The clinical picture of pernicious anemia is indistinguishable from megaloblastic anemia of vitamin B12 deficiency resulting from any etiology.

Symptoms

The onset of symptoms is insidious. The predominant symptoms include the following.

• Features of anemia: Pallor, weakness, tachycardia and dyspnea are present in all the patients suffering from pernicious anemia.
• Jaundice: There is mild jaundice caused by the excessive breakdown of hemoglobin due to ineffective erythropoiesis in the bone marrow.
• Mucosal changes: Angular stomatitis may be present at angle of the mouth. Red, sore tongue (glossitis) may also be present.
• Polyneuropathy: There may be symmetric loss of sensations in the fingers and toes. Later on, there is difficulty in balance due to loss of sense of vibration and proprioception. In advanced stages, abnormalities of cerebral function also develop that cause progressive weakness and ataxia.

Signs

The signs indicative of pernicious anemia include the following.

• Signs of anemia are present upon the physical examination of the hands and eyes.
• Jaundice is seen in the skin and the sclera.
• Spleenomegaly may be present.
• There may be low grade fever due to infection or anemia itself.
• Signs of polyneuropathy are seen upon the examination of the nervous system.
• Purpurae may be present due to thrombocytopenia.

• Splenomegaly

  Occasionally, splenomegaly and hepatomegaly occur. Various gastrointestinal symptoms, including weight loss and poorly localized abdominal pain, may occur. Glossitis, usually described as burning of the tongue, is uncommon. [msdmanuals.com]

  Hepatomegaly and splenomegaly may be present. [patient.info]

  Some people with Pernicious Anemia may have an abnormally enlarged liver (hepatomegaly) or spleen (splenomegaly). Other problems involving urinary function may also develop. [rarediseases.org]

• Anemia

  Pernicious anemia (Biermer's anemia, Addison's anemia) is a type of megaloblastic anemia, due to an inability to absorb vitamin B12 (cobalamin). [symptoma.com]

  Pernicious anemia is one of many types of anemia, a disease marked by a reduction in red blood cells or in the oxygen-carrying substance hemoglobin found in those cells. [britannica.com]

  Pernicious anemia can occur at any age; among younger individuals it is most common in African American women. What Causes Pernicious Anemia? Pernicious anemia almost always results from an impaired ability to absorb vitamin B12. [healthcommunities.com]

  PA is identified with a high MCV ( macrocytic anemia ) and a normal MCHC ( normochromic anemia). [38] Ovalocytes are also typically seen on the blood smear, and a pathognomonic feature of megaloblastic anemias (which include PA and others) is hypersegmented [en.wikipedia.org]

  IFBA positive Consistent with pernicious anemia, Graves disease, or Hashimoto thyroiditis. Gastrin >200 pg/mL Result consistent with pernicious anemia. Gastrin Result does not suggest pernicious anemia. [mayomedicallaboratories.com]

• Weight Loss

  Here, I show that her physical ailments spanned 30 years and included sore mouth, pallor, paresthesias, the Lhermitte symptom, fever, headaches, fatigue, resting tachycardia, edema, episodic weight loss, progressive weakness, ataxia, and visual impairment [muse.jhu.edu]

  An elderly black man was admitted to our institution with macrocytic anemia, dysphagia, and significant weight loss. Results of an esophagogram were suggestive of achalasia. [ncbi.nlm.nih.gov]

  Weight loss and lack of appetite ( anorexia ) may also occur, as well as jaundice, confusion and depression. Lesions in the gastrointestinal tract may cause abnormal activity in the intestines and difficulties with the absorption of food. [diagnose-me.com]

  Weight loss, depressed mood, and memory loss are common in affected persons. [britannica.com]

• Pallor

  When to Call a Doctor Consult your doctor if you experience persistent fatigue, weakness, or pallor. [healthcommunities.com]

  Definition of pernicious anemia : a severe megaloblastic anemia that is marked by a progressive decrease in the number of red blood cells and by pallor, weakness, and gastrointestinal and nervous disturbances and is caused by malabsorption of vitamin [merriam-webster.com]

  Here, I show that her physical ailments spanned 30 years and included sore mouth, pallor, paresthesias, the Lhermitte symptom, fever, headaches, fatigue, resting tachycardia, edema, episodic weight loss, progressive weakness, ataxia, and visual impairment [muse.jhu.edu]

  Symptoms Symptoms of pernicious anemia include fatigue, weakness, waxy pallor, shortness of breath, rapid heartbeat, unsteady gait, smooth tongue, gastrointestinal disturbances, and neurological problems. [britannica.com]

• Congestive Heart Failure

  We present the unusual case of vitiligo associated with pernicious anemia in a patient who presented to the hospital because of hyperdynamic congestive heart failure. [ncbi.nlm.nih.gov]

  However, the cardiac output is usually increased with hematocrits less than 20%, and the heart rate accelerates. Congestive heart failure and coronary insufficiency can occur, most particularly in patients with preexisting heart disease. [web.archive.org]

  Compensatory increased cardiac output results in palpitations, wide pulse pressure, dyspnea, orthopnea, tachycardia, premature beats, and eventually, congestive heart failure. [innvista.com]

• Falling

  The fall in cobalamin concentration runs in parallel with these abnormalities. The concentration of this vitamin was below normal levels in as much as 15.2% of cases. [ncbi.nlm.nih.gov]

  If B12 levels fall too far, the result is lagging energy, depression, indigestion, diarrhea, and ultimately, anemia. [innvista.com]

  As the B12 level falls, an individual becomes progressively anaemic and pale, dizzy and short of breath. [familydoctor.co.nz]

  As the gum line shrinks, the pockets enlarge, and you run the risk of teeth falling out and suffering from other serious oral conditions. Causes of Periodontitis The major culprit of periodontitis is plaque. [oralb.com]

• Nausea

  Anorexia, nausea, vomiting, heartburnand dyspepsia Non specific gastrointestinal symptoms, that are associated with pernicious anemia. [medicaljoyworks.com]

  Dyspeptic symptoms are common, and nausea and vomiting, with diarrhea, are often present. [henriettes-herb.com]

  […] noticeable in the lips, gums, eyelids, and nail beds) Shortness of breath or chest pain on exertion Sore, red, and glazed-looking tongue Irritability or inability to concentrate Mild jaundice of the eyes or skin Loss of appetite leading to weight loss Nausea [healthcommunities.com]

  These symptoms include nausea (feeling sick to your stomach) and vomiting, heartburn, abdominal bloating and gas, constipation or diarrhea, loss of appetite, and weight loss. An enlarged liver is another symptom. [web.archive.org]

• Dyspepsia

  Anorexia, nausea, vomiting, heartburnand dyspepsia Non specific gastrointestinal symptoms, that are associated with pernicious anemia. [medicaljoyworks.com]

  Less commonly, the disease is suspected to be caused by dyspepsia. PA is frequently associated with autoimmune thyroid disease (40%) and other autoimmune disorders, such as diabetes mellitus (10%), as part of the autoimmune polyendocrine syndrome. [ncbi.nlm.nih.gov]

  […] presents with decreased free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) and normal free thyroxine (FT4).6 7 Case report Herein, the case of a 44-year-old female patient admitted to the Emergency Room with complaints of asthenia and dyspepsia [scielo.br]

  Only 3% of PA patients presented directly to our gastroenterology unit for long-standing dyspepsia, and only 3% were referred from a neurologist. [doi.org]

  tongue soreness ( glossitis ), and fatigue and general weakness. [17] [18] [19] [ page needed ] It presents with a number of further common symptoms, [19] [ page needed ] [20] [ page needed ] including depressive mood, low-grade fevers, diarrhea, dyspepsia [en.wikipedia.org]

• Abdominal Pain

  Rarely, patients present with severe abdominal pain associated with abdominal rigidity; this has been attributed to spinal cord pathology. Neurologic symptoms Neurologic symptoms can be elicited in patients with pernicious anemia. [web.archive.org]

  A 60-year-old Indian man presented with epigastric pain, diarrhea and vomiting. An abdominal imaging scan showed that he had concomitant pernicious anemia and concomitant portal, superior mesenteric and splenic vein thrombosis. [ncbi.nlm.nih.gov]

  Rarely, patients present with severe abdominal pain associated with abdominal rigidity; this has been attributed to spinal cord pathology. [emedicine.medscape.com]

  Gastrointestinal symptoms (eg, abdominal pain, diarrhea, and constipation) may be present. If treated, many of these manifestations are reversible. However, if undiagnosed and untreated, some neurologic manifestations can be permanent. [visualdx.com]

  When hemoglobin has decreased significantly (7 to 8 g/dl), the individual experiences the classic symptoms of anemia: weakness, fatigue, paresthesias (abnormal sensations) of feet and fingers, sore tongue, loss of appetite, abdominal pain, weight loss [innvista.com]

• Regurgitation

  […] needed ] In 1907, Richard Clarke Cabot reported on a series of 1200 patients with PA; their average survival was between one and three years. [ citation needed ] William Bosworth Castle performed an experiment whereby he ingested raw hamburger meat and regurgitated [en.wikipedia.org]

• Abdominal Bloating

  These symptoms include nausea (feeling sick to your stomach) and vomiting, heartburn, abdominal bloating and gas, constipation or diarrhea, loss of appetite, and weight loss. An enlarged liver is another symptom. [web.archive.org]

  *=most common in pernicious anemia Remember the mnemonic: Pernicious P ale E nergy gone (very fatigued)* R ed, smooth tongue* N umbness or tingling in hands and feet* I ntestinal issues (abdominal bloating, diarrhea/constipation, indigestion) C onfusion [registerednursern.com]

  Hematological manifestations: pallor, fatigue, shortness of breath, dizziness, tachycardia, lightheadedness, and decreased cognitive and physical function Gastrointestinal manifestations: abdominal bloating, loss of appetite, weight loss, and diarrhea [statpearls.com]

• Tachycardia

  Here, I show that her physical ailments spanned 30 years and included sore mouth, pallor, paresthesias, the Lhermitte symptom, fever, headaches, fatigue, resting tachycardia, edema, episodic weight loss, progressive weakness, ataxia, and visual impairment [muse.jhu.edu]

  Features of anemia: Pallor, weakness, tachycardia and dyspnea are present in all the patients suffering from pernicious anemia. [symptoma.com]

  Compensatory increased cardiac output results in palpitations, wide pulse pressure, dyspnea, orthopnea, tachycardia, premature beats, and eventually, congestive heart failure. [innvista.com]

• Sore Mouth

  Here, I show that her physical ailments spanned 30 years and included sore mouth, pallor, paresthesias, the Lhermitte symptom, fever, headaches, fatigue, resting tachycardia, edema, episodic weight loss, progressive weakness, ataxia, and visual impairment [muse.jhu.edu]

  Other symptoms that may occur include a sore mouth and tongue. What is vitamin B12 deficiency? Vitamin B12 is essential for life. It is needed to make new cells in the body, such as the many new red blood cells which are made every day. [patient.info]

  Symptoms that can appear include: Pallor Fatigue Diarrhea Sore mouth Bleeding gums Loss of appetite Rapid heart rate Tongue problems Shortness of breath Positive Babinski's sign Impaired sense of smell Loss of deep tendon reflexes Personality or memory [disabled-world.com]

• Aphthous Stomatitis

  The aim of this report is to present the management of a patient with pernicious anemia afflicted with recurrent aphthous stomatitis (RAS). RAS is one of the most common lesions of the oral mucosa. [ncbi.nlm.nih.gov]

• Jaundice

  Jaundice: There is mild jaundice caused by the excessive breakdown of hemoglobin due to ineffective erythropoiesis in the bone marrow. Mucosal changes: Angular stomatitis may be present at angle of the mouth. [symptoma.com]

  A physician should also be contacted if the tongue becomes slick or smooth or the patient: bruises or tires easily feels ill for more than five days feels weak or out of breath looks pale or jaundiced. [diagnose-me.com]

  She was readmitted with jaundice and macrocytic anemia. The diagnosis of pernicious anemia was confirmed by the low level of serum vitamin B12 and the presence of anti-parietal cell antibody and anti-intrinsic factor antibody. [ncbi.nlm.nih.gov]

• Hepatomegaly

  Occasionally, splenomegaly and hepatomegaly occur. Various gastrointestinal symptoms, including weight loss and poorly localized abdominal pain, may occur. Glossitis, usually described as burning of the tongue, is uncommon. [msdmanuals.com]

  Hepatomegaly and splenomegaly may be present. [patient.info]

  Some people with Pernicious Anemia may have an abnormally enlarged liver (hepatomegaly) or spleen (splenomegaly). Other problems involving urinary function may also develop. [rarediseases.org]

• Tinnitus

  Stinging sensation on the tongue, or a smooth red tongue Weight loss Problems between colors yellow and blue Fatigue Paleness Loss of hunger Change in taste sensational Confusion Depression Problems with balance, especially in the dark Ringing in the ears— tinnitus [lahey.org]

  […] burning), disturbed sense of position, lack of coordination and muscle coordination (ataxia), impaired fine finger movement, positive Babinski’s and Romberg’s signs, light-headedness, altered vision (diplopia, blurred vision), altered taste and hearing (tinnitus [innvista.com]

  […] tongue, or a smooth red tongue Substantial weight loss Inability to distinguish the colors yellow and blue Fatigue Paleness Loss of hunger Altered sense of taste Confusion Depression Impaired sense of balance, especially in the dark Ringing in the ears— tinnitus [cancercarewny.com]

• Acroparesthesia

  Neurological symptoms may include numbness, tingling, loss of sensation in the arms and/or legs (acroparesthesias). [rarediseases.org]

• Restless Legs Syndrome

  Restless legs syndrome. A review. Arch Intern Med. 1996;156:243-248. [forum.parkinson.org]

  leg syndrome US9248104B2 ( en ) 2016-02-02 Transdermal methods and systems for treating Alzheimer's disease KR20060114338A ( en ) 2006-11-06 Transdermal drug delivery devices CN101528207B ( en ) 2012-12-26 Transdermal therapeutic system for administering [google.com]

• Numbness of the Feet

  Tingling or numb hands and feet Problems with balance or walking Digestive issues such as nausea, heartburn or gas Tongue that is thick, red and smooth Desire to eat nonfood items such as dirt, ice or paint (called pica) How can I get help for pernicious [rush.edu]

• Alopecia

  Alopecia areata occurred 9 years later. 2007 Wiley-Liss, Inc [ncbi.nlm.nih.gov]

  […] hypogammaglobulinemia 8 Baba and Maharaj [15] 1988 1 71 F Hypocalcemia 9 Pelosio et al. [16] 1989 1 61 F Vitiligo 10 Feld et al. [17] 1989 1 66 F SLE, Sjögren, Hashimoto’s thyroiditis 11 Rabinowitz et al. [6] 1990 1 61 F None 12 Zafad et al. [18] 2007 1 16 M Alopecia [hindawi.com]

  For example, pernicious anemia may occur together with autoimmune thyroid disease, type 1A diabetes mellitus, alopecia, vitiligo, and chronic atrophic gastritis in type III polyglandular autoimmune (PGA) syndrome—one of a rare group of disorders also [emedicine.medscape.com]

• Purpura

  Thrombotic thrombocytopenic purpura (TTP) is a microangiopathic hemolytic anemia that requires emergent treatment with plasma exchange and is one of the most important conditions for which apheresis service professionals are consulted. [ncbi.nlm.nih.gov]

  Purpurae may be present due to thrombocytopenia. The following investigations are helpful in establishing the diagnosis of pernicious anemia. Blood picture: Blood tests demonstrate low hemoglobin levels. [symptoma.com]

  During the current ER visit, the physical exam was significant for tachycardia, pallor, oral wet purpura, and petechiae on the lower extremities. [tandfonline.com]

• Yellow Discoloration of the Skin

  Enlargement of liver and spleen (hepatosplenomegaly) may also occur, accompanied by yellow discoloration of the skin (jaundice) or pallor. Weakness, heart palpitations, difficulty breathing, as well as pain in the limbs are other possible symptoms. [diagnose-me.com]

• Petechiae

  During the current ER visit, the physical exam was significant for tachycardia, pallor, oral wet purpura, and petechiae on the lower extremities. [tandfonline.com]

  Petechiae in the mammillary bodies. WKS, acute lesion. Periaqueductal lesions. WKS, acute lesion. Periaqueductal lesions. WKS, burned out lesion. WKS, burned out lesion. Small brownish mammillary bodies. [neuropathology-web.org]

• Hyperpigmentation

  Physical examination revealed hypotension and marked hyperpigmentation. Laboratory testing showed hyponatremia, hyperkaliemia and severe normocytic anemia. [ncbi.nlm.nih.gov]

• Psychiatric Manifestation

  Pernicious anemia has been associated with various psychiatric manifestations, such as depression, mania and psychosis. [ncbi.nlm.nih.gov]

  Despite these facts, the need for universal screening in older adults remains a matter of controversy. 3, 4 Clinical Manifestations Vitamin B 12 deficiency is associated with hematologic, neurologic, and psychiatric manifestations ( Table 1 ). [aafp.org]

• Visual Hallucination

  CNS Manifestations Dementia And Acute Psychosis (Megaloblastic Madness) Neuropsychiatric manifestations such as memory loss, depression, hypomania, paranoid psychosis with auditory and visual hallucinations the so called megaloblastic madness have been [ispub.com]

• Confusion

  People with untreated pernicious anemia for the long term may be subject to heart failure, heart attacks, strokes, stomach cancer, confusion, and memory loss. [change.org]

  Related damage to the nervous system can cause such diverse symptoms as numbness and tingling in the hands and feet, difficulty with balance, vision changes, memory loss, and confusion. Other symptoms include fatigue, loss of appetite, and diarrhea. [diabetesselfmanagement.com]

  Common symptoms include fatigue, irritability, confusion, depression, gastrointestinal symptoms, weight loss, neuropathic pain and glossitis. [symptoma.com]

  Symptoms of Pernicious Anemia Fatigue and weakness Abdominal cramps Imbalance, changes in reflexes, irritability, confusion and depression Heart palpitations; lightheadedness or dizziness Pallor (may be especially noticeable in the lips, gums, eyelids [healthcommunities.com]

  Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances See individual test listings. [mayomedicallaboratories.com]

• Headache

  Here, I show that her physical ailments spanned 30 years and included sore mouth, pallor, paresthesias, the Lhermitte symptom, fever, headaches, fatigue, resting tachycardia, edema, episodic weight loss, progressive weakness, ataxia, and visual impairment [muse.jhu.edu]

  It manifests with failure to thrive and symptoms of anemia (e.g. asthenia, weakness, headache, infections). If untreated, neurological damage may occur such as peripheral neuropathy, subacute combined degeneration of the spinal cord and/or ataxia. [orpha.net]

  A low red blood cell count also can cause shortness of breath, dizziness, headache, coldness in your hands and feet, pale or yellowish skin, and chest pain. [web.archive.org]

  Lincoln’s long list of physical symptoms, including weakness, fatigue, fevers, headaches, gait problems, rapid heartbeat, mouth soreness, swelling and vision trouble. [history.com]

• Dizziness

  Symptoms of Pernicious Anemia Fatigue and weakness Abdominal cramps Imbalance, changes in reflexes, irritability, confusion and depression Heart palpitations; lightheadedness or dizziness Pallor (may be especially noticeable in the lips, gums, eyelids [healthcommunities.com]

  A low red blood cell count also can cause shortness of breath, dizziness, headache, coldness in your hands and feet, pale or yellowish skin, and chest pain. [web.archive.org]

  If you have any of the following symptoms of pernicious anemia and they don’t go away, call your primary care physician to schedule an appointment: Fatigue Dizziness Shortness of breath (dyspnea) Pale skin Cold hands and feet Headache Irregular heartbeat [rush.edu]

  As the condition worsens, you may experience: weakness and fatigue lightheadedness and dizziness palpitations and rapid heartbeat shortness of breath a sore tongue that has a red, beefy appearance nausea or poor appetite weight loss If your B12 levels [askdoctork.com]

  Do you get dizzy or short of breath whenever you climb the stairs? There are a few possible reasons for the way you feel, but you could have anemia. You could even have anemia without noticing any symptoms at all. [mountsinai.org]

• Peripheral Neuropathy

  Pernicious Anemia Macrocytic anemia, glossitis, peripheral neuropathy, weakness, hyperreflexia, ataxia, and other neurological manifestations characterize classical vitamin B12 (cobalamin) deficiency. [clinlabnavigator.com]

  If untreated, neurological damage may occur such as peripheral neuropathy, subacute combined degeneration of the spinal cord and/or ataxia. Neurological symptoms may include muscular weakness and abnormal gait. [orpha.net]

  neuropathy, weakness, hyperreflexia, ataxia, loss of proprioception, poor coordination, and affective behavioral changes. [mayomedicallaboratories.com]

  Neuropathy, specifically peripheral neuropathy, occurs in patients with pernicious anemia. Neuropathy is also known to be an underlying symptom of physical injury, infection, toxin exposure, and metabolic problems. [findatopdoc.com]

• Ataxia

  Here, I show that her physical ailments spanned 30 years and included sore mouth, pallor, paresthesias, the Lhermitte symptom, fever, headaches, fatigue, resting tachycardia, edema, episodic weight loss, progressive weakness, ataxia, and visual impairment [muse.jhu.edu]

  We describe a case of a young black woman with gradually progressive lower extremity paresthesias, weakness, and ataxia as the primary presenting symptoms of pernicious anemia. [ncbi.nlm.nih.gov]

  Pernicious Anemia Macrocytic anemia, glossitis, peripheral neuropathy, weakness, hyperreflexia, ataxia, and other neurological manifestations characterize classical vitamin B12 (cobalamin) deficiency. [clinlabnavigator.com]

The following investigations are helpful in establishing the diagnosis of pernicious anemia.

• Blood picture: Blood tests demonstrate low hemoglobin levels. The mean corpuscular volume is usually raised to around 110 to 140 fl. However, it may be normal if there is coexisting thalassemia or iron deficiency. Peripheral blood film shows anisocytosis and poikilocytosis. Neutrophils are characteristically hypersegmented with multilobed nuclei. The reticulocyte count is also reduced.
• Bone marrow biopsy: The abnormalities seen in bone marrow include large cell size, giant metamyelocytes and marked erythroid hyperplasia [4].
• Serum vitamin B12: Serum vitamin B12 is usually below 100 pg/ml in symptomatic disease. The normal vitamin B12 level is 150 to 350 pg/ml.
• Serum lactate dehydrogenase (LDH) and unconjugated bilirubin: The levels of lactate dehydrogenase and unconjugated bilirubin in the serum is also raised [5] [6].
• Schilling test: This is also known as vitamin B12 absorption test. It is the traditional test to detect decreased oral absorption of vitamin B12 that is characteristic of pernicious anemia. Addition of intrinsic factor causes an increased absorption of vitamin B12 in the patients suffering from pernicious anemia [7] [8].
• Anti-intrinsic factor antibodies: Antibodies against intrinsic factor are present in around 50% of the cases.

• Abnormal Schilling Test

  The underlying diseases themselves (eg, PA) are often asymptomatic and could not be detected otherwise. 1 An abnormal Schilling test result also helps select the optimal final test (eg, intestinal biopsy). [doi.org]

• Macrocytic Anemia

  These manifestations may occur in any combination; many patients present with neurologic symptoms without macrocytic anemia. [mayomedicallaboratories.com]

  Pernicious Anemia Macrocytic anemia, glossitis, peripheral neuropathy, weakness, hyperreflexia, ataxia, and other neurological manifestations characterize classical vitamin B12 (cobalamin) deficiency. [clinlabnavigator.com]

  Her macrocytic anemia dramatically improved after intramuscular administration of vitamin B12. In conclusion, attention should be given to the association of pernicious anemia during the follow up of primary biliary cirrhosis. [ncbi.nlm.nih.gov]

• Macrocytosis

  BACKGROUND/PURPOSE: Macrocytosis is defined as having the mean corpuscular volume (MCV) ≥ 100 fL. This study assessed hematinic deficiencies and pernicious anemia (PA) in oral mucosal disease patients with macrocytosis. [ncbi.nlm.nih.gov]

• Hypochlorhydria

  Pernicious anemia is associated with atrophic body gastritis, whose diagnostic criteria are based on the histologic evidence of gastric body atrophy associated with hypochlorhydria. [ncbi.nlm.nih.gov]

  Hypochlorhydria leads to overgrowth of nitrosamine-producing bacteria with potential carcinogen activity[ 66 ]. [doi.org]

  Etiology Cobalamin deficiency may result from the following: Inadequate dietary intake (ie, vegetarian diet) Atrophy or loss of gastric mucosa (eg, pernicious anemia, gastrectomy, ingestion of caustic material, hypochlorhydria, histamine 2 [H2] blockers [emedicine.medscape.com]

• Folic Acid Increased

  Because the demand for folic acid increases among pregnant women and among patients on hemodialysis, risk becomes even higher for these people. [diagnose-me.com]

• Reticulocyte Count Decreased

  At this time her Hb was 11.4 g/dl, platelet count was at 49,000/µL, and reticulocyte count decreased to 5.29%. Her MMA and B12 both normalized. She was tested for intrinsic factor antibody, which was positive confirming pernicious anemia. [tandfonline.com]

• Megaloblastic Bone Marrow

  DOYLE Pediatrics July 1951, 8 (1) 88-106; Abstract Histories have been presented of two pairs of sibling children with recurrent macrocytic anemia with megaloblastic bone marrow responding specifically to liver extract and vitamin B12. [pediatrics.aappublications.org]

• Hypercellular Bone Marrow

  Bone marrow aspiration testing identified hypercellular bone marrow and abnormal erythroblast carrying megaloblastic change and abnormality of nuclear division [Fig. 1A and B]. [academic.oup.com]

Therapy for pernicious anemia

Parenteral vitamin B12 therapy: Pernicious anemia is treated by the parenteral administration of vitamin B12 [9]. The parenteral forms of vitamin B12 are cyanocobalamin and hydroxocobalamin. 1000 micrograms of vitamin B12 are injected daily for first week, weekly for first month and then monthly for life. Clinical improvement may occur in as less as 48 hours.

Supportive measures for anemia

Blood transfusion: If the levels of hemoglobin are very low (below 4 g/dl), blood should be transfused in the form of packed cells and furosemide should also be given.

Iron: Ferrous sulphate should be given after treatment with vitamin B12 is started. This is done because in some patients, rapid restoration of blood volume can deplete the iron stores of the body.

With early diagnosis and proper treatment, the prognosis of the patients suffering from pernicious anemia is excellent. However, if the treatment is delayed, anemia and later neurological complications may develop; the latter may be permanent.
There may be an association between pernicious anemia and gastric cancer but it has not yet been proved.

Pernicious anemia is caused by the deficiency of intrinsic factor that is produced by the gastric parietal cells. In adults, it usually results from gastrectomy or the autoimmune destruction of parietal cells. Congenital deficiency of intrinsic factor without gastric atrophy may also cause pernicious anemia but is very rare.

Pernicious anemia is the most common cause of vitamin B12 deficiency. It usually affects people in the late adulthood at the age of 45 to 60 years [1]. The incidence in northern Europe is 1 in 10,000 cases. It is estimated that 0.1% of the general population is affected worldwide. The female to male ratio is 1.6:1 in Europe but equal in the US. It is associated with other autoimmune diseases including thyroid diseases, Addison's disease and vitiligo.

For the proliferation of hematopoietic tissue, DNA is required in large amounts. Since vitamin B12 is necessary for the formation of DNA, its deficiency leads to reduced synthesis of DNA. As a result, there is a delay or arrest of the cell division in the bone marrow. The division of cells is sluggish but cytoplasmic development progresses normally. Large megaloblasts are formed which tend to be destroyed by the bone marrow causing ineffective erythropoiesis.

The absorption of vitamin B12 from the lower ileum is facilitated by gastric intrinsic factor which is released by the parietal cells of the gastric mucosa. Intrinsic factor binds with vitamin B12 and forms a complex that is taken up by the binding sites on the ileal cells. Vitamin B12 is transferred into the cells and absorbed into the blood bound with a carrier protein. In the absence of gastric intrinsic factor, vitamin B12 can not be absorbed and pernicious anemia ultimately develops when the stores of vitamin B12 in the liver are exhausted [2] [3].

Primary (congenital) pernicious anemia can not be detected. However, pernicious anemia resulting from secondary causes such as gastrectomy can be prevented by initiating parenteral vitamin B12 substitution soon after the surgery is completed [10].

Pernicious anemia is the megaloblastic anemia that results from vitamin B12 deficiency as a result of the failure of secretion of intrinsic factor from the gastric parietal cells. It accounts for 30-50% of all cases of megaloblastic anemia due to vitamin deficiency.

Pernicious anemia is caused because of the deficiency of vitamin B12 due to poor absorption from the intestine. Normal blood cells can not form in the absence of vitamin B12. Vitamin B12 is administered by injections for life in all the patients suffering from pernicious anemia. The outcome of this treatment is excellent.

1. Andres E, Vogel T, Federici L, Zimmer J, Ciobanu E, Kaltenbach G. Cobalamin deficiency in elderly patients: a personal view. Current gerontology and geriatrics research. 2008:848267.
2. Horanyi M, Sarfy E. [Pathogenesis of pernicious anemia]. Orvosi hetilap. Jan 21 1973;114(3):143-145.
3. Horanyi M, Sarfy E. [Current data on the pathogenesis of pernicious anemia and its treatment with duodenal intrinsic factor]. Orvosi hetilap. Oct 26 1975;116(43):2538-2540.
4. Macukanovic-Golubovic L, Rancic G, Milenovic M, Marjanovic G, Vojvodic S, Golubovic Z. [Morphometrical analysis of bone marrow metamyelocyte in pernicious anemia]. Medicinski pregled. Nov-Dec 2008;61(11-12):562-565.
5. Weinreich J, Kustner W. [Lactate dehydrogenase and its isoenzymes in pernicious anemia]. Die Medizinische Welt. Sep 24 1966;39:2050-2053.
6. Myhrman G. [Determination of lactate dehydrogenase as an aid in the diagnosis of pernicious anemia]. Lakartidningen. Oct 5 1966;63(40):3734-3735.
7. Fairbanks VF, Wahner HW, Phyliky RL. Tests for pernicious anemia: the "Schilling test". Mayo Clinic proceedings. Aug 1983;58(8):541-544.
8. The schilling test for pernicious anemia. South Dakota journal of medicine. Mar 1967;20(3):50.
9. Andres E, Serraj K. Optimal management of pernicious anemia. Journal of blood medicine. 2012;3:97-103.
10. De Paz R, Hernandez-Navarro F. [Management, prevention and control of pernicious anemia]. Nutricion hospitalaria. Nov-Dec 2005;20(6):433-435.