Excess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?

BACKGROUND: In the 1940s to 1950s, high-dose folic acid supplements (>5 mg/d) were used clinically to reverse the megaloblastic anemia of vitamin B12 deficiency caused by pernicious anemia. However, this treatment strategy masked the underlying B12 deficiency and possibly exacerbated its neuropathological progression. The issue of masking and exacerbating B12 deficiency has recently been rekindled with the institution of folic acid fortification and the wide-spread use of folic acid supplements. OBJECTIVES: The objectives of this review are to describe clinical and epidemiological evidence that excess folic acid exacerbates B12 deficiency, to summarize a hypothesis to explain this phenomenon, and to provide guidance for clinicians. RESULTS: Cognitive function test scores are lower and blood homocysteine and methylmalonic acid concentrations are higher in people with low B12 and elevated folate than in those with low B12 and nonelevated folate. High-dose folic acid supplementation in patients with pernicious anemia or epilepsy cause significant reductions in serum B12. It is hypothesized that high-dose folic acid supplements cause depletion of serum holotranscobalamin and thus exacerbate B12 deficiency. CONCLUSION: The evidence for excess folic acid exacerbating B12 deficiency is primarily correlative or from uncontrolled clinical observations, and the hypothesis to explain the phenomenon has not yet been tested. Nonetheless, the evidence is sufficiently compelling to warrant increased vigilance for identifying B12 deficiency in at risk individuals, including older adults and others with low B12 intake or conditions that are associated with B12 malabsorption, who also ingest excessive folic acid or are prescribed folic acid in high doses.

Plain language titleExcess Folic Acid and Vitamin B12 Deficiency: Clinical Implications?Plain language summaryIt has been known for many decades that high doses of the B vitamin supplement, folic acid, can alleviate the anemia of vitamin B12 deficiency, at least temporarily. However, by alleviating the anemia, such folic acid supplements were said to "mask" the underlying vitamin B12 deficiency, thus allowing neurological damage to continue or possibly be exacerbated. Consequently, treating vitamin B12 deficiency with high dose folic acid was discontinued in the 1970s. The issue of whether folic acid supplements can exacerbate vitamin B12 deficiency reemerged in the 1990s with folic acid fortification of cereals and grains in the United States and Canada (and now in over 80 countries around the world) to prevent spina bifida and other birth defects. This narrative review summarizes the results of studies that have assessed the relationships between folic acid and folate and vitamin B12 status in patients and in populations. A recent hypothesis on how folic acid might exacerbate vitamin B12 deficiency is summarized, and recommendations to clinicians are made for increased vigilance in assessing vitamin B12 status in certain groups at risk of vitamin B12 deficiency, including older adults, people with gastrointestinal issues and other factors that cause vitamin B12 malabsorption, people with unexplained neurological problems, and people who follow vegan or vegetarian diets which are naturally low in vitamin B12.

A Systematic Review of Symptoms of Pernicious Anemia.

BACKGROUND: Pernicious anemia (PA) is a type of macrocytic anemia caused by autoimmune gastritis. To facilitate timely diagnosis and treatment of PA there is a pressing need for improved understanding among Healthcare providers of the condition's symptoms and diagnostic criteria. OBJECTIVE: This systematic review aims to extend existing clinical knowledge on the presentation of PA by determining which symptoms and clinical complications are reported in published adult case studies. METHODS: Relevant studies were identified through electronic searches of PsycINFO, Embase, and MEDLINE, via OvidSP. During data extraction symptoms were categorized according to the International Classification of Diseases and were grouped based on frequency. RESULTS: Symptoms were documented for 103 adults with a diagnosis of PA; the most frequent symptoms were fatigue (55%), loss of sensation in limbs (32%), excessive weight loss (27%), and a sore tongue (23%). CONCLUSIONS: This review highlights the diverse symptomology of adults who are diagnosed with PA. Most symptoms documented in case studies are consistent with the core signs of B12 and folate deficiencies. Research is needed to identify if there are common clusters of PA symptoms that can be used as prompts for diagnostic testing in patients with suspected B12 deficiency.

Plain language titleA Review of Symptoms of Pernicious AnemiaPlain language summaryThis study reviewed case studies that have been written about adults with pernicious anemia, it has documented the frequency of the core symptoms and the impact these have on health.

Causes and Risk Factors of Vitamin B12 Deficiency at the Bookends of Life, From Infancy to Old Age.

The causes and risk factors of vitamin B12 deficiency are many and varied. Importantly, they vary considerably across the lifespan, from infancy to old age. The complexity of the physiology of vitamin B12 bespeaks the myriad of possible causes of deficiency and possible disruptions of its functional integrity. These lead ultimately to the pathobiological effects witnessed in deficiency of this fascinating micronutrient. This brief overview of the multiplicity of mechanisms that can result in vitamin B12 deficiency, and the panoply of its manifestations explores the underlying reasons for the protean presentations of the disease. As the human organism progresses through the chronology and milestones of age, various susceptibility factors arise resulting from the interplay of environmental and genetic factors. Acting independently and in concert, these factors produce the common denominator of vitamin B12 deficiency. However, the rate at which such deficiency develops and the way in which it presents clinically vary widely, subject to such influences as genetic variability, end-organ susceptibility, and concomitant micronutrient status. Some examples of unusual cases of vitamin B12 deficiency are described. Much has been learned about the last of the numbered vitamins in almost a century. Much yet remains to be discovered.

Oral manifestations of vitamin B12 deficiency associated with pernicious anemia: A case report.

INTRODUCTION AND IMPORTANCE: Vitamin B12 deficiency can manifest through various oral manifestations such as glossitis, glossodynia, recurrent ulcers, cheilitis, dysgeusia, lingual paresthesia, burning sensations, and pruritus. These oral signs can serve as early indicators of systemic conditions such pernicious anemia. CASE PRESENTATION: A 67 year old northern African female presented at the oral surgery service with complaints of a sore mouth and difficulty eating certain types of food. Her medical history revealed hypothyroidism and no history of gastrectomy. She was diagnosed with pernicious anemia in 2014 and is under hydroxocobalamin injection 5000µg/month since then. Dental history indicated extraction of all teeth, and in 2014, the patient was diagnosed with oral lichen planus. There were no contributory oral habits. Intraoral examination revealed a band like erythematous lesion on the palate with two superficial ulcerations, diagnosed as related to her pernicious anemia. The patient was prescribed a mouthwash containing sodium bicarbonate and corticosteroid to reduce inflammation and alleviate pain. A low level laser therapy was also considered to reduce the burning sensations. CLINICAL DISCUSSION: Pernicious anemia (PA) is an autoimmune disease characterized by the gradual atrophy of the gastric mucosa, predominantly affecting the body and fundus of the stomach, leading to vitamin B12 deficiency. Its insidious onset often masks its presence. Patients have no anemic symptoms. However, they can present with oral manifestations related to vitamin B12 deficiency. Those oral signs can precede hematological symptoms helping in early diagnosis of PA. CONCLUSION: Dentists and other oral health care providers must be aware of this condition and its oral manifestations. Investigating vitamin B12 levels should be considered in patients presenting with oral ulcers, oral erythema or burning sensations without an apparent origin.

Neurological and Cardiovascular Complications Revealing Biermer's Disease: A Case Report.

Biermer's disease (BD) or pernicious anemia (PA) is an autoimmune atrophic gastritis characterized by the absence of intrinsic factor (IF) secretion, leading to malabsorption of vitamin B12 in the ileum. Its clinical manifestations are primarily hematological, with neuropsychiatric and cardiovascular manifestations being less common. We present the case of a patient with PA diagnosed based on neurological and cardiovascular complications. The patient, a 56-year-old man with no specific medical history, presented with an episode of melena without other associated digestive symptoms. He also complained of memory and gait disturbances. Clinical examination revealed a cerebellar ataxia with impaired proprioceptive and vibratory sensitivity, and a swollen and red right lower limb with a positive Homan sign. The blood count showed macrocytic anemia. Gastroscopy revealed flattened fundic folds resembling a fundus appearance, and histopathological examination confirmed fundic atrophic gastritis with pseudopyloric metaplasia and lymphoplasmacytic infiltration. Anti-intrinsic factor antibodies were positive, while anti-parietal cell antibodies were negative. Vitamin B12 levels were severely low, and vitamin B9 levels were normal. TSH and HbA1c levels were within normal ranges. The abdominal CT scan showed no abnormalities. Lower limb Doppler ultrasound confirmed the diagnosis of deep vein thrombosis (DVT). Cardiac evaluation revealed sinus bradycardia suggestive of secondary dysautonomia. Therapeutically, the patient was started on vitamin B12 supplementation and anticoagulant therapy for DVT, resulting in a good clinical and biological outcome.

Causal inference between pernicious anemia and cancers: a bidirectional two-sample mendelian randomization analysis.

BACKGROUND: Observational study investigated the association between pernicious anemia (PA) and cancers. However, with the exception of gastric cancer, the results are mostly contradictory. The purpose of this study was to investigate the potential causal relationship between PA and cancers through bidirectional two-sample Mendelian randomized (MR) analysis. METHODS: The European sample FinnGen project provided the genetic summary data for PA and 20 site-specific cancers. This bidirectional two-sample MR design mainly used the inverse variance weighting (IVW) method to evaluate the causal relationship between PA and cancer risk. Benjamini-Hochberg correction was performed to reduce the bias caused by multiple tests. RESULTS: Our study shows that there was a causal relationship between PA and gastric cancer, prostate cancer, testicular cancer and malignant melanoma of skin, and there was a reverse causal relationship between prostate cancer or gastric cancer and PA (P < 0.05). After Benjamini-Hochberg correction test, there was still a causal correlation between PA and gastric or prostate cancer (P' < 0.05), while there was only an implied causal association between PA and testicular cancer and malignant melanoma of skin (P'> 0.05). There was still a reverse causal relationship between gastric cancer and PA (P'< 0.05), while prostate cancer shows an implied reverse causal relationship(P'> 0.05). In addition, MR-Egger and MR-PRESSO tests showed no significant horizontal pleiotropy. CONCLUSIONS: PA may be genetically associated with testicular cancer, prostate cancer, gastric cancer, and malignant melanoma of skin.

Pernicious anemia presenting with dysphagia and melanoderma: a confusing manifestation.

Vitamin B12 deficiency is widely recognized as a common cause of anemia. However, symptoms such as dysphagia, melanoderma, and pancytopenia, although less frequent, can also be associated with this deficiency. We report the case of a 47-year-old Caucasian man presented with dysphagia to solids associated to high heart rate, dyspnea and melanoderma. He was diagnosed with severe anemia (hemoglobin 4 g/dl) in association with pancytopenia. Further investigation confirmed that the underlying cause was severe vitamin B12 deficiency secondary to pernicious anemia. Subsequent treatment with vitamin B12 supplements led to a significant improvement in all symptoms. A review of the existing literature corroborated the rarity of severe anemia occurring in conjunction with dysphagia and melanoderma due to B12 deficiency.

Anemia is a condition where your body does not have enough healthy red blood cells. We report the case of a 47-year-old man who presented with difficulty swallowing solid food (dysphagia), a fast heart rate, difficulty breathing (dyspnea), and changes in skin color (melanoderma). After some tests, we diagnosed the patient with severe anemia and low counts of different types of blood cells (pancytopenia). The underlying cause was a severe lack of Vitamin B12, and the specific type of anemia was called pernicious anemia. Subsequent treatment with Vitamin B12 supplements led to significant improvement. Physicians should be aware of uncommon presentations of pernicious anemia to diagnose it early, avoid unnecessary investigations and to initiate rapidly simple and efficient treatment.

Oral vitamin B12 supplementation in pernicious anemia: a prospective cohort study.

BACKGROUND: The absorption of vitamin B12 is hindered in pernicious anemia (PA) owing to intrinsic factor deficiency. Traditionally, intramuscular vitamin B12 injections were the standard treatment, bypassing the impaired absorption. Although there is potential for oral vitamin B12 supplementation through passive enteral absorption, it is not commonly prescribed in PA owing to limited studies assessing its efficacy. OBJECTIVES: We aimed to assess the efficacy of oral vitamin B12 supplementation in PA. METHODS: We enrolled participants diagnosed with incident vitamin B12 deficiency related to PA. The diagnosis of PA was based on the presence of classical immune gastritis and of anti-intrinsic factor and/or antiparietal cell antibodies. To evaluate the vitamin B12 status, we measured total plasma vitamin B12, plasma homocysteine, and plasma methylmalonic acid (pMMA) concentration and urinary methylmalonic acid-to-creatinine ratio. Participants were treated with oral cyanocobalamin at a dosage of 1000 µg/d throughout the study duration. Clinical and biological vitamin B12 deficiency related features were prospectively and systematically assessed over the 1-y study duration. RESULTS: We included 26 patients with vitamin B12 deficiency revealing PA. Following 1 mo of oral vitamin B12 supplementation, 88.5% of patients were no longer deficient in vitamin B12, with significant improvement of plasma vitamin B12 [407 (297-485) compared with 148 (116-213) pmol/L; P < 0.0001], plasma homocysteine [13.5 (10.9-29.8) compared with 18.6 (13.7-46.8) µmol/L; P < 0.0001], and pMMA [0.24 (0.16-0.38) compared with 0.56 (0.28-1.09) pmol/L; P < 0.0001] concentrations than those at baseline. The enhancement of these biological parameters persisted throughout the 12-month follow-up, with no patients showing vitamin B12 deficiency by the end of the follow-up period. The median time to reverse initial vitamin B12 deficiency abnormalities ranged from 1 mo for hemolysis to 4 mo for mucosal symptoms. CONCLUSIONS: Oral supplementation with 1000 µg/d of cyanocobalamin has been shown to improve vitamin B12 deficiency in PA.

Hemolytic Anemia and Pancytopenia Secondary to Vitamin B12 Deficiency: Evaluation and Clinical Significance.

Severe vitamin B12 deficiency presents a diagnostic challenge due to its diverse clinical manifestations, which can mimic serious hematologic disorders such as thrombotic thrombocytopenic purpura (TTP) or leukemia. The case we present here illustrates the unique characteristics of severe B12 deficiency, highlighting key differentiators from other conditions, including decreased reticulocyte counts and markedly elevated lactate dehydrogenase levels indicative of suppressed erythropoiesis. Advanced cobalamin deficiency affects all cell lines, leading to peripheral pancytopenia. Proposed mechanisms include fragile red blood cells prone to shearing, resulting in schistocyte formation, and hyperhomocysteinemia-induced oxidative stress exacerbating hemolysis. Prompt recognition and treatment with B12 replacement are critical, as illustrated by this case of hemolytic anemia and pancytopenia secondary to pernicious anemia, to prevent severe hematologic complications.

Pernicious Anemia Unveiled: Unusual Hemolytic Complications and Clinical Implications.

Pernicious anemia (PA) is an autoimmune condition resulting in impaired vitamin B12 absorption that commonly presents with gastritis and neurological symptoms. In rare cases, associated vitamin B12 deficiency can contribute to significant red blood cell lysis, and patients can present with PA-induced pseudo-thrombotic microangiopathy (TMA) hemolytic anemia. This case describes a 59-year-old male presenting with a two-week history of gastrointestinal pain with bleeding who had anemia and hemodynamic instability on initial evaluation. After the endoscopy/colonoscopy did not reveal any active sources of bleeding and packed red blood cells failed to stabilize the patient, it was found that he had low serum B12 with anti-intrinsic factor and anti-parietal cell antibodies. A coordinated clinical approach, including parenteral cyanocobalamin and daily oral folic acid supplementation, stabilized the patient, highlighting the importance of distinguishing PA-induced pseudo-TMA from true TMA hemolytic anemia.

Utilidad de los anticuerpos anti-células parietales gástricas y anti-factor intrínseco en el estudio de la deficiencia de vitamina B12 asociada a gastritis autoinmune y anemia perniciosa / Usefulness of anti-gastric parietal cell and anti-intrinsic factor antibodies in the study of vitamin B12 deficiency associated with autoimmune gastritis and pernicious anemia / Utilidade de anticorpos anti-células parietais gástricas e anti-fator intrínseco no estudo da deficiência de vitamina B12 associada à gastrite autoimune e à anemia perniciosa

Resumen La gastritis autoinmune (GAI) es una afección inflamatoria progresiva de la mucosa oxíntica caracterizada por la destrucción de células parietales, pérdida de factor intrínseco, malabsorción de vitamina B12 (cobalamina), hierro y otros micronutrientes y puede progresar hacia un estado avanzado de anemia megaloblástica conocida como anemia perniciosa (AP). El objetivo de este estudio fue determinar la deficiencia de vitamina B12 debida a malabsorción utilizando la detección de anticuerpos anti-células parietales gástricas (ACPG) y anti-factor intrínseco (AFI). Se analizaron 2050 sueros de pacientes con un inmunoanálisis quimioluminiscente para vitamina B12 total y 2,8% de éstos con las pruebas de inmunofluorescencia indirecta para ACPG y enzimoinmunoanálisis para AFI. La deficiencia de vitamina B12 (<200 ng/mL) fue del 13,1%. En la detección de anticuerpos se encontró: 2 doble positivos ACPG/AFI, 17 simple positivos ACPG y 4 simple positivos AFI. Todas las muestras ACPG y/o AFI positivas tuvieron valores de vitamina B12 total <200 ng/mL. En 5 pacientes con ACPG positivos se diagnosticó gastritis crónica confirmada por biopsia. En los 6 pacientes AFI positivos se realizó el diagnóstico de AP y en 2 de ellos se confirmó por histopatología. La positividad de ACPG y/o AFI permitió la clasificación de pacientes con sospecha de GAI en candidatos para la examinación histológica y la aplicación de esquemas terapéuticos adecuados. Se destaca la importancia de las pruebas de laboratorio como parte de una estrategia de diagnóstico temprano y vigilancia endoscópica, para evitar las manifestaciones relacionadas con la deficiencia de hierro y vitamina B12 y las complicaciones de la enfermedad avanzada.

Abstract Autoimmune gastritis (AIG) is a progressive inflammatory condition of the oxyntic mucosa, characterised by gastric parietal cell destruction, loss of intrinsic factor, and malabsorption of vitamin B12 (cobalamin), iron and other micronutrients; conditioning progress to a state of megaloblastic anemia known as pernicious anemia (PA). The aim of this study was to determine vitamin B12 deficiency due to malabsorption utilizing anti-parietal cell (APCA) and anti-intrinsic factor (IFA) antibodies detection. 2050 patient serum samples were analised by chemiluminescent immunoassay for vitamin B12. A total of 2.8% of them were tested for APCA by indirect immunofluorescence and for IFA by enzyme immunoessay. Vitamin B12 deficiency (<200 ng/mL) was 13.1%. Regarding antibody detection: 2 APCA/IFA double positives, 17 APCA simple positives and 4 IFA simple positives were found. APCA and/or IFA positive samples had total vitamin B12 values <200 ng/mL. Chronic gastritis confirmed by biopsy was diagnosed in 5 patients with positive ACPG antibodies. All 6 IFA positive patients were diagnosed with PA, while 2 of them also received histopatologic confirmation. APCA and/or IFA confirmation allowed for the classification of patients with suspicion of AIG as possible candidates for histologic examination and application of appropriate therapeutic schemes. Importance of laboratory testing is to be noted; as part of a strategy that enables early diagnosis and adequate endoscopic surveillance, to avoid manifestations related to iron and vitamin B12 deficiency and the complications of advanced disease.

Resumo A gastrite autoimune (GAI) é uma doença inflamatória progressiva da mucosa oxíntica, caracterizada pela destruição das células parietais gástricas, perda do fator intrínseco, má absorção de vitamina B12 (cobalamina), ferro e outros micronutrientes pode progredir para um estado avançado de anemia megaloblástica conhecida como anemia perniciosa (AP). O objetivo deste estudo foi determinar a deficiência de vitamina B12 por má absorção usando a detecção de anticorpos anti-células parietais gástricas (ACPG) e anti-fator intrínseco (AFI). Foram analisados 2050 soros de pacientes com um imunoensaio quimioluminiscente para vitamina B12 total, 2,8% deles com testes de imunofluorescência indireta para ACPG e enzimaimunoensaio para AFI. A deficiência de vitamina B12 (<200 ng/mL) foi de 13,1%. Na detecção de anticorpos foram encontrados: 2 duplo positivos ACPG/AFI, 17 simples positivos ACPG e 4 simples positivos AFI. Todas as amostras ACPG e/ou AFI positivas apresentaram valores de vitamina B12 total <200 ng/mL. Gastrite crônica confirmada por biópsia foi diagnosticada em 5 pacientes positivos para ACPG. Nos 6 pacientes AFI positivos o diagnóstico de AP foi feito e em 2 deles foi confirmado por histopatologia. A positividade para ACPG e/ou AFI permitiu a classificação de pacientes com suspeita de GAI em candidatos para exame histológico e a aplicação de esquemas terapêuticos adequados. Destaca-se a importancia dos testes laboratoriais, como parte de uma estratégia de diagnóstico precoce e vigilância endoscópica, para evitar manifestações relacionadas à deficiência de ferro e vitamina B12 e complicações da doença avançada.

Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid.

Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts-both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG.

Iron deficiency in pernicious anemia: Specific features of iron deficient patients and preliminary data on response to iron supplementation.

BACKGROUND & AIMS: While vitamin B12 (B12) deficiency is considered as the hallmark of pernicious anemia (PA), iron deficiency (ID) is also prevalent. Indeed, this auto immune gastritis is responsible for parietal cell atrophy and increase in gastric pH, leading to impaired iron absorption. We compared PA patients' features according to their iron status at PA diagnosis, and we assessed the iron status recovery after oral or intravenous iron supplementation. METHODS: We prospectively included patients presenting with a newly diagnosed PA in a tertiary referral hospital between November 2018 and October 2020. Iron status was assessed at PA diagnosis then regularly during a standardized follow-up. In case of ID, the decision of treatment with oral and/or intravenous iron supplementation was left to the clinician convenience. RESULTS: We included 28 patients with newly diagnosed PA. ID was observed in 21/28 (75.0%) patients: from the PA diagnosis in 13 patients, or during the follow-up in 8 patients. Iron deficient PA patients had higher plasma B12 (p = 0.04) and lower homocysteine levels (p = 0.04). Also, ID was independently associated with the 'APCA (anti-parietal cell antibodies) alone' immunological status (absence of anti-intrinsic factor antibodies) after adjustment for age, gender and B12 level (aOR 12.1 [1.1-141.8], p = 0.04). High level of APCA was associated with lower ferritin level. After 3 months of supplementation, 3/11 PA patients normalized the iron status with oral iron supplementation, versus 7/8 with intravenous iron supplementation (p = 0.02). CONCLUSION: The high frequency of iron deficiency in PA highlights the interest of regular assessment of iron status in this condition. ID was associated with a profile including APCA alone and less pronounced B12 deficiency. Intravenous iron supplementation seemed to be more efficient than an oral supplementation in these preliminary data.

Pernicious Anemia With Spuriously Normal B12 Levels.

We present a 29-year-old man admitted to our hospital with fatigue for two months of duration and recent palpitations, lightheadedness, blurred vision and nausea. Workup showed pancytopenia with severe macrocytic anemia, laboratory and blood smear features of hemolysis, low reticulocyte percentage and a negative direct Coombs test. B12 and folate levels were normal. As bone marrow aspirate was suggestive of megaloblastic anemia and upper endoscopy showed atrophic gastritis, we ordered homocysteine (elevated) and intrinsic factor (IF) antibodies (positive). The workup led to the diagnosis of pernicious anemia with spuriously normal B12 levels. Replacement therapy allowed a rapid recovery. We highlight that the presence of IF antibodies can interfere with the competitive binding assays commonly used to measure B12 levels.

[Pernicious anemia with false normal vitamin B12 levels caused by intrinsic factor antibodies interference: a case report]. / Maladie de Biermer avec dosage de vitamine B12 faussement normal par interférence avec les anticorps anti-facteur intrinsèque : à propos d'un cas.

We present a case of a 48-year-old woman with a fortuitous discovery of macrocytic anemia and thrombocytopenia. Serum folate and vitamin B12 levels were normal. However, due to the presence of indirect signs of cobalamin deficiency, such as elevated homocysteine and methylmalonic acid, and signs of dyserythropoiesis on the bone marrow aspirate, pernicious anemia was suspected. Vitamin B12 dosage was repeated finding fluctuating but always normal results. Anti-intrinsic factor antibodies were present at a very high level, explaining the fluctuations and the interference found on the assay using competitive binding chemiluminescence (CBLA). Serum vitamin B12 dosage by electrochemiluminescence, a method described as not interfering with intrinsic factor antibodies, showed a collapsed vitamin B12 level. Measurement of vitamin B12 with CBLA after adsorption of immunoglobulins in the sample using protein G SepharoseTM, confirmed the interference of the cobalamin assay with autoantibodies. This case illustrates the difficulties regarding the analysis and standardization of the vitamin B12 assay for the diagnosis of pernicious anemia.

Pernicious Anemia Following COVID-19 Vaccination: A Report of Two Cases.

Since December 2019 and the global epidemic of COVID-19 different countries have focused on vaccines, and one of the inactivated produced vaccines was the Sinopharm COVID-19 vaccine. Some side effects of this vaccine were reported previously, including pain at the vaccination site, fatigue, lethargy, headache, and tenderness, which were more prevalent among individuals <49 years old. Herein, we reported two patients aged 45 and 51 years old. Both patients have different signs and symptoms after receiving the second dose of the vaccine. None had a history of chronic disease. On examination and following labs and other diagnostic investigations, we found megaloblastic anemia due to atrophic gastritis and low intrinsic factor. These cases showed an autoimmune side effect of the Sinopharm COVID-19 vaccine that was previously reported with an exact mechanism but other features called Covid Arm, Guillain-Barré syndrome, and thrombocytopenia. The mechanism of this reaction is unclear yet.

Exploring the Association of Helicobacter pylori With Anti-intrinsic Factor and Anti-parietal Cell Antibodies in Pernicious Anemia: A Systematic Review.

Pernicious anemia, historically tied to vitamin B12 malabsorption due to intrinsic factor secretion impairment, has evolved in understanding, especially concerning its association with autoimmune gastritis. This systematic review dives deep into the multifaceted relationship between Helicobacter pylori (H. pylori) infection, autoimmune gastritis, and the presence of anti-intrinsic factors and anti-parietal cell antibodies. Comprehensive database searches revealed a higher prevalence of H. pylori infection in pernicious anemia patients, with some studies suggesting a consequential increase in the aforementioned antibodies. Interestingly, eradication of H. pylori displayed potential therapeutic effects; patients showcased reductions in antibody titers, improved histopathological findings, and reversion of atrophic changes in gastric corpus. Such outcomes highlight the conceivable benefits of considering H. pylori infection during the evaluation and management of pernicious anemia and autoimmune gastritis. However, disparities across studies make direct comparisons challenging. It's essential to approach the potential role of H. pylori in these conditions with caution. Further research is warranted to cement conclusions and refine clinical management strategies. This review seeks to prompt new investigative avenues into the intricate link between H. pylori, autoimmune gastritis, and pernicious anemia, ultimately enhancing patient care.

Elderly Patient With Hematological and Neurological Manifestations of Undetermined Origin: A Diagnostic Dilemma of Pernicious Anemia.

Pernicious anemia (PA) is a chronic inflammatory destructive disease of parietal cells of predominantly the gastric fundus. It leads to vitamin B12 (cobalamin) deficiency secondary to a deficiency of intrinsic factors. Despite the medical advances nowadays, diagnosing PA can be challenging. This report highlights a neglected case of PA with ongoing subacute combined degeneration of the cord (SCDS) in an elderly patient. An 86-year-old lady with multiple comorbidities was referred to the hematology outpatient clinic for refractory anemia for the last two months. At first, her general practitioner (GP) treated her as a case of anemia of chronic disease but without improvement. Her initial clinical assessment revealed hematological and neurological manifestations of undetermined origin, including global weakness, hypertonia, and hyperreflexia with sensory deficits, especially in the lower limbs. On investigation, the hemoglobin level was 9 g/dL with high indirect bilirubinemia and lactate dehydrogenase (LDH). Despite the normal mean corpuscular volume (MCV) and peripheral blood smear, positive anti-intrinsic factor and parietal cell antibodies tests were subsequently reported, suggesting the diagnosis of PA. As a result, she was commenced on lifelong parenteral cobalamin replacement therapy. On follow-up visits of three months, she illustrated a clinical recovery in fatigability and paranesthesia. As expected, the laboratory parameters revealed a rise in hemoglobin level (11 g/dL) and serum vitamin B12 (418 pg/mL). However, she remained bedridden with spastic limbs. Clinicians should have a high index of suspicion since PA is a rare disease with variable clinical presentations. The optimal management approach is by a multidisciplinary care team of internists, neurologists, gastroenterologists, and hematologists.