Introduction 

Pernicious anaemia is a type of megaloblastic anaemia caused by vitamin B12 deficiency, primarily due to an autoimmune process that impairs its absorption. This condition results from the immune system attacking the stomach’s parietal cells, which are responsible for producing intrinsic factor, a protein essential for vitamin B12 absorption in the small intestine.¹

In this article, you will learn about pernicious anaemia, mainly focusing on the factors that contribute to the development of pernicious anaemia.

Epidemiology

Pernicious anaemia is an uncommon condition. Despite its rarity, it remains a leading global cause of megaloblastic anaemia. The condition can occur at any age, but is more frequently diagnosed in individuals aged 60–70.¹

It affects both men and women, though the female-to-male ratio varies depending on the geographic region. Populations of Asian descent tend to have a lower prevalence of pernicious anaemia compared to other groups studied.¹

Understanding vitamin B12 absorption and the pathophysiology of pernicious anaemia

Vitamin B12, or cobalamin, is essential for DNA synthesis, neurological function, and red blood cell formation, and is commonly found in animal-derived foods like meat, eggs, and dairy. A deficiency in B12 leads to megaloblastic anaemia due to disrupted DNA synthesis and also contributes to nerve demyelination.²

The deficiency affects all blood cell types, but red blood cells show the most prominent morphological changes (larger size, reduction in number), and the degree of these changes correlates with the severity of anaemia.²

The Vitamin B12 absorption process involves several steps:¹

• Release from food: In the stomach, hydrochloric acid and pepsin release B12 from dietary proteins
• Binding to intrinsic factor: Parietal cells in the stomach lining secrete intrinsic factor(IF), which binds to free B12
• Absorption in the ileum: The B12-IF complex travels to the terminal ileum (the final part of the small intestine), where it binds to specific receptors on enterocytes for absorption into the bloodstream

Disruption at any stage can lead to B12 deficiency, but pernicious anaemia specifically involves the autoimmune destruction of parietal cells and subsequent intrinsic factor deficiency.¹

Aetiology

The primary cause of pernicious anaemia is the destruction of parietal cells in the stomach, which consequently leads to a reduced production of hydrochloric acid (achlorhydria). As a result, the release of B12 from dietary proteins is limited, and there is a decrease in the secretion of intrinsic factor, which causes impaired B12 absorption.¹

Individuals with other autoimmune diseases, including type 1 diabetes, autoimmune thyroid disorders, and vitiligo, often have a higher prevalence of pernicious anaemia. Studies have also shown that various hereditary risk factors play a role in the development of pernicious anaemia.

Clinical presentation 

Pernicious anaemia has various clinical features.

It progresses slowly, often taking 2 to 5 years for clinical signs of vitamin B12 deficiency to appear. Symptoms may remain unnoticed until anaemia becomes significant, as the body compensates through increased cardiopulmonary oxygen delivery. Patients may also present with symptoms affecting multiple systems, many of which are common to other medical conditions, often resulting in delayed or missed diagnosis.^1,3

Common symptoms include:³

• Fatigue, low energy, poor appetite, unintended weight loss
• Neurological: headaches, confusion, difficulty focusing, memory issues, cognitive impairment, tingling sensations, numbness, and balance problems
• Psychiatric: mood swings, depression, changes in personality, psychosis
• Otolaryngologic (ears, nose and throat): reduced or lost sense of taste, inflamed tongue (glossitis)
• Cardiopulmonary: heart palpitations, shortness of breath
• Gastrointestinal: indigestion, diarrhoea, poor appetite

Pernicious anaemia may also present with neurological symptoms. Peripheral neuropathy is often an early sign, typically affecting the legs more than the arms and is usually symmetric. Findings may include a reduced sensitivity to touch, pinprick, and vibration. In addition, ankle reflexes are often diminished or absent, though other reflexes may remain intact.^1,3

Subacute Combined Degeneration (a late-stage neurological complication involving the spinal cord) is seen in some patients. Symptoms include: muscle weakness, unsteady gait (ataxia), and visual disturbances.⁴

Diagnosis

Diagnosing pernicious anaemia is challenging, partly because the Schilling test – a method where patients consume radioactive B12 to measure absorption – is now outdated.⁹ Currently, no approved modern test for B12 absorption exists.²

Various diagnostic methods include:⁵

• Initial blood tests:
  • Complete Blood Count (CBC)
  • Vitamin B12 (cobalamin) levels
  • Folate levels
  • Iron studies: serum iron, total iron-binding capacity (TIBC), and ferritin
  • Reticulocyte count
  • Peripheral blood smear to observe red blood cell morphology

• Follow-up serologic tests:⁵
  • Anti-intrinsic factor (IF) antibodies
  • Anti-parietal cell antibodies
  • Additional specialised tests:
  • Methylmalonic acid (MMA)
  • Fasting homocysteine
  • Holotranscobalamin (HTC), the biologically active form of B12

A bone marrow biopsy, in selected cases, may be conducted to assess marrow morphology and rule out other causes of megaloblastic anaemia. An upper gastrointestinal endoscopy with biopsies may be carried out to evaluate for autoimmune gastritis and related gastric pathology.^5,6

Treatment

There are various ways to treat pernicious anaemia. Treatment begins with either frequent intramuscular (IM) injections of 1000 micrograms of vitamin B12 (daily or every other day) for the first 1-2 weeks of treatment, after which the patient will be given weekly injections for the next 1-2 months. This is then transitioned into either monthly injections or injections every 2-3 months, depending on the type of B12 prescribed.⁷

In the long-term, regular IM injections are continued, or the patient is switched onto high-dose oral B12 supplementation, an effective alternative to injections.^7,8

Summary 

Pernicious anaemia is a type of blood disorder resulting from vitamin B12 deficiency, primarily due to the autoimmune destruction of gastric parietal cells and intrinsic factor deficiency. The symptoms of pernicious anaemia can come on slowly and are often missed at first. People may feel very tired, weak, or dizzy. Some may have pale skin, shortness of breath, or heart palpitations. More serious symptoms include numbness or tingling in the hands and feet, memory problems, mood changes, and difficulty walking. These occur because vitamin B12 is also essential for nerve function and brain health. Diagnosing pernicious anaemia usually involves blood tests to check for low red blood cell count, low vitamin B12 levels, and sometimes the presence of antibodies that attack intrinsic factor or stomach cells.

Once diagnosed, treatment is quite effective. Since the body cannot absorb B12 normally, people with pernicious anaemia often receive B12 shots, especially at first. Some can later switch to high-dose B12 pills that the body can absorb in smaller amounts without intrinsic factor. With regular treatment, most people can live healthy lives, although they will likely need lifelong B12 therapy. There are promising developments in how pernicious anaemia is managed and understood. Scientists are learning more about the immune system’s role, which could eventually lead to treatments that target the root autoimmune problem rather than just replacing B12. Advances in genetic research and gut health are also helping experts understand why some people develop this condition while others do not. There is also hope that improved B12 delivery methods, like longer-lasting injections, could make treatment easier and more convenient.