Sickle cell disease

Contributed by Dr Emma Drasar, specialist registrar in haematology, and Dr David C Rees, senior lecturer and honorary consultant in paediatric haematology at King's College Hospital NHS Foundation Trust, London

 1.AETIOLOGY AND EPIDEMIOLOGY

Sickle cell disease (SCD) is a group of autosomal recessive inherited disorders. About 70 per cent of people with SCD are homozygous for the sickle beta globin mutation (HbSS), with

25 per cent having the less severe HbSC. Rarer conditions (HbS beta thalassaemia, HbSOArab and HbSDPunjab) make up the remainder.

People who only have sickle cell traits do not have symptoms of SCD and are usually healthy. However, they require extra oxygen during anaesthesia and are advised against some sports, such as scuba diving or high altitude mountaineering, where oxygen might be reduced.

SCD patients tend to be from African or African-Caribbean backgrounds, although SCD also occurs in Greek, Turkish and Middle Eastern families, and in increasing numbers of mixed-race patients. Approximately 12,500 people are affected by SCD in the UK and it is thought that about 80 per cent of these are in London.

There are 240,000 carriers of the condition in England.

Haematological tests

FBC reveals a normocytic haemolytic anaemia with classical microscopic appearance of the sickle-shaped red cells due to polymerisation of the haemoglobin. Haemoglobin electrophoresis shows the presence of the abnormal sickle haemoglobin. A raised unconjugated bilirubin may be noted.

All newborn babies born in England are now tested for SCD on the heel prick blood spot taken at five to seven days. The primary aim of the screening programme is to identify babies with SCD so that prophylactic penicillin can be started at two to three months.

Pregnant women should also be tested for HbS and thalassaemia. In high prevalence areas, which includes most cities and many towns, all women have haemoglobin analysis, whereas in low prevalence areas, tests will be performed depending on the ethnic origin of the woman and the results of her FBC. The aim of antenatal screening is to identify couples that are at risk of having a baby with SCD so that prenatal diagnosis can be offered.

Most patients with SCD should have been identified through screening. Occasionally, patients who have not been tested present with symptoms suggestive of the condition, for example children born overseas or those who did not undergo neonatal screening.

2.CLINICAL FEATURES

Although SCD is present from birth, symptoms are rare before the age of three to six months, due to the persistence of foetal haemoglobin. The main symptoms of sickle cell disorders are pain, anaemia and infection.

Acute pain

Acute pain is one of the most common presentations. Painful and hot hands and feet (dactylitis) is the typical presenting sign in infants and young children with SCD, and the diagnosis should be considered in anyone presenting with this.

Acute pain commonly affects long bones, back and pelvis but can involve any part of the body. These areas can feel warm to the touch and overlying oedema may be noted. An important differential is osteomyelitis, which may be suggested by high fevers.

Patients are encouraged to manage acute pain at home with combinations of paracetamol, ibuprofen and codeine. Severe or complicated pain typically requires hospital admission.

Acute infection

The most common cause of death in young children with SCD is acute infection. The increased tendency to infection results from splenic damage and results in a particular susceptibility to capsulated bacteria, such as pneumococcus.

Despite penicillin prophylaxis, young children are at risk of severe infection and in general children under the age of two years with temperatures greater than 38°C for more than four hours require IV antibiotics.

Older children and adults remain vulnerable to infections and their complications, and febrile illnesses should generally be treated aggressively.

 Features of SCD
Haematological
  •  Normocytic haemolytic anaemia.
  •   Sickle-shaped red cells.
  •  Abnormal sickle haemoglobin.
  • Raised unconjugated bilirubin.

Symptoms

  •   Acute pain.
  •   Dactylitis.
  •  Acute infection, particularly with pneumococcus.

Prevention of infection

People with SCD should take regular penicillin, and this is particularly important in children under five.

Children with SCD should receive all routine immunisations, including pneumococcal polysaccharide conjugate vaccine (Prevenar).

Pneumococcal polysaccharide vaccine (Pneumovax II) should be given at two years, and boosted every five years, and yearly vaccination against influenza is also recommended.

3. MANAGING COMPLICATIONS

Chronic pain

Some patients develop chronic pain requiring daily administration of opioid analgesia.

This pain can be related to chronic organ damage such as avascular necrosis of the hips or shoulders, and sometimes the pain is more complicated and not clearly related to any particular area of damage. This problem should ideally be handled in a multidisciplinary way, with a team including the GP, haematologist, psychologist and pain specialist.

Adults and occasionally children can develop stiff and painful joints or ulcers on the lower legs. In general, people with SCD have an increased incidence of gallstones, jaundice, haematuria and difficulties during pregnancy and childbirth.

Neurological complications

In children with SCD, stroke is an important complication, occurring from the age of two to three years and affecting about 6 per cent of children by the age of 10. Stroke can be difficult to diagnose in young children and sometimes difficulty walking or using a limb is attributed to acute pain rather than weakness. If a stroke is suspected, the child should be referred urgently for brain imaging and urgent blood transfusion.

Small brain infarcts occur in up to 20 per cent of children and may cause developmental delays or difficulty at school. Adults have an increased risk of both infarctive and haemorrhagic stroke, probably secondary to the undetected ischaemic events.

Acute anaemia

The average haemoglobin is 7g/dl in SCD, but this can fall acutely and result in life-threatening anaemia.

It is important to consider the possibility of severe anaemia in SCD, which is not typically accompanied by pain. This can result from either infection with parvovirus B19 (aplastic crisis), which switches off erythroid activity for about a week and causes severe anaemia due to the shortened lifespan of red cells in SCD, or from the acute sequestration of blood in the spleen or liver (sequestration crisis).

Both tend to be more common in younger children. The latter can be detected by abdominal examination showing marked enlargement of the liver or spleen. Urgent transfusion and sometimes splenectomy are required. When this occurs in the liver severe abdominal pain accompanied by deranged liver function tests.

Lungs

Acute chest syndrome is one of the most common causes of hospital admission and death. Chlamydia pneumoniae and Mycoplasma pneumoniae are important aetiological agents. It typically presents with chest pain, fever and shortness of breath. Low oxygen saturations may be noted and signs in the chest can be scanty. Assessment is necessary if this is suspected. Treatment with oxygen, analgesia and antibiotics is usually necessary, with blood transfusions and ventilatory support in severe cases.

Pulmonary hypertension is increasingly recognised, affecting up to 30 per cent adults with SCD.

Priapism

Priapism is an often under-treated and under-reported complication of SCD. It occurs in 20 per cent of men with SCD before the age of 20. If a patient has had a painful erection for more than two hours he should be assessed urgently in hospital with a view to aspiration and washout of the penis. Shorter episodes can be averted by adequate analgesia, gentle exercise or a warm bath.

Prevention of complications

Penicillin, patient education and early recognition of problems contribute to the improved outcome of sickle cell disease in developed countries, with a life expectancy of about 50 years.

Hydroxyurea is used in some patients with frequent episodes of acute pain or acute chest syndrome and has been shown to modify the natural history of the condition.

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