The management of pernicious anaemia

Pernicious anaemia may present with neurological symptoms, reports Dr Laurence Knott Pernicious anaemia is caused by impaired absorption of vitamin B12 in the terminal ileum.

The process of absorption requires a substance called intrinsic factor, secreted by parietal cells. In pernicious anaemia, intrinsic factor is lacking; 90 per cent of patients have antibodies to intrinsic factor and to the proton pump   H+/K+ATPase.

Pernicious anaemia may also be associated with gastric atrophy (partial or complete absence of parietal cells), which is found in 15 per cent of people age 40–60 years, and 20–30 per cent of older patients. The peak age of presentation is 60 years and is more common in patients with blue eyes, blood group A, early greying and a positive family history.

Initial diagnosis
The onset of symptoms is usually gradual, starting with dyspnoea and lethargy. Later there may be anorexia, dyspepsia, weight loss, diarrhoea and glossitis. Neurological symptoms include loss of vibration sense, loss of reflexes and mild to moderate weakness. Later, ataxia, Babinski’s reflex and spasticity can develop.

Occasionally, neuropathic pain and touch sensation are affected; these symptoms will affect the legs and feet more commonly than the hands. Yellow-green colour blindness may ensue.

In severe cases, some patients may present with heart failure or hepatomegaly. In these cases, psychological changes can occur, including  depression, paranoia and delirium.

The differential diagnosis should include causes of vitamin B deficiency, such as poor quality diet, gastric causes and intestinal causes such as stagnant loop and the various causes of intestinal malabsorption.

Other causes of megaloblastic anaemia should be considered, such as congestive cardiac failure, folic acid deficiency and gluten-induced enteropathy.

Causes of macrocytosis such as alcoholism and myelodysplastic disorders need to be excluded.

Investigations
Most conditions can be ruled out by measuring serum vitamin B12 level. Levels below 150ng/l generally indicate deficiency.

Supportive evidence can be obtained from the full blood count, which may show neutrophils with hypersegmented nuclei and Howell-Jolly bodies.

Intrinsic factor antibodies, if present, are virtually pathognomonic of pernicious anaemia, but are absent in 50 per cent of cases.

Gastric parietal antibodies are present in 85 per cent of patients with pernicious anaemia, but also in 3–10 per cent of patients who do not have this condition.

In practice, a trial of treatment is carried out, and testing for antibodies can be avoided if there is symptomatic improvement and increases in the reticulocyte count.

Management
Initial management consists of  IM hydroxocobolamin.

If there is no neurological involvement, 1mg hydroxocobolamine should be given IM three times a week for two weeks, followed by 1mg every three months.

If neurological involvement is present, 1mg IM hydroxocobolamine should be given on alternate days until there is no further improvement, followed by 1mg every two months.

Folic acid should not be given to any patient who is vitamin B12 deficient because this can result in fulminant neurological complications. Any concomitant iron deficiency should be treated orally before vitamin B12 is given.

The use of oral therapy for long-term management is controversial, but there is sufficient evidence to support it.

Patients should be monitored for complications such as neuropathy, heart failure and gastric carcinoma, and for associated diseases such as myxoedema and diabetes.  

Dr Knott is a GP in Enfield, Middlesex 

Key points

  • Pernicious anaemia is caused by impaired absorption of vitamin B12 due to a lack of intrinsic factor.
  • The onset of symptoms is usually gradual, with dyspnoea and lethargy.
  • Neurological symptoms such as loss of vibration sense and mild weakness may occur before the onset of anaemia, particularly in patients over the age of 60.
  • Physical signs include anaemia and jaundice.
  • The main differential diagnoses are poor diet and intestinal malabsorption.
  • Treatment is by hydroxocobalamin injections. Oral treatment is an option for long-term maintenance.

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