Pernicious anaemia🎥
Pernicious anaemia
Introduction
Pernicious anaemia is a form of megaloblastic anaemia caused by vitamin B12 deficiency, most commonly due to autoimmune destruction of gastric parietal cells. This leads to a lack of intrinsic factor, which is essential for vitamin B12 absorption in the terminal ileum. It is the most common cause of vitamin B12 deficiency in the UK.
Peak Incidence
- Most commonly presents in individuals aged 50 years and above.
- More common in women and those with other autoimmune conditions (e.g. autoimmune thyroid disease, vitiligo).
Pathophysiology
- Autoimmune antibodies target gastric parietal cells and/or intrinsic factor, resulting in reduced production of intrinsic factor.
- Without intrinsic factor, vitamin B12 cannot be effectively absorbed, leading to impaired DNA synthesis and defective red blood cell production (megaloblastosis).
- Vitamin B12 is also essential for myelin synthesis; deficiency leads to neurological symptoms, particularly subacute combined degeneration of the spinal cord.
Symptoms
Neurological
- Peripheral neuropathy – Numbness, tingling, and weakness (usually symmetrical, more in legs than arms)
- Ataxia and paraesthesia
- Subacute combined degeneration of the spinal cord – Can present with:
- Progressive weakness
- Spasticity
- Loss of vibration and proprioception
- Paraplegia in advanced cases
- Optic neuropathy – Visual disturbance
- Cognitive changes – Confusion, memory loss, poor concentration, irritability, depression
Cardiovascular
- Dyspnoea (shortness of breath)
- Palpitations and tachycardia
- Angina or heart murmurs in severe cases
- Congestive heart failure if longstanding and untreated
Gastrointestinal
- Glossitis – Red, swollen, sore tongue
- Mild jaundice – From ineffective erythropoiesis and haemolysis
- Hepatomegaly
- Anorexia, indigestion, and weight loss
- Angular cheilitis – Cracks at the corners of the mouth
Signs
General
- Pallor
- Lemon-tinged skin – Combination of pallor and jaundice
Gastrointestinal
- Glossitis – Smooth, beefy-red tongue
- Angular cheilitis
- Hepatomegaly
Cardiovascular
- Murmurs in severe anaemia
- Signs of heart failure (e.g. peripheral oedema, raised JVP) in advanced cases
Neurological
- Loss of vibration and proprioception
- Positive Romberg’s test
- Hyperreflexia and spasticity
- Paraplegia in severe, untreated disease
Diagnosis
- Treatment should not be delayed in patients with severe neurological symptoms.
Investigations
- Full blood count (FBC)
- May show macrocytic anaemia (but this is absent in up to 30% of cases)
- Vitamin B12 levels
- Measured via total serum cobalamin or active serum holotranscobalamin
- Folate levels – To rule out folate deficiency as a cause of macrocytosis
- Peripheral blood film – May show hypersegmented neutrophils
- Antibody testing:
- Intrinsic factor antibodies – Highly specific but low sensitivity
- Parietal cell antibodies – High sensitivity but low specificity (less useful clinically)
Complications
- Irreversible neurological damage if not promptly treated
- Subacute combined degeneration of the spinal cord
- Heart failure – Due to prolonged, severe anaemia
- Increased risk of gastric carcinoma due to chronic atrophic gastritis
Management
- Vitamin B12 replacement with intramuscular hydroxocobalamin
Dosing Regimen
- Without neurological symptoms:
- 1 mg IMÂ three times per week for 2 weeks
- Then 1 mg every 3 months for life
- With neurological symptoms:
- 1 mg IMÂ on alternate days until improvement, then
- 1 mg every 3 months for life
Important Considerations
-
If both folate and B12 are deficient, replace vitamin B12 first
-
Giving folate before correcting B12 can worsen neurological complications
FAQ from our users
Is pernicious anaemia the same as vitamin B12 deficiency?
- No, pernicious anaemia is a common cause of B12 deficiency however it is not the only cause.
- Other causes include: malnutrition, gastrectomy (bariatric surgery), alcoholism & atrophic gastritis (commonly caused by H.pylori).
Why do you measure folate (vitamin B9) levels in pernicious anaemia?
- Folate deficiency is another cause of macrocytic anaemia so it is important to consider this when investigating patients. It is also important to be aware of any folate deficiency so that you manage patients in the correct order (B12 supplementation before folate).
What is the pathophysiology of pernicious anaemia?
- The parietal cells of the stomach produce intrinsic factor, which is essential for vitamin B12 absorption in the terminal ileum.
- In pernicious anaemia, autoantibodies develop against intrinsic factor and, in some cases, against the parietal cells themselves.
- Autoantibodies against intrinsic factor prevent it from binding to vitamin B12, leading to reduced absorption.
- Autoantibodies against gastric parietal cells contribute to atrophic gastritis, which results in reduced acid production and impaired intrinsic factor secretion.
- This further affects vitamin B12 absorption since food is less effectively broken down.
Common pitfalls in a clinical setting
Common pitfalls in a clinical setting
- Always rule out reversible causes of vitamin B12 deficiency by asking about:
- Recent dietary changes, including new vegetarian or vegan diets.
- Alcohol intake.
- Nitrous oxide abuse (also known as ‘baloons’)
- Consider malabsorption syndromes such as:
- Crohn’s disease.
- Coeliac disease.
- Pernicious anaemia is an autoimmune condition, so check for a history of other autoimmune diseases such as:
- Thyroid disease.
- Type 1 diabetes.
- Addison’s disease.
- Rheumatoid arthritis.
- Coeliac disease.
- Symptoms can be non-specific, but always consider pernicious anaemia in patients presenting with:
- Peripheral neuropathy.
- Multiple unexplained symptoms.
- Specific testing considerations:
- During pregnancy, use active B12 testing instead of total B12.
- If nitrous oxide abuse is suspected, use serum methylmalonic acid or plasma homocysteine testing instead.
- Patients with pernicious anaemia have an increased risk of gastric cancer, which should be considered when providing long-term follow-up care.