Case 30

2-YEAR-OLD WITH SICKLE CELL DISEASE -

GERARDO
Author: Roger Berkow, M.D., University of Alabama at Birmingham
Learning Objectives
Discuss appropriate communication with the child, the family, and the
health care team, especially regarding issues of chronic disease.
1.
Describe the signs of respiratory distress. 2.
Describe health maintenance and expected course for children with sickle
cell disease.
3.
Recognize the complications of sickle cell disease that may lead to additional
morbidity and mortality, including sepsis, vaso-occlusive crises, acute chest
syndrome (ACS), cholecystitis, stroke, and others.
4.
Describe the management of ACS. 5.
Work through a differential diagnosis of a child with sickle cell disease with
fever and/or cough and/or chest pain.
6.
Identify immunization priorities in children with sickle cell disease. 7.
Summary of clinical scenario: Gerardo is a 2-year-old African-American boy
with sickle cell disease. We initially meet Gerardo at the Comprehensive Sickle
Cell Clinic for routine follow-up. He has splenic enlargement, a flow murmur, mild
scleral icterus, and a normal neurological exam. All are expected findings in a
child with sickle cell disease. Four days later, he returns to the clinic with difficulty
breathing, chest pain, and a temperature of 102 degrees. On physical exam, his
nares are flaring, he is tachypneic with decreased breath sounds, and abdominal
exam reveals splenomegaly. Chest X-ray displays bilateral infiltrates and
cardiomegaly. Gerardo is diagnosed with ACS and appropriately treated in the
hospital for seven days. At the conclusion of this case, we learn about the course
of Gerardos disease over the following several years.
Key Findings from History Chest pain
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Key Findings from Physical
Exam
Tachypnea with rhonchi
Decreased breath sounds
Hypoxia
Fever
Increased splenomegaly
Differential Diagnosis
Acute chest syndrome
Sepsis
Rib infarction
Congestive heart failure
Pericarditis
Key Findings from Testing
New infiltrates on chest X-ray
Cardiomegaly
Leukocytosis
Final Diagnosis
Sickle cell disease with acute chest
syndrome
Case highlights: Students work through the history and physical to arrive at a
diagnosis of acute chest syndrome. In the process they learn how to evaluate pain
in a child with sickle cell disease, recognize the complications of the disease, and
learn how to manage both acute chest syndrome and pain in vaso-occlusive
crises. Students also learn about inheritance of an autosomal recessive disorder
and how to explain compound heterozygotes. Multimedia features include: Audio
of patient wheezing and its interpretation and a photo of enlarged tonsils.
Key Teaching Points
Knowledge
Sickle cell disease (SCD):
Pathophysiology
Substitution of valine for glutamic acid at the sixth amino acid position of
the hemoglobin molecule.
This abnormal hemoglobin polymerizes when deoxygenated.
Polymers then deform the red blood cell into characteristic sickle cells.
Sickle cells have increased adherence and block blood flow in the
microvasculature.
Result: Local tissue hypoxia, pain, and tissue damage
The abnormal hemoglobin also induces hemolysis of the red blood cells
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(RBCs), leading to chronic anemia and elevation of the reticulocyte count.
Inheritance
Gene mutation frequency 710% among African-Americans living in the
United States.
Sickle cell trait is also seen in the Hispanic population but with a lower gene
frequency.
Autosomal recessive:
Normal gene (A)
Sickle hemoglobin gene (S)
If both parents have one copy of the sickle cell gene (S), then:
25% of offspring could have sickle cell disease (SS)
25% are expected to have normal AA globin
50% are expected to have sickle cell trait (AS):
A S
A AA AS
S AS SS
Potential developmental effects of chronic disease
Impaired academic progress due to frequent absences from school as a
result of hospitalization, illness, or physician appointments
Diminished socialization and self-esteem since unable to do many of the
things other children may do
Disrupted family interactions due to financial hardship from cost of
medications and lost work time
Sibling issues due to attention imbalance or sibling guilt
Because of missed school, complications from stroke, and/or frequent pain,
adolescents with SCD have significant challenges in our education system.
Skills
History:
Comprehensive visit for SCD
Assess how family accesses health care and how they are coping with stress
of chronic illness:
Teach what to do/where to go for specific issues.
Refer to appropriate counseling resources if needed.
Ask how they deal with complications:
Assess frequency of painful or other vaso-occlusive problems to
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understand if there is an indication for more aggressive interventions
(e.g., use of hydroxyurea).
Evaluating pain
A scale that shows faces (in stages from happy to crying) is validated for
children age ! 4 years.
Children with SCD who have frequent pain crises sometimes understand the
faces scale earlier than age 4 (even as young as 2).
Sometimes, even children over 4 years are too ill to comply with the
request. In this case, parental judgment is best tool for assessing childs
pain.
Physical exam:
General: Growth impairment common in children with SCD due to chronic
anemia, poor nutrition, painful crises, endocrine dysfunction, and/or poor
pulmonary function.
HEENT: Observe sclera for signs of icterus (clue to the degree of RBC hemolysis).
CV: Flow murmur common in SCD
Abdomen:
Enlargement of the spleen is common during first few years of life in
children with SCD.
Massive enlargement or rapid change in spleen size can indicate sepsis or
splenic sequestration crisis (life-threatening complication that occurs when
blood pools in the spleen, leading to severe anemia and shock).
Routine assessment of the spleen size by the parents can lead to earlier
detection and treatment.
Spleen becomes progressively fibrotic and, by the time the child is four to
six years old, is no longer palpable.
Children with hemoglobin SC or S beta thalassemia can have splenic
enlargement into adolescence.
Neurologic: Evaluate for potential stroke.
Differential diagnosis
Acute chest syndrome (ACS):
One of the most common causes of death in patients with SCD.
Clinical features: Fever, cough, chest pain, shortness of breath, and
decreased oxygenation.
Chest X-ray findings: Multilobar infiltrates (more commonly lower and
middle lobes), effusions, and atelectasis.
Difficult to discern if lung infiltrate due to infection, pneumonia, or
atelectasis.
1.
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Sepsis:
Decreased splenic function in SCD leads to decreased resistance to
infection with encapsulated organisms (Streptococcus pneumoniae,
Haemophilus influenzae type b, Neisseria meningitidis).
Usually non-focal
New infiltrates would not be a usual finding unless the sepsis leads to
acquired/adult respiratory distress syndrome (ARDS).
2.
Rib infarction:
Always consider when child with SCD presents with chest pain (could
be vaso-occlusive crisis)
3.
Congestive heart failure (CHF):
Can occur in patients with SCD and chronic anemia.
Tachypnea is common sign of CHF in children.
Usually does not cause chest pain on its own.
4.
Pericarditis:
Uncommon cause of chest pain
Presents with tachypnea and fever
Can present with effusion and infiltrate
5.
Studies
Newborn screening for SCD:
Knowing a newborns screening results is important, because beginning
penicillin prophylaxis as soon as possible (definitely by two months of age)
is vital in preventing pneumococcal sepsis.
Universal screening for inherited blood cell disorders now occurs in virtually
all of the states and in the District of Columbia.
Nomenclature seen on the newborn screen
At birth, the predominant hemoglobin is hemoglobin F (fetal).
Normal adult hemoglobin is hemoglobin A.
Hemoglobin F is always listed first, followed by other hemoglobins listed in
order of concentration:
FS would be the most common hemoglobin pattern when looking for
sickle cell disease.
When one of the globin genes has a mutation for S and the other has
a mutation for thalassemia (i.e., produces little or no normal
hemoglobin) you may see patterns such as FSA (S-beta thalassemia
+) or FS (S-beta thalassemia 0), both of which are sickling disorders.
When one gene has the S mutation and one gene has the mutation for
hemoglobin C, then the pattern is FSC.
Hemoglobin patterns (at birth, hemoglobin F
predominant)
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FS
Most common hemoglobin pattern for sickle
cell disease
FSA or
FS
One globin gene has a mutation for S, and the
other has a mutation for thalassemia,
producing sickling disorders of a milder
phenotype
FSC
One gene has the S mutation and the other
has the mutation for hemoglobin C
Prenatal diagnosis of SCD:
Sample fetal blood obtained in utero.
DNA extraction from chorionic villi.
Complete blood count (CBC):
Hemoglobin, hematocrit, and reticulocyte count can be interpreted only in
relation to prior values and whether or not the child has had recent
transfusion therapy.
Baseline hemoglobin for children with sickle cell is often between 6 and 9
mg/dL.
Although there is accommodation to the chronic anemia, the lower the
baseline hemoglobin, the more difficult it is for the patient to withstand any
acute change.
Patients with SCD frequently demonstrate an exaggerated leukocytosis and
thrombocytosis in response to stress; CBC findings do not usually
definitively help to identify pneumonia or which of the ACS causes is
present.
Transcranial Doppler:
Study of intracranial blood-vessel flow to assess risk of stroke.
Management
Chronic issues in SCD: Anemia can cause chronic fatigue; will be more severe
due to myelosuppression from infections such as Parvovirus or from
hypersplenism (when spleen enlarges and traps blood cells).
Signs of medical emergencies in SCD:
Fever
May be the only sign of serious infection
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Slurred speech
Stroke
10% of children with SCD have a stroke by age 15 years.
An exchange transfusion may be indicated to lower the hemoglobin-S
level and prevent progression or recurrence.
Tachypnea, chest pain, cough
Lungs are a site of sickling problems:
Acute chest syndrome (ACS)
May be result of infectious process, intrapulmonary sickling or
pulmonary fat embolism (all appear similar on chest X-ray)
Requires supplemental oxygen and transfusion therapy
Increased jaundice
Baseline jaundice typical in SCD and not an emergency
Marked increase in the level of jaundice, however, may indicate an increase
in the degree of hemolysis and a need for transfusion (may be associated
with a viral illness)
Increased pallor
Baseline pallor is a typical finding from the anemia of SCD and does not
constitute an emergency.
Increased pallor, however, can be due to splenic sequestration, increased
hemolysis, or a temporary inhibition of erythroid production (aplastic crisis).
Priapism
Sickling in the penile arteries can cause permanent damage.
Prevention of complications:
Antibiotic prophylaxis
Due to decreased splenic function and consequent decreased resistance to
infection with encapsulated organisms (Streptococcus pneumoniae,
Haemophilus influenzae type b, Neisseria meningitidis), infants and young
children with SCD are at increased risk for sepsis.
When given to infants with sickling disorders, penicillin significantly
decreases the risk of mortality from overwhelming sepsis.
Prophylaxis is usually continued until the child is five or six years of age
(after this, little data to support its use except in patients who have had
documented sepsis and bacteremia, or who have had their spleens
removed).
Immunization
Hemophilus influenza type B conjugate vaccine and 13-valent pneumococcal
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conjugate vaccine (Prevnar 13) given at two, four, and six months.
To expand antibody coverage beyond the 13 initial serotypes, children with
sickling disorders also receive the 23-valent pneumococcal polysaccharide
vaccine at two years of age, with a repeat dose three to five years later.
The meningococcal conjugate vaccine is also given at age two years to
children with functional asplenia (most children with SCD), with a booster
dose three to five years later.
Annual influenza vaccine
Management of complications:
Acute chest syndrome (ACS)
Pain
Can decrease the ability to fully expand the lungs.
Narcotic analgesia relieves the pain and improves ability to take a deep
breath
Narcotics are respiratory depressants, however, and therapeutic balance
must be carefully maintained.
Hydration
Intravenous infusion because respiratory distress and tachypnea both
increase fluid demands and make it difficult for the child to tolerate oral
liquids.
Correct dehydration, provide replacement for insensible losses (increased
with fever and tachypnea), and give maintenance fluids.
1.5 times normal maintenance because dehydration may contribute to
intracellular hemoglobin polymerization and RBC sickling
With ACS, avoid hydrating too vigorously and causing pulmonary edema
from volume overload
Incentive spirometry
Encourage deep breathing to avoid atelectasis
Antibiotics
Practice guidelines and clinical data support the use of antibiotics in ACS
Infectious agents causing ACS include: Viruses, chlamydia, mycoplasma,
and bacteria.
Effective antibiotic choices depend on local patterns of antimicrobial
resistance.
Transfusion of packed RBCs if:
Hemoglobin below baseline
Increasing respiratory rate or chest symptoms
Declining oxygen saturation
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Progressive infiltrates
Exchange transfusion or erythrocytapheresis
Reserve for especially severe disease and/or hypoxemia not corrected by
oxygen therapy.
Sepsis
Fever may be the only sign of sepsis in children with sickle cell disease and
must be dealt with as a medical emergency, with rapid evaluation, blood
cultures and institution of broad-spectrum parenteral antibiotics while
waiting for culture results to guide therapy.
Children with sickle cell disease also get normal colds and other viral
illnesses.
Lack of normal splenic function as well as other more subtle immunologic
deficiencies call for a rapid and aggressive approach.
Waldeyers ring lymphoidal-tissue hypertrophy
Common in children with SCD, evidenced by:
Excessive snoring
Obstructive sleep apnea
Treatment: Tonsillectomy with adenoidectomy
Bilirubin gallstones
Result of increased release of hemoglobin during the breakdown of the
abnormal red blood cells.
Rare in the first five years of life; found increasingly in adolescents.
Treatment: Cholecystectomy (if symptomatic cholelithiasis)
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