eMedicine Specialties > Emergency Medicine > Pediatric

Pediatrics, Sickle Cell Disease

Author: Nedra R Dodds, MD, Medical Director, Opulence Aesthetic Medicine
Coauthor(s): Hosseinali Shahidi, MD, MPH, Assistant Professor, Departments of Emergency Medicine and Pediatrics, State University of New York and Health Science Center at Brooklyn
Contributor Information and Disclosures

Updated: Nov 21, 2007

Introduction

Background

Sickle cell disease is an inherited disorder of hemoglobin synthesis. The resulting abnormality produces a normocytic, hemolytic anemia with multiple diversely shaped RBCs that are susceptible to morphologically changing into a sickle shape. The sickle cells produce thrombosis and obstruction in small vessels, leading to ischemia and necrosis of distal tissue.

Pathophysiology

Sickle cell disease results from a single amino acid substitution (valine for glutamate) in position 6 of the beta-globin chain of hemoglobin. This genetic alteration yields an unstable RBC with a shortened survival that under stress becomes sickle shaped.

Frequency

United States

Approximately 8-10% of African Americans in the population carry the gene S. Homozygous (SS) sickle disease occurs in about 0.15% of African American newborns.

International

Other sickle syndromes may be present in individuals from India, the Middle East, and the Mediterranean.

Mortality/Morbidity

The clinical course of sickle cell disease is one of chronic illness precipitated by multiple acute exacerbations that can become life threatening at any time.

• Today, approximately 50% of patients survive beyond the fifth decade.
• A third of deaths during an acute crisis occur in patients who are clinically free of organ failure.
• Infection is the leading cause of death in affected children aged 1-3 years.
• Strokes and trauma are the leading causes of death in patients aged 10-20 years. Children in this age range also die from acute chest syndrome, splenic sequestration crisis, and aplastic crisis.

Race

Sickle hemoglobinopathy syndromes are genetically predetermined hemolytic anemias that predominantly occur in individuals of Central African descent. In Latin America, high frequencies are observed in the Caribbean, Guyanese, Panamanian, and Brazilian populations.

Age

• Hematologic changes indicative of the disorder are evident as early as the age of 10 weeks, though symptoms are usually delayed until the age of 6-12 months because of high levels of circulating fetal hemoglobin.
• Beta-chain (adult) hemoglobulin is usually not prominent until the age of 3 months.
• After infancy, erythrocytes of patients with sickle cell anemia contain approximately 90% hemoglobin S (HbS), 2-10% hemoglobin F (HbF), a normal amount of minor fraction of adult hemoglobin (HbA2), and no hemoglobin A (HbA).

Clinical

History

Patients with sickle cell disease, at some point in their lifetime, may experience exacerbations in their clinical course. Children at different ages are susceptible to differing types of crisis, which each may occur in a given child at some point.

• A painful vaso-occlusive crisis is the most frequent clinical symptom of sickle cell disease.
  • In infants, painful symmetrical swelling of the hands and feet (dactylitis or hand-foot syndrome) caused by infarctions of the small bones may be the initial manifestation of sickle cell anemia.
  • Most bony vaso-occlusive events occur primarily in the bone marrow cavity. Most are multifocal and associated with mild tenderness and localized edema.
  • As the child matures, the painful episodes usually affect the joints, especially the hips and knees and those of the chest wall and back. Document the frequency, the precipitants, and the similarity of painful episodes on each visit to exclude more serious causes, such as infection.
• Promptly evaluate older patients who complain of chest pain, cough, dyspnea, or tachypnea to exclude acute chest syndrome.
  • The acute febrile pneumonic process is associated with new infiltrates on chest radiographs. Chest pain may precede the radiographic findings, or they may occur with the onset of pain. Although initial chest radiographs may be normal, subsequent radiographs reveal an infiltrate, which may rapidly extend to involve 1 or more lobes and the pleura.
  • The etiology may be infectious (eg, pneumonia), vaso-occlusive, or both. This syndrome often results in hypoxia and, occasionally, death.
• Abdominal pain often occurs as excruciating pain with diffuse tenderness, distension, and muscular rigidity of the abdominal wall.
  • The pain often is caused by small infarcts of the mesentery and viscera, usually without peritoneal signs.
  • A thorough history, obtained from the patient or the parents, is crucial because their recognition of the nature of the pain helps in distinguishing vaso-occlusive pain from that of other etiologies, such as cholecystitis, perforated viscus, or appendicitis.
• Sequestration crisis is a distinct form of acute hypersplenism unique to infants and young children.
  • Vascular occlusion occurs in the splenic sinusoids, resulting in large volumes of blood trapped in the substance of the spleen.
  • If these events occur gradually, the patient may present with progressive pallor, fatigue, left-sided abdominal pain, and increasing splenomegaly.
  • This event may occur before or after autoinfarction of the spleen transpires. If splenic sequestration occurs more abruptly, patients may present in extremis, manifesting severe hypovolemic shock.
• If vascular occlusion occurs in large or small cerebral vessels, a neurologic event may occur.
  • Patients may have gait disturbances, hemipareses, paresthesias, aphasias, altered consciousness, or seizures.
  • MRI findings or high flow on transcranial Doppler sonography of silent lesions are associated with a high risk of stroke.
• Men may present with priapism (ie, prolonged, acute, and painful erection due to venous occlusion). Priapism may recur often.
• Infants and children are susceptible to aplastic anemia crisis.
  • During episodes of crisis, the degree of anemia worsens, and jaundice decreases due to a profound reticulocytopenia, resulting in no erythrocyte precursors in the bone marrow.
  • The patient appears acutely ill, tachycardic, and pale, yet nonicteric.
  • Occasionally, patients recover in several days.
  • The symptoms are usually due to an infection by the parvovirus B19 prototype.
• Patients with sickle trait have erythrocytes that contain only 30-40% HbS. Heterozygosity for the sickle gene has a benign clinical course. Sickling does not occur under physiologic conditions.
  • In rare cases, patients may have hypoxia or shock when flying at high altitudes in an unpressurized aircraft, which causes vaso-occlusive phenomena.
  • Spontaneous hematuria, usually from the left kidney, has also occurred in patients with the sickle trait. The bleeding is often mild, but blood transfusion is often needed.
  • Patients with sickle cell disease and trait often have a high incidence of enuresis because their bodies cannot appropriately concentrate urine.

Physical

In evaluating the patient with sickle cell disease, it is important to consider the pattern of past events, baseline laboratory values, and current status of disease.

• Patients most often present with pain complaints; but younger children, who cannot communicate well, must be observed for irritability, poor feeding, or fussiness.
• Vital signs must be evaluated for fever, tachycardia, and tachypnea, which may be present due to pain or infection.
• As the patient matures, he or she may have icteric sclera and pallor of the conjunctiva and mucous membranes. Funduscopic examination may reveal retinopathy.
  • Dental malocclusion may be present secondary to maxillary hyperplasia due to expansion of the bone-marrow space.
  • Perform cardiac examination to determine presence of a murmur.
  • Auscultation rales, or breath sounds may be decreased bilaterally due to extensive pulmonary consolidation. Infarction is difficult to distinguish from pneumonia.
• The presence of active bowel sounds, absence of emesis, and patient recognition of pain helps distinguish vaso-occlusive pain from other etiologies.
  • Abdominal examination of the young child may reveal splenomegaly if sequestration is occurring. Otherwise, the spleen recedes and should not be palpable by the age of 3-4 years as a result of autoinfarction.
  • In patients with mild variants of sickle disease, splenomegaly may persist into adulthood.
  • Note the size of the liver and examine for evidence of gallstones, as these can form in patients as young as 3 years.
• Inspect the genitalia for priapism if the patient complains of pain.
• The most dramatic physical finding often is observed in the extremities.
  • Young infants may have recurrent edema of the dorsum of the hands and feet.
  • Infarction of the cortex of the long bones may lead to prominent signs of local inflammation, including tenderness, edema, and erythema.
  • As the child grows, repetitive infarctions in the joints of large and small bones may produce abnormally angled digits and enlarged, malformed, and (occasionally) frozen joints, particularly at the knees and ankles.
  • Chronic leg ulcers are common in the adolescent patient.
• Thoroughly examine any patient who complains of mental status changes, paresis, or other symptoms compatible with a stroke because strokes are prominent in this age group.
• By mid childhood, most patients are underweight compared with children of their same age and height.

Causes

• The sickling process that frequently occurs with sickle cell anemia may be precipitated by multiple factors.
  • A crisis may be induced by local tissue hypoxia, dehydration secondary to a viral illness, or nausea and vomiting, all of which lead to hypertonicity of the plasma.
  • Any process that can lead to acidosis, such as infection or extreme dehydration, can cause sickling.
  • More benign factors and environmental changes, such as fatigue, exposure to cold, and psychosocial stress, can elicit the sickling process that prompts a crisis.

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