Sickle cell disease
Updates to Article Attributes
Sickle cell disease (SCD) is a hereditary (autosomal recessive) condition resulting in the formation of abnormal haemoglobin (a haemoglobinopathy), which manifests as multisystem ischaemia and infarction, as well as haemolytic anaemia.
Epidemiology
There is no recognised gender predilection. The highest incidence occurs in individuals of African descent, followed by eastern Mediterranean and Middle Eastern populations. Malaria is the strongest known selective pressure on the human genome. The sickle cell mutation is prevalent in part as it confers a human genetic resistance to malaria as the abnormal haemoglobin has a higher turnover and increased phagocytosis while sickled red cells have reduced cell-cell cytoadherence preventing the parasite from multiplying during the erythrocytic phase of its life cycle. It is estimated that approximately 8% of the African population is homozygous for sickle cell (where malaria is most prevalent).
Clinical presentation
The earliest manifestation is usually in early childhood, as babies are protected by elevated levels of fetal haemoglobin (HbF) in the first 6 months 3. The first presentation is commonly with a painful vaso-occlusive crisis: sudden onset of bone or visceral pain due to micro-vascularmicrovascular occlusion and ischaemia, often in the setting of sepsis or dehydration. Sickle cell disease is known to have a wide rangespectrum of clinical presentationpresentations from completely asymptomatic to a severe overwhelming crisis.
Clinical findings are wide and include 1:
- bone pain
- pulmonary
- acute chest syndrome
- recurrent pneumonia (impaired immunity due to functional asplenia)
- chronic lung disease
- abdominal
- abdominal pain from vaso-occlusive crises
- sequestration syndrome (rapid pooling of blood in the spleen leading to intravascular volume depletion)
- haemolytic anaemia
- impaired immunity from autosplenectomy
- multiple renal manifestations, with end result of renal failure 5
- cerebral
- stroke
- cognitive impairment
- ocular and orbital complications
- priapism
- leg ulcers
Pathology
The disease results from a mutation in a gene coding for the beta chain of the haemoglobin molecule termed HbS. Specifically, there is a substitution of glutamine for valine at the 6th position in the beta globin chain.
The term "sickle cell disease" applies to all patients who have two abnormal beta chains. The resultant haemoglobin molecules tend to clump together into long polymers, making the red blood cell (RBC) elongated (sickle-shaped), rigid and unable to deform appropriately when passing through small vessels, resulting in vascular occlusion. The abnormal RBCs are also removed from the bloodstream at an increased rate, leading to a haemolytic anaemia 1.
Individuals with one HbS beta chain and one normal beta chain are said to have the "sickle cell trait". They are usually asymptomatic, although there is an association with increased risk of renal medullary carcinoma 2. Perhaps of some consolation to individuals with the sickle cell trait is the increased resistance to malaria.
Radiographic features
The radiographic manifestations of sickle cell disease are protean, and are best discussed individually. Below is a summary of the main findings with links to individual articles.
Skeletal
Musculoskeletal manifestations of sickle cell disease are discussed separately. They are the result of expansion of the medullary spaces due to chronic anaemia, bone infarction and the consequent complications, such as growth disturbance and pathological fractures.
Pulmonary
Pulmonary involvement is a leading cause of mortality among sickle cell disease patients and can be acute or chronic:
Abdominal
Abdominal manifestations of sickle cell disease are discussed separately. Splenic infarction and subsequent functional asplenia tend to occur early in the disease. The hepatobiliary and renal systems are also commonly involved.
Cerebral
Cerebral manifestations of sickle cell disease are discussed separately. Stroke and cerebral atrophy are common neurologic sequelae of sickle cell disease.
Extramedullary haematopoiesis
Extramedullary haematopoiesis is discussed separately. Less common in sickle cell disease than in other haemolytic anaemias. The most common site is liver, followed by spleen, thorax, and adrenals 4.
Treatment and prognosis
Management of vaso-occlusive crises includes oxygen, hydration and analgesia. Hydroxyurea decreases the severity of vaso-occlusive crises 1. Anaemia is usually well tolerated-tolerated, however, blood transfusions may be indicated in some cases. Bone marrow transplantation may provide a cure.
Sickle cell disease is associated with reduced life expectancy, whereas individuals with sickle cell trait have a normal life expectancy.
See also
-<p><strong>Sickle cell disease (SCD)</strong> is a hereditary (autosomal recessive) condition resulting in the formation of abnormal haemoglobin (a <a href="/articles/haemoglobinopathies">haemoglobinopathy</a>), which manifests as multisystem ischaemia and infarction, as well as <a href="/articles/haemolytic-anaemia">haemolytic anaemia</a>. </p><h4>Epidemiology</h4><p>There is no recognised gender predilection. The highest incidence occurs in individuals of African descent, followed by eastern Mediterranean and Middle Eastern populations. Malaria is the strongest known selective pressure on the human genome. The sickle cell mutation is prevalent in part as it confers a human genetic resistance to malaria as the abnormal haemoglobin has a higher turnover and increased phagocytosis while sickled red cells have reduced cell-cell cytoadherence preventing the parasite from multiplying during the erythrocytic phase of its life cycle. It is estimated that approximately 8% of the African population is homozygous for sickle cell (where malaria is most prevalent).</p><h4>Clinical presentation</h4><p>The earliest manifestation is usually in early childhood, as babies are protected by elevated levels of fetal haemoglobin (HbF) in the first 6 months <sup>3</sup>. The first presentation is commonly with a painful vaso-occlusive crisis: sudden onset of bone or visceral pain due to micro-vascular occlusion and ischaemia, often in the setting of sepsis or dehydration. Sickle cell disease is known to have a wide range of clinical presentation from completely asymptomatic to severe overwhelming crisis.</p><p>Clinical findings are wide and include <sup>1</sup>:</p><ul>- +<p><strong>Sickle cell disease (SCD)</strong> is a hereditary (autosomal recessive) condition resulting in the formation of abnormal haemoglobin (a <a href="/articles/haemoglobinopathies">haemoglobinopathy</a>), which manifests as multisystem ischaemia and infarction, as well as <a href="/articles/haemolytic-anaemia">haemolytic anaemia</a>. </p><h4>Epidemiology</h4><p>There is no recognised gender predilection. The highest incidence occurs in individuals of African descent, followed by eastern Mediterranean and Middle Eastern populations. Malaria is the strongest known selective pressure on the human genome. The sickle cell mutation is prevalent in part as it confers a human genetic resistance to malaria as the abnormal haemoglobin has a higher turnover and increased phagocytosis while sickled red cells have reduced cell-cell cytoadherence preventing the parasite from multiplying during the erythrocytic phase of its life cycle. It is estimated that approximately 8% of the African population is homozygous for sickle cell (where malaria is most prevalent).</p><h4>Clinical presentation</h4><p>The earliest manifestation is usually in early childhood, as babies are protected by elevated levels of fetal haemoglobin (HbF) in the first 6 months <sup>3</sup>. The first presentation is commonly with a painful vaso-occlusive crisis: sudden onset of bone or visceral pain due to microvascular occlusion and ischaemia, often in the setting of sepsis or dehydration. Sickle cell disease is known to have a wide spectrum of clinical presentations from completely asymptomatic to a severe overwhelming crisis.</p><p>Clinical findings are wide and include <sup>1</sup>:</p><ul>
-<li>ocular and orbital complications </li>- +<li>ocular and orbital complications</li>
-</ul><h5>Abdominal</h5><p><a href="/articles/sickle-cell-disease-abdominal-manifestations-1">Abdominal manifestations of sickle cell disease</a> are discussed separately. <a href="/articles/splenic-infarction">Splenic infarction</a> and subsequent <a href="/articles/asplenia">functional asplenia</a> tend to occur early in the disease. The hepatobiliary and renal systems are also commonly involved.</p><h5>Cerebral</h5><p><a href="/articles/sickle-cell-disease-cerebral-manifestations-1">Cerebral manifestations of sickle cell disease</a> are discussed separately. Stroke and cerebral atrophy are common neurologic sequelae of sickle cell disease.</p><h5>Extramedullary haematopoiesis</h5><p><a href="/articles/extramedullary-haematopoiesis">Extramedullary haematopoiesis</a> is discussed separately. Less common in sickle cell disease than in other haemolytic anaemias. The most common site is liver, followed by spleen, thorax, adrenals <sup>4</sup>.</p><h4>Treatment and prognosis</h4><p>Management of vaso-occlusive crises includes oxygen, hydration and analgesia. Hydroxyurea decreases the severity of vaso-occlusive crises <sup>1</sup>. Anaemia is usually well tolerated, however, blood transfusions may be indicated in some cases. Bone marrow transplantation may provide a cure.</p><p>Sickle cell disease is associated with reduced life expectancy, whereas individuals with sickle cell trait have a normal life expectancy.</p><h4>See also</h4><ul>- +</ul><h5>Abdominal</h5><p><a href="/articles/sickle-cell-disease-abdominal-manifestations-1">Abdominal manifestations of sickle cell disease</a> are discussed separately. <a href="/articles/splenic-infarction">Splenic infarction</a> and subsequent <a href="/articles/asplenia">functional asplenia</a> tend to occur early in the disease. The hepatobiliary and renal systems are also commonly involved.</p><h5>Cerebral</h5><p><a href="/articles/sickle-cell-disease-cerebral-manifestations-1">Cerebral manifestations of sickle cell disease</a> are discussed separately. Stroke and cerebral atrophy are common neurologic sequelae of sickle cell disease.</p><h5>Extramedullary haematopoiesis</h5><p><a href="/articles/extramedullary-haematopoiesis">Extramedullary haematopoiesis</a> is discussed separately. Less common in sickle cell disease than in other haemolytic anaemias. The most common site is liver, followed by spleen, thorax, and adrenals <sup>4</sup>.</p><h4>Treatment and prognosis</h4><p>Management of vaso-occlusive crises includes oxygen, hydration and analgesia. Hydroxyurea decreases the severity of vaso-occlusive crises <sup>1</sup>. Anaemia is usually well-tolerated, however, blood transfusions may be indicated in some cases. <a title="Bone marrow transplantation" href="/articles/haematopoietic-stem-cell-transplantation">Bone marrow transplantation</a> may provide a cure.</p><p>Sickle cell disease is associated with reduced life expectancy, whereas individuals with sickle cell trait have a normal life expectancy.</p><h4>See also</h4><ul>
-<li><a href="/articles/thalassemia">thalassemia</a></li>- +<li><a href="/articles/thalassemia">thalassaemia</a></li>
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