Pediatric Examination and Board Review (154 page)

4.
(A)
Children with sickle cell disease are at increased risk for severe bacterial infections because of splenic hypofunction, secondary to slowly progressive autoinfarction of splenic tissue. The average age of complete splenic infarction is approximately 2-4 years old in patients with hemoglobin SS but can be delayed to 6-8 years of age in patients with hemoglobin SC or Sβ
⁺
thalassemia. Even before this age, however, children with sickle cell disease are more susceptible to encapsulated organism infection and rapidly progressive sepsis in the absence of treatment. Potential organisms include
S pneumoniae
,
H influenzae
,
N meningitidis
,
Salmonella
species, and
E coli
. Therefore, children with sickle cell disease should receive all recommended vaccines on time, and those who have fevers should always be evaluated by a physician. They should undergo laboratory evaluation including complete blood count with a reticulocyte count, blood culture, urinalysis, urine culture, and chest radiograph.

Ceftriaxone, a broad-spectrum third-generation cephalosporin, is the antibiotic most likely to cover most of the potential pathogens in children with sickle cell disease, and particularly
S pneumoniae
, the most common cause of infections and infectious morbidity in sickle cell patients. Other thirdgeneration cephalosporins are also acceptable options. A macrolide such as azithromycin is frequently added to cover possible
Chlamydia
and
Mycoplasma
pulmonary infections. Although clindamycin and vancomycin are effective against most gram-positive bacteria, including
S aureus
, they are not effective against the encapsulated gramnegative bacteria that are potential causes of infections and therefore are not optimal choices for initial management. Anaerobic infections are not more frequent in patients with sickle cell disease, and so metronidazole is not an appropriate initial choice.

5.
(D)
Opiates have several common side effects, including impaired GI motility and constipation, nausea and vomiting, hypotension, respiratory depression, lowered seizure threshold, and pruritus, which must be managed to maximize the pain management in children with sickle cell crises. Hematuria is not a side effect of opiates but does occur commonly in patients with sickle cell disease.

6.
(B)
Patients with hemoglobin SS and Sβ
⁰
thalassemia tend to have the most severe complications from sickle cell disease, including more frequent episodes of acute chest syndrome. Patients with hemoglobins SC and Sβ
⁺
thalassemia generally have milder symptoms, although the range of severity is wide and patients with hemoglobins SC or Sβ
⁺
thalassemia can have very severe complications. Patients with beta-thalassemia do not have complications from red blood cell sickling, such as acute chest syndrome. Other factors, such as the amount of fetal hemoglobin (hemoglobin F), the presence of coexisting alpha-thalassemia or other unknown factors may play a role in modifying sickle cell disease severity. People with hemoglobin AS, or sickle cell trait, do not experience acute chest syndrome and have virtually no symptoms, but they should receive genetic counselling regarding the risks of sickle cell disease in their offspring.

7.
(C)
Recurrent acute chest syndrome results in pulmonary injury with intimal hyperplasia and fibrosis. Chronic pulmonary infiltrates, chest pain, hypoxia, and the eventual development of pulmonary hypertension and cor pulmonale can all ensue. Emphysema does not occur as a result of recurrent acute chest syndrome.

8.
(D)
The results of neonatal hemoglobin electrophoresis are reported in order of decreasing amounts of the expressed hemoglobin molecules. For example, patients with normal hemoglobin, or hemoglobin AA, will have more fetal hemoglobin (hemoglobin F) than hemoglobin A at birth, and they will have a neonatal hemoglobin electrophoresis result of “FA.” Patients with homozygous hemoglobin SS will still have more fetal hemoglobin at birth than sickle hemoglobin, and so their neonatal electrophoresis result will be “FS.” Patients with hemoglobin SC disease will have a neonatal electrophoresis result of “FSC.” Patients with sickle cell trait have more hemoglobin A than hemoglobin S, because A is more stable than S, and so the correct result for patients with sickle trait is “FAS.” Patients with hemoglobin Sβ
⁺
thalassemia will have some hemoglobin A but not as much as the hemoglobin S, and therefore the result will be “FSA.”

9.
(B)
Approximately 8% of U.S. African Americans carry the hemoglobin S gene, resulting in a sickle cell disease frequency of approximately 1 in 600 African Americans. By comparison, approximately 4% of African Americans in the United States carry the hemoglobin C gene, 1% carry a gene mutation for beta-thalassemia, and 1-3% carry a gene mutation for alpha-thalassemia. Sickle cell disease can also be found in Middle Eastern, Indian, and Central and South American populations; the hemoglobin S gene mutation is extremely rare in whites. The prevalence of sickle cell disease has been linked to protection from malaria infection, with those patients with sickle cell trait or disease relatively spared from the severe complications of malaria.

10.
(C)
Howell-Jolly bodies are intracellular collections of precipitated hemoglobin that, under normal circumstances, cause the red blood cell to be trapped in the spleen, either to be totally destroyed or to have the Howell-Jolly body “removed” by splenic macrophages, resulting in smaller, more fragile red blood cells that leave the spleen. The presence of red blood cells with these bodies in the peripheral circulation suggests the loss of the splenic filtration function, either because of surgical splenectomy or functional splenectomy from progressive infarction that occurs in patients with sickle cell disease. The average age of complete splenic infarction is approximately 2-4 years old for patients with hemoglobin SS but is delayed to 6-8 years of age in patients with hemoglobin SC. Auer bodies are white blood cell inclusions found in patients with acute promyelocytic leukemia. Basophilic stippling is seen in lead poisoning and represents residual ribosomal material within the red blood cells precipitated as a result of the presence of toxins. Polychromasia refers to the presence of reticulocytes on the peripheral smear, which appear more purplish than the mature red blood cells. Although patients with sickle cell disease do have an increase in reticulocytes and have significant polychromasia on their peripheral smears, it is not associated with their splenic function.

11.
(D)
Renal disease is a common complication of patients with sickle cell disease. The kidney is particularly susceptible to injury in patients with sickle cell disease because of the relatively hypoxic environment of the renal medulla and the high oxygen requirements of the renal parenchyma. Renal disease occurs in up to 25% of adolescents with sickle cell disease. Also, up to 40% of adults with sickle cell disease have renal insufficiency, with many progressing to end-stage renal disease requiring dialysis and possibly renal transplant. Components of “sickle cell nephropathy” include hyposthenuria, hematuria, proteinuria, renal cortical infarction, papillary necrosis, pyelonephritis, and, rarely, renal cell carcinoma. Glucosuria is not a complication seen in patients with sickle cell disease.

Hyposthenuria refers to the inability of patients with sickle cell disease to concentrate their urine because of the infarction of and damage to the renal medulla. The presence of hyposthenuria can be found in sickle cell patients by 5-10 years of age and becomes irreversible by 15 years of age. Hyposthenuria can cause significant dehydration, particularly in patients experiencing complications of their sickle cell disease. Hematuria can be microscopic or gross and primarily arises from the left kidney (80% of cases), although in approximately 10% of cases, hematuria arises from both kidneys. Proteinuria can range from microalbuminuria to nephrotic syndrome.

12.
(B)
The gallstones of patients with chronic hemolytic anemias (including sickle cell disease) are composed of bilirubin, a breakdown product of hemoglobin. Cholelithiasis with or without associated cholecystitis occurs in up to 70% of patients with sickle cell disease, and it can occur in children as young as 4 years of age. Approximately a third of children with gallstones have an underlying hemolytic anemia. Recurrent or severe abdominal pain is common in patients with sickle cell disease and frequently is a result of cholelithiasis or cholecystitis, although hepatitis, pancreatitis, and other intra-abdominal processes must be considered, in addition to abdominal vaso-occlusive pain crises. Recurrent or severe abdominal pain in sickle cell patients with gallstones or episodes of acute cholecystitis are indications for cholecystectomy.

13.
(B)
Acute stroke in patients with sickle cell disease is one of the indications for emergent exchange transfusion. Approximately 10% of children with sickle cell disease have at least one stroke episode by the mean age of 7-8 years. Symptoms can range from headaches, changes in vision, cranial nerve palsies, hemiparesis, seizures, coma, or death. The diagnosis is made with magnetic resonance imaging (MRI), although urgent computed tomography (CT) scanning to rule out intracranial hemorrhage (rare in children but more common in adults with sickle cell disease) can also be performed. The use of emergent exchange transfusion in a patient with sickle cell disease and acute neurologic symptoms decreases the percent of hemoglobin S to less than 30% and results in decreased symptom severity and decreased incidence of long-term complications. Simple red blood cell transfusions are not effective in the treatment of stroke in patients with sickle cell disease, and nonsteroidal anti-inflammatory agents and hyperbaric oxygen have no role in stroke management in these cases.

14.
(C)
Patients with sickle cell disease who have strokes have similar symptoms to other patients with acute cerebrovascular injuries, including the acute onset of cranial nerve palsies, hemiparesis, and, possibly, seizures or coma. Although most sickle cell patients have a complete neurologic recovery from their strokes, complications such as residual neurologic dysfunction, persistent seizure disorder, cognitive delay, behavioral changes, and recurrent strokes can occur. Optic neuritis is not a neurologic complication of strokes in patients with sickle cell disease. Stroke recurrence in patients with sickle cell disease can occur in up to 60% of patients within 3 years of the initial stroke in the absence of treatment. Slowly progressive cognitive delay because of recurrent, otherwise asymptomatic strokes is a common problem in children with sickle cell disease and requires early identification and intervention. Neovascularization occurs in the areas of the brain that are left underperfused by the stroke. The network of small, delicate vessels that appear as cloud-like puffs on an arteriogram are called
moyamoya
. The name derives from a disorder described most often in people of Japanese ancestry in which a similar network of vessels develops idiopathically. The network of vessels in moyamoya has a propensity to rupture. Hemorrhage produces additional neurologic deficits. Bleeds from moyamoya can be extremely debilitating and even fatal in patients with sickle cell disease.

15.
(D)
Regular blood transfusions to maintain a baseline hemoglobin level of 8-10 g/ dL and a hemoglobin S fraction of less than 30% is the only proven therapy that can prevent stroke recurrence in children with sickle cell disease. The incidence of stroke recurrence can be decreased from 60% within 3 years of an initial stroke without treatment to less than 10% with regular blood transfusions. However, the hemoglobin should be maintained less than 10 g/dL to avoid hyperviscosity associated with higher hemoglobin levels and an increase in stroke risk.

16.
(D)
Parvovirus B19 infections are associated with aplastic crises in any patient with shortened red blood cell lifespan. Therefore, patients with sickle cell disease, red blood cell enzyme deficiencies, or red blood cell structural defects are susceptible to aplastic crises from parvovirus B19. Parvovirus infects the erythroid precursors within the bone marrow, temporarily halting new red blood cell production. The otherwise normal patient, with a red blood cell lifespan of 120 days, will suffer a small, likely asymptomatic fall in total hemoglobin, followed by bone marrow recovery and new red blood cell production. Patients with a decreased red blood cell lifespan because of the inability of the marrow to produce new red blood cells appropriately have severe, possibly life-threatening falls in hemoglobin levels. Infections with bacteria and other viruses, such as Epstein-Barr virus (EBV) or adenovirus, do not commonly have bone marrow toxicity and generally do not cause aplastic crises.

17.
(D)
Dactylitis, or hand-foot syndrome, is a complication of sickle cell disease that most commonly occurs in infants younger than 1 year of age. Dactylitis is characterized by painful nonpitting edema of the dorsal surfaces of the hands and feet bilaterally, without other locations of pain or swelling. Dactylitis is also frequently accompanied by a low-grade fever. The etiology is not completely understood but most likely involves vaso-occlusion within the distal extremities. Management is similar to other types of vaso-occlusive pain crises. Priapism is a condition of prolonged, painful erection that occurs in up to 40% of adolescent males with sickle cell disease and requires urgent intervention with intravenous fluids, pain control, and either medical or surgical interventions to reduce the erection. Priapism rarely occurs in children younger than 10 years of age and never occurs in infancy. The erections of priapism can last for 30 minutes to several days, and recurrence can lead to eventual impotence. Acute chest syndrome and transient ischemic attacks can both occur in infancy but are more common in older children and adults. The average age of the initial cerebral vascular accidents in children with sickle cell disease is 7-8 years.