A 4-year-old boy with known sickle cell disease is brought to the emergency department with worsening pain in his thighs, lower back, abdomen, and chest. He developed pain in both thighs 2 days ago, and was treated with ibuprofen without improvement. His chest pain began today and he refused to walk or eat. In the emergency department, he was tachypneic and had an oxygen saturation by pulse oximetry of 84 percent on room air, which increased to 95 percent on 2 liters oxygen by nasal canula. A chest x-ray showed bilateral infiltrates (Figure 211-1). He was diagnosed with acute chest syndrome and admitted to the pediatric intensive care unit, where he was treated with intravenous fluids, pain medications, and antibiotics, and made a full recovery.

Sickle cell diseases (SCD) are a group of genetic disorders in which the affected individual has at least one copy of the genes that encode b-globin chains affected by the sickle cell mutation. This mutation causes sickling of red blood cells with resultant hypoxia and acidosis leading to a chronic progressive multisystem disorder. Sickle cell trait (SCT) is a condition in which affected individuals have one normal copy of the β chain gene and one sickle mutated copy. These individuals are generally unaffected. Hemoglobin SS disease (SCD-SS) is a condition in which affected individuals are homozygous for the sickle mutated β chain gene.¹

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  Sickle cell disease (SCD), Sickle cell anemia, Hemoglobin SS disease (SCD-SS).

  
  
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  Hemoglobin SC disease (SCD-SC) and Hemoglobin S β-thalassemia (SCD-S-β Thalassemia) are types of sickle cell disease with different mutations than SCD-SS.

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  SCD affects 90,000 to 100,000 Americans.

  
  
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  SCD occurs in approximately 1 out of every 500 Black or African-American births.

  
  
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  SCD occurs in approximately 1 out of every 36,000 Hispanic-American births.

  
  
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  SCT occurs in approximately 1 in 12 Blacks or African-Americans.²

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  Sickle cell disease is caused by a hemoglobin structural defect that results from the substitution of valine for glutamic acid at the 6th position on the gene coding for β globin.

  
  
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  The mutation causes sickling in deoxygenated cells and leads to red cell membrane rigidity, increased red blood cell adhesion to the vascular endothelium, venous occlusion, and a decreased red cell life span of 10 to 20 days.

  
  
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  The point mutation in Hemoglobin C disease results from a hemoglobin structural defect that results from the substitution of lysine for glutamic acid at the 6th position on the gene coding for β globin.

  
  
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  This mutation results in persistent cellular potassium loss and cellular dehydration, causing increased blood viscosity and subsequent vaso-occlusion.

  
  
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  The clinical problems associated with sickle cell diseases are a consequence of hypoxia and acidosis, which are caused by tissue ischemia that results from vaso-occlusion by irreversibly sickled red blood cells.

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  Hemoglobin S occurs frequently in areas previously exposed to falciparum malaria. This includes western coastal Africa, central Africa, India, Saudi Arabia, and the Mediterranean. It is also seen in South America.

  
  
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  Hemoglobin C occurs more frequently in individuals of western African descent.

  
  
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  In the US, SCD is found most commonly among African Americans.

Clinical Features

Sickle cell diseases are chronic progressive multisystem disorders.³ The acute clinical manifestations may be grouped into three categories:

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  Vaso-occlusive events.

  
  
  
  
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    Vaso-occlusive crisis commonly affects bone, lung, liver, and spleen.

    
    
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    Bone infarction or ischemia of periarticular tissues is the most common form of acute pain crisis.

    
    
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    Diffuse or localized pain and tenderness, along with swelling and limited range of motion, is common.

    
    
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    Dactylitis (hand-foot syndrome) is a painful swelling of the metacarpals, metatarsals and phalanges and usually occurs in children under 2 years of age (Figures 211-2 and 211-3).

    
    
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    Cerebrovascular events include occlusive stroke in large vessels and aneurysms in small vessels.

    
    
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    Acute chest syndrome is defined as a new infiltrate on chest x-ray associated with one or more new symptoms including fever, cough, sputum production, dyspnea, or hypoxia and may be the result of sickling in the lungs with or without infection (Figure 211-1).⁴

    
    
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    Priapism is a painful and persistent erection secondary to sickling in the corpora cavernosa.

  
  
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  Hemolytic events.

  
  
  
  
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    Hemolytic crises occur when the patient experiences an increase in their baseline level of hemolysis.

    
    
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    Aplastic crisis occurs when there is temporary suppression of the markedly increased production of reticulocytes in the marrow. It can be associated with many viral and bacterial infections, but is most frequently associated with parvovirus B19 infection (Figure 211-4).

    
    
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    Cholecystitis occurs due to gallstones and results from persistent hemolytic anemia.

    
    
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    Splenic sequestration is the acute pooling of blood within the spleen with a resultant precipitous drop in the hemoglobin level and/or platelet count.

  
  
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  Infectious Events.

  
  
  
  
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    Patients with SCD are at increased risk for infection as a result of functional asplenia. They are particularly susceptible to infection with encapsulated organisms, such as Streptococcus pneumoniae Haemophilus influenzae, and Neisseria meningitides.

    
    
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    Overwhelming sepsis from pneumococcal infection was especially common prior to universal antimicrobial prophylaxis in young children and a major cause of early death in young children with SCD.⁵

    
    
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    Osteomyelitis most often occurs at the site of necrotic segments of bone, and is most frequently caused by Salmonella and Staphylococcus aureus.

  
  
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  Chronic complications of sickle cell diseases are the result of persistent ischemic damage and include pulmonary, cardiac, renal, central nervous system, orthopedic, urinary, and ophthalmologic complications.

  
  
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  Decreased growth, frontal bossing of the forehead (Figure 211-5), signs of chronic anemia (Figure 211-6), and delayed puberty are possible manifestations of long standing sickle cell disease.

  
  
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  Patients who have received chronic red cell transfusions are at risk for organ damage from iron overload.