BRANDON C. KU
HISTORY OF PRESENT ILLNESS
A 5-year-old African-American girl was brought to the emergency department for complaints of pallor and fatigue. For the past 3-4 days she seemed tired. She had not been eating or drinking as usual and had been relatively inactive. There have been no fevers. She denied nausea, vomiting, and diarrhea. Her urinary pattern has not changed. She has no specific sites of pain or discomfort. The mother stated that her eyes are always somewhat yellow and the color had not changed.
The girl was full-term product of a spontaneous vaginal delivery. At 2 years of age she developed painful swelling of her hands. Her 5-year-old sibling had witnessed a “bee sting.” She was treated with diphenhydramine and corticosteriods for a possible allergic reaction. The swelling resolved over the course of several days. She required emergency department evaluation at 4 years of age for persistent left knee and back pain after falling. Radiographs of her spine, hips, and left femur, tibia, and fibula were normal. She was treated with a combination of ibuprofen and oxycodone. She has not received any medications recently. She was born in Jamaica and moved to the United States at 2 years of age. Her immunizations were reportedly up-to-date although written confirmation was not available.
T 37.3°C; HR 140 bpm; RR 30/min; BP 100/60 mmHg; SpO2 95% in room air; Weight 5th percentile
Physical examination revealed a thin child with obvious scleral icterus. She was in mild respiratory distress. The neck was supple. There were several small cervical lymph nodes palpable. The lungs were clear. There was a 1/6 systolic ejection murmur at the lower left sternal border. The abdomen was soft. The liver edge was palpable 1-2 cm below the right costal margin. The spleen was massively enlarged and could be felt at the pelvic brim. The remainder of the examination was normal.
A WBC count of 8200/mm3 (2% band forms, 23% segmented neutrophils, 61% lymphocytes, 12% monocytes, and 2% eosinophils) Hemoglobin, 4.6 g/dL; platelets, 156 000/mm3; reticulocyte count, 16%; total bilirubin, 2.4 mg/dL; hepatic function panel was normal; chest radiograph was normal.
COURSE OF ILLNESS
The peripheral blood smear revealed the diagnosis (Figure 10-4).
FIGURE 10-4. Peripheral blood smear.
DISCUSSION CASE 10-5
The findings on peripheral blood smear were suggestive of sickle cell disease (see below). In patients known to have sickle cell disease who present with the signs of pallor and fatigue, the differential diagnosis consists of four elements—infection, acute red cell aplasia (aplastic crisis), acute hemolytic crisis, or sequestration. Infections until recently were the major cause of mortality in children. Infection is usually heralded by fever. Any fever in a patient with sickle cell disease or one of the variants must be taken seriously and treated aggressively. Acute red cell aplasia occurs when red cell production fails to keep up with the need produced by a shortened red cell survival. Often parvovirus B19 is the cause of this type of acute drop in hemoglobin. Acute hemolysis may also occur and cause a worsening of anemia. Often parents will detect an increase in jaundice or a darkening of the child’s urine. Sequestration can be diagnosed by clinical examination and tends to occur in young children whose spleens have not yet auto-infarcted. Table 10-6 shows the comparison of findings in the different manifestations of sickle cell disease.
TABLE 10-6. Comparison of findings in sequestration, aplastic, and hemolytic crises in sickle cell disease.
The peripheral blood smear revealed numerous blunted and boxy sickled cells more typically seen with SC type sickle cell disease (Figure 10-4). This diagnosis was confirmed by hemoglobin electrophoresis. The clinical picture in light of the peripheral blood smear suggested the diagnosis of sickle cell disease (SC type) with associated splenic sequestration. In retrospect, the episode of hand swelling at 2 years of age may have been dactylitis, a complication of sickle cell disease in young children. The episode of pain requiring narcotics may have been a vasoocclusive episode causing pain. Obviously, this would be difficult to prove in retrospect. She promptly received penicillin prophylaxis.
INCIDENCE AND EPIDEMIOLOGY OF SICKLE CELL DISEASE WITH SEQUESTRATION
The cultural incidence of sequestration is not known. Sickle cell disease affects one in every 400-500 African-Americans. It also occurs in people of Mediterranean, Arabic, and Indian origins. There are three major forms of sickle cell disease in the United States population: Hgb SS Disease (60%), Hgb SC Disease (30%), and Sickle B+ Thalassemia (10%). In patients with Hgb SS type, sequestration usually occurs early in life since the spleen ultimately undergoes auto infarction. Children with milder forms of disease, typically SC type, may develop sequestration as late as 10 or 11 years of age.
CLINICAL PRESENTATION OF SICKLE CELL DISEASE WITH SEQUESTRATION
The manifestations of sequestrations are varied. The patient may have a mild form of sequestration with only a minor drop in hemoglobin or may present in full cardiovascular collapse. In all cases, there is splenic enlargement and evidence of a decrease in circulating blood volume. There may be a fatal outcome if therapeutic response is not adequate. Splenic sequestration may recur.
The diagnosis is established by having a high index of suspicion and a careful physical examination. Laboratory studies will rule out other conditions in the differential diagnosis but there is no single laboratory test to confirm sequestration. Part of the high index of suspicion comes in having a well-educated patient and patient population that is capable of recognizing and reporting every sign and symptom.
Hemoglobin electrophoresis. Hemoglobin electrophoresis establishes the diagnosis of sickle cell disease. In a patient with homozygous sickle cell disease, electrophoresis reveals more than 80% HbSS, less than 20% HbF (fetal hemoglobin), and less than 4% HbA2. Patients with hemoglobin SC disease, as in this case, will have equal proportions of HbS and HbC. In contrast, carriers will have approximately 35% HbSS and more than 60% HbA.
Complete blood count. The hemoglobin concentration in children with homozygous sickle cell disease (HbSS) is low, typically less than 9 g/dL. In contrast, the hemoglobin concentration of children with hemoglobin SC disease is higher, typically 10-12 g/dL.
Peripheral blood smear. The peripheral blood smear reveals characteristic sickle cells. Other findings include target cells (excess red cell membrane relative to the amount of hemoglobin) and, as a result of hemolysis, schisocytes.
Reticulocyte count. The reticulocyte count is elevated, but the value depends on the extent of hemolysis.
Other studies. Laboratory findings that indicate hemolysis include increased lactate dehydrogenase, increased unconjugated bilirubin, reduced serum haptoglobin, and hemoglobinuria.
In mild cases with hemodynamic stability, hydration and careful watching in an inpatient setting may be all that is required. In severe cases, prompt transfusion therapy is required. Some patients are placed on a routine transfusion program. In frequently recurring episodes, splenectomy may be indicated. Splenic infarct occurs over time and the splenic function is usually already compromised.
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