Pernicious anaemia, a common cause of vitamin B12 deficiency typically presenting in older adults, is an autoimmune condition characterised by gastric parietal cell antibodies leading to intrinsic factor deficiency, macrocytic anaemia, and neurological symptoms.
Description
Pernicious anaemia is a condition characterised by vitamin B12 deficiency due to impaired absorption. This is a result of a lack of intrinsic factor, a protein made by the stomach, that is necessary for vitamin B12 absorption.
Pathogenesis
Pernicious anaemia is an autoimmune condition in which the body’s immune system attacks the gastric parietal cells that produce intrinsic factor. This results in chronic atrophic gastritis, marked by a thinning of the gastric mucosa and a decrease in gastric secretions. Consequently, the production of intrinsic factor is impaired, leading to a diminished absorption of vitamin B12. This vitamin is essential for DNA synthesis and red blood cell production, and its deficiency results in pernicious anaemia.
Epidemiology, Risk Factors & Associations
- It is more common in individuals of northern European descent and in the African population.
- The prevalence increases with age, being more common in individuals over the age of 60.
- Associated with other autoimmune conditions such as autoimmune thyroid disease, type 1 diabetes, and vitiligo.
Clinical Features
- Fatigue and weakness due to anaemia.
- Neurological complications such as paraesthesia, balance problems, and cognitive changes due to vitamin B12 deficiency.
- Glossitis (inflamed, “beefy” red tongue), and occasionally symptoms of gastric atrophy like early satiety and abdominal discomfort.
Complications
- If untreated, pernicious anaemia can lead to severe and irreversible neurological complications.
- There is an increased risk of developing gastric carcinoids and adenocarcinomas due to chronic atrophic gastritis.
Pathological Features
Histopathology
- Macroscopic: No specific gross features.
- Microscopic: Gastric mucosa examination may show chronic atrophic gastritis with loss of parietal and chief cells, lymphocytic infiltration and presence of intestinal metaplasia.
Serology
- Low serum vitamin B12 levels.
- Elevated homocysteine and methylmalonic acid levels.
- Autoantibodies against intrinsic factor and/or gastric parietal cells.
Grading and Staging
There is no specific grading or staging system for pernicious anaemia. The severity is typically determined by the degree of anaemia and the extent of neurological involvement.
Diagnosis
The diagnosis of pernicious anaemia is based on the clinical presentation, low serum vitamin B12 levels, and the presence of anti-intrinsic factor and/or anti-parietal cell antibodies. A Schilling test, although rarely used today, can confirm the diagnosis.
Differential Diagnosis
- Other causes of vitamin B12 deficiency: Dietary deficiency, malabsorption due to other causes such as Crohn’s disease or after gastric surgery.
- Other causes of macrocytic anaemia: Folate deficiency, alcoholism, myelodysplastic syndrome.
Management
Pernicious anaemia is typically managed with lifelong intramuscular injections of vitamin B12. Regular follow-ups are important to monitor the response to treatment and screen for potential gastric malignancies.