Paediatrics: Sickle cell disease

Sickle cell disease

·  SCD is autosomal recessive. The most severe form is homozygous sickle haemoglobin HbSS, with less severe disease in compound heterozygotes, e.g. HbSC, HbSD, HbSB⁰, or HbSB⁺ thalassaemia. A mutation in codon 6 of B-globin gene (chromosome 11) with single amino acid substitution (glutamine for valine).

·  Found in Caribbean, Africa, Middle East, Mediterranean, and India. In Jamaica, carrier rate is 10%, with disease (HbSS) in 1 in 300 births. HbC carriers represent 3.5% of Jamaicans. Heterozygous carriers of HbS have increased resistance to malaria, accounting for the high gene prevalence in malarial regions. In England SCD now occurs in more than 1 in 2000 live births.

The disease is due to vaso-occlusion and haemolysis. RBCs show ‘rise’blood viscosity, reducing flow through small vessels causing tissue infarction. Sickle RBCs are prematurely destroyed resulting in a haemolytic anaemia.

Clinical features

A spectrum of disease, ranging from asymptomatic to severe, frequent crises and organ damage. Usually presents between 3mths and 6yrs.

·  Infancy: high HbF is protective (reduces tactoid formation) in the first months of life. Common problems are dactylitis, splenic sequestration and pneumococcal sepsis (if not vaccinated and on penicillin V prophylaxis).

·  Young children: infection from encapsulated organisms (if not vaccinated and on penicillin V prophylaxis) and parvovirus, vaso-occlusive crises in long bones, upper airway obstruction, stroke.

·  Older children: vaso-occlusive crises, avascular necrosis and stroke.

·  Risk of pneumococcal sepsis greatest in the first 3yrs of life.

Sickle crises and problems

·  Vaso-occlusive (VOD)crises: presents as excruciating pain in bones and joints, commonly involving hands and feet, becoming more central with increasing age. Dactylitis is an early manifestation of disease. It is precipitated by cold weather, dehydration, infections and hypoxia.

·  Acute chest syndrome: can be precipitated by chest infection with shortness of breath, cough, chest pain, falling SpO₂. CXR changes may be late, and progress within hours. Prompt treatment essential.

·  Sequestration: body organs trap sickled RBCs. Splenic sequestration is more common in first year; later liver and lung sequestration occurs. Rapid fall in Hb may be fatal. Recurrent episodes warrant splenectomy.

·  Stroke: most common in 5–10-yr-olds, and by 20yrs up to 20% will have had silent stroke. Untreated, mortality is 20%; recurrence rate is 70% within 3yrs. Requires prompt treatment with exchange transfusion to reduce HbS <20%. All UK children over the age of 2yrs require an annual transcranial Doppler: those with high velocity flow should start serial exchange transfusion to prevent stroke.

·  Infections: patients are functionally hyposplenic by 1yr, resulting in high risk of infection from Pneumococcus, Meningococcus, Haemophilus Inf. B. Ensure vaccination is up to date and give penicillin V prophylaxis.

·Aplastic crises: typically after infection with parvovirus B19. Reticulocytes and consequently Hb falls. Spontaneous recovery usually occurs in 10 days. The patient may require transfusion.

·Priapism: affects 3–5% of pre- and 30–40% of post-pubertal boys. May be acute fulminant (painful, lasting >3hr) or minor ‘stuttering’ priapism (shorter <3hr, self-limiting episodes). May result in erectile dysfunction. Major episodes require urgent urology. Recurrent stuttering priapism is managed with exercise, warm baths or oral etilefrine.

·Avascular necrosis: hip joint, humerus or any bone.

·Renal impairment: hyposthenuria (urine concentration defect) with high urine output and susceptibility to dehydration. Enuresis is common. Papillary necrosis causes haematuria. Chronic renal failure can occur later.

·Retinopathy: small vessel occlusion l neovascularization l vitreous haemorrhage l resorption l fibrous strands l retinal detachment. More common in HbSC disease. Surveillance needed. Treat with photocoagulation.

·ENT problems: adenotonsillar hypertrophy is common and may lead to nocturnal hypoxia precipitating crises. Ask about ‘snoring’.

·Leg ulcers: uncommon in childhood.

·Growth and development: generally delayed although final height is usually normal. Specific SCD growth charts exist.

Diagnosis

·In the UK all newborns are screened

·Clinical suspicion: required in unscreened population

·Haematology: Hb 5–9g/dL, reticulocytes i, sickle cells on blood film. Hb electrophoresis (HPLC) is definitive test.

·Routine screening of Afro-Caribbean children prior to anaesthesia.

·Prenatal diagnosis: may be performed on fetal red cells or fibroblasts.

Management of acute crises

·Investigations: Hb d, reticulocytes i, blood culture, U&E, creatinine, LFT, CRP (i with sickling/infection), group and save, CXR.

·Hydration: aim for 150% normal maintenance (oral or IV).

·Analgesia: titrate to severity of pain. Initially treat at home with simple analgesia, e.g. paracetamol, NSAIDs; give opiates if required.

·Antibiotics: broad spectrum cephalosporin, after blood culture if fever >38*C.  Add a macrolide if atypical pneumonia.

·Oxygen: to maintain arterial oxygen saturation (SaO₂) >95%. Keep warm.

·Blood: transfusion for aplastic crisis, sequestration, or anaemia; exchange transfusion for sequestration, chest syndrome, or stroke.

Maintenance treatment

·Avoid precipitating factors: e.g. hypoxia (air travel), cold, dehydration.

·Vaccination

·Lifetime oral penicillin V prophylaxis.

·Daily oral folic acid.

·Hydroxycarbamide (hydroxyurea): may reduce crises and need for blood. A rise in MCV shows compliance and myelosuppression is most common adverse effect. Use in patients with moderate to severe disease.

·Bone marrow transplantation: if successful is curative.