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Sickle cell disease

Specialties > Child health

Background knowledge 🧠

Definition

  • Sickle cell disease (SCD) is a group of inherited haemoglobin disorders characterised by the presence of sickle-shaped red blood cells (RBCs).
  • Caused by a mutation in the HBB gene leading to abnormal haemoglobin S (HbS).
  • Results in chronic haemolytic anaemia, vaso-occlusion, and various complications.

Epidemiology

  • Most common in individuals of African, Caribbean, Middle Eastern, and Indian ancestry.
  • In the UK, it affects approximately 15,000 individuals, with around 300 new cases diagnosed annually.
  • Carriers of the sickle cell trait (HbAS) are asymptomatic and account for about 300,000 individuals in the UK.
  • Higher prevalence in regions with endemic malaria due to a protective advantage of the carrier state.

Aetiology and pathophysiology

  • Caused by a point mutation in the Ξ²-globin gene, resulting in valine replacing glutamic acid at the sixth position.
  • Abnormal HbS polymerises under low oxygen tension, causing RBCs to sickle and become rigid.
  • Sickled cells have a shortened lifespan (10-20 days vs. 120 days for normal RBCs), leading to haemolysis and anaemia.
  • Vaso-occlusion results from the rigid sickle cells blocking microcirculation, causing tissue ischaemia and pain.
  • Chronic haemolysis leads to complications such as gallstones, pulmonary hypertension, and leg ulcers.

Types

  • Sickle cell anaemia (HbSS):Β most severe form, homozygous for HbS.
  • Sickle-haemoglobin C disease (HbSC):Β less severe, compound heterozygosity for HbS and HbC.
  • Sickle Ξ²-thalassaemia (HbSΞ²+ and HbSΞ²0):Β variable severity, depends on the Ξ²-thalassaemia mutation.
  • Other rare compound heterozygous forms involving other haemoglobinopathies.

Clinical Features 🌑️

Symptoms

  • Chronic anaemia: fatigue, pallor, jaundice.
  • Vaso-occlusive crises: severe pain, commonly in bones, joints, and abdomen.
  • Acute chest syndrome: chest pain, cough, dyspnoea, fever, often precipitated by infection.
  • Frequent infections due to functional asplenia, particularly with encapsulated organisms.
  • Growth retardation and delayed puberty.
  • Cerebrovascular accidents, especially in children.
  • Priapism, which can lead to erectile dysfunction.
  • Chronic pain syndrome, leading to opioid dependency in some cases.
  • Psychosocial issues, including depression and anxiety.

Signs

  • Pallor and jaundice.
  • Splenomegaly (mainly in childhood).
  • Delayed growth and development.
  • Leg ulcers, particularly in the malleolar region.
  • Cardiac murmurs due to chronic anaemia.
  • Hand-foot syndrome (dactylitis) in infants and young children.
  • Avascular necrosis of hip or shoulder, leading to joint pain and reduced mobility.
  • Retinal damage or proliferative retinopathy.

Investigations πŸ§ͺ

Tests

  • Full blood count (FBC): normocytic anaemia, raised reticulocyte count.
  • Blood film: presence of sickle cells, target cells, Howell-Jolly bodies (indicative of hyposplenism).
  • Haemoglobin electrophoresis: confirms the diagnosis by detecting HbS.
  • Sickle solubility test: rapid screening tool but less specific.
  • Imaging: chest X-ray for acute chest syndrome, MRI for stroke assessment, ultrasound for hepatobiliary complications.
  • Transcranial Doppler ultrasound: used in children to assess stroke risk.
  • Infection screen: blood cultures, urine cultures, and chest X-ray if infection is suspected.

Management πŸ₯Ό

Management

  • Hydroxycarbamide: reduces frequency of vaso-occlusive crises and acute chest syndrome.
  • Blood transfusions: used in acute crises, pre-operatively, or in chronic management for those with recurrent complications.
  • Pain management: opioids for acute pain crises, with careful monitoring for dependency.
  • Infection prophylaxis: penicillin prophylaxis and immunisations against encapsulated organisms (e.g., pneumococcus, Haemophilus influenzae type B).
  • Bone marrow transplantation: only curative treatment, considered in severe cases.
  • Psychosocial support: crucial for managing chronic pain and the psychological impact of the disease.

Complications

  • Acute chest syndrome: a leading cause of mortality, requires prompt treatment with oxygen, antibiotics, and blood transfusion.
  • Stroke: common in children, necessitates regular screening and possibly chronic transfusion therapy.
  • Pulmonary hypertension: chronic complication leading to right heart failure.
  • Renal impairment: from hyposthenuria to end-stage renal disease.
  • Leg ulcers: chronic and difficult to heal, particularly in adults.
  • Priapism: recurrent episodes can lead to erectile dysfunction.
  • Chronic pain syndrome: results in significant morbidity and can lead to opioid dependence.
  • Osteonecrosis: particularly of the femoral and humeral heads.

Prognosis

  • Median life expectancy in the UK is around 45-55 years, with improvements due to better management and screening.
  • Prognosis depends on the type of SCD, frequency of complications, and access to care.
  • Early diagnosis and comprehensive management significantly improve outcomes.
  • Bone marrow transplant offers a potential cure but is only suitable for a minority of patients.
  • Ongoing research into gene therapy and new treatments offers hope for the future.

Key points

  • SCD is a severe inherited blood disorder with significant morbidity and mortality.
  • Multidisciplinary care is essential to manage acute crises, chronic complications, and the psychosocial aspects of the disease.
  • Early intervention and preventive care can reduce the impact of the disease and improve quality of life.
  • Emerging treatments such as gene therapy hold promise for the future management of SCD.

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Child health