Vitamin B12 deficiency anemia, including pernicious anemia, is a condition characterized by a lack of red blood cell production due to insufficient levels of vitamin B12. Fatigue is the most common initial symptom, and other indicators may include shortness of breath, pale skin, chest pain, numbness in the hands and feet, poor balance, a smooth red tongue, poor reflexes, depression, and confusion. Without treatment, these symptoms can become permanent.
Pernicious anemia specifically refers to anemia resulting from a deficiency of intrinsic factor, which is primarily caused by an autoimmune attack on the cells responsible for its production in the stomach. It can also occur following stomach surgery or due to an inherited disorder. Other causes of low vitamin B12 include inadequate dietary intake (such as in a vegan diet), celiac disease, or tapeworm infection. Diagnosis is typically made through blood tests, which may reveal fewer but larger red blood cells, low levels of vitamin B12, and antibodies to intrinsic factor.
Prevention of pernicious anemia is challenging since it is caused by a lack of intrinsic factor. However, vitamin B12 deficiency due to other causes can be prevented through a balanced diet or supplements. Pernicious anemia can be effectively treated with vitamin B12 injections or pills. In severe cases, injections are often recommended initially, and a nasal spray option is available for those who have difficulty swallowing pills. Treatment is usually lifelong.
Autoimmune-related pernicious anemia affects approximately one in 1000 individuals and is more prevalent in people of northern European descent. Women are more commonly affected than men. With proper treatment, most people with pernicious anemia can lead normal lives. Regular check-ups for stomach cancer are recommended due to a higher risk associated with this condition. The term “pernicious” was used historically as the disease was often fatal before the availability of treatment.
The symptoms of pernicious anemia develop gradually and, if left untreated, can lead to neurological complications and, in severe cases, even death. Many of the signs and symptoms are related to anemia itself. Common symptoms include tingling sensations (paresthesia), tongue soreness (glossitis), fatigue, general weakness, depressive mood, low-grade fevers, diarrhea, dyspepsia, weight loss, neuropathic pain, jaundice, sores at the corner of the mouth (angular cheilitis), pale and dehydrated or cracked lips, dark circles around the eyes, brittle nails, thinning and early greying of the hair, difficulty in proprioception, memory changes, mild cognitive impairment, psychoses, impaired urination, loss of sensation in the feet, unsteady gait, difficulty in walking, muscle weakness, clumsiness, tachycardia, cardiac murmurs, altered blood pressure, shortness of breath, and thyroid disorders. Severe chronic pernicious anemia can lead to subacute combined degeneration of the spinal cord, resulting in sensory loss, absent ankle reflex, increased knee reflex response, and extensor plantar response. Hematological symptoms may include cytopenias, intramedullary hemolysis, and pseudothrombotic microangiopathy. Pernicious anemia can also cause delays in physical growth in children and delay in puberty in adolescents.
The main cause of vitamin B12 deficiency is the inability of the human body to produce the vitamin, necessitating its intake through the diet. After consuming B12-containing foods, proteases released by the pancreas in the small intestine release the vitamin, which is then absorbed in the small bowel (ileum) after binding to intrinsic factor, a protein produced by parietal cells in the stomach lining. In the case of pernicious anemia, the deficiency is caused by the absence of intrinsic factor.
Pernicious anemia is strongly associated with autoimmune gastritis, a condition characterized by stomach atrophy and the presence of antibodies to parietal cells and intrinsic factor. This autoimmune disorder primarily affects the body of the stomach, where parietal cells are located. Antibodies to intrinsic factor and parietal cells lead to the destruction of the gastric mucosa, resulting in the loss of intrinsic factor synthesis. Without intrinsic factor, the ileum cannot absorb vitamin B12.
Although the role of Helicobacter pylori infection in pernicious anemia is still debated, evidence suggests its involvement in the disease’s pathogenesis. Long-standing H. pylori infection can cause gastric autoimmunity through a process known as molecular mimicry, where antibodies produced by the immune system target both H. pylori antigens and those found in the gastric mucosa. Impaired B12 absorption can also occur after gastric surgery or bypass procedures. In these cases, intrinsic factor and other factors required for B12 absorption are either removed or bypassed. However, clinical B12 deficiency is uncommon after these surgeries due to the liver’s ability to store several years’ worth of B12.
While specific susceptibility genes for pernicious anemia have not been identified, a genetic factor likely plays a role in the disease. Pernicious anemia often coexists with other autoimmune disorders, suggesting the involvement of common autoimmune susceptibility genes. Family studies and case reports focusing on pernicious anemia indicate a genetic heritance tendency, with close relatives of affected individuals having a higher incidence of pernicious anemia and related conditions. Additionally, it has been suggested that the presence of antibodies to gastric cells is determined by an autosomal dominant gene and may not necessarily correlate with the occurrence of atrophic gastritis associated with pernicious anemia.