Pernicious anaemia

Question 1

Aetiology of pernicious anaemia

Answer 1

Pernicious anaemia is an autoimmune disorder affecting the gastric mucosa that results in vitamin B12 deficiency. It is helpful to remember that pernicious means ‘causing harm, especially in a gradual or subtle way’ - the symptoms of signs are often subtle and diagnose is often delayed.

Whilstpernicious anaemia is the most common cause of vitamin B12 deficiency, it’s not the only cause. Other causes include atrophic gastritis (e.g. secondary to H. pylori infection), gastrectomy, malnutrition (e.g. alcoholism).

Question 2

Pathophysiology of pernicious anaemia

Answer 2

• antibodies to intrinsic factor +/- gastric parietal cells
  • intrinsic factor antibodies → bind to intrinsic factor blocking the vitamin B12 binding site
  • gastric parietal cell antibodies → reduced acid production and atrophic gastritis. Reduced intrinsic factor production → reduced vitamin B12 absorption
• vitamin B12 is important in both the production of blood cells and themyelination of nerves→ megaloblastic anaemia and neuropathy

Question 3

Risk factors of pernicious anaemia

Answer 3

• more common in females (F:M = 1.6:1) and typically develops in middle to old age
• associated with otherautoimmune disorders: thyroid disease, type 1 diabetes mellitus, Addison’s, rheumatoid and vitiligo
• more common if blood group A

Question 4

Clinical presentation of pernicious anaemia

Answer 4

anaemia features:
- lethargy
- pallor
- dyspnoea

neurological features:

- peripheral neuropathy: 'pins and needles', numbness. Typically symmetrical and affects the legs more than the arms

- subacute combined degeneration of the spinal cord: progressive weakness, ataxia and paresthesias that may progress to spasticity and paraplegia

- neuropsychiatric features: memory loss, poor concentration, confusion, depression, irritabiltiy

other features:

- mild jaundice: combined with pallor results in a'lemon tinge'

- glossitis → sore tongue

Question 5

Investigation/diagnosis of pernicious anaemia

Answer 5

Full blood count:
- macrocytic anaemia: macrocytosis may be absent in around of 30% of patients

- hypersegmented polymorphs on blood film

- low WCC and platelets may also be seen

Vitamin B12 and folate levels:
- a vitamin B12 level of >= 200 nh/L is generally considered to be normal

Antibodies:
- anti intrinsic factor antibodies: sensivity is only 50% but highly specific for pernicious anaemia (95-100%)

- anti gastric parietal cell antibodies in 90% but low specificity so often not useful clinically

• Schilling test is no longer routinely done
  • radiolabelled B12 given on two occasions, firstly on its own, secondly with oral IF. Urine B12 levels are then measured

Question 6

Treatment of pernicious anaemia?

Answer 6

• vitamin B12 replacement
  • usually given intramuscularly
  • no neurological features:3 injections per week for 2 weeks followed by 3 monthly treatment of vitamin B12 injections
  • more frequent doses are given for patients with neurological features
  • there is some evidence that oral vitamin B12 may be effective for providing maintenance levels of vitamin B12 but it is not yet common practice
• folic acid supplementation may also be required

Question 7

Complications of pernicious anaemia

Answer 7

Complications other than the haematological and neurological features detailed above

• increased risk of gastric cancer

Pernicious anaemia predisposes to gastric carcinoma