Pernicious anemia

Pernicious anemia is a disease where not enough red blood cells are produced due to a deficiency of vitamin B₁₂. Those affected often have a gradual onset. The most common initial symptoms are feeling tired and weak. Other symptoms may include shortness of breath, feeling faint, a smooth red tongue, pale skin, chest pain, nausea and vomiting, loss of appetite, heartburn, numbness in the hands and feet, difficulty walking, memory loss, muscle weakness, poor reflexes, blurred vision, clumsiness, depression, and confusion. Without treatment, some of these problems may become permanent.

Pernicious anemia refers to a type of vitamin B₁₂ deficiency anemia that results from lack of intrinsic factor. Lack of intrinsic factor is most commonly due to an autoimmune attack on the cells that create it in the stomach. It can also occur following the surgical removal of all or part of the stomach or small intestine; from an inherited disorder or illnesses that damage the stomach lining. When suspected, diagnosis is made by blood tests initially a complete blood count, and occasionally, bone marrow tests. Blood tests may show fewer but larger red blood cells, low numbers of young red blood cells, low levels of vitamin B₁₂, and antibodies to intrinsic factor. Diagnosis is not always straightforward and can be challenging.

Because pernicious anemia is due to a lack of intrinsic factor, it is not preventable. Pernicious anemia can be treated with injections of vitamin B₁₂. If the symptoms are serious, frequent injections are typically recommended initially. There are not enough studies that pills are effective in improving or eliminating symptoms. Often, treatment may be needed for life.

Pernicious anemia is the most common cause of clinically evident vitamin B₁₂ deficiency worldwide. Pernicious anemia due to autoimmune problems occurs in about one per 1000 people in the US. Among those over the age of 60, about 2% have the condition. It more commonly affects people of northern European descent. Women are more commonly affected than men. With proper treatment, most people live normal lives. Due to a higher risk of stomach cancer, those with pernicious anemia should be checked regularly for this. The first clear description was by Thomas Addison in 1849. The term "pernicious" means "deadly", and this term came into use because, before the availability of treatment, the disease was often fatal.

Pernicious anemia often presents slowly, and can cause harm insidiously and unnoticeably. Untreated, it can lead to neurological complications, and in serious cases, death. The onset may be vague and slow and the condition can be confused with other conditions, and there may be few to many symptoms without anemia. Pernicious anemia may be present without a person experiencing symptoms at first, over time, feeling tired and weak, lightheadedness, dizziness, headaches, rapid or irregular heartbeat, breathlessness, glossitis (a sore red tongue), poor ability to exercise, low blood pressure, cold hands and feet, pale or yellow skin, easy bruising and bleeding, low-grade fevers, tremor, cold sensitivity, chest pain, upset stomach, nausea, loss of appetite, heartburn, weight loss, diarrhea, constipation, severe joint pain, feeling abnormal sensations including tingling or numbness to the fingers and toes (pins and needles), and tinnitus, may occur. Anemia may present with a number of further common symptoms, including hair thinning and loss, early greying of the hair, mouth ulcers, bleeding gums, angular cheilitis, a look of exhaustion with pale and dehydrated or cracked lips and dark circles around the eyes, as well as brittle nails.

In more severe or prolonged cases of pernicious anemia, nerve cell damage may occur. This is may result in sense loss, difficulty in proprioception, neuropathic pain, difficulty walking, poor balance, loss of sensation in the feet, muscle weakness, blurred vision (either due to retinopathy or optic neuropathy), impaired urination, fertility problems, decreased sense of taste and smell, decreased level of consciousness, changes in reflexes, memory loss, mood swings, depression, irritability, cognitive impairment, confusion, anxiety, clumsiness, psychosis, and, in more severe cases, dementia. Anemia may also lead to cardiac murmurs and/or altered blood pressure (low or high). The deficiency may also present with thyroid disorders. In severe cases, the anemia may cause congestive heart failure. A complication of severe chronic PA is subacute combined degeneration of spinal cord, which leads to distal sensory loss (posterior column), absent ankle reflex, increased knee reflex response, and extensor plantar reflex response. Other than anemia, hematological symptoms may include cytopenias, intramedullary hemolysis, and pseudothrombotic microangiopathy. Vitamin B₁₂ deficiency, which is reversible, is occasionally confused with acute myeloid leukemia, which is an irreversible condition presenting with some of the same hematological symptoms, including hypercellular bone marrow with blastic differentiation and hypersegmented neutrophils. Pernicious anemia can cause osteoporosis and may lead to bone fractures. Pernicious anemia can contribute to a delay in physical growth in children, and may also be a cause for delay in puberty for adolescents.

Vitamin B₁₂ cannot be produced by the human body, and must be obtained from the diet. When foods containing B₁₂ are eaten, the vitamin is usually bound to protein and is released by proteases released by the pancreas into the small bowel. Following its release, most B₁₂ is absorbed by the body in the small bowel (ileum) after binding to a protein known as intrinsic factor. Intrinsic factor is produced by parietal cells of the gastric mucosa (stomach lining) and the intrinsic factor-B₁₂-complex is absorbed by enterocytes in the ileum's cubam receptors. PA is characterised by B₁₂ deficiency caused by the absence of intrinsic factor. Other disorders that can disrupt the absorption of vitamin B₁₂ in the small intestine include coeliac disease, surgical removal, Crohn's disease, and HIV.

PA may be considered as an end stage of autoimmune atrophic gastritis, a disease characterised by stomach atrophy and the presence of antibodies to parietal cells and intrinsic factor. Autoimmune atrophic gastritis, is localised to the body of the stomach, where parietal cells are located. Antibodies to intrinsic factor and parietal cells cause the destruction of the oxyntic gastric mucosa, in which the parietal cells are located, leading to the subsequent loss of intrinsic factor synthesis. Without intrinsic factor, the ileum can no longer absorb the B₁₂. Atrophic gastritis is often a precursor to gastric cancer.