Vaso-occlusive crises causing severe extremity pain are the most common manifestation of SCA, accounting for 79% to 91% of ED visits.2 Common triggers include stress, cold, dehydration, altitude, hypoxia, or illness. Pain preferentially affects the long bones and lower back. Individual patients tend to manifest their pain crises in characteristic locations, but the frequency of vaso-occlusive pain crisis is variable, even among SS homozygotes. Five percent of children with SCA account for 33% of total episodes, averaging between 3 and 10 pain crises per year.3 Children display variable degrees of tenderness over affected sites and may have slight temperature elevations without true fever. Because anemia can precipitate a crisis, assess patients for an acute drop in hemoglobin; experienced families may know the patient's baseline values.
Severe vaso-occlusive crises can lead to bony infarction. Pain episodes caused by bony infarcts typically cause more debilitating and refractory pain than past episodes, and there is often significant localized bone tenderness and an elevated peripheral WBC count. Fat embolism can be a complication. Signs and symptoms of fat embolism include acute respiratory distress, hypoxia, and systemic symptoms of petechiae, altered mental status, liver damage, and renal failure. Fat embolism can occur without acute extremity pain, and the aforementioned symptoms should prompt consideration of fat embolization.
When vaso-occlusive crises affect the nutrient arteries of the metacarpals and/or metatarsals, dactylitis results, and children develop tender, painful, swollen hands and feet, which may be accompanied by a low-grade fever (Figure 142-1). Dactylitis occurs in children <2 years old and may be the initial clinical presentation of SCA, but dactylitis is extremely rare beyond 5 years of age. Any number of extremities can be affected, and symptoms can last from days to 2 weeks. Recurrences are common.
Acute sickle dactylitis. Bilateral cylindrical swelling of soft tissue of the fingers in sickle cell anemia consistent with vaso-occlusive crisis of the hands. [Photo contributed by Donald L. Rucknagel, MD, PhD. Reproduced with permission from Knoop K, Stack L, Storrow A, Thurman RJ: Atlas of Emergency Medicine, 3rd ed. © 2009, McGraw-Hill, Inc., New York.]
Avascular necrosis of the femoral head occurs in 30% of patients by age 30 years old. Children present with afebrile inguinal pain with weight bearing. Radiographs may demonstrate flattening and collapse of the femoral head (Figure 142-2). Less commonly, ischemia can cause similar pain in the humeral head.
Avascular necrosis. Note the flattening of the femoral head (arrow). [Image used with permission of Dr. Hollie Jackson, MD.]
Bone and joint infections affect patients with SCA at higher rates than the general population. Infections are often difficult to distinguish from bony infarcts. Symptoms of tenderness, warmth, and swelling may be indistinguishable from those of a vaso-occlusive crisis, although a high fever is more typical of infection. Limited range of motion of a joint is unusual in vaso-occlusive crisis and should prompt evaluation for a septic joint. Although leukocytosis occurs with vaso-occlusive crisis, a left shift is unique to infection. Erythrocyte sedimentation rates are unreliable in patients with SCA. Radionuclide imaging or MRI may distinguish infection from infarct.
Abdominal pain is a difficult symptom to assess in any child and is complicated by the potential abdominal manifestations of SCA. Any acute abdominal condition, such as appendicitis, pancreatitis, and hepatitis, must be considered. However, the abdomen is the next most common site of pain from a vaso-occlusive crisis after the extremities and back. Abdominal vaso-occlusive crises are due to mesenteric, splenic, and hepatic ischemia and present as sudden onset of poorly localized abdominal pain. Physical examination may reveal tenderness and guarding but typically should not demonstrate rebound or rigidity.
Gallstones are common due to the elevated bilirubin levels from hemolysis in SCA and can occur as early as 2 to 4 years of age. Diagnosis is by US. Although symptoms in children may resolve with time, occasionally, cholecystitis can be severe, and infection can progress rapidly (see chapters 79, "Pancreatitis and Cholecystitis," and 131, "Gastrointestinal Bleeding in Infants and Children"). Right upper quadrant syndrome due to intrahepatic cholestasis is not common. Signs and symptoms include sudden right upper quadrant pain, jaundice, anorexia, tender hepatomegaly, and, often, fever. Bilirubin levels can be as high as 50 milligrams/dL. Although patients with SCA often have bilirubin levels above baseline, bilirubin levels rarely exceed 4 milligrams/dL and are predominantly unconjugated bilirubin. Confirm the diagnosis by US. Acute hepatic sequestration is another cause of abdominal pain, and the liver enlarges rapidly. Laboratories are variable, except for low hemoglobin. US or CT scan shows diffuse hepatomegaly in hepatic sequestration.
RESPIRATORY DISTRESS AND CHEST PAIN
Acute chest crisis, due to pulmonary ischemia and infarction, is frequently a complication of pneumonia (Figure 142-3). The incidence of acute chest crisis in children is higher than in adults (21 per 100 person-years in patients with HbSS), but is associated with better outcomes. Children develop any combination of pleuritic chest pain, cough, fever, and dyspnea. Examination findings include retractions, hypoxia, tachypnea, rhonchi, or rales, although dehydration can minimize the presence of rales on examination. An elevated WBC count is often present in both infarct and pneumonia, and thrombocytopenia may accompany severe crises. Chest radiograph is indicated in any patient with chest symptoms or hypoxia, although findings may be minimal early on and should not dissuade treatment of a patient with potential chest crisis on clinical grounds only. Radiography demonstrates a new alveolar pulmonary infiltrate, which is typically located in the upper or middle lobe in children, although adults often have multilobar disease. The cause of pneumonia is typically Chlamydia, Mycoplasma, viral, Streptococcus pneumoniae, Staphylococcus aureus, or Haemophilus influenzae. Sputum or blood cultures are rarely positive and not generally recommended, except in patients ill enough to require mechanical ventilation. Multilobe involvement, history of cardiac disease, and low platelets predict poor outcomes.4 Chest crisis can result in decreased lung function,5 poor integrity of the pulmonary vessels, and a propensity to pulmonary edema. Asthma is common in patients with SCA, occurring in 17% to 53%. Asthma not only complicates the diagnosis of acute chest crisis but also increases the likelihood of chest syndrome by four- to six-fold.5
Acute chest crisis. Note the areas of infiltrate in the right lower lobe and left upper lobe. [Image used with permission of Dr. Hollie Jackson, MD.]
Pulmonary hypertension develops in 16% to 35% of children with SCA. By adulthood, about one-third have pulmonary hypertension, a condition that is associated with diastolic dysfunction and increased mortality. Increased intensity of the second heart sound, evidence of right ventricular enlargement, or unexplained desaturation should suggest pulmonary hypertension (see chapters 57 and 58, "Systemic Hypertension" and "Pulmonary Hypertension," respectively, section on pulmonary hypertension). Diagnosis is made by echocardiogram and right heart cardiac catheterization demonstrating a pulmonary artery pressure above 25 mm Hg. Progressive disease can cause chest pain, dyspnea on exertion, resting hypoxia, right-sided heart failure, syncope, and pulmonary thromboembolism.
Cardiomegaly and heart murmurs are common in children with SCA. However, overt heart failure is uncommon in children, except in cases of iatrogenic volume overload associated with transfusion. Heart failure is managed by the usual methods and by correcting anemia.
Across all ages, infection is the leading cause of death in patients with SCA.6 Splenic dysfunction and inability to form immunoglobulin G antibodies to polysaccharide antigens increase susceptibility to infection, particularly with encapsulated organisms. Children age 6 months to 3 years old are at the greatest risk for sepsis, with H. influenzae and S. pneumoniae more common in the very young, and Escherichia coli and Salmonella more frequent in older children. The rate of bacteremia in children ≤3 years old has been about 8 per 100 patient-years. In children who receive pneumococcal 7-valent conjugate vaccine, invasive pneumococcal disease has decreased by as much as 93.4%.7 Table 142-1 reviews risk factors for bacteremia. Workup of potential infection in SCA patients should include a CBC, urinalysis, chest radiograph, oxygen saturation measurement, and cultures of the blood, throat, urine, or other potential source of infection.
TABLE 142-1Risk Factors for Bacteremia in Children with Sickle Cell Anemia ||Download (.pdf) TABLE 142-1 Risk Factors for Bacteremia in Children with Sickle Cell Anemia
Temperature >40°C (104°F)
WBC count >30,000 or <5000 cells/mm3
Platelet count <100,000/mm3
Hemoglobin <5 grams/dL
Ill appearance, poor perfusion, hypotension
Infiltrate on chest radiograph
History of pneumococcal sepsis
Children with SCA also have an increased prevalence of meningitis, pneumonia, arthritis, and osteomyelitis compared to the general population, and have poorer outcomes for these diseases. Similarly, viral infections, including influenza, result in greater morbidity, and yearly vaccination for influenza is recommended.
Parvovirus B19 infection is of particular concern. The initial infection is usually asymptomatic or associated with nonspecific upper respiratory symptoms. However, parvovirus can cause several different clinical syndromes. Erythema infectiosum is characterized by fever, headache, nausea, coryza, and slapped cheek appearance with circumoral pallor followed by diffuse maculopapular rash. Gloves and socks syndrome describes well-demarcated painful erythema and edema of the hands and feet that evolves into petechiae, purpura, vesicles, and skin sloughing. Finally, parvovirus can cause symmetric or asymmetric arthropathy of knees and ankles. Regardless of the clinical presentation, parvovirus can cause a transient aplastic crisis, with the reticulocyte count dropping 5 days after exposure, followed by a decline in hemoglobin (see chapter 143, "Oncologic and Hematologic Emergencies in Children"). Because of the shortened life span of the red cells in SCA, parvovirus can cause serious anemia, which lasts for 2 weeks. Upon recovery, there is an outpouring of nucleated red blood cells from the marrow, and patients late in the illness may have a high reticulocyte count.8 Infection usually imparts subsequent lifelong immunity to parvovirus.
Splenic sequestration, or intrasplenic trapping of red cells, is a major cause of mortality in children <5 years old. Two types exist, major and minor. Major splenic sequestration causes a rapid drop of more than three points in the hemoglobin, with the development of pallor, left upper quadrant abdominal pain, and splenomegaly. This can progress within hours to altered mental status, hypotension, and cardiovascular collapse. Minor splenic sequestration tends to be more insidious, with a smaller change in hemoglobin levels. Often, attacks occur along with bacterial or viral infections. Laboratory studies in either syndrome demonstrate a decline from baseline hemoglobin level, a normal to increased reticulocyte count, and no change in bilirubin, because there is no hemolytic component to this complication. Mild neutropenia or thrombocytopenia may be noted. Patients with HbSS rarely experience this complication beyond 5 years of age (peak, 3 months to 5 years old) due to infarction and scarring of the spleen, but most patients with HbSC and homozygous S/β-thalassemia have a spleen that persists into adulthood, and thus have a risk of splenic sequestration.
As noted earlier, aplastic crisis is an important cause of anemia in SCA patients and can be induced by parvovirus infection or medications. Signs are the gradual onset of pallor without pain or jaundice. Laboratories demonstrate a decline in hemoglobin and a low reticulocyte count. Full recovery is expected within weeks.
Stroke is 250 times more common in children with SCA than in the baseline population9: 11% of children with SCA suffer a clinically overt stroke, and another 20% are found to have silent strokes on imaging. The risk of recurrence, untreated, after one stroke is 49% to 90%, and children with HbSS are at four times greater risk than those with HbSC. SCA patients typically have cerebral vasculopathy involving the intima and media of large arteries, usually the middle cerebral artery. Screening transcranial Doppler studies can identify abnormal flow patterns associated with this vasculopathy, which, if untreated, are associated with a 10% risk of stroke within 2 to 3 years of diagnosis.3 Additionally some children will develop a moyamoya-like syndrome in which clotted vessels induce the development of diffuse small collateral vessels. These weak vessels are prone to aneurysm formation and spontaneous hemorrhage and demonstrate a characteristic "puff of smoke" appearance on cerebral angiography.
Cerebral ischemia can present with fleeting symptoms of transient ischemic attacks, or with hemiparesis, seizure, altered mental status, or coma. Common vascular territories involved include the internal carotid or middle cerebral arteries, but venous sinus thrombosis may cause parieto-occipital or thalamic involvement (Figure 142-4).9 As in adult stroke, the CT scan is less reliable to detect ischemic infarct in the first 36 hours, although CT scan does rule out hemorrhage. Diffusion-weighted MRI demonstrates changes within minutes and T2-weighted MRI within hours of ischemia.
Acute stroke. T2-weighted MRI scan of the brain shows areas of increased signal intensity (arrow) involving the gray and white matter of the left parietal lobe, consistent with an acute infarct. [Reproduced with permission from Shah BR, Laude TL: Atlas of Pediatric Clinical Diagnosis, © 2000 WB Saunders, Philadelphia.]
Patients with SCA also have a higher rate of cerebral aneurysms and intra-cranial hemorrhage than the general population, although hemorrhagic stroke only accounts for 10% of strokes in SCA patients. This complication is rarely seen in children but becomes a concern during late adolescence. Hemorrhagic strokes typically present with headache, vomiting, and alterations in level of consciousness but may present with hemiparesis similar to an ischemic stroke if bleeding is intraparenchymal. There are three potential sites of hemorrhage: subarachnoid from an aneurysm, intraparenchymal from large-vessel vasculopathy or moyamoya, and intraventricular from moyamoya.
Neurologic symptoms are not uncommon in patients with acute chest crisis as well and have been noted in 7% to 10% of cases.9 Other considerations in the patient with altered mental status and SCA previously mentioned include severe anemia from splenic sequestration and meningitis.
Priapism is common in males, with 27% having at least one episode by age 20 years old.10 There is a bimodal age peak—5 to 13 years old and 21 to 29 years old. Patients present with a painful, swollen, edematous, tender penis, often with difficulty urinating (Figure 142-5). The glans itself remains soft. Sickling of the red cells in the sinusoids of the corpus cavernosum cause decreased venous outflow from the penis.10
Priapism in an adolescent male with sickle cell anemia. [Reproduced with permission from Shah BR, Lucchesi M: Atlas of Pediatric Emergency Medicine. © 2006, McGraw-Hill, New York.]
The most common renal abnormality is hyposthenuria, the inability to maximally concentrate urine. This may cause enuresis, nocturia, and a propensity for dehydration and hyperkalemia. Renal vaso-occlusive crises are also common and can be asymptomatic or accompanied by colicky intermittent flank pain, costovertebral angle tenderness, gross or microscopic hematuria, and passage of renal tissue. Chronic damage to the kidneys can lead to renal insufficiency at an early age.
Hematuria can also occur with papillary necrosis, a complication seen in both homozygous and sickle trait patients. Urinalysis demonstrates red blood cells without casts or associated pyuria or significant proteinuria.