Pernicious anaemia is a type of macrocytic anaemia caused by vitamin B12 deficiency, secondary to impaired absorption due to a lack of intrinsic factor (IF). It is an autoimmune condition and a key topic for UKMLA.

Aetiology:

1. Autoimmune Destruction:
   • Autoantibodies against gastric parietal cells or intrinsic factor impair IF production.
2. Associated Conditions:
   • Often linked with other autoimmune diseases (e.g., Hashimoto’s thyroiditis, type 1 diabetes, vitiligo).
3. Risk Factors:
   • Northern European ancestry.
   • Family history of pernicious anaemia.
   • Advanced age (most common in people over 60 years).

Pathophysiology:

• Intrinsic Factor Deficiency:
  • Parietal cells in the stomach produce intrinsic factor, essential for B12 absorption in the terminal ileum.
  • Autoimmune damage to parietal cells leads to reduced intrinsic factor and B12 malabsorption.
• Vitamin B12 Deficiency:
  • Impairs DNA synthesis, leading to defective red cell maturation (megaloblastosis).
  • Affects myelin synthesis, resulting in neurological symptoms.

Clinical Features:

1. General Anaemia Symptoms:
   • Fatigue, pallor, dyspnoea, palpitations.
2. Neurological Symptoms:
   • Paraesthesia, peripheral neuropathy.
   • Subacute combined degeneration of the spinal cord (ataxia, weakness, spasticity).
   • Cognitive impairment or mood disturbances.
3. Gastrointestinal Symptoms:
   • Glossitis (smooth, red tongue), anorexia, weight loss.
4. Other Signs:
   • Jaundice (due to ineffective erythropoiesis and haemolysis).
   • Lemon-tinted skin (combination of pallor and jaundice).

Investigations:

1. Full Blood Count:
   • Macrocytic anaemia (MCV > 100 fL).
   • Hypersegmented neutrophils on blood film.
2. Vitamin B12 Levels:
   • Low serum B12.
3. Intrinsic Factor Antibodies:
   • Positive in ~50% of cases.
4. Gastric Parietal Cell Antibodies:
   • Positive in ~90% of cases (less specific).
5. Serum Folate:
   • May be concurrently low; rule out coexisting folate deficiency.
6. Liver and Thyroid Function Tests:
   • To exclude alternative causes of macrocytosis.
7. Schilling Test (Historical):
   • Rarely used now; measures B12 absorption.

Management:

1. Vitamin B12 Replacement:
   • IM Hydroxocobalamin:
     • Loading dose: 1 mg every 2–3 days for 2 weeks.
     • Maintenance: 1 mg every 2–3 months for life.
   • Oral B12 may be considered in rare cases where absorption is intact (not standard for pernicious anaemia).
2. Monitor and Treat Folate Deficiency:
   • If folate deficiency is present, treat with oral folic acid after starting B12 to avoid neurological complications.
3. Follow-Up:
   • Regular monitoring of blood counts and B12 levels.
   • Screen for associated autoimmune conditions.

Complications:

1. Neurological:
   • Irreversible neurological damage if untreated.
2. Gastrointestinal:
   • Increased risk of gastric carcinoma and gastric polyps due to chronic atrophic gastritis.
3. Anaemia-Related:
   • Heart failure in severe untreated cases.

Prognosis:

• Excellent with early diagnosis and lifelong B12 supplementation.
• Delayed treatment may result in permanent neurological deficits.

Key Exam Points for UKMLA:

1. Cause:
   • Autoimmune destruction of parietal cells leading to intrinsic factor deficiency.
2. Diagnosis:
   • Low B12 levels with positive intrinsic factor or parietal cell antibodies.
3. Management:
   • IM hydroxocobalamin is the treatment of choice.
4. Complications:
   • Focus on neurological damage and risk of gastric carcinoma.
5. Differentials:
   • Folate deficiency, dietary B12 deficiency, alcohol misuse, hypothyroidism.