA) is an acute, self-limited disease in most children. In addition to the signs and symptoms listed previously, fever and abdominal pain can be seen in the autoimmune type of hemolysis. AHA is most common before the fourth birthday and is often associated with an otherwise unremarkable infection, most commonly mycoplasma, cytomegalovirus and Epstein-Barr virus.

Red blood cell autoantibodies mediate the hemolytic process. They are classified as either “warm” or “cold,” depending on the temperature at which they are maximally active.

Question 29

cold vs warm antibodies?

Answer 29

Cold antibodies are generally IgM and require complement for in vivo hemolysis. Warm antibodies are generally IgG and cause hemolysis without complement.

Laboratory studies show an anemia and reticulocytosis, although the reticulocyte response may be delayed for several days.

A positive direct Coombs test is crucial to differentiate AHA from other acute causes of anemia; however, both direct and in-direct Coombs tests occasionally may be negative.

Corticosteroids remain the cornerstone of therapy.

Most patients show an increase in hemoglobin within a few days of treatment with 2 to 10 mg/kg per day of Prednisone.

Patients often require prolonged tapering of steroid therapy

Question 30

tx of sickle cell?

Answer 30

hydroxyurea - enhances production fo Fetal hemoglobin improving many issues in sickle cell.

Simple transfusions, exchange transfusions, BMT

Question 31

BIND (Bilirubin Induced Neurologic Dysfunction)

Answer 31

“kernicterus”

Question 32

ABE (Acute Bilirubin Encephalopathy)

Answer 32

b

Question 33

reasons of increased bili in newborn?

Answer 33

1) Increased red cell mass
2) Shorter ½ life of red cells with fetal hemoglobin
3) Decreased clearance due to lack of induction of infant’s liver enzymes
4) Enterohepatic circulation

Question 34

Etiology of increased production of bilirubin

Answer 34

1) ABO incompatability or Rh
2) Red cell membrane defects (spherocytosis or eliptocytosis
3) G6PD, pyruvate kinase deficiency, congenital erythropoetic porphyria
4) Sepsis
5) Polycythemia, hematoma
6) IDM resulting in polycythemia or ineffective erythropoiesis

Question 35

Etiology of decreased clearance of bilirubin:

Answer 35

1) Crigler Najjar type 1 or 2
2) Gilbert’s
3) G6PD plus Gilbert’s
4) Hypothyroidism, galactosemia
5) Increased enterohepatic circulation

Question 36

Risk factors forhigh bili –> need to treat

Answer 36

1) Jaundice in first 24 hrs
2) Total bilirubin in high risk zone at discharge
3) Early discharge
4) Prematurity
5) ABO incompatability with positive DAT, Rh, G6PD
6) Sibling requiring phototherapy
7) Significant bruising or Cephalohematoma
8) Exclusive breast feeding, especially if not going well or excessive weight loss
9) East Asian race

Question 37

Evaluation of jaundice:

Answer 37

1) Total and possibly fractionated bilirubin (peak usually at 72-96 hrs, later in preterm)
2) CBC with smear
3) Retic count
4) G6PD possibly

Question 38

Treatment: of jaundice

Answer 38

1) Phototherapy
2) Hydration
3) IVIG
4) Exchange transfusion