What is Pernicious Anemia? Its Causes, Symptoms, and Treatment

Introduction Pernicious anemia is a type of megaloblastic anemia caused by the body’s inability to absorb vitamin B12 (cobalamin) properly. Vitamin B12 is essential for the production of red blood cells and the maintenance of the nervous system. Pernicious anemia occurs when the stomach lacks a substance known as intrinsic factor, which is necessary for the absorption of vitamin B12 from the diet. Without adequate vitamin B12, the body produces fewer and larger red blood cells, leading to a variety of symptoms that can affect multiple organ systems.

Pernicious anemia was once a fatal disease, but with the discovery of vitamin B12 and the development of effective treatments, it is now manageable with proper medical care.

Epidemiology Pernicious anemia is relatively uncommon, affecting approximately 0.1% of the general population and about 1.9% of people over the age of 60. It is more prevalent in individuals of Northern European descent but can occur in people of any ethnic background. The condition is slightly more common in women than in men and is typically diagnosed in middle-aged or older adults.

Causes and Risk Factors The primary cause of pernicious anemia is an autoimmune process in which the body’s immune system attacks the cells in the stomach that produce intrinsic factor or the intrinsic factor itself. Without intrinsic factor, vitamin B12 cannot be absorbed in the small intestine, leading to a deficiency.

Several factors can contribute to the development of pernicious anemia, including:

1. Autoimmune Destruction of Parietal Cells: Parietal cells in the stomach lining produce intrinsic factor. In pernicious anemia, the immune system attacks these cells, reducing the production of intrinsic factor and leading to vitamin B12 deficiency.
2. Antibodies Against Intrinsic Factor: In some cases, the immune system produces antibodies that specifically target intrinsic factor, preventing it from binding to vitamin B12 and facilitating its absorption.
3. Genetic Predisposition: There is a hereditary component to pernicious anemia, as it tends to run in families. Individuals with a family history of autoimmune diseases, such as thyroid disease or type 1 diabetes, are at an increased risk of developing pernicious anemia.
4. Age: The risk of developing pernicious anemia increases with age, as the production of intrinsic factor naturally decreases over time.
5. Gastrointestinal Surgery: Individuals who have undergone surgery that removes part of the stomach (such as gastric bypass surgery) or the small intestine may be at risk of pernicious anemia due to the reduced ability to produce or absorb intrinsic factor.
6. Dietary Factors: While pernicious anemia is primarily caused by an autoimmune process, a diet lacking in vitamin B12 can exacerbate the condition. Vitamin B12 is found in animal products such as meat, dairy, and eggs, so strict vegetarians or vegans may be at risk if they do not take B12 supplements.

Clinical Presentation The symptoms of pernicious anemia can develop gradually and may be subtle at first, often resembling other types of anemia. However, as the deficiency worsens, more severe symptoms can emerge, affecting multiple body systems:

1. Fatigue and Weakness: One of the most common symptoms, caused by the reduced oxygen-carrying capacity of the blood due to fewer and larger red blood cells.
2. Pallor: The skin may appear pale due to the anemia.
3. Shortness of Breath: Patients may experience difficulty breathing, especially during physical exertion.
4. Heart Palpitations: Anemia can lead to an increased heart rate as the body tries to compensate for the reduced oxygen supply.
5. Neurological Symptoms: A hallmark of vitamin B12 deficiency, neurological symptoms can include numbness and tingling in the hands and feet, difficulty walking, balance problems, and memory loss. If left untreated, these symptoms can become permanent.
6. Glossitis and Mouth Ulcers: The tongue may become swollen, red, and sore, a condition known as glossitis. Mouth ulcers are also common.
7. Gastrointestinal Symptoms: Some patients experience nausea, diarrhea, or constipation.
8. Cognitive Changes: Vitamin B12 deficiency can lead to mental changes such as depression, confusion, or dementia, particularly in older adults.
9. Jaundice: In severe cases, a yellowing of the skin and eyes (jaundice) can occur due to the breakdown of red blood cells.

Diagnosis Diagnosing pernicious anemia involves a combination of clinical evaluation, laboratory tests, and sometimes imaging studies. Key diagnostic tools include:

1. Complete Blood Count (CBC): This test measures the levels of red blood cells, white blood cells, and platelets in the blood. In pernicious anemia, the red blood cells are often larger than normal (macrocytic) and fewer in number.
2. Serum Vitamin B12 Levels: A low level of vitamin B12 in the blood is a key indicator of pernicious anemia.
3. Intrinsic Factor Antibody Test: This blood test detects the presence of antibodies against intrinsic factor, which are present in about 50-70% of patients with pernicious anemia.
4. Parietal Cell Antibody Test: This test checks for antibodies against the stomach’s parietal cells, which are found in about 85-90% of patients with pernicious anemia.
5. Methylmalonic Acid (MMA) and Homocysteine Levels: Elevated levels of MMA and homocysteine in the blood or urine can indicate vitamin B12 deficiency.
6. Bone Marrow Biopsy: In rare cases, a bone marrow biopsy may be performed to confirm the diagnosis, especially if other causes of macrocytic anemia are being considered.

Treatment The primary treatment for pernicious anemia is vitamin B12 replacement therapy. Since the condition is caused by the inability to absorb vitamin B12 through the digestive tract, oral supplementation is often insufficient for those with pernicious anemia. Treatment options include:

1. Intramuscular Injections of Vitamin B12: The most common and effective treatment involves regular injections of vitamin B12 (usually cyanocobalamin or hydroxocobalamin) directly into the muscle. Initially, injections are given more frequently (daily or weekly) until B12 levels are normalized, followed by maintenance injections every one to three months.
2. High-Dose Oral Vitamin B12 Supplements: In some cases, high-dose oral B12 supplements may be used, especially for patients who prefer not to receive injections or for those who have some ability to absorb B12. Sublingual (under the tongue) B12 is another option that bypasses the gastrointestinal tract.
3. Dietary Changes: While dietary B12 alone cannot correct pernicious anemia, ensuring an adequate intake of B12-rich foods can help maintain overall health. Foods rich in vitamin B12 include meat, dairy products, eggs, and fortified cereals.
4. Management of Complications: If neurological symptoms or other complications are present, additional treatments and therapies may be required, such as physical therapy for mobility issues or cognitive therapy for memory problems.

Prognosis With prompt and appropriate treatment, most individuals with pernicious anemia can lead healthy lives. The prognosis is generally good, especially if the condition is diagnosed early and managed effectively. However, if left untreated, pernicious anemia can lead to severe and potentially irreversible complications, including neurological damage and an increased risk of gastric cancer.

Conclusion Pernicious anemia is a serious but treatable condition caused by the body’s inability to absorb vitamin B12. Early diagnosis and treatment are essential to prevent long-term complications and improve the quality of life for affected individuals. With regular monitoring and ongoing medical care, most people with pernicious anemia can manage their symptoms effectively and maintain good health. Advances in understanding the underlying causes of pernicious anemia continue to improve the outlook for patients, offering hope for even better management and outcomes in the future.